Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord

PubMed Central

McCormick, Barry; Lukito, Veny; Wilson, Kirsten L.

2017-01-01

C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1–10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity. SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation. PMID:28576935

Differences in Pain, Psychological Symptoms, and Gender Distribution Among Patients with Left vs. Right-Sided Chronic Spinal Pain

PubMed Central

Wasan, Ajay D.; Anderson, Nina K.; Giddon, Donald B.

2010-01-01

Objective To determine pain levels, function, and psychological symptoms in relation to predominant sidedness of pain (right or left) and gender in patients being treated for chronic spinal pain. Design Prospective cohort study Patients Patients with chronic neck or low back pain undergoing a nerve block procedure in a speciality pain medicine clinic Interventions/Outcomes Patients completed the Hospital Anxiety and Depression Scale and the Brief Pain Inventory just prior to the procedure. Pain history and demographic variables were collected from a chart review. Chi-square, Pearson correlations, and multivariate statistics were used to characterize the relationships between side of pain, gender, pain levels, pain interference, and psychological symptoms. Results Among 519 subjects, men with left-sided pain (n=98) were found to have significantly greater depression and anxiety symptoms and worse pain-related quality of life (p<.01), despite having similar pain levels as men with right-sided pain (n=91) or women with left or right-sided pain (n=289). In men, psychological symptoms had a significantly greater correlation with pain levels than in women (p<.01). Conclusion In this sample, men with left-sided spinal pain report worse quality of life and more psychological symptoms than women. These data provide clinical evidence corroborating basic neuroscience findings indicating that the right cerebral hemisphere is preferentially involved in the processing of pain and negative affect. These data suggest that men appear more right hemisphere dominant in pain and affect processing. These findings have implications for multidisciplinary assessment and treatment planning in men. PMID:20667025

From nociception to pain perception: imaging the spinal and supraspinal pathways

PubMed Central

Brooks, Jonathan; Tracey, Irene

2005-01-01

Functional imaging techniques have allowed researchers to look within the brain, and revealed the cortical representation of pain. Initial experiments, performed in the early 1990s, revolutionized pain research, as they demonstrated that pain was not processed in a single cortical area, but in several distributed brain regions. Over the last decade, the roles of these pain centres have been investigated and a clearer picture has emerged of the medial and lateral pain system. In this brief article, we review the imaging literature to date that has allowed these advances to be made, and examine the new frontiers for pain imaging research: imaging the brainstem and other structures involved in the descending control of pain; functional and anatomical connectivity studies of pain processing brain regions; imaging models of neuropathic pain-like states; and going beyond the brain to image spinal function. The ultimate goal of such research is to take these new techniques into the clinic, to investigate and provide new remedies for chronic pain sufferers. PMID:16011543

Recurrent and Transient Spinal Pain Among Commercial Helicopter Pilots.

PubMed

Andersen, Knut; Baardsen, Roald; Dalen, Ingvild; Larsen, Jan Petter

2015-11-01

The aim of this study was to provide information on the occurrence of spinal pain, i.e., low back and neck pain, among commercial helicopter pilots, along with possible associations between pain and anthropometric and demographic factors and flying exposure. Data were collected through a subjective and retrospective survey among all the 313 (294 men, 19 women) full-time pilots employed by two helicopter companies. A questionnaire was used to assess the extent of spinal complaints in a transient and recurrent pain pattern along with information on physical activities, occupational flying experience, and airframes. The survey had 207 responders (194 men, 13 women). The pilots had extensive flying experience. Spinal pain was reported by 67%. Flying-related transient pain was reported among 50%, whereas recurrent spinal pain, not necessarily associated with flying, was reported by 52%. Women experienced more pain, but sample size prevented further conclusions. Male pilots reporting any spinal pain flew significantly more hours last year (median 500 h, IQR 400-650) versus men with no pain (median 445 h, IQR 300-550). Male pilots with transient or recurrent spinal pain did not differ from nonaffected male colleagues in the measured parameters. Spinal pain is a frequent problem among male and female commercial helicopter pilots. For men, no significant associations were revealed for transient or recurrent spinal pain with age, flying experience in years, total hours, annual flying time, type of aircraft, or anthropometric factors except for any spinal pain related to hours flown in the last year.

Coregulation of endoplasmic reticulum stress and oxidative stress in neuropathic pain and disinhibition of the spinal nociceptive circuitry.

PubMed

Ge, Yanhu; Jiao, Yingfu; Li, Peiying; Xiang, Zhenghua; Li, Zhi; Wang, Long; Li, Wenqian; Gao, Hao; Shao, Jiayun; Wen, Daxiang; Yu, Weifeng

2018-05-01

The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen leads to ER stress, which is related to cellular reactive oxygen species production. Neuropathic pain may result from spinal dorsal horn (SDH) ER stress. In this study, we examined the cause-effect relationship between ER stress and neuropathic pain using the spinal nerve ligation (SNL) rat model. We showed that ER stress was mutually promotive with oxidative stress during the process. We also tested the hypothesis that spinal sensitization arose from reduced activities of GABA-ergic interneurons and that spinal sensitization was mediated by SDH ER stress. Other important findings in this study including the following: (1) nociceptive behavior was alleviated in SNL rat as long as tauroursodeoxycholic acid injections were repeated to inhibit ER stress; (2) inducing SDH ER stress in healthy rat resulted in mechanical hyperalgesia; (3) blocking protein disulfide isomerase pharmacologically reduced ER stress and nociceptive behavior in SNL rat; (4) cells in the dorsal horn with elevated ER stress were mainly neurons; and (5) whole-cell recordings made in slide preparations revealed significant inhibition of GABA-ergic interneuron activity in the dorsal horn with ER stress vs in the healthy dorsal horn. Taken together, results of the current study demonstrate that coregulation of ER stress and oxidative stress played an important role in neuropathic pain process. Inhibiting SDH ER stress could be a potential novel strategy to manage neuropathic pain.

What do monoamines do in pain modulation?

PubMed

Bannister, Kirsty; Dickenson, Anthony H

2016-06-01

Here, we give a topical overview of the ways in which brain processing can alter spinal pain transmission through descending control pathways, and how these change in pain states. We link preclinical findings on the transmitter systems involved and discuss how the monoamines, noradrenaline, 5-hydroxytryptamine (5-HT), and dopamine, can interact through inhibitory and excitatory pathways. Descending pathways control sensory events and the actions of the neurotransmitters noradrenaline and 5-HT in the dorsal horn of the spinal cord are chiefly implicated in nociception or antinociception according to the receptor that is activated. Abnormalities in descending controls effect central pain processing. Following nerve injury a noradrenaline-mediated control of spinal excitability is lost, whereas its restoration reduces neuropathic hypersensitivity. The story with 5-HT remains more complex because of the myriad of receptors that it can act upon; however the most recent findings support that facilitations may dominate over inhibitions. The monoaminergic system can be manipulated to great effect in the clinic resulting in improved treatment outcomes and is the basis for the actions of the antidepressant drugs in pain. Looking to the future, prediction of treatment responses will possible by monitoring a form of inhibitory descending control for optimized pain relief.

The importance of the descending monoamine system for the pain experience and its treatment

PubMed Central

Dickenson, Anthony H

2009-01-01

Brainstem and midbrain areas engage descending facilitatory and inhibitory neurones to potentiate or suppress the passage of sensory inputs from spinal loci to the brain. The balance between descending controls, both excitatory and inhibitory, can be altered in various pain states and can critically determine the efficacy of certain analgesic drugs. There is good evidence for a prominent α2 adrenoceptor-mediated inhibitory system and for 5-HT3 receptor-mediated excitatory control of spinal cord activity that originates in supraspinal areas. Given the multiple roles of these transmitters in pain and functions such as sleep, depression, and anxiety, the link between spinal and supraspinal processing of noxious inputs (via the monoamine transmitters) could be pivotal for linking the sensory and affective components of pain and their common co-morbidities, and also may potentially explain differences in pain scores and treatment outcomes in the patient population. PMID:20948695

Ablating spinal NK1-bearing neurons eliminates the development of pain & reduces spinal neuronal hyperexcitability & inflammation from mechanical joint injury in the rat

PubMed Central

Weisshaar, Christine L.; Winkelstein, Beth A.

2014-01-01

The facet joint is a common source of pain especially from mechanical injury. Although chronic pain is associated with altered spinal glial and neuronal responses, the contribution of specific spinal cells to joint pain are not understood. This study used the neurotoxin [Sar9,Met(O2)11]-substance P-saporin (SSP-SAP) to selectively eliminate spinal cells expressing neurokinin-1 receptor (NK1R) in a rat model of painful facet joint injury to determine the role of those spinal neurons in pain from facet injury. Following spinal administration of SSP-SAP or its control (blank-SAP), a cervical facet injury was imposed and behavioral sensitivity assessed. Spinal extracellular recordings were made on day 7 to classify neurons and quantify evoked firing. Spinal glial activation and IL1α expression also were evaluated. SSP-SAP prevented the development of mechanical hyperalgesia that is induced by joint injury and reduced NK1R expression and mechanically-evoked neuronal firing in the dorsal horn. SSP-SAP also prevented a shift toward wide dynamic range neurons that is seen after injury. Spinal astrocytic activation and IL1α expression were reduced to sham levels with SSP-SAP treatment. These results suggest that spinal NK1R-bearing cells are critical in initiating spinal nociception and inflammation associated with a painful mechanical joint injury. Perspective Results demonstrate that cells expressing NK1R in the spinal cord are critical for the development of joint pain and spinal neuroplasticity and inflammation after trauma to the joint. These findings have utility for understanding mechanisms of joint pain and developing potential targets to treat pain. PMID:24389017

Fos expression in the rat brain and spinal cord evoked by noxious stimulation to low back muscle and skin.

PubMed

Ohtori, S; Takahashi, K; Chiba, T; Takahashi, Y; Yamagata, M; Sameda, H; Moriya, H

2000-10-01

Acute noxious stimulation delivered to lumbar muscles and skin of rats was used to study Fos expression patterns in the brain and spinal cord. The present study was conducted to determine the differences in Fos expression in the brain and spinal cord as evoked by stimuli delivered to lumbar muscles and skin in rats. Patients with low back pain sometimes show psychological symptoms, such as quiescence, loss of interest, decreased activities, appetite loss, and restlessness. The pathway of deep somatic pain to the brain has been reported to be different from that of cutaneous pain. However, Fos expression has not been studied in the central nervous systems after stimulation of low back muscles. Rats were injected with 100 L of 5% formalin into the multifidus muscle (deep pain group; n = 10) and into the back skin of the L5 dermatome (cutaneous pain group; n = 10). Two hours after injection, the distribution of Fos-immunoreactive neurons was studied in the brain and spinal cord. Fos-immunoreactive neurons were observed in laminae I-V in the spinal cord in the cutaneous pain group, but they were not seen in lamina II in the deep pain group. In the brain, Fos-immunoreactive neurons were significantly more numerous in the deep pain group than in the cutaneous pain group in the piriform cortex, the accumbens nucleus core, the basolateral nucleus of amygdala, the paraventricular hypothalamic nucleus, the ventral tegmental area, and the ventrolateral periaqueductal gray. The finding that Fos-immunoreactive neurons were absent from lamina II of the spinal cord in the deep pain group is similar to that of the projection pattern of the visceral pain pathway. Fos expression in the ventrolateral periaqueductal gray in the deep pain group may represent a reaction of quiescence and a loss of interest, activities, or appetite. Furthermore, the detection of large numbers of Fos-immunoreactive neurons in the core of accumbens nucleus, basolateral nucleus of amygdala, paraventricular hypothalamic nucleus, and ventral tegmental area in the deep pain group may suggest a dominant reaction of dopaminergic neurons to stress, and a different information processing pathway than from that of cutaneous pain.

A preclinical physiological assay to test modulation of knee joint pain in the spinal cord: effects of oxycodone and naproxen.

PubMed

Miranda, Jason A; Stanley, Phil; Gore, Katrina; Turner, Jamie; Dias, Rebecca; Rees, Huw

2014-01-01

Sensory processing in the spinal cord during disease states can reveal mechanisms for novel treatments, yet very little is known about pain processing at this level in the most commonly used animal models of articular pain. Here we report a test of the prediction that two clinically effective compounds, naproxen (an NSAID) and oxycodone (an opiate), are efficacious in reducing the response of spinal dorsal horn neurons to noxious knee joint rotation in the monosodium iodoacetate (MIA) sensitized rat. The overall objective for these experiments was to develop a high quality in vivo electrophysiology assay to confidently test novel compounds for efficacy against pain. Given the recent calls for improved preclinical experimental quality we also developed and implemented an Assay Capability Tool to determine the quality of our assay and ensure the quality of our results. Spinal dorsal horn neurons receiving input from the hind limb knee joint were recorded in anesthetized rats 14 days after they were sensitized with 1 mg of MIA. Intravenous administered oxycodone and naproxen were each tested separately for their effects on phasic, tonic, ongoing and afterdischarge action potential counts in response to innocuous and noxious knee joint rotation. Oxycodone reduced tonic spike counts more than the other measures, doing so by up to 85%. Tonic counts were therefore designated the primary endpoint when testing naproxen which reduced counts by up to 81%. Both reductions occurred at doses consistent with clinically effective doses for osteoarthritis. These results demonstrate that clinically effective doses of standard treatments for osteoarthritis reduce pain processing measured at the level of the spinal cord for two different mechanisms. The Assay Capability Tool helped to guide experimental design leading to a high quality and robust preclinical assay to use in discovering novel treatments for pain.

A Preclinical Physiological Assay to Test Modulation of Knee Joint Pain in the Spinal Cord: Effects of Oxycodone and Naproxen

PubMed Central

Miranda, Jason A.; Stanley, Phil; Gore, Katrina; Turner, Jamie; Dias, Rebecca; Rees, Huw

2014-01-01

Sensory processing in the spinal cord during disease states can reveal mechanisms for novel treatments, yet very little is known about pain processing at this level in the most commonly used animal models of articular pain. Here we report a test of the prediction that two clinically effective compounds, naproxen (an NSAID) and oxycodone (an opiate), are efficacious in reducing the response of spinal dorsal horn neurons to noxious knee joint rotation in the monosodium iodoacetate (MIA) sensitized rat. The overall objective for these experiments was to develop a high quality in vivo electrophysiology assay to confidently test novel compounds for efficacy against pain. Given the recent calls for improved preclinical experimental quality we also developed and implemented an Assay Capability Tool to determine the quality of our assay and ensure the quality of our results. Spinal dorsal horn neurons receiving input from the hind limb knee joint were recorded in anesthetized rats 14 days after they were sensitized with 1 mg of MIA. Intravenous administered oxycodone and naproxen were each tested separately for their effects on phasic, tonic, ongoing and afterdischarge action potential counts in response to innocuous and noxious knee joint rotation. Oxycodone reduced tonic spike counts more than the other measures, doing so by up to 85%. Tonic counts were therefore designated the primary endpoint when testing naproxen which reduced counts by up to 81%. Both reductions occurred at doses consistent with clinically effective doses for osteoarthritis. These results demonstrate that clinically effective doses of standard treatments for osteoarthritis reduce pain processing measured at the level of the spinal cord for two different mechanisms. The Assay Capability Tool helped to guide experimental design leading to a high quality and robust preclinical assay to use in discovering novel treatments for pain. PMID:25157947

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord.

PubMed

Dickie, Allen C; McCormick, Barry; Lukito, Veny; Wilson, Kirsten L; Torsney, Carole

2017-07-05

C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1-10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity. SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation. Copyright © 2017 Dickie et al.

Impact of spinal pain on daily living activities in postmenopausal women working in agriculture.

PubMed

Raczkiewicz, Dorota; Owoc, Alfred; Sarecka-Hujar, Beata; Saran, Tomasz; Bojar, Iwona

2017-03-22

Postmenopausal women working in agriculture suffer from spinal pain for two overlapping reasons, the first is related to the menopause and the second to the specificity of rural work, which includes lifting heavy objects and changing weather conditions. Spinal pain affects the daily life of women as well as their ability to work. The objective of the study was to analyse the impact of spinal pain on activities of daily life in Polish postmenopausal women performing agricultural work. The study was conducted in 2016 in Poland and included 1,119 post-menopausal women living in rural areas and working in agriculture. The women assessed the severity of spinal pain in 3 sections: neck, thorax and lumbar. Neck Disability Index (NDI) and Oswestry Low Back Disability Index (ODI) questionnaires were used to assess the impact of spinal pain on daily life activities. Generalized linear models were estimated in statistical analyses. Postmenopausal women working in agriculture suffered most often from pain in the lumbar spine, less frequently in the neck, and the least in the thoracic. The most common was an isolated pain in only one section of the spine. Spinal pain disturbed the most the women's rest, standing, lifting objects, while sleep, concentration, and walking the least. The impact of spinal pain on the activities of daily life, on average, was moderate, and increased with greater pain severity, the earlier the age the pain started, the higher the body weight, the lower education level and if there was a co-existing pain in any of the other spine sections. The impact of spinal pain on daily life activities did not depend on age between 45-65, WHR, age at last menstruation, parity, and number and types of births. The impact of spinal pain on daily life activities in postmenopausal women working in agriculture was assessed as moderate, on average, and depended mainly on spinal pain-related characteristics, such as severity, age at onset and co-existence of pain in any other spinal sections.

Cancer pain physiology

PubMed Central

Falk, Sarah; Bannister, Kirsty

2014-01-01

Mechanisms of inflammatory and neuropathic pains have been elucidated and translated to patient care by the use of animal models of these pain states. Cancer pain has lagged behind since early animal models of cancer-induced bone pain were based on the systemic injection of carcinoma cells. This precluded systematic investigation of specific neuronal and pharmacological alterations that occur in cancer-induced bone pain. In 1999, Schwei et al. described a murine model of cancer-induced bone pain that paralleled the clinical condition in terms of pain development and bone destruction, confined to the mouse femur. This model prompted related approaches, and we can now state that cancer pain may include elements of inflammatory and neuropathic pains but also unique changes in sensory processing. Cancer-induced bone pain results in progressive bone destruction, elevated osteoclast activity and distinctive nocifensive behaviours (indicating the triad of ongoing, spontaneous and movement-induced hyperalgesia). In addition, cancer cells induce an inflammatory infiltrate and release growth factors, cytokines, interleukins, chemokines, prostanoids and endothelins, resulting in a reduction of pH to below 5 and direct deformation of primary afferents within bone. These peripheral changes, in turn, drive hypersensitivity of spinal cord sensory neurons, many of which project to the parts of the brain involved in the emotional response to pain. Within the spinal cord, a unique neuronal function reorganization within segments of the dorsal horn of the spinal cord receiving nociceptive input from the bone are discussed. Changes in certain neurotransmitters implicated in brain modulation of spinal function are also altered with implications for the affective components of cancer pain. Treatments are described in terms of mechanistic insights and in the case of opioids, which modulate pain transmission at spinal and supraspinal sites, their use can be compromised by opioid-induced hyperalgesia. We discuss evidence for how this comes about and how it may be treated. PMID:26516549

Neuropathy-induced spinal GAP-43 expression is not a main player in the onset of mechanical pain hypersensitivity.

PubMed

Jaken, Robby J; van Gorp, Sebastiaan; Joosten, Elbert A; Losen, Mario; Martínez-Martínez, Pilar; De Baets, Marc; Marcus, Marco A; Deumens, Ronald

2011-12-01

Structural plasticity within the spinal nociceptive network may be fundamental to the chronic nature of neuropathic pain. In the present study, the spatiotemporal expression of growth-associated protein-43 (GAP-43), a protein which has been traditionally implicated in nerve fiber growth and sprouting, was investigated in relation to mechanical pain hypersensitivity. An L5 spinal nerve transection model was validated by the presence of mechanical pain hypersensitivity and an increase in the early neuronal activation marker cFos within the superficial spinal dorsal horn upon innocuous hindpaw stimulation. Spinal GAP-43 was found to be upregulated in the superficial L5 dorsal horn from 5 up to 10 days after injury. GAP-43 was co-localized with calcitonin-gene related peptide (CGRP), but not vesicular glutamate transporter-1 (VGLUT-1), IB4, or protein kinase-γ (PKC-γ), suggesting the regulation of GAP-43 in peptidergic nociceptive afferents. These GAP-43/CGRP fibers may be indicative of sprouting peptidergic fibers. Fiber sprouting largely depends on growth factors, which are typically associated with neuro-inflammatory processes. The putative role of neuropathy-induced GAP-43 expression in the development of mechanical pain hypersensitivity was investigated using the immune modulator propentofylline. Propentofylline treatment strongly attenuated the development of mechanical pain hypersensitivity and glial responses to nerve injury as measured by microglial and astroglial markers, but did not affect neuropathy-induced levels of spinal GAP-43 or GAP-43 regulation in CGRP fibers. We conclude that nerve injury induces structural plasticity in fibers expressing CGRP, which is regarded as a main player in central sensitization. Our data do not, however, support a major role of these structural changes in the onset of mechanical pain hypersensitivity.

Spine Day 2012: spinal pain in Swiss school children- epidemiology and risk factors.

PubMed

Wirth, Brigitte; Knecht, Christina; Humphreys, Kim

2013-10-05

The key to a better understanding of the immense problem of spinal pain seems to be to investigate its development in adolescents. Based on the data of Spine Day 2012 (an annual action day where Swiss school children were examined by chiropractors on a voluntary basis for back problems), the aim of the present study was to gain systematic epidemiologic data on adolescent spinal pain in Switzerland and to explore risk factors per gender and per spinal area. Data (questionnaires and physical examinations) of 836 school children were descriptively analyzed for prevalence, recurrence and severity of spinal pain. Of those, 434 data sets were included in risk factor analysis. Using logistic regression analysis, psycho-social parameters (presence of parental back pain, parental smoking, media consumption, type of school bag) and physical parameters (trunk symmetry, posture, mobility, coordination, BMI) were analyzed per gender and per spinal area. Prevalence of spinal pain was higher for female gender in all areas apart from the neck. With age, a steep increase in prevalence was observed for low back pain (LBP) and for multiple pain sites. The increasing impact of spinal pain on quality of life with age was reflected in an increase in recurrence, but not in severity of spinal pain. Besides age and gender, parental back pain (Odds ratio (OR)=3.26, p=0.011) and trunk asymmetry (OR=3.36, p=0.027) emerged as risk factors for spinal pain in girls. Parental smoking seemed to increase the risk for both genders (boys: OR=2.39, p=0.020; girls: OR=2.19, p=0.051). Risk factor analysis per spinal area resulted in trunk asymmetry as risk factor for LBP (OR=3.15, p=0.015), while parental smoking increased the risk for thoracic spinal pain (TSP) (OR=2.83, p=0.036) and neck pain (OR=2.23, p=0.038). The risk for TSP was further enhanced by a higher BMI (OR=1.15, p=0.027). This study supports the view of adolescent spinal pain as a bio-psycho-social problem that should be investigated per spinal area, age and gender. The role of trunk asymmetry and passive smoking as risk factors as well as the association between BMI and TSP should be further investigated, preferably in prospective studies.

Blockade of NMDA receptors decreased spinal microglia activation in bee venom induced acute inflammatory pain in rats.

PubMed

Li, Li; Wu, Yongfang; Bai, Zhifeng; Hu, Yuyan; Li, Wenbin

2017-03-01

Microglial cells in spinal dorsal horn can be activated by nociceptive stimuli and the activated microglial cells release various cytokines enhancing the nociceptive transmission. However, the mechanisms underlying the activation of spinal microglia during nociceptive stimuli have not been well understood. In order to define the role of NMDA receptors in the activation of spinal microglia during nociceptive stimuli, the present study was undertaken to investigate the effect of blockade of NMDA receptors on the spinal microglial activation induced by acute peripheral inflammatory pain in rats. The acute inflammatory pain was induced by subcutaneous bee venom injection to the plantar surface of hind paw of rats. Spontaneous pain behavior, thermal withdrawal latency and mechanical withdrawal threshold were rated. The expression of specific microglia marker CD11b/c was assayed by immunohistochemistry and western blot. After bee venom treatment, it was found that rats produced a monophasic nociception characterized by constantly lifting and licking the injected hind paws, decreased thermal withdrawal latency and mechanical withdrawal threshold; immunohistochemistry displayed microglia with enlarged cell bodies, thickened, extended cellular processes with few ramifications, small spines, and intensive immunostaining; western blot showed upregulated expression level of CD11b/c within the period of hyperalgesia. Prior intrathecal injection of MK-801, a selective antagonist of NMDA receptors, attenuated the pain behaviors and suppressed up-regulation of CD11b/c induced by bee venom. It can be concluded that NMDA receptors take part in the mediation of spinal microglia activation in bee venom induced peripheral inflammatory pain and hyperalgesia in rats.

21 CFR 882.5880 - Implanted spinal cord stimulator for pain relief.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Implanted spinal cord stimulator for pain relief. (a) Identification. An implanted spinal cord stimulator for pain relief is a device that is used to stimulate electrically a patient's spinal cord to relieve... on the patient's spinal cord and an external transmitter for transmitting the stimulating pulses...

Electroencephalographic evoked pain response is suppressed by spinal cord stimulation in complex regional pain syndrome: a case report.

PubMed

Hylands-White, Nicholas; Duarte, Rui V; Beeson, Paul; Mayhew, Stephen D; Raphael, Jon H

2016-12-01

Pain is a subjective response that limits assessment. The purpose of this case report was to explore how the objectivity of the electroencephalographic response to thermal stimuli would be affected by concurrent spinal cord stimulation. A patient had been implanted with a spinal cord stimulator for the management of complex regional pain syndrome of both hands for 8 years. Following ethical approval and written informed consent we induced thermal stimuli using the Medoc PATHWAY Pain & Sensory Evaluation System on the right hand of the patient with the spinal cord stimulator switched off and with the spinal cord stimulator switched on. The patient reported a clinically significant reduction in thermal induced pain using the numerical rating scale (71.4 % reduction) with spinal cord stimulator switched on. Analysis of electroencephalogram recordings indicated the occurrence of contact heat evoked potentials (N2-P2) with spinal cord stimulator off, but not with spinal cord stimulator on. This case report suggests that thermal pain can be reduced in complex regional pain syndrome patients with the use of spinal cord stimulation and offers objective validation of the reported outcomes with this treatment.

Back Pain Prevalence Is Associated With Curve-type and Severity in Adolescents With Idiopathic Scoliosis: A Cross-sectional Study.

PubMed

Théroux, Jean; Le May, Sylvie; Hebert, Jeffrey J; Labelle, Hubert

2017-08-01

A cross-sectional study. The aim of this study was to investigate spinal pain prevalence in adolescents with idiopathic scoliosis (AIS) and to explore associations between pain intensity and pain-related disability with scoliosis site, severity, and spinal bracing. The causal link between spinal pain and AIS remains unclear. Spinal asymmetry has been recognized as a back pain risk factor, which is a known cause of care-seeking in adolescents. Participants were recruited from an outpatient tertiary-care scoliosis clinic. Pain intensity and pain-related disability were measured by the Brief Pain Inventory questionnaire and the Roland-Morris Disability Questionnaire. Scoliosis severity estimation was performed using Cobb angles. Associations were explored using multiple linear regressions and reported with unstandardized beta coefficients (β) adjusted for age and sex. We recruited 500 patients (85% female) with mean (SD) age of 14.2 (1.8) years. Means (SD) of thoracic and lumbar Cobb angle were 24.54(9.77) and 24.13 (12.40), respectively. Spinal pain prevalence was 68% [95% confidence interval (95% CI): 64.5-72.4] with a mean intensity of 1.63 (SD, 1.89). Spinal pain intensity was positively associated with scoliosis severity in the main thoracic (P = 0.003) and lumbar (P = 0.001) regions. The mean (SD) disability score was 1.73 (2.98). Disability was positively associated with scoliosis severity in the proximal thoracic (P = 0.035), main thoracic (P = 0.000), and lumbar (P = 0.000) regions.Spinal bracing was associated with lower spinal pain intensity in the thoracic (P = 0.000) and lumbar regions (P = 0.009). Bracing was also related with lower disability for all spinal areas (P < 0.045). Spinal pain is common among patients with AIS, and greater spinal deformity was associated with higher pain intensity. These findings should inform clinical decision-making when caring for patients with AIS. 3.

Inhibitory effects of aspirin-triggered resolvin D1 on spinal nociceptive processing in rat pain models.

PubMed

Meesawatsom, Pongsatorn; Burston, James; Hathway, Gareth; Bennett, Andrew; Chapman, Victoria

2016-09-02

Harnessing the actions of the resolvin pathways has the potential for the treatment of a wide range of conditions associated with overt inflammatory signalling. Aspirin-triggered resolvin D1 (AT-RvD1) has robust analgesic effects in behavioural models of pain; however, the potential underlying spinal neurophysiological mechanisms contributing to these inhibitory effects in vivo are yet to be determined. This study investigated the acute effects of spinal AT-RvD1 on evoked responses of spinal neurones in vivo in a model of acute inflammatory pain and chronic osteoarthritic (OA) pain and the relevance of alterations in spinal gene expression to these neurophysiological effects. Pain behaviour was assessed in rats with established carrageenan-induced inflammatory or monosodium iodoacetate (MIA)-induced OA pain, and changes in spinal gene expression of resolvin receptors and relevant enzymatic pathways were examined. At timepoints of established pain behaviour, responses of deep dorsal horn wide dynamic range (WDR) neurones to transcutaneous electrical stimulation of the hind paw were recorded pre- and post direct spinal administration of AT-RvD1 (15 and 150 ng/50 μl). AT-RvD1 (15 ng/50 μl) significantly inhibited WDR neurone responses to electrical stimuli at C- (29 % inhibition) and Aδ-fibre (27 % inhibition) intensities. Both wind-up (53 %) and post-discharge (46 %) responses of WDR neurones in carrageenan-treated animals were significantly inhibited by AT-RvD1, compared to pre-drug response (p < 0.05). These effects were abolished by spinal pre-administration of a formyl peptide receptor 2 (FPR2/ALX) antagonist, butoxy carbonyl-Phe-Leu-Phe-Leu-Phe (BOC-2) (50 μg/50 μl). AT-RvD1 did not alter evoked WDR neurone responses in non-inflamed or MIA-treated rats. Electrophysiological effects in carrageenan-inflamed rats were accompanied by a significant increase in messenger RNA (mRNA) for chemerin (ChemR23) receptor and 5-lipoxygenase-activating protein (FLAP) and a decrease in 15-lipoxygenase (15-LOX) mRNA in the ipsilateral spinal cord of the carrageenan group, compared to controls. Our data suggest that peripheral inflammation-mediated changes in spinal FLAP expression may contribute to the novel inhibitory effects of spinal AT-RvD1 on WDR neuronal excitability, which are mediated by FPR2/ALX receptors. Inflammatory-driven changes in this pathway may offer novel targets for inflammatory pain treatment.

Spinal cord injury below-level neuropathic pain relief with dorsal root entry zone microcoagulation performed caudal to level of complete spinal cord transection.

PubMed

Falci, Scott; Indeck, Charlotte; Barnkow, Dave

2018-06-01

OBJECTIVE Surgically created lesions of the spinal cord dorsal root entry zone (DREZ) to relieve central pain after spinal cord injury (SCI) have historically been performed at and cephalad to, but not below, the level of SCI. This study was initiated to investigate the validity of 3 proposed concepts regarding the DREZ in SCI central pain: 1) The spinal cord DREZ caudal to the level of SCI can be a primary generator of SCI below-level central pain. 2) Neuronal transmission from a DREZ that generates SCI below-level central pain to brain pain centers can be primarily through sympathetic nervous system (SNS) pathways. 3) Perceived SCI below-level central pain follows a unique somatotopic map of DREZ pain-generators. METHODS Three unique patients with both intractable SCI below-level central pain and complete spinal cord transection at the level of SCI were identified. All 3 patients had previously undergone surgical intervention to their spinal cords-only cephalad to the level of spinal cord transection-with either DREZ microcoagulation or cyst shunting, in failed attempts to relieve their SCI below-level central pain. Subsequent to these surgeries, DREZ lesioning of the spinal cord solely caudal to the level of complete spinal cord transection was performed using electrical intramedullary guidance. The follow-up period ranged from 1 1/2 to 11 years. RESULTS All 3 patients in this study had complete or near-complete relief of all below-level neuropathic pain. The analyzed electrical data confirmed and enhanced a previously proposed somatotopic map of SCI below-level DREZ pain generators. CONCLUSIONS The results of this study support the following hypotheses. 1) The spinal cord DREZ caudal to the level of SCI can be a primary generator of SCI below-level central pain. 2) Neuronal transmission from a DREZ that generates SCI below-level central pain to brain pain centers can be primarily through SNS pathways. 3) Perceived SCI below-level central pain follows a unique somatotopic map of DREZ pain generators.

Does experimental low back pain change posteroanterior lumbar spinal stiffness and trunk muscle activity? A randomized crossover study.

PubMed

Wong, Arnold Y L; Parent, Eric C; Prasad, Narasimha; Huang, Christopher; Chan, K Ming; Kawchuk, Gregory N

2016-05-01

While some patients with low back pain demonstrate increased spinal stiffness that decreases as pain subsides, this observation is inconsistent. Currently, the relation between spinal stiffness and low back pain remains unclear. This study aimed to investigate the effects of experimental low back pain on temporal changes in posteroanterior spinal stiffness and concurrent trunk muscle activity. In separate sessions five days apart, nine asymptomatic participants received equal volume injections of hypertonic or isotonic saline in random order into the L3-L5 interspinous ligaments. Pain intensity, spinal stiffness (global and terminal stiffness) at the L3 level, and the surface electromyographic activity of six trunk muscles were measured before, immediately after, and 25-minute after injections. These outcome measures under different saline conditions were compared by generalized estimating equations. Compared to isotonic saline injections, hypertonic saline injections evoked significantly higher pain intensity (mean difference: 5.7/10), higher global (mean difference: 0.73N/mm) and terminal stiffness (mean difference: 0.58N/mm), and increased activity of four trunk muscles during indentation (P<0.05). Both spinal stiffness and trunk muscle activity returned to baseline levels as pain subsided. While previous clinical research reported inconsistent findings regarding the association between spinal stiffness and low back pain, our study revealed that experimental pain caused temporary increases in spinal stiffness and concurrent trunk muscle co-contraction during indentation, which helps explain the temporal relation between spinal stiffness and low back pain observed in some clinical studies. Our results substantiate the role of spinal stiffness assessments in monitoring back pain progression. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immediate Changes Following Manual Therapy in Resting State Functional Connectivity As Measured By Magnetic Resonance Imaging (fMRI) In Subjects With Induced Low Back Pain

PubMed Central

Gay, Charles W.; Robinson, Michael E.; George, Steven Z.; Perlstein, William M.; Bishop, Mark D.

2014-01-01

Objective The purpose of this study was to use functional magnetic resonance imaging (fMRI) to investigate the immediate changes in functional connectivity (FC) between brain regions that process and modulate the pain experience following 3 different types of manual therapies (MT) and to identify reductions in experimentally induced myalgia and changes in local and remote pressure pain sensitivity. Methods Twenty-four participants (17 females, mean age ± SD = 21.6 ± 4.2 years), who completed an exercise-injury protocol to induce low back pain, were randomized into 3 groups: chiropractic spinal manipulation (n=6), spinal mobilization (n=8) or therapeutic touch (n=10). The primary outcome was the immediate change in FC as measured on fMRI between the following brain regions: somatosensory cortex, secondary somatosensory cortex, thalamus, anterior and posterior cingulate cortices, anterior and poster insula, and periaqueductal grey. Secondary outcomes were immediate changes in pain intensity measured with a 101-point numeric rating scale, and pain sensitivity, measured with a hand-held dynamometer. Repeated measures ANOVA models and correlation analyses were conducted to examine treatment effects and the relationship between within-person changes across outcome measures. Results Changes in FC were found between several brain regions that were common to all 3 manual therapy interventions. Treatment-dependent changes in FC were also observed between several brain regions. Improvement was seen in pain intensity following all interventions (p<0.05) with no difference between groups (p>0.05). There were no observed changes in pain sensitivity, or an association between primary and secondary outcome measures. Conclusion These results suggest that manual therapies (chiropractic spinal manipulation, spinal mobilization, and therapeutic touch) have an immediate effect on the FC between brain regions involved in processing and modulating the pain experience. This suggests that neurophysiological changes following MT may be an underlying mechanism of pain relief. PMID:25284739

Spinal cord processing of cardiac nociception: are there sex differences between male and proestrous female rats?

PubMed

Little, Janine M; Qin, Chao; Farber, Jay P; Foreman, Robert D

2011-09-21

Sex differences in the characteristics of cardiac pain have been reported from clinical studies. For example, women experience chest pain less frequently than men. Women describe their chest pain as sharp and stabbing, while men have chest pain that is felt as a pressure or heaviness. Pain is also referred to the back more often in women than men. The mechanisms underlying sex differences in cardiac pain are unknown. One possible mechanism for the observed differences could be related to plasma estradiol. This study investigated the actions of estradiol on the activity of T(3) spinal neurons that process cardiosomatic information in male and female rats. Extracellular potentials of T(3) spinal neurons were recorded in response to mechanical somatic stimulation and noxious chemical cardiac stimulation in pentobarbital-anesthetized male and proestrous female rats. Fifty one percent and fifty percent of neurons responded to intrapericardial algogenic chemicals (0.2 ml) in male and female rats, respectively. Somatic fields were located by applying brush, pressure, and pinch to the upper body. Of those neurons receiving cardiac input, 54% in female and 55% in male rats also received somatic input. In both male and female rats, 81% of neurons responding to somatic stimuli had somatic fields located on the side of the upper body, while 19% of neurons had somatic fields located on the chest. These results indicate there are no significant differences in the responses of T(3) spinal neurons to cardiosomatic stimulation between male and proestrous female rats, despite differences in estradiol levels. Published by Elsevier B.V.

The NAv1.7 blocker protoxin II reduces burn injury-induced spinal nociceptive processing.

PubMed

Torres-Pérez, Jose Vicente; Adamek, Pavel; Palecek, Jiri; Vizcaychipi, Marcela; Nagy, Istvan; Varga, Angelika

2018-01-01

Controlling pain in burn-injured patients poses a major clinical challenge. Recent findings suggest that reducing the activity of the voltage-gated sodium channel Na v 1.7 in primary sensory neurons could provide improved pain control in burn-injured patients. Here, we report that partial thickness scalding-type burn injury on the rat paw upregulates Na v 1.7 expression in primary sensory neurons 3 h following injury. The injury also induces upregulation in phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB), a marker for nociceptive activation in primary sensory neurons. The upregulation in p-CREB occurs mainly in Na v 1.7-immunopositive neurons and exhibits a peak at 5 min and, following a decline at 30 min, a gradual increase from 1 h post-injury. The Na v 1.7 blocker protoxin II (ProTxII) or morphine injected intraperitoneally 15 min before or after the injury significantly reduces burn injury-induced spinal upregulation in phosphorylated serine 10 in histone H3 and phosphorylated extracellular signal-regulated kinase 1/2, which are both markers for spinal nociceptive processing. Further, ProTxII significantly reduces the frequency of spontaneous excitatory post-synaptic currents in spinal dorsal horn neurons following burn injury. Together, these findings indicate that using Na v 1.7 blockers should be considered to control pain in burn injury. • Burn injury upregulates Na v 1.7 expression in primary sensory neurons. • Burn injury results in increased activity of Na v 1.7-expressing primary sensory neurons. • Inhibiting Na v 1.7 by protoxin II reduces spinal nociceptive processing. • Na v 1.7 represents a potential target to reduce pain in burn injury.

Spinal pain and co-occurrence with stress and general well-being among young adolescents: a study within the Danish National Birth Cohort.

PubMed

Stallknecht, Sandra Elkjær; Strandberg-Larsen, Katrine; Hestbæk, Lise; Andersen, Anne-Marie Nybo

2017-06-01

This study aims to describe the patterns in low back, mid back, and neck pain complaints in young adolescents from the Danish National Birth Cohort (DNBC) and to investigate the co-occurrence of spinal pain and stress and general well-being, respectively. Cross-sectional data from the 11-year follow-up of DNBC were used. As part of a web-based survey, a total of 45,371 young adolescents between 10 and 14 years old completed the Young Spine Questionnaire, the Stress in Children Questionnaire, and a one-item question on general well-being. Associations between spinal pain and, respectively, stress and general well-being were estimated by means of multiple logistic regression models. Almost one fifth of boys and one quarter of girls reported spinal pain. Compared with adolescents who reported no stress, adolescents reporting medium and high values of stress had odds ratios (OR) of 2.19 (95% CI 2.08-2.30) and 4.73 (95% CI 4.28-5.23), respectively, of reporting spinal pain (adjusted for age, gender, and maternal education). Adolescents who reported poor general well-being had an OR of 2.50 (95% CI 2.31-2.72) for reporting spinal pain compared to adolescents with good general well-being. Spinal pain is a common complaint among young adolescents and co-occurs with stress and poor general well-being. The mutual dependency between the factors remained to be explained. What is Known: • The prevalence of spinal pain increases rapidly during childhood and adolescence, but different measurement instruments result in great variation in the estimates of spinal pain in children and adolescents. • Some studies have shown that different psychosocial measures are associated with spinal pain in children and adolescents. What is New: • Spinal pain, as measured by the newly developed and validated Young Spine Questionnaire, is a common complaint in young adolescents aged 10-14 years. • Spinal pain in young adolescents co-occurs with stress and poor general well-being.

Interdisciplinary Cognitive-Behavioral Therapy as Part of Lumbar Spinal Fusion Surgery Rehabilitation: Experience of Patients With Chronic Low Back Pain.

PubMed

Lindgreen, Pil; Rolving, Nanna; Nielsen, Claus Vinther; Lomborg, Kirsten

2016-01-01

Patients receiving lumbar spinal fusion surgery often have persisting postoperative pain negatively affecting their daily life. These patients may be helped by interdisciplinary cognitive-behavioral therapy which is recognized as an effective intervention for improving beneficial pain coping behavior, thereby facilitating the rehabilitation process of patients with chronic pain. The purpose of this study was to describe the lived experience of patients recovering from lumbar spinal fusion surgery and to explore potential similarities and disparities in pain coping behavior between receivers and nonreceivers of interdisciplinary cognitive-behavioral group therapy. We conducted semistructured interviews with 10 patients; 5 receiving cognitive-behavioral therapy in connection with their lumbar spinal fusion surgery and 5 receiving usual care. We conducted a phenomenological analysis to reach our first aim and then conducted a comparative content analysis to reach our second aim. Patients' postoperative experience was characterized by the need to adapt to the limitations imposed by back discomfort (coexisting with the back), need for recognition and support from others regarding their pain, a relatively long rehabilitation period during which they "awaited the result of surgery", and ambivalence toward analgesics. The patients in both groups had similar negative perception of analgesics and tended to abstain from them to avoid addiction. Coping behavior apparently differed among receivers and nonreceivers of interdisciplinary cognitive-behavioral group therapy. Receivers prevented or minimized pain by resting before pain onset, whereas nonreceivers awaited pain onset before resting. The postoperative experience entailed ambivalence, causing uncertainty, worry and insecurity. This ambivalence was relieved when others recognized the patient's pain and offered support. Cognitive-behavioral therapy as part of rehabilitation may have encouraged beneficial pain coping behavior by altering patients' pain perception and coping behavior, thereby reducing adverse effects of pain.

The VGF-derived peptide TLQP-21 contributes to inflammatory and nerve injury-induced hypersensitivity.

PubMed

Fairbanks, Carolyn A; Peterson, Cristina D; Speltz, Rebecca H; Riedl, Maureen S; Kitto, Kelley F; Dykstra, Jaclyn A; Braun, Patrick D; Sadahiro, Masato; Salton, Stephen R; Vulchanova, Lucy

2014-07-01

VGF (nonacronymic) is a granin-like protein that is packaged and proteolytically processed within the regulated secretory pathway. VGF and peptides derived from its processing have been implicated in neuroplasticity associated with learning, memory, depression, and chronic pain. In sensory neurons, VGF is rapidly increased following peripheral nerve injury and inflammation. Several bioactive peptides generated from the C-terminus of VGF have pronociceptive spinal effects. The goal of the present study was to examine the spinal effects of the peptide TLQP-21 and determine whether it participates in spinal mechanisms of persistent pain. Application of exogenous TLQP-21 induced dose-dependent thermal hyperalgesia in the warm-water immersion tail-withdrawal test. This hyperalgesia was inhibited by a p38 mitogen-activated protein kinase inhibitor, as well as inhibitors of cyclooxygenase and lipoxygenase. We used immunoneutralization of TLQP-21 to determine the function of the endogenous peptide in mechanisms underlying persistent pain. In mice injected intradermally with complete Freund adjuvant, intrathecal treatment with anti-TLQP-21 immediately prior to or 5hours after induction of inflammation dose-dependently inhibited tactile hypersensitivity and thermal hyperalgesia. Intrathecal anti-TL21 administration also attenuated the development and maintenance of tactile hypersensitivity in the spared nerve injury model of neuropathic pain. These results provide evidence that endogenous TLQP-21 peptide contributes to the mechanisms of spinal neuroplasticity after inflammation and nerve injury. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Intrathecal injection of carbenoxolone, a gap junction decoupler, attenuates the induction of below-level neuropathic pain after spinal cord injury in rats.

PubMed

Roh, Dae-Hyun; Yoon, Seo-Yeon; Seo, Hyoung-Sig; Kang, Suk-Yun; Han, Ho-Jae; Beitz, Alvin J; Lee, Jang-Hern

2010-07-01

The most common type of chronic pain following spinal cord injury (SCI) is central neuropathic pain and SCI patients typically experience mechanical allodynia and thermal hyperalgesia. The present study was designed to examine the potential role of astrocyte gap junction connectivity in the induction and maintenance of "below-level" neuropathic pain in SCI rats. We examined the effect of intrathecal treatment with carbenoxolone (CARB), a gap junction decoupler, on SCI-induced bilateral thermal hyperalgesia and mechanical allodynia during the induction phase (postoperative days 0 to 5) and the maintenance phase (days 15 to 20) following T13 spinal cord hemisection. Immunohistochemistry was performed to determine potential SCI-induced changes in spinal astrocyte activation and phosphorylation of the NMDA receptor NR1 subunit (pNR1). CARB administered during the induction period dose-dependently attenuated the development of bilateral thermal hyperalgesia and mechanical allodynia. Intrathecal CARB also significantly reduced the bilateral SCI-induced increase in GFAP-immunoreactive (ir) staining and the number of pNR1-ir cell profiles in the spinal cord dorsal horn compared to vehicle-treated rats. In contrast, CARB treatment during the maintenance phase had no effect on the established thermal hyperalgesia and mechanical allodynia nor on spinal GFAP expression or the number of pNR1-ir cell profiles. These results indicate that gap junctions play a critical role in the activation of astrocytes distant from the site of SCI and in the subsequent phosphorylation of NMDA receptors in the lumbar spinal cord. Both of these processes appear to contribute to the induction of bilateral below-level pain in SCI rats. Copyright 2010 Elsevier Inc. All rights reserved.

JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain

PubMed Central

Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R.; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

2009-01-01

Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, TNF-α transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-α/JNK pathway. MCP-1 upregulation by TNF-α was dose-dependently inhibited by the JNK inhibitors SP600125 and D-JNKI-1. Spinal injection of TNF-α produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Further, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase (ERK) in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous excitatory synaptic currents (sEPSCs) but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Taken together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes following JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management. PMID:19339605

Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

PubMed Central

2011-01-01

Long-term potentiation (LTP) in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents. PMID:21443797

Subclinical recurrent neck pain and its treatment impacts motor training-induced plasticity of the cerebellum and motor cortex

PubMed Central

Baarbé, Julianne K.; Yielder, Paul; Haavik, Heidi; Holmes, Michael W. R.

2018-01-01

The cerebellum processes pain inputs and is important for motor learning. Yet, how the cerebellum interacts with the motor cortex in individuals with recurrent pain is not clear. Functional connectivity between the cerebellum and motor cortex can be measured by a twin coil transcranial magnetic stimulation technique in which stimulation is applied to the cerebellum prior to stimulation over the motor cortex, which inhibits motor evoked potentials (MEPs) produced by motor cortex stimulation alone, called cerebellar inhibition (CBI). Healthy individuals without pain have been shown to demonstrate reduced CBI following motor acquisition. We hypothesized that CBI would not reduce to the same extent in those with mild-recurrent neck pain following the same motor acquisition task. We further hypothesized that a common treatment for neck pain (spinal manipulation) would restore reduced CBI following motor acquisition. Motor acquisition involved typing an eight-letter sequence of the letters Z,P,D,F with the right index finger. Twenty-seven neck pain participants received spinal manipulation (14 participants, 18–27 years) or sham control (13 participants, 19–24 years). Twelve healthy controls (20–27 years) also participated. Participants had CBI measured; they completed manipulation or sham control followed by motor acquisition; and then had CBI re-measured. Following motor acquisition, neck pain sham controls remained inhibited (58 ± 33% of test MEP) vs. healthy controls who disinhibited (98 ± 49% of test MEP, P<0.001), while the spinal manipulation group facilitated (146 ± 95% of test MEP, P<0.001). Greater inhibition in neck pain sham vs. healthy control groups suggests that neck pain may change cerebellar-motor cortex interaction. The change to facilitation suggests that spinal manipulation may reverse inhibitory effects of neck pain. PMID:29489878

21 CFR 882.5880 - Implanted spinal cord stimulator for pain relief.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted spinal cord stimulator for pain relief. 882.5880 Section 882.5880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Implanted spinal cord stimulator for pain relief. (a) Identification. An implanted spinal cord stimulator...

Sensory processing of deep tissue nociception in the rat spinal cord and thalamic ventrobasal complex.

PubMed

Sikandar, Shafaq; West, Steven J; McMahon, Stephen B; Bennett, David L; Dickenson, Anthony H

2017-07-01

Sensory processing of deep somatic tissue constitutes an important component of the nociceptive system, yet associated central processing pathways remain poorly understood. Here, we provide a novel electrophysiological characterization and immunohistochemical analysis of neural activation in the lateral spinal nucleus (LSN). These neurons show evoked activity to deep, but not cutaneous, stimulation. The evoked responses of neurons in the LSN can be sensitized to somatosensory stimulation following intramuscular hypertonic saline, an acute model of muscle pain, suggesting this is an important spinal relay site for the processing of deep tissue nociceptive inputs. Neurons of the thalamic ventrobasal complex (VBC) mediate both cutaneous and deep tissue sensory processing, but in contrast to the lateral spinal nucleus our electrophysiological studies do not suggest the existence of a subgroup of cells that selectively process deep tissue inputs. The sensitization of polymodal and thermospecific VBC neurons to mechanical somatosensory stimulation following acute muscle stimulation with hypertonic saline suggests differential roles of thalamic subpopulations in mediating cutaneous and deep tissue nociception in pathological states. Overall, our studies at both the spinal (lateral spinal nucleus) and supraspinal (thalamic ventrobasal complex) levels suggest a convergence of cutaneous and deep somatosensory inputs onto spinothalamic pathways, which are unmasked by activation of muscle nociceptive afferents to produce consequent phenotypic alterations in spinal and thalamic neural coding of somatosensory stimulation. A better understanding of the sensory pathways involved in deep tissue nociception, as well as the degree of labeled line and convergent pathways for cutaneous and deep somatosensory inputs, is fundamental to developing targeted analgesic therapies for deep pain syndromes. © 2017 University College London. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Increased excitability of spinal pain reflexes and altered frequency-dependent modulation in the dopamine D3-receptor knockout mouse.

PubMed

Keeler, Benjamin E; Baran, Christine A; Brewer, Kori L; Clemens, Stefan

2012-12-01

Frequency-dependent modulation and dopamine (DA) receptors strongly modulate neural circuits in the spinal cord. Of the five known DA receptor subtypes, the D3 receptor has the highest affinity to DA, and D3-mediated actions are mainly inhibitory. Using an animal model of spinal sensorimotor dysfunction, the D3 receptor knockout mouse (D3KO), we investigated the physiological consequences of D3 receptor dysfunction on pain-associated signaling pathways in the spinal cord, the initial integration site for the processing of pain signaling. In the D3KO spinal cord, inhibitory actions of DA on the proprioceptive monosynaptic stretch reflex are converted from depression to facilitation, but its effects on longer-latency and pain-associated reflex responses and the effects of FM have not been studied. Using behavioral approaches in vivo, we found that D3KO animals exhibit reduced paw withdrawal latencies to thermal pain stimulation (Hargreaves' test) over wild type (WT) controls. Electrophysiological and pharmacological approaches in the isolated spinal cord in vitro showed that constant current stimulation of dorsal roots at a pain-associated frequency was associated with a significant reduction in the frequency-dependent modulation of longer-latency reflex (LLRs) responses but not monosynaptic stretch reflexes (MSRs) in D3KO. Application of the D1 and D2 receptor agonists and the voltage-gated calcium-channel ligand, pregabalin, but not DA, was able to restore the frequency-dependent modulation of the LLR in D3KO to WT levels. Thus we demonstrate that nociception-associated LLRs and proprioceptive MSRs are differentially modulated by frequency, dopaminergics and the Ca(2+) channel ligand, pregabalin. Our data suggest a role for the DA D3 receptor in pain modulation and identify the D3KO as a possible model for increased nociception. Copyright © 2012 Elsevier Inc. All rights reserved.

Spinal Actions of Lipoxin A4 and 17(R)-Resolvin D1 Attenuate Inflammation-Induced Mechanical Hypersensitivity and Spinal TNF Release

PubMed Central

Abdelmoaty, Sally; Wigerblad, Gustaf; Bas, Duygu B.; Codeluppi, Simone; Fernandez-Zafra, Teresa; El-Awady, El-Sayed; Moustafa, Yasser; Abdelhamid, Alaa El-din S.; Brodin, Ernst; Svensson, Camilla I.

2013-01-01

Lipoxins and resolvins have anti-inflammatory and pro-resolving actions and accumulating evidence indicates that these lipid mediators also attenuate pain-like behavior in a number of experimental models of inflammation and tissue injury-induced pain. The present study was undertaken to assess if spinal administration of lipoxin A4 (LXA4) or 17 (R)-resolvin D1 (17(R)-RvD1) attenuates mechanical hypersensitivity in the carrageenan model of peripheral inflammation in the rat. Given the emerging role of spinal cytokines in the generation and maintenance of inflammatory pain we measured cytokine levels in the cerebrospinal fluid (CSF) after LXA4 or 17(R)-RvD1 administration, and the ability of these lipid metabolites to prevent stimuli-induced release of cytokines from cultured primary spinal astrocytes. We found that intrathecal bolus injection of LXA4 and17(R)-RvD1 attenuated inflammation-induced mechanical hypersensitivity without reducing the local inflammation. Furthermore, both LXA4 and 17(R)-RvD1 reduced carrageenan-induced tumor necrosis factor (TNF) release in the CSF, while only 17(R)-RvD1attenuated LPS and IFN-γ-induced TNF release in astrocyte cell culture. In conclusion, this study demonstrates that lipoxins and resolvins potently suppress inflammation-induced mechanical hypersensitivity, possibly by attenuating cytokine release from spinal astrocytes. The inhibitory effect of lipoxins and resolvins on spinal nociceptive processing puts them in an intriguing position in the search for novel pain therapeutics. PMID:24086560

Distinct functions of opioid-related peptides and gastrin-releasing peptide in regulating itch and pain in the spinal cord of primates.

PubMed

Lee, Heeseung; Ko, Mei-Chuan

2015-06-29

How neuropeptides in the primate spinal cord regulate itch and pain is largely unknown. Here we elucidate the sensory functions of spinal opioid-related peptides and gastrin-releasing peptide (GRP) in awake, behaving monkeys. Following intrathecal administration, β-endorphin (10-100 nmol) and GRP (1-10 nmol) dose-dependently elicit the same degree of robust itch scratching, which can be inhibited by mu-opioid peptide (MOP) receptor and GRP receptor (BB2) antagonists, respectively. Unlike β-endorphin, which produces itch and attenuates inflammatory pain, GRP only elicits itch without affecting pain. In contrast, enkephalins (100-1000 nmol) and nociceptin-orphanin FQ (3-30 nmol) only inhibit pain without eliciting itch. More intriguingly, dynorphin A(1-17) (10-100 nmol) dose-dependently attenuates both β-endorphin- and GRP-elicited robust scratching without affecting pain processing. The anti-itch effects of dynorphin A can be reversed by a kappa-opioid peptide (KOP) receptor antagonist nor-binaltorphimine. These nonhuman primate behavioral models with spinal delivery of ligands advance our understanding of distinct functions of neuropeptides for modulating itch and pain. In particular, we demonstrate causal links for itch-eliciting effects by β-endorphin-MOP receptor and GRP-BB2 receptor systems and itch-inhibiting effects by the dynorphin A-KOP receptor system. These studies will facilitate transforming discoveries of novel ligand-receptor systems into future therapies as antipruritics and/or analgesics in humans.

The CanPain SCI Clinical Practice Guidelines for Rehabilitation Management of Neuropathic Pain after Spinal Cord: screening and diagnosis recommendations.

PubMed

Mehta, S; Guy, S D; Bryce, T N; Craven, B C; Finnerup, N B; Hitzig, S L; Orenczuk, S; Siddall, P J; Widerström-Noga, E; Casalino, A; Côté, I; Harvey, D; Kras-Dupuis, A; Lau, B; Middleton, J W; Moulin, D E; O'Connell, C; Parrent, A G; Potter, P; Short, C; Teasell, R; Townson, A; Truchon, C; Wolfe, D; Bradbury, C L; Loh, E

2016-08-01

Clinical practice guidelines. To develop the first Canadian clinical practice guidelines for screening and diagnosis of neuropathic pain in people with spinal cord injury (SCI). The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. The CanPainSCI Working Group reviewed evidence to address clinical questions regarding screening and diagnosis of neuropathic pain after SCI. A consensus process was followed to achieve agreement on recommendations and clinical considerations. Twelve recommendations, based on expert consensus, were developed for the screening and diagnosis of neuropathic pain after SCI. The recommendations address methods for assessment, documentation tools, team member accountability, frequency of screening and considerations for diagnostic investigation. Important clinical considerations accompany each recommendation. The expert Working Group developed recommendations for the screening and diagnosis of neuropathic pain after SCI that should be used to inform practice.

The Animal Model of Spinal Cord Injury as an Experimental Pain Model

PubMed Central

Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

2011-01-01

Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. PMID:21436995

A multidisciplinary cognitive behavioural programme for coping with chronic neuropathic pain following spinal cord injury: the protocol of the CONECSI trial

PubMed Central

2010-01-01

Background Most people with a spinal cord injury rate neuropathic pain as one of the most difficult problems to manage and there are no medical treatments that provide satisfactory pain relief in most people. Furthermore, psychosocial factors have been considered in the maintenance and aggravation of neuropathic spinal cord injury pain. Psychological interventions to support people with spinal cord injury to deal with neuropathic pain, however, are sparse. The primary aim of the CONECSI (COping with NEuropathiC Spinal cord Injury pain) trial is to evaluate the effects of a multidisciplinary cognitive behavioural treatment programme on pain intensity and pain-related disability, and secondary on mood, participation in activities, and life satisfaction. Methods/Design CONECSI is a multicentre randomised controlled trial. A sample of 60 persons with chronic neuropathic spinal cord injury pain will be recruited from four rehabilitation centres and randomised to an intervention group or a waiting list control group. The control group will be invited for the programme six months after the intervention group. Main inclusion criteria are: having chronic (> 6 months) neuropathic spinal cord injury pain as the worst pain complaint and rating the pain intensity in the last week as 40 or more on a 0-100 scale. The intervention consists of educational, cognitive, and behavioural elements and encompasses 11 sessions over a 3-month period. Each meeting will be supervised by a local psychologist and physical therapist. Measurements will be perfomed before starting the programme/entering the control group, and at 3, 6, 9, and 12 months. Primary outcomes are pain intensity and pain-related disability (Chronic Pain Grade questionnaire). Secondary outcomes are mood (Hospital Anxiety and Depression Scale), participation in activities (Utrecht Activities List), and life satisfaction (Life Satisfaction Questionnaire). Pain coping and pain cognitions will be assessed with three questionnaires (Coping Strategy Questionnaire, Pain Coping Inventory, and Pain Cognition List). Discussion The CONECSI trial will reveal the effects of a multidisciplinary cognitive behavioural programme for people with chronic neuropathic spinal cord injury pain. This intervention is expected to contribute to the rehabilitation treatment possibilities for this population. Trial Registration Dutch Trial Register NTR1580. PMID:20961406

Spinal Cord Stimulation (SCS) and Functional Magnetic Resonance Imaging (fMRI): Modulation of Cortical Connectivity With Therapeutic SCS.

PubMed

Deogaonkar, Milind; Sharma, Mayur; Oluigbo, Chima; Nielson, Dylan M; Yang, Xiangyu; Vera-Portocarrero, Louis; Molnar, Gregory F; Abduljalil, Amir; Sederberg, Per B; Knopp, Michael; Rezai, Ali R

2016-02-01

The neurophysiological basis of pain relief due to spinal cord stimulation (SCS) and the related cortical processing of sensory information are not completely understood. The aim of this study was to use resting state functional magnetic resonance imaging (rs-fMRI) to detect changes in cortical networks and cortical processing related to the stimulator-induced pain relief. Ten patients with complex regional pain syndrome (CRPS) or neuropathic leg pain underwent thoracic epidural spinal cord stimulator implantation. Stimulation parameters associated with "optimal" pain reduction were evaluated prior to imaging studies. Rs-fMRI was obtained on a 3 Tesla, Philips Achieva MRI. Rs-fMRI was performed with stimulator off (300TRs) and stimulator at optimum (Opt, 300 TRs) pain relief settings. Seed-based analysis of the resting state functional connectivity was conducted using seeds in regions established as participating in pain networks or in the default mode network (DMN) in addition to the network analysis. NCUT (normalized cut) parcellation was used to generate 98 cortical and subcortical regions of interest in order to expand our analysis of changes in functional connections to the entire brain. We corrected for multiple comparisons by limiting the false discovery rate to 5%. Significant differences in resting state connectivity between SCS off and optimal state were seen between several regions related to pain perception, including the left frontal insula, right primary and secondary somatosensory cortices, as well as in regions involved in the DMN, such as the precuneus. In examining changes in connectivity across the entire brain, we found decreased connection strength between somatosensory and limbic areas and increased connection strength between somatosensory and DMN with optimal SCS resulting in pain relief. This suggests that pain relief from SCS may be reducing negative emotional processing associated with pain, allowing somatosensory areas to become more integrated into default mode activity. SCS reduces the affective component of pain resulting in optimal pain relief. Study shows a decreased connectivity between somatosensory and limbic areas associated with optimal pain relief due to SCS. © 2015 International Neuromodulation Society.

Spinal Disinhibition in Experimental and Clinical Painful Diabetic Neuropathy

PubMed Central

Marshall, Andrew G.; Lee-Kubli, Corinne; Azmi, Shazli; Zhang, Michael; Ferdousi, Maryam; Mixcoatl-Zecuatl, Teresa; Petropoulos, Ioannis N.; Ponirakis, Georgios; Fineman, Mark S.; Fadavi, Hassan; Frizzi, Katie; Tavakoli, Mitra; Jolivalt, Corinne G.; Boulton, Andrew J.M.; Efron, Nathan; Calcutt, Nigel A.

2017-01-01

Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal γ-aminobutyric acid type A receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5-hydroxytryptamine type 2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy compared with healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fiber pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine. PMID:28202580

The impact of pain on spiritual well-being in people with a spinal cord injury.

PubMed

Siddall, P J; McIndoe, L; Austin, P; Wrigley, P J

2017-01-01

The study uses a cross-sectional, group comparison, questionnaire-based design. To determine whether spinal cord injury and pain have an impact on spiritual well-being and whether there is an association between spiritual well-being and measures of pain and psychological function. University teaching hospital in Sydney, New South Wales, Australia. Questionnaires evaluating pain, psychological and spiritual well-being were administered to a group of people with a spinal cord injury (n=53) and a group without spinal cord injury (n=37). Spiritual well-being was assessed using the Functional Assessment of Chronic Illness and Therapy - Spirituality Extended Scale (FACIT-Sp-Ex). Pain and psychological function were also assessed using standard, validated measures of pain intensity, pain interference, mood and cognition. Levels of spiritual well-being in people with a spinal cord injury were significantly lower when compared with people without a spinal cord injury. In addition, there was a moderate but significant negative correlation between spiritual well-being and pain intensity. There was also a strong and significant negative correlation between depression and spiritual well-being and a strong and significant positive correlation between spiritual well-being and both pain self-efficacy and satisfaction with life. Consequences of a spinal cord injury include increased levels of spiritual distress, which is associated, with higher levels of pain and depression and lower levels of pain self-efficacy and satisfaction with life. These findings indicate the importance of addressing spiritual well-being as an important component in the long-term rehabilitation of any person following spinal cord injury. This study was supported by grant funding from the Australian and New Zealand College of Anaesthetists, and the National Health and Medical Research Council of Australia.

Three combinations of manual therapy techniques within naprapathy in the treatment of neck and/or back pain: a randomized controlled trial.

PubMed

Paanalahti, Kari; Holm, Lena W; Nordin, Margareta; Höijer, Jonas; Lyander, Jessica; Asker, Martin; Skillgate, Eva

2016-04-23

Manual therapy as spinal manipulation, spinal mobilization, stretching and massage are common treatment methods for neck and back pain. The objective was to compare the treatment effect on pain intensity, pain related disability and perceived recovery from a) naprapathic manual therapy (spinal manipulation, spinal mobilization, stretching and massage) to b) naprapathic manual therapy without spinal manipulation and to c) naprapathic manual therapy without stretching for male and female patients seeking care for back and/or neck pain. Participants were recruited among patients, ages 18-65, seeking care at the educational clinic of Naprapathögskolan - the Scandinavian College of Naprapathic Manual Medicine in Stockholm. The patients (n = 1057) were randomized to one of three treatment arms a) manual therapy (i.e. spinal manipulation, spinal mobilization, stretching and massage), b) manual therapy excluding spinal manipulation and c) manual therapy excluding stretching. The primary outcomes were minimal clinically important improvement in pain intensity and pain related disability. Treatments were provided by naprapath students in the seventh semester of eight total semesters. Generalized estimating equations and logistic regression were used to examine the association between the treatments and the outcomes. At 12 weeks follow-up, 64% had a minimal clinically important improvement in pain intensity and 42% in pain related disability. The corresponding chances to be improved at the 52 weeks follow-up were 58% and 40% respectively. No systematic differences in effect when excluding spinal manipulation and stretching respectively from the treatment were found over 1 year follow-up, concerning minimal clinically important improvement in pain intensity (p = 0.41) and pain related disability (p = 0.85) and perceived recovery (p = 0.98). Neither were there disparities in effect when male and female patients were analyzed separately. The effect of manual therapy for male and female patients seeking care for neck and/or back pain at an educational clinic is similar regardless if spinal manipulation or if stretching is excluded from the treatment option. Current Controlled Trials ISRCTN92249294.

Indicating spinal joint mobilisations or manipulations in patients with neck or low-back pain: protocol of an inter-examiner reliability study among manual therapists.

PubMed

van Trijffel, Emiel; Lindeboom, Robert; Bossuyt, Patrick Mm; Schmitt, Maarten A; Lucas, Cees; Koes, Bart W; Oostendorp, Rob Ab

2014-01-01

Manual spinal joint mobilisations and manipulations are widely used treatments in patients with neck and low-back pain. Inter-examiner reliability of passive intervertebral motion assessment of the cervical and lumbar spine, perceived as important for indicating these interventions, is poor within a univariable approach. The diagnostic process as a whole in daily practice in manual therapy has a multivariable character, however, in which the use and interpretation of passive intervertebral motion assessment depend on earlier results from the diagnostic process. To date, the inter-examiner reliability among manual therapists of a multivariable diagnostic decision-making process in patients with neck or low-back pain is unknown. This study will be conducted as a repeated-measures design in which 14 pairs of manual therapists independently examine a consecutive series of a planned total of 165 patients with neck or low-back pain presenting in primary care physiotherapy. Primary outcome measure is therapists' decision about whether or not manual spinal joint mobilisations or manipulations, or both, are indicated in each patient, alone or as part of a multimodal treatment. Therapists will largely be free to conduct the full diagnostic process based on their formulated examination objectives. For each pair of therapists, 2×2 tables will be constructed and reliability for the dichotomous decision will be expressed using Cohen's kappa. In addition, observed agreement, prevalence of positive decisions, prevalence index, bias index, and specific agreement in positive and negative decisions will be calculated. Univariable logistic regression analysis of concordant decisions will be performed to explore which demographic, professional, or clinical factors contributed to reliability. This study will provide an estimate of the inter-examiner reliability among manual therapists of indicating spinal joint mobilisations or manipulations in patients with neck or low-back pain based on a multivariable diagnostic reasoning and decision-making process, as opposed to reliability of individual tests. As such, it is proposed as an initial step toward the development of an alternative approach to current classification systems and prediction rules for identifying those patients with spinal disorders that may show a better response to manual therapy which can be incorporated in randomised clinical trials. Potential methodological limitations of this study are discussed.

Indicating spinal joint mobilisations or manipulations in patients with neck or low-back pain: protocol of an inter-examiner reliability study among manual therapists

PubMed Central

2014-01-01

Background Manual spinal joint mobilisations and manipulations are widely used treatments in patients with neck and low-back pain. Inter-examiner reliability of passive intervertebral motion assessment of the cervical and lumbar spine, perceived as important for indicating these interventions, is poor within a univariable approach. The diagnostic process as a whole in daily practice in manual therapy has a multivariable character, however, in which the use and interpretation of passive intervertebral motion assessment depend on earlier results from the diagnostic process. To date, the inter-examiner reliability among manual therapists of a multivariable diagnostic decision-making process in patients with neck or low-back pain is unknown. Methods This study will be conducted as a repeated-measures design in which 14 pairs of manual therapists independently examine a consecutive series of a planned total of 165 patients with neck or low-back pain presenting in primary care physiotherapy. Primary outcome measure is therapists’ decision about whether or not manual spinal joint mobilisations or manipulations, or both, are indicated in each patient, alone or as part of a multimodal treatment. Therapists will largely be free to conduct the full diagnostic process based on their formulated examination objectives. For each pair of therapists, 2×2 tables will be constructed and reliability for the dichotomous decision will be expressed using Cohen’s kappa. In addition, observed agreement, prevalence of positive decisions, prevalence index, bias index, and specific agreement in positive and negative decisions will be calculated. Univariable logistic regression analysis of concordant decisions will be performed to explore which demographic, professional, or clinical factors contributed to reliability. Discussion This study will provide an estimate of the inter-examiner reliability among manual therapists of indicating spinal joint mobilisations or manipulations in patients with neck or low-back pain based on a multivariable diagnostic reasoning and decision-making process, as opposed to reliability of individual tests. As such, it is proposed as an initial step toward the development of an alternative approach to current classification systems and prediction rules for identifying those patients with spinal disorders that may show a better response to manual therapy which can be incorporated in randomised clinical trials. Potential methodological limitations of this study are discussed. PMID:24982754

JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.

PubMed

Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

2009-04-01

Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.

Effect of spinal monoaminergic neuronal system dysfunction on pain threshold in rats, and the analgesic effect of serotonin and norepinephrine reuptake inhibitors.

PubMed

Tamano, Ryuta; Ishida, Mitsuhiro; Asaki, Toshiyuki; Hasegawa, Minoru; Shinohara, Shunji

2016-02-26

Dysfunction in the central serotonin (5-HT) and norepinephrine (NE) systems cause depression and pain. Descending spinal pain modulatory pathways are important in the analgesic mechanisms of antidepressants, particularly serotonin and norepinephrine reuptake inhibitors (SNRIs). While many non-clinical studies have demonstrated the roles of central monoaminergic systems in pain, there is little evidence to illuminate the direct contribution of spinal descending pain modulatory systems independently of depressive-like behavior. To examine the effects of dysfunction of spinal monoaminergic systems on pain sensitivity, we established a rat chronic pain model by administering lumbar-intrathecal reserpine to minimize its influence on brain. Lumbar-intrathecal reserpine evoked persistent mechanical hypersensitivity and corresponding reductions in spinal 5-HT and NE concentrations (from 767.2 to 241.6ng/g and from 455.9 to 41.7ng/g, respectively after reserpine 30nmol). Lumbar-intrathecal reserpine did not deplete brain monoamines or bring about depressive-like behavior in the forced swim test. Spinal monoamines depletion-induced pain sensitivity was ameliorated by lumbar-intrathecal administration of the SNRIs (duloxetine and milnacipran) in dose-dependent manners. These suggest that increased pain sensitivity could be induced by dysfunction solely of the descending pain modulatory system, regardless of depressive-like behavior, and lumbar-intrathecal administration of SNRIs could ameliorate the pain sensitivity which might be mediated by affecting the descending pain modulatory system in the spinal cord, not via their antidepressant effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Emerging Role of Spinal Dynorphin in Chronic Pain, a Therapeutic Perspective

PubMed Central

Podvin, Sonia; Yaksh, Tony; Hook, Vivian

2016-01-01

Notable findings point to the significance of the dynorphin peptide neurotransmitter in chronic pain. Spinal dynorphin neuropeptide levels are elevated during development of chronic pain. Importantly, knockout of the dynorphin gene prevents development of chronic pain in mice, but acute nociception is unaffected. Intrathecal (IT) administration of opioid and non-opioid dynorphin peptides initiate allodynia through a non-opioid receptor mechanism; furthermore, anti-dynorphin antibodies administered by the IT route attenuate chronic pain. Thus, this review presents the compelling evidence in the field supporting the role of dynorphin in facilitating the development of a persistent pain state. These observations raise the question of the control mechanisms responsible for the upregulation of spinal dynorphin leading to chronic pain development. Also, spinal dynorphin regulation of downstream signaling molecules may be implicated in hyperpathic states. Therapeutic strategies to reduce spinal dynorphin may provide a non-addictive approach to improve the devastating condition of chronic pain that occurs in numerous human diseases. PMID:26738478

Prevalence of chronic spinal pain and identification of associated factors in a sample of the population of São Paulo, Brazil: cross-sectional study.

PubMed

Depintor, Jidiene Dylese Presecatan; Bracher, Eduardo Sawaya Botelho; Cabral, Dayane Maia Costa; Eluf-Neto, José

2016-01-01

Chronic spinal pain, especially low-back pain and neck pain, is a leading cause of years of life with disability. The aim of the present study was to estimate the prevalence of chronic spinal pain among individuals aged 15 years or older and to identify the factors associated with it. Cross-sectional epidemiological study on a sample of the population of the city of São Paulo. Participants were selected using random probabilistic sampling and data were collected via face-to-face interviews. The Hospital Anxiety and Depression Scale (HADS), EuroQol-5D, Alcohol Use Disorders Identification Test (AUDIT), Fagerström test for nicotine dependence and Brazilian economic classification criteria were used. A total of 826 participants were interviewed. The estimated prevalence of chronic spinal pain was 22% (95% confidence interval, CI: 19.3-25.0%). The factors independently associated with chronic spinal pain were: female sex, age 30 years or older, schooling level of four years or less, symptoms compatible with anxiety and high physical exertion during the main occupation. Quality of life and self-rated health scores were significantly worse among individuals with chronic spinal pain. The prevalence of chronic spinal pain in this segment of the population of São Paulo was 22.0%. The factors independently associated with chronic pain were: female sex, age 30 years or older, low education, symptoms compatible with anxiety and physical exertion during the main occupation.

Inhibition of Neuroinflammation by AIBP: Spinal Effects upon Facilitated Pain States.

PubMed

Woller, Sarah A; Choi, Soo-Ho; An, Eun Jung; Low, Hann; Schneider, Dina A; Ramachandran, Roshni; Kim, Jungsu; Bae, Yun Soo; Sviridov, Dmitri; Corr, Maripat; Yaksh, Tony L; Miller, Yury I

2018-05-29

Apolipoprotein A-I binding protein (AIBP) reduces lipid raft abundance by augmenting the removal of excess cholesterol from the plasma membrane. Here, we report that AIBP prevents and reverses processes associated with neuroinflammatory-mediated spinal nociceptive processing. The mechanism involves AIBP binding to Toll-like receptor-4 (TLR4) and increased binding of AIBP to activated microglia, which mediates selective regulation of lipid rafts in inflammatory cells. AIBP-mediated lipid raft reductions downregulate LPS-induced TLR4 dimerization, inflammatory signaling, and expression of cytokines in microglia. In mice, intrathecal injections of AIBP reduce spinal myeloid cell lipid rafts, TLR4 dimerization, neuroinflammation, and glial activation. Intrathecal AIBP reverses established allodynia in mice in which pain states were induced by the chemotherapeutic cisplatin, intraplantar formalin, or intrathecal LPS, all of which are pro-nociceptive interventions known to be regulated by TLR4 signaling. These findings demonstrate a mechanism by which AIBP regulates neuroinflammation and suggest the therapeutic potential of AIBP in treating preexisting pain states. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Chiropractic management of a patient with lumbar spine pain due to synovial cyst: a case report

PubMed Central

Cox, James M.

2012-01-01

Introduction The purpose of this study is to report the findings resulting from chiropractic care using flexion distraction spinal manipulation for a patient with low back and radicular pain due to spinal stenosis caused by a synovial cyst. Case Report A 75-year-old man presented with low back pain radiating to the right anterior thigh and down the left posterior leg of 3 years' duration. Physical and imaging examinations showed a synovial cyst–induced spinal stenosis at the right L3-L4 level and bilateral L4-L5 spinal stenosis. Intervention and Outcomes Flexion distraction spinal manipulation and physiological therapeutics were applied at the levels of stenosis. After 4 visits, the patient noted total absence of the right and left lower extremity pain and no adverse reaction to treatment. After 3 months of treatment and 16 visits, his low back and buttock pain were minimal; and he had no leg pain. Conclusion Lumbar synovial cyst and stenosis–generated low back and radicular pain was 80% relieved in a 75-year-old man following Cox flexion distraction spinal manipulation. PMID:22942836

Intrathecal ketorolac does not improve acute or chronic pain after hip arthroplasty: a randomized controlled trial

PubMed Central

Wang, Lu; Bauer, Maria; Curry, Regina; Larsson, Anders; Sessler, Daniel I.; Eisenach, James C.

2014-01-01

Hypersensitivity to mechanical stimuli following surgery has been reported in patients who subsequently develop chronic pain after surgery. In animals, peripheral injury increases prostaglandin production in the spinal cord, and spinal cyclooxygenase inhibitors reduce hypersensitivity after injury. We therefore tested the hypothesis that spinal ketorolac reduces hypersensitivity and acute and chronic pain after hip arthroplasty (www.clinicaltrials.gov NCT 00621530). Sixty-two patients having total hip arthroplasty with spinal anesthesia were randomized to receive 13.5 mg hyperbaric bupivacaine with spinal saline or 13.5 mg hyperbaric bupivacaine with 2 mg preservative-free ketorolac. The primary outcome was area of hypersensitivity surrounding the wound 48 hr after surgery, but this only occurred in 4 patients, precluding assessment of this outcome. The groups did not differ in acute pain, acute opioid use, or pain incidence or severity 2 and 6 months after surgery. There were no serious adverse events. Our results suggest that a single spinal dose of ketorolac does not substantially reduce acute surgical pain, and is thus unlikely to reduce the risk of persistent incisional pain. PMID:24535482

Analgesic effects of the COX-2 inhibitor parecoxib on surgical pain through suppression of spinal ERK signaling.

PubMed

Guo, Ya-Jing; Shi, Xu-Dan; Fu, DI; Yang, Yong; Wang, Ya-Ping; Dai, Ru-Ping

2013-07-01

Cyclooxygenase (COX)-2 inhibitors are widely used for postoperative pain control in clinical practice. However, it is unknown whether spinal sensitization is involved in the analgesic effects of COX-2 inhibitors on surgical pain. Extracellular signal-regulated kinase (ERK) in the spinal cord is implicated in various types of pain, including surgical pain. The present study investigated the role of spinal ERK signaling in the analgesic effect of the COX-2 inhibitor parecoxib on surgical pain. Surgical pain was produced in rats by surgical incision of the hind paw. Phosphorylated (p)-ERK1/2 expression was determined by immunohistochemistry. Pain hypersensitivity was evaluated by measuring the paw withdrawal threshold using the von Frey test. The selective COX-2 inhibitor parecoxib was delivered 20 min before or 20 min after the incision by intraperitoneal injection. Pretreatment with parecoxib markedly attenuated the pain hypersensitivity induced by incision. However, post-treatment with parecoxib produced minimal analgesic effects. Parecoxib inhibited the increase in spinal p-ERK expression following surgical incision. The present study thus suggests that the COX-2 inhibitor parecoxib exerts its analgesic effect on surgical pain through the inhibition of neuronal ERK activation in the spinal cord. COX-2 inhibitor delivery prior to surgery has more potent analgesic effects, suggesting the advantage of preventive analgesia for post-operative pain control.

Combination Drug Therapy for Pain following Chronic Spinal Cord Injury

PubMed Central

Hama, Aldric; Sagen, Jacqueline

2012-01-01

A number of mechanisms have been elucidated that maintain neuropathic pain due to spinal cord injury (SCI). While target-based therapeutics are being developed based on elucidation of these mechanisms, treatment for neuropathic SCI pain has not been entirely satisfactory due in part to the significant convergence of neurological and inflammatory processes that maintain the neuropathic pain state. Thus, a combination drug treatment strategy, wherein several pain-related mechanism are simultaneously engaged, could be more efficacious than treatment against individual mechanisms alone. Also, by engaging several targets at once, it may be possible to reduce the doses of the individual drugs, thereby minimizing the potential for adverse side effects. Positive preclinical and clinical studies have demonstrated improved efficacy of combination drug treatment over single drug treatment in neuropathic pain of peripheral origin, and perhaps such combinations could be utilized for neuropathic SCI pain. At the same time, there are mechanisms that distinguish SCI from peripheral neuropathic pain, so novel combination therapies will be needed. PMID:22550581

Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: an in vivo electrophysiological study.

PubMed

Dalmolin, Gerusa D; Bannister, Kirsty; Gonçalves, Leonor; Sikandar, Shafaq; Patel, Ryan; Cordeiro, Marta do Nascimento; Gomez, Marcus Vinícius; Ferreira, Juliano; Dickenson, Anthony H

2017-07-01

Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models. In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL). In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain. Tx3-3 (0.3-100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Aδ-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy. Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.

Spinal pain in adolescents: prevalence, incidence, and course: a school-based two-year prospective cohort study in 1,300 Danes aged 11-13.

PubMed

Aartun, Ellen; Hartvigsen, Jan; Wedderkopp, Niels; Hestbaek, Lise

2014-05-29

The severity and course of spinal pain is poorly understood in adolescents. The study aimed to determine the prevalence and two-year incidence, as well as the course, frequency, and intensity of pain in the neck, mid back, and low back (spinal pain). This study was a school-based prospective cohort study. All 5th and 6th grade students (11-13 years) at 14 schools in the Region of Southern Denmark were invited to participate (N=1,348). Data were collected in 2010 and again two years later, using an e-survey completed during school time. The lifetime prevalence of spinal pain was 86% and 89% at baseline and follow-up, respectively. A group of 13.6% (95% CI: 11.8, 15.6) at baseline and 19.5% (95% CI: 17.1, 22.0) at follow-up reported that they had pain frequently. The frequency of pain was strongly associated with the intensity of pain, i.e., the majority of the participants reported their pain as relatively infrequent and of low intensity, whereas the participants with frequent pain also experienced pain of higher intensity. The two-year incidence of spinal pain varied between 40% and 60% across the physical locations. Progression of pain from one to more locations and from infrequent to more frequent was common over the two-year period. Spinal pain is common at the age of 11-15 years, but some have more pain than others. The pain is likely to progress, i.e., to more locations, higher frequency, and higher pain intensity over a two-year period.

Role of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in complete Freund's adjuvant-induced inflammatory pain.

PubMed

Park, Jang-Su; Yaster, Myron; Guan, Xiaowei; Xu, Ji-Tian; Shih, Ming-Hung; Guan, Yun; Raja, Srinivasa N; Tao, Yuan-Xiang

2008-12-30

Spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) mediate acute spinal processing of nociceptive and non-nociceptive information, but whether and how their activation contributes to the central sensitization that underlies persistent inflammatory pain are still unclear. Here, we examined the role of spinal AMPARs in the development and maintenance of complete Freund's adjuvant (CFA)-induced persistent inflammatory pain. Intrathecal application of two selective non-competitive AMPAR antagonists, CFM-2 (25 and 50 microg) and GYKI 52466 (50 microg), significantly attenuated mechanical and thermal hypersensitivities on the ipsilateral hind paw at 2 and 24 h post-CFA injection. Neither CFM-2 nor GYKI 52466 affected the contralateral basal responses to thermal and mechanical stimuli. Locomotor activity was not altered in any of the drug-treated animals. CFA-induced inflammation did not change total expression or distribution of AMPAR subunits GluR1 and GluR2 in dorsal horn but did alter their subcellular distribution. The amount of GluR2 was markedly increased in the crude cytosolic fraction and decreased in the crude membrane fraction from the ipsilateral L4-5 dorsal horn at 24 h (but not at 2 h) post-CFA injection. Conversely, the level of GluR1 was significantly decreased in the crude cytosolic fraction and increased in the crude membrane fraction from the ipsilateral L4-5 dorsal horn at 24 h (but not at 2 h) post-CFA injection. These findings suggest that spinal AMPARs might participate in the central spinal mechanism of persistent inflammatory pain.

The association of adolescent spinal-pain-related absenteeism with early adulthood work absenteeism: A six-year follow-up data from a population-based cohort.

PubMed

Coenen, Pieter; Smith, Anne; Kent, Peter; Harris, Mark; Linton, Steven J; Pransky, Glenn; Beales, Darren; O'Sullivan, Peter; Straker, Leon

2018-06-11

Objectives Spinal (ie, back and neck) pain often develops as early as during adolescence and can set a trajectory for later life. However, whether early-life spinal-pain-related behavioral responses of missing school/work are predictive of future work absenteeism is yet unknown. We assessed the association of adolescent spinal-pain-related work or school absenteeism with early adulthood work absenteeism in a prospective population-based cohort. Methods Six year follow-up data from the Western Australian Pregnancy Cohort (Raine) study were used (N=476; with a 54% response rate). At age 17, participants reported spinal pain (using the Nordic questionnaire) and adolescent spinal-pain-related work/school absenteeism (with a single item question). Annual total and health-related work absenteeism was assessed with the Health and Work Performance questionnaire distributed in four quarterly text messages during the 23rd year of age. We modelled the association of adolescent spinal-pain-related absenteeism with work absenteeism during early adulthood, using negative binomial regression adjusting for sex, occupation and comorbidities. Results Participants with adolescent low-back or neck pain with work/school absenteeism reported higher total work absenteeism in early adulthood [148.7, standard deviation (SD) 243.4 hours/year], than those without pain [43.7 (SD 95.2) hours/year); incidence rate ratio 3.4 (95% CI 1.2-9.2)]. Comparable findings were found when considering low-back and neck separately, and when considering health-related absenteeism. Conclusions We found a more than three-fold higher risk of work absenteeism in early adulthood among those with adolescent spinal-pain-related absenteeism, compared to those without. These findings suggest that, to keep a sustainable workforce, pain prevention and management should focus on pain-related behaviors as early as in adolescence.

10 kHz High-Frequency Spinal Cord Stimulation for Chronic Axial Low Back Pain in Patients With No History of Spinal Surgery: A Preliminary, Prospective, Open Label and Proof-of-Concept Study.

PubMed

Al-Kaisy, Adnan; Palmisani, Stefano; Smith, Thomas E; Pang, David; Lam, Khai; Burgoyne, William; Houghton, Russell; Hudson, Emma; Lucas, Jonathan

2017-01-01

To explore the effectiveness of 10 kHz high frequency spinal cord stimulation (HF10 therapy) treatment of chronic low back pain in patients who have not had spinal surgery. Patients with chronic low back pain without prior spinal surgery were evaluated by a team of spine surgeons to rule out any spinal pathology amenable to surgical interventions and by a multidisciplinary pain team to confirm eligibility for the study. After a successful (>50% back pain reduction) trial of HF10 therapy, enrolled subjects underwent permanent system implantation and were followed-up one year post-implant. About 95% of the enrolled subjects (20/21) received the permanent system. At 12 months post-implant, both back pain VAS score and ODI were significantly reduced compared with baseline values (by 73% and 48%, respectively); an estimated quality-adjusted life year gain of 0.47 and a reduction in opioid use by 64% was observed. Four more patients among those unable to work at baseline due to back pain were employed at 12 months post-implant. There were no serious adverse events. HF10 therapy may provide significant back pain relief, reduction in disability, improvement quality of life, and reduction in opioid use in chronic low back pain not resulting from spinal surgery. © 2016 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.

Innovations in interventional pain management of chronic spinal pain.

PubMed

Manchikanti, Laxmaiah; Boswell, Mark V; Hirsch, Joshua A

2016-09-01

Interventional pain management dates back to 1901, with significant innovations, which include the definition, literature synthesis, pathophysiology, and technical interventions. Interventional pain management and interventional techniques include neural blockade, neural ablative procedures, spinal cord and peripheral nerve stimulation, intrathecal drug delivery systems, minimally invasive lumbar decompression (MILD®), percutaneous endoscopic spinal decompression, and regenerative medicine. In addition, advances are also related to the evidence synthesis of comparative effectiveness research. Expert commentary: Multiple innovations in interventional pain management and potential innovations may reduce costs and improve care and outcomes with proper evidence synthesis and application of principles of evidence-based medicine. Innovations in interventional pain management in managing chronic spinal pain depend on extensive research and appropriate evidence synthesis. Innovations should be developed in conjunction with health care policy based on principles of evidence-based medicine.

Experiences of Living with Pain after a Spinal Cord Injury

DTIC Science & Technology

2013-09-01

AD_________________ Award Number: W81XWH-12-1-0465 TITLE: Experiences of Living with Pain after a...COVERED 01 September 2012 – 31 August 2013 4. TITLE AND SUBTITLE Experiences of Living with Pain after a Spinal Cord Injury 5a. CONTRACT NUMBER...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Persistent chronic pain is prevalent after a spinal cord injury (SCI), with

Spinal Manipulation for Low-Back Pain

MedlinePlus

... often have limited benefit in managing back and neck pain. The AHRQ analysis also found that spinal manipulation ... manipulation and mobilization for low back pain and neck pain: a systematic review and best evidence synthesis. Spine ...

Vitamin C is not the Missing Link Between Cigarette Smoking and Spinal Pain.

PubMed

Dionne, Clermont E; Laurin, Danielle; Desrosiers, Thérèse; Abdous, Belkacem; Le Sage, Natalie; Frenette, Jérôme; Mondor, Myrto; Pelletier, Sylvie

2018-06-15

A nationwide cross-sectional study. To measure the associations between cigarette smoking (defined as serum cotinine concentration >15 ng/mL) and the 3-month prevalence of spinal pain (neck pain, low back pain, low back pain with pain below knee, and self-reported diagnosis of arthritis/rheumatism) and related limitations, and to verify whether these associations are mediated by serum concentrations of vitamin C. Cigarette smoking has been consistently associated with back pain, but this association has never been explained. Because vitamin C has recently been reported to be associated with spinal pain and related functional limitations, and the metabolism of vitamin C differs between smokers and nonsmokers, we hypothesized that the prevalence of spinal pain and related limitations might be greater among smokers because they are more susceptible to be in a state of hypovitaminosis C. We conducted secondary analyses of National Health and Nutrition Examination Survey (NHANES) 2003 to 2004 data on 4438 individuals aged ≥20 years. Serum concentrations of vitamin C and cotinine were strongly and inversely correlated (r = -0.35, P < 0.0001). Smoking was statistically associated with the prevalence of neck pain [adjusted odds ratio: aOR: 1.25; 95% confidence interval (95% CI): 1.06-1.47], low back pain (aOR: 1.20; 95% CI: 1.04-1.39), and low back pain with pain below knee (aOR: 1.58; 95% CI: 1.13-2.22) and related limitations, with a dose-response relationship (P < 0.05). However, the associations between smoking and spinal pain were not mediated by concentrations of vitamin C. These results confirm the relationship between smoking and spinal pain, but they do not support a mediating effect of vitamin C on this relationship. 2.

Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain.

PubMed

Zhang, Zhi-Jun; Jiang, Bao-Chun; Gao, Yong-Jing

2017-09-01

Neuropathic pain resulting from damage or dysfunction of the nervous system is a highly debilitating chronic pain state and is often resistant to currently available treatments. It has become clear that neuroinflammation, mainly mediated by proinflammatory cytokines and chemokines, plays an important role in the establishment and maintenance of neuropathic pain. Chemokines were originally identified as regulators of peripheral immune cell trafficking and were also expressed in neurons and glial cells in the central nervous system. In recent years, accumulating studies have revealed the expression, distribution and function of chemokines in the spinal cord under chronic pain conditions. In this review, we provide evidence showing that several chemokines are upregulated after peripheral nerve injury and contribute to the pathogenesis of neuropathic pain via different forms of neuron-glia interaction in the spinal cord. First, chemokine CX3CL1 is expressed in primary afferents and spinal neurons and induces microglial activation via its microglial receptor CX3CR1 (neuron-to-microglia signaling). Second, CCL2 and CXCL1 are expressed in spinal astrocytes and act on CCR2 and CXCR2 in spinal neurons to increase excitatory synaptic transmission (astrocyte-to-neuron signaling). Third, we recently identified that CXCL13 is highly upregulated in spinal neurons after spinal nerve ligation and induces spinal astrocyte activation via receptor CXCR5 (neuron-to-astrocyte signaling). Strategies that target chemokine-mediated neuron-glia interactions may lead to novel therapies for the treatment of neuropathic pain.

Injury-Dependent and Disability-Specific Lumbar Spinal Gene Regulation following Sciatic Nerve Injury in the Rat

PubMed Central

Denyer, Gareth S.; Keay, Kevin A.

2015-01-01

Allodynia, hyperalgesia and spontaneous pain are cardinal sensory signs of neuropathic pain. Clinically, many neuropathic pain patients experience affective-motivational state changes, including reduced familial and social interactions, decreased motivation, anhedonia and depression which are severely debilitating. In earlier studies we have shown that sciatic nerve chronic constriction injury (CCI) disrupts social interactions, sleep-wake-cycle and endocrine function in one third of rats, a subgroup reliably identified six days after injury. CCI consistently produces allodynia and hyperalgesia, the intensity of which was unrelated either to the altered social interactions, sleep-wake-cycle or endocrine changes. This decoupling of the sensory consequences of nerve injury from the affective-motivational changes is reported in both animal experiments and human clinical data. The sensory changes triggered by CCI are mediated primarily by functional changes in the lumbar dorsal horn, however, whether lumbar spinal changes may drive different affective-motivational states has never been considered. In these studies, we used microarrays to identify the unique transcriptomes of rats with altered social behaviours following sciatic CCI to determine whether specific patterns of lumbar spinal adaptations characterised this subgroup. Rats underwent CCI and on the basis of reductions in dominance behaviour in resident-intruder social interactions were categorised as having Pain & Disability, Pain & Transient Disability or Pain alone. We examined the lumbar spinal transcriptomes two and six days after CCI. Fifty-four ‘disability-specific’ genes were identified. Sixty-five percent were unique to Pain & Disability rats, two-thirds of which were associated with neurotransmission, inflammation and/or cellular stress. In contrast, 40% of genes differentially regulated in rats without disabilities were involved with more general homeostatic processes (cellular structure, transcription or translation). We suggest that these patterns of gene expression lead to either the expression of disability, or to resilience and recovery, by modifying local spinal circuitry at the origin of ascending supraspinal pathways. PMID:25905723

Injury-Dependent and Disability-Specific Lumbar Spinal Gene Regulation following Sciatic Nerve Injury in the Rat.

PubMed

Austin, Paul J; Bembrick, Alison L; Denyer, Gareth S; Keay, Kevin A

2015-01-01

Allodynia, hyperalgesia and spontaneous pain are cardinal sensory signs of neuropathic pain. Clinically, many neuropathic pain patients experience affective-motivational state changes, including reduced familial and social interactions, decreased motivation, anhedonia and depression which are severely debilitating. In earlier studies we have shown that sciatic nerve chronic constriction injury (CCI) disrupts social interactions, sleep-wake-cycle and endocrine function in one third of rats, a subgroup reliably identified six days after injury. CCI consistently produces allodynia and hyperalgesia, the intensity of which was unrelated either to the altered social interactions, sleep-wake-cycle or endocrine changes. This decoupling of the sensory consequences of nerve injury from the affective-motivational changes is reported in both animal experiments and human clinical data. The sensory changes triggered by CCI are mediated primarily by functional changes in the lumbar dorsal horn, however, whether lumbar spinal changes may drive different affective-motivational states has never been considered. In these studies, we used microarrays to identify the unique transcriptomes of rats with altered social behaviours following sciatic CCI to determine whether specific patterns of lumbar spinal adaptations characterised this subgroup. Rats underwent CCI and on the basis of reductions in dominance behaviour in resident-intruder social interactions were categorised as having Pain & Disability, Pain & Transient Disability or Pain alone. We examined the lumbar spinal transcriptomes two and six days after CCI. Fifty-four 'disability-specific' genes were identified. Sixty-five percent were unique to Pain & Disability rats, two-thirds of which were associated with neurotransmission, inflammation and/or cellular stress. In contrast, 40% of genes differentially regulated in rats without disabilities were involved with more general homeostatic processes (cellular structure, transcription or translation). We suggest that these patterns of gene expression lead to either the expression of disability, or to resilience and recovery, by modifying local spinal circuitry at the origin of ascending supraspinal pathways.

Neurobiological and clinical relationship between psychiatric disorders and chronic pain.

PubMed

Bras, Marijana; Dordević, Veljko; Gregurek, Rudolf; Bulajić, Masa

2010-06-01

Pain is one of the most ubiquitous problems of today's world, its impact being far-reaching. Current conceptualizations of pain medicine adopt a bio-psycho-social perspective. In this model, pain is best described as an interactive, psycho-physiological behavioral pattern that cannot be divided into independent psycho-social and physical components. Neurophysiologic substrates of the pain experience can be broken down into the pain transmission elements emanating from peripheral, spinal, and supra-spinal processes. There are many complex mechanisms involved in pain processing within the central nervous system, being influenced by genetics, interaction of neurotransmitters and their receptors, and pain- augmenting and pain-inhibiting neural circuits. The patient's emotional experiences, beliefs and expectations may determine the outcome of treatment, and are fully emphasized in the focus of treatment interventions. There are several common psychiatric disorders accompanying and complicating the experience of pain that warrant clinical attention and that can be the focus of psychiatric treatment. These include depression, anxiety, sleep disorders, somatoform disorders, substance-related disorders and personality disorders. Complex and disabling pain conditions often require comprehensive pain treatment programs, involving interdisciplinary and multimodal treatment approaches. There are many roles that the psychiatrist can perform in the assessment and treatment of the patients with pain, individually tailored to meet the specific needs of the patient. Rational poly-pharmacy is of a high importance in the treatment of patients with chronic pain, with antidepressants and anticonvulsants contributing as the important adjuvant analgesic agents.

Psychological distress in chronic craniomandibular and cervical spinal pain patients.

PubMed

Visscher, C M; Lobbezoo, F; de Boer, W; van der Meulen, M; Naeije, M

2001-06-01

Recent studies to chronic pain have shown that the number of painful body areas is related to the level of psychological distress. Therefore, the first aim of this study was to analyse differences in level of psychological distress between craniomandibular pain patients with or without cervical spinal pain. In this analysis, the number of painful body areas below the cervical spine was also taken into account. The second aim was to determine psychological differences between subgroups of craniomandibular pain patients. In this study, 103 out of 250 persons with or without craniomandibular pain were included in the final analyses. Patients who suffered from both craniomandibular and cervical spinal pain showed higher levels of psychological distress, as measured with the Symptom Checklist 90 (SCL-90) than patients with local craniomandibular pain and persons without pain. Further, a positive relationship was found between the number of painful body areas below the cervical spine, as measured on a body drawing, and the SCL-90 scores. No psychological differences were found between myogenous and arthrogenous craniomandibular pain patients. In conclusion, chronic craniomandibular pain patients with a coexistent cervical spinal pain showed more psychological distress compared to patients with only a local craniomandibular pain and asymptomatic persons.

Extracellular caspase-6 drives murine inflammatory pain via microglial TNF-α secretion

PubMed Central

Berta, Temugin; Park, Chul-Kyu; Xu, Zhen-Zhong; Xie, Ruo-Gang; Liu, Tong; Lü, Ning; Liu, Yen-Chin; Ji, Ru-Rong

2014-01-01

Increasing evidence indicates that the pathogenesis of neuropathic pain is mediated through spinal cord microglia activation. The intracellular protease caspase-6 (CASP6) is known to regulate neuronal apoptosis and axonal degeneration; however, the contribution of microglia and CASP6 in modulating synaptic transmission and pain is unclear. Here, we found that CASP6 is expressed specifically in C-fiber axonal terminals in the superficial spinal cord dorsal horn. Animals exposed to intraplantar formalin or bradykinin injection exhibited CASP6 activation in the dorsal horn. Casp6-null mice had normal baseline pain, but impaired inflammatory pain responses. Furthermore, formalin-induced second-phase pain was suppressed by spinal injection of CASP6 inhibitor or CASP6-neutralizing antibody, as well as perisciatic nerve injection of CASP6 siRNA. Recombinant CASP6 (rCASP6) induced marked TNF-α release in microglial cultures, and most microglia within the spinal cord expressed Tnfa. Spinal injection of rCASP6 elicited TNF-α production and microglia-dependent pain hypersensitivity. Evaluation of excitatory postsynaptic currents (EPSCs) revealed that rCASP6 rapidly increased synaptic transmission in spinal cord slices via TNF-α release. Interestingly, the microglial inhibitor minocycline suppressed rCASP6 but not TNF-α–induced synaptic potentiation. Finally, rCASP6-activated microglial culture medium increased EPSCs in spinal cord slices via TNF-α. Together, these data suggest that CASP6 released from axonal terminals regulates microglial TNF-α secretion, synaptic plasticity, and inflammatory pain. PMID:24531553

Dutch Multidisciplinary Guideline for Invasive Treatment of Pain Syndromes of the Lumbosacral Spine.

PubMed

Itz, Coen J; Willems, Paul C; Zeilstra, Dick J; Huygen, Frank J

2016-01-01

When conservative therapies such as pain medication or exercise therapy fail, invasive treatment may be indicated for patients with lumbosacral spinal pain. The Dutch Society of Anesthesiologists, in collaboration with the Dutch Orthopedic Association and the Dutch Neurosurgical Society, has taken the initiative to develop the guideline "Spinal low back pain," which describes the evidence regarding diagnostics and invasive treatment of the most common spinal low back pain syndromes, that is, facet joint pain, sacroiliac joint pain, coccygodynia, pain originating from the intervertebral disk, and failed back surgery syndrome. The aim of the guideline is to determine which invasive treatment intervention is preferred for each included pain syndrome when conservative treatment has failed. Diagnostic studies were evaluated using the EBRO criteria, and studies on therapies were evaluated with the Grading of Recommendations Assessment, Development and Evaluation system. For the evaluation of invasive treatment options, the guideline committee decided that the outcome measures of pain, function, and quality of life were most important. The definition, epidemiology, pathophysiological mechanism, diagnostics, and recommendations for invasive therapy for each of the spinal back pain syndromes are reported. The guideline committee concluded that the categorization of low back pain into merely specific or nonspecific gives insufficient insight into the low back pain problem and does not adequately reflect which therapy is effective for the underlying disorder of a pain syndrome. Based on the guideline "Spinal low back pain," facet joint pain, pain of the sacroiliac joint, and disk pain will be part of a planned nationwide cost-effectiveness study. © 2015 World Institute of Pain.

Spinal Endocannabinoids and CB1 Receptors Mediate C-Fiber-Induced Heterosynaptic Pain Plasticity

PubMed Central

Pernía-Andrade, Alejandro J.; Kato, Ako; Witschi, Robert; Nyilas, Rita; Katona, István; Freund, Tamás F.; Watanabe, Masahiko; Filitz, Jörg; Koppert, Wolfgang; Schüttler, Jürgen; Ji, Guangchen; Neugebauer, Volker; Marsicano, Giovanni; Lutz, Beat; Vanegas, Horacio; Zeilhofer, Hanns Ulrich

2010-01-01

Diminished synaptic inhibition in the spinal dorsal horn is a major contributor to chronic pain. Pathways, which reduce synaptic inhibition in inflammatory and neuropathic pain states, have been identified, but central hyperalgesia and diminished dorsal horn synaptic inhibition also occur in the absence of inflammation or neuropathy, solely triggered by intense nociceptive (C–fiber) input to the spinal dorsal horn. We found that endocannabinoids produced upon strong nociceptive stimulation activated CB1 receptors on inhibitory dorsal horn neurons to reduce the synaptic release of GABA and glycine and thus rendered nociceptive neurons excitable by non-painful stimuli. Spinal endocannabinoids and CB1 receptors on inhibitory dorsal horn interneurons act as mediators of heterosynaptic pain sensitization and play an unexpected role in dorsal horn pain controlling circuits. PMID:19661434

Chronic spontaneous activity generated in the somata of primary nociceptors is associated with pain-related behavior after spinal cord injury.

PubMed

Bedi, Supinder S; Yang, Qing; Crook, Robyn J; Du, Junhui; Wu, Zizhen; Fishman, Harvey M; Grill, Raymond J; Carlton, Susan M; Walters, Edgar T

2010-11-03

Mechanisms underlying chronic pain that develops after spinal cord injury (SCI) are incompletely understood. Most research on SCI pain mechanisms has focused on neuronal alterations within pain pathways at spinal and supraspinal levels associated with inflammation and glial activation. These events might also impact central processes of primary sensory neurons, triggering in nociceptors a hyperexcitable state and spontaneous activity (SA) that drive behavioral hypersensitivity and pain. SCI can sensitize peripheral fibers of nociceptors and promote peripheral SA, but whether these effects are driven by extrinsic alterations in surrounding tissue or are intrinsic to the nociceptor, and whether similar SA occurs in nociceptors in vivo are unknown. We show that small DRG neurons from rats (Rattus norvegicus) receiving thoracic spinal injury 3 d to 8 months earlier and recorded 1 d after dissociation exhibit an elevated incidence of SA coupled with soma hyperexcitability compared with untreated and sham-treated groups. SA incidence was greatest in lumbar DRG neurons (57%) and least in cervical neurons (28%), and failed to decline over 8 months. Many sampled SA neurons were capsaicin sensitive and/or bound the nociceptive marker, isolectin B4. This intrinsic SA state was correlated with increased behavioral responsiveness to mechanical and thermal stimulation of sites below and above the injury level. Recordings from C- and Aδ-fibers revealed SCI-induced SA generated in or near the somata of the neurons in vivo. SCI promotes the entry of primary nociceptors into a chronic hyperexcitable-SA state that may provide a useful therapeutic target in some forms of persistent pain.

Role of spinal p38α and β MAPK in inflammatory hyperalgesia and spinal COX-2 expression

PubMed Central

Fitzsimmons, Bethany L.; Zattoni, Michela; Svensson, Camilla I.; Steinauer, Joanne; Hua, Xiao-Ying; Yaksh, Tony L.

2010-01-01

Pharmacological studies indicate that spinal p38 MAPK plays a role in the development of hyperalgesia. We investigated whether either the spinal isoform p38α or p38β is involved in peripheral inflammation-evoked pain state and increased expression of spinal COX-2. Using intrathecal antisense oligonucleotides, we show that hyperalgesia is prevented by downregulation of p38β but not p38α, while increases in spinal COX-2 protein expression at eight hours is mediated by both p38α and β isoforms. These data suggest that early activation of spinal p38β isoform may affect acute facilitatory processing, and both p38β and α isforms mediate temporally delayed upregulation of spinal COX-2. PMID:20134354

Immediate effects of spinal manipulation on thermal pain sensitivity: an experimental study

PubMed Central

George, Steven Z; Bishop, Mark D; Bialosky, Joel E; Zeppieri, Giorgio; Robinson, Michael E

2006-01-01

Background The underlying causes of spinal manipulation hypoalgesia are largely unknown. The beneficial clinical effects were originally theorized to be due to biomechanical changes, but recent research has suggested spinal manipulation may have a direct neurophysiological effect on pain perception through dorsal horn inhibition. This study added to this literature by investigating whether spinal manipulation hypoalgesia was: a) local to anatomical areas innervated by the lumbar spine; b) correlated with psychological variables; c) greater than hypoalgesia from physical activity; and d) different for A-delta and C-fiber mediated pain perception. Methods Asymptomatic subjects (n = 60) completed baseline psychological questionnaires and underwent thermal quantitative sensory testing for A-delta and C-fiber mediated pain perception. Subjects were then randomized to ride a stationary bicycle, perform lumbar extension exercise, or receive spinal manipulation. Quantitative sensory testing was repeated 5 minutes after the intervention period. Data were analyzed with repeated measures ANOVA and post-hoc testing was performed with Bonferroni correction, as appropriate. Results Subjects in the three intervention groups did not differ on baseline characteristics. Hypoalgesia from spinal manipulation was observed in lumbar innervated areas, but not control (cervical innervated) areas. Hypoalgesic response was not strongly correlated with psychological variables. Spinal manipulation hypoalgesia for A-delta fiber mediated pain perception did not differ from stationary bicycle and lumbar extension (p > 0.05). Spinal manipulation hypoalgesia for C-fiber mediated pain perception was greater than stationary bicycle riding (p = 0.040), but not for lumbar extension (p = 0.105). Conclusion Local dorsal horn mediated inhibition of C-fiber input is a potential hypoalgesic mechanism of spinal manipulation for asymptomatic subjects, but further study is required to replicate this finding in subjects with low back pain. PMID:16911795

Management of chronic low back pain: rationales, principles, and targets of imaging-guided spinal injections.

PubMed

Fritz, Jan; Niemeyer, Thomas; Clasen, Stephan; Wiskirchen, Jakub; Tepe, Gunnar; Kastler, Bruno; Nägele, Thomas; König, Claudius W; Claussen, Claus D; Pereira, Philippe L

2007-01-01

If low back pain does not improve with conservative management, the cause of the pain must be determined before further therapy is initiated. Information obtained from the patient's medical history, physical examination, and imaging may suffice to rule out many common causes of chronic pain (eg, fracture, malignancy, visceral or metabolic abnormality, deformity, inflammation, and infection). However, in most cases, the initial clinical and imaging findings have a low predictive value for the identification of specific pain-producing spinal structures. Diagnostic spinal injections performed in conjunction with imaging may be necessary to test the hypothesis that a particular structure is the source of pain. To ensure a valid test result, diagnostic injection procedures should be monitored with fluoroscopy, computed tomography, or magnetic resonance imaging. The use of controlled and comparative injections helps maximize the reliability of the test results. After a symptomatic structure has been identified, therapeutic spinal injections may be administered as an adjunct to conservative management, especially in patients with inoperable conditions. Therapeutic injections also may help hasten the recovery of patients with persistent or recurrent pain after spinal surgery. RSNA, 2007

The international spinal cord injury pain basic data set.

PubMed

Widerström-Noga, E; Biering-Sørensen, F; Bryce, T; Cardenas, D D; Finnerup, N B; Jensen, M P; Richards, J S; Siddall, P J

2008-12-01

To develop a basic pain data set (International Spinal Cord Injury Basic Pain Data Set, ISCIPDS:B) within the framework of the International spinal cord injury (SCI) data sets that would facilitate consistent collection and reporting of pain in the SCI population. International. The ISCIPDS:B was developed by a working group consisting of individuals with published evidence of expertise in SCI-related pain regarding taxonomy, psychophysics, psychology, epidemiology and assessment, and one representative of the Executive Committee of the International SCI Standards and Data Sets. The members were appointed by four major organizations with an interest in SCI-related pain (International Spinal Cord Society, ISCoS; American Spinal Injury Association, ASIA; American Pain Society, APS and International Association for the Study of Pain, IASP). The initial ISCIPDS:B was revised based on suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the ISCoS Scientific Committee, ASIA and APS Boards, and the Neuropathic Pain Special Interest Group of the IASP, individual reviewers and societies and the ISCoS Council. The final ISCIPDS:B contains core questions about clinically relevant information concerning SCI-related pain that can be collected by health-care professionals with expertise in SCI in various clinical settings. The questions concern pain severity, physical and emotional function and include a pain-intensity rating, a pain classification and questions related to the temporal pattern of pain for each specific pain problem. The impact of pain on physical, social and emotional function, and sleep is evaluated for each pain.

Metaplasticity within the spinal cord: Evidence brain-derived neurotrophic factor (BDNF), tumor necrosis factor (TNF), and alterations in GABA function (ionic plasticity) modulate pain and the capacity to learn.

PubMed

Grau, James W; Huang, Yung-Jen

2018-04-07

Evidence is reviewed that behavioral training and neural injury can engage metaplastic processes that regulate adaptive potential. This issue is explored within a model system that examines how training affects the capacity to learn within the lower (lumbosacral) spinal cord. Response-contingent (controllable) stimulation applied caudal to a spinal transection induces a behavioral modification indicative of learning. This behavioral change is not observed in animals that receive stimulation in an uncontrollable manner. Exposure to uncontrollable stimulation also engages a process that disables spinal learning for 24-48 h. Controllable stimulation has the opposite effect; it engages a process that enables learning and prevents/reverses the learning deficit induced by uncontrollable stimulation. These observations suggest that a learning episode can impact the capacity to learn in future situations, providing an example of behavioral metaplasticity. The protective/restorative effect of controllable stimulation has been linked to an up-regulation of brain-derived neurotrophic factor (BDNF). The disruption of learning has been linked to the sensitization of pain (nociceptive) circuits, which is enabled by a reduction in GABA-dependent inhibition. After spinal cord injury (SCI), the co-transporter (KCC2) that regulates the outward flow of Cl - is down-regulated. This causes the intracellular concentration of Cl - to increase, reducing (and potentially reversing) the inward flow of Cl - through the GABA-A receptor. The shift in GABA function (ionic plasticity) increases neural excitability caudal to injury and sets the stage for nociceptive sensitization. The injury-induced shift in KCC2 is related to the loss of descending serotonergic (5HT) fibers that regulate plasticity within the spinal cord dorsal horn through the 5HT-1A receptor. Evidence is presented that these alterations in spinal plasticity impact pain in a brain-dependent task (place conditioning). The findings suggest that ionic plasticity can affect learning potential, shifting a neural circuit from dampened/hard-wired to excitable/plastic. Copyright © 2018 Elsevier Inc. All rights reserved.

Back Pain Facts and Statistics

MedlinePlus

... Spinal Health Winter Activities Kids and Sports Exercising Outdoors with Baby Gardening Chronic Pain and Depression Preventing ... Spinal Health Winter Activities Kids and Sports Exercising Outdoors with Baby Gardening Chronic Pain and Depression Preventing ...

Spinal microglia are required for long-term maintenance of neuropathic pain.

PubMed

Echeverry, Stefania; Shi, Xiang Qun; Yang, Mu; Huang, Hao; Wu, YiChen; Lorenzo, Louis-Etienne; Perez-Sanchez, Jimena; Bonin, Robert P; De Koninck, Yves; Zhang, Ji

2017-09-01

While spinal microglia play a role in early stages of neuropathic pain etiology, whether they are useful targets to reverse chronic pain at late stages remains unknown. Here, we show that microglia activation in the spinal cord persists for >3 months following nerve injury in rodents, beyond involvement of proinflammatory cytokine and chemokine signalling. In this chronic phase, selective depletion of spinal microglia in male rats with the targeted immunotoxin Mac1-saporin and blockade of brain-derived neurotrophic factor-TrkB signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost completely reversed pain hypersensitivity. By contrast, local spinal administration of Mac1-saporin did not affect nociceptive withdrawal threshold in control animals nor did it affect the strength of afferent-evoked synaptic activity in the spinal dorsal horn in normal conditions. These findings show that the long-term, chronic phase of nerve injury-induced pain hypersensitivity is maintained by microglia-neuron interactions. The findings also effectively separate the central signalling pathways underlying the maintenance phase of the pathology from the early and peripheral inflammatory reactions to injury, pointing to different targets for the treatment of acute vs chronic injury-induced pain.

Does the Removal of Spinal Implants Reduce Back Pain?

PubMed Central

Ak, Hakan; Gulsen, Ismail; Atalay, Tugay; Gencer, Muzaffer

2015-01-01

Background The importance of the removal of spinal implants is known in the presence of infection. However, the benefits and/or risks of the removal of spinal implant for the management of back pain are not clear. Methods In this retrospective study, we aimed to evaluate the beneficial effects of the removal of spinal implants for back pain. Study included 25 patients with thoracolumbar instrumentation. Results Seventeen (68%) of them were male. Indications for spinal instrumentation were vertebra fracture (n = 9), iatrogenic instability due to multiple segment laminectomy (n = 12), and instrumentation after recurrent disk herniations (n = 4). Mean visual analog score (VAS) before the removal was 8.08. Mean VAS was 3.36 after the removal. Spinal instruments were removed after the observance of the presence of fusion. All patients were prescribed analgesics and muscle relaxants for 3 weeks before removal. Back pain did not decrease in five (20%) patients in total. Four of them had been instrumented due to recurrent lumbar disk herniation. None of the patients reported the complete relief of pain. Conclusion In conclusion, patients should be cautioned that their back pain might not decrease after a successful removal of their instruments. PMID:25883710

Pain in the three spinal regions: the same disorder? Data from a population-based sample of 34,902 Danish adults.

PubMed

Leboeuf-Yde, Charlotte; Fejer, René; Nielsen, Jan; Kyvik, Kirsten O; Hartvigsen, Jan

2012-04-05

Studies of back pain are typically based on the assumption that symptoms from different parts of the spine are distinctive entities. Recently, however, the assumption that back pain is a site-specific disorder has been challenged, suggesting that localized back pain should be seen as part of a general musculoskeletal syndrome. To describe and compare the patterns of reporting of pain and consequences of pain in the three spinal regions. In all, 34,902 (74%) twin individuals representative of the general Danish population, aged 20 to 71, participated in a cross-sectional nation-wide survey. Identical questions from the Standardised Nordic Questionnaire for each of the three spinal regions were used for lumbar, mid-back and neck pain respectively: Pain past year, pain ever, radiating pain, and consequences of back pain (care-seeking, reduced physical activities, sick-leave, change of work/work duties and disability pension). The relative prevalence estimates of these variables were compared for the three spinal regions. The relative proportions of individuals with pain ever, who also reported to have had pain in the past year varied between 75% and 80%, for the three spinal regions. The proportions of individuals with pain in the past year and for various pain durations were also very similar. Regardless if pain was reported in the lumbar, thoracic or cervical regions, the proportions of individuals reporting radiating pain were equally large. The relative number of consequences was the same across the spinal regions, as were the relative proportions of each these consequences. However, low back pain resulted more often in some kind of consequence compared to the consequences of pain in the neck and mid back. Back pain and its consequences share many characteristics and may, at least in a general population, be regarded as the same condition regardless of where the pain happens to manifest itself. However, because some exceptions were noted for the lumbar spine, separate entities for a smaller group of individuals with back pain cannot be ruled out.

Effects of wheelchair propulsion on neuropathic pain and resting electroencephalography after spinal cord injury.

PubMed

Sato, Gosuke; Osumi, Michihiro; Morioka, Shu

2017-01-31

To investigate the effects of wheelchair propulsion on neuropathic pain and to examine resting electroencephalography pre- and post-wheelchair propulsion after spinal cord injury. Cross-sectional study. Eleven individuals with spinal cord injury and pain and 10 healthy controls. Single-session 15-min wheelchair propulsion and measurement of resting electroence-phalography. Effects of wheelchair propulsion were investigated using numerical rating scale (NRS) for neuropathic pain and short-form Profile of Mood States-Brief for mood. Peak alpha frequency on electroencephalography was calculated in 4 regions of interest; frontal, central, parietal and occipital areas. These outcomes were compared between pre- and post-wheelchair propulsion. Ten participants with spinal cord injury and all healthy controls completed the wheelchair propulsion exercise. NRS scores and negative mood were significantly improved following the wheelchair propulsion exercise. Pre-wheelchair propulsion, parietal and occipital peak alpha frequencies were significantly lower in the spinal cord injury group compared with the healthy controls group. Post-wheelchair propulsion, central peak alpha frequency increased in the spinal cord injury group. Wheelchair propulsion exercise temporarily decreased neuropathic pain intensity, improved negative mood, and modified alpha activity in spinal cord injury.

Combined spinal-epidural anesthesia and non-pharmacological methods of pain relief during normal childbirth and maternal satisfaction: a randomized clinical trial.

PubMed

Orange, Flavia Augusta de; Passini, Renato; Melo, Adriana S O; Katz, Leila; Coutinho, Isabela Cristina; Amorim, Melania M R

2012-01-01

The objective of this study was to compare maternal satisfaction with childbirth according to whether or not combined spinal-epidural anesthesia (CSE) of pain relief was used during labor. A randomized, open clinical trial was performed with 70 pregnant women, 35 of whom received CSE anesthesia while 35 received only non-pharmacological forms of pain relief during labor. The variables evaluated were visual analogue scale (VAS) pain score, maternal satisfaction with the technique of pain relief used during childbirth and with delivery, the patient's intention to request the same technique in a subsequent delivery, and loss of control during delivery. VAS pain score decreased significantly in patients receiving CSE during vaginal delivery. Furthermore, maternal satisfaction with the technique of pain relief and with delivery was higher in the CSE group, and around 97% of the patients would repeat the same technique at future deliveries compared to 82.4% of the women in the group using only non-pharmacological methods. With respect to the women's impressions of their control during delivery, approximately half the women in both groups felt that they had lost control at some point during the process. The use of CSE was associated with a significant reduction in VAS pain scores during delivery and with greater maternal satisfaction with the pain relief method and with the childbirth process.

Spinal sigma-1 receptors activate NADPH oxidase 2 leading to the induction of pain hypersensitivity in mice and mechanical allodynia in neuropathic rats.

PubMed

Choi, Sheu-Ran; Roh, Dae-Hyun; Yoon, Seo-Yeon; Kang, Suk-Yun; Moon, Ji-Young; Kwon, Soon-Gu; Choi, Hoon-Seong; Han, Ho-Jae; Beitz, Alvin J; Oh, Seog-Bae; Lee, Jang-Hern

2013-08-01

We have recently demonstrated that spinal sigma-1 receptors (Sig-1Rs) mediate pain hypersensitivity in mice and neuropathic pain in rats. In this study, we examine the role of NADPH oxidase 2 (Nox2)-induced reactive oxygen species (ROS) on Sig-1R-induced pain hypersensitivity and the induction of chronic neuropathic pain. Neuropathic pain was produced by chronic constriction injury (CCI) of the right sciatic nerve in rats. Mechanical allodynia and thermal hyperalgesia were evaluated in mice and CCI-rats. Western blotting and dihydroethidium (DHE) staining were performed to assess the changes in Nox2 activation and ROS production in spinal cord, respectively. Direct activation of spinal Sig-1Rs with the Sig-1R agonist, PRE084 induced mechanical allodynia and thermal hyperalgesia, which were dose-dependently attenuated by pretreatment with the ROS scavenger, NAC or the Nox inhibitor, apocynin. PRE084 also induced an increase in Nox2 activation and ROS production, which were attenuated by pretreatment with the Sig-1R antagonist, BD1047 or apocynin. CCI-induced nerve injury produced an increase in Nox2 activation and ROS production in the spinal cord, all of which were attenuated by intrathecal administration with BD1047 during the induction phase of neuropathic pain. Furthermore, administration with BD1047 or apocynin reversed CCI-induced mechanical allodynia during the induction phase, but not the maintenance phase. These findings demonstrate that spinal Sig-1Rs modulate Nox2 activation and ROS production in the spinal cord, and ultimately contribute to the Sig-1R-induced pain hypersensitivity and the peripheral nerve injury-induced induction of chronic neuropathic pain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ketorolac reduces spinal astrocytic activation and PAR1 expression associated with attenuation of pain after facet joint injury.

PubMed

Dong, Ling; Smith, Jenell R; Winkelstein, Beth A

2013-05-15

Chronic neck pain affects up to 70% of persons, with the facet joint being the most common source. Intra-articular injection of the non-steroidal anti-inflammatory drug ketorolac reduces post-operative joint-mediated pain; however, the mechanism of its attenuation of facet-mediated pain has not been evaluated. Protease-activated receptor-1 (PAR1) has differential roles in pain maintenance depending on the type and location of painful injury. This study investigated if the timing of intra-articular ketorolac injection after painful cervical facet injury affects behavioral hypersensitivity by modulating spinal astrocyte activation and/or PAR1 expression. Rats underwent a painful joint distraction and received an injection of ketorolac either immediately or 1 day later. Separate control groups included injured rats with a vehicle injection at day 1 and sham operated rats. Forepaw mechanical allodynia was measured for 7 days, and spinal cord tissue was immunolabeled for glial fibrillary acidic protein (GFAP) and PAR1 expression in the dorsal horn on day 7. Ketorolac administered on day 1 after injury significantly reduced allodynia (p=0.0006) to sham levels, whereas injection immediately after the injury had no effect compared with vehicle. Spinal astrocytic activation followed behavioral responses and was significantly decreased (p=0.009) only for ketorolac given at day 1. Spinal PAR1 (p=0.0025) and astrocytic PAR1 (p=0.012) were significantly increased after injury. Paralleling behavioral data, astrocytic PAR1 was returned to levels in sham only when ketorolac was administered on day 1. Yet, spinal PAR1 was significantly reduced (p<0.0001) by ketorolac independent of timing. Spinal astrocyte expression of PAR1 appears to be associated with the maintenance of facet-mediated pain.

Ketorolac Reduces Spinal Astrocytic Activation and PAR1 Expression Associated with Attenuation of Pain after Facet Joint Injury

PubMed Central

Dong, Ling; Smith, Jenell R.

2013-01-01

Abstract Chronic neck pain affects up to 70% of persons, with the facet joint being the most common source. Intra-articular injection of the non-steroidal anti-inflammatory drug ketorolac reduces post-operative joint-mediated pain; however, the mechanism of its attenuation of facet-mediated pain has not been evaluated. Protease-activated receptor-1 (PAR1) has differential roles in pain maintenance depending on the type and location of painful injury. This study investigated if the timing of intra-articular ketorolac injection after painful cervical facet injury affects behavioral hypersensitivity by modulating spinal astrocyte activation and/or PAR1 expression. Rats underwent a painful joint distraction and received an injection of ketorolac either immediately or 1 day later. Separate control groups included injured rats with a vehicle injection at day 1 and sham operated rats. Forepaw mechanical allodynia was measured for 7 days, and spinal cord tissue was immunolabeled for glial fibrillary acidic protein (GFAP) and PAR1 expression in the dorsal horn on day 7. Ketorolac administered on day 1 after injury significantly reduced allodynia (p=0.0006) to sham levels, whereas injection immediately after the injury had no effect compared with vehicle. Spinal astrocytic activation followed behavioral responses and was significantly decreased (p=0.009) only for ketorolac given at day 1. Spinal PAR1 (p=0.0025) and astrocytic PAR1 (p=0.012) were significantly increased after injury. Paralleling behavioral data, astrocytic PAR1 was returned to levels in sham only when ketorolac was administered on day 1. Yet, spinal PAR1 was significantly reduced (p<0.0001) by ketorolac independent of timing. Spinal astrocyte expression of PAR1 appears to be associated with the maintenance of facet-mediated pain. PMID:23126437

Stress induces pain transition by potentiation of AMPA receptor phosphorylation.

PubMed

Li, Changsheng; Yang, Ya; Liu, Sufang; Fang, Huaqiang; Zhang, Yong; Furmanski, Orion; Skinner, John; Xing, Ying; Johns, Roger A; Huganir, Richard L; Tao, Feng

2014-10-08

Chronic postsurgical pain is a serious issue in clinical practice. After surgery, patients experience ongoing pain or become sensitive to incident, normally nonpainful stimulation. The intensity and duration of postsurgical pain vary. However, it is unclear how the transition from acute to chronic pain occurs. Here we showed that social defeat stress enhanced plantar incision-induced AMPA receptor GluA1 phosphorylation at the Ser831 site in the spinal cord and greatly prolonged plantar incision-induced pain. Interestingly, targeted mutation of the GluA1 phosphorylation site Ser831 significantly inhibited stress-induced prolongation of incisional pain. In addition, stress hormones enhanced GluA1 phosphorylation and AMPA receptor-mediated electrical activity in the spinal cord. Subthreshold stimulation induced spinal long-term potentiation in GluA1 phosphomimetic mutant mice, but not in wild-type mice. Therefore, spinal AMPA receptor phosphorylation contributes to the mechanisms underlying stress-induced pain transition. Copyright © 2014 the authors 0270-6474/14/3413737-10$15.00/0.

The Interface of Mechanics and Nociception in Joint Pathophysiology: Insights From the Facet and Temporomandibular Joints

PubMed Central

Sperry, Megan M.; Ita, Meagan E.; Kartha, Sonia; Zhang, Sijia; Yu, Ya-Hsin; Winkelstein, Beth

2017-01-01

Chronic joint pain is a widespread problem that frequently occurs with aging and trauma. Pain occurs most often in synovial joints, the body's load bearing joints. The mechanical and molecular mechanisms contributing to synovial joint pain are reviewed using two examples, the cervical spinal facet joints and the temporomandibular joint (TMJ). Although much work has focused on the macroscale mechanics of joints in health and disease, the combined influence of tissue mechanics, molecular processes, and nociception in joint pain has only recently become a focus. Trauma and repeated loading can induce structural and biochemical changes in joints, altering their microenvironment and modifying the biomechanics of their constitutive tissues, which themselves are innervated. Peripheral pain sensors can become activated in response to changes in the joint microenvironment and relay pain signals to the spinal cord and brain where pain is processed and perceived. In some cases, pain circuitry is permanently changed, which may be a potential mechanism for sustained joint pain. However, it is most likely that alterations in both the joint microenvironment and the central nervous system (CNS) contribute to chronic pain. As such, the challenge of treating joint pain and degeneration is temporally and spatially complicated. This review summarizes anatomy, physiology, and pathophysiology of these joints and the sensory pain relays. Pain pathways are postulated to be sensitized by many factors, including degeneration and biochemical priming, with effects on thresholds for mechanical injury and/or dysfunction. Initiators of joint pain are discussed in the context of clinical challenges including the diagnosis and treatment of pain. PMID:28056123

Development of the young spine questionnaire.

PubMed

Lauridsen, Henrik Hein; Hestbaek, Lise

2013-06-12

Back pain in children is common and early onset of back pain has been shown to increase the risk of back pain significantly in adulthood. Consequently, preventive efforts must be targeted the young population but research relating to spinal problems in this age group is scarce. Focus has primarily been on the working age population, and therefore specific questionnaires to measure spinal pain and its consequences, specifically aimed at children and adolescents are absent. The purpose of this study was to develop a questionnaire for schoolchildren filling this gap. The Young Spine Questionnaire (YSQ) was developed in three phases--a conceptualisation, development and testing phase. The conceptualisation phase followed the Wilson and Cleary model and included questions regarding spinal prevalence estimates, pain frequency and intensity, activity restrictions, care seeking behaviour and influence of parental back trouble. Items from existing questionnaires and the "Revised Faces Pain Scale" (rFPS) were included during the development phase. The testing phase consisted of a mixed quantitative and qualitative iterative method carried out in two pilot tests using 4th grade children and focusing on assessment of spinal area location and item validity. The testing phase resulted in omission of the pain drawings and the questions and answer categories were simplified in several questions. Agreement between the questionnaire prevalence estimates and the interviews ranged between 83.7% (cervical pain today) and 97.9% (thoracic pain today). To improve the understanding of the spinal boundaries we added bony landmarks to the spinal drawings after pilot test I. This resulted in an improved sense of spinal boundary location in pilot test II. Correlations between the rFPS and the interview pain score ranged between 0.67 (cervical spine) and 0.79 (lumbar spine). The Young Spine Questionnaire contains questions that assess spinal pain and its consequences. The items have been tested for content understanding and agreement between questionnaire scores and interview findings among target respondents. These preliminary results suggest that the YSQ is feasible, has content validity and is a well understood questionnaire to be used in studies of children aged 9 to 11 years.

Pain severity and mobility one year after spinal cord injury: a multicenter, cross-sectional study.

PubMed

Marcondes, Bianca F; Sreepathi, Shruti; Markowski, Justin; Nguyen, Dung; Stock, Shannon R; Carvalho, Sandra; Tate, Denise; Zafonte, Ross; Morse, Leslie R; Fregni, Felipe

2016-10-01

Following a spinal cord injury, patients are often burdened by chronic pain. Preliminary research points to activation of the motor cortex through increased mobility as a potential means of alleviating postinjury chronic pain. The aim of this study was to assess the relationship between pain severity and mobility among patients who have sustained a traumatic spinal cord injury while controlling for clinically-relevant covariates. A multi-center, cross-sectional study. The SCIMS is composed of 14 centers, all located in the United States and funded by the National Institute on Disability and Rehabilitation Research (NIDRR). The study cohort included 1980 patients who completed the one-year SCIMS follow-up assessment between October 2000- December 2013. A multi-center, cross-sectional study was performed to assess the impact of mobility on self-reported pain using information from 1980 subjects who sustained a traumatic spinal cord injury and completed a year-one follow-up interview between October 2000 and December 2013. Patient information was acquired using the Spinal Cord Injury National Database, compiled by the affiliated Spinal Cord Injury Model Systems. Analyses included a multivariable linear regression of patients' self-reported pain scores on mobility, quantified using the CHART-SF mobility total score, and other clinically relevant covariates. After controlling for potential confounders, a significant quadratic relationship between mobility and patients' self-reported pain was observed (P=0.016). Furthermore, female gender, "unemployed" occupational status, paraplegia, and the presence of depressive symptoms were associated with significantly higher pain scores (P<0.02 for all variables). Statistically significant quadratic associations between pain scores and age at injury, life satisfaction total score, and the CHART-SF occupational total subscale were also observed (P≤0.03 for all variables). Among patients with moderate to high levels of mobility, pain scores decreased with increasing mobility. Enhancing a patient's physical activity by increasing his or her mobility may reduce neuropathic pain if begun shortly after a spinal cord injury.

Attenuation of inflammatory and neuropathic pain behaviors in mice through activation of free fatty acid receptor GPR40.

PubMed

Karki, Prasanna; Kurihara, Takashi; Nakamachi, Tomoya; Watanabe, Jun; Asada, Toshihide; Oyoshi, Tatsuki; Shioda, Seiji; Yoshimura, Megumu; Arita, Kazunori; Miyata, Atsuro

2015-02-12

The G-protein-coupled receptor 40 (GPR40) is suggested to function as a transmembrane receptor for medium- to long-chain free fatty acids and is implicated to play a role in free fatty acids-mediated enhancement of glucose-stimulated insulin secretion from pancreas. However, the functional role of GPR40 in nervous system including somatosensory pain signaling has not been fully examined yet. Intrathecal injection of GPR40 agonist (MEDICA16 or GW9508) dose-dependently reduced ipsilateral mechanical allodynia in CFA and SNL models and thermal hyperalgesia in carrageenan model. These anti-allodynic and anti-hyperalgesic effects were almost completely reversed by a GPR40 antagonist, GW1100. Immunohistochemical analysis revealed that GPR40 is expressed in spinal dorsal horn and dorsal root ganglion neurons, and immunoblot analysis showed that carrageenan or CFA inflammation or spinal nerve injury resulted in increased expression of GPR40 in these areas. Patch-clamp recordings from spinal cord slices exhibited that bath-application of either MEDICA16 or GW9508 significantly decreased the frequency of spontaneous excitatory postsynaptic currents in the substantia gelatinosa neurons of the three pain models. Our results indicate that GPR40 signaling pathway plays an important suppressive role in spinal nociceptive processing after inflammation or nerve injury, and that GPR40 agonists might serve as a new class of analgesics for treating inflammatory and neuropathic pain.

A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing

PubMed Central

Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H. Sophie; Wahis, Jérôme; Gouveia, Miriam da Silva; Tang, Yan; Ciobanu, Alexandru Cristian; del Rio, Rodrigo Triana; Roth, Lena C.; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L.; Mitre, Mariela; Froemke, Robert C.; Chao, Moses V.; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H.; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

2017-01-01

SUMMARY Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery. PMID:26948889

A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.

PubMed

Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H Sophie; Wahis, Jérôme; da Silva Gouveia, Miriam; Tang, Yan; Ciobanu, Alexandru Cristian; Triana Del Rio, Rodrigo; Roth, Lena C; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L; Mitre, Mariela; Froemke, Robert C; Chao, Moses V; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

2016-03-16

Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk factors of non-specific spinal pain in childhood.

PubMed

Szita, Julia; Boja, Sara; Szilagyi, Agnes; Somhegyi, Annamaria; Varga, Peter Pal; Lazary, Aron

2018-05-01

Non-specific spinal pain can occur at all ages and current evidence suggests that pediatric non-specific spinal pain is predictive for adult spinal conditions. A 5-year long, prospective cohort study was conducted to identify the lifestyle and environmental factors leading to non-specific spinal pain in childhood. Data were collected from school children aged 7-16 years, who were randomly selected from three different geographic regions in Hungary. The risk factors were measured with a newly developed patient-reported questionnaire (PRQ). The quality of the instrument was assessed by the reliability with the test-retest method. Test (N = 952) and validity (N = 897) datasets were randomly formed. Risk factors were identified with uni- and multivariate logistic regression models and the predictive performance of the final model was evaluated using the receiver operating characteristic (ROC) method. The final model was built up by seven risk factors for spinal pain for days; age > 12 years, learning or watching TV for more than 2 h/day, uncomfortable school-desk, sleeping problems, general discomfort and positive familiar medical history (χ 2  = 101.07; df = 8; p < 0.001). The probabilistic performance was confirmed with ROC analysis on the test and validation cohorts (AUC = 0.76; 0.71). A simplified risk scoring system showed increasing possibility for non-specific spinal pain depending on the number of the identified risk factors (χ 2  = 65.0; df = 4; p < 0.001). Seven significant risk factors of non-specific spinal pain in childhood were identified using the new, easy to use and reliable PRQ which makes it possible to stratify the children according to their individual risk. These slides can be retrieved under Electronic Supplementary Material.

[HEART RHYTHM VARIABILITY ANALYSIS AND ASSESSMENT OF THE SPINAL PAIN SYNDROME DURING DRY IMMERSION].

PubMed

Sun, I; Voronkov, Yu I; Ardashev, V N; Glukhova, S I

2015-01-01

The spinal pain syndrome appears in cosmonauts on both short and long-duration missions. This untoward factor may affect body systems functioning and complicate the successful accomplishment of space mission. Purpose of the investigation was to examine the lumbar spine and to elucidate whether its condition relates to the spinal pain development and changes in heart rate variability (HRV) in the microgravity environment. The experiment was conducted in dry immersion as a method of microgravity effects simulation. It was shown that in dry immersion locomotion reproduces the patterns peculiar for significant gravitational unloading. Spinal pain intensity, angles and heights of the lumbar intervertebral discs and HRV were measured in 19 selected volunteers. During the experiment, all the volunteers developed pains in the back that abated gradually. Pain dependence on the height of intervertebral discs and cardiac regulatory mechanisms were investigated.

Low back pain, radiculopathy, and bilateral proximal hamstring ruptures: a case report.

PubMed

Deren, Matthew E; DeFroda, Steven F; Mukand, Nita H; Mukand, Jon A

2015-12-01

Low back pain (LBP) is a common complaint in the United States, with an incidence of 6.3%-15.4% and yearly recurrence in 54%-90% of patients.1 Trends show more frequent diagnostic testing, opioid use, and surgical intervention as the incidence of LBP increases.2 LBP is defined as pain at and near the lumbosacral region that can vary with physical activity and time. LBP is usually related to pathology of muscles, ligaments, spinal column joints, nerve roots, and the spinal cord. During the assessment of LBP, practitioners must also consider less common causes of pain in that region. For instance, patients with indolent or nighttime pain may have infectious or malignant processes. Referred pain from injuries to pelvic musculature or abdominal contents should be considered, especially following a traumatic event. One of these injuries, which can present as acute low back pain, is rupture of the proximal hamstring tendon. On rare occasion, concomitant LBP, radiculopathy, and hamstring injuries can occur;. This diagnostic challenge is described in the following case.

NMDA Receptor Activation Underlies the Loss of Spinal Dorsal Horn Neurons and the Transition to Persistent Pain after Peripheral Nerve Injury.

PubMed

Inquimbert, Perrine; Moll, Martin; Latremoliere, Alban; Tong, Chi-Kun; Whang, John; Sheehan, Gregory F; Smith, Brendan M; Korb, Erica; Athié, Maria C P; Babaniyi, Olusegun; Ghasemlou, Nader; Yanagawa, Yuchio; Allis, C David; Hof, Patrick R; Scholz, Joachim

2018-05-29

Peripheral nerve lesions provoke apoptosis in the dorsal horn of the spinal cord. The cause of cell death, the involvement of neurons, and the relevance for the processing of somatosensory information are controversial. Here, we demonstrate in a mouse model of sciatic nerve injury that glutamate-induced neurodegeneration and loss of γ-aminobutyric acid (GABA)ergic interneurons in the superficial dorsal horn promote the transition from acute to chronic neuropathic pain. Conditional deletion of Grin1, the essential subunit of N-methyl-d-aspartate-type glutamate receptors (NMDARs), protects dorsal horn neurons from excitotoxicity and preserves GABAergic inhibition. Mice deficient in functional NMDARs exhibit normal nociceptive responses and acute pain after nerve injury, but this initial increase in pain sensitivity is reversible. Eliminating NMDARs fully prevents persistent pain-like behavior. Reduced pain in mice lacking proapoptotic Bax confirmed the significance of neurodegeneration. We conclude that NMDAR-mediated neuron death contributes to the development of chronic neuropathic pain. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Coordination of spinal motion in the transverse and frontal planes during walking in people with and without recurrent low back pain.

PubMed

Crosbie, Jack; de Faria Negrão Filho, Ruben; Nascimento, Dafne Port; Ferreira, Paulo

2013-03-01

Observational cohort study. To investigate spinal coordination during preferred and fast speed walking in pain-free subjects with and without a history of recurrent low back pain (LBP). Dynamic motion of the spine during walking is compromised in the presence of back pain (LBP), but its analysis often presents some challenges. The coexistence of significant symptoms may change gait because of pain or adaptation of the musculoskeletal structures or both. A history of LBP without the overlay of a current symptomatic episode allows a better model in which to explore the impact on spinal coordination during walking. Spinal and lower limb segmental motions were tracked using electromagnetic sensors. Analyses were conducted to explore the synchrony and spatial coordination of the segments and to compare the control and subjects with LBP. We found no apparent differences between the groups for either overall amplitude of motion or most indicators of coordination in the lumbar region; however, there were significant postural differences in the mid-stance phase and other indicators of less phase locking in controls compared with subjects with LBP. The lower thoracic spinal segment was more affected by the history of back pain than the lumbar segment. Although small, there were indicators that alterations in spinal movement and coordination in subjects with recurrent LBP were due to adaptive changes rather than the presence of pain.

Pain following Spinal Cord Injury: The Impact on Community Reintegration

PubMed Central

Donnelly, Catherine; Eng, Janice J

2011-01-01

Study Design Prospective, correlational Objectives 1) describe how pain changes over recovery from admission to spinal cord injury (SCI) rehabilitation, discharge and after 6 months of community living and 2) examine the relationship between pain and community integration at 6 months of community living. Setting Tertiary rehabilitation centre, spinal cord injury unit, Vancouver, Canada. Methods Subjects from 66 consecutive admissions to the Spinal Cord Injury Program of a tertiary rehabilitation centre for the treatment of a traumatic spinal cord injury during the years 2000 to 2002 were followed using data from the National Rehabilitation Reporting System (NRRS). Information was obtained from NRRS standardized assessments performed on admission, discharge and 6 month community living. Early community living was defined as 6-months post-discharge. Community re-integration was assessed by the Reintegration to Normal Living Index (RNL). Pain presence, pain impact and pain intensity were assessed using single item Likhert type scales. Results 86% of individuals with a SCI reported pain at 6-months post discharge, with 27% of these individuals reporting pain that impacted on many or most activities. Pain impact and pain intensity were related to the community re-integration (r=−0.39 and r=−0.55, p<.001), with pain intensity accounting for 25% of the variance in RNL scores. Conclusions Pain is a major consequence of a SCI, impacting on an individual’s activities and perception of how well they are integrated into the community. The results of this study highlight the need to address pain during both the rehabilitation phase of treatment and the early transition into the community. PMID:15570317

Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat

PubMed Central

Sagar, D.R.; Nwosu, L.; Walsh, D.A.; Chapman, V.

2015-01-01

Summary Objective Although analgesic approaches targeting nerve growth factor (NGF) for the treatment of osteoarthritis (OA) pain remain of clinical interest, neurophysiological mechanisms by which NGF contribute to OA pain remain unclear. We investigated the impact of local elevation of knee joint NGF on knee joint, vs remote (hindpaw), evoked responses of spinal neurones in a rodent model of OA pain. Design In vivo spinal electrophysiology was carried out in anaesthetised rats with established pain behaviour and joint pathology following intra-articular injection of monosodium iodoacetate (MIA), vs injection of saline. Neuronal responses to knee joint extension and flexion, mechanical punctate stimulation of the peripheral receptive fields over the knee and at a remote site (ipsilateral hind paw) were studied before, and following, intra-articular injection of NGF (10 μg/50 μl) or saline. Results MIA-injected rats exhibited significant local (knee joint) and remote (lowered hindpaw withdrawal thresholds) changes in pain behaviour, and joint pathology. Intra-articular injection of NGF significantly (P < 0.05) increased knee extension-evoked firing of spinal neurones and the size of the peripheral receptive fields of spinal neurones (100% increase) over the knee joint in MIA rats, compared to controls. Intra-articular NGF injection did not significantly alter responses of spinal neurones following noxious stimulation of the ipsilateral hind paw in MIA-injected rats. Conclusion The facilitatory effects of intra-articular injection of NGF on spinal neurones receiving input from the knee joint provide a mechanistic basis for NGF mediated augmentation of OA knee pain, however additional mechanisms may contribute to the spread of pain to remote sites. PMID:25623624

Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat.

PubMed

Sagar, D R; Nwosu, L; Walsh, D A; Chapman, V

2015-06-01

Although analgesic approaches targeting nerve growth factor (NGF) for the treatment of osteoarthritis (OA) pain remain of clinical interest, neurophysiological mechanisms by which NGF contribute to OA pain remain unclear. We investigated the impact of local elevation of knee joint NGF on knee joint, vs remote (hindpaw), evoked responses of spinal neurones in a rodent model of OA pain. In vivo spinal electrophysiology was carried out in anaesthetised rats with established pain behaviour and joint pathology following intra-articular injection of monosodium iodoacetate (MIA), vs injection of saline. Neuronal responses to knee joint extension and flexion, mechanical punctate stimulation of the peripheral receptive fields over the knee and at a remote site (ipsilateral hind paw) were studied before, and following, intra-articular injection of NGF (10 μg/50 μl) or saline. MIA-injected rats exhibited significant local (knee joint) and remote (lowered hindpaw withdrawal thresholds) changes in pain behaviour, and joint pathology. Intra-articular injection of NGF significantly (P < 0.05) increased knee extension-evoked firing of spinal neurones and the size of the peripheral receptive fields of spinal neurones (100% increase) over the knee joint in MIA rats, compared to controls. Intra-articular NGF injection did not significantly alter responses of spinal neurones following noxious stimulation of the ipsilateral hind paw in MIA-injected rats. The facilitatory effects of intra-articular injection of NGF on spinal neurones receiving input from the knee joint provide a mechanistic basis for NGF mediated augmentation of OA knee pain, however additional mechanisms may contribute to the spread of pain to remote sites. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Low back pain vs. leg dominant pain].

PubMed

Kovac, Ida

2011-01-01

There are two patterns of back pain: 1) back-dominant pain and 2) leg pain dominant, greater than back pain. The causes of back pain are very different and numerous, but mostly are due to vertebral, mechanical etiology, and rarely because of non vertebral, visceral etiology. Leg pain greater than back pain is mostly disease of spinal nerve root, generally presented by radicular pain in a dermatomal distribution. Mechanical compression of spinal roots, caused by disc herniation or by spinal stenosis, results in radicular symptoms. Rarely, in about 1% of patients, there are some other reasons except vertebral mechanical cause, like infection, tumor or fracture. There are several causes of pseudoradicular pain like periferal neuropathy, myifascial syndromes, vascular diseases, osteoarthritis. Spondylarthropathies should be taken in cosideration as well. A complete history and physical examination is important to determine further diagnostic evaluation and to provide eficient therapy.

[Combined surgical and physical treatment in traumatic painful syndromes of the cervical spine].

PubMed

Stachowski, B; Kaczmarek, J; Nosek, A; Kocur, L

1976-01-01

Clinical observations suggest the need for changing therapeutic management to a more active one in cases of cervical spine injury with damage to the spinal cord and nerve roots or brachial plexus. In 248 patients with these injuries treated initially conservatively the incidence of cervicobrachial pain was analysed. Neuralgic pains were present in 31.5% of cases, causalgic pains in 2.4% and sympathalgic pains in 2%. Conservative treatment conducted in these patients (89 cases) during many months after trauma had no effect on return of mobility. Long-term application of physioterapy prevented only temporarily the development of trophic changes and only partially relieved pains. Only surgical decompression of the spinal cord or spinal nerves with stabilization of damaged vertebrae caused disappearance of painful syndromes and improvement in the motor activity of the extremities. These observations show that early surgical intervention for decompression of the spinal cord, roots or brachial plexus should be advocated in these cases.

Pain intensity and duration can be enhanced by prior challenge: Initial evidence suggestive of a role of microglial priming

PubMed Central

Hains, Leah E.; Loram, Lisa C.; Weiseler, Julie L.; Frank, Matthew G.; Bloss, Erik B.; Sholar, Paige; Taylor, Frederick R; Harrison, Jacqueline A; Martin, Thomas J.; Eisenach, James C.; Maier, Steven F.; Watkins, Linda R.

2010-01-01

Activation of spinal microglia and consequent release of pro-inflammatory mediators facilitate pain. Under certain conditions, responses of activated microglia can become enhanced. Enhanced microglial production of pro-inflammatory products may result from priming (sensitization), similar to macrophage priming. We hypothesized that if spinal microglia were primed by an initial inflammatory challenge, subsequent challenges may create enhanced pain. Here, we used a "two-hit" paradigm using two successive challenges, which affect overlapping populations of spinal microglia, presented two weeks apart. Mechanical allodynia and/or activation of spinal glia were assessed. Initially, laparotomy preceded systemic lipopolysaccharide (LPS). Prior laparotomy caused prolonged microglial (not astrocyte) activation plus enhanced LPS-induced allodynia. In this “two-hit” paradigm, minocycline, a microglial activation inhibitor, significantly reduced later exaggerated pain induced by prior surgery when minocycline was administered intrathecally for 5 days starting either at the time of surgery or 5 days before LPS administration. To test generality of the priming effect, subcutaneous formalin preceded intrathecal HIV-1 gp120, which activates spinal microglia and causes robust allodynia. Prior formalin enhanced intrathecal gp120-induced allodynia, suggesting that microglial priming is not limited to laparotomy and again supporting a spinal site of action. Therefore, spinal microglial priming may increase vulnerability to pain enhancement. PMID:20434956

Efficacy of preventive spinal manipulation for chronic low-back pain and related disabilities: a preliminary study.

PubMed

Descarreaux, Martin; Blouin, Jean-Sébastien; Drolet, Marc; Papadimitriou, Stanislas; Teasdale, Normand

2004-10-01

To document the potential role of maintenance chiropractic spinal manipulation to reduce overall pain and disability levels associated with chronic low-back conditions after an initial phase of intensive chiropractic treatments. Thirty patients with chronic nonspecific low-back pain were separated into 2 groups. The first group received 12 treatments in an intensive 1-month period but received no treatment in a subsequent 9-month period. For this group, a 4-week period preceding the initial phase of treatment was used as a control period to examine the sole effect of time on pain and disability levels. The second group received 12 treatments in an intensive 1-month period and also received maintenance spinal manipulation every 3 weeks for a 9-month follow-up period. Pain and disability levels were evaluated with a visual analog scale and a modified Oswestry questionnaire, respectively. The 1-month control period did not modify the pain and disability levels. For both groups, the pain and disability levels decreased after the intensive phase of treatments. Both groups maintained their pain scores at levels similar to the postintensive treatments throughout the follow-up period. For the disability scores, however, only the group that was given spinal manipulations during the follow-up period maintained their postintensive treatment scores. The disability scores of the other group went back to their pretreatment levels. Intensive spinal manipulation is effective for the treatment of chronic low back pain. This experiment suggests that maintenance spinal manipulations after intensive manipulative care may be beneficial to patients to maintain subjective postintensive treatment disability levels. Future studies, however, are needed to confirm the finding in a larger group of patients with chronic low-back pain.

Ionotropic Glutamate Receptors and Voltage-Gated Ca2+ Channels in Long-Term Potentiation of Spinal Dorsal Horn Synapses and Pain Hypersensitivity

PubMed Central

Youn, Dong-ho; Gerber, Gábor; Sather, William A.

2013-01-01

Over the last twenty years of research on cellular mechanisms of pain hypersensitivity, long-term potentiation (LTP) of synaptic transmission in the spinal cord dorsal horn (DH) has emerged as an important contributor to pain pathology. Mechanisms that underlie LTP of spinal DH neurons include changes in the numbers, activity, and properties of ionotropic glutamate receptors (AMPA and NMDA receptors) and of voltage-gated Ca2+ channels. Here, we review the roles and mechanisms of these channels in the induction and expression of spinal DH LTP, and we present this within the framework of the anatomical organization and synaptic circuitry of the spinal DH. Moreover, we compare synaptic plasticity in the spinal DH with classical LTP described for hippocampal synapses. PMID:24224102

Proinflammatory cytokines oppose opioid induced acute and chronic analgesia

PubMed Central

Hutchinson, Mark R.; Coats, Benjamen D.; Lewis, Susannah S.; Zhang, Yingning; Sprunger, David B.; Rezvani, Niloofar; Baker, Eric M.; Jekich, Brian M.; Wieseler, Julie L.; Somogyi, Andrew A.; Martin, David; Poole, Stephen; Judd, Charles M.; Maier, Steven F.; Watkins, Linda R.

2008-01-01

Spinal proinflammatory cytokines are powerful pain-enhancing signals that contribute to pain following peripheral nerve injury (neuropathic pain). Recently, one proinflammatory cytokine, interleukin-1, was also implicated in the loss of analgesia upon repeated morphine exposure (tolerance). In contrast to prior literature, we demonstrate that the action of several spinal proinflammatory cytokines oppose systemic and intrathecal opioid analgesia, causing reduced pain suppression. In vitro morphine exposure of lumbar dorsal spinal cord caused significant increases in proinflammatory cytokine and chemokine release. Opposition of analgesia by proinflammatory cytokines is rapid, occurring ≤5 minutes after intrathecal (perispinal) opioid administration. We document that opposition of analgesia by proinflammatory cytokines cannot be accounted for by an alteration in spinal morphine concentrations. The acute anti-analgesic effects of proinflammatory cytokines occur in a p38 mitogen-activated protein kinase and nitric oxide dependent fashion. Chronic intrathecal morphine or methadone significantly increased spinal glial activation (toll-like receptor 4 mRNA and protein) and the expression of multiple chemokines and cytokines, combined with development of analgesic tolerance and pain enhancement (hyperalgesia, allodynia). Statistical analysis demonstrated that a cluster of cytokines and chemokines was linked with pain-related behavioral changes. Moreover, blockade of spinal proinflammatory cytokines during a stringent morphine regimen previously associated with altered neuronal function also attenuated enhanced pain, supportive that proinflammatory cytokines are importantly involved in tolerance induced by such regimens. These data implicate multiple opioid-induced spinal proinflammatory cytokines in opposing both acute and chronic opioid analgesia, and provide a novel mechanism for the opposition of acute opioid analgesia. PMID:18599265

Abdominal pain of spinal origin. Value of intercostal block.

PubMed Central

Ashby, E. C.

1977-01-01

A prospective study was made of 73 patients presenting in one year with abdominal pain provisionally diagnosed as of spinal origin. The criteria for audit of diagnosis and treatment are defined. The diagnosis was confirmed in 53 patients, 49 of whom had been treated with a lignocaine intercostal block in the relevant segment. Thirty-three of these (67.3%) had both complete and prolonged relief. It is suggested that the block causes interruption of a vicious circle of pain and muscle spasm in a 'spinal reflex pain syndrome'. PMID:860866

The regional effect of spinal manipulation on the pressure pain threshold in asymptomatic subjects: a systematic literature review.

PubMed

Honoré, Margaux; Leboeuf-Yde, Charlotte; Gagey, Olivier

2018-01-01

Spinal manipulation (SM) has been shown to have an effect on pain perception. More knowledge is needed on this phenomenon and it would be relevant to study its effect in asymptomatic subjects. To compare regional effect of SM on pressure pain threshold (PPT) vs. sham, inactive control, mobilisation, another SM, and some type of physical therapy. In addition, we reported the results for the three different spinal regions. A systematic search of literature was done using PubMed, Embase and Cochrane. Search terms were ((spinal manipulation) AND (experimental pain)); ((spinal manipulative therapy OR spinal manipulation) AND ((experimental pain OR quantitative sensory testing OR pressure pain threshold OR pain threshold)) (Final search: June 13th 2017). The inclusion criteria were SM performed anywhere in the spine; the use of PPT, PPT tested in an asymptomatic region and on the same day as the SM. Studies had to be experimental with at least one external or internal control group. Studies on only spinal motion or tenderness, other reviews, case reports, and less than 15 invited participants in each group were excluded. Evidence tables were constructed with information relevant to each research question and by spinal region. Results were reported in relation to statistical significance and were interpreted taking into account their quality. Only 12 articles of 946 were accepted. The quality of studies was generally good. In 8 sham controlled studies, a psychologically and physiologically "credible" sham was found in only 2 studies. A significant difference was noted between SM vs. Sham, and between SM and an inactive control. No significant difference in PPT was found between SM and another SM, mobilisation or some type of physical therapy. The cervical region more often obtained significant findings as compared to studies in the thoracic or lumbar regions. SM has an effect regionally on pressure pain threshold in asymptomatic subjects. The clinical significance of this must be quantified. More knowledge is needed in relation to the comparison of different spinal regions and different types of interventions.

Anti-allodynic effect of intrathecal processed Aconitum jaluense is associated with the inhibition of microglial activation and P2X7 receptor expression in spinal cord.

PubMed

Yang, Jihoon; Park, Keun Suk; Yoon, Jae Joon; Bae, Hong-Beom; Yoon, Myung Ha; Choi, Jeong Il

2016-07-13

For their analgesic and anti-arthritic effects, Aconitum species have been used in folk medicine in some East Asian countries. Although their analgesic effect is attributed to its action on voltage-dependent sodium channels, they also suppress purinergic receptor expression in dorsal root ganglion neurons in rats with neuropathic pain. In vitro study also demonstrated that the Aconitum suppresses ATP-induced P2X7 receptor (P2X7R)-mediated inflammatory responses in microglial cell lines. Herein, we examined the effect of intrathecal administration of thermally processed Aconitum jaluense (PA) on pain behavior, P2X7R expression and microglial activation in a rat spinal nerve ligation (SNL) model. Mechanical allodynia induced by L5 SNL in Sprague-Dawley rats was measured using the von Frey test to evaluate the effect of intrathecal injection of PA. Changes in the expression of P2X7R in the spinal cord were examined using RT-PCR and Western blot analysis. In addition, the effect of intrathecal PA on microglial activation was evaluated by immunofluorescence. Intrathecal PA attenuated mechanical allodynia in a dose-dependent manner showing both acute and chronic effects with 65 % of the maximal possible effect. The expression and production of spinal P2X7R was increased five days after SNL, but daily intrathecal PA injection significantly inhibited the increase to the level of naïve animals. Immunofluorescence of the spinal cord revealed a significant increase in P2X7R expression and activation of microglia in the dorsal horn, which was inhibited by intrathecal PA treatment. P2X7R co-localized with microglia marker, but not neurons. Intrathecal PA exerts anti-allodynic effects in neuropathic pain, possibly by suppressing P2X7R production and expression as well as reducing microglial activation in the spinal cord.

Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment

DTIC Science & Technology

2013-10-01

collection in underway. 15. SUBJECT TERMS Spinal Cord Injury, Immunogenetics, Chronic pain, Opioids 16. SECURITY CLASSIFICATION OF: 17...prototypic opioid , morphine, is capable of TLR4-mediated proinflammation6-8 . As such, exposure to morphine at the time of injury may result in...fashion to the spinal cord injury and/or to experience inflammation in response to opioid exposure. Critically, this genetic variability may

Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment

DTIC Science & Technology

2014-10-01

collection in underway. 15. SUBJECT TERMS Spinal Cord Injury, Immunogenetics, Chronic pain, Opioids 16. SECURITY CLASSIFICATION OF: 17...The prototypic opioid , morphine, is capable of TLR4-mediated proinflammation6-8. As such, exposure to morphine at the time of injury may result in...proinflammatory fashion to the spinal cord injury, and/or to experience inflammation in response to opioid exposure. Critically, this genetic variability

Epigenetic suppression of potassium-chloride co-transporter 2 expression in inflammatory pain induced by complete Freund's adjuvant (CFA).

PubMed

Lin, C-R; Cheng, J-K; Wu, C-H; Chen, K-H; Liu, C-K

2017-02-01

Multiple mechanisms contribute to the stimulus-evoked pain hypersensitivity that may be experienced after peripheral inflammation. Persistent pathological stimuli in many pain conditions affect the expression of certain genes through epigenetic alternations. The main purpose of our study was to investigate the role of epigenetic modification on potassium-chloride co-transporter 2 (KCC2) gene expression in the persistence of inflammatory pain. Persistent inflammatory pain was induced through the injection of complete Freund's adjuvant (CFA) in the left hind paw of rats. Acetyl-histone H3 and H4 level was determined by chromatin immunoprecipitation in the spinal dorsal horn. Pain behaviour and inhibitory synaptic function of spinal cord were determined before and after CFA injection. KCC2 expression was determined by real time RT-PCR and Western blot. Intrathecal KCC2 siRNA (2 μg per 10 μL per rat) or HDAC inhibitor (10 μg per 10 μL per rat) was injected once daily for 3 days before CFA injection. Persistent inflammatory pain epigenetically suppressed KCC2 expression through histone deacetylase (HDAC)-mediated histone hypoacetylation, resulting in decreased inhibitory signalling efficacy. KCC2 knock-down caused by intrathecal administration of KCC2 siRNA in naïve rats reduced KCC2 expression in the spinal cord, leading to sensitized pain behaviours and impaired inhibitory synaptic transmission in their spinal cords. Moreover, intrathecal HDAC inhibitor injection in CFA rats increased KCC2 expression, partially restoring the spinal inhibitory synaptic transmission and relieving the sensitized pain behaviour. These findings suggest that the transcription of spinal KCC2 is regulated by histone acetylation epigenetically following CFA. Persistent pain suppresses KCC2 expression through HDAC-mediated histone hypoacetylation and consequently impairs the inhibitory function of inhibitory interneurons. Drugs such as HDAC inhibitors that suppress the influences of persistent pain on the expression of KCC2 may serve as a novel analgesic. © 2016 European Pain Federation - EFIC®.

Optogenetic exploration and modulation of pain processing.

PubMed

Xie, Yu-Feng; Wang, Jing; Bonin, Robert P

2018-08-01

Intractable pain is the single most common cause of disability, affecting more than 20% of the population world-wide. There is accordingly a global effort to decipher how changes in nociceptive processing in the peripheral and central nervous systems contribute to the onset and maintenance of chronic pain. The past several years have brought rapid progress in the adaptation of optogenetic approaches to study and manipulate the activity of sensory afferents and spinal cord neurons in freely behaving animals, and to investigate cortical processing and modulation of pain responses. This review discusses methodological advances that underlie this recent progress, and discusses practical considerations for the optogenetic modulation of nociceptive sensory processing. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Phosphorylation of spinal signaling-regulated kinases by acute uterine cervical distension in rats.

PubMed

Wang, L Z; Liu, X; Wu, W X; Chai, R K; Chang, X Y

2010-01-01

Spinal extracellular signaling-regulated kinase 1 and 2 (ERK 1/2) have been found to contribute to nociceptive processing, but the role of spinal ERK 1/2 in visceral pain related to the uterine cervix, the source of pain during the first stage of labor, is unknown. The aim of this study was to investigate ERK activation (phosphorylation) in spinal dorsal horn neurons after acute uterine cervical distension. Under intraperitoneal anesthesia using chloral hydrate 300 mg/kg, female Sprague-Dawley rats were exposed to a 10-s uterine cervical distension of 25, 50, 75, and 100g or no distension (sham). The electromyographic response in the rectus abdominis muscle and mean arterial blood pressure and heart rate changes to uterine cervical distension were determined. The numbers of phosphorylated-ERK 1/2- immunoreactive (pERK 1/2-IR) dorsal horn neurons in cervical (C5-8), thoracic (T5-8), thoracolumbar (T12-L2) and lumbosacral (L(6)-S(1)) segments were counted using immunohistochemistry. Compared with the non-distended sham rats, uterine cervical distension resulted in a stimulus-dependent increase in electromyographic activity and the number of pERK-IR neurons that selectively located to the thoracolumbar segment, mostly in the deep dorsal and the central canal regions. The time course study demonstrated that spinal ERK activation peaked at 60 min with a slow decline for 120 min after uterine cervical distension stimulation. This study suggests that activation of spinal ERK might be involved in acute visceral pain arising from the uterine cervix. Copyright 2009 Elsevier Ltd. All rights reserved.

[Constitutional narrowing of the cervical spinal canal. Radiological and clinical findings].

PubMed

Ritter, G; Rittmeyer, K; Hopf, H C

1975-02-21

A constitutional narrowing of the cervical spinal canal was seen in 31 patients with neurological disorders. The ratio of the inner diameter of the spinal canal to the diameter of the vertebral body was smaller than 1 (normal greater than 1). Clinical signs were observed from 45 years upwards where reactivedegenerative changes cause additional narrowing. The majority of patients were male, predominantly heavy manual labourers. There is often a trauma preceding. On myelography multilocular deformations of the spinal subarachnoid space and nerve roots are seen. On the mechanical narrowing of the spinal canal a vascular factor supervenes, caused by exostoses, intervertebral disc protrusions, and fibrosing processes. Clinically a chronic progressive spinal transection syndrome (cervical myelopathy) dominates besides a multilocular root involvement. Posterior column sensibility is predominantly lost. Pain in the extemities and the cervical column is an early symptom. Non-specific CSF changes occur frequently. In case of root involvement the electromyogram is pathological. The prognosis is bad. Operation can only remove reactive processes but not the constitutional anomaly.

A comprehensive review of pulsed radiofrequency in the treatment of pain associated with different spinal conditions

PubMed Central

Facchini, Giancarlo; Spinnato, Paolo; Guglielmi, Giuseppe; Bazzocchi, Alberto

2017-01-01

Objective: The objective of this review was to evaluate the efficacy of pulsed radiofrequency (PRF) treatment of pain associated with different spinal conditions. The mechanisms of action and biological effects are shortly discussed to provide the scientific basis for this radiofrequency modality. Methods: We systematically searched for clinical studies on spinal clinical conditions using PRF. We searched the MEDLINE (PubMed) database. We classified the information in one table focusing on randomized controlled trials (RCTs) and other types of studies. Date of last electronic search was October 2016. Results: We found four RCTs that evaluated the efficacy of PRF on cervical radicular pain and five observational studies. Two trials and three observational studies were conducted in patients with facet pain. For disc-related pathology, we found one RCT with PRF applied intradiscally and three RCTs for dorsal root ganglia PRF modulation lumbosacral radicular pain. For sacroiliac joint pain, spondylolisthesis, malignancies and other minor spinal pathology, limited studies were conducted. Conclusion: From the available evidence, the use of PRF to the dorsal root ganglion in cervical radicular pain is compelling. With regard to its lumbosacral counterpart, the use of PRF cannot be similarly advocated in view of the absence of standardization of PRF parameters, enrolment criteria and different methods in reporting results; but, the evidence is interesting. The use of PRF in lumbar facet pain was found to be less effective than conventional RF techniques. For the other different spinal conditions, we need further studies to assess the effectiveness of PRF. Advances in knowledge: The use of PRF in lumbar facet pain was found to be less effective than conventional RF techniques. For the other different spinal conditions, we need further studies to assess the effectiveness of PRF. PMID:28186832

Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.

PubMed

Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.

Neck pain in children: a retrospective case series.

PubMed

Cox, Jocelyn; Davidian, Christine; Mior, Silvano

2016-09-01

Spinal pain in the paediatric population is a significant health issue, with an increasing prevalence as they age. Paediatric patients attend for chiropractor care for spinal pain, yet, there is a paucity of quality evidence to guide the practitioner with respect to appropriate care planning. A retrospective chart review was used to describe chiropractic management of paediatric neck pain. Two researchers abstracted data from 50 clinical files that met inclusion criteria from a general practice chiropractic office in the Greater Toronto Area, Canada. Data were entered into SPSS 15 and descriptively analyzed. Fifty paediatric neck pain patient files were analysed. Patients' age ranged between 6 and 18 years (mean 13 years). Most (98%) were diagnosed with Grade I-II mechanical neck pain. Treatment frequency averaged 5 visits over 19 days; with spinal manipulative therapy used in 96% of patients. Significant improvement was recorded in 96% of the files. No adverse events were documented. Paediatric mechanical neck pain appears to be successfully managed by chiropractic care. Spinal manipulative therapy appears to benefit paediatric mechanical neck pain resulting from day-today activities with no reported serious adverse events. Results can be used to inform clinical trials assessing effectiveness of manual therapy in managing paediatric mechanical neck pain.

Effects of intrathecal ketorolac on human experimental pain

PubMed Central

Eisenach, James C.; Curry, Regina; Tong, Chuanyao; Houle, Timothy T.; Yaksh, Tony L.

2010-01-01

Background Nonsteroidal antiinflammatory drugs, the most commonly used analgesics, reduce pain by inhibiting cyclooxygenase at peripheral sites of inflammation, but potentially also by inhibiting cyclooxygenase in the central nervous system, especially the spinal cord. Animal studies suggest that products of cyclooxygenase in the spinal cord do not alter pain responses to acute noxious stimuli, but reduce pain and sensitization following peripheral inflammation. We used spinal injection of small doses of the cyclooxygenase inhibitor, ketorolac, to survey the role of spinal cyclooxygenase in human experimental pain and hypersensitivity states. Methods Following regulatory agency approval and informed consent, we examined the effect of 2.0 mg intrathecal ketorolac in 41 healthy volunteers to acute noxious thermal stimuli in normal skin and to mechanical stimuli in skin sensitized by topical capsaicin or ultraviolet burn. We also examined the effect of intravenous ketorolac, Results Intrathecal ketorolac reduced hypersensitivity when it was induced by a combination of ultraviolet burn plus intermittent heat and, according to one of two analytical strategies, when it was induced by ultraviolet burn alone. Conclusions These data suggest a more limited role for spinal cord cyclooxygenase in human pain states than predicted by studies in animals. PMID:20395821

Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav1.3 expression and decreasing spinal microglial activation

PubMed Central

2011-01-01

Background Intrathecal lidocaine reverses tactile allodynia after nerve injury, but whether neuropathic pain is attenuated by intrathecal lidocaine pretreatment is uncertain. Methods Sixty six adult male Sprague-Dawley rats were divided into three treatment groups: (1) sham (Group S), which underwent removal of the L6 transverse process; (2) ligated (Group L), which underwent left L5 spinal nerve ligation (SNL); and (3) pretreated (Group P), which underwent L5 SNL and was pretreated with intrathecal 2% lidocaine (50 μl). Neuropathic pain was assessed based on behavioral responses to thermal and mechanical stimuli. Expression of sodium channels (Nav1.3 and Nav1.8) in injured dorsal root ganglia and microglial proliferation/activation in the spinal cord were measured on post-operative days 3 (POD3) and 7 (POD7). Results Group L presented abnormal behavioral responses indicative of mechanical allodynia and thermal hyperalgesia, exhibited up-regulation of Nav1.3 and down-regulation of Nav1.8, and showed increased microglial activation. Compared with ligation only, pretreatment with intrathecal lidocaine before nerve injury (Group P), as measured on POD3, palliated both mechanical allodynia (p < 0.01) and thermal hyperalgesia (p < 0.001), attenuated Nav1.3 up-regulation (p = 0.003), and mitigated spinal microglial activation (p = 0.026) by inhibiting phosphorylation (activation) of p38 MAP kinase (p = 0.034). p38 activation was also suppressed on POD7 (p = 0.002). Conclusions Intrathecal lidocaine prior to SNL blunts the response to noxious stimuli by attenuating Nav1.3 up-regulation and suppressing activation of spinal microglia. Although its effects are limited to 3 days, intrathecal lidocaine pretreatment can alleviate acute SNL-induced neuropathic pain. PMID:21676267

Prevalence and factors associated with a higher risk of neck and back pain among permanent wheelchair users: a cross-sectional study.

PubMed

Kovacs, Francisco M; Seco, Jesús; Royuela, Ana; Barriga, Andrés; Zamora, Javier

2018-04-01

Cross-sectional study. To determine the prevalence of, and factors associated with, spinal pain among wheelchair users. Four Spanish hospitals specialized in providing care for wheelchair users. Persons who had used a wheelchair for a median (IRQ) of 10 (5;19) years, 27% of them due to reasons other than spinal cord injury, were recruited consecutively (n = 750). Data on 43 demographic, psychosocial, ergonomic, and clinical variables were collected, and analyzed. Main outcome measures were: point prevalence of neck (NP), thoracic (TP), low back pain (LBP), and pain at any spinal level (PASL); and factors associated with them. Point prevalence was 56% for NP, 54% for TP, 45% for LBP, and 76% for PSAL. PASL was associated with a lower quality of life (OR (95% CI) 0.91 (0.86; 0.97)). Multivariable regression models showed that the main factors associated with significant pain (≥1.5 VAS points) were: (a) For NP: cervical spinal injury and wheelchair seat cushion thickness, (b) For TP: thoracic spinal injury and sagittal index, (c) For LBP: thoracic or lumbar spinal injury, with some sensitivity remaining, (d) For PASL: being female, living alone, and using a non-power wheelchair. Discrimination (AUC) of these models ranged between 0.638 and 0.818. p-values in the Hosmer-Lemeshow test ranged between 0.420 and 0.701. Prevalence of spinal pain among wheelchair users is high. It is associated with a lower quality of life. Future studies should assess whether using a power wheelchair affects PASL, and if the thickness of seat cushion affects NP. Spanish Back Pain Research Network.

Spinal cord compression in a patient with a pain pump for failed back syndrome: a chalk-like precipitate mimicking a spinal cord neoplasm: case report.

PubMed

Wadhwa, Rishi K; Shaya, Mark R; Nanda, Anil

2006-02-01

The use of intrathecal morphine has been effective with few complications for chronic intractable pain of both benign and malignant origins. A rare but serious problem that exists is the formation of an inflammatory mass at the catheter tip of the pain pump. We report the case of a 67-year-old female patient with failed back syndrome who presented with sensory complaints and back pain. Magnetic resonance imaging revealed impingement on the thoracic cord by a mass. The mass was originally thought to be a spinal cord tumor; however, operation and chemical analysis of the mass showed that it was a bupivacaine precipitate at the tip of the catheter of the pain pump. This is the first such case, to our knowledge, of a bupivacaine precipitate mimicking a spinal cord tumor.

Progressive Paraplegia from Spinal Cord Stimulator Lead Fibrotic Encapsulation: A Case Report.

PubMed

Benfield, Jon; Maknojia, Asif; Epstein, Franklin

2016-03-01

Ten years after placement of a spinal cord stimulator (SCS) and resolution of pain, this patient presented with progressive paraplegia, worsening thoracic radicular pain at the same dermatome level of the electrodes, and bowel and bladder incontinence. Computed tomographic myelogram confirmed thoracic spinal cord central canal stenosis at the level of electrodes. After removal of the fibrotic tissue and electrodes, the patient had resolution of his thoracic radicular pain and a return of his pre-SCS pain and minimal neurologic and functional return. To the authors' knowledge, no studies have been identified with thoracic SCS lead fibrosis in the United States causing permanent paraplegia. Only one other case has been reported in Madrid, Spain. Patients with SCS presenting with loss of pain relief, new-onset radicular or neuropathic pain in same dermatome(s) as SCS electrodes, worsening neuromuscular examination, or new bladder or bowel incontinence need to be evaluated for complications regarding SCS implantation causing spinal stenosis and subsequent cord compression to avoid permanent neurologic deficits.

Altered spinal arachidonic acid turnover after peripheral nerve injury regulates regional glutamate concentration and neuropathic pain behaviors in rats.

PubMed

Sung, Backil; Wang, Shuxing; Zhou, Bei; Lim, Grewo; Yang, Liling; Zeng, Qing; Lim, Jeong-Ae; Wang, Jing Dong; Kang, Jing X; Mao, Jianren

2007-09-01

Spinal glutamate transporters (GT) have been implicated in the mechanisms of neuropathic pain; however, how spinal GT uptake activity is regulated remains unclear. Here we show that alteration of spinal arachidonic acid (AA) turnover after peripheral nerve injury regulated regional GT uptake activity and glutamate homeostasis. Chronic constriction nerve injury (CCI) in rats significantly reduced spinal GT uptake activity ((3)H-glutamate uptake) with an associated increase in extracellular AA and glutamate concentration from spinal microdialysates on postoperative day 8. AACOCF3 (a cytosolic phospholipase A2 inhibitor, 30mug) given intrathecally twice a day for postoperative day 1-7 reversed this CCI-induced spinal AA production, prevented the reduced spinal GT uptake activity and increased extracellular glutamate concentration. Conversely, alteration of spinal AA metabolism by diclofenac (a cyclooxygenase 1/2 inhibitor, 200mug) further reduced spinal GT uptake activity and increased extracellular glutamate concentration in CCI rats. GT uptake activity was also attenuated when AA (10 or 100nM) was directly added into spinal samples of naïve rats in an in vitro(3)H-glutamate uptake assay, indicating a direct inhibitory effect of AA on GT uptake activity. Consistent with these findings, AACOCF3 reduced the development of both thermal hyperalgesia and mechanical allodynia, whereas diclofenac exacerbated thermal hyperalgesia, in CCI rats. Thus, spinal AA turnover may serve as a regulator in CCI-induced changes in regional GT uptake activity, glutamate homeostasis, and neuropathic pain behaviors. These data suggest that regulating spinal AA turnover may be a useful approach to improving the clinical management of neuropathic pain.

Percutaneous and Endoscopic Adhesiolysis in Managing Low Back and Lower Extremity Pain: A Systematic Review and Meta-analysis.

PubMed

Helm, Standiford; Racz, Gabor B; Gerdesmeyer, Ludger; Justiz, Rafael; Hayek, Salim M; Kaplan, Eugene D; El Terany, Mohamed Ahamed; Knezevic, Nebojsa Nick

2016-02-01

Chronic refractory low back and lower extremity pain is frustrating to treat. Percutaneous adhesiolysis and spinal endoscopy are techniques which can treat chronic refractory low back and lower extremity pain.Percutaneous adhesiolysis is performed by placing the catheter into the tissue plane at the ventrolateral aspect of the foramen so that medications can be injected. Adhesiolysis is used both for pain caused by scarring which is not resistant to catheter placement and other sources of pain, including inflammation in the absence of scarring.Mechanical lysis of scars with a catheter may or may not be necessary for percutaneous adhesiolysis to be effective. Spinal endoscopy allows direct visualization of the epidural space and has the possibility to use laser energy to treat pathology. A systematic review of the effectiveness of percutaneous adhesiolysis and spinal endoscopic adhesiolysis to treat chronic refractory low back and lower extremity pain. To evaluate and update the effectiveness of percutaneous adhesiolysis and spinal endoscopic adhesiolysis to treat chronic refractory low back and lower extremity pain. The available literature on percutaneous adhesiolysis and spinal endoscopic adhesiolysis in treating persistent low back and leg pain was reviewed. The quality of each article used in this analysis was assessed. The level of evidence was classified on a 5-point scale from strong, based upon multiple randomized controlled trials to weak, based upon consensus, as developed by the U.S. Preventive Services Task Force (USPSTF) and modified by ASIPP. Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to September 2015, and manual searches of the bibliographies of known primary and review articles. Pain relief of at least 50% and functional improvement of at least 40% were the primary outcome measures. Short-term efficacy was defined as improvement of 6 months or less; whereas, long-term efficacy was defined more than 6 months. For this systematic review, 45 studies were identified. Of these, for percutaneous adhesiolysis there were 7 randomized controlled trials and 3 observational studies which met the inclusion criteria. For spinal endoscopy, there was one randomized controlled trial and 3 observational studies. Based upon 7 randomized controlled trials showing efficacy, with no negative trials, there is Level I or strong evidence of the efficacy of percutaneous adhesiolysis in the treatment of chronic refractory low back and lower extremity pain. Based upon one high-quality randomized controlled trial, there is Level II to III evidence supporting the use of spinal endoscopy in treating chronic refractory low back and lower extremity pain. The evidence is Level I or strong that percutaneous adhesiolysis is efficacious in the treatment of chronic refractory low back and lower extremity pain. Percutaneous adhesiolysis may be considered as a first-line treatment for chronic refractory low back and lower extremity pain. The evidence is Level II to III that spinal endoscopy is effective in the treatment of chronic refractory low back and lower extremity pain. Spinal pain, chronic low back pain, post lumbar surgery syndrome, epidural scarring, adhesiolysis, endoscopy, radicular pain.

Differential effects of left and right neuropathy on opioid gene expression in lumbar spinal cord.

PubMed

Kononenko, Olga; Mityakina, Irina; Galatenko, Vladimir; Watanabe, Hiroyuki; Bazov, Igor; Gerashchenko, Anna; Sarkisyan, Daniil; Iatsyshyna, Anna; Yakovleva, Tatiana; Tonevitsky, Alex; Marklund, Niklas; Ossipov, Michael H; Bakalkin, Georgy

2018-05-28

The endogenous opioid system (EOS) controls the processing of nociceptive stimuli and is a pharmacological target for opioids. Alterations in expression of the EOS genes under neuropathic pain condition may account for low efficacy of opioid drugs. We here examined whether EOS expression patterns are altered in the lumbar spinal cord of the rats with spinal nerve ligation (SNL) as a neuropathic pain model. Effects of the left- and right-side SNL on expression of EOS genes in the ipsi- and contralateral spinal domains were analysed. The SNL-induced changes were complex and different between the genes; between the dorsal and ventral spinal domains; and between the left and right sides of the spinal cord. Prodynorphin (Pdyn) expression was upregulated in the ipsilateral dorsal domains by each the left and right-side SNL, while changes in expression of μ-opioid receptor (Oprm1) and proenkephalin (Penk) genes were dependent on the SNL side. Changes in expression of the Pdyn and κ-opioid receptor (Oprk1) genes were coordinated between the ipsi- and contralateral sides. Withdrawal response thresholds, indicators of mechanical allodynia correlated negatively with Pdyn expression in the right ventral domain after right side SNL. These findings suggest multiple roles of the EOS gene products in spinal sensitization and changes in motor reflexes, which may differ between the left and right sides. Copyright © 2018. Published by Elsevier B.V.

Opioid administration following spinal cord injury: Implications for pain and locomotor recovery

PubMed Central

Woller, Sarah A.; Hook, Michelle A.

2013-01-01

Approximately one-third of people with a spinal cord injury (SCI) will experience persistent neuropathic pain following injury. This pain negatively affects quality of life and is difficult to treat. Opioids are among the most effective drug treatments, and are commonly prescribed, but experimental evidence suggests that opioid treatment in the acute phase of injury can attenuate recovery of locomotor function. In fact, spinal cord injury and opioid administration share several common features (e.g. central sensitization, excitotoxicity, aberrant glial activation) that have been linked to impaired recovery of function, as well as the development of pain. Despite these effects, the interactions between opioid use and spinal cord injury have not been fully explored. A review of the literature, described here, suggests that caution is warranted when administering opioids after SCI. Opioid administration may synergistically contribute to the pathology of SCI to increase the development of pain, decrease locomotor recovery, and leave individuals at risk for infection. Considering these negative implications, it is important that guidelines are established for the use of opioids following spinal cord and other central nervous system injuries. PMID:23501709

Lycopene ameliorates neuropathic pain by upregulating spinal astrocytic connexin 43 expression.

PubMed

Zhang, Fang Fang; Morioka, Norimitsu; Kitamura, Tomoya; Fujii, Shiori; Miyauchi, Kazuki; Nakamura, Yoki; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

2016-06-15

Peripheral nerve injury upregulates tumor necrosis factor (TNF) expression. In turn, connexin 43 (Cx43) expression in spinal astrocytes is downregulated by TNF. Therefore, restoration of spinal astrocyte Cx43 expression to normal level could lead to the reduction of nerve injury-induced pain. While the non-provitaminic carotenoid lycopene reverses thermal hyperalgesia in mice with painful diabetic neuropathy, the antinociceptive mechanism is not entirely clear. The current study evaluated whether the antinociceptive effect of lycopene is mediated through the modulation of Cx43 expression in spinal astrocytes. The effect of lycopene on Cx43 expression was examined in cultured rat spinal astrocytes. The effect of intrathecal lycopene on Cx43 expression and neuropathic pain were evaluated in mice with partial sciatic nerve ligation (PSNL). Treatment of cultured rat spinal astrocytes with lycopene reversed TNF-induced downregulation of Cx43 protein expression through a transcription-independent mechanism. By contrast, treatment of cultured spinal astrocytes with either pro-vitamin A carotenoid β-carotene or antioxidant N-acetyl cysteine had no effect on TNF-induced downregulation of Cx43 protein expression. In addition, repeated, but not single, intrathecal treatment with lycopene of mice with a partial sciatic nerve ligation significantly prevented not only the downregulation of Cx43 expression in spinal dorsal horn but mechanical hypersensitivity as well. The current findings suggest a significant spinal mechanism that mediates the analgesic effect of lycopene, through the restoration of normal spinal Cx43 expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Mast cell degranulation distinctly activates trigemino-cervical and lumbosacral pain pathways and elicits widespread tactile pain hypersensitivity.

PubMed

Levy, Dan; Kainz, Vanessa; Burstein, Rami; Strassman, Andrew M

2012-02-01

Mast cells (MCs) are tissue resident immune cells that participate in a variety of allergic and other inflammatory conditions. In most tissues, MCs are found in close proximity to nerve endings of primary afferent neurons that signal pain (i.e. nociceptors). Activation of MCs causes the release of a plethora of mediators that can activate these nociceptors and promote pain. Although MCs are ubiquitous, conditions associated with systemic MC activation give rise primarily to two major types of pain, headache and visceral pain. In this study we therefore examined the extent to which systemic MC degranulation induced by intraperitoneal administration of the MC secretagogue compound 48/80 activates pain pathways that originate in different parts of the body and studied whether this action can lead to development of behavioral pain hypersensitivity. Using c-fos expression as a marker of central nervous system neural activation, we found that intraperitoneal administration of 48/80 leads to the activation of dorsal horn neurons at two specific levels of the spinal cord; one responsible for processing cranial pain, at the medullary/C2 level, and one that processes pelvic visceral pain, at the caudal lumbar/rostral sacral level (L6-S2). Using behavioral sensory testing, we found that this nociceptive activation is associated with development of widespread tactile pain hypersensitivity within and outside the body regions corresponding to the activated spinal levels. Our data provide a neural basis for understanding the primacy of headache and visceral pain in conditions that involve systemic MC degranulation. Our data further suggest that MC activation may lead to widespread tactile pain hypersensitivity. Copyright © 2011 Elsevier Inc. All rights reserved.

Resolving TRPV1 and TNF-α Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1

PubMed Central

Park, Chul-Kyu; Lü, Ning; Xu, Zhen-Zhong; Liu, Tong; Serhan, Charles N.; Ji, Ru-Rong

2011-01-01

Mechanisms of inflammatory pain are not fully understood. We investigated the role of TRPV1 and TNF-α, two critical mediators for inflammatory pain, in regulating spinal cord synaptic transmission. We found in mice lacking Trpv1 the frequency but not the amplitude of spontaneous EPSCs (sEPSCs) in lamina II neurons of spinal cord slices is reduced. Further, C-fiber-induced spinal long-term potentiation (LTP) in vivo is abolished in Trpv1 knockout mice. TNF-α also increases sEPSC frequency but not amplitude in spinal lamina IIo neurons, and this increase is abolished in Trpv1 knockout mice. Single-cell PCR analysis revealed that TNF-α-responding neurons in lamina IIo are exclusively excitatory (vGluT2+) neurons. Notably, neuroprotectin-1 (NPD1), an anti-inflammatory lipid mediator derived from omega-3 polyunsaturated fatty acid (docosahexaenoic acid) blocks TNF-α- and capsaicin-evoked sEPSC frequency increases but has no effect on basal synaptic transmission. Strikingly, NPD1 potently inhibits capsaicin-induced TRPV1 current (IC50=0.4 nM) in dissociated dorsal root ganglion neurons, and this IC50 is ≈ 500 times lower than that of AMG9810, a commonly used TRPV1 antagonist. NPD1 inhibition of TRPV1 is mediated by GPCRs, since the effects were blocked by pertussis toxin. In contrast, NPD1 had not effect on mustard oil-induced TRPA1 currents. Spinal injection of NPD1, at very low doses (0.1–10 ng), blocks spinal LTP and reduces TRPV1-dependent inflammatory pain, without affecting baseline pain. NPD1 also reduces TRPV1-independent but TNF-α-dependent pain hypersensitivity. Our findings demonstrate a novel role of NPD1 in regulating TRPV1/TNF-α-mediated spinal synaptic plasticity and identify NPD1 as a novel analgesic for treating inflammatory pain. PMID:22016541

Transcutaneous electrical neurostimulation in musculoskeletal pain of acute spinal cord injuries.

PubMed

Richardson, R R; Meyer, P R; Cerullo, L J

1980-01-01

Cervical, thoracic, thoracolumbar, and lumbar fractures associated with physiologic complete or incomplete spinal cord injuries frequently have severe soft-tissue injury as well as severe pain associated with the site or area of injury. Transcutaneous electrical neurostimulation has proved effective in the treatment of various causes of severe acute and chronic intractable pains. We applied this modality to a group of 20 patients who had acute spinal cord injuries and pain associated with severe, extensive soft-tissue injury. Its advantages include ease of application, lack of major complications, increased intestinal peristalsis, and avoidance of narcotic analgesic medications. It also produced significant (greater than 50%) pain relief in 75% of patients treated by transcutaneous electrical neurostimulation.

Maintaining Shoulder Health After Spinal Cord Injury: A Guide to Understanding Treatments for Shoulder Pain

PubMed Central

Van Straaten, Meegan G.; Cloud, Beth A.; Zhao, Kristin D.; Fortune, Emma; Morrow, Melissa M. B.

2017-01-01

Shoulder pain from overuse of the arm is common after spinal cord injury (SCI). This pain can be difficult to eliminate. There are many other complications after SCI; therefore, shoulder pain is sometimes not the first priority. However, if neglected for too long, shoulder pain could mean that more serious problems are happening inside the shoulder joint. Here we present the options available when treatment for shoulder pain is needed. PMID:28185640

Pain in adolescents with spinal muscular atrophy and Duchenne and Becker muscular dystrophy.

PubMed

Lager, Christina; Kroksmark, Anna-Karin

2015-09-01

The purpose of this study was to explore the prevalence, nature and scope of pain in adolescents with spinal muscular atrophy and Duchenne and Becker muscular dystrophy and whether the pain differs between diagnostic groups or between adolescents with different ambulation status. Furthermore to study the consequences of pain and to identify pain-exacerbating and pain-relieving factors. In a national survey, fifty-five adolescents with spinal muscular atrophy and dystrophinopathy completed a questionnaire assessing pain frequency, duration, location using a body map, intensity and discomfort using visual analogue scales, pain interference using a modified version of Brief Pain Inventory and factors exacerbating and relieving pain. Sixty-nine per cent of the adolescents reported pain during the past three months and 50% reported chronic pain. The pain prevalence did not differ significantly between diagnostic groups or between ambulators and non-ambulators. The average pain intensity was graded as mild and the worst pain as moderate. The pain typically occurred weekly, most frequently in the neck/back or legs. General activity and mood were the areas that were most affected by pain. Common pain-exacerbating factors were sitting, too much movement/activity and being lifted or transferred. Pain is a frequent problem in adolescents with spinal muscular atrophy and dystrophinopathy. The assessments used enable an understanding both of the nature and scope of pain and of the impact of pain in everyday life. The study highlights the importance of assessing pain in a systematic manner and offering an individual approach to interventions designed to reduce pain in this population. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Back pain: a real target for spinal cord stimulation?

PubMed

Rigoard, Philippe; Delmotte, Alexandre; D'Houtaud, Samuel; Misbert, Lorraine; Diallo, Bakari; Roy-Moreau, Aline; Durand, Sylvain; Royoux, Solène; Giot, Jean-Philippe; Bataille, Benoit

2012-03-01

Failed back surgery syndrome represents one of the most frequent etiologies of chronic back pain and is a major public health issue. Neurostimulation has currently not been validated in the treatment of back pain because of technological limitations in implantable spinal cord stimulation (SCS) systems. New-generation leads using several columns of stimulation can generate longitudinal and/or transverse stimulation fields into the spinal cord. To investigate, through extensive stimulation testing, the capacity of multicolumn tripolar leads to achieve back territory paresthesia coverage in refractory failed back surgery syndrome patients. Eleven patients implanted with a 16-contact spinal cord stimulation lead (Specify 5-6-5, Medtronic Inc) were assessed with a systematic exploration of 43 selected stimulation configurations to generate bilateral back paresthesia in addition to leg territory coverage. The tripolar lead successfully generated paresthesia in both bilateral back and leg territories in 9 patients (81.8%). Success rates of multicolumn stimulation patterns were significantly higher than for longitudinal configurations for lombodorsal paresthesia coverage. Six months after implantation, significant pain relief was obtained compared with preoperative evaluation for global pain (Visual Analog Scale, 2.25 vs 8.2 preoperatively; P < .05), leg pain (Visual Analog Scale, 0.5 vs 7.6 preoperatively; P < .05), and back pain (Visual Analog Scale, 1.5 vs 7.8 preoperatively; P < .05). These results suggest that multicolumn leads can reliably generate back pain coverage and favor pain relief outcomes. This may lead physicians to reconsider new indications for spinal cord stimulation. Expanding neurostimulation perspectives to intractable back pain syndromes could become realistic in the near future.

The Global Spine Care Initiative: a systematic review of individual and community-based burden of spinal disorders in rural populations in low- and middle-income communities.

PubMed

Hurwitz, Eric L; Randhawa, Kristi; Torres, Paola; Yu, Hainan; Verville, Leslie; Hartvigsen, Jan; Côté, Pierre; Haldeman, Scott

2017-12-27

The purpose of this review was to synthesize literature on the burden of spinal disorders in rural communities to inform the Global Spine Care Initiative care pathway and model of care for their application in medically underserved areas and low- and middle-income countries. A systematic review was conducted. Inclusion criteria included all age groups with nonspecific low back pain, neck pain, and associated disorders, nonspecific thoracic spinal pain, musculoskeletal chest pain, radiculopathy, or spinal stenosis. Study designs included observational study design (case-control, cross-sectional, cohort, ecologic, qualitative) or review or meta-analysis. After study selection, studies with low or moderate risk of bias were qualitatively synthesized. Of 1150 potentially relevant articles, 43 were eligible and included in the review. All 10 low and 18 moderate risk of bias studies were cross-sectional, 14 of which included rural residents only. All studies included estimates of low back pain prevalence, one included neck pain and one reported estimates for spinal disorders other than back or neck pain. The prevalence of low back pain appears greater among females and in those with less education, psychological factors (stress, anxiety, depression), and alcohol consumers. The literature is inconsistent as to whether back pain is more common in rural or urban areas. High risk of bias in many studies, lack of data on disability and other burden measures and few studies on conditions other than back and neck pain preclude a more comprehensive assessment of the individual and community-based burden of spinal disorders in less-developed communities. We identified few high-quality studies that may inform patients, providers, policymakers, and other stakeholders about spinal disorders and their burden on individuals and communities in most rural places of the developing world. These findings should be a call to action to devote resources for high-quality research to fill these knowledge gaps in medically underserved areas and low and middle-income countries. These slides can be retrieved under Electronic Supplementary Material.

What Is Chiropractic?

MedlinePlus

... Spinal Health Winter Activities Kids and Sports Exercising Outdoors with Baby Gardening Chronic Pain and Depression Preventing ... Spinal Health Winter Activities Kids and Sports Exercising Outdoors with Baby Gardening Chronic Pain and Depression Preventing ...

Mechanisms of Acupuncture-Electroacupuncture on Persistent Pain

PubMed Central

Zhang, Ruixin; Lao, Lixing; Ren, Ke; Berman, Brian M.

2014-01-01

In the last decade, preclinical investigations of electroacupuncture mechanisms on persistent tissue-injury (inflammatory), nerve-injury (neuropathic), cancer, and visceral pain have increased. These studies show that electroacupuncture activates the nervous system differently in health than in pain conditions, alleviates both sensory and affective inflammatory pain, and inhibits inflammatory and neuropathic pain more effectively at 2–10 Hz than at 100 Hz. Electroacupuncture blocks pain by activating a variety of bioactive chemicals through peripheral, spinal, and supraspinal mechanisms. These include opioids, which desensitize peripheral nociceptors and reduce pro-inflammatory cytokines peripherally and in the spinal cord, and serotonin and norepinephrine, which decrease spinal n-methyl-d-aspartate receptor subunit GluN1 phosphorylation. Additional studies suggest that electroacupuncture, when combined with low dosages of conventional analgesics, provides effective pain management that can forestall the side effects of often-debilitating pharmaceuticals. PMID:24322588

Prevalence of spinal disorders and their relationships with age and gender

PubMed Central

Alshami, Ali M.

2015-01-01

Objectives: To establish the period prevalence of spinal disorders referred to physical therapy in a university hospital over a 3-year period, and to determine the relationships of common spinal disorders with patients’ age and gender. Methods: This retrospective study was conducted in the Physical Therapy Department, King Fahd Hospital of the University, Dammam, Saudi Arabia. Computer data of all new electronic referrals from January 2011 to December 2013 were retrieved and reviewed. The computer data included demographic information, referring facility, and diagnosis/disorder. Results: One thousand six hundred and sixty-nine (28.1%) of all referred patients (5929) had spinal disorders. The most common disorders affected the lumbar spine (53.1%) and cervical spine (27.1%), and pain was the most common disorder. Neck pain (60.5%) was more common in patients <30 years old (p<0.001). Cervical spondylosis was common (~30%) in the >30 age groups. Spondylosis and low back pain were more prevalent in women (7.8% and 76.2%) than in men (73.9% and 3.3%). Conclusion: Spinal disorders were common compared with other disorders. Low back pain and neck pain were the most common spinal disorders. Age and gender were weakly related to some of the disorders that affected the lumbar and cervical spine. PMID:25987116

Dose response and structural injury in the disability of spinal injury.

PubMed

Patel, Mohammed Shakil; Sell, Philip

2013-03-01

In traumatic injury there is a clear relationship between the dose of energy involved, structural tissue damage and resultant disability after recovery. This relationship is often absent in cases of non-specific chronic low back pain that is perceived by patients as attributed to a workplace injury. There are many studies assessing risk factors for non-specific low back pain. However, studies addressing causality of back pain are deficient. To establish whether there exists a causal relationship between structural injury, low back pain and spinal disability. Retrospective analysis of prospectively gathered validated spinal outcome measures [Oswestry disability index (ODI), low back outcome score (LBO), modified somatic perception (MSP), modified Zung depression index (MZD)] between patients with healed high energy thoracolumbar spinal fractures and patients with self-perceived work-related low back pain. Causality was established according to two of Bradford Hill's criteria of medical causality, temporal and dose-response relationships. Twenty-three patients with spinal fractures (group 1) of average age 44 years were compared to 19 patients with self-reported back pain in the workplace pursuing claims for compensation (group 2) of average age 48 years. Both groups were comparable in terms of age and sex. The average ODI in group 1 was 28 % (SD 19) compared to 42 % (SD 19) in group 2 (P < 0.05). Similarly, LBOS was 39.7 versus 24.3 (P < 0.05), MSP 4.3 versus 9.3 (P < 0.05) and MZD 20.2 versus 34.8 (P < 0.05) in groups 1 and 2, respectively. Despite high-energy trauma and significant structural damage to the spine, patients with the high energy injuries had better spinal outcome scores in all measures. There is no 'dose-response' relationship between structural injury, low back pain and spinal disability. This is the reverse of what would be anticipated if structural injury was the cause of disability in workplace reported onset of low back pain.

Electroacupuncture attenuates mechanical allodynia by suppressing the spinal JNK1/2 pathway in a rat model of inflammatory pain.

PubMed

Du, Jun-Ying; Fang, Jian-Qiao; Liang, Yi; Fang, Jun-Fan

2014-09-01

Electroacupuncture (EA) has a substantial analgesic effect on inflammatory pain induced by complete Freund's adjuvant (CFA). The activation of the c-Jun N-terminal kinase 1/2 (JNK1/2) signal transduction pathway in the spinal cord is associated with inflammatory pain. However, the relationship between EA's analgesic effect and the JNK1/2 signal transduction pathway in the inflammatory pain remain unclear. In the present study, we used the established rat model of CFA-induced inflammatory pain to investigate the role of the spinal JNK1/2 pathway in EA-mediated analgesia. We observed a decrease in paw withdrawal thresholds and an increase in paw edema at 1 and 3 days after injecting CFA into the right hindpaw. CFA, 3 days after injection, upregulated expression of phospho-c-Jun N-terminal kinase1/2 (p-JNK1/2) protein and its downstream targets, the transcriptional regulators p-c-Jun and activator protein-1 (AP-1), as well as cyclooxygenase-2 (COX-2) and the transient receptor potential vanilloid 1 (TRPV1). EA significantly alleviated CFA-induced inflammatory pain. In addition, EA reduced p-JNK1/2 protein levels and COX-2 mRNA expressions, a degree of down-regulated p-c-Jun protein level and AP-1 DNA binding activity in the spinal dorsal horn of CFA-administered animals, but it had no effect on TRPV1 mRNA expression. Furthermore, EA and the JNK inhibitor SP600125 synergistically inhibited CFA-induced hyperalgesia and suppressed the COX-2 mRNA expression in the spinal dorsal horn. Our findings indicate that EA alleviates inflammatory pain behavior, at least in part, by reducing COX-2 expression in the spinal cord via the JNK1/2 signaling pathway. Inactivation of the spinal JNK1/2 signal transduction pathway maybe the potential mechanism of EA's antinociception in the inflammatory pain model. Copyright © 2014 Elsevier Inc. All rights reserved.

Overexpression of GDNF in the uninjured DRG exerts analgesic effects on neuropathic pain following segmental spinal nerve ligation in mice.

PubMed

Takasu, Kumiko; Sakai, Atsushi; Hanawa, Hideki; Shimada, Takashi; Suzuki, Hidenori

2011-11-01

Glial cell line-derived neurotrophic factor (GDNF), a survival-promoting factor for a subset of nociceptive small-diameter neurons, has been shown to exert analgesic effects on neuropathic pain. However, its detailed mechanisms of action are still unknown. In the present study, we investigated the site-specific analgesic effects of GDNF in the neuropathic pain state using lentiviral vector-mediated GDNF overexpression in mice with left fifth lumbar (L5) spinal nerve ligation (SNL) as a neuropathic pain model. A lentiviral vector expressing both GDNF and enhanced green fluorescent protein (EGFP) was constructed and injected into the left dorsal spinal cord, uninjured fourth lumbar (L4) dorsal root ganglion (DRG), injured L5 DRG, or plantar skin of mice. In SNL mice, injection of the GDNF-EGFP-expressing lentivirus into the dorsal spinal cord or uninjured L4 DRG partially but significantly reduced the mechanical allodynia in association with an increase in GDNF protein expression in each virus injection site, whereas injection into the injured L5 DRG or plantar skin had no effects. These results suggest that GDNF exerts its analgesic effects in the neuropathic pain state by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by the uninjured DRG neurons. This article shows that GDNF exerts its analgesic effects on neuropathic pain by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by these neurons. Therefore, research focusing on these GDNF-dependent neurons in the uninjured DRG would provide a new strategy for treating neuropathic pain. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Morphine Spinal Block Anesthesia in Patients Who Undergo an Open Hemorrhoidectomy: A Prospective Analysis of Pain Control and Postoperative Complications

PubMed Central

Moreira, José PT; Isaac, Raniere R; Alves-Neto, Onofre; Moreira, Thiago AC; Vieira, Tiago HM; Brasil, Andressa MS

2014-01-01

Purpose This study evaluated the use of adding morphine to bupivacaine in spinal anesthesia for pain control in patients who underwent an open hemorrhoidectomy. Methods Forty patients were prospectively selected for an open hemorrhoidectomy at the same institution and were randomized into two groups of 20 patients each: group 1 had a spinal with 7 mg of heavy bupivacaine associated with 80 µg of morphine (0.2 mg/mL). Group 2 had a spinal with 7 mg of heavy bupivacaine associated with distilled water, achieving the same volume of spinal infusion as that of group 1. Both groups were prescribed the same pain control medicine during the postoperative period. Pain scores were evaluated at the anesthetic recovery room and at 3, 6, 12, and 24 hours after surgery. Postoperative complications, including pruritus, nausea, headaches, and urinary retention, were also recorded. Results There were no anthropometric statistical differences between the two groups. Pain in the anesthetic recovery room and 3 hours after surgery was similar for both groups. However, pain was better controlled in group 1 at 6 and 12 hours after surgery. Although pain was better controlled for group 1 after 24 hours of surgery, the difference between the groups didn't achieved statistical significance. Complications were more common in group 1. Six patients (6/20) presented coetaneous pruritus and 3 with (3/20) urinary retention. Conclusion A hemorrhoidectomy under a spinal with morphine provides better pain control between 6 and 12 hours after surgery. However, postoperative complications, including cutaneous pruritus (30%) and urinary retention (15%), should be considered as a negative side of this procedure. PMID:24999465

Spinal Manipulative Therapy Specific Changes In Pain Sensitivity In Individuals With Low Back Pain (NCT01168999)

PubMed Central

Bialosky, Joel E; George, Steven Z; Horn, Maggie E; Price, Donald D; Staud, Roland; Robinson, Michael E

2013-01-01

Spinal Manipulative Therapy (SMT) is effective for some individuals experiencing low back pain (LBP); however, the mechanisms are not established regarding the role of placebo. SMT is associated with changes in pain sensitivity suggesting related altered central nervous system response or processing of afferent nociceptive input. Placebo is also associated with changes in pain sensitivity and the efficacy of SMT for changes in pain sensitivity beyond placebo has not been adequately considered. We randomly assigned 110 participants with LBP to receive SMT, placebo SMT, placebo SMT with the instructional set, “The manual therapy technique you will receive has been shown to significantly reduce low back pain in some people”, or no intervention. Participants receiving the SMT and placebo SMT received their assigned intervention 6 times over two weeks. Pain sensitivity was assessed prior to and immediately following the assigned intervention during the first session. Clinical outcomes were assessed at baseline and following two weeks of participation in the study. Immediate attenuation of suprathreshold heat response was greatest following SMT (p= 0.05, partial η2= 0.07). Group dependent differences were not observed for changes in pain intensity and disability at two week. Participant satisfaction was greatest following the enhanced placebo SMT. PMID:24361109

Lentiviral-mediated Targeted NF-κB Blockade in Dorsal Spinal Cord Glia Attenuates Sciatic Nerve Injury-induced Neuropathic Pain in the Rat.

PubMed

Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor κB (NF-κB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-κB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-κB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-κB super- repressor IκBα resulted in an inhibition of the NF-κB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IκBα overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-κB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-κB pathway in the development of neuropathic pain after peripheral nerve injury. Copyright © 2007 The American Society of Gene Therapy. Published by Elsevier Inc. All rights reserved.

Spinal intracellular metabotropic glutamate receptor 5 (mGluR5) contributes to pain and c-fos expression in a rat model of inflammatory pain.

PubMed

Vincent, Kathleen; Wang, Shu Fan; Laferrière, André; Kumar, Naresh; Coderre, Terence J

2017-04-01

Metabotropic glutamate receptor 5 (mGluR5) is an excitatory G-protein-coupled receptor (GPCR) present in the spinal cord dorsal horn (SCDH) where it has a well-established role in pain. In addition to its traditional location on the cytoplasmic membrane, recent evidence shows that these receptors are present intracellularly on the nuclear membrane in the spinal cord dorsal horn and are implicated in neuropathic pain. Nuclear mGluR5 is a functional receptor that binds glutamate entering the cell through the neuronal glutamate transporter (GT) EAAT3 and activates transcription factor c-fos, whereas plasma membrane mGluR5 is responsible for c-jun activation. Here, we extend these findings to a model of inflammatory pain using complete Freund's adjuvant (CFA) and show that nuclear mGluR5 is also upregulated in the spinal cord dorsal horn following inflammation. We also show that pretreatment with an excitatory amino acid transporter (EAAT) inhibitor attenuates pain and decreases Fos, but not Jun, expression in complete Freund's adjuvant rats. In contrast, selective glial glutamate transporter inhibitors are pronociceptive and increase spinal glutamate concentrations. Additionally, we found that permeable mGluR5 antagonists are more effective at attenuating pain and Fos expression than nonpermeable group I mGluR antagonists. Taken together, these results suggest that under inflammatory conditions, intracellular mGluR5 is actively involved in the relay of nociceptive information in the spinal cord.

Intervention of electroacupuncture on spinal p38 MAPK/ATF-2/VR-1 pathway in treating inflammatory pain induced by CFA in rats.

PubMed

Fang, Jian-Qiao; Du, Jun-Ying; Liang, Yi; Fang, Jun-Fan

2013-03-22

Previous studies have demonstrated that p38 MAPK signal transduction pathway plays an important role in the development and maintenance of inflammatory pain. Electroacupuncture (EA) can suppress the inflammatory pain. However, the relationship between EA effect and p38 MAPK signal transduction pathway in inflammatory pain remains poorly understood. It is our hypothesis that p38 MAPK/ATF-2/VR-1 and/or p38 MAPK/ATF-2/COX-2 signal transduction pathway should be activated by inflammatory pain in CFA-injected model. Meanwhile, EA may inhibit the activation of p38 MAPK signal transduction pathway. The present study aims to investigate that anti-inflammatory and analgesic effect of EA and its intervention on the p38 MAPK signal transduction pathway in a rat model of inflammatory pain. EA had a pronounced anti-inflammatory and analgesic effect on CFA-induced chronic inflammatory pain in rats. EA could quickly raise CFA-rat's paw withdrawal thresholds (PWTs) and maintain good and long analgesic effect, while it subdued the ankle swelling of CFA rats only at postinjection day 14. EA could down-regulate the protein expressions of p-p38 MAPK and p-ATF-2, reduced the numbers of p-p38 MAPK-IR cells and p-ATF-2-IR cells in spinal dorsal horn in CFA rats, inhibited the expressions of both protein and mRNA of VR-1, but had no effect on the COX-2 mRNA expression. The present study indicates that inhibiting the activation of spinal p38 MAPK/ATF-2/VR-1 pathway may be one of the main mechanisms via central signal transduction pathway in the process of anti-inflammatory pain by EA in CFA rats.

Intervention of electroacupuncture on spinal p38 MAPK/ATF-2/VR-1 pathway in treating inflammatory pain induced by CFA in rats

PubMed Central

2013-01-01

Background Previous studies have demonstrated that p38 MAPK signal transduction pathway plays an important role in the development and maintenance of inflammatory pain. Electroacupuncture (EA) can suppress the inflammatory pain. However, the relationship between EA effect and p38 MAPK signal transduction pathway in inflammatory pain remains poorly understood. It is our hypothesis that p38 MAPK/ATF-2/VR-1 and/or p38 MAPK/ATF-2/COX-2 signal transduction pathway should be activated by inflammatory pain in CFA-injected model. Meanwhile, EA may inhibit the activation of p38 MAPK signal transduction pathway. The present study aims to investigate that anti-inflammatory and analgesic effect of EA and its intervention on the p38 MAPK signal transduction pathway in a rat model of inflammatory pain. Results EA had a pronounced anti-inflammatory and analgesic effect on CFA-induced chronic inflammatory pain in rats. EA could quickly raise CFA-rat’s paw withdrawal thresholds (PWTs) and maintain good and long analgesic effect, while it subdued the ankle swelling of CFA rats only at postinjection day 14. EA could down-regulate the protein expressions of p-p38 MAPK and p-ATF-2, reduced the numbers of p-p38 MAPK-IR cells and p-ATF-2-IR cells in spinal dorsal horn in CFA rats, inhibited the expressions of both protein and mRNA of VR-1, but had no effect on the COX-2 mRNA expression. Conclusions The present study indicates that inhibiting the activation of spinal p38 MAPK/ATF-2/VR-1 pathway may be one of the main mechanisms via central signal transduction pathway in the process of anti-inflammatory pain by EA in CFA rats. PMID:23517865

Frequently Asked Questions about Chiropractic

MedlinePlus

... Spinal Health Winter Activities Kids and Sports Exercising Outdoors with Baby Gardening Chronic Pain and Depression Preventing ... Spinal Health Winter Activities Kids and Sports Exercising Outdoors with Baby Gardening Chronic Pain and Depression Preventing ...

Impaired health status, sleep disorders, and pain in the craniomandibular and cervical spinal regions.

PubMed

Lobbezoo, Frank; Visscher, Corine M; Naeije, Machiel

2004-02-01

This study investigated the relationship between health status (i.e., physical well-being and quality of life), sleep disorders (e.g., insomnia, sleep-related depression and anxiety), and musculoskeletal pain in the craniomandibular and cervical spinal regions. The number of painful body areas below the cervical spine (i.e., widespread pain) was also taken into account. Two questionnaires, viz., the RAND 36-item Health Survey Questionnaire and the Dutch Sleep Disorders Questionnaire (SDQ), were administered to 103 persons who could unequivocally be classified into one of four mutually exclusive groups: No pain, craniomandibular pain (CMP), cervical spinal pain (CSP), and both CMP and CSP. Body drawings were used for the self-report of widespread pain. Multivariate analysis of variance showed effects of gender, group, and widespread pain on the questionnaire scales; not of age. As shown by univariate analysis of variance, men suffered more from sleep apnea than did women. No other gender differences were found. Simple contrast analyses following univariate analyses of the group and widespread pain effects showed that, in general, more questionnaire scales, both of the RAND-36 and of the SDQ, reached statistical significance with an increase in the number of painful areas. It was concluded that both musculoskeletal pain in the trigemino-cervical area and widespread body pain are associated with an increased impairment of health status. Also, sleep disorders are frequently found in patients with chronic pain in the craniomandibular and cervical spinal regions as well as in patients with widespread pain. The more painful areas there are, the likelier it is that sleep disorders are present.

[Subcutaneous stimulation as additional therapy to spinal cord stimulation in a post-laminectomy syndrome patient].

PubMed

Akbaş, Mert; Yeğin, Mehmet Arif; Özdemir, İrem; Göksu, Ethem; Akyüz, Mahmut

2016-01-01

Spinal cord stimulation as treatment of chronic low back pain via neuromodulation has been frequently performed in recent years. The dorsal column is stimulated by an electrode placed at the epidural region. In the case presently described, subcutaneous lead was implanted in a patient with failed back syndrome after spinal cord stimulation was inadequate to treat back and gluteal pain. A 65-year-old male had undergone surgery to treat lumbar disc herniation, after which he received physical therapy and multiple steroid injections due to unrelieved pain. He was admitted to the pain clinic with pain radiating to right gluteal muscle and leg. Spinal cord stimulation was performed and, as pain was not relieved, subcutaneous lead was applied to the right cluneal nerve distribution. Following treatment, the patient scored 1-2 on visual analog scale. Pain had been reduced by over 80%. Octad electrode was placed between T8 and T10 vertebrae after Tuohy needle was introduced to intervertebral area between L1 and L2. Paresthesia occurred in the right extremity. Boundaries were determined by area of right gluteal region in which paresthesia did not occur. Octad electrode was placed subcutaneously after vertical line was drawn from center point. Paresthesia occurred throughout the region. Pulse wave was 390-450 msec; frequency was 10-30 Hz. Subcutaneous electrode replacement is effective additional therapy when pain is not relieved by spinal cord stimulation.

Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-α expression in a mouse model.

PubMed

Gu, Xiaoping; Zheng, Yaguo; Ren, Bingxu; Zhang, Rui; Mei, Fengmei; Zhang, Juan; Ma, Zhengliang

2010-10-05

Tumor necrosis factor α (TNF-α) may have a pivotal role in the genesis of mechanical allodynia and thermal hyperalgesia during inflammatory and neuropathic pain. Thalidomide has been shown to selectively inhibit TNF-α production. Previous studies have suggested that thalidomide exerts anti-nociceptive effects in various pain models, but its effects on bone cancer pain have not previously been studied. Therefore, in the present study, we investigated the effect of thalidomide on bone cancer-induced hyperalgesia and up-regulated expression of spinal TNF-α in a mouse model. Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce ongoing bone cancer related pain behaviors. At day 5, 7, 10 and 14 after operation, the expression of TNF-α in the spinal cord was higher in tumor-bearing mice compared to the sham mice. Intraperitoneal injection of thalidomide (50 mg/kg), started at day 1 after surgery and once daily thereafter until day 7, attenuated bone cancer-evoked mechanical allodynia and thermal hyperalgesia as well as the up-regulation of TNF-α in the spinal cord. These results suggest that thalidomide can efficiently alleviate bone cancer pain and it may be a useful alternative or adjunct therapy for bone cancer pain. Our data also suggest a role of spinal TNF-α in the development of bone cancer pain.

Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-α expression in a mouse model

PubMed Central

2010-01-01

Background Tumor necrosis factor α (TNF-α) may have a pivotal role in the genesis of mechanical allodynia and thermal hyperalgesia during inflammatory and neuropathic pain. Thalidomide has been shown to selectively inhibit TNF-α production. Previous studies have suggested that thalidomide exerts anti-nociceptive effects in various pain models, but its effects on bone cancer pain have not previously been studied. Therefore, in the present study, we investigated the effect of thalidomide on bone cancer-induced hyperalgesia and up-regulated expression of spinal TNF-α in a mouse model. Results Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce ongoing bone cancer related pain behaviors. At day 5, 7, 10 and 14 after operation, the expression of TNF-α in the spinal cord was higher in tumor-bearing mice compared to the sham mice. Intraperitoneal injection of thalidomide (50 mg/kg), started at day 1 after surgery and once daily thereafter until day 7, attenuated bone cancer-evoked mechanical allodynia and thermal hyperalgesia as well as the up-regulation of TNF-α in the spinal cord. Conclusions These results suggest that thalidomide can efficiently alleviate bone cancer pain and it may be a useful alternative or adjunct therapy for bone cancer pain. Our data also suggest a role of spinal TNF-α in the development of bone cancer pain. PMID:20923560

Positioning and spinal bracing for pain relief in metastatic spinal cord compression in adults.

PubMed

Lee, Siew Hwa; Grant, Robin; Kennedy, Catriona; Kilbride, Lynn

2015-09-24

This is an updated version of the original Cochrane review published in Issue 3 (Lee 2012) on patient positioning (mobilisation) and bracing for pain relief and spinal stability in adults with metastatic spinal cord compression.Many patients with metastatic spinal cord compression (MSCC) have spinal instability, but their clinician has determined that due to their advanced disease they are unsuitable for surgical internal fixation. Mobilising may be hazardous in the presence of spinal instability as further vertebral collapse can occur. Current guidance on positioning (whether a patient should be managed with bed rest or allowed to mobilise) and whether spinal bracing is helpful, is contradictory. To investigate the correct positioning and examine the effects of spinal bracing to relieve pain or to prevent further vertebral collapse in patients with MSCC. For this update, we searched for relevant studies from February 2012 to 31 March 2015. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and MEDLINE In Process, EMBASE, AMED, CINAHL, TRIP, SIGN, NICE, UK Clinical Research Network, National Guideline Clearinghouse and PEDro database. We also searched the metaRegister of Controlled Trials (mRCT), ClinicalTrials.gov, UK Clinical Trials Gateway (UKCTG), WHO International Clinical Trials Registry Platform (ICTRP) and Australia New Zealand Clinical Trials Registry (ANZCTR).For the original version, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, CANCERLIT, NICE, SIGN, AMED, TRIP, National Guideline Clearinghouse, and PEDro database, in February 2012. We selected randomised controlled trials (RCTs) of adults with MSCC of interventions on positioning (mobilisation) and bracing. Two review authors independently assessed each possible study for inclusion and quality. For the original version of the review, we screened 1611 potentially relevant studies. No studies met the inclusion criteria. Many papers identified the importance of mobilisation, but no RCTs of bed rest versus mobilisation have been undertaken. We identified no RCTs of bracing in MSCC.For this update, we identified 347 potential titles. We screened 300 titles and abstracts after removal of duplicates. We did not identify any additional studies for inclusion. Since publication of the original version of this review, no new studies were found and our conclusions remain unchanged.There is a lack of evidence-based guidance around how to correctly position and when to mobilise patients with MSCC or if spinal bracing is an effective technique for reducing pain or improving quality of life. RCTs are required in this important area.

Descending serotonergic facilitation mediated by spinal 5-HT3 receptors engages spinal rapamycin-sensitive pathways in the rat

PubMed Central

Asante, Curtis O.; Dickenson, Anthony H.

2010-01-01

We have recently reported the importance of spinal rapamycin-sensitive pathways in maintaining persistent pain-like states. A descending facilitatory drive mediated through spinal 5-HT3 receptors (5-HT3Rs) originating from superficial dorsal horn NK1-expressing neurons and that relays through the parabrachial nucleus and the rostroventral medial medulla to act on deep dorsal horn neurons is known be important in maintaining these pain-like states. To determine if spinal rapamycin-sensitive pathways are activated by a descending serotonergic drive, we investigated the effects of spinally administered rapamycin on responses of deep dorsal horn neurons that had been pre-treated with the selective 5-HT3R antagonist ondansetron. We also investigated the effects of spinally administered cell cycle inhibitor (CCI)-779 (a rapamycin ester analogue) on deep dorsal horn neurons from rats with carrageenan-induced inflammation of the hind paw. Unlike some other models of persistent pain, this model does not involve an altered 5-HT3R-mediated descending serotonergic drive. We found that the inhibitory effects of rapamycin were significantly reduced for neuronal responses to mechanical and thermal stimuli when the spinal cord was pre-treated with ondansetron. Furthermore, CCI-779 was found to be ineffective in attenuating spinal neuronal responses to peripheral stimuli in carrageenan-treated rats. Therefore, we conclude that 5-HT3R-mediated descending facilitation is one requirement for activation of rapamycin-sensitive pathways that contribute to persistent pain-like states. PMID:20709148

Neurophysiology of pain.

PubMed

Aguggia, M

2003-05-01

The transmission of pain-related information from the periphery to the cortex depends on signal integration at three levels of the nervous system: the spinal medulla, brainstem and telencephalon. In fulfilling its task of safeguarding human health, pain may develop as a result of damaged or altered primary afferent neurons (stimulus-dependent) or arise spontaneously without any apparent causal stimulus (stimulus-independent). Hyperalgesia (i.e. an exaggerated perception of pain after a painful stimulus) is due to an anomaly in the processing of nociceptive inputs in the central and peripheral nervous systems leading to the activation of the primary afferents by stimuli other than the usual stimuli.

Effects of Therapy in Patients Suffering from Chronic Back Pain Treated with Spinal Cord Stimulation.

PubMed

Mosiewicz, Anna; Rutkowska, Elżbieta; Matacz, Monika; Mosiewicz, Barbara; Kaczmarczyk, Robert; Trojanowski, Tomasz

2015-10-01

Pain in the lumbosacral part of the spine in the course of degenerative disease is the most common cause of physical activity limitation in adults. Treatment includes pharmacotherapy, physiotherapy, psychotherapy, health promotion, and sometimes surgery. Surgical treatment is not always successful, and the various clinical and psychosomatic symptoms that result from surgical treatment failure are known as failed back surgery syndrome. For some patients with this condition, spinal cord stimulation can provide relief. The aim of the work was to define subjective and objective spinal cord stimulation effects by assessing chosen disability and physical activity limitation ratios. Pain intensity, level of disability, and presence of neurological symptoms were assessed. The examination was performed twice: before the stimulator implantation and at least 6 months postimplantation. The study was conducted at the Department of Neurosurgery and Paediatric Neurosurgery in Lublin. Thirty-six patients suffering from failed back surgery syndrome were recruited for this study. The Visual Analog Scale, modified Laitinen's pain questionnaire, and Oswestry Disability Index were used in this work. The study showed that spinal cord stimulation was effective in treating spinal and lower limb pain in 64% of patients, similar to results obtained in other departments. Although back pain and neuropathic pain radiating to the lower limbs decreased, moderate physical activity impairment was still observed according to the Oswestry Disability Index scale. The decrease in neuropathic pain radiating to the lower limbs had the most significant influence on reducing physical activity impairment. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms.

PubMed

Sdrulla, Andrei D; Guan, Yun; Raja, Srinivasa N

2018-03-11

Spinal cord stimulation (SCS) is a minimally invasive therapy used for the treatment of chronic neuropathic pain. SCS is a safe and effective alternative to medications such as opioids, and multiple randomized controlled studies have demonstrated efficacy for difficult-to-treat neuropathic conditions such as failed back surgery syndrome. Conventional SCS is believed mediate pain relief via activation of dorsal column Aβ fibers, resulting in variable effects on sensory and pain thresholds, and measurable alterations in higher order cortical processing. Although potentiation of inhibition, as suggested by Wall and Melzack's gate control theory, continues to be the leading explanatory model, other segmental and supraspinal mechanisms have been described. Novel, non-standard, stimulation waveforms such as high-frequency and burst have been shown in some studies to be clinically superior to conventional SCS, however their mechanisms of action remain to be determined. Additional studies are needed, both mechanistic and clinical, to better understand optimal stimulation strategies for different neuropathic conditions, improve patient selection and optimize efficacy. © 2018 World Institute of Pain.

A critical role of spinal Shank2 proteins in NMDA-induced pain hypersensitivity

PubMed Central

Yoon, Seo-Yeon; Kwon, Soon-Gu; Kim, Yong Ho; Yeo, Ji-Hee; Ko, Hyoung-Gon; Roh, Dae-Hyun; Kaang, Bong-Kiun; Beitz, Alvin J; Lee, Jang-Hern

2017-01-01

Background Self-injurious behaviors (SIBs) are devastating traits in autism spectrum disorder (ASD). Although deficits in pain sensation might be one of the contributing factors underlying the development of SIBs, the mechanisms have yet to be addressed. Recently, the Shank2 synaptic protein has been considered to be a key component in ASD, and mutations of SHANK2 gene induce the dysfunction of N-methyl-D-aspartate (NMDA) receptors, suggesting a link between Shank2 and NMDA receptors in ASD. Given that spinal NMDA receptors play a pivotal role in pain hypersensitivity, we investigated the possible role of Shank2 in nociceptive hypersensitivity by examining changes in spontaneous pain following intrathecal NMDA injection in Shank2−/− (Shank2 knock-out, KO) mice. Results Intrathecal NMDA injection evoked spontaneous nociceptive behaviors. These NMDA-induced nociceptive responses were significantly reduced in Shank2 KO mice. We also observed a significant decrease of NMDA currents in the spinal dorsal horn of Shank2 KO mice. Subsequently, we examined whether mitogen-activated protein kinase or AKT signaling is involved in this reduced pain behavior in Shank2 KO mice because the NMDA receptor is closely related to these signaling molecules. Western blotting and immunohistochemistry revealed that spinally administered NMDA increased the expression of a phosphorylated form of extracellular signal-regulated kinase (p-ERK) which was significantly reduced in Shank2 KO mice. However, p38, JNK, or AKT were not changed by NMDA administration. The ERK inhibitor, PD98059, decreased NMDA-induced spontaneous pain behaviors in a dose-dependent manner in wild-type mice. Moreover, it was found that the NMDA-induced increase in p-ERK was primarily colocalized with Shank2 proteins in the spinal cord dorsal horn. Conclusion Shank2 protein is involved in spinal NMDA receptor-mediated pain, and mutations of Shank2 may suppress NMDA-ERK signaling in spinal pain transmission. This study provides new clues into the mechanisms underlying pain deficits associated with SIB and deserves further study in patients with ASD. PMID:28326932

A critical role of spinal Shank2 proteins in NMDA-induced pain hypersensitivity.

PubMed

Yoon, Seo-Yeon; Kwon, Soon-Gu; Kim, Yong Ho; Yeo, Ji-Hee; Ko, Hyoung-Gon; Roh, Dae-Hyun; Kaang, Bong-Kiun; Beitz, Alvin J; Lee, Jang-Hern; Oh, Seog Bae

2017-01-01

Background Self-injurious behaviors (SIBs) are devastating traits in autism spectrum disorder (ASD). Although deficits in pain sensation might be one of the contributing factors underlying the development of SIBs, the mechanisms have yet to be addressed. Recently, the Shank2 synaptic protein has been considered to be a key component in ASD, and mutations of SHANK2 gene induce the dysfunction of N-methyl-D-aspartate (NMDA) receptors, suggesting a link between Shank2 and NMDA receptors in ASD. Given that spinal NMDA receptors play a pivotal role in pain hypersensitivity, we investigated the possible role of Shank2 in nociceptive hypersensitivity by examining changes in spontaneous pain following intrathecal NMDA injection in S hank2-/- ( Shank2 knock-out, KO) mice. Results Intrathecal NMDA injection evoked spontaneous nociceptive behaviors. These NMDA-induced nociceptive responses were significantly reduced in Shank2 KO mice. We also observed a significant decrease of NMDA currents in the spinal dorsal horn of Shank2 KO mice. Subsequently, we examined whether mitogen-activated protein kinase or AKT signaling is involved in this reduced pain behavior in Shank2 KO mice because the NMDA receptor is closely related to these signaling molecules. Western blotting and immunohistochemistry revealed that spinally administered NMDA increased the expression of a phosphorylated form of extracellular signal-regulated kinase (p-ERK) which was significantly reduced in Shank2 KO mice. However, p38, JNK, or AKT were not changed by NMDA administration. The ERK inhibitor, PD98059, decreased NMDA-induced spontaneous pain behaviors in a dose-dependent manner in wild-type mice. Moreover, it was found that the NMDA-induced increase in p-ERK was primarily colocalized with Shank2 proteins in the spinal cord dorsal horn. Conclusion Shank2 protein is involved in spinal NMDA receptor-mediated pain, and mutations of Shank2 may suppress NMDA-ERK signaling in spinal pain transmission. This study provides new clues into the mechanisms underlying pain deficits associated with SIB and deserves further study in patients with ASD.

Anatomy and Pathophysiology of Spinal Cord Injury Associated With Regional Anesthesia and Pain Medicine: 2015 Update.

PubMed

Neal, Joseph M; Kopp, Sandra L; Pasternak, Jeffrey J; Lanier, William L; Rathmell, James P

2015-01-01

In March 2012, the American Society of Regional Anesthesia and Pain Medicine convened its second Practice Advisory on Neurological Complications in Regional Anesthesia and Pain Medicine. This update is based on the proceedings of that conference and relevant information published since its conclusion. This article updates previously described information on the pathophysiology of spinal cord injury and adds new material on spinal stenosis, blood pressure control during neuraxial blockade, neuraxial injury subsequent to transforaminal procedures, cauda equina syndrome/local anesthetic neurotoxicity/arachnoiditis, and performing regional anesthetic or pain medicine procedures in patients concomitantly receiving general anesthesia or deep sedation. Recommendations are based on extensive review of research on humans or employing animal models, case reports, pathophysiology research, and expert opinion. The pathophysiology of spinal cord injury associated with regional anesthetic techniques is reviewed in depth, including that related to mechanical trauma from direct needle/catheter injury or mass lesions, spinal cord ischemia or vascular injury from direct needle/catheter trauma, and neurotoxicity from local anesthetics, adjuvants, or antiseptics. Specific recommendations are offered that may reduce the likelihood of spinal cord injury associated with regional anesthetic or interventional pain medicine techniques. The practice advisory's recommendations may, in select cases, reduce the likelihood of injury. However, many of the described injuries are neither predictable nor preventable based on our current state of knowledge. Since publication of initial recommendations in 2008, new information has enhanced our understanding of 5 specific entities: spinal stenosis, blood pressure control during neuraxial anesthesia, neuraxial injury subsequent to transforaminal techniques, cauda equina syndrome/local anesthetic neurotoxicity/arachnoiditis, and performing regional anesthetic or pain procedures in patients concomitantly receiving general anesthesia or deep sedation.

Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation

DTIC Science & Technology

2015-10-01

currently investigating the effects of CG stimulation in subjects with debilitating pain due to cervical or thoracic SCI. This study stemmed from...had a low thoracic injury and pain in lumbar dermatomes, whereas Subject 1 had mainly mid- cervical pain that responded minimally to DBS and matched...AWARD NUMBER: W81XWH-12-1-0559 TITLE: Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation PRINCIPAL

Topical Ketamine 10% for Neuropathic Pain in Spinal Cord Injury Patients: An Open-Label Trial.

PubMed

Rabi, Joseph; Minori, Joshua; Abad, Hasan; Lee, Ray; Gittler, Michelle

2016-01-01

Topical ketamine, an N-methyl-D-aspartate antagonist, has been shown to be effective in certain neuropathic pain syndromes. The objective of this study was to determine the efficacy of topical ketamine in spinal cord injury patients with neuropathic pain. An open label trial enrolled five subjects at an outpatient rehabilitation hospital with traumatic spinal cord injuries who had neuropathic pain at or below the level of injury. Subjects applied topical ketamine 10% three times a day for a two-week duration. Subjects recorded their numerical pain score-ranging from 0 to 10, with 0 representing "no pain, 5 representing "moderate pain," and 10 being described as "worst possible pain"-in a journal at the time of application of topical ketamine and one hour after application. Using a numerical pain scale allows for something as subjective as pain to be given an objective quantification. Subjects also recorded any occurrence of adverse events and level of satisfaction. All five subjects had a decrease in their numerical pain scale by the end of two weeks, ranging from 14% to 63%. The duration ranged from one hour in one subject to the next application in other subjects. There were no adverse effects. Overall, four out of the five subjects stated they were satisfied. Topical ketamine 10% is an effective neuropathic pain medicine in patients with spinal cord injuries; however, further studies need to be done with a placebo and larger sample size. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Appearance of burning abdominal pain during cesarean section under spinal anesthesia in a patient with complex regional pain syndrome: a case report.

PubMed

Kato, Jitsu; Gokan, Dai; Hirose, Noriya; Iida, Ryoji; Suzuki, Takahiro; Ogawa, Setsuro

2013-02-01

The mechanism of complex regional pain syndrome (CRPS) was reported as being related to both the central and peripheral nervous systems. Recurrence of CRPS was, reportedly, induced by hand surgery in a patient with upper limb CRPS. However, there is no documentation of mechanical allodynia and burning abdominal pain induced by Cesarean section under spinal anesthesia in patients with upper limb CRPS. We report the case of a patient who suffered from burning abdominal pain during Cesarean section under spinal anesthesia 13 years after the occurrence of venipuncture-induced CRPS of the upper arm. The patient's pain characteristics were similar to the pain characteristics of her right arm during her previous CRPS episode 13 years earlier. In addition, mechanical allodynia around the incision area was confirmed after surgery. We provided ultrasound-guided rectus sheath block using 20 mL of 0.4% ropivacaine under ultrasound guidance twice, which resulted in the disappearance of the spontaneous pain and allodynia. The pain relief was probably related to blockade of the peripheral input by this block, which in turn would have improved her central sensitization. Our report shows that attention should be paid to the appearance of neuropathic pain of the abdomen during Cesarean section under spinal anesthesia in patients with a history of CRPS. Wiley Periodicals, Inc.

Migration of an Intracranial Subdural Hematoma to the Spinal Subdural Space: A Case Report.

PubMed

Kwon, O Ik; Son, Dong Wuk; Kim, Young Ha; Kim, Young Soo; Sung, Soon Ki; Lee, Sang Weon; Song, Geun Sung

2015-09-01

A 57-year-old man complained of severe lower back pain and radicular pain in both legs for 1 week after falling from a ladder. Magnetic resonance imaging (MRI) of the spine showed a subdural hematoma (SDH), which was surgically removed. The patient had no back pain or the radicular leg pain at 2 weeks post-surgery. However, he complained of diffuse headaches upon follow-up. Brain computed tomography (CT) and MRI revealed an intracranial SDH, which was immediately removed by surgery. During his 1-year follow-up, he reported that the pain had resolved without recurrence. Simultaneous spinal and intracranial SDH are rare and no standard treatment exists for this condition. This case suggests that it is possible that an intracranial SDH can migrate into the cerebrospinal fluid (CSF) space through an arachnoid tear. CSF circulation allows the intracranial SDH to enter subarachnoid spaces encasing the spinal cord. In order to prevent irreversible damage, surgical intervention should be considered for case of spinal SDH with progressive neurological deficits.

Minimally Invasive Drainage of a Post-Laminectomy Subfascial Seroma with Cervical Spinal Cord Compression.

PubMed

Kitshoff, Adriaan Mynhardt; Van Goethem, Bart; Cornelis, Ine; Combes, Anais; Dvm, Ingeborgh Polis; Gielen, Ingrid; Vandekerckhove, Peter; de Rooster, Hilde

2016-01-01

A 14 mo old female neutered Doberman pinscher was evaluated for difficulty in rising, a wide based stance, pelvic limb gait abnormalities, and cervical pain of 2 mo duration. Neurologic examination revealed pelvic limb ataxia and cervical spinal hyperesthesia. Spinal reflexes and cranial nerve examination were normal. The pathology was localized to the C1-C5 or C6-T2 spinal cord segments. Computed tomography (CT) findings indicated bony proliferation of the caudal articular processes of C6 and the cranial articular processes of C7, resulting in bilateral dorsolateral spinal cord compression that was more pronounced on the left side. A limited dorsal laminectomy was performed at C6-C7. Due to progressive neurological deterioration, follow-up CT examination was performed 4 days postoperatively. At the level of the laminectomy defect, a subfacial seroma had developed, entering the spinal canal and causing significant spinal cord compression. Under ultrasonographic guidance a closed-suction wound catheter was placed. Drainage of the seroma successfully relieved its compressive effects on the spinal cord and the patient's neurological status improved. CT was a valuable tool in assessing spinal cord compression as a result of a postoperative subfascial seroma. Minimally invasive application of a wound catheter can be successfully used to manage this condition.

Somatostatin and its 2A receptor in dorsal root ganglia and dorsal horn of mouse and human: expression, trafficking and possible role in pain

PubMed Central

2014-01-01

Background Somatostatin (SST) and some of its receptor subtypes have been implicated in pain signaling at the spinal level. In this study we have investigated the role of SST and its sst2A receptor (sst2A) in dorsal root ganglia (DRGs) and spinal cord. Results SST and sst2A protein and sst2 transcript were found in both mouse and human DRGs, sst2A-immunoreactive (IR) cell bodies and processes in lamina II in mouse and human spinal dorsal horn, and sst2A-IR nerve terminals in mouse skin. The receptor protein was associated with the cell membrane. Following peripheral nerve injury sst2A-like immunoreactivity (LI) was decreased, and SST-LI increased in DRGs. sst2A-LI accumulated on the proximal and, more strongly, on the distal side of a sciatic nerve ligation. Fluorescence-labeled SST administered to a hind paw was internalized and retrogradely transported, indicating that a SST-sst2A complex may represent a retrograde signal. Internalization of sst2A was seen in DRG neurons after systemic treatment with the sst2 agonist octreotide (Oct), and in dorsal horn and DRG neurons after intrathecal administration. Some DRG neurons co-expressed sst2A and the neuropeptide Y Y1 receptor on the cell membrane, and systemic Oct caused co-internalization, hypothetically a sign of receptor heterodimerization. Oct treatment attenuated the reduction of pain threshold in a neuropathic pain model, in parallel suppressing the activation of p38 MAPK in the DRGs Conclusions The findings highlight a significant and complex role of the SST system in pain signaling. The fact that the sst2A system is found also in human DRGs and spinal cord, suggests that sst2A may represent a potential pharmacologic target for treatment of neuropathic pain. PMID:24521084

Beliefs in the population about cracking sounds produced during spinal manipulation.

PubMed

Demoulin, Christophe; Baeri, Damien; Toussaint, Geoffrey; Cagnie, Barbara; Beernaert, Axel; Kaux, Jean-François; Vanderthommen, Marc

2018-03-01

To examine beliefs about cracking sounds heard during high-velocity low-amplitude (HVLA) thrust spinal manipulation in individuals with and without personal experience of this technique. We included 100 individuals. Among them, 60 had no history of spinal manipulation, including 40 who were asymptomatic with or without a past history of spinal pain and 20 who had nonspecific spinal pain. The remaining 40 patients had a history of spinal manipulation; among them, 20 were asymptomatic and 20 had spinal pain. Participants attended a one-on-one interview during which they completed a questionnaire about their history of spinal manipulation and their beliefs regarding sounds heard during spinal manipulation. Mean age was 43.5±15.4years. The sounds were ascribed to vertebral repositioning by 49% of participants and to friction between two vertebras by 23% of participants; only 9% of participants correctly ascribed the sound to the formation of a gas bubble in the joint. The sound was mistakenly considered to indicate successful spinal manipulation by 40% of participants. No differences in beliefs were found between the groups with and without a history of spinal manipulation. Certain beliefs have documented adverse effects. This study showed a high prevalence of unfounded beliefs regarding spinal manipulation. These beliefs deserve greater attention from healthcare providers, particularly those who practice spinal manipulation. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Differential fMRI Activation Patterns to Noxious Heat and Tactile Stimuli in the Primate Spinal Cord

PubMed Central

Yang, Pai-Feng; Wang, Feng

2015-01-01

Mesoscale local functional organizations of the primate spinal cord are largely unknown. Using high-resolution fMRI at 9.4 T, we identified distinct interhorn and intersegment fMRI activation patterns to tactile versus nociceptive heat stimulation of digits in lightly anesthetized monkeys. Within a spinal segment, 8 Hz vibrotactile stimuli elicited predominantly fMRI activations in the middle part of ipsilateral dorsal horn (iDH), along with significantly weaker activations in ipsilateral (iVH) and contralateral (cVH) ventral horns. In contrast, nociceptive heat stimuli evoked widespread strong activations in the superficial part of iDH, as well as in iVH and contralateral dorsal (cDH) horns. As controls, only weak signal fluctuations were detected in the white matter. The iDH responded most strongly to both tactile and heat stimuli, whereas the cVH and cDH responded selectively to tactile versus nociceptive heat, respectively. Across spinal segments, iDH activations were detected in three consecutive segments in both tactile and heat conditions. Heat responses, however, were more extensive along the cord, with strong activations in iVH and cDH in two consecutive segments. Subsequent subunit B of cholera toxin tracer histology confirmed that the spinal segments showing fMRI activations indeed received afferent inputs from the stimulated digits. Comparisons of the fMRI signal time courses in early somatosensory area 3b and iDH revealed very similar hemodynamic stimulus–response functions. In summary, we identified with fMRI distinct segmental networks for the processing of tactile and nociceptive heat stimuli in the cervical spinal cord of nonhuman primates. SIGNIFICANCE STATEMENT This is the first fMRI demonstration of distinct intrasegmental and intersegmental nociceptive heat and touch processing circuits in the spinal cord of nonhuman primates. This study provides novel insights into the local functional organizations of the primate spinal cord for pain and touch, information that will be valuable for designing and optimizing therapeutic interventions for chronic pain management. PMID:26203144

Electrical peripheral nerve stimulation relieves bone cancer pain by inducing Arc protein expression in the spinal cord dorsal horn

PubMed Central

Sun, Ke-fu; Feng, Wan-wen; Liu, Yue-peng; Dong, Yan-bin; Gao, Li; Yang, Hui-lin

2018-01-01

Objective The analgesic effect on chronic pain of peripheral nerve stimulation (PNS) has been proven, but its underlying mechanism remains unknown. Therefore, this study aimed to assess the analgesic effect of PNS on bone cancer pain in a rat model and to explore the underlying mechanism. Materials and methods PNS on sciatic nerves with bipolar electrode was performed in both naïve and bone cancer pain model rats. Then, the protein levels of activity-regulated cytoskeleton-associated protein (Arc), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid–type glutamate receptor 1 (GluA1), and phosphate N-methyl-d-aspartic acid-type glutamate receptor subunit 2B (pGluNR2B) in spinal cord were evaluated by immunohistochemistry and Western blotting. Thermal paw withdraw latency and mechanical paw withdraw threshold were used to estimate the analgesic effect of PNS on bone cancer pain. Intrathecal administration of Arc shRNA was used to inhibit Arc expression in the spinal cord. Results PNS at 60 and 120 Hz for 20 min overtly induced Arc expression in the spinal cord, increased thermal pain thresholds in naïve rats, and relieved bone cancer pain; meanwhile, 10 Hz PNS did not achieve those results. In addition, PNS at 60 and 120 Hz also reduced the expression of GluA1, but not pGluNR2B, in the spinal cord. Finally, the anti-nociceptive effect and GluA1 downregulation induced by PNS were inhibited by intrathecal administration of Arc shRNA. Conclusion PNS (60 Hz, 0.3 mA) can relieve bone-cancer-induced allodynia and hyperalgesia by upregulating Arc protein expression and then by decreasing GluA1 transcription in the spinal cord dorsal horn. PMID:29606887

Sensory function after cavernous haemangioma: a case report of thermal hypersensitivity at and below an incomplete spinal cord injury.

PubMed

Gómez-Soriano, J; Goiriena, E; Florensa-Vila, J; Gómez-Arguelles, J M; Mauderli, A; Vierck, C J; Albu, S; Simón-Martinez, C; Taylor, J

2012-09-01

Case report of a 42-year-old woman with non-evoked pain diagnosed with a cavernous C7-Th6 spinal haemangioma. To assess the effect of intramedullary haemorrhage (IH) on nociception and neuropathic pain (NP) at and below an incomplete spinal cord injury (SCI). Sensorimotor Function Group, Hospital Nacional de Parapléjicos de Toledo (HNPT). T2*-susceptibility weighted image (SWI) magnetic resonance imaging (MRI) of spinal haemosiderin and a complete pain history were performed 8 months following initial dysaesthesia complaint. Thermal pain thresholds were assessed with short 1 s stimuli, while evidence for central sensitization was obtained with psychophysical electronic Visual Analogue Scale rating of tonic 10 s 3 °C and 48 °C stimuli, applied at and below the IH. Control data were obtained from 10 healthy volunteers recruited from the HNPT. Non-evoked pain was present within the Th6 dermatome and lower legs. T2*-SWI MRI imaging detected extensive haemosiderin-rich IH (C7-Th5/6 spinal level). Cold allodynia was detected below the IH (left L5 dermatome) with short thermal stimuli. Tonic thermal stimuli applied to the Th6, Th10 and C7 dermatomes revealed widespread heat and cold allodynia. NP was diagnosed following IH, corroborated by an increase in below-level cold pain threshold with at- and below-level cold and heat allodynia. Psychophysical evidence for at- and below-level SCI central sensitization was obtained with tonic thermal stimuli. Early detection of IH could lead to better management of specific NP symptoms, an appreciation of the role of haemorrhage as an aggravating SCI physical factor, and the identification of specific spinal pathophysiological pain mechanisms.

Icariin, a flavonoid with anti-cancer effects, alleviated paclitaxel-induced neuropathic pain in a SIRT1-dependent manner.

PubMed

Gui, Yulong; Zhang, Jie; Chen, Liang; Duan, Shunyuan; Tang, Jing; Xu, Wei; Li, Aiyuan

2018-01-01

Background One of the most common side effects of paclitaxel was dosage-dependently painful neuropathy. Various reports indicated that spinal neuroinflammation was involved in paclitaxel-induced neuropathic pain. This study investigated the effect of icariin on paclitaxel-induced neuroinflammation and peripheral neuropathy in rats. Methods Two parts were included in this study. In part one, the effect of icariin on paclitaxel-induced neuropathic pain was investigated. Mechanical thresholds were measured as primary outcomes. Production of proinflammatory factors (tumor necrosis factor-α, interleukin-1 β, and interleukin-6), activation of nuclear factor-κB (NF-κB(p65)) signal, and activation of astrocytes were detected as secondary outcomes. Spinal Sirtuin 1 (SIRT1) expression, H4 acetylation, and NAD + content were measured to investigate the effect of icariin on spinal SIRT1 signal pathway. In part two, the role of SIRT1 signal on icariin-induced effect in rats was investigated, and EX527, a SIRT1 inhibitor, was employed. Results The results showed paclitaxel treatment induced significant decrease in mechanical thresholds. Paclitaxel treatment also induced NF-κB(p65) activation and upregulation of proinflammatory factors (TNF-α, IL-1β, and IL-6). Paclitaxel also induced astrocyte activation in the spinal cord. However, 100 mg/kg icariin treatment significantly alleviated paclitaxel-induced mechanical allodynia and spinal neuroinflammation. Furthermore, icariin treatment dosage-dependently reversed paclitaxel-induced SIRT1 downregulation and H4 acetylation. EX527, a selective SIRT1 inhibitor, completely reversed icariin-induced anti-neuroinflammation and anti-allodynia effects in paclitaxel-induced neuropathic pain rats. Conclusions This meant that spinal SIRT1 activation was involved in icariin-induced effects in paclitaxel-induced neuropathic pain rats. Icariin could be a potential agent for the treatment of paclitaxel-induced neuropathic pain.

Fast non-genomic effects of progesterone-derived neurosteroids on nociceptive thresholds and pain symptoms.

PubMed

Charlet, Alexandre; Lasbennes, François; Darbon, Pascal; Poisbeau, Pierrick

2008-10-31

Fast Inhibitory controls mediated by glycine (GlyRs) and GABAA receptors (GABAARs) play an important role to prevent the apparition of pathological pain symptoms of allodynia and hyperalgesia. The use of positive allosteric modulators of these receptors, specifically expressed in the spinal cord, may represent an interesting strategy to limit or block pain expression. In this study, we have used stereoisomers of progesterone metabolites, acting only via non-genomic effects, in order to evaluate the contribution of GlyRs and GABAARs for the reduction of mechanical and thermal heat hypernociception. We show that 3alpha neurosteroids were particularly efficient to elevate nociceptive thresholds in naive animal. It also reduced mechanical allodynia and thermal heat hyperalgesia in the carrageenan model of inflammatory pain. This effect is likely to be mediated by GABAA receptors since 3beta isomer was inefficient. More interestingly, 3alpha5beta neurosteroid was only efficient on mechanical allodynia while having no effect on thermal heat hyperalgesia. We characterized these paradoxical effects of 3alpha5beta neurosteroid using the strychnine and bicuculline models of allodynia. We clearly show that 3alpha5beta neurosteroid exerts an antinociceptive effect via a positive allosteric modulation of GABAARs but, at the same time, is pronociceptive by reducing GlyR function. This illustrates the importance of the inhibitory amino acid receptor channels and their allosteric modulators in spinal pain processing. Moreover, our results indicate that neurosteroids, which are synthesized in the dorsal horn of the spinal cord and have limited side effects, may be of significant interest in order to treat pathological pain symptoms.

Brain-derived neurotrophic factor (BDNF) in the rostral anterior cingulate cortex (rACC) contributes to neuropathic spontaneous pain-related aversion via NR2B receptors.

PubMed

Zhang, Le; Wang, Gongming; Ma, Jinben; Liu, Chengxiao; Liu, Xijiang; Zhan, Yufeng; Zhang, Mengyuan

2016-10-01

The rostral anterior cingulate cortex (rACC) plays an important role in pain affect. Previous investigations have reported that the rACC mediates the negative affective component of inflammatory pain and contributed to the aversive state of nerve injury-induced neuropathic pain. Brain-derived neurotrophic factor (BDNF), an activity-dependent neuromodulator in the adult brain, is believed to play a role in the development and maintenance of inflammatory and neuropathic pain in the spinal cord. However, whether and how BDNF in the rACC regulates pain-related aversion due to peripheral nerve injury is largely unknown. Behaviorally, using conditioned place preference (CPP) training in rats, which is thought to reveal spontaneous pain-related aversion, we found that CPP was acquired following spinal clonidine in rats with partial sciatic nerve transection. Importantly, BDNF was upregulated within the rACC in of rats with nerve injury and enhanced the CPP acquisition, while a local injection of a BDNF-tropomyosin receptor kinase B (TrkB) antagonist into the rACC completely blocked this process. Finally, we demonstrated that the BDNF/TrkB pathway exerted its function by activating the NR2B receptor, which is widely accepted to be a crucial factor contributing to pain affect. In conclusion, our results demonstrate that the BDNF/TrkB-mediated signaling pathway in the rACC is involved in the development of neuropathic spontaneous pain-related aversion and that this process is dependent upon activation of NR2B receptors. These findings suggest that suppression of the BDNF-related signaling pathway in the rACC may provide a novel strategy to overcome pain-related aversion. Copyright © 2016 Elsevier Inc. All rights reserved.

Spinal Stenosis

MedlinePlus

... or back Numbness, weakness, cramping, or pain in your arms or legs Pain going down the leg Foot problems Doctors diagnose spinal stenosis with a physical exam and imaging tests. Treatments include medications, physical therapy, braces, and surgery. NIH: National Institute of Arthritis ...

Spinal Subdural Abscess Following Laminectomy for Symptomatic Stenosis: A Report of 2 Cases and Review of the Literature.

PubMed

Ramos, Alexander D; Rolston, John D; Gauger, Grant E; Larson, Paul S

2016-07-12

BACKGROUND Spinal subdural abscesses, also known as empyemas, are rare infectious lesions, the exact incidence of which is unknown. Presentation is typically dramatic, with back pain, fever, motor, and sensory deficits. Rapid identification and surgical intervention with laminectomy, durotomy, and washout provides the best outcomes. While hematogenous spread of an extra-spinal infection is the most common cause of this condition, a significant number of cases result from iatrogenic mechanisms, including lumbar punctures, epidural injections, and surgery. CASE REPORT Here we present 2 cases: 1) an 87-year-old man with type 2 diabetes, schizophrenia, mild cognitive impairment, and symptomatic lumbar spinal stenosis and 2) a 62-year-old man with a prior L3-4 spinal fusion with symptomatic lumbar spinal stenosis. In both cases, patients underwent laminectomy for spinal stenosis and developed epidural abscess. Following successful drainage of the epidural abscess, they continued to be symptomatic, and repeat imaging revealed the presence of a subdural abscess that was subsequently evacuated. Case 1 had significant improvement with residual lower-extremity weakness, while Case 2 made a complete neurological recovery. CONCLUSIONS These cases illustrate patients at increased risk for developing this rare spinal infection, and demonstrate that rapid recognition and surgical treatment is key to cure and recovery. Review of the literature highlights pertinent risk factors and demonstrates nearly one-third of reported cases have an iatrogenic etiology. The cases presented here demonstrate that a subdural process should be suspected in any patient with intractable pain following treatment of an epidural abscess.

Anthropometry, spinal canal width, and flexibility of the spine and hamstring muscles in 45-55-year-old men with and without low back pain.

PubMed

Hultman, G; Saraste, H; Ohlsen, H

1992-09-01

One hundred fifty 45-55-year-old men were divided into three groups: those with healthy backs, recurrent low back pain (LBP), and chronic LBP. These groups were studied with respect to anthropometry, spinal canal width, spinal sagittal configuration and flexibility, and the flexibility of the hamstrings musculature with straight leg raising (SLR). There were no differences between the groups with respect to anthropometry. The group with healthy backs had significantly greater lordosis and sagittal flexibility than the other groups. The width of the spinal canal was correlated to body height. The SLR test showed significantly higher values in the group with healthy backs and in the recurrent pain group than in the chronic pain group. The possible role of restoring normal range of motion to minimize the risk of LBP recurrence is discussed.

Orofacial inflammatory pain affects the expression of MT1 and NADPH-d in rat caudal spinal trigeminal nucleus and trigeminal ganglion

PubMed Central

Huang, Fang; He, Hongwen; Fan, Wenguo; Liu, Yongliang; Zhou, Hongyu; Cheng, Bin

2013-01-01

Very little is known about the role of melatonin in the trigeminal system, including the function of melatonin receptor 1. In the present study, adult rats were injected with formaldehyde into the right vibrissae pad to establish a model of orofacial inflammatory pain. The distribution of melatonin receptor 1 and nicotinamide adenine dinucleotide phosphate diaphorase in the caudal spinal trigeminal nucleus and trigeminal ganglion was determined with immunohistochemistry and histochemistry. The results show that there are significant differences in melatonin receptor 1 expression and nicotinamide adenine dinucleotide phosphate diaphorase expression in the trigeminal ganglia and caudal spinal nucleus during the early stage of orofacial inflammatory pain. Our findings suggest that when melatonin receptor 1 expression in the caudal spinal nucleus is significantly reduced, melatonin's regulatory effect on pain is attenuated. PMID:25206619

Reducing risk of spinal haematoma from spinal and epidural pain procedures.

PubMed

Breivik, Harald; Norum, Hilde; Fenger-Eriksen, Christian; Alahuhta, Seppo; Vigfússon, Gísli; Thomas, Owain; Lagerkranser, Michael

2018-04-25

Central neuraxial blocks (CNB: epidural, spinal and their combinations) and other spinal pain procedures can cause serious harm to the spinal cord in patients on antihaemostatic drugs or who have other risk-factors for bleeding in the spinal canal. The purpose of this narrative review is to provide a practise advisory on how to reduce risk of spinal cord injury from spinal haematoma (SH) during CNBs and other spinal pain procedures. Scandinavian guidelines from 2010 are part of the background for this practise advisory. We searched recent guidelines, PubMed (MEDLINE), SCOPUS and EMBASE for new and relevant randomised controlled trials (RCT), case-reports and original articles concerning benefits of neuraxial blocks, risks of SH due to anti-haemostatic drugs, patient-related risk factors, especially renal impairment with delayed excretion of antihaemostatic drugs, and specific risk factors related to the neuraxial pain procedures. Epidural and spinal analgesic techniques, as well as their combination provide superior analgesia and reduce the risk of postoperative and obstetric morbidity and mortality. Spinal pain procedure can be highly effective for cancer patients, less so for chronic non-cancer patients. We did not identify any RCT with SH as outcome. We evaluated risks and recommend precautions for SH when patients are treated with antiplatelet, anticoagulant, or fibrinolytic drugs, when patients' comorbidities may increase risks, and when procedure-specific risk factors are present. Inserting and withdrawing epidural catheters appear to have similar risks for initiating a SH. Invasive neuraxial pain procedures, e.g. spinal cord stimulation, have higher risks of bleeding than traditional neuraxial blocks. We recommend robust monitoring routines and treatment protocol to ensure early diagnosis and effective treatment of SH should this rare but potentially serious complication occur. When neuraxial analgesia is considered for a patient on anti-haemostatic medication, with patient-related, or procedure-related risk factors, the balance of benefits against risks of bleeding is decisive; when CNB are offered exclusively to patients who will have a reduction of postoperative morbidity and mortality, then a higher risk of bleeding may be accepted. Robust routines should ensure appropriate discontinuation of anti-haemostatic drugs and early detection and treatment of SH. There is an on-going development of drugs for prevention of thromboembolic events following surgery and childbirth. The present practise advisory provides up-to-date knowledge and experts' experiences so that patients who will greatly benefit from neuraxial pain procedures and have increased risk of bleeding can safely benefit from these procedures. There are always individual factors for the clinician to evaluate and consider. Increasingly it is necessary for the anaesthesia and analgesia provider to collaborate with specialists in haemostasis. Surgeons and obstetricians must be equally well prepared to collaborate for the best outcome for their patients suffering from acute or chronic pain. Optimal pain management is a prerequisite for enhanced recovery after surgery, but there is a multitude of additional concerns, such as early mobilisation, early oral feeding and ileus prevention that surgeons and anaesthesia providers need to optimise for the best outcome and least risk of complications.

Leaky gate model: intensity-dependent coding of pain and itch in the spinal cord

PubMed Central

Sun, Shuohao; Xu, Qian; Guo, Changxiong; Guan, Yun; Liu, Qin; Dong, Xinzhong

2017-01-01

SUMMARY Coding of itch versus pain has been heatedly debated for decades. However, the current coding theories (labeled line, intensity and selectivity theory) cannot accommodate all experimental observations. Here we identified a subset of spinal interneurons, labeled by gastrin releasing peptide (Grp), that receive direct synaptic input from both pain and itch primary sensory neurons. When activated, these Grp+ neurons generated rarely-seen simultaneous robust pain and itch responses that were intensity-dependent. Accordingly, we propose a “leaky gate” model, in which Grp+ neurons transmit both itch and weak pain signals, however upon strong painful stimuli the recruitment of endogenous opioids works to close this gate, reducing overwhelming pain generated by parallel pathways. Consistent with our model, loss of these Grp+ neurons increased pain responses while itch was decreased. Our new model serves as an example of non-monotonic coding in the spinal cord and better explains observations in human psychophysical studies. PMID:28231466

Magnesium attenuates chronic hypersensitivity and spinal cord NMDA receptor phosphorylation in a rat model of diabetic neuropathic pain

PubMed Central

Rondón, L J; Privat, A M; Daulhac, L; Davin, N; Mazur, A; Fialip, J; Eschalier, A; Courteix, C

2010-01-01

Neuropathic pain is a common diabetic complication affecting 8–16% of diabetic patients. It is characterized by aberrant symptoms of spontaneous and stimulus-evoked pain including hyperalgesia and allodynia. Magnesium (Mg) deficiency has been proposed as a factor in the pathogenesis of diabetes-related complications, including neuropathy. In the central nervous system, Mg is also a voltage-dependant blocker of the N-methyl-d-aspartate receptor channels involved in abnormal processing of sensory information. We hypothesized that Mg deficiency might contribute to the development of neuropathic pain and the worsening of clinical and biological signs of diabetes and consequently, that Mg administration could prevent or improve its complications. We examined the effects of oral Mg supplementation (296 mg l−1 in drinking water for 3 weeks) on the development of neuropathic pain and on biological and clinical parameters of diabetes in streptozocin (STZ)-induced diabetic rats. STZ administration induced typical symptoms of type 1 diabetes. The diabetic rats also displayed mechanical hypersensitivity and tactile and thermal allodynia. The level of phosphorylated NMDA receptor NR1 subunit (pNR1) was higher in the spinal dorsal horn of diabetic hyperalgesic/allodynic rats. Magnesium supplementation failed to reduce hyperglycaemia, polyphagia and hypermagnesiuria, or to restore intracellular Mg levels and body growth, but increased insulinaemia and reduced polydipsia. Moreover, it abolished thermal and tactile allodynia, delayed the development of mechanical hypersensitivity, and prevented the increase in spinal cord dorsal horn pNR1. Thus, neuropathic pain symptoms can be attenuated by targeting the Mg-mediated blockade of NMDA receptors, offering new therapeutic opportunities for the management of chronic neuropathic pain. PMID:20837644

The Effect of Repeated Electroacupuncture Analgesia on Neurotrophic and Cytokine Factors in Neuropathic Pain Rats

PubMed Central

Wang, Junying; Duanmu, Chenlin; Feng, Xiumei; Yan, Yaxia

2016-01-01

Chronic pain is a common disability influencing quality of life. Results of previous studies showed that acupuncture has a cumulative analgesic effect, but the relationship with spinal cytokines neurotrophic factors released by astrocytes remains unknown. The present study was designed to observe the effect of electroacupuncture (EA) treatment on spinal cytokines neurotrophic factors in chronic neuropathic pain rats. The chronic neuropathic pain was established by chronic constrictive injury (CCI). EA treatment was applied at Zusanli (ST36) and Yanglingquan (GB34) (both bilateral) once a day, for 30 min. IL-1β mRNA, TNF-α mRNA, and IL-1 mRNA were detected by quantitative real-time PCR, and the proteins of BDNF, NGF, and NT3/4 were detected by Western blot. The expression levels of cytokines such as IL-1β mRNA, TNF-α mRNA, IL-6 mRNA, and neurotrophic factors such as BDNF, NGF, and NT3/4 in the spinal cord were increased significantly after CCI. The astrocytes released more IL-1β and BDNF after CCI. Repeated EA treatment could suppress the elevated expression of IL-1β mRNA, TNFα mRNA, and BDNF, NGF, and NT3/4 but had no effect on IL-6 mRNA. It is suggested that cytokines and neurotrophic factors which may be closely associated with astrocytes participated in the process of EA relieving chronic pain. PMID:27800006

Gastric Electrical Stimulation Decreases Gastric Distension-Induced Central Nociception Response through Direct Action on Primary Afferents

PubMed Central

Ouelaa, Wassila; Ghouzali, Ibtissem; Langlois, Ludovic; Fetissov, Serguei; Déchelotte, Pierre; Ducrotté, Philippe; Leroi, Anne Marie; Gourcerol, Guillaume

2012-01-01

Background & Aims Gastric electrical stimulation (GES) is an effective therapy to treat patients with chronic dyspepsia refractory to medical management. However, its mechanisms of action remain poorly understood. Methods Gastric pain was induced by performing gastric distension (GD) in anesthetized rats. Pain response was monitored by measuring the pseudo-affective reflex (e.g., blood pressure variation), while neuronal activation was determined using c-fos immunochemistry in the central nervous system. Involvement of primary afferents was assessed by measuring phosphorylation of ERK1/2 in dorsal root ganglia. Results GES decreased blood pressure variation induced by GD, and prevented GD-induced neuronal activation in the dorsal horn of the spinal cord (T9–T10), the nucleus of the solitary tract and in CRF neurons of the hypothalamic paraventricular nucleus. This effect remained unaltered within the spinal cord when sectioning the medulla at the T5 level. Furthermore, GES prevented GD-induced phosphorylation of ERK1/2 in dorsal root ganglia. Conclusions GES decreases GD-induced pain and/or discomfort likely through a direct modulation of gastric spinal afferents reducing central processing of visceral nociception. PMID:23284611

Cyclic Sciatica and Back Pain Responds to Treatment of Underlying Endometriosis: Case Illustration.

PubMed

Uppal, Jaya; Sobotka, Stanislaw; Jenkins, Arthur L

2017-01-01

Multiple causes outside the spine can mimic spinal back pain. Endometriosis is an important gynecologic disorder, which commonly affects the lower region of the female pelvis and less frequently the spine and soft tissues. The lumbosacral trunk is vulnerable to pressure from any abdominal mass originating from the uterus and the ovaries. Therefore symptoms of endometriosis include severe reoccurring pain in the pelvic area as well as lower back and abdominal pain. We report on a 39-year-old gymnast with cyclic sciatica and back pain, whose initial presentation initially led to a spinal fusion at L4/5 and L5/S1, but that procedure did not change her symptoms. Her diagnosis of endometriosis was not made until 2 years after her spinal fusion. Ultimately, once diagnosed with endometriosis of the retroperitoneal spinal and neural elements, her back and leg pain responded completely to hormonal therapy and then to a hysterectomy and a bilateral salpingo-oophorectomy. Because her true diagnosis of endometriosis was unknown and she had some degenerative changes in her spine, she underwent a spinal fusion that would probably not have been done if the diagnosis of endometriosis had been suggested. It is critical for any clinician who deals with back pain to at least consider the diagnosis of endometriosis in female patients who have a history of pelvic pain. The diagnosis of endometriosis should be considered in candidate patients by asking whether there is a significant hormonal cyclic nature to the symptoms, to prevent such unnecessary surgical adventures. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiotherapy Suppresses Bone Cancer Pain through Inhibiting Activation of cAMP Signaling in Rat Dorsal Root Ganglion and Spinal Cord.

PubMed

Zhu, Guiqin; Dong, Yanbin; He, Xueming; Zhao, Ping; Yang, Aixing; Zhou, Rubing; Ma, Jianhua; Xie, Zhong; Song, Xue-Jun

2016-01-01

Radiotherapy is one of the major clinical approaches for treatment of bone cancer pain. Activation of cAMP-PKA signaling pathway plays important roles in bone cancer pain. Here, we examined the effects of radiotherapy on bone cancer pain and accompanying abnormal activation of cAMP-PKA signaling. Female Sprague-Dawley rats were used and received tumor cell implantation (TCI) in rat tibia (TCI cancer pain model). Some of the rats that previously received TCI treatment were treated with X-ray radiation (radiotherapy). Thermal hyperalgesia and mechanical allodynia were measured and used for evaluating level of pain caused by TCI treatment. PKA mRNA expression in dorsal root ganglion (DRG) was detected by RT-PCR. Concentrations of cAMP, IL-1β, and TNF-α as well as PKA activity in DRG and the spinal cord were measured by ELISA. The results showed that radiotherapy significantly suppressed TCI-induced thermal hyperalgesia and mechanical allodynia. The level of PKA mRNA in DRG, cAMP concentration and PKA activity in DRG and in the spinal cord, and concentrations of IL-1β and TNF-α in the spinal cord were significantly reduced by radiotherapy. In addition, radiotherapy also reduced TCI-induced bone loss. These findings suggest that radiotherapy may suppress bone cancer pain through inhibition of activation of cAMP-PKA signaling pathway in DRG and the spinal cord.

Do people with recurrent back pain constrain spinal motion during seated horizontal and downward reaching?

PubMed

Crosbie, Jack; Nascimento, Dafne Port; Filho, Ruben de Faria Negrão; Ferreira, Paulo

2013-10-01

Although the effect of symptomatic back pain on functional movement has been investigated, changes to spinal movement patterns in essentially pain-free people with a history of recurrent back pain are largely unreported. Reaching activities, important for everyday and occupational function, often present problems to such people, but have not been considered in this population. The purpose of this study was to compare the amplitude and timing of spinal and hip motions during two, seated reaching activities in people with and without a history of recurrent low back pain (RLBP). Spinal and hip motions during reaching downward and across the body, in both directions, were tracked using electromagnetic sensors. Analyses were conducted to explore the amplitudes, velocities and timings of 3D segmental movements and to compare controls with subjects with recurrent, but asymptomatic lumbar or lumbosacral pain. We detected significant differences in the amplitude and timing of movement in the lower thoracic region, with the RLBP group restricting movement and demonstrating compensatory increased motion at the hip. The lumbar region displayed no significant between-group differences. The order in which the spinal segments achieved peak velocity in cross-reaching was reversed in RLBP compared to controls, with lumbar motion leading in controls and lagging in RLBP. Subjects with a history of RLBP show a number of altered kinematic features during reaching activities which are not related to the presence or intensity of pain, but which suggest adaptive changes to movement control. © 2013.

Inhibition of spinal astrocytic c-Jun N-terminal kinase (JNK) activation correlates with the analgesic effects of ketamine in neuropathic pain

PubMed Central

2011-01-01

Background We have previously reported that inhibition of astrocytic activation contributes to the analgesic effects of intrathecal ketamine on spinal nerve ligation (SNL)-induced neuropathic pain. However, the underlying mechanisms are still unclear. c-Jun N-terminal kinase (JNK), a member of mitogen-activated protein kinase (MAPK) family, has been reported to be critical for spinal astrocytic activation and neuropathic pain development after SNL. Ketamine can decrease lipopolysaccharide (LPS)-induced phosphorylated JNK (pJNK) expression and could thus exert its anti-inflammatory effect. We hypothesized that inhibition of astrocytic JNK activation might be involved in the suppressive effect of ketamine on SNL-induced spinal astrocytic activation. Methods Immunofluorescence histochemical staining was used to detect SNL-induced spinal pJNK expression and localization. The effects of ketamine on SNL-induced mechanical allodynia were confirmed by behavioral testing. Immunofluorescence histochemistry and Western blot were used to quantify the SNL-induced spinal pJNK expression after ketamine administration. Results The present study showed that SNL induced ipsilateral pJNK up-regulation in astrocytes but not microglia or neurons within the spinal dorsal horn. Intrathecal ketamine relieved SNL-induced mechanical allodynia without interfering with motor performance. Additionally, intrathecal administration of ketamine attenuated SNL-induced spinal astrocytic JNK activation in a dose-dependent manner, but not JNK protein expression. Conclusions The present results suggest that inhibition of JNK activation may be involved in the suppressive effects of ketamine on SNL-induced spinal astrocyte activation. Therefore, inhibition of spinal JNK activation may be involved in the analgesic effects of ketamine on SNL-induced neuropathic pain. PMID:21255465

Transient Receptor Potential Channel and Interleukin-17A Involvement in LTTL Gel Inhibition of Bone Cancer Pain in a Rat Model.

PubMed

Wang, Juyong; Zhang, Ruixin; Dong, Changsheng; Jiao, Lijing; Xu, Ling; Liu, Jiyong; Wang, Zhengtao; Lao, Lixing

2015-07-01

Cancer pain management is a challenge for which Chinese herbal medicine might be useful. To study the spinal mechanisms of the Chinese medicated gel Long-Teng-Tong-Luo (LTTL), a 7-herb compound, on bone cancer pain, a bone cancer pain model was made by inoculating the tibias of female rats with Walker 256 cells. LTTL gel or inert gel, 0.5 g/cm(2)/d, was applied to the skin of tumor-bearing tibias for 21 days beginning a day after the inoculation. Mechanical threshold and paw withdrawal latency to thermal stimulation was measured. Transient receptor potential (TRP) cation channels in lumbar dorsal root ganglia (DRG) were immunostained and counted, and lumbar spinal cord interleukin-17A (IL-17A) was measured with real-time polymerase chain reaction and enzyme-linked immunosorbent assay. TRP antagonists and interleukin (IL)-17A antibodies were intrathecally administered to determine their effects on bone cancer pain. The gel significantly (P < .05) alleviated cancer-induced mechanical allodynia and thermal hyperalgesia and inhibited cancer-enhanced expression of IL-17A in spinal astrocytes and the TRP subfamily members V1, A1, and V4 in lumbar DRG. Intrathecal TRP antagonists at 10 µg significantly (P < .05) attenuated mechanical allodynia, thermal hyperalgesia, and IL-17A expression, indicating that TRP channels facilitate spinal IL-17 expression and cancer pain. IL-17A antibodies inhibited cancer pain, suggesting that IL-17A promotes such pain. The data show that LTTL gel inhibits cancer pain, and this might be accounted for by the decrease in expression of DRG TRP channels and spinal astrocyte IL-17A. © The Author(s) 2015.

Fyn kinase-mediated phosphorylation of NMDA receptor NR2B subunit at Tyr1472 is essential for maintenance of neuropathic pain.

PubMed

Abe, Tetsuya; Matsumura, Shinji; Katano, Tayo; Mabuchi, Tamaki; Takagi, Kunio; Xu, Li; Yamamoto, Akitsugu; Hattori, Kotaro; Yagi, Takeshi; Watanabe, Masahiko; Nakazawa, Takanobu; Yamamoto, Tadashi; Mishina, Masayoshi; Nakai, Yoshihide; Ito, Seiji

2005-09-01

Despite abundant evidence implicating the importance of N-methyl-D-aspartate (NMDA) receptors in the spinal cord for pain transmission, the signal transduction coupled to NMDA receptor activation is largely unknown for the neuropathic pain state that lasts over periods of weeks. To address this, we prepared mice with neuropathic pain by transection of spinal nerve L5. Wild-type, NR2A-deficient, and NR2D-deficient mice developed neuropathic pain; in addition, phosphorylation of NR2B subunits of NMDA receptors at Tyr1472 was observed in the superficial dorsal horn of the spinal cord 1 week after nerve injury. Neuropathic pain and NR2B phosphorylation at Tyr1472 were attenuated by the NR2B-selective antagonist CP-101,606 and disappeared in mice lacking Fyn kinase, a Src-family tyrosine kinase. Concomitant with the NR2B phosphorylation, an increase in neuronal nitric oxide synthase activity was visualized in the superficial dorsal horn of neuropathic pain mice by NADPH diaphorase histochemistry. Electron microscopy showed that the phosphorylated NR2B was localized at the postsynaptic density in the spinal cord of mice with neuropathic pain. Indomethacin, an inhibitor of prostaglandin (PG) synthesis, and PGE receptor subtype EP1-selective antagonist reduced the NR2B phosphorylation in these mice. Conversely, EP1-selective agonist stimulated Fyn kinase-dependent nitric oxide formation in the spinal cord. The present study demonstrates that Tyr1472 phosphorylation of NR2B subunits by Fyn kinase may have dual roles in the retention of NMDA receptors in the postsynaptic density and in activation of nitric oxide synthase, and suggests that PGE2 is involved in the maintenance of neuropathic pain via the EP1 subtype.

INTRA-ARTICULAR NERVE GROWTH FACTOR REGULATES DEVELOPMENT, BUT NOT MAINTENANCE, OF INJURY-INDUCED FACET JOINT PAIN & SPINAL NEURONAL HYPERSENSITIVITY

PubMed Central

Kras, Jeffrey V.; Kartha, Sonia; Winkelstein, Beth A.

2015-01-01

Objective The objective of the current study is to define whether intra-articular nerve growth factor (NGF), an inflammatory mediator that contributes to osteoarthritic pain, is necessary and sufficient for the development or maintenance of injury-induced facet joint pain and its concomitant spinal neuronal hyperexcitability. Method Male Holtzman rats underwent painful cervical facet joint distraction or sham procedures. Mechanical hyperalgesia was assessed in the forepaws, and NGF expression was quantified in the C6/C7 facet joint. An anti-NGF antibody was administered intra-articularly in additional rats immediately or 1 day following facet distraction or sham procedures to block intra-articular NGF and test its contribution to initiation and/or maintenance of facet joint pain and spinal neuronal hyperexcitability. NGF was injected into the bilateral C6/C7 facet joints in separate rats to determine if NGF alone is sufficient to induce these behavioral and neuronal responses. Results NGF expression increases in the cervical facet joint in association with behavioral sensitivity after that joint’s mechanical injury. Intra-articular application of anti-NGF immediately after a joint distraction prevents the development of both injury-induced pain and hyperexcitability of spinal neurons. Yet, intra-articular anti-NGF applied after pain has developed does not attenuate either behavioral or neuronal hyperexcitability. Intra-articular NGF administered to the facet in naïve rats also induces behavioral hypersensitivity and spinal neuronal hyperexcitability. Conclusion Findings demonstrate that NGF in the facet joint contributes to the development of injury-induced joint pain. Localized blocking of NGF signaling in the joint may provide potential treatment for joint pain. PMID:26521746

Intra-articular nerve growth factor regulates development, but not maintenance, of injury-induced facet joint pain & spinal neuronal hypersensitivity.

PubMed

Kras, J V; Kartha, S; Winkelstein, B A

2015-11-01

The objective of the current study is to define whether intra-articular nerve growth factor (NGF), an inflammatory mediator that contributes to osteoarthritic pain, is necessary and sufficient for the development or maintenance of injury-induced facet joint pain and its concomitant spinal neuronal hyperexcitability. Male Holtzman rats underwent painful cervical facet joint distraction (FJD) or sham procedures. Mechanical hyperalgesia was assessed in the forepaws, and NGF expression was quantified in the C6/C7 facet joint. An anti-NGF antibody was administered intra-articularly in additional rats immediately or 1 day following facet distraction or sham procedures to block intra-articular NGF and test its contribution to initiation and/or maintenance of facet joint pain and spinal neuronal hyperexcitability. NGF was injected into the bilateral C6/C7 facet joints in separate rats to determine if NGF alone is sufficient to induce these behavioral and neuronal responses. NGF expression increases in the cervical facet joint in association with behavioral sensitivity after that joint's mechanical injury. Intra-articular application of anti-NGF immediately after a joint distraction prevents the development of both injury-induced pain and hyperexcitability of spinal neurons. Yet, intra-articular anti-NGF applied after pain has developed does not attenuate either behavioral or neuronal hyperexcitability. Intra-articular NGF administered to the facet in naïve rats also induces behavioral hypersensitivity and spinal neuronal hyperexcitability. Findings demonstrate that NGF in the facet joint contributes to the development of injury-induced joint pain. Localized blocking of NGF signaling in the joint may provide potential treatment for joint pain. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Percutaneous Radiofrequency Ablation of Painful Spinal Tumors Adjacent to the Spinal Cord with Real-Time Monitoring of Spinal Canal Temperature: A Prospective Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakatsuka, Atsuhiro, E-mail: nakatuka@clin.medic.mie-u.ac.jp; Yamakado, Koichiro; Takaki, Haruyuki

2009-01-15

PurposeTo prospectively evaluate the feasibility, safety, and clinical utility of bone radiofrequency (RF) ablation with real-time monitoring of the spinal canal temperature for the treatment of spinal tumors adjacent to the spinal cord.Materials and MethodsOur Institutional Review Board approved this study. Patients gave informed consent. The inclusion criteria were (a) a painful spinal metastasis and (b) a distance of 1 cm or less between the metastasis and the spinal cord. The thermocouple was placed in the spinal canal under CT fluoroscopic guidance. When the spinal canal temperature reached 45{sup o}C, RF application was immediately stopped. RF ablation was considered technicallymore » successful when the procedure was performed without major complications. Clinical success was defined as a fall in the visual analogue scale score of at least 2 points.ResultsTen patients with spinal tumors measuring 3-8 cm (mean, 4.9 {+-} 1.5 cm) were enrolled. The distance between the tumor and the spinal cord was 1-6 mm (mean, 2.4 {+-} 1.6 mm). All procedures were judged technically successful (100%). The spinal canal temperature did not exceed 45{sup o}C in 9 of the 10 patients (90%). In the remaining patient, the temperature rose to 48{sup o}C, resulting in transient neural damage, although RF application was immediately stopped when the temperature reached 45{sup o}C. Clinical success was achieved within 1 week in all patients (100%).ConclusionBone RF ablation with real-time monitoring of the spinal canal temperature is feasible, safe, and clinically useful for the treatment of painful spinal metastases adjacent to the spinal cord.« less

The plasticity of descending controls in pain: translational probing.

PubMed

Bannister, Kirsty; Dickenson, A H

2017-07-01

Descending controls, comprising pathways that originate in midbrain and brainstem regions and project onto the spinal cord, have long been recognised as key links in the multiple neural networks that interact to produce the overall pain experience. There is clear evidence from preclinical and clinical studies that both peripheral and central sensitisation play important roles in determining the level of pain perceived. Much emphasis has been put on spinal cord mechanisms in central excitability, but it is now becoming clear that spinal hyperexcitability can be regulated by descending pathways from the brain that originate from predominantly noradrenergic and serotonergic systems. One pain can inhibit another. In this respect diffuse noxious inhibitory controls (DNIC) are a unique form of endogenous descending inhibitory pathway since they can be easily evoked and quantified in animals and man. The spinal pharmacology of pathways that subserve DNIC are complicated; in the normal situation these descending controls produce a final inhibitory effect through the actions of noradrenaline at spinal α 2 -adrenoceptors, although serotonin, acting on facilitatory spinal 5-HT 3 receptors, influences the final expression of DNIC also. These descending pathways are altered in neuropathy and the effects of excess serotonin may now become inhibitory through activation of spinal 5-HT 7 receptors. Conditioned pain modulation (CPM) is the human counterpart of DNIC and requires a descending control also. Back and forward translational studies between DNIC and CPM, gauged between bench and bedside, are key for the development of analgesic therapies that exploit descending noradrenergic and serotonergic control pathways. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Oxycodone Plus Ultra-Low-Dose Naltrexone Attenuates Neuropathic Pain and Associated μ-Opioid Receptor–Gs Coupling

PubMed Central

Largent-Milnes, Tally M.; Guo, Wenhong; Wang, Hoau-Yan; Burns, Lindsay H.; Vanderah, Todd W.

2017-01-01

Both peripheral nerve injury and chronic opioid treatment can result in hyperalgesia associated with enhanced excitatory neurotransmission at the level of the spinal cord. Chronic opioid administration leads to a shift in μ-opioid receptor (MOR)–G protein coupling from Gi/o to Gs that can be prevented by cotreatment with an ultra-low-dose opioid antagonist. In this study, using lumbar spinal cord tissue from rats with L5/L6 spinal nerve ligation (SNL), we demonstrated that SNL injury induces MOR linkage to Gs in the damaged (ipsilateral) spinal dorsal horn. This MOR-Gs coupling occurred without changing Gi/o coupling levels and without changing the expression of MOR or Gα proteins. Repeated administration of oxycodone alone or in combination with ultra-low-dose naltrexone (NTX) was assessed on the SNL-induced MOR-Gs coupling as well as on neuropathic pain behavior. Repeated spinal oxycodone exacerbated the SNL-induced MOR-Gs coupling, whereas ultra-low-dose NTX cotreatment slightly but significantly attenuated this Gs coupling. Either spinal or oral administration of oxycodone plus ultra-low-dose NTX markedly enhanced the reductions in allodynia and thermal hyperalgesia produced by oxycodone alone and minimized tolerance to these effects. The MOR-Gs coupling observed in response to SNL may in part contribute to the excitatory neurotransmission in spinal dorsal horn in neuropathic pain states. The antihyperalgesic and antiallodynic effects of oxycodone plus ultra-low-dose NTX (Oxytrex, Pain Therapeutics, Inc., San Mateo, CA) suggest a promising new treatment for neuropathic pain. PMID:18468954

Mu-Opioid Receptors in Ganglia, But Not in Muscle, Mediate Peripheral Analgesia in Rat Muscle Pain.

PubMed

Bagues, Ana; Martín, María Isabel; Higuera-Matas, Alejandro; Esteban-Hernández, Jesús; Ambrosio, Emilio; Sánchez-Robles, Eva María

2018-04-01

Previous studies have demonstrated the participation of peripheral μ-opioid receptors (MOR) in the antinociceptive effect of systemically administered morphine and loperamide in an orofacial muscle pain model, induced by hypertonic saline, but not in a spinally innervated one, in rats. In this study, we determine whether this peripheral antinociceptive effect is due to the activation of MOR localized in the muscle, ganglia, or both. To determine the local antinociceptive effect of morphine and loperamide, 2 models of acute muscle pain (trigeminal and spinal) were used. Also, to study the MOR expression, protein quantification was performed in the trigeminal and spinal ganglia, and in the muscles. The behavioral results show that the intramuscular injection of morphine and loperamide did not exert an antinociceptive effect in either muscle (morphine: P = .63, loperamide: P = .9). On the other hand, MOR expression was found in the ganglia but not in the muscles. This expression was on average 44% higher (95% confidence interval, 33.3-53.9) in the trigeminal ganglia than in the spinal one. The peripheral antinociceptive effect of systemically administered opioids may be due to the activation of MOR in ganglia. The greater expression of MOR in trigeminal ganglia could explain the higher antinociceptive effect of opioids in orofacial muscle pain than in spinal muscle pain. Therefore, peripheral opioids could represent a promising approach for the treatment of orofacial pain.

Spinal Changes of a Newly Isolated Neuropeptide Endomorphin-2 Concomitant with Vincristine-Induced Allodynia

PubMed Central

Huang, Ben-Qing; Liu, Ji-Dong; Liu, Hui; Zhang, Nan; Li, Li; Chen, Jian-Hua

2014-01-01

Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain unclear. There is increasing evidence implicating the involvement of spinal endomorphin-2 (EM2) in neuropathic pain. In this study, we used a vincristine-evoked rat CNP model displaying mechanical allodynia and central sensitization, and observed a significant decrease in the expression of spinal EM2 in CNP. Also, while intrathecal administration of exogenous EM2 attenuated allodynia and central sensitization, the mu-opioid receptor antagonist β-funaltrexamine facilitated these events. We found that the reduction in spinal EM2 was mediated by increased activity of dipeptidylpeptidase IV, possibly as a consequence of chemotherapy-induced oxidative stress. Taken together, our findings suggest that a decrease in spinal EM2 expression causes the loss of endogenous analgesia and leads to enhanced pain sensation in CNP. PMID:24586889

Syringomyelia and Arnold-Chiari malformation associated with neck pain and left arm radiculopathy treated with spinal manipulation

PubMed Central

Tieppo Francio, Vinicius

2014-01-01

An 18-year-old female patient presented with left dominant neck pain after a motor vehicle collision. Her cervical spine MRI revealed syringomyelia with associated Type I Arnold-Chiari malformation. Some researchers have reported that these might be considered contraindications to spinal manipulation. Nevertheless, her benign and functional clinical examination suggested otherwise and she underwent four manipulative treatments in 2 weeks. By the end of the treatment plan and after 1-month follow-up, she was asymptomatic, no adverse effects were noted and her outcome assessment score decreased from 56% to 0%. This case illustrates that spinal manipulation may be a useful adjunctive treatment procedure for spinal pain, even in the presence of syringomyelia and Chiari malformation, which may not necessarily be a contraindication to spinal manipulation, when performed by a skilled and well-trained physician. PMID:25385566

Steadiness of Spinal Regions during Single-Leg Standing in Older Adults with and without Chronic Low Back Pain

PubMed Central

Kuo, Yi-Liang; Huang, Kuo-Yuan; Chiang, Pei-Tzu; Lee, Pei-Yun; Tsai, Yi-Ju

2015-01-01

The aims of this study were to compare the steadiness index of spinal regions during single-leg standing in older adults with and without chronic low back pain (LBP) and to correlate measurements of steadiness index with the performance of clinical balance tests. Thirteen community-dwelling older adults (aged 55 years or above) with chronic LBP and 13 age- and gender-matched asymptomatic volunteers participated in this study. Data collection was conducted in a university research laboratory. Measurements were steadiness index of spinal regions (trunk, thoracic spine, lumbar spine, and pelvis) during single-leg standing including relative holding time (RHT) and relative standstill time (RST), and clinical balance tests (timed up and go test and 5-repetition sit to stand test). The LBP group had a statistically significantly smaller RHT than the control group, regardless of one leg stance on the painful or non-painful sides. The RSTs on the painful side leg in the LBP group were not statistically significantly different from the average RSTs of both legs in the control group; however, the RSTs on the non-painful side leg in the LBP group were statistically significantly smaller than those in the control group for the trunk, thoracic spine, and lumbar spine. No statistically significant intra-group differences were found in the RHTs and RSTs between the painful and non-painful side legs in the LBP group. Measurements of clinical balance tests also showed insignificant weak to moderate correlations with steadiness index. In conclusion, older adults with chronic LBP demonstrated decreased spinal steadiness not only in the symptomatic lumbar spine but also in the other spinal regions within the kinetic chain of the spine. When treating older adults with chronic LBP, clinicians may also need to examine their balance performance and spinal steadiness during balance challenging tests. PMID:26024534

Using multilevel growth curve modeling to examine emotional modulation of temporal summation of pain (TS-pain) and the nociceptive flexion reflex (TS-NFR).

PubMed

Rhudy, Jamie L; Martin, Satin L; Terry, Ellen L; Delventura, Jennifer L; Kerr, Kara L; Palit, Shreela

2012-11-01

Emotion can modulate pain and spinal nociception, and correlational data suggest that cognitive-emotional processes can facilitate wind-up-like phenomena (ie, temporal summation of pain). However, there have been no experimental studies that manipulated emotion to determine whether within-subject changes in emotion influence temporal summation of pain (TS-pain) and the nociceptive flexion reflex (TS-NFR, a physiological measure of spinal nociception). The present study presented a series of emotionally charged pictures (mutilation, neutral, erotic) during which electric stimuli at 2 Hz were delivered to the sural nerve to evoke TS-pain and TS-NFR. Participants (n=46 healthy; 32 female) were asked to rate their emotional reactions to pictures as a manipulation check. Pain outcomes were analyzed using statistically powerful multilevel growth curve models. Results indicated that emotional state was effectively manipulated. Further, emotion modulated the overall level of pain and NFR; pain and NFR were highest during mutilation and lowest during erotic pictures. Although pain and NFR both summated in response to the 2-Hz stimulation series, the magnitude of pain summation (TS-pain) and NFR summation (TS-NFR) was not modulated by picture-viewing. These results imply that, at least in healthy humans, within-subject changes in emotions do not promote central sensitization via amplification of temporal summation. However, future studies are needed to determine whether these findings generalize to clinical populations (eg, chronic pain). Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Increased miR-132-3p expression is associated with chronic neuropathic pain

PubMed Central

Leinders, M.; Üçeyler, N.; Pritchard, R.A.; Sommer, C.; Sorkin, L.S.

2016-01-01

Alterations in the neuro-immune balance play a major role in the pathophysiology of chronic neuropathic pain. MicroRNAs (miRNA) can regulate both immune and neuronal processes and may function as master switches in chronic pain development and maintenance. We set out to analyze the role of miR-132-3p, first in patients with peripheral neuropathies and second in an animal model of neuropathic pain. We initially determined miR-132-3p expression by measuring its levels in white blood cells (WBC) of 30 patients and 30 healthy controls and next in sural nerve biopsies of 81 patients with painful or painless inflammatory or non-inflammatory neuropathies based on clinical diagnosis. We found a 2.6 fold increase in miR-132-3p expression in WBC of neuropathy patients compared to healthy controls (p<0.001). MiR-132-3p expression was also slightly up-regulated in sural nerve biopsies from neuropathy patients suffering from neuropathic pain compared to those without pain (1.2 fold; p<0.001). These promising findings were investigated further in an animal model of neuropathic pain, the spared nerve injury model (SNI). For this purpose miR-132-3p expression levels were measured in dorsal root ganglia and spinal cord of rats. Subsequently, miR-132-3p expression was pharmacologically modulated with miRNA antagonists or mimetics, and evoked pain and pain aversion were assessed. Spinal miR-132-3p levels were highest 10 days after SNI, a time when persistent allodynia was established (p<0.05). Spinal administration of miR-132-3p antagonists via intrathecal (i.t.) catheters dose dependently reversed mechanical allodyina (p<0.001) and eliminated pain behavior in the place escape avoidance paradigm (p<0.001). Intrathecal administration of miR-132-3p mimetic dose-dependently induced pain behavior in naïve rats (p<0.001). Taken together these results indicate a pro-nociceptive effect of miR-132-3p in chronic neuropathic pain. PMID:27349406

Calcium Channel α2δ1 Proteins Mediate Trigeminal Neuropathic Pain States Associated with Aberrant Excitatory Synaptogenesis*

PubMed Central

Li, Kang-Wu; Yu, Yanhui Peter; Zhou, Chunyi; Kim, Doo-Sik; Lin, Bin; Sharp, Kelli; Steward, Oswald; Luo, Z. David

2014-01-01

To investigate a potential mechanism underlying trigeminal nerve injury-induced orofacial hypersensitivity, we used a rat model of chronic constriction injury to the infraorbital nerve (CCI-ION) to study whether CCI-ION caused calcium channel α2δ1 (Cavα2δ1) protein dysregulation in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 cervical dorsal spinal cord (Vc/C2). Furthermore, we studied whether this neuroplasticity contributed to spinal neuron sensitization and neuropathic pain states. CCI-ION caused orofacial hypersensitivity that correlated with Cavα2δ1 up-regulation in trigeminal ganglion neurons and Vc/C2. Blocking Cavα2δ1 with gabapentin, a ligand for the Cavα2δ1 proteins, or Cavα2δ1 antisense oligodeoxynucleotides led to a reversal of orofacial hypersensitivity, supporting an important role of Cavα2δ1 in orofacial pain processing. Importantly, increased Cavα2δ1 in Vc/C2 superficial dorsal horn was associated with increased excitatory synaptogenesis and increased frequency, but not the amplitude, of miniature excitatory postsynaptic currents in dorsal horn neurons that could be blocked by gabapentin. Thus, CCI-ION-induced Cavα2δ1 up-regulation may contribute to orofacial neuropathic pain states through abnormal excitatory synapse formation and enhanced presynaptic excitatory neurotransmitter release in Vc/C2. PMID:24459143

Clinical application of the Panjabi neutral zone hypothesis: the Stabilimax NZ posterior lumbar dynamic stabilization system.

PubMed

Yue, James J; Timm, Jens P; Panjabi, Manohar M; Jaramillo-de la Torre, Jorge

2007-01-15

The neutral zone (NZ) is a region of intervertebral motion around the neutral posture where little resistance is offered by the passive spinal column. The NZ appears to be a clinically important measure of spinal stability function. Its size may increase with injury to the spinal column, which in turn may result in spinal instability or low-back pain. Dynamic stabilization systems are designed to support and stabilize the spine while maintaining range of motion (ROM). The Stabilimax NZ device has been designed to reduce the NZ after spinal injury to treat pain while preserving ROM.

Neuro magnetic resonance spectroscopy using wavelet decomposition and statistical testing identifies biochemical changes in people with spinal cord injury and pain.

PubMed

Stanwell, Peter; Siddall, Philip; Keshava, Nirmal; Cocuzzo, Daniel; Ramadan, Saadallah; Lin, Alexander; Herbert, David; Craig, Ashley; Tran, Yvonne; Middleton, James; Gautam, Shiva; Cousins, Michael; Mountford, Carolyn

2010-11-01

Spinal cord injury (SCI) can be accompanied by chronic pain, the mechanisms for which are poorly understood. Here we report that magnetic resonance spectroscopy measurements from the brain, collected at 3T, and processed using wavelet-based feature extraction and classification algorithms, can identify biochemical changes that distinguish control subjects from subjects with SCI as well as subdividing the SCI group into those with and without chronic pain. The results from control subjects (n=10) were compared to those with SCI (n=10). The SCI cohort was made up of subjects with chronic neuropathic pain (n=5) and those without chronic pain (n=5). The wavelet-based decomposition of frequency domain MRS signals employs statistical significance testing to identify features best suited to discriminate different classes. Moreover, the features benefit from careful attention to the post-processing of the spectroscopy data prior to the comparison of the three cohorts. The spectroscopy data, from the thalamus, best distinguished control subjects without SCI from those with SCI with a sensitivity and specificity of 0.9 (Percentage of Correct Classification). The spectroscopy data obtained from the prefrontal cortex and anterior cingulate cortex both distinguished between SCI subjects with chronic neuropathic pain and those without pain with a sensitivity and specificity of 1.0. In this study, where two underlying mechanisms co-exist (i.e. SCI and pain), the thalamic changes appear to be linked more strongly to SCI, while the anterior cingulate cortex and prefrontal cortex changes appear to be specifically linked to the presence of pain. Copyright 2010 Elsevier Inc. All rights reserved.

An 8-week thoracic spine stabilization exercise program improves postural back pain, spine alignment, postural sway, and core endurance in university students:a randomized controlled study.

PubMed

Toprak Çelenay, Şeyda; Özer Kaya, Derya

2017-04-18

To investigate the effects of an 8-week thoracic stabilization exercise program on back pain, spinal alignment, postural sway, and core endurance in university students. University students were randomly allocated into exercise (n: 28) and control (n: 25) groups. The exercise program was carried out 3 days a week for 8 weeks. Postural pain, spinal alignment, postural sway, and core endurance were assessed via visual analogue scale, Spinal Mouse, Biodex Balance System, and McGill's trunk muscle endurance tests at the baseline and after 8 weeks of training. Differences were observed for postural pain, thoracic and lumbar curvature, dynamic stability index (eyes closed), and core endurance scores in the exercise group between baseline and week 8 (P < 0.05) and all the parameters were significantly different when compared to those of the control group (P < 0.05). The program decreased postural pain, spinal curvatures, and postural sway, and increased core endurance in university students. The program can be effective in postural pain and misalignment of spine problems related to core weakness and balance disorders.

Nucleus reticularis gigantocellularis and nucleus raphe magnus in the brain stem exert opposite effects on behavioral hyperalgesia and spinal Fos protein expression after peripheral inflammation.

PubMed

Wei, F; Dubner, R; Ren, K

1999-03-01

Previous findings indicate that the brain stem descending system becomes more active in modulating spinal nociceptive processes during the development of persistent pain. The present study further identified the supraspinal sites that mediate enhanced descending modulation of behavior hyperalgesia and dorsal horn hyperexcitability (as measured by Fos-like immunoreactivity) produced by subcutaneous complete Freund's adjuvant (CFA). Selective chemical lesions were produced in the nucleus raphe magnus (NRM), the nuclei reticularis gigantocellularis (NGC), or the locus coeruleus/subcoeruleus (LC/SC). Compared to vehicle-injected animals with injection of vehicle alone, microinjection of a serotoninergic neurotoxin 5,7-dihydroxytryptamine into the NRM significantly increased thermal hyperalgesia and Fos protein expression in lumbar spinal cord after hindpaw inflammation. In contrast, the selective bilateral destruction of the NGC with a soma-selective excitotoxic neurotoxin, ibotenic acid, led to an attenuation of hyperalgesia and a reduction of inflammation-induced spinal Fos expression. Furthermore, if the NGC lesion was extended to involve the NRM, the behavioral hyperalgesia and CFA-induced Fos expression were similar to that in vehicle-injected rats. Bilateral LC/SC lesions were produced by microinjections of a noradrenergic neurotoxin, DSP-4. There was a significant increase in inflammation-induced spinal Fos expression, especially in the ipsilateral superficial dorsal horn following LC/SC lesions. These results demonstrated that multiple specific brain stem sites are involved in descending modulation of inflammatory hyperalgesia. Both NRM and LC/SC descending pathways are major sources of enhanced inhibitory modulation in inflamed animals. The persistent hyperalgesia and neuronal hyperexcitability may be mediated in part by a descending pain facilitatory system involving NGC. Thus, the intensity of perceived pain and hyperalgesia is fine-tuned by descending pathways. The imbalance of these modulating systems may be one mechanism underlying variability in acute and chronic pain conditions.

Spinal Plasticity and Behavior: BDNF-Induced Neuromodulation in Uninjured and Injured Spinal Cord

PubMed Central

Huie, J. Russell

2016-01-01

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic factor family of signaling molecules. Since its discovery over three decades ago, BDNF has been identified as an important regulator of neuronal development, synaptic transmission, and cellular and synaptic plasticity and has been shown to function in the formation and maintenance of certain forms of memory. Neural plasticity that underlies learning and memory in the hippocampus shares distinct characteristics with spinal cord nociceptive plasticity. Research examining the role BDNF plays in spinal nociception and pain overwhelmingly suggests that BDNF promotes pronociceptive effects. BDNF induces synaptic facilitation and engages central sensitization-like mechanisms. Also, peripheral injury-induced neuropathic pain is often accompanied with increased spinal expression of BDNF. Research has extended to examine how spinal cord injury (SCI) influences BDNF plasticity and the effects BDNF has on sensory and motor functions after SCI. Functional recovery and adaptive plasticity after SCI are typically associated with upregulation of BDNF. Although neuropathic pain is a common consequence of SCI, the relation between BDNF and pain after SCI remains elusive. This article reviews recent literature and discusses the diverse actions of BDNF. We also highlight similarities and differences in BDNF-induced nociceptive plasticity in naïve and SCI conditions. PMID:27721996

Early CALP2 expression and microglial activation are potential inducers of spinal IL-6 up-regulation and bilateral pain following motor nerve injury.

PubMed

Chen, Shao-Xia; Wang, Shao-Kun; Yao, Pei-Wen; Liao, Guang-Jie; Na, Xiao-Dong; Li, Yong-Yong; Zeng, Wei-An; Liu, Xian-Guo; Zang, Ying

2018-04-01

Previous work from our laboratory showed that motor nerve injury by lumbar 5 ventral root transection (L5-VRT) led to interleukin-6 (IL-6) over-expression in bilateral spinal cord, and that intrathecal administration of IL-6 neutralizing antibody delayed the induction of mechanical allodynia in bilateral hind paws. However, early events and upstream mechanisms underlying spinal IL-6 expression following L5-VRT require elucidation. The model of L5-VRT was used to induce neuropathic pain, which was assessed with von Frey hairs and the plantar tester in adult male Sprague-Dawley rats. Calpain-2 (CALP2, a calcium-dependent protease) knockdown or over-expression and microglia depletion were conducted intrathecally. Western blots and immunohistochemistry were performed to explore the possible mechanisms. Here, we provide the first evidence that both IL-6 and CALP2 levels are increased in lumbar spinal cord within 30 min following L5-VRT. IL-6 and CALP2 co-localized in both spinal dorsal horn (SDH) and spinal ventral horn. Post-operative (PO) increase in CALP2 in ipsilateral SDH was evident at 10 min PO, preceding increased IL-6 at 20 min PO. Knockdown of spinal CALP2 by intrathecal CALP2-shRNA administration prevented VRT-induced IL-6 overproduction in ipsilateral spinal cord and alleviated bilateral mechanical allodynia. Spinal microglia activation also played a role in early IL-6 up-regulation. Macrophage/microglia markers ED1/Iba1 were increased at 30 min PO, while glial fibrillary acidic protein (astrocyte) and CNPase (oligodendrocyte) markers were not. Increased Iba1 was detected as early as 20 min PO and peaked at 3 days. Morphology changed from a small soma with fine processes in resting cells to an activated ameboid shape. Depletion of microglia using Mac-1-saporin partially prevented IL-6 up-regulation and attenuated VRT-induced bilateral mechanical allodynia. Taken together, our findings provide evidence that increased spinal cord CALP2 and microglia cell activation may have early causative roles in IL-6 over-expression following motor nerve injury. Agents that inhibit CALP2 and/or microglia activation may therefore prove valuable for treating neuropathic pain. © 2018 International Society for Neurochemistry.

Spinal mobilization vs conventional physiotherapy in the management of chronic low back pain due to spinal disk degeneration: a randomized controlled trial.

PubMed

Krekoukias, Georgios; Gelalis, Ioannis D; Xenakis, Theodoros; Gioftsos, Georgios; Dimitriadis, Zacharias; Sakellari, Vasiliki

2017-05-01

The aim of the study was to examine the efficacy of spinal mobilization in subjects with low back pain (LBP) and associated spinal disk degeneration. Seventy-five subjects suffering from chronic LBP (>3 months) were randomly allocated into 3 groups of 25 subjects each. Each group received five treatment sessions with the first group receiving manual therapy (MT) (spinal mobilization), the second a sham treatment, and the third conventional physiotherapy (CP) (stretching exercises, transcutaneous electrical nerve stimulation, and massage). Subjects were assessed for their pain intensity using the numerical pain rating scale and for their self-reported disability using the Oswestry and Roland-Morris Questionnaire at baseline and after the completion of the five treatment sessions. Paired t -tests showed a significant improvement for all outcome measures in the MT and CP group ( p  < 0.05). Analysis of covariance revealed that the MT group had significant improvement in all outcome measures in comparison with the sham and CP group ( p  < 0.05), whereas no significant difference was observed between the sham and CP group ( p  > 0.05). MT is preferable to CP in order to reduce the pain intensity and disability in subjects with chronic LBP and associated disk degeneration. The findings of this study may lead to the establishment of spinal mobilization as one of the most preferable approaches for the management of LBP due to disk degeneration. 1b.

Migration of an Intracranial Subdural Hematoma to the Spinal Subdural Space: A Case Report

PubMed Central

Kwon, O Ik; Kim, Young Ha; Kim, Young Soo; Sung, Soon Ki; Lee, Sang Weon; Song, Geun Sung

2015-01-01

A 57-year-old man complained of severe lower back pain and radicular pain in both legs for 1 week after falling from a ladder. Magnetic resonance imaging (MRI) of the spine showed a subdural hematoma (SDH), which was surgically removed. The patient had no back pain or the radicular leg pain at 2 weeks post-surgery. However, he complained of diffuse headaches upon follow-up. Brain computed tomography (CT) and MRI revealed an intracranial SDH, which was immediately removed by surgery. During his 1-year follow-up, he reported that the pain had resolved without recurrence. Simultaneous spinal and intracranial SDH are rare and no standard treatment exists for this condition. This case suggests that it is possible that an intracranial SDH can migrate into the cerebrospinal fluid (CSF) space through an arachnoid tear. CSF circulation allows the intracranial SDH to enter subarachnoid spaces encasing the spinal cord. In order to prevent irreversible damage, surgical intervention should be considered for case of spinal SDH with progressive neurological deficits. PMID:26512286

Spinal cord stimulation to abort painful spasms of atypical stiff limb syndrome.

PubMed

Ughratdar, I; Sivakumar, G; Basu, S

2010-01-01

Stiff limb syndrome (SLS) is a rare chronic condition which can result in significant debility. We report the case of a 44-year-old man suffering from severe painful spasms in his right leg with a diagnosis of SLS. He had been initially treated for his pain with a spinal cord stimulator but presented with exacerbation of pain secondary to a lead fracture for which he underwent revision of the stimulator. Postoperative programming unexpectedly resulted in not only control of his pain but also an ability to abort his spasmodic episodes related to SLS. To our knowledge, spinal cord stimulation has not been previously used for SLS and our report opens up another avenue for this rare condition. We provide a brief overview of SLS and propose an underlying mechanism for the observed phenomenon.

Chronic pain and pain processing in Parkinson's disease.

PubMed

Blanchet, Pierre J; Brefel-Courbon, Christine

2017-10-12

Pain is experienced by the vast majority of patients living with Parkinson's disease. It is most often of nociceptive origin, but may also be ascribed to neuropathic (radicular or central) or miscellaneous sources. The recently validated King's Parkinson's Disease Pain Scale is based on 7 domains including musculoskeletal pain, chronic body pain (central or visceral), fluctuation-related pain, nocturnal pain, oro-facial pain, pain with discolouration/oedema/swelling, and radicular pain. The basal ganglia integrate incoming nociceptive information and contribute to coordinated motor responses in pain avoidance and nocifensive behaviors. In Parkinson's disease, nigral and extra-nigral pathology, involving cortical areas, brainstem nuclei, and spinal cord, may contribute to abnormal central nociceptive processing in patients experiencing pain or not. The dopamine deficit lowers multimodal pain thresholds that are amenable to correction following levodopa dosing. Functional brain imaging with positron emission tomography following administration of H 2 15 O revealed abnormalities in the sensory discriminative processing of pain (insula/SII), as well as in the affective motivational processing of pain (anterior cingulate cortex, prefrontal cortex). Pain management is dependent on efforts invested in diagnostic accuracy to distinguish nociceptive from neuropathic pain. Treatment requires an integrated approach including strategies to lessen levodopa-related response fluctuations, in addition to other pharmacological and non-pharmacological options such as deep brain stimulation and rehabilitation. Copyright © 2017. Published by Elsevier Inc.

Loxoprofen sodium and celecoxib for postoperative pain in patients after spinal surgery: a randomized comparative study.

PubMed

Sekiguchi, Hiroyuki; Inoue, Gen; Nakazawa, Toshiyuki; Imura, Takayuki; Saito, Wataru; Uchida, Kentaro; Miyagi, Masayuki; Takahira, Naonobu; Takaso, Masashi

2015-07-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used to treat inflammation, pain, and fever, but no criterion standard exists for the management of postoperative pain following spinal surgery. In the present study, we compared the analgesic efficacy of loxoprofen sodium (loxoprofen) and celecoxib for the management of postoperative pain following spinal surgery. One-hundred forty-one patients (mean age 62.2 years) were randomly assigned to two groups before spinal surgery: a loxoprofen group (n = 73, 180 mg/day) and a celecoxib group (n = 68, 200 mg/day). The drugs were administered from 1 day until 7 days after surgery. A numeric rating scale (NRS) was used to evaluate pain at nine predefined times every day and the findings were compared between the two groups. Laboratory data and adverse events were also recorded. There was no significant difference in the maximum and mean NRS scores on each day between loxoprofen and celecoxib, suggesting a comparable analgesic effect for these two NSAIDs. Greater improvement in the NRS score between preadministration (baseline) and 30 min or 2 h after administration was obtained for loxoprofen. This tendency was shown for both slight (NRS score <5 at baseline) and severe pain (NRS score ≥ 5 at baseline). Loxoprofen was discontinued in one patient on day 4 because of renal dysfunction. Celecoxib was discontinued in one patient on day 2 at the patient's request. Both loxoprofen sodium and celecoxib were well tolerated for the relief of acute postoperative pain after spinal surgery. A single administration of loxoprofen showed superior and rapid effectiveness compared with celecoxib for both slight and severe postoperative pain.

Comparing parecoxib and ketorolac as preemptive analgesia in patients undergoing posterior lumbar spinal fusion: a prospective randomized double-blinded placebo-controlled trial.

PubMed

Siribumrungwong, Koopong; Cheewakidakarn, Julin; Tangtrakulwanich, Boonsin; Nimmaanrat, Sasikaan

2015-03-18

Poor postoperative pain control is frequently associated with complications and delayed discharge from a hospital. Preemptive analgesia is one of the methods suggested for reducing postoperative pain. Opioids are effective for pain control, but there known addictive properties make physicians cautious about using them. Parecoxib and ketorolac are potent non-opioid NSAIDs that are attractive alternative drugs to opioids to avoid opioid-related side effects. However, there are no good head-to-head comparisons between these two drugs in the aspect of preemptive analgesic effects in lumbar spinal fusion surgery. This study aimed to compare the efficacy in terms of postoperative pain control and safety of parecoxib with ketorolac as preemptive analgesia in posterior lumbar spinal fusion patients. A prospective, double-blinded randomized controlled trial was carried out in patients undergoing posterior lumbar spinal fusion, who were randomized into 3 groups (n = 32). Parecoxib, ketorolac or a placebo was given to each patient via injection around 30 minutes prior to incision. The efficacy of postoperative pain control was assessed by a verbal numerical rating score (0-10). And various postoperative things were monitored for analysis, such as total opioid consumption, complications, and estimated blood loss. Both the ketorolac and parecoxib groups showed significantly better early postoperative pain reduction at the postanesthesia care unit (PACU) than the control group (p < 0.05). There were no differences between the pain scores of ketorolac and parecoxib at any time points. Complications and bleeding were not significantly different between all three groups. Preemptive analgesia using both ketorolac and parecoxib showed a significantly better early postoperative pain control in the PACU than the control group in patients undergoing lumbar spinal fusion. ClinicalTrials.gov NCT01859585. Registered 15 May 2013.

Spinal fusion surgery: From relief to insecurity.

PubMed

Damsgaard, Janne B; Jørgensen, Lene B; Norlyk, Annelise; Birkelund, Regner

2017-02-01

During their decision-making process patients perceive surgery as a voluntary yet necessary choice. Surgery initiates hope for a life with less pain but also creates a feeling of existential insecurity in terms of fear, isolation and uncertainty. The aim of this study was to explore how patients experience their situation from the point of making the decision to undergo spinal fusion surgery to living their everyday life after surgery. A phenomenological-hermeneutic study design was applied based on the French philosopher Paul Ricoeur's theory of interpretation. Data were collected through observations and semi-structured interviews. The recommendation and decision to undergo spinal fusion surgery felt like a turning point for the patients and brought hope of regaining their normal lives, of being a more resourceful parent, partner, friend and colleague with no or less pain. Thus, deciding to undergo surgery created a brief feeling of relief. However, life with back pain had changed the patients' understanding of themselves. Consequently, some patients postoperatively experienced insecurity and a weakened self-image with difficulties creating meaning in their lives. Being recommended and undergoing spinal fusion surgery initiates hope for a life with less pain and altered life conditions. At the same time, paradoxically, this creates a feeling of existential insecurity in terms of facing the surgery and the future to come. It is, therefore, important to recognise and include the patients' everyday life experiences concerning how they give (or may not give) meaning to their illness, i.e. their understanding of how it is affecting them. These aspects are essential for the patients' definition and re-definition of themselves and thus crucial to draw upon in the relationship and communication between patient and healthcare professional. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of spinal cord stimulation in angina pectoris induced by pacing and possible mechanisms of action.

PubMed Central

Mannheimer, C; Eliasson, T; Andersson, B; Bergh, C H; Augustinsson, L E; Emanuelsson, H; Waagstein, F

1993-01-01

OBJECTIVE--To investigate the effects of spinal cord stimulation on myocardial ischaemia, coronary blood flow, and myocardial oxygen consumption in angina pectoris induced by atrial pacing. DESIGN--The heart was paced to angina during a control phase and treatment with spinal cord stimulation. Blood samples were drawn from a peripheral artery and the coronary sinus. SETTING--Multidisciplinary pain centre, department of medicine, Ostra Hospital, and Wallenberg Research Laboratory, Sahlgrenska Hospital, Gothenburg, Sweden. SUBJECTS--Twenty patients with intractable angina pectoris, all with a spinal cord stimulator implanted before the study. RESULTS--Spinal cord stimulation increased patients' tolerance to pacing (p < 0.001). At the pacing rate comparable to that producing angina during the control recording, myocardial lactate production during control session turned into extraction (p = 0.003) and, on the electrocardiogram, ST segment depression decreased, time to ST depression increased, and time to recovery from ST depression decreased (p = 0.01; p < 0.05, and p < 0.05, respectively). Spinal cord stimulation also reduced coronary sinus blood flow (p = 0.01) and myocardial oxygen consumption (p = 0.02). At the maximum pacing rate during treatment, all patients experienced anginal pain. Myocardial lactate extraction reverted to production (p < 0.01) and the magnitude and duration of ST segment depression increased to the same values as during control pacing, indicating that myocardial ischaemia during treatment with spinal cord stimulation gives rise to anginal pain. CONCLUSIONS--Spinal cord stimulation has an anti-anginal and anti-ischaemic effect in severe coronary artery disease. These effects seem to be secondary to a decrease in myocardial oxygen consumption. Furthermore, myocardial ischemia during treatment gives rise to anginal pain. Thus, spinal cord stimulation does not deprive the patient of a warning signal. PMID:8400930

Intrathecal Drug Delivery and Spinal Cord Stimulation for the Treatment of Cancer Pain.

PubMed

Xing, Fangfang; Yong, R Jason; Kaye, Alan David; Urman, Richard D

2018-02-05

The purpose of the present investigation is to summarize the body and quality of evidence including the most recent studies in support of intrathecal drug delivery systems and spinal cord stimulation for the treatment of cancer-related pain. In the past 3 years, a number of prospective studies have been published supporting intrathecal drug delivery systems for cancer pain. Additional investigation with adjuvants to morphine-based analgesia including dexmedetomidine and ziconotide support drug-induced benefits of patient-controlled intrathecal analgesia. A study has also been recently published regarding cost-savings for intrathecal drug delivery system compared to pharmacologic management, but an analysis in the Ontario, Canada healthcare system projects additional financial costs. Finally, the Polyanalgesic Consensus Committee has updated its recommendations regarding clinical guidelines for intrathecal drug delivery systems to include new information on dosing, trialing, safety, and systemic opioid reduction. There is still a paucity of clinical evidence for spinal cord stimulation in the treatment of cancer pain. There are new intrathecal drugs under investigation including various conopeptides and AYX1. Large, prospective, modern, randomized controlled studies are still needed to support the use of both intrathecal drug delivery systems as well as spinal cord stimulation for cancer pain populations. There are multiple prospective and small randomized controlled studies that highlight a potential promising future for these interventional modalities. Related to the challenge and urgency of cancer pain, the pain practitioner community is moving toward a multimodal approach that includes discussions regarding the role of intrathecal therapies and spinal cord stimulation to the individualized treatment of patients.

Factors associated with acute and chronic pain after inguinal herniorraphy.

PubMed

Erdogan, Elif; Ozenc, Ecder

2018-04-01

The aim of this study was to analyse the relationship between types of anaesthesia, patients' demographic variables, preoperative emotional states and the prevalence of postoperative pain. In this randomized prospective study, postoperative pain was assessed in 100 patients, who were ASA (American Society of Anaesthesiologist) I-II and between 18-65 years old, undergoing inguinal herniorrhaphy with either general or spinal anaesthesia. In addition, postoperative pain compared with patients' demographic properties and psychological conditions in each group was also considered. Acute pain was evaluated at 1, 2, 4, 6, 12 and 24 th hours with the Numerical Rating Scale (NRS) and chronic neuropathic pain was at 1, 2 and 3 rd months with Douleur Neuropathique 4 Questions (DN4). All patients were treated with the same analgesics after operation. Group spinal anaesthesia had lower acute pain at 1 and 2 nd hours but they felt more severe pain at the 24 th hour. Also patients' anxieties were correlated with acute and chronic postoperative pain. Ten patients complained about postoperative chronic pain after 3 months and there was no significant difference between groups. Spinal anaesthesia decreased acute pain intensity at the first postoperative hours. Patients with anxiety felt high pain levels and they had an increased chronic pain prevalence.

A technical report on video-assisted thoracoscopy in thoracic spinal surgery. Preliminary description.

PubMed

Regan, J J; Mack, M J; Picetti, G D

1995-04-01

This report is a preliminary description of the efficacy of video-assisted thoracoscopic surgery in thoracic spinal procedures that otherwise require open thoracotomy. This report sought to describe the efficacy of video-assisted thoracoscopic surgery in thoracic spinal procedures that otherwise require open thoracotomy. In a landmark study that compared video-assisted thoracoscopic surgery for peripheral lung lesions with thoracotomy, video-assisted thoracoscopic surgery reduced postoperative pain, improved early shoulder girdle function, and shortened hospital stay. Video-assisted thoracoscopic surgery was performed in 12 thoracic spinal patients (herniated nucleus pulposus, infection, tumor, or spinal deformity) and is described in detail in this report. Video-assisted thoracoscopic surgery in thoracic spinal surgery resulted in little postoperative pain, short intensive care unit and hospital stays, and little or no morbidity. In the short follow-up period, there was no post-thoracotomy pain syndrome nor neurologic sequelae in these patients. Operative time decreased dramatically as experience was gained with the procedure. Given consistently improving surgical skills, a number of thoracic spinal procedures using video-assisted thoracoscopic surgery, including thoracic discectomy, internal rib thoracoplasty, anterior osteotomy, corpectomy, and fusion, can be performed safely with no additional surgical time or risk to the patient.

DREAM regulates BDNF-dependent spinal sensitization

PubMed Central

2010-01-01

Background The transcriptional repressor DREAM (downstream regulatory element antagonist modulator) controls the expression of prodynorphin and has been involved in the modulation of endogenous responses to pain. To investigate the role of DREAM in central mechanisms of pain sensitization, we used a line of transgenic mice (L1) overexpressing a Ca2+- and cAMP-insensitive DREAM mutant in spinal cord and dorsal root ganglia. Results L1 DREAM transgenic mice showed reduced expression in the spinal cord of several genes related to pain, including prodynorphin and BDNF (brain-derived neurotrophic factor) and a state of basal hyperalgesia without change in A-type currents. Peripheral inflammation produced enhancement of spinal reflexes and increased expression of BDNF in wild type but not in DREAM transgenic mice. The enhancement of the spinal reflexes was reproduced in vitro by persistent electrical stimulation of C-fibers in wild type but not in transgenic mice. Exposure to exogenous BDNF produced a long-term enhancement of dorsal root-ventral root responses in transgenic mice. Conclusions Our results indicate that endogenous BDNF is involved in spinal sensitization following inflammation and that blockade of BDNF induction in DREAM transgenic mice underlies the failure to develop spinal sensitization. PMID:21167062

Diabetes-induced microvascular complications at the level of the spinal cord; a contributing factor in diabetic neuropathic pain.

PubMed

Ved, N; Da Vitoria Lobo, M E; Bestall, S M; L Vidueira, C; Beazley-Long, N; Ballmer-Hofer, K; Hirashima, M; Bates, D O; Donaldson, L F; Hulse, R P

2018-05-17

Abnormalities of neurovascular interactions within the central nervous system of diabetic patients is associated with the onset of many neurological disease states. However, to date, the link between the neurovascular network within the spinal cord and regulation of nociception has not been investigated despite neuropathic pain being common in diabetes. We hypothesised that hyperglycaemia-induced endothelial degeneration in the spinal cord, due to suppression of VEGF-A/VEGFR2 signalling, induces diabetic neuropathic pain. Nociceptive pain behaviour was investigated in a chemically induced model of type 1 diabetes (streptozotocin induced, insulin supplemented; either vehicle or VEGF-A 165 b treated) and an inducible endothelial knockdown of VEGFR2 (tamoxifen induced). Diabetic animals developed mechanical allodynia and heat hyperalgesia. This was associated with a reduction in the number of blood vessels and reduction in Evans blue extravasation in the lumbar spinal cord of diabetic animals versus age-matched controls. Endothelial markers occludin, CD31 and VE-cadherin were downregulated in the spinal cord of the diabetic group versus controls, as well as a concurrent reduction of VEGF-A 165 b expression. In diabetic animals, VEGF-A 165 b treatment (biweekly intraperitoneal, 20 ng g -1 ) restored normal Evans blue extravasation and prevented vascular degeneration, diabetes-induced central neuron activation and neuropathic pain. Inducible knockdown of VEGFR2 (tamoxifen treated Tie2CreER T2 -vegfr2 flfl mice) led to a reduction in blood vessel network volume in the lumbar spinal cord and development of heat hyperalgesia. These findings indicate that hyperglycaemia leads to a reduction in the VEGF-A/VEGFR2 signalling cascade resulting in endothelial dysfunction in the spinal cord, which could be an undiscovered contributing factor to diabetic neuropathic pain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The science of spinal motion palpation: a review and update with implications for assessment and intervention

PubMed Central

Nyberg, Richard Edward; Russell Smith, A

2013-01-01

Spinal motion palpation (SMP) is a standard component of a manual therapy examination despite questionable reliability. The present research is inconclusive as to the relevance of the findings from SMP, with respect to the patient’s pain complaints. Differences in the testing methods and interpretation of spinal mobility testing are problematic. If SMP is to be a meaningful component of a spinal examination, the methods for testing and interpretation must be carefully scrutinized. The intent of this narrative review is to facilitate a better understanding of how SMP should provide the examiner with relevant information for assessment and treatment of patients with spinal pain disorders. The concept of just noticeable difference is presented and applied to SMP as a suggestion for determining the neutral zone behavior of a spinal segment. In addition, the use of a lighter, or more passive receptive palpation technique, is considered as a means for increasing tactile discrimination of spinal movement behavior. Further understanding of the scientific basis of testing SMP may improve intra- and inter-examiner reliability. The significance of the findings from SMP should be considered in context of the patient’s functional problem. Methodological changes may be indicated for the performance of SMP techniques, such as central posterior-anterior (PA) pressure and passive intervertebral motion tests, in order to improve reliability. Instructors of manual therapy involved in teaching SMP should be knowledgeable of the neurophysiological processes of touch sensation so as to best advise students in the application of the various testing techniques. PMID:24421627

Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome (CRPS) Recurrence after Amputation for CRPS, and Failure of Conventional Spinal Cord Stimulation.

PubMed

Goebel, Andreas; Lewis, Sarah; Phillip, Rhodri; Sharma, Manohar

2018-01-01

Limb amputation is sometimes being performed in long-standing complex regional pain syndrome (CRPS), although little evidence is available guiding management decisions, including how CRPS recurrence should be managed. This report details the management of a young soldier with CRPS recurrence 2 years after midtibial amputation for CRPS. Conventional spinal cord stimulation did not achieve paraesthetic coverage, or pain relief in the stump, whereas L4 dorsal root ganglion stimulation achieved both coverage and initially modest pain relief, and over time, substantial pain relief. Current evidence does not support the use of amputation to improve either pain or function in CRPS. Before a decision is made, in exceptional cases, about referral for amputation, dorsal root ganglion stimulation should be considered as a potentially effective treatment, even where conventional spinal cord stimulator treatment has failed to achieve reliable paraesthetic cover. Furthermore, this treatment may provide pain relief in those patients with CRPS recurrence in the stump after amputation. © 2017 World Institute of Pain.

Impact of McKenzie Method Therapy Enriched by Muscular Energy Techniques on Subjective and Objective Parameters Related to Spine Function in Patients with Chronic Low Back Pain

PubMed Central

Szulc, Paweł; Wendt, Michał; Waszak, Małgorzata; Tomczak, Maciej; Cieślik, Krystyna; Trzaska, Tadeusz

2015-01-01

Background The high incidence and inconsistencies in diagnostic and therapeutic process of low back pain (LBP) stimulate the continuing search for more efficient treatment modalities. Integration of the information obtained with various therapeutic methods and a holistic approach to the patient seem to be associated with positive outcomes. The aim of this study was to analyze the efficacy of combined treatment with McKenzie method and Muscle Energy Technique (MET), and to compare it with the outcomes of treatment with McKenzie method or standard physiotherapy in specific chronic lumbar pain. Material/Methods The study included 60 men and women with LBP (mean age 44 years). The patients were randomly assigned to 1 of 3 therapeutic groups, which were further treated with: 1) McKenzie method and MET, 2) McKenzie method alone, or 3) standard physiotherapy for 10 days. The extent of spinal movements (electrogoniometry), level of experienced pain (Visual Analogue Scale and Revised Oswestry Pain Questionnaire), and structure of the spinal discs (MRI) were examined prior to the intervention, immediately thereafter, and 3 months after the intervention. Results McKenzie method enriched with MET had the best therapeutic outcomes. The mobility of cervical, thoracic, and lumbar spine normalized at levels corresponding to 87.1%, 66.7%, and 95% of respective average normative values. Implementation of McKenzie method, both alone and combined with MET, was associated with a significant decrease in Oswestry Disability Index, significant alleviation of pain (VAS), and significantly reduced size of spinal disc herniation. Conclusions The combined method can be effectively used in the treatment of chronic LBP. PMID:26418868

MiR-203 involves in neuropathic pain development and represses Rap1a expression in nerve growth factor differentiated neuronal PC12 cells.

PubMed

Li, Haixia; Huang, Yuguang; Ma, Chao; Yu, Xuerong; Zhang, Zhiyong; Shen, Le

2015-01-01

Although microRNAs (miRNAs) have been shown to play a role in numerous biological processes, their function in neuropathic pain is not clear. The rat bilateral sciatic nerve chronic constriction injury (bCCI) is an established model of neuropathic pain, so we examined miRNA expression and function in the spinal dorsal horn in bCCI rats. Microarray and real-time polymerase chain reaction were used to examine the expression of miRNA in nerve system of bCCI rats, and the targets of miRNA were predicted by bioinformatic approaches. The function of specific miRNA was estimated through the methods of gene engineering. This study revealed substantially (∼10-fold) decreased miR-203 expression in the spinal dorsal horns but not the dorsal root ganglions, hippocampus, or anterior cingulate cortexes of bCCI rats. Rap1a protein expression was upregulated in bCCI rat spinal dorsal horns. We further verified that miR-203 directly targeted the 3'-untranslated region of the rap1a gene, thereby decreasing rap1a protein expression in neuron-like cells. Rap1a has diverse neuronal functions and their perturbation is responsible for several mental disorders. For example, Rap1a/MEK/ERK is involved in peripheral sensitization. These data suggest a potential role for miR-203 in regulating neuropathic pain development, and Rap1a is a validated target gene in vitro. Results from our study and others indicate the possibility that Rap1a may be involved in pain. We hope that these results can provide support for future research into miR-203 in gene therapy for neuropathic pain.

Superion Interspinous Spacer Treatment of Moderate Spinal Stenosis: 4-Year Results.

PubMed

Nunley, Pierce D; Patel, Vikas V; Orndorff, Douglas G; Lavelle, William F; Block, Jon E; Geisler, Fred H

2017-08-01

To determine 4-year clinical outcomes in patients with moderate lumbar spinal stenosis treated with minimally invasive stand-alone interspinous process decompression using the Superion device. The 4-year Superion data were extracted from a randomized, controlled Food and Drug Administration investigational device exemption trial. Patients with intermittent neurogenic claudication relieved with back flexion who failed at least 6 months of nonsurgical management were enrolled. Outcomes included Zurich Claudication Questionnaire (ZCQ) symptom severity (ss), physical function (pf) and patient satisfaction (ps) subdomains, leg and back pain visual analog scale (VAS), and Oswestry Disability Index (ODI). At 4-year follow-up, 89 of the 122 patients (73%) provided complete clinical outcome evaluations. At 4 years after index procedure, 75 of 89 patients with Superion (84.3%) demonstrated clinical success on at least 2 of 3 ZCQ domains. Individual component responder rates were 83% (74/89), 79% (70/89), and 87% (77/89) for ZCQss, ZCQpf, and ZCQps; 78% (67/86) and 66% (57/86) for leg and back pain VAS; and 62% (55/89) for ODI. Patients with Superion also demonstrated percentage improvements over baseline of 41%, 40%, 73%, 69%, and 61% for ZCQss, ZCQpf, leg pain VAS, back pain VAS, and ODI. Within-group effect sizes all were classified as very large (>1.0): 1.49, 1.65, 1.42, 1.12, and 1.46 for ZCQss, ZCQpf, leg pain VAS, back pain VAS, and ODI. Minimally invasive implantation of the Superion device provides long-term, durable relief of symptoms of intermittent neurogenic claudication for patients with moderate lumbar spinal stenosis. Copyright © 2017 Elsevier Inc. All rights reserved.

The Outcomes of Manipulation or Mobilization Therapy Compared with Physical Therapy or Exercise for Neck Pain: A Systematic Review

PubMed Central

Schroeder, Josh; Kaplan, Leon; Fischer, Dena J.; Skelly, Andrea C.

2013-01-01

Study Design Systematic review. Study Rationale Neck pain is a prevalent condition. Spinal manipulation and mobilization procedures are becoming an accepted treatment for neck pain. However, data on the effectiveness of these treatments have not been summarized. Objective To compare manipulation or mobilization of the cervical spine to physical therapy or exercise for symptom improvement in patients with neck pain. Methods A systematic review of the literature was performed using PubMed, the National Guideline Clearinghouse Database, and bibliographies of key articles, which compared spinal manipulation or mobilization therapy with physical therapy or exercise in patients with neck pain. Articles were included based on predetermined criteria and were appraised using a predefined quality rating scheme. Results From 197 citations, 7 articles met all inclusion and exclusion criteria. There were no differences in pain improvement when comparing spinal manipulation to exercise, and there were inconsistent reports of pain improvement in subjects who underwent mobilization therapy versus physical therapy. No disability improvement was reported between treatment groups in studies of acute or chronic neck pain patients. No functional improvement was found with manipulation therapy compared with exercise treatment or mobilization therapy compared with physical therapy groups in patients with acute pain. In chronic neck pain subjects who underwent spinal manipulation therapy compared to exercise treatment, results for short-term functional improvement were inconsistent. Conclusion The data available suggest that there are minimal short- and long-term treatment differences in pain, disability, patient-rated treatment improvement, treatment satisfaction, health status, or functional improvement when comparing manipulation or mobilization therapy to physical therapy or exercise in patients with neck pain. This systematic review is limited by the variability of treatment interventions and lack of standardized outcomes to assess treatment benefit. PMID:24436697

Behavioral and molecular processing of visceral pain in the brain of mice: impact of colitis and psychological stress

PubMed Central

Jain, Piyush; Hassan, Ahmed M.; Koyani, Chintan N.; Mayerhofer, Raphaela; Reichmann, Florian; Farzi, Aitak; Schuligoi, Rufina; Malle, Ernst; Holzer, Peter

2015-01-01

Gastrointestinal disorders with abdominal pain are associated with central sensitization and psychopathologies that are often exacerbated by stress. Here we investigated the impact of colitis induced by dextran sulfate sodium (DSS) and repeated water avoidance stress (WAS) on spontaneous and nociception-related behavior and molecular signaling in the mouse brain. DSS increased the mechanical pain sensitivity of the abdominal skin while both WAS and DSS enhanced the mechanical and thermal pain sensitivity of the plantar skin. These manifestations of central sensitization were associated with augmented c-Fos expression in spinal cord, thalamus, hypothalamus, amygdala and prefrontal cortex. While WAS stimulated phosphorylation of mitogen-activated protein kinase (MAPK) p42/44, DSS activated another signaling pathway, both of which converged on c-Fos. The DSS- and WAS-induced hyperalgesia in the abdominal and plantar skin and c-Fos expression in the brain disappeared when the mice were subjected to WAS+DSS treatment. Intrarectal allyl isothiocyanate (AITC) evoked aversive behavior (freezing, reduction of locomotion and exploration) in association with p42/44 MAPK and c-Fos activation in spinal cord and brain. These effects were inhibited by morphine, which attests to their relationship with nociception. DSS and WAS exerted opposite effects on AITC-evoked p42/44 MAPK and c-Fos activation, which indicates that these transduction pathways subserve different aspects of visceral pain processing in the brain. In summary, behavioral perturbations caused by colitis and psychological stress are associated with distinct alterations in cerebral signaling. These findings provide novel perspectives on central sensitization and the sensory and emotional processing of visceral pain stimuli in the brain. PMID:26217204

Spinal stenosis presenting as "the postpolio syndrome". Review of four cases.

PubMed

LaBan, M M; Sanitate, S S; Taylor, R S

1993-12-01

The diagnosis of postpolio syndrome is based primarily on a thorough history supported by both clinical and laboratory examination. Similarly, the presence of an occult spinal stenosis may be suspected initially by a history of progressive lumbar or cervical radicular pain, as well as concomitant extremity weakness and/or myelopathic signs. Appropriate electrodiagnostic examinations, including somatosensory spinal-evoked potentials and electroneuromyography, as well as imaging studies, computer-assisted tomography scan, magnetic resonance imaging and/or myelography are all useful in confirming the clinical diagnosis of either cervical spinal stenosis or lumbar spinal stenosis in patients who also may have had a history of poliomyelitis. Four patients (three men and one woman) previously diagnosed as having postpolio syndrome were referred with predominate complaints of spinal and extremity pain as well as associated motor weakness. It was subsequently recognized that these patients, ranging in age from 45-65 yr, were actually presenting with symptomatic spinal stenosis. It was discovered that two patients had cervical spinal stenosis; the other two had lumbar spinal stenosis.

Oxycodone plus ultra-low-dose naltrexone attenuates neuropathic pain and associated mu-opioid receptor-Gs coupling.

PubMed

Largent-Milnes, Tally M; Guo, Wenhong; Wang, Hoau-Yan; Burns, Lindsay H; Vanderah, Todd W

2008-08-01

Both peripheral nerve injury and chronic opioid treatment can result in hyperalgesia associated with enhanced excitatory neurotransmission at the level of the spinal cord. Chronic opioid administration leads to a shift in mu-opioid receptor (MOR)-G protein coupling from G(i/o) to G(s) that can be prevented by cotreatment with an ultra-low-dose opioid antagonist. In this study, using lumbar spinal cord tissue from rats with L(5)/L(6) spinal nerve ligation (SNL), we demonstrated that SNL injury induces MOR linkage to G(s) in the damaged (ipsilateral) spinal dorsal horn. This MOR-G(s) coupling occurred without changing G(i/o) coupling levels and without changing the expression of MOR or Galpha proteins. Repeated administration of oxycodone alone or in combination with ultra-low-dose naltrexone (NTX) was assessed on the SNL-induced MOR-G(s) coupling as well as on neuropathic pain behavior. Repeated spinal oxycodone exacerbated the SNL-induced MOR-G(s) coupling, whereas ultra-low-dose NTX cotreatment slightly but significantly attenuated this G(s) coupling. Either spinal or oral administration of oxycodone plus ultra-low-dose NTX markedly enhanced the reductions in allodynia and thermal hyperalgesia produced by oxycodone alone and minimized tolerance to these effects. The MOR-G(s) coupling observed in response to SNL may in part contribute to the excitatory neurotransmission in spinal dorsal horn in neuropathic pain states. The antihyperalgesic and antiallodynic effects of oxycodone plus ultra-low-dose NTX (Oxytrex, Pain Therapeutics, Inc., San Mateo, CA) suggest a promising new treatment for neuropathic pain. The current study investigates whether Oxytrex (oxycodone with an ultra-low dose of naltrexone) alleviates mechanical and thermal hypersensitivities in an animal model of neuropathic pain over a period of 7 days, given locally or systemically. In this report, we first describe an injury-induced shift in mu-opioid receptor coupling from G(i/o) to G(s), suggesting why a mu-opioid agonist may have reduced efficacy in the nerve-injured state. These data present a novel approach to neuropathic pain therapy.

A web-based neurological pain classifier tool utilizing Bayesian decision theory for pain classification in spinal cord injury patients

NASA Astrophysics Data System (ADS)

Verma, Sneha K.; Chun, Sophia; Liu, Brent J.

2014-03-01

Pain is a common complication after spinal cord injury with prevalence estimates ranging 77% to 81%, which highly affects a patient's lifestyle and well-being. In the current clinical setting paper-based forms are used to classify pain correctly, however, the accuracy of diagnoses and optimal management of pain largely depend on the expert reviewer, which in many cases is not possible because of very few experts in this field. The need for a clinical decision support system that can be used by expert and non-expert clinicians has been cited in literature, but such a system has not been developed. We have designed and developed a stand-alone tool for correctly classifying pain type in spinal cord injury (SCI) patients, using Bayesian decision theory. Various machine learning simulation methods are used to verify the algorithm using a pilot study data set, which consists of 48 patients data set. The data set consists of the paper-based forms, collected at Long Beach VA clinic with pain classification done by expert in the field. Using the WEKA as the machine learning tool we have tested on the 48 patient dataset that the hypothesis that attributes collected on the forms and the pain location marked by patients have very significant impact on the pain type classification. This tool will be integrated with an imaging informatics system to support a clinical study that will test the effectiveness of using Proton Beam radiotherapy for treating spinal cord injury (SCI) related neuropathic pain as an alternative to invasive surgical lesioning.

A scoping review of biopsychosocial risk factors and co-morbidities for common spinal disorders.

PubMed

Green, Bart N; Johnson, Claire D; Haldeman, Scott; Griffith, Erin; Clay, Michael B; Kane, Edward J; Castellote, Juan M; Rajasekaran, Shanmuganathan; Smuck, Matthew; Hurwitz, Eric L; Randhawa, Kristi; Yu, Hainan; Nordin, Margareta

2018-01-01

The purpose of this review was to identify risk factors, prognostic factors, and comorbidities associated with common spinal disorders. A scoping review of the literature of common spinal disorders was performed through September 2016. To identify search terms, we developed 3 terminology groups for case definitions: 1) spinal pain of unknown origin, 2) spinal syndromes, and 3) spinal pathology. We used a comprehensive strategy to search PubMed for meta-analyses and systematic reviews of case-control studies, cohort studies, and randomized controlled trials for risk and prognostic factors and cross-sectional studies describing associations and comorbidities. Of 3,453 candidate papers, 145 met study criteria and were included in this review. Risk factors were reported for group 1: non-specific low back pain (smoking, overweight/obesity, negative recovery expectations), non-specific neck pain (high job demands, monotonous work); group 2: degenerative spinal disease (workers' compensation claim, degenerative scoliosis), and group 3: spinal tuberculosis (age, imprisonment, previous history of tuberculosis), spinal cord injury (age, accidental injury), vertebral fracture from osteoporosis (type 1 diabetes, certain medications, smoking), and neural tube defects (folic acid deficit, anti-convulsant medications, chlorine, influenza, maternal obesity). A range of comorbidities was identified for spinal disorders. Many associated factors for common spinal disorders identified in this study are modifiable. The most common spinal disorders are co-morbid with general health conditions, but there is a lack of clarity in the literature differentiating which conditions are merely comorbid versus ones that are risk factors. Modifiable risk factors present opportunities for policy, research, and public health prevention efforts on both the individual patient and community levels. Further research into prevention interventions for spinal disorders is needed to address this gap in the literature.

A scoping review of biopsychosocial risk factors and co-morbidities for common spinal disorders

PubMed Central

Smuck, Matthew; Hurwitz, Eric L.; Randhawa, Kristi; Yu, Hainan; Nordin, Margareta

2018-01-01

Objective The purpose of this review was to identify risk factors, prognostic factors, and comorbidities associated with common spinal disorders. Methods A scoping review of the literature of common spinal disorders was performed through September 2016. To identify search terms, we developed 3 terminology groups for case definitions: 1) spinal pain of unknown origin, 2) spinal syndromes, and 3) spinal pathology. We used a comprehensive strategy to search PubMed for meta-analyses and systematic reviews of case-control studies, cohort studies, and randomized controlled trials for risk and prognostic factors and cross-sectional studies describing associations and comorbidities. Results Of 3,453 candidate papers, 145 met study criteria and were included in this review. Risk factors were reported for group 1: non-specific low back pain (smoking, overweight/obesity, negative recovery expectations), non-specific neck pain (high job demands, monotonous work); group 2: degenerative spinal disease (workers’ compensation claim, degenerative scoliosis), and group 3: spinal tuberculosis (age, imprisonment, previous history of tuberculosis), spinal cord injury (age, accidental injury), vertebral fracture from osteoporosis (type 1 diabetes, certain medications, smoking), and neural tube defects (folic acid deficit, anti-convulsant medications, chlorine, influenza, maternal obesity). A range of comorbidities was identified for spinal disorders. Conclusion Many associated factors for common spinal disorders identified in this study are modifiable. The most common spinal disorders are co-morbid with general health conditions, but there is a lack of clarity in the literature differentiating which conditions are merely comorbid versus ones that are risk factors. Modifiable risk factors present opportunities for policy, research, and public health prevention efforts on both the individual patient and community levels. Further research into prevention interventions for spinal disorders is needed to address this gap in the literature. PMID:29856783

Direct intrathecal drug delivery in mice for detecting in vivo effects of cGMP on pain processing.

PubMed

Lu, Ruirui; Schmidtko, Achim

2013-01-01

Intrathecal delivery of drugs is an important method in pain research in order to investigate pain-relevant effects in the spinal cord in vivo. Here, we describe a method of intrathecal drug delivery by direct lumbar puncture in mice. The procedure does not require surgery, is rapidly performed, and does not produce neurological deficits. If cGMP analogs are injected, a state of transient hindpaw hypersensitivity can be induced which is quantifiable by measurement of hindpaw withdrawal latency in response to mechanical stimulation.

[Effect of electroacupuncture on expression of ionotropic glutamate receptor subunits and their genes in lumbar segments of spinal cord in rats with neuropathic pain].

PubMed

Ma, Cheng; Yu, Li; Yan, Li-ping

2010-12-01

To observe the effect of electroacupuncture (EA) on the expression of ionotropic glutamate receptor (iGluR) subunits and their mRNAs in the lumbar segments of spinal cord in rats with neuropathic pain, so as to explore its underlying mechanism in relieving spinal hyperalgesia. Thirty SD rats were randomly divided into control, model, and EA groups, with 10 rats in each. The spared nerve injury (SNI) model was established by ligature of the sural nerve after cutting off the common peroneal nerve and anterior tibial nerve. EA (2 Hz, 1 mA) was applied to "Huantiao" (GB 30) and "Weizhong" (BL 40) for 30 min, once daily for 7 days. Mechanical pain threshold was detected before and after modeling and before and after EA treatment. The expression levels of N-methyl-d-aspartic acid (NMDA) receptor subunits NR1 and NR 2 B,and AMPA receptor subunit GluR 1 of iGluR and their genes were assayed by Western blot and reverse transcription polymerase chain reaction (RT-PCR) separately. In comparison with control group, the mechanical pain thresholds were decreased significantly on day 2, 7 and day 14 following modeling in the model group (P < 0.05, P < 0.01). While compared with the model group, the pain threshold was increased considerably on day 14 in the EA group (P < 0.01). Compared with the control group, the expression levels of lumbar spinal cord NR 2 B and NR 2 B mRNA in the model group were increased significantly (P < 0.05), and those of lumbar spinal cord NR 1 and NR 1 mRNA, GluR 1 and GluR 1 mRNA in the model group increased slightly (P > 0.05). In comparison with the model group, the expression levels of lumbar spinal cord NR 2 B and NR 2 B mRNA in the EA group were downregulated remarkably (P < 0.05), and those of lumbar spinal cord NR 1 and NR 1 mRNA, GluR 1 and GluR 1 mRNA in the EA group down-regulated slightly (P > 0.05). EA can significantly suppress pain reaction in rats with neuropathic pain probably through down-regulating the expression of lumbar spinal cord NR 2 B protein and NR 2 B mRNA.

[Prostatic inflammation-induced chronic pelvic pain: Roles of substance P and c-fos in the spinal cord].

PubMed

Liu, Ying-jia; Song, Guo-hong; Zhang, Chen

2015-08-01

To explore the possible pain mechanism of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The models of CP/CPPS were established in male Wistar rats by the autoimmune method. The paw withdrawal threshold (PWT) was detected using Von Frey filament. The expressions of the substance P and c-fos in the prostate and spinal L5-S2 segments were determined by immunohistochemistry followed by analysis of their correlation with CP/CPPS. Compared with the control rats, the CP/CPPS models showed significantly decreased PWT (P < 0.05), remarkable prostatic inflammation, enlarged scope of lesions, and obvious interstitial lymphocytic infiltration (P < 0.05). Both the expressions of substance P and c-fos were markedly elevated in the prostate and spinal dorsal horn (L5-S2) of the rat models (P < 0.05), but the expression of substance P in the prostate exhibited no correlation with that in the spinal cord (r = 0.099, P = 0.338), nor did that of c-fos (r = 0.027, P = 0.454). The upregulated expressions of substance P and c-fos in the spinal cord L5-S2 sections may be associated with the pain mechanism of CP/CPPS.

Spinal versus brain microglial and macrophage activation traits determine the differential neuroinflammatory responses and analgesic effect of minocycline in chronic neuropathic pain.

PubMed

Li, Zhilin; Wei, Hong; Piirainen, Sami; Chen, Zuyue; Kalso, Eija; Pertovaara, Antti; Tian, Li

2016-11-01

Substantial evidence indicates involvement of microglia/macrophages in chronic neuropathic pain. However, the temporal-spatial features of microglial/macrophage activation and their pain-bound roles remain elusive. Here, we evaluated microglia/macrophages and the subtypes in the lumbar spinal cord (SC) and prefrontal cortex (PFC), and analgesic-anxiolytic effect of minocycline at different stages following spared nerve injury (SNI) in rats. While SNI enhanced the number of spinal microglia/macrophages since post-operative day (POD)3, pro-inflammatory MHCII + spinal microglia/macrophages were unexpectedly less abundant in SNI rats than shams on POD21. By contrast, less abundant anti-inflammatory CD172a (SIRPα) + microglia/macrophages were found in the PFC of SNI rats. Interestingly in naïve rats, microglial/macrophage expression of CD11b/c, MHCII and MHCII + /CD172a + ratio were higher in the SC than the cortex. Consistently, multiple immune genes involved in anti-inflammation, phagocytosis, complement activation and M2 microglial/macrophage polarization were upregulated in the spinal dorsal horn and dorsal root ganglia but downregulated in the PFC of SNI rats. Furthermore, daily intrathecal minocycline treatment starting from POD0 for two weeks alleviated mechanical allodynia most robustly before POD3 and attenuated anxiety on POD9. Although minocycline dampened spinal MHCII + microglia/macrophages until POD13, it failed to do so on cortical microglia/macrophages, indicating that dampening only spinal inflammation may not be enough to alleviate centralized pain at the chronic stage. Taken together, our data provide the first evidence that basal microglial/macrophage traits underlie differential region-specific responses to SNI and minocycline treatment, and suggest that drug treatment efficiently targeting not only spinal but also brain inflammation may be more effective in treating chronic neuropathic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

Spinal Infections

MedlinePlus

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Low back pain and its treatment by spinal manipulation: measures of flexibility and asymmetry.

PubMed

Hoehler, F K; Tobis, J S

1982-02-01

Nineteen low back pain patients and eight patients not suffering from low back pain were given several tests of flexibility and asymmetry by two different examiners. Three criteria of reliability and validity were used: (1) significant agreement between independent observers, (2) significantly different scores in the groups with and without low back pain, and (3) significant improvement following a successful spinal manipulation. Tests of anterior flexion and asymmetry of foot eversion met only the first and second criteria while tests of hamstring tightness and asymmetry of voluntary straight leg raising met only the first and third criteria. Passive and voluntary straight leg raising tests were the only measures that met all three criteria. Therefore, of the objective tests investigated here, only passive or voluntary straight leg raising can be strongly recommended for use in the evaluation of spinal manipulative therapy for low back pain.

Is altered central pain processing related to disease stage in chronic pancreatitis patients with pain? An exploratory study.

PubMed

Bouwense, Stefan A W; Olesen, Søren S; Drewes, Asbjørn M; Frøkjær, Jens B; van Goor, Harry; Wilder-Smith, Oliver H G

2013-01-01

The most dominant feature in chronic pancreatitis is intense abdominal pain. Changes in spinal and/or supraspinal central nervous system pain processing due to visceral nociceptive input play an important role in this pain. How altered pain processing is related to disease stage still needs study. Sixty chronic pancreatitis patients were compared to 15 healthy controls. Two subgroups of pancreatitis patients were defined based on the M-ANNHEIM severity index of chronic pancreatitis; i.e. moderate and severe. Pain detection and tolerance thresholds for pressure and electric stimuli were measured in six selected dermatomes (C5, T4, T10, L1, L4 and T10BACK). In addition, the conditioned pain modulation response to cold pressor task was determined. These measures were compared between the healthy controls and chronic pancreatitis patients. Severe pancreatitis patients showed lower pain thresholds than moderate pancreatitis patients or healthy volunteers. Healthy controls showed a significantly larger conditioned pain modulation response compared to all chronic pancreatitis patients taken together. The present study confirms that chronic pancreatitis patients show signs of altered central processing of nociception compared to healthy controls. The study further suggests that these changes, i.e. central sensitization, may be influenced by disease stage. These findings underline the need to take altered central pain processing into account when managing the pain of chronic pancreatitis.

DRG Spinal Cord Stimulation as Solution for Patients With Severe Pain Due to Anterior Cutaneous Nerve Entrapment Syndrome: A Case Series.

PubMed

Mol, Frédérique Mathilde Ulrike; Roumen, Rudi M H

2018-04-01

Anterior Cutaneous Nerve Entrapment Syndrome (ACNES) is a debilitating neuropathic pain condition. A small portion of patients do not respond to any currently available treatment modalities. These patients, often young women, might benefit from targeted spinal cord stimulation of the dorsal root ganglion (DRG). This retrospective case series describes five ACNES patients who were referred from a Dutch dedicated tertiary referral center to collaborating sites with extensive experience in DRG stimulation to be implanted with a DRG Axium System (St. Jude/Abbott, IL, USA) in the period of 2013-2016. Numeric pain rating scores at routine 6- and 12-month follow-up visits were analyzed. Three patients experienced >50% pain reduction at 12 months follow-up. Four patients experienced device-related complications, such as lead dislocation, lead breakage, pain at the battery site, and overstimulation. This case series suggests DRG spinal cord stimulation can be safe and effective for some patients with persistent pain due to ACNES. © 2017 International Neuromodulation Society.

Dendritic spine remodeling following early and late Rac1 inhibition after spinal cord injury: evidence for a pain biomarker

PubMed Central

Zhao, Peng; Hill, Myriam; Liu, Shujun; Chen, Lubin; Bangalore, Lakshmi; Waxman, Stephen G.

2016-01-01

Neuropathic pain is a significant complication following spinal cord injury (SCI) with few effective treatments. Drug development for neuropathic pain often fails because preclinical studies do not always translate well to clinical conditions. Identification of biological characteristics predictive of disease state or drug responsiveness could facilitate more effective clinical translation. Emerging evidence indicates a strong correlation between dendritic spine dysgenesis and neuropathic pain. Because dendritic spines are located on dorsal horn neurons within the spinal cord nociceptive system, dendritic spine remodeling provides a unique opportunity to understand sensory dysfunction after SCI. In this study, we provide support for the postulate that dendritic spine profiles can serve as biomarkers for neuropathic pain. We show that dendritic spine profiles after SCI change to a dysgenic state that is characteristic of neuropathic pain in a Rac1-dependent manner. Suppression of the dysgenic state through inhibition of Rac1 activity is accompanied by attenuation of neuropathic pain. Both dendritic spine dysgenesis and neuropathic pain return when inhibition of Rac1 activity is lifted. These findings suggest the utility of dendritic spines as structural biomarkers for neuropathic pain. PMID:26936986

Subacute effects of cervicothoracic spinal thrust/non-thrust in addition to shoulder manual therapy plus exercise intervention in individuals with subacromial impingement syndrome: a prospective, randomized controlled clinical trial pilot study.

PubMed

Wright, Alexis A; Donaldson, Megan; Wassinger, Craig A; Emerson-Kavchak, Alicia J

2017-09-01

To determine the subacute effects of cervicothoracic spinal thrust/non-thrust in addition to shoulder non-thrust plus exercise in patients with subacromial pathology. This was a randomized, single blinded controlled trial pilot study. This trial was registered at ClinicalTrials.gov (NCT01753271) and reported according to Consolidated Standards of Reporting Trials requirements. Patients were randomly assigned to either shoulder treatment plus cervicothoracic spinal thrust/non-thrust or shoulder treatment-only group. Primary outcomes were average pain intensity (Numeric Pain Rating Scale) and physical function (Shoulder Pain and Disability Index) at 2 weeks, 4 weeks, and patient discharge. 18 patients, mean age 43.1(15.8) years satisfied the eligibility criteria and were analyzed for follow-up data. Both groups showed statistically significant improvements in both pain and function at 2 weeks, 4 weeks, and discharge. The between-group differences for changes in pain or physical function were not significant at any time point. The addition of cervicothoracic spinal thrust/non-thrust to the shoulder treatment-only group did not significantly alter improvement in pain or function in patients with subacromial pathology. Both approaches appeared to provide an equally notable benefit. Both groups improved on all outcomes and met the criteria for clinical relevance for both pain and function. 2b.

Shoulder Pain in Cases of Spinal Injury: Influence of the Position of the Wheelchair Seat

ERIC Educational Resources Information Center

Giner-Pascual, Manuel; Alcanyis-Alberola, Modesto; Millan Gonzalez, Luis; Aguilar-Rodriguez, Marta; Querol, Felipe

2011-01-01

The objective of this study was to determine the relationship between shoulder pain and the position of the seat of a wheelchair relative to the ground and to determine the relationship between shoulder pain and structural damage. A transversal study of a patient cohort of 140 patients with grade A and B spinal cord injuries below the T1 vertebra,…

Altered spinal kinematics and muscle recruitment pattern of the cervical and thoracic spine in people with chronic neck pain during functional task.

PubMed

Tsang, Sharon M H; Szeto, Grace P Y; Lee, Raymond Y W

2014-02-01

Knowledge on the spinal kinematics and muscle activation of the cervical and thoracic spine during functional task would add to our understanding of the performance and interplay of these spinal regions during dynamic condition. The purpose of this study was to examine the influence of chronic neck pain on the three-dimensional kinematics and muscle recruitment pattern of the cervical and thoracic spine during an overhead reaching task involving a light weight transfer by the upper limb. Synchronized measurements of the three-dimensional spinal kinematics and electromyographic activities of cervical and thoracic spine were acquired in thirty individuals with chronic neck pain and thirty age- and gender-matched asymptomatic controls. Neck pain group showed a significantly decreased cervical velocity and acceleration while performing the task. They also displayed with a predominantly prolonged coactivation of cervical and thoracic muscles throughout the task cycle. The current findings highlighted the importance to examine differential kinematic variables of the spine which are associated with changes in the muscle recruitment in people with chronic neck pain. The results also provide an insight to the appropriate clinical intervention to promote the recovery of the functional disability commonly reported in patients with neck pain disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

Low back pain tied to spinal endometriosis.

PubMed

Dongxu, Zhao; Fei, Yin; Xing, Xiao; Bo-Yin, Zhang; Qingsan, Zhu

2014-05-01

Case report. We present a case of endometriosis of lumbar vertebrae. The literatures are reviewed with endometriosis of spine. Endometriosis is a common condition, which is defined as endometrial tissue lying outside the endometrial cavity. It is usually found within the peritoneal cavity, predominantly within the pelvis, commonly on the uterosacral ligaments. It can also be found in other sites such as umbilicus, abdominal scars, nasal passages and pleural cavity. But it is very rarely seen in the spine, with no report of endometriosis found in the lumbar vertebrae. A 33-year-old woman presented with severe low back pain. She had the low back pain periodically for 3 years, and the pain was associated with menstruation. Radiographs showed a lesion in the posterior L3 body. After surgery, tissue biopsy indicated the presence of endometrial tissue in the lesion and thus confirmed endometriosis. Most cases of spine endometriosis that have been reported are usually found inside spinal canal, endorachis or spinal cord. But spinal vertebrae can also be involved in endometriosis. Although endometriosis is a rare possible cause of periodical low back pain in women of childbearing age, we suggest that if a woman suffering from periodical low back pain is encountered, do not ignore the possibility of endometriosis in the spine.

Do "whiplash" victims with neck pain differ from those with neck pain and other symptoms?

PubMed

Tencer, A F; Mirza, S; Cummings, P

2001-01-01

Studying 432 patients with "whiplash" neck pain after a low speed rear-end crash, we determined whether those who reported associated symptoms (arm or low back pain) differed from those with neck pain only. Exposure variables were: age, gender, height, weight, surprised by impact, rotated position of the head, and pre-existing cervical or lumbar spinal degeneration. Immediate symptoms were considered. Odds ratios (OR) were derived from logistic regression. Only pre-existing lumbar spinal degeneration was associated with having arm symptoms (OR = 9.6, CI = 1.1, 83.6) or low back pain (OR = 23.3, CI = 2.6, 206.7) along with neck pain.

Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α2-Adrenergic Receptor

PubMed Central

Choi, Jiho; Jeon, Changhoon; Jang, Jo Ung; Quan, Fu Shi; Lee, Kyungjin; Kim, Woojin

2017-01-01

Paclitaxel, a chemotherapy drug for solid tumors, induces peripheral painful neuropathy. Bee venom acupuncture (BVA) has been reported to have potent analgesic effects, which are known to be mediated by activation of spinal α-adrenergic receptor. Here, we investigated the effect of BVA on mechanical hyperalgesia and spinal neuronal hyperexcitation induced by paclitaxel. The role of spinal α-adrenergic receptor subtypes in the analgesic effect of BVA was also observed. Administration of paclitaxel (total 8 mg/kg, intraperitoneal) on four alternate days (days 0, 2, 4, and 6) induced significant mechanical hyperalgesic signs, measured using a von Frey filament. BVA (1 mg/kg, ST36) relieved this mechanical hyperalgesia for at least two hours, and suppressed the hyperexcitation in spinal wide dynamic range neurons evoked by press or pinch stimulation. Both melittin (0.5 mg/kg, ST36) and phospholipase A2 (0.12 mg/kg, ST36) were shown to play an important part in this analgesic effect of the BVA, as they significantly attenuated the pain. Intrathecal pretreatment with the α2-adrenergic receptor antagonist (idazoxan, 50 µg), but not α1-adrenergic receptor antagonist (prazosin, 30 µg), blocked the analgesic effect of BVA. These results suggest that BVA has potent suppressive effects against paclitaxel-induced neuropathic pain, which were mediated by spinal α2-adrenergic receptor. PMID:29088102

Osteopathic manipulative treatment is effective on pain control associated to spinal cord injury.

PubMed

Arienti, C; Daccò, S; Piccolo, I; Redaelli, T

2011-04-01

This study was designed as an experimental study (trial). To verify the effects of the association between conventional pharmacological treatment and osteopathic manipulative treatment (OMT) for chronic pain management in spinal cord injury (SCI). This study was carried out at Spinal Unit, Ospedale Niguarda Ca' Granda, Milan, Italy. Istituto Superiore di Osteopatia, Milan, Italy. We enrolled 47 patients with SCI, 26 with pain of both nociceptive and neuropathic origin, and 21 with pure neuropathic pain. In all, 33 patients had a complete spinal cord lesion (ASIA level A) and 14 had incomplete lesion (ASIA level B, C and D). The patients were subdivided in a pharmacological group (Ph), a pharmacological osteopathic (PhO) group and a osteopathic (Os) group. The verbal numeric scale (VNS) was used at various time intervals to evaluate treatment outcomes. Ph patients reached a 24% improvement in their pain perception, assessed by the VNS scale after 3 weeks of treatment, whereas Os patients reached a 16% improvement in their pain perception for the same weeks. Both treatments per se failed to induce further improvements at later time points. In contrast, the combination of the two approaches yielded a significantly better pain relief both in patients with nociceptive or pure neuropathic pain in the PhO group. Our results suggest the OMT is a feasible approach in patients in whom available drugs cannot be used. Moreover, a benefit can be expected by the association of OMT in patients treated according to existing pharmacological protocols.

Efficacy and Safety of Transdermal Buprenorphine versus Oral Tramadol/Acetaminophen in Patients with Persistent Postoperative Pain after Spinal Surgery.

PubMed

Lee, Jae Hyup; Kim, Jin-Hyok; Kim, Jin-Hwan; Kim, Hak-Sun; Min, Woo-Kie; Park, Ye-Soo; Lee, Kyu-Yeol; Lee, Jung-Hee

2017-01-01

Control of persistent pain following spinal surgery is an unmet clinical need. This study compared the efficacy and safety of buprenorphine transdermal system (BTDS) to oral tramadol/acetaminophen (TA) in Korean patients with persistent, moderate pain following spinal surgery. Open-label, interventional, randomized multicenter study. Adults with persistent postoperative pain (Numeric Rating Scale [NRS] ≥ 4 at 14-90 days postsurgery) were enrolled. Patients received once-weekly BTDS ( n = 47; 5  μ g/h titrated to 20  μ g/h) or twice-daily TA ( n = 40; tramadol 37.5 mg/acetaminophen 325 mg, one tablet titrated to 4 tablets) for 6 weeks. The study compared pain reduction with BTDS versus TA at week 6. Quality of life (QoL), treatment satisfaction, medication compliance, and adverse events (AEs) were assessed. At week 6, both groups reported significant pain reduction (mean NRS change: BTDS -2.02; TA -2.76, both P < 0.0001) and improved QoL (mean EQ-5D index change: BTDS 0.10; TA 0.19, both P < 0.05). The BTDS group achieved better medication compliance (97.8% versus 91.0%). Incidence of AEs (26.1% versus 20.0%) and adverse drug reactions (20.3% versus 16.9%) were comparable between groups. For patients with persistent pain following spinal surgery, BTDS is an alternative to TA for reducing pain and supports medication compliance. This trial is registered with Clinicaltrials.gov: NCT01983111.

Spinal Fusion for Chronic Low Back Pain: A ‘Magic Bullet’ or Wishful Thinking?

PubMed Central

2016-01-01

Chronic low back pain is a common, disabling and costly health problem. The treatment of chronic low back is difficult and is often ineffective. For treatment to be effective the cause of the pain has to be established but unfortunately in 80% to 95% of the patients the cause cannot be determined despite the existence of modern imaging techniques. A pathoanatomical diagnosis which fits into a classical disease model where successful treatment can be carried out, can only be made in 5% to 7% of the patients. The back pain in the rest of the patients where no pathoanatomical diagnosis can be made is often labelled, unscientifically, as chronic low back pain. Despite the existence of sophisticated imaging techniques and a plethora of diagnostic test the source of pain in patients with nonspecific back pain cannot be established. There exist no causal relationship between imaging findings of degenerated disc, lumbar facet arthritis, spondylosis, spondylolysis and spondylolisthesis, to the pain in these patients. Surgical treatment of non-specific back pain where no pathoanatomical diagnosis has been established is bound to fail. Therefore the outcome of spinal fusion in these patients can be no better than nonsurgical treatment. Spinal fusion is a major surgery which can be associated with significant morbidity and occasionally with mortality. Yet there is rapid rise in the rates of spinal fusion. There is a growing tension between ethics and conflicts of interest for surgeons. The spine, unfortunately, has been labelled as a profit centre and there are allegations of conflicts of interest in the relationship of doctors with the multi-billion dollar spinal devices industry. The devices industry has a significant influence on not only research publications in peer review journals but also on decisions made by doctors which can have a detrimental effect on the welfare of the patient. PMID:28435551

The Pain of Labour

PubMed Central

Labor, Simona

2008-01-01

Labour is an emotional experience and involves both physiological and psychological mechanisms. The pain of labour is severe but despite this its memory diminishes with time. Labour pain has two components: visceral pain which occurs during the early first stage and the second stage of childbirth, and somatic pain which occurs during the late first stage and the second stage. The pain of labour in the first stage is mediated by T10 to L1 spinal segments, whereas that in the second stage is carried by T12 to L1, and S2 to S4 spinal segments. Pain relief in labour is complex and often challenging without regional analgesia. Effective management of labour pain plays a relatively minor role in a woman's satisfaction with childbirth. PMID:26526404

Early transcutaneous electrical nerve stimulation reduces hyperalgesia and decreases activation of spinal glial cells in mice with neuropathic pain.

PubMed

Matsuo, Hideaki; Uchida, Kenzo; Nakajima, Hideaki; Guerrero, Alexander Rodriguez; Watanabe, Shuji; Takeura, Naoto; Sugita, Daisuke; Shimada, Seiichiro; Nakatsuka, Terumasa; Baba, Hisatoshi

2014-09-01

Although transcutaneous electrical nerve stimulation (TENS) is widely used for the treatment of neuropathic pain, its effectiveness and mechanism of action in reducing neuropathic pain remain uncertain. We investigated the effects of early TENS (starting from the day after surgery) in mice with neuropathic pain, on hyperalgesia, glial cell activation, pain transmission neuron sensitization, expression of proinflammatory cytokines, and opioid receptors in the spinal dorsal horn. Following nerve injury, TENS and behavioral tests were performed every day. Immunohistochemical, immunoblot, and flow cytometric analysis of the lumbar spinal cord were performed after 8 days. Early TENS reduced mechanical and thermal hyperalgesia and decreased the activation of microglia and astrocytes (P<0.05). In contrast, the application of TENS at 1 week (TENS-1w) or 2 weeks (TENS-2w) after injury was ineffective in reducing hyperalgesia (mechanical and thermal) or activation of microglia and astrocytes. Early TENS decreased p-p38 within microglia (P<0.05), the expression levels of protein kinase C (PKC-γ), and phosphorylated anti-phospho-cyclic AMP response element-binding protein (p-CREB) in the superficial spinal dorsal horn neurons (P<0.05), mitogen-activated protein (MAP) kinases, and proinflammatory cytokines, and increased the expression levels of opioid receptors (P<0.05). The results suggested that the application of early TENS relieved hyperalgesia in our mouse model of neuropathic pain by inhibiting glial activation, MAP kinase activation, PKC-γ, and p-CREB expression, and proinflammatory cytokines expression, as well as maintenance of spinal opioid receptors. The findings indicate that TENS treatment is more effective when applied as early after nerve injury as possible. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitera, Gunita, E-mail: Gunita.Mitera@Sunnybrook.ca; Probyn, Linda; Ford, Michael

Purpose: To correlate computed tomography (CT) imaging features of spinal metastases with pain relief after radiotherapy (RT). Methods and Materials: Thirty-three patients receiving computed tomography (CT)-simulated RT for spinal metastases in an outpatient palliative RT clinic from January 2007 to October 2008 were retrospectively reviewed. Forty spinal metastases were evaluated. Pain response was rated using the International Bone Metastases Consensus Working Party endpoints. Three musculoskeletal radiologists and two orthopaedic surgeons evaluated CT features, including osseous and soft tissue tumor extent, presence of a pathologic fracture, severity of vertebral height loss, and presence of kyphosis. Results: The mean patient age wasmore » 69 years; 24 were men and 9 were women. The mean worst pain score was 7/10, and the mean total daily oral morphine equivalent was 77.3 mg. Treatment doses included 8 Gy in one fraction (22/33), 20 Gy in five fractions (10/33), and 20 Gy in eight fractions (1/33). The CT imaging appearance of spinal metastases included vertebral body involvement (40/40), pedicle involvement (23/40), and lamina involvement (18/40). Soft tissue component (10/40) and nerve root compression (9/40) were less common. Pathologic fractures existed in 11/40 lesions, with resultant vertebral body height loss in 10/40 and kyphosis in 2/40 lesions. At months 1, 2, and 3 after RT, 18%, 69%, and 70% of patients experienced pain relief. Pain response was observed with various CT imaging features. Conclusions: Pain response after RT did not differ in patients with and without pathologic fracture, kyphosis, or any other CT features related to extent of tumor involvement. All patients with painful spinal metastases may benefit from palliative RT.« less

Effect of yogic colon cleansing (Laghu Sankhaprakshalana Kriya) on pain, spinal flexibility, disability and state anxiety in chronic low back pain

PubMed Central

Haldavnekar, Richa Vivek; Tekur, Padmini; Nagarathna, Raghuram; Nagendra, Hongasandra Ramarao

2014-01-01

Background: Studies have shown that Integrated Yoga reduces pain, disability, anxiety and depression and increases spinal flexibility and quality-of-life in chronic low back pain (CLBP) patients. Objective: The objective of this study was to compare the effect of two yoga practices namely laghu shankha prakshalana (LSP) kriya, a yogic colon cleansing technique and back pain specific asanas (Back pain special technique [BST]) on pain, disability, spinal flexibility and state anxiety in patients with CLBP. Materials and Methods: In this randomized control (self as control) study, 40 in-patients (25 were males, 15 were females) between 25 and 70 years (44.05 ± 13.27) with CLBP were randomly assigned to receive LSP or BST sessions. The measurements were taken immediately before and after each session of either of the practices (30 min) in the same participant. Randomization was used to decide the day of the session (3rd or 5th day after admission) to ensure random distribution of the hang over effect of the two practices. Statistical analysis was performed using the repeated measures analysis of variance. Results: Significant group * time interaction (P < 0.001) was observed in 11 point numerical rating scale, spinal flexibility (on Leighton type Goniometer) and (straight leg raise test in both legs), Oswestry Disability Index, State Anxiety (XI component of Spieldberger's state and trait anxiety inventory. There was significantly (P < 0.001, between groups) better reduction in LSP than BST group on all variables. No adverse effects were reported by any participant. Conclusion: Clearing the bowel by yoga based colon cleansing technique (LSP) is safe and offers immediate analgesic effect with reduced disability, anxiety and improved spinal flexibility in patients with CLBP. PMID:25035620

Gene Transfer of Glutamic Acid Decarboxylase 67 by Herpes Simplex Virus Vectors Suppresses Neuropathic Pain Induced by Human Immunodeficiency Virus gp120 Combined with ddC in Rats.

PubMed

Kanao, Megumi; Kanda, Hirotsugu; Huang, Wan; Liu, Shue; Yi, Hyun; Candiotti, Keith A; Lubarsky, David A; Levitt, Roy C; Hao, Shuanglin

2015-06-01

Human immunodeficiency virus (HIV)-related painful sensory neuropathies primarily consist of the HIV infection-related distal sensory polyneuropathy and antiretroviral toxic neuropathies. Pharmacotherapy provides only partial relief of pain in patients with HIV/acquired immune deficiency syndrome because little is known about the exact neuropathological mechanisms for HIV-associated neuropathic pain (NP). Hypofunction of γ-aminobutyric acid (GABA) GABAergic inhibitory mechanisms has been reported after peripheral nerve injury. In this study, we tested the hypothesis that HIV gp120 combined with antiretroviral therapy reduces spinal GABAergic inhibitory tone and that restoration of GABAergic inhibitory tone will reduce HIV-related NP in a rat model. The application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve plus systemic ddC (one antiretroviral drug) induced mechanical allodynia. The hind paws of rats were inoculated with replication-defective herpes simplex virus (HSV) vectors genetically encoding gad1 gene to express glutamic acid decarboxylase 67 (GAD67), an enzyme that catalyzes the decarboxylation of glutamate to GABA. Mechanical threshold was tested using von Frey filaments before and after treatments with the vectors. The expression of GAD67 in both the lumbar spinal cord and the L4-5 dorsal root ganglia was examined using western blots. The expression of mitochondrial superoxide in the spinal dorsal horn was examined using MitoSox imaging. The immunoreactivity of spinal GABA, pCREB, and pC/EBPβ was tested using immunohistochemistry. In the gp120 with ddC-induced neuropathic pain model, GAD67 expression mediated by the HSV vector caused an elevation of mechanical threshold that was apparent on day 3 after vector inoculation. The antiallodynic effect of the single HSV vector inoculation expressing GAD67 lasted >28 days. The area under the time-effect curves in the HSV vector expressing GAD67 was increased compared with that in the control vectors (P = 0.0005). Intrathecal GABA-A/B agonists elevated mechanical threshold in the pain model. The HSV vectors expressing GAD67 reversed the lowered GABA immunoreactivity in the spinal dorsal horn in the neuropathic rats. HSV vectors expressing GAD67 in the neuropathic rats reversed the increased signals of mitochondrial superoxide in the spinal dorsal horn. The vectors expressing GAD67 reversed the upregulated immunoreactivity expression of pCREB and pC/EBPβ in the spinal dorsal horn in rats exhibiting NP. Based on our results, we suggest that GAD67 mediated by HSV vectors acting through the suppression of mitochondrial reactive oxygen species and transcriptional factors in the spinal cord decreases pain in the HIV-related neuropathic pain model, providing preclinical evidence for gene therapy applications in patients with HIV-related pain states.

Cost Utility Analysis of Percutaneous Adhesiolysis in Managing Pain of Post-lumbar Surgery Syndrome and Lumbar Central Spinal Stenosis.

PubMed

Manchikanti, Laxmaiah; Helm, Standiford; Pampati, Vidyasagar; Racz, Gabor B

2015-06-01

The increase in the number of interventions for the management of chronic pain and associated escalation of healthcare costs has captured the attention of health policymakers, in no small part due to the lack of documentation of efficacy, cost-effectiveness, or cost utility analysis. A recent cost utility analysis of caudal epidural injections in managing chronic low back pain of various pathologies showed a high cost utility with improvement in quality of life years, competitive with various other modalities of treatments. However, there are no analyses derived from high-quality controlled studies related to the cost utility of percutaneous adhesiolysis in the treatment of post-lumbar surgery syndrome or lumbar central spinal stenosis. This analysis is based on 2 previously published controlled studies. To assess the cost utility of percutaneous adhesiolysis procedures in managing chronic low back and lower extremity pain secondary to post-lumbar surgery syndrome and lumbar central spinal stenosis. A private, specialty referral interventional pain management center in the United States. Two controlled studies were conducted assessing the clinical effectiveness of percutaneous adhesiolysis for post-lumbar surgery syndrome and lumbar central spinal stenosis in an interventional pain management setting utilizing contemporary interventional pain management practices. A cost utility analysis was performed with direct payment data for a total of 130 patients in treatment groups over a 2-year period. Various outcome measures were included with significant improvement, defined as at least 50% improvement with reduction in pain and disability status. The results of 2 controlled studies of low back pain with 60 and 70 patients and a 2-year follow-up with the actual reimbursement data showed cost utility for 1 year of quality-adjusted life year (QALY) of USD $2,652 for post-lumbar surgery syndrome and USD $2,649 for lumbar central spinal stenosis. The results of this assessment show that the cost utility of managing chronic, intractable low back pain with percutaneous adhesiolysis at a QALY that is similar or lower in price than medical therapy only, physical therapy, manipulation, spinal cord stimulation, and surgery. The limitations of this cost utility analysis are that it is a single-center evaluation, with the inclusion of costs of adhesiolysis procedures in an ambulatory surgery center and physician visits, rather than all related costs including drug therapy and costs of disability in multiple settings. This cost utility analysis of percutaneous adhesiolysis in the treatment of post-lumbar surgery syndrome and lumbar central spinal stenosis shows the clinical effectiveness and cost utility of these procedures at USD $2,650 per one year of QALY when performed in an ambulatory surgery center. © 2014 World Institute of Pain.

Spinal epidural neurostimulation for treatment of acute and chronic intractable pain: initial and long term results.

PubMed

Richardson, R R; Siqueira, E B; Cerullo, L J

1979-09-01

Spinal epidural neurostimulation, which evolved from dorsal column stimulation, has been found to be effective in the treatment of acute and chronic intractable pain. Urban and Hashold have shown that it is a safe, simplified alternative to dorsal column stimulation, especially because laminectomy is not required if the electrodes are inserted percutaneously. Percutaneous epidural neurostimulation is also advantageous because there can be a diagnostic trial period before permanent internalization and implantation. This diagnostic and therapeutic modality has been used in 36 patients during the past 3 years at Northwestern Memorial Hospital. Eleven of these patients had acute intractable pain, which was defined as pain of less than 1 year in duration. Initial postimplantation results from the 36 patients indicate that spinal epidural neurostimulation is most effective in treating the intractable pain of diabetes, arachnoiditis, and post-traumatic and postamputation neuroma. Long term follow-up, varying from 1 year to 3 years postimplantation in the 20 initially responding patients, indicates that the neurostimulation continues to provide significant pain relief (50% or greater) in a majority of the patients who experienced initial significant pain relief.

Height increase, neuromuscular function, and back pain during 6 degrees head-down tilt with traction

NASA Technical Reports Server (NTRS)

Styf, J. R.; Ballard, R. E.; Fechner, K.; Watenpaugh, D. E.; Kahan, N. J.; Hargens, A. R.

1997-01-01

BACKGROUND: Spinal lengthening and back pain are commonly experienced by astronauts exposed to microgravity. METHODS: To develop a ground-based simulation for spinal adaptation to microgravity, we investigated height increase, neuromuscular function and back pain in 6 subjects all of whom underwent two forms of bed rest for 3 d. One form consisted of 6 degrees of head-down tilt (HDT) with balanced traction, while the other was horizontal bed rest (HBR). Subjects had a 2-week recovery period in between the studies. RESULTS: Total body and spinal length increased significantly more and the subjects had significantly more back pain during HDT with balanced traction compared to HBR. The distance between the lower endplate of L4 and upper endplate of S1, as measured by ultrasonography, increased significantly in both treatments to the same degree. Intramuscular pressures in the erector spinae muscles and ankle torque measurements during plantarflexion and dorsiflexion did not change significantly during either treatment. CONCLUSION: Compared to HBR, HDT with balanced traction may be a better method to simulate changes of total body and spinal lengths, as well as back pain seen in microgravity.

Clinical Evidence for Spinal Cord Stimulation for Failed Back Surgery Syndrome (FBSS): Systematic Review.

PubMed

Kapural, Leonardo; Peterson, Erika; Provenzano, David A; Staats, Peter

2017-07-15

A systematic review. A systematic literature review of the clinical data from prospective studies was undertaken to assess the efficacy of spinal cord stimulation (SCS) in the treatment of failed back surgery syndrome (FBSS) in adults. For patients with unrelenting back pain due to mechanical instability of the spine, degenerative disc disease, spinal injury, or deformity, spinal surgery is a well-accepted treatment option; however, even after surgical intervention, many patients continue to experience chronic back pain that can be notoriously difficult to treat. Clinical evidence suggests that for patients with FBSS, repeated surgery will not likely offer relief. Additionally, evidence suggests long-term use of opioid pain medications is not effective in this population, likely presents additional complications, and requires strict management. A systematic literature review was performed using several bibliographic databases, prospective studies in adults using SCS for FBSS were included. SCS has been shown to be a safe and efficacious treatment for this patient population. Recent technological developments in SCS offer even greater pain relief to patients' refractory to other treatment options, allowing patients to regain functionality and improve their quality of life with significant reductions in pain. N/A.

Forebrain Mechanisms of Nociception and Pain: Analysis through Imaging

NASA Astrophysics Data System (ADS)

Casey, Kenneth L.

1999-07-01

Pain is a unified experience composed of interacting discriminative, affective-motivational, and cognitive components, each of which is mediated and modulated through forebrain mechanisms acting at spinal, brainstem, and cerebral levels. The size of the human forebrain in relation to the spinal cord gives anatomical emphasis to forebrain control over nociceptive processing. Human forebrain pathology can cause pain without the activation of nociceptors. Functional imaging of the normal human brain with positron emission tomography (PET) shows synaptically induced increases in regional cerebral blood flow (rCBF) in several regions specifically during pain. We have examined the variables of gender, type of noxious stimulus, and the origin of nociceptive input as potential determinants of the pattern and intensity of rCBF responses. The structures most consistently activated across genders and during contact heat pain, cold pain, cutaneous laser pain or intramuscular pain were the contralateral insula and anterior cingulate cortex, the bilateral thalamus and premotor cortex, and the cerebellar vermis. These regions are commonly activated in PET studies of pain conducted by other investigators, and the intensity of the brain rCBF response correlates parametrically with perceived pain intensity. To complement the human studies, we developed an animal model for investigating stimulus-induced rCBF responses in the rat. In accord with behavioral measures and the results of human PET, there is a progressive and selective activation of somatosensory and limbic system structures in the brain and brainstem following the subcutaneous injection of formalin. The animal model and human PET studies should be mutually reinforcing and thus facilitate progress in understanding forebrain mechanisms of normal and pathological pain.

Multivariable modeling of factors associated with spinal pain in young adolescence.

PubMed

Dolphens, Mieke; Vansteelandt, Stijn; Cagnie, Barbara; Vleeming, Andry; Nijs, Jo; Vanderstraeten, Guy; Danneels, Lieven

2016-09-01

To investigate the factors related to the 1-month period prevalence of low back pain (LBP), neck pain (NP) and thoracic spine pain (TSP) in young adolescents, thereby considering potential correlates from the physical, sociodemographic, lifestyle, psychosocial and comorbid pain domains. In this cross-sectional baseline study, 69 factors potentially associated with spinal pain were assessed among 842 healthy adolescents before pubertal peak growth. With consideration for possible sex differences in associations, multivariable analysis was used to simultaneously evaluate contributions of all variables collected in the five domains. A significantly higher odds of LBP was shown for having high levels of psychosomatic complaints (odds ratio: 4.4; 95 % confidence interval: 1.6-11.9), a high lumbar lordotic apex, retroversed pelvis, introverted personality, and high levels of negative over positive affect. Associations with a higher prevalence and odds of NP were found for psychosomatic complaints (7.8; 2.5-23.9), TSP in the last month (4.9; 2.2-10.8), backward trunk lean, high levels of negative over positive affect and depressed mood. Having experienced LBP (2.7; 1.3-5.7) or NP (5.5; 2.6-11.8) in the preceding month was associated with a higher odds of TSP, as were low self-esteem, excessive physical activity, sedentarism and not achieving the Fit-norm. Psychosomatic symptoms and pain comorbidities had the strongest association with 1-month period prevalence of spinal pain in young adolescents, followed by factors from the physical and psychosocial domains. The role that "physical factors" play in non-adult spinal pain may have been underestimated by previous studies.

Alpha-1 adrenoceptor hyperresponsiveness in three neuropathic pain states: complex regional pain syndrome 1, diabetic peripheral neuropathic pain and central pain states following spinal cord injury.

PubMed

Teasell, Robert W; Arnold, J Malcolm O

2004-01-01

The pathophysiology of the pain associated with complex regional pain syndrome, spinal cord injury and diabetic peripheral neuropathy is not known. The pain of complex regional pain syndrome has often been attributed to abnormal sympathetic nervous system activity based on the presence of vasomotor instability and a frequently reported positive response, albeit a temporary response, to sympathetic blockade. In contrast, the pain below the level of spinal cord injury and diabetic peripheral neuropathy are generally seen as deafferentation phenomena. Each of these pain states has been associated with abnormal sympathetic nervous system function and increased peripheral alpha-1 adrenoceptor activity. This increased responsiveness may be a consequence of alpha-1 adrenoceptor postsynaptic hypersensitivity, or alpha-2 adrenoceptor presynaptic dysfunction with diminished noradrenaline reuptake, increased concentrations of noradrenaline in the synaptic cleft and increased stimulation of otherwise normal alpha-1 adrenoceptors. Plausible mechanisms based on animal research by which alpha-1 adrenoceptor hyperresponsiveness can lead to chronic neuropathic-like pain have been reported. This raises the intriguing possibility that sympathetic nervous system dysfunction may be an important factor in the generation of pain in many neuropathic pain states. Although results to date have been mixed, there may be a greater role for new drugs which target peripheral alpha-2 adrenoceptors (agonists) or alpha-1 adrenoceptors (antagonists).

Comprehensive review of neurophysiologic basis and diagnostic interventions in managing chronic spinal pain.

PubMed

Manchikanti, Laxmaiah; Boswell, Mark V; Singh, Vijay; Derby, Richard; Fellows, Bert; Falco, Frank J E; Datta, Sukdeb; Smith, Howard S; Hirsch, Joshua A

2009-01-01

Understanding the neurophysiological basis of chronic spinal pain and diagnostic interventional techniques is crucial in the proper diagnosis and management of chronic spinal pain. Central to the understanding of the structural basis of chronic spinal pain is the provision of physical diagnosis and validation of patient symptomatology. It has been shown that history, physical examination, imaging, and nerve conduction studies in non-radicular or discogenic pain are unable to diagnose the precise cause in 85% of the patients. In contrast, controlled diagnostic blocks have been shown to determine the cause of pain in as many as 85% of the patients. To provide evidence-based clinical practice guidelines for diagnostic interventional techniques. Best evidence synthesis. Strength of evidence was assessed by the U.S. Preventive Services Task Force (USPSTF) criteria utilizing 5 levels of evidence ranging from Level I to III with 3 subcategories in Level II. Diagnostic criteria established by systematic reviews were utilized with controlled diagnostic blocks. Diagnostic criteria included at least 80% pain relief with controlled local anesthetic blocks with the ability to perform multiple maneuvers which were painful prior to the diagnostic blocks for facet joint and sacroiliac joint blocks, whereas for provocation discography, the criteria included concordant pain upon stimulation of the target disc with 2 adjacent discs producing no pain at all. The indicated level of evidence for diagnostic lumbar, cervical, and thoracic facet joint nerve blocks is Level I or II-1. The indicated evidence is Level II-2 for lumbar and cervical discography, whereas it is Level II-3 for thoracic provocation discography. The evidence for diagnostic sacroiliac joint nerve blocks is Level II-2. Level of evidence for selective nerve root blocks for diagnostic purposes is Level II-3. Limitations of this guideline preparation include a continued paucity of literature and conflicts in preparation of systematic reviews and guidelines. These guidelines include the evaluation of evidence for diagnostic interventional procedures in managing chronic spinal pain and recommendations. However, these guidelines do not constitute inflexible treatment recommendations. These guidelines also do not represent a "standard of care."

Human psychophysics and rodent spinal neurones exhibit peripheral and central mechanisms of inflammatory pain in the UVB and UVB heat rekindling models.

PubMed

O'Neill, Jessica; Sikandar, Shafaq; McMahon, Stephen B; Dickenson, Anthony H

2015-09-01

Translational research is key to bridging the gaps between preclinical findings and the patients, and a translational model of inflammatory pain will ideally induce both peripheral and central sensitisation, more effectively mimicking clinical pathophysiology in some chronic inflammatory conditions. We conducted a parallel investigation of two models of inflammatory pain, using ultraviolet B (UVB) irradiation alone and UVB irradiation with heat rekindling. We used rodent electrophysiology and human quantitative sensory testing to characterise nociceptive processing in the peripheral and central nervous systems in both models. In both species, UVB irradiation produces peripheral sensitisation measured as augmented evoked activity of rat dorsal horn neurones and increased perceptual responses of human subjects to mechanical and thermal stimuli. In both species, UVB with heat rekindling produces central sensitisation. UVB irradiation alone and UVB with heat rekindling are translational models of inflammation that produce peripheral and central sensitisation, respectively. The predictive value of laboratory models for human pain processing is crucial for improving translational research. The discrepancy between peripheral and central mechanisms of pain is an important consideration for drug targets, and here we describe two models of inflammatory pain that involve ultraviolet B (UVB) irradiation, which can employ peripheral and central sensitisation to produce mechanical and thermal hyperalgesia in rats and humans. We use electrophysiology in rats to measure the mechanically- and thermally-evoked activity of rat spinal neurones and quantitative sensory testing to assess human psychophysical responses to mechanical and thermal stimulation in a model of UVB irradiation and in a model of UVB irradiation with heat rekindling. Our results demonstrate peripheral sensitisation in both species driven by UVB irradiation, with a clear mechanical and thermal hypersensitivity of rat dorsal horn neurones and enhanced perceptual responses of human subjects to both mechanical and thermal stimulation. Additional heat rekindling produces markers of central sensitisation in both species, including enhanced receptive field sizes. Importantly, we also showed a correlation in the evoked activity of rat spinal neurones to human thermal pain thresholds. The parallel results in rats and humans validate the translational use of both models and the potential for such models for preclinical assessment of prospective analgesics in inflammatory pain states. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Considerations in Spinal Fusion Surgery for Chronic Lumbar Pain: Psychosocial Factors, Rating Scales, and Perioperative Patient Education-A Review of the Literature.

PubMed

Gaudin, Daniel; Krafcik, Brianna M; Mansour, Tarek R; Alnemari, Ahmed

2017-02-01

Despite widespread use of lumbar spinal fusion as a treatment for back pain, outcomes remain variable. Optimizing patient selection can help to reduce adverse outcomes. This literature review was conducted to better understand factors associated with optimal postoperative results after lumbar spinal fusion for chronic back pain and current tools used for evaluation. The PubMed database was searched for clinical trials related to psychosocial determinants of outcome after lumbar spinal fusion surgery; evaluation of commonly used patient subjective outcome measures; and perioperative cognitive, behavioral, and educational therapies. Reference lists of included studies were also searched by hand for additional studies meeting inclusion and exclusion criteria. Patients' perception of good health before surgery and low cardiovascular comorbidity predict improved postoperative physical functional capacity and greater patient satisfaction. Depression, tobacco use, and litigation predict poorer outcomes after lumbar fusion. Incorporation of cognitive-behavioral therapy perioperatively can address these psychosocial risk factors and improve outcomes. The 36-Item Short Form Health Survey, European Quality of Life five dimensions questionnaire, visual analog pain scale, brief pain inventory, and Oswestry Disability Index can provide specific feedback to track patient progress and are important to understand when evaluating the current literature. This review summarizes current information and explains commonly used assessment tools to guide clinicians in decision making when caring for patients with lower back pain. When determining a treatment algorithm, physicians must consider predictive psychosocial factors. Use of perioperative cognitive-behavioral therapy and patient education can improve outcomes after lumbar spinal fusion. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of depression and pain interference with disease-management self-efficacy in community-dwelling individuals with spinal cord injury.

PubMed

Pang, Marco Y C; Eng, Janice J; Lin, Kwan-Hwa; Tang, Pei-Fang; Hung, Chihya; Wang, Yen-Ho

2009-11-01

To determine factors influencing disease-management self-efficacy in individuals with spinal cord injury. A cross-sectional study. Forty-nine community-dwelling individuals with chronic spinal cord injury (mean age 44 years) participated in the study. Each subject was evaluated for disease-management self-efficacy (Self-efficacy for Managing Chronic Disease), depression (10-item Center for Epidemiologic Studies Depression Scale), pain interference (Pain Interference Scale), and availability of support (Interpersonal Support Evaluation List short form). Multiple regression analysis was performed to determine the relative contributions of these factors to disease-management self-efficacy. The mean disease-management self-efficacy score was 6.5 out of 10 (standard deviation 1.6). Bivariate correlation analysis showed that higher self-efficacy was significantly correlated with longer time since injury (r = 0.367, p = 0.010), better social support (r = 0.434, p = 0.002), lower pain interference (r = -0.589, p <0.001), and less severe depressive symptoms (r=-0.463, p=0.001). In multiple regression analysis, only lower pain interference and less severe depressive symptoms were significantly associated with higher disease-management self-efficacy (F 4,44=10.249, R2=0.482, p<0.001). Disease-management self-efficacy is suboptimal in many community-living people with spinal cord injury. This research suggests that rehabilitation of patients with spinal cord injury should include self-efficacy-enhancing strategies. Alleviation of depressive symptoms and pain self-management may be important for improving disease-management self-efficacy in this population, but this requires further study.

Spinal Anesthesia and Minimal Invasive Laminotomy for Paddle Electrode Placement in Spinal Cord Stimulation: Technical Report and Clinical Results at Long-Term Followup

PubMed Central

Sarubbo, S.; Latini, F.; Tugnoli, V.; Quatrale, R.; Granieri, E.; Cavallo, M. A.

2012-01-01

Object. We arranged a mini-invasive surgical approach for implantation of paddle electrodes for SCS under spinal anesthesia obtaining the best paddle electrode placement and minimizing patients' discomfort. We describe our technique supported by neurophysiological intraoperative monitoring and clinical results. Methods. 16 patients, affected by neuropathic pain underwent the implantation of paddle electrodes for spinal cord stimulation in lateral decubitus under spinal anesthesia. The paddle was introduced after flavectomy and each patient confirmed the correct distribution of paresthesias induced by intraoperative test stimulation. VAS and patients' satisfaction rate were recorded during the followup and compared to preoperative values. Results. No patients reported discomfort during the procedure. In all cases, paresthesias coverage of the total painful region was achieved, allowing the best final electrode positioning. At the last followup (mean 36.7 months), 87.5% of the implanted patients had a good rate of satisfaction with a mean VAS score improvement of 70.5%. Conclusions. Spinal cord stimulation under spinal anesthesia allows an optimal positioning of the paddle electrodes without any discomfort for patients or neurosurgeons. The best intraoperative positioning allows a better postoperative control of pain, avoiding the risk of blind placements of the paddle or further surgery for their replacement. PMID:22566761

Double Crush of L5 Spinal Nerve Root due to L4/5 Lateral Recess Stenosis and Bony Spur Formation of Lumbosacral Transitional Vertebra Pseudoarticulation: A Case Report and Review

PubMed Central

Iwasaki, Motoyuki; Akiyama, Masahiko; Koyanagi, Izumi; Niiya, Yoshimasa; Ihara, Tatsuo; Houkin, Kiyohiro

2017-01-01

We present a case of double-crushed L5 nerve root symptoms caused by inside and outside of the spinal canal with spur formation of the lumbosacral transitional vertebra (LSTV). A 78-year-old man presented with 7-year history of moderate paresis of his toe and left leg pain when walking. Magnetic resonance imaging (MRI) revealed spinal stenosis at the L3/4 and 4/5 spinal levels and he underwent wide fenestration of both levels. Leg pain disappeared and 6-min walk distance (6MWD) improved after surgery, however, the numbness in his toes increased and 6MWD decreased 9 months after surgery. Repeated MR and 3D multiplanar reconstructed computed tomography (CT) images showed extraforaminal impingement of the L5 root by bony spur of the left LSTV. He underwent second decompression surgery of the L5/S via the left sided Wiltse approach, resulting in the improvement of his symptoms. The impingement of L5 spinal nerve root between the transverse process of the fifth lumbar vertebra and the sacral ala is a rare entity of the pathology called “far-out syndrome (FOS)”. Especially, the bony spur formation secondary to the anomalous articulation of the LSTV (LSPA) has not been reported. These articulations could be due to severe disc degeneration, following closer distance and contact between the transverse process and the sacral ala. To our knowledge, this is the first report describing a case with this pathology and may be considered in cases of failed back surgery syndromes (FBSS) of the L5 root symptoms. PMID:29018654

Measuring Neuromuscular Fatigue in Cervical Spinal Musculature of Military Helicopter Aircrew

DTIC Science & Technology

2009-11-01

BSct ABSTRACT Neck pain and muscle furiLiion in aircrew have received considerable attention. We hypothesized nor- niali/ed olectromyography (EMG...the literature with aiicrew-specitic publications indicates a growing concern with regard to cervical spinal injuries and pain in the helicop- ter...individual article.’"’’ Regardless of the exact prevalence. Ilight-induced neck pain results in lost working days from highly trained aircrew that negatively

New insights into the mechanisms of itch: are pain and itch controlled by distinct mechanisms?

PubMed Central

Liu, Tong; Ji, Ru-Rong

2013-01-01

Itch and pain are closely related but distinct sensations. They share largely overlapping mediators and receptors, and itch-responding neurons are also sensitive to pain stimuli. Itch-mediating primary sensory neurons are equipped with distinct receptors and ion channels for itch transduction, including Mas-related G protein-coupled receptors (Mrgprs), protease-activated receptors (PARs), histamine receptors, bile acid receptor (TGR5), toll-like receptors (TLRs), and transient receptor potential subfamily V1/A1 (TRPV1/A1). Recent progress has indicated the existence of an itch-specific neuronal circuitry. The MrgprA3-expressing primary sensory neurons exclusively innervate the epidermis of skin and their central axons connect with gastrin-releasing peptide receptor (GRPR)-expressing neurons in the superficial spinal cord. Notably, ablation of MrgprA3-expressing primary sensory neurons or GRPR-expressing spinal cord neurons results in selective reduction in itch but not pain. Chronic itch results from dysfunction of the immune and nervous system and can manifest as neural plasticity, despite the fact that chronic itch is often treated by dermatologists. While differences between acute pain and acute itch are striking, chronic itch and chronic pain share many similar mechanisms, including peripheral sensitization (increased responses of primary sensory neurons to itch and pain mediators), central sensitization (hyperactivity of spinal projection neurons and excitatory interneurons), loss of inhibitory control in the spinal cord, and neuro-immune and neuro-glial interactions. Notably, painful stimuli can elicit itch in some chronic conditions (e.g., atopic dermatitis) and some drugs for treating chronic pain are also effective in chronic itch. Thus, itch and pain have more similarities in pathological and chronic conditions. PMID:23636773

Correlations of hip mobility with degree of back pain and lumbar spinal mobility in chronic low-back pain patients.

PubMed

Mellin, G

1988-06-01

Mobility of hips and lumbar spine were measured in 301 men and 175 women who were in employment but suffered from chronic or recurrent low-back pain. The degree of low-back pain (LBP) was assessed with a questionnaire. Hip flexion, extension, internal rotation, and hamstring flexibility in the men, and hip flexion and extension in the women had statistically significant negative correlations with LBP. Among the correlations between hip and lumbar spinal mobility, hip flexion and extension with lumbar rotation were strongest.

Post-Flight Back Pain Following International Space Station Missions: Evaluation of Spaceflight Risk Factors

NASA Technical Reports Server (NTRS)

Laughlin, Mitzi S.; Murray, Jocelyn D.; Wear, Mary L.; Van Baalen, Mary

2016-01-01

Back pain during spaceflight has often been attributed to the lengthening of the spinal column due to the absence of gravity during both short and long-duration missions. Upon landing and re-adaptation to gravity, the spinal column reverts back to its original length thereby causing some individuals to experience pain and muscular spasms, while others experience no ill effects. With International Space Station (ISS) missions, cases of back pain and injury are more common post-flight, but little is known about the potential risk factors.

Group III metabotropic glutamate receptors inhibit hyperalgesia in animal models of inflammation and neuropathic pain.

PubMed

Goudet, Cyril; Chapuy, Eric; Alloui, Abdelkrim; Acher, Francine; Pin, Jean-Philippe; Eschalier, Alain

2008-07-01

Glutamate plays a key role in modulation of nociceptive processing. This excitatory amino acid exerts its action through two distinct types of receptors, ionotropic and metabotropic glutamate receptors (mGluRs). Eight mGluRs have been identified and divided in three groups based on their sequence similarity, pharmacology and G-protein coupling. While the role of group I and II mGluRs is now well established, little is known about the part played by group III mGluRs in pain. In this work, we studied comparatively the involvement of spinal group III mGluR in modulation of acute, inflammatory and neuropathic pain. While intrathecal injection of ACPT-I, a selective group III mGluR agonist, failed to induce any change in vocalization thresholds of healthy animals submitted to mechanical or thermal stimuli, it dose-dependently inhibited the nociceptive behavior of rats submitted to the formalin test and the mechanical hyperalgesia associated with different animal models of inflammatory (carrageenan-treated and monoarthritic rats) or neuropathic pain (mononeuropathic and vincristine-treated rats). Similar effects were also observed following intrathecal injection of PHCCC, a positive allosteric modulator of mGlu4. Antihyperalgesia induced by ACPT-I was blocked either by LY341495, a nonselective antagonist of mGluR, by MAP4, a selective group III antagonist. This study provide new evidences supporting the role of spinal group III mGluRs in the modulation of pain perception in different pathological pain states of various etiologies but not in normal conditions. It more particularly highlights the specific involvement of mGlu4 in this process and may be a useful therapeutic approach to chronic pain treatment.

Spinal neuromodulation as a novel surgical option for failed back surgery syndrome following rhBMP exuberant bony growth in instrumented lumbar fusion: A case report and literature review

PubMed Central

Ghaly, Ramsis F.; Lissounov, Alexei; Tverdohleb, Tatiana; Kohanchi, David; Candido, Kenneth D.; Knezevic, Nebojsa Nick

2016-01-01

Background: Bone morphogenic protein (BMP) for instrumented lumbar fusion was approved in 2002, and since then has led to an increasing incidence of BMP-related neuropathic pain. These patients are usually resistant to conventional medical therapy and frequently undergo multiple surgical revisions without any pain relief. Case Description: A 58-year-old male was referred to the author's outpatient clinic after four lumbar surgeries did not provide satisfactory pain relief. During his 10 years of suffering from low back pain after an injury, the patient was resistant to conventional and interventional treatment options. He was experiencing severe back pain rated 10/10, as well as right lower extremity pain, numbness, tingling, and motor deficits. Outside spine specialists had performed revision surgeries for BMP-related exuberant bone formation at L5–S1, which included the removal of the ipsilateral hardware and debridement of intradiscal and intraforamina heterotrophic exuberant bony formation. The author implanted the patient with a permanent continuous spinal cord stimulator, after which he achieved complete pain relief (0/10) and restoration of motor, sensory, autonomic, and sphincter functions. Conclusion: This is the first reported case of restorative function with neuromodulation therapy in a BMP-induced postoperative complication, which is considered as a primarily inflammatory process, rather than nerve root compression due to exuberant bony formation. We hypothesize that neuromodulation may enhance blood flow and interfere with inflammatory processes, in addition to functioning by the accepted gate control theory mechanism. The neuromodulation therapy should be strongly considered as a therapeutic approach, even with confirmed BMP-induced postoperative radiculitis, rather than proposing multiple surgical revisions. PMID:27843683

Pain Relief in CRPS-II after Spinal Cord and Motor Cortex Simultaneous Dual Stimulation.

PubMed

Lopez, William Oc; Barbosa, Danilo C; Teixera, Manoel J; Paiz, Martin; Moura, Leonardo; Monaco, Bernardo A; Fonoff, Erich T

2016-05-01

We describe a case of a 30-year-old woman who suffered a traumatic injury of the right brachial plexus, developing severe complex regional pain syndrome type II (CRPS-II). After clinical treatment failure, spinal cord stimulation (SCS) was indicated with initial positive pain control. However, after 2 years her pain progressively returned to almost baseline intensity before SCS. Additional motor cortex electrode implant was then proposed as a rescue therapy and connected to the same pulse generator. This method allowed simultaneous stimulation of the motor cortex and SCS in cycling mode with independent stimulation parameters in each site. At 2 years follow-up, the patient reported sustained improvement in pain with dual stimulation, reduction of painful crises, and improvement in quality of life. The encouraging results in this case suggests that this can be an option as add-on therapy over SCS as a possible rescue therapy in the management of CRPS-II. However, comparative studies must be performed in order to determine the effectiveness of this therapy. Chronic neuropathic pain, Complex regional pain syndrome Type II, brachial plexus injury, motor cortex stimulation, spinal cord stimulation.

ANALGESIC EFFECT OF INTRATHECAL BACLOFEN BOLUS ON NEUROPATHIC PAIN IN SPINAL CORD INJURY PATIENTS.

PubMed

Kumru, Hatice; Benito-Penalva, Jesus; Kofler, Markus; Vidal, Joan

2018-05-18

GABA-ergic neurons are widely distributed throughout the central nervous system, including the spinal cord which is important for the transmission of pain impulses to the brain. Here we hypothesized that intrathecal baclofen (ITB) which is a GABA analogue might exert analgesic effects on neuropathic pain, which could be related to subtypes of pain in spinal cord injury (SCI). SCI patients with a cervical or thoracic lesion and neuropathic pain were randomized to receive either a single ITB bolus or placebo. Numerical Rating Scale (NRS), Neuropathic Pain Symptom Inventory (NPSI), and Brief Pain Inventory (BPI) were obtained for assessment of neuropathic pain. Spasticity was assessed using Modified Ashworth Scale and visual analogue scale. Evaluations were performed at baseline, and 4, 8, and 24 hours after application of ITB or placebo. Eight patients received ITB, 5 placebo. Neuropathic pain improved significantly in the ITB group based on NRS, BPI, and NPSI, which revealed an effect on all subtypes of pain. Spasticity declined significantly. In the placebo group, there was neither significant change in pain nor in spasticity. An ITB bolus exerted a significant analgesic effect on all subtypes of neuropathic pain in SCI patients. ITB has analgesic effects on all subtypes of neuropathic pain and can improve interference of neuropathic pain with activities of daily living. ITB might be a promising analgesic treatment to control neuropathic pain. Copyright © 2018. Published by Elsevier Inc.

Dural ectasia associated with Mounier-Kuhn syndrome: a novel association in the context of spinal stenosis.

PubMed

Sheridan, Gerard Anthony; Godkin, Owen; Devitt, Aiden

2017-08-30

We present the case of a patient undergoing lumbar spine decompression for stenosis with a history of Mounier-Kuhn syndrome. The patient presented with axial lumbar spine pain over 6 months with progressive radicular pain to the left L3 dermatome. MRI confirmed spinal stenosis at L3/4 level with associated dural ectasia. The patient had an uneventful spinal decompression with resolution of radicular symptoms and axial spine pain. Dural ectasia poses a significant risk when operating on the lumbosacral spine. Larger cerebrospinal fluid volumes and a capacious dural canal can result in anaesthetic and orthopaedic complications such as inadequate spinal anaesthesia, complicated epidural analgesia, intraoperative dural tears and difficult pedicle screw insertion due to narrow pedicles. This is the first case in the literature detailing the association between dural ectasia and Mounier-Kuhn syndrome. We recommend adequate spinal imaging in patients with Mounier-Kuhn syndrome to exclude dural ectasia prior to undergoing lumbosacral spinal procedures. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Applying Current Concepts in Pain-Related Brain Science to Dance Rehabilitation.

PubMed

Wallwork, Sarah B; Bellan, Valeria; Moseley, G Lorimer

2017-03-01

Dance involves exemplary sensory-motor control, which is subserved by sophisticated neural processing at the spinal cord and brain level. Such neural processing is altered in the presence of nociception and pain, and the adaptations within the central nervous system that are known to occur with persistent nociception or pain have clear implications for movement and, indeed, risk of further injury. Recent rapid advances in our understanding of the brain's representation of the body and the role of cortical representations, or "neurotags," in bodily protection and regulation have given rise to new strategies that are gaining traction in sports medicine. Those strategies are built on the principles that govern the operation of neurotags and focus on minimizing the impact of pain, injury, and immobilization on movement control and optimal performance. Here we apply empirical evidence from the chronic pain clinical neurosciences to introduce new opportunities for rehabilitation after dance injury.

Pain-relieving prospects for adenosine receptors and ectonucleotidases

PubMed Central

Zylka, Mark J.

2010-01-01

Adenosine receptor agonists have potent antinociceptive effects in diverse preclinical models of chronic pain. In contrast, the efficacy of adenosine or adenosine receptor agonists at treating pain in humans is unclear. Two ectonucleotidases that generate adenosine in nociceptive neurons were recently identified. When injected spinally, these enzymes have long-lasting adenosine A1 receptor (A1R)-dependent antinociceptive effects in inflammatory and neuropathic pain models. Furthermore, recent findings indicate that spinal adenosine A2A receptor activation can enduringly inhibit neuropathic pain symptoms. Collectively, these studies suggest the possibility of treating chronic pain in humans by targeting specific adenosine receptor subtypes in anatomically defined regions with agonists or with ectonucleotidases that generate adenosine. PMID:21236731

Spine Injuries and Disorders

MedlinePlus

... spinal stenosis and herniated disks Spinal diseases often cause pain when bone changes put pressure on the spinal cord or nerves. They can also limit movement. Treatments differ by disease, but sometimes they include back braces and surgery.

NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain

PubMed Central

Kim, Donghoon; You, Byunghyun; Jo, Eun-Kyeong; Han, Sang-Kyou; Simon, Melvin I.; Lee, Sung Joong

2010-01-01

Increasing evidence supports the notion that spinal cord microglia activation plays a causal role in the development of neuropathic pain after peripheral nerve injury; yet the mechanisms for microglia activation remain elusive. Here, we provide evidence that NADPH oxidase 2 (Nox2)-derived ROS production plays a critical role in nerve injury-induced spinal cord microglia activation and subsequent pain hypersensitivity. Nox2 expression was induced in dorsal horn microglia immediately after L5 spinal nerve transection (SNT). Studies using Nox2-deficient mice show that Nox2 is required for SNT-induced ROS generation, microglia activation, and proinflammatory cytokine expression in the spinal cord. SNT-induced mechanical allodynia and thermal hyperalgesia were similarly attenuated in Nox2-deficient mice. In addition, reducing microglial ROS level via intrathecal sulforaphane administration attenuated mechanical allodynia and thermal hyperalgesia in SNT-injured mice. Sulforaphane also inhibited SNT-induced proinflammatory gene expression in microglia, and studies using primary microglia indicate that ROS generation is required for proinflammatory gene expression in microglia. These studies delineate a pathway involving nerve damage leading to microglial Nox2-generated ROS, resulting in the expression of proinflammatory cytokines that are involved in the initiation of neuropathic pain. PMID:20679217

Coping with Low Back Pain.

ERIC Educational Resources Information Center

Kindig, L. E.; Mrvos, S. R.

Guidelines are offered for the prevention and relief of lower back pain. The structure of the spine is described, and the functions and composition of spinal disks are explained. A list is included of common causes of abnormalities of the spinal column, and injuries which may cause the fracture of the vertebrae are described. Factors causing low…

Intracellular mGluR5 plays a critical role in neuropathic pain

PubMed Central

Vincent, Kathleen; Cornea, Virginia M.; Jong, Yuh-Jiin I.; Laferrière, André; Kumar, Naresh; Mickeviciute, Aiste; Fung, Jollee S. T.; Bandegi, Pouya; Ribeiro-da-Silva, Alfredo; O'Malley, Karen L.; Coderre, Terence J.

2016-01-01

Spinal mGluR5 is a key mediator of neuroplasticity underlying persistent pain. Although brain mGluR5 is localized on cell surface and intracellular membranes, neither the presence nor physiological role of spinal intracellular mGluR5 is established. Here we show that in spinal dorsal horn neurons >80% of mGluR5 is intracellular, of which ∼60% is located on nuclear membranes, where activation leads to sustained Ca2+ responses. Nerve injury inducing nociceptive hypersensitivity also increases the expression of nuclear mGluR5 and receptor-mediated phosphorylated-ERK1/2, Arc/Arg3.1 and c-fos. Spinal blockade of intracellular mGluR5 reduces neuropathic pain behaviours and signalling molecules, whereas blockade of cell-surface mGluR5 has little effect. Decreasing intracellular glutamate via blocking EAAT-3, mimics the effects of intracellular mGluR5 antagonism. These findings show a direct link between an intracellular GPCR and behavioural expression in vivo. Blockade of intracellular mGluR5 represents a new strategy for the development of effective therapies for persistent pain. PMID:26837579

A diagnosis-based clinical decision rule for spinal pain part 2: review of the literature

PubMed Central

Murphy, Donald R; Hurwitz, Eric L; Nelson, Craig F

2008-01-01

Background Spinal pain is a common and often disabling problem. The research on various treatments for spinal pain has, for the most part, suggested that while several interventions have demonstrated mild to moderate short-term benefit, no single treatment has a major impact on either pain or disability. There is great need for more accurate diagnosis in patients with spinal pain. In a previous paper, the theoretical model of a diagnosis-based clinical decision rule was presented. The approach is designed to provide the clinician with a strategy for arriving at a specific working diagnosis from which treatment decisions can be made. It is based on three questions of diagnosis. In the current paper, the literature on the reliability and validity of the assessment procedures that are included in the diagnosis-based clinical decision rule is presented. Methods The databases of Medline, Cinahl, Embase and MANTIS were searched for studies that evaluated the reliability and validity of clinic-based diagnostic procedures for patients with spinal pain that have relevance for questions 2 (which investigates characteristics of the pain source) and 3 (which investigates perpetuating factors of the pain experience). In addition, the reference list of identified papers and authors' libraries were searched. Results A total of 1769 articles were retrieved, of which 138 were deemed relevant. Fifty-one studies related to reliability and 76 related to validity. One study evaluated both reliability and validity. Conclusion Regarding some aspects of the DBCDR, there are a number of studies that allow the clinician to have a reasonable degree of confidence in his or her findings. This is particularly true for centralization signs, neurodynamic signs and psychological perpetuating factors. There are other aspects of the DBCDR in which a lesser degree of confidence is warranted, and in which further research is needed. PMID:18694490

Intrathecal Infusion of Hydrogen-Rich Normal Saline Attenuates Neuropathic Pain via Inhibition of Activation of Spinal Astrocytes and Microglia in Rats

PubMed Central

Sun, Xuejun; Xiang, Zhenghua; Yang, Liqun; Huang, Shengdong; Lu, Zhijie; Sun, Yuming; Yu, Wei-Feng

2014-01-01

Background Reactive oxygen and nitrogen species are key molecules that mediate neuropathic pain. Although hydrogen is an established antioxidant, its effect on chronic pain has not been characterized. This study was to investigate the efficacy and mechanisms of hydrogen-rich normal saline induced analgesia. Methodology/Principal findings In a rat model of neuropathic pain induced by L5 spinal nerve ligation (L5 SNL), intrathecal injection of hydrogen-rich normal saline relieved L5 SNL-induced mechanical allodynia and thermal hyperalgesia. Importantly, repeated administration of hydrogen-rich normal saline did not lead to tolerance. Preemptive treatment with hydrogen-rich normal saline prevented development of neuropathic pain behavior. Immunofluorochrome analysis revealed that hydrogen-rich normal saline treatment significantly attenuated L5 SNL-induced increase of 8-hydroxyguanosine immunoreactive cells in the ipsilateral spinal dorsal horn. Western blot analysis of SDS/PAGE-fractionated tyrosine-nitrated proteins showed that L5 SNL led to increased expression of tyrosine-nitrated Mn-containing superoxide dismutase (MnSOD) in the spinal cord, and hydrogen-rich normal saline administration reversed the tyrosine-nitrated MnSOD overexpression. We also showed that the analgesic effect of hydrogen-rich normal saline was associated with decreased activation of astrocytes and microglia, attenuated expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the spinal cord. Conclusion/Significance Intrathecal injection of hydrogen-rich normal saline produced analgesic effect in neuropathic rat. Hydrogen-rich normal saline-induced analgesia in neuropathic rats is mediated by reducing the activation of spinal astrocytes and microglia, which is induced by overproduction of hydroxyl and peroxynitrite. PMID:24857932

Ionic plasticity and pain: The loss of descending serotonergic fibers after spinal cord injury transforms how GABA affects pain.

PubMed

Huang, Yung-Jen; Grau, James W

2018-05-02

Activation of pain (nociceptive) fibers can sensitize neural circuits within the spinal cord, inducing an increase in excitability (central sensitization) that can foster chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. In adult animals, the co-transporter KCC2 maintains a low intracellular concentration of the anion Cl - . As a result, when the GABA-A receptor is engaged, Cl - flows in the neuron which has a hyperpolarizing (inhibitory) effect. Spinal cord injury (SCI) can down-regulate KCC2 and reverse the flow of Cl - . Under these conditions, engaging the GABA-A receptor can have a depolarizing (excitatory) effect that fosters the development of nociceptive sensitization. The present paper explores how SCI alters GABA function and provides evidence that the loss of descending fibers alters pain transmission to the brain. Prior work has shown that, after SCI, administration of a GABA-A antagonist blocks the development of capsaicin-induced nociceptive sensitization, implying that GABA release plays an essential role. This excitatory effect is linked to serotonergic (5HT) fibers that descend through the dorsolateral funiculus (DLF) and impact spinal function via the 5HT-1A receptor. Supporting this, blocking the 5HT-1A receptor, or lesioning the DLF, emulated the effect of SCI. Conversely, spinal application of a 5HT-1A agonist up-regulated KCC2 and reversed the effect of bicuculline treatment. Finally, lesioning the DLF reversed how a GABA-A antagonist affects a capsaicin-induced aversion in a place conditioning task; in sham operated animals, bicuculline enhanced aversion whereas in DLF-lesioned rats biciculline had an antinociceptive effect. Copyright © 2018 Elsevier Inc. All rights reserved.

Adolescents' perceptions of music therapy following spinal fusion surgery.

PubMed

Kleiber, Charmaine; Adamek, Mary S

2013-02-01

To explore adolescents' memories about music therapy after spinal fusion surgery and their recommendations for future patients. Spinal fusion for adolescent idiopathic scoliosis is one of the most painful surgeries performed. Music therapy is shown to decrease postoperative pain in children after minor surgery. In preparation for developing a preoperative information program, we interviewed adolescents who had spinal fusion and postoperative music therapy to find out what they remembered and what they recommended for future patients. Eight adolescents who had spinal fusion for adolescent idiopathic scoliosis were interviewed about their experiences. For this qualitative study, the investigators independently used thematic analysis techniques to formulate interpretive themes. Together they discussed their ideas and assigned overall meanings to the information. The eight participants were 13-17 years of age and had surgery between 2-24 months previously. The overarching themes identified from the interviews were relaxation and pain perception, choice and control, therapist interaction and preoperative information. Participants stated that music therapy helped with mental relaxation and distraction from pain. It was important to be able to choose the type of music for the therapy and to use self-control to focus on the positive. Their recommendation was that future patients should be provided with information preoperatively about music therapy and pain management. Participants recommended a combination of auditory and visual information, especially the experiences of previous patients who had spinal fusion and music therapy. Music provided live at the bedside by a music therapist was remembered vividly and positively by most of the participants. The presence of a music therapist providing patient-selected music at the bedside is important. Methods to introduce adolescents to music therapy and how to use music for relaxation should be developed and tested. © 2012 Blackwell Publishing Ltd.

An imaging informatics-based system to support animal studies for treating pain in spinal cord injury utilizing proton-beam radiotherapy

NASA Astrophysics Data System (ADS)

Verma, Sneha K.; Liu, Brent J.; Gridley, Daila S.; Mao, Xiao W.; Kotha, Nikhil

2015-03-01

In previous years we demonstrated an imaging informatics system designed to support multi-institutional research focused on the utilization of proton radiation for treating spinal cord injury (SCI)-related pain. This year we will demonstrate an update on the system with new modules added to perform image processing on evaluation data using immunhistochemistry methods to observe effects of proton therapy. The overarching goal of the research is to determine the effectiveness of using the proton beam for treating SCI-related neuropathic pain as an alternative to invasive surgical lesioning. The research is a joint collaboration between three major institutes, University of Southern California (data collection/integration and image analysis), Spinal Cord Institute VA Healthcare System, Long Beach (patient subject recruitment), and Loma Linda University and Medical Center (human and preclinical animal studies). The system that we are presenting is one of its kind which is capable of integrating a large range of data types, including text data, imaging data, DICOM objects from proton therapy treatment and pathological data. For multi-institutional studies, keeping data secure and integrated is very crucial. Different kinds of data within the study workflow are generated at different stages and different groups of people who process and analyze them in order to see hidden patterns within healthcare data from a broader perspective. The uniqueness of our system relies on the fact that it is platform independent and web-based which makes it very useful in such a large-scale study.

Five-year durability of stand-alone interspinous process decompression for lumbar spinal stenosis

PubMed Central

Nunley, Pierce D; Patel, Vikas V; Orndorff, Douglas G; Lavelle, William F; Block, Jon E; Geisler, Fred H

2017-01-01

Background Lumbar spinal stenosis is the most common indication for spine surgery in older adults. Interspinous process decompression (IPD) using a stand-alone spacer that functions as an extension blocker offers a minimally invasive treatment option for intermittent neurogenic claudication associated with spinal stenosis. Methods This study evaluated the 5-year clinical outcomes for IPD (Superion®) from a randomized controlled US Food and Drug Administration (FDA) noninferiority trial. Outcomes included Zurich Claudication Questionnaire (ZCQ) symptom severity (ss), physical function (pf), and patient satisfaction (ps) subdomains, leg and back pain visual analog scale (VAS), and Oswestry Disability Index (ODI). Results At 5 years, 84% of patients (74 of 88) demonstrated clinical success on at least two of three ZCQ domains. Individual ZCQ domain success rates were 75% (66 of 88), 81% (71 of 88), and 90% (79 of 88) for ZCQss, ZCQpf, and ZCQps, respectively. Leg and back pain success rates were 80% (68 of 85) and 65% (55 of 85), respectively, and the success rate for ODI was 65% (57 of 88). Percentage improvements over baseline were 42%, 39%, 75%, 66%, and 58% for ZCQss, ZCQpf, leg and back pain VAS, and ODI, respectively (all P<0.001). Within-group effect sizes were classified as very large for four of five clinical outcomes (ie, >1.0; all P<0.0001). Seventy-five percent of IPD patients were free from reoperation, revision, or supplemental fixation at their index level at 5 years. Conclusion After 5 years of follow-up, IPD with a stand-alone spacer provides sustained clinical benefit. PMID:28919727

Five-year durability of stand-alone interspinous process decompression for lumbar spinal stenosis.

PubMed

Nunley, Pierce D; Patel, Vikas V; Orndorff, Douglas G; Lavelle, William F; Block, Jon E; Geisler, Fred H

2017-01-01

Lumbar spinal stenosis is the most common indication for spine surgery in older adults. Interspinous process decompression (IPD) using a stand-alone spacer that functions as an extension blocker offers a minimally invasive treatment option for intermittent neurogenic claudication associated with spinal stenosis. This study evaluated the 5-year clinical outcomes for IPD (Superion ® ) from a randomized controlled US Food and Drug Administration (FDA) noninferiority trial. Outcomes included Zurich Claudication Questionnaire (ZCQ) symptom severity (ss), physical function (pf), and patient satisfaction (ps) subdomains, leg and back pain visual analog scale (VAS), and Oswestry Disability Index (ODI). At 5 years, 84% of patients (74 of 88) demonstrated clinical success on at least two of three ZCQ domains. Individual ZCQ domain success rates were 75% (66 of 88), 81% (71 of 88), and 90% (79 of 88) for ZCQss, ZCQpf, and ZCQps, respectively. Leg and back pain success rates were 80% (68 of 85) and 65% (55 of 85), respectively, and the success rate for ODI was 65% (57 of 88). Percentage improvements over baseline were 42%, 39%, 75%, 66%, and 58% for ZCQss, ZCQpf, leg and back pain VAS, and ODI, respectively (all P <0.001). Within-group effect sizes were classified as very large for four of five clinical outcomes (ie, >1.0; all P <0.0001). Seventy-five percent of IPD patients were free from reoperation, revision, or supplemental fixation at their index level at 5 years. After 5 years of follow-up, IPD with a stand-alone spacer provides sustained clinical benefit.

Efficacy of transverse tripolar spinal cord stimulator for the relief of chronic low back pain from failed back surgery.

PubMed

Buvanendran, Asokumar; Lubenow, Timothy J

2008-01-01

Failed back surgery syndrome is a common clinical entity for which spinal cord stimulation has been found to be an effective mode of analgesia, but with variable success rates. To determine if focal stimulation of the dorsal columns with a transverse tripolar lead might achieve deeper penetration of the electrical stimulus into the spinal cord and therefore provide greater analgesia to the back. Case report. We describe a 42-year-old female with failed back surgery syndrome that had greater back pain than leg pain. The tripolar lead configuration was achieved by placing percutaneously an octapolar lead in the spinal midline followed by 2 adjacent quadripolar leads, advanced to the T7-T10 vertebral bodies. Tripolar stimulation pattern resulted in more than 70% pain relief in this patient during the screening trial, while stimulation of one or 2 electrodes only provided 20% pain relief. After implantation of a permanent tripolar electrode system with a single rechargeable battery, the pain relief was maintained for one year. This is case report describing a case of a patient with chronic low back pain with a diagnosis of failed back surgery syndrome in which transverse tripolar stimulation using an octapolar and 2 quadripolar leads appeared to be beneficial. The transverse tripolar system consists of a central cathode surrounded by anodes, using 3 leads. This arrangement may contribute to maximum dorsal column stimulation with minimal dorsal root stimulation and provide analgesia to the lower back.

Making Better Lives: Patient-Focused Care for Low Back Pain (LBP)

ClinicalTrials.gov

2018-03-26

Chronic Low Back Pain; Hip Ostearthritis; Myofascial Pain Syndrome; Fibromyalgia; Depression; Maladaptive Coping; Lumbar Spinal Stenosis; Insomnia; Sacroiliac Joint Pain; Lateral Hip and Thigh Pain; Anxiety; Dementia; Recent Leg Length Discrepancy

[The role of brain-derived neurotrophic factor in pain facilitation and spinal mechanism in rat model of bone cancer pain].

PubMed

Wang, Li-na; Yang, Jian-ping; Ji, Fu-hai; Wang, Xiu-yun; Zuo, Jian-ling; Xu, Qi-nian; Jia, Xiao-ming; Zhou, Jing; Ren, Chun-guang; Li, Wei

2011-05-10

To investigate the role of brain-derived neurotrophic factor (BDNF) in pain facilitation and spinal mechanisms in the rat model of bone cancer pain. The bone cancer pain model was developed by inoculated Walker 256 mammary gland carcinoma cells into the tibia medullary cavity. Sixty SD female rats were divided into 5 groups (n = 12 each) randomly; group I: control group (sham operation); group II: model group; group III: control group + anti-BDNF intrathecal (i.t.); group IV: model group + control IgG i.t.; group V: model group + anti-BDNF i.t.. Anti-BDNF or control IgG was injected i.t. during 7 to 9th day. Von-Frey threshold was measured one day before operation and every 2 days after operation. On the 9th day after threshold tested, rats were sacrificed after i.t. injection of either anti-BDNF or control IgG, the lumbar 4-6 spinal cord was removed. The expression of the spinal BDNF and the phosphorylation of extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) were detected by immunohistochemistry assay and Western-Blot. Co-expression pattern of BDNF and p-ERK1/2 were determined by double-labeling immunofluorescence. We demonstrated the coexistence of BDNF and p-ERK1/2 in the spinal cord of rats. From the 7 to 9th day after operation, von-Frey threshold in groups II and IV was significantly lower than that in group I and group V (P < 0.01), group V was remarkly higher than that in group IV (P < 0.01). The spinal BDNF and p-ERK1/2 expression in group II or IV were significantly increased compared with that in group I or V (P < 0.01), intrathecal anti-BDNF was significantly suppressed BDNF and p-ERK1/2 expression (P < 0.01). BDNF and p-ERK1/2 was coexistence in the spinal cord of rats, and it maybe involved in the bone cancer pain.

Chronic pain experience and pain management in persons with spinal cord injury in Nepal.

PubMed

Thapa, Sagun; Kitrungrote, Luppana; Damkliang, Jintana

2018-04-25

Chronic pain is the frequent and significantly challenging complications in persons with spinal cord injury (SCI). Socio-cultural background may lead people perceive and manage pain differently. The study aims to describe the chronic pain experience and pain management of SCI persons in Nepal. A descriptive cross sectional study was conducted among purposively selected sample of 120 SCI persons with chronic pain living in the eight districts of Bagmati Zone of Nepal. The data were collected using the International Spinal Cord Injury Pain Basic Data Set Version 2 (ISCIPBDS-2) and Open-ended Pain Management Questionnaire. The data were analyzed using descriptive statistics and content analysis method. The back (n=84), lower legs/feet (n=63) and buttocks/hips (n=51) was found as the common pain locations. In common, the onset of pain was found within the first 6 month of the injury. Overall pain intensity and pain interference were found to be at the moderate level. The SCI persons used pain medications and non-pharmacological pain management. Ibuprofen was the commonly used pain medication and commonly used non-pharmacological pain management methods included physical support (e.g. massage, exercise), relaxation (e.g. distraction, substance abuse), coping (e.g. acceptance, praying), and traditional herbs. SCI persons had chronic pain experience which interfered with their daily living. They used pain medications and non-pharmacological pain management methods based on their beliefs, knowledge, and community resources in Nepal. This study provides some evidence to help the team of rehabilitation professional to plan and help SCI persons with chronic pain. Based on these findings, chronic pain management intervention for SCI persons should be developed and supported continuously from hospital to home based community context of Nepal.

Efficacy and Safety of Transdermal Buprenorphine versus Oral Tramadol/Acetaminophen in Patients with Persistent Postoperative Pain after Spinal Surgery

PubMed Central

Kim, Jin-Hwan; Kim, Hak-Sun; Min, Woo-Kie; Park, Ye-Soo; Lee, Kyu-Yeol; Lee, Jung-Hee

2017-01-01

Purpose Control of persistent pain following spinal surgery is an unmet clinical need. This study compared the efficacy and safety of buprenorphine transdermal system (BTDS) to oral tramadol/acetaminophen (TA) in Korean patients with persistent, moderate pain following spinal surgery. Methods Open-label, interventional, randomized multicenter study. Adults with persistent postoperative pain (Numeric Rating Scale [NRS] ≥ 4 at 14–90 days postsurgery) were enrolled. Patients received once-weekly BTDS (n = 47; 5 μg/h titrated to 20 μg/h) or twice-daily TA (n = 40; tramadol 37.5 mg/acetaminophen 325 mg, one tablet titrated to 4 tablets) for 6 weeks. The study compared pain reduction with BTDS versus TA at week 6. Quality of life (QoL), treatment satisfaction, medication compliance, and adverse events (AEs) were assessed. Findings At week 6, both groups reported significant pain reduction (mean NRS change: BTDS −2.02; TA −2.76, both P < 0.0001) and improved QoL (mean EQ-5D index change: BTDS 0.10; TA 0.19, both P < 0.05). The BTDS group achieved better medication compliance (97.8% versus 91.0%). Incidence of AEs (26.1% versus 20.0%) and adverse drug reactions (20.3% versus 16.9%) were comparable between groups. Implications For patients with persistent pain following spinal surgery, BTDS is an alternative to TA for reducing pain and supports medication compliance. This trial is registered with Clinicaltrials.gov: NCT01983111. PMID:29056859

Impact of Behavioral Control on the Processing of Nociceptive Stimulation

PubMed Central

Grau, James W.; Huie, J. Russell; Garraway, Sandra M.; Hook, Michelle A.; Crown, Eric D.; Baumbauer, Kyle M.; Lee, Kuan H.; Hoy, Kevin C.; Ferguson, Adam R.

2012-01-01

How nociceptive signals are processed within the spinal cord, and whether these signals lead to behavioral signs of neuropathic pain, depends upon their relation to other events and behavior. Our work shows that these relations can have a lasting effect on spinal plasticity, inducing a form of learning that alters the effect of subsequent nociceptive stimuli. The capacity of lower spinal systems to adapt, in the absence of brain input, is examined in spinally transected rats that receive a nociceptive shock to the tibialis anterior muscle of one hind leg. If shock is delivered whenever the leg is extended (controllable stimulation), it induces an increase in flexion duration that minimizes net shock exposure. This learning is not observed in subjects that receive the same amount of shock independent of leg position (uncontrollable stimulation). These two forms of stimulation have a lasting, and divergent, effect on subsequent learning: controllable stimulation enables learning whereas uncontrollable stimulation disables it (learning deficit). Uncontrollable stimulation also enhances mechanical reactivity. We review evidence that training with controllable stimulation engages a brain-derived neurotrophic factor (BDNF)-dependent process that can both prevent and reverse the consequences of uncontrollable shock. We relate these effects to changes in BDNF protein and TrkB signaling. Controllable stimulation is also shown to counter the effects of peripheral inflammation (from intradermal capsaicin). A model is proposed that assumes nociceptive input is gated at an early sensory stage. This gate is sensitive to current environmental relations (between proprioceptive and nociceptive input), allowing stimulation to be classified as controllable or uncontrollable. We further propose that the status of this gate is affected by past experience and that a history of uncontrollable stimulation will promote the development of neuropathic pain. PMID:22934018

Spinal activation of alpha7-nicotinic acetylcholine receptor attenuates posttraumatic stress disorder-related chronic pain via suppression of glial activation.

PubMed

Sun, Rao; Zhang, Wei; Bo, Jinhua; Zhang, Zuoxia; Lei, Yishan; Huo, Wenwen; Liu, Yue; Ma, Zhengliang; Gu, Xiaoping

2017-03-06

The high prevalence of chronic pain in posttraumatic stress disorder (PTSD) individuals has been widely reported by clinical studies, which emphasized an urgent need to uncover the underlying mechanisms and identify potential therapeutic targets. Recent studies suggested that targeting activated glia and their pro-inflammatory products may provide a novel and effective therapy for the stress-related pain. In this study, we investigated whether activation of alpha-7 nicotinic acetylcholine receptor (α7 nAChR), a novel anti-inflammatory target, could attenuate PTSD-related chronic pain. The experiments were conducted in a rat model of single prolonged stress (SPS), an established model of PTSD-pain comorbidity. We found that SPS exposure produced persistent mechanical allodynia. Immunohistochemical and enzyme-linked immuno sorbent assay analysis showed that SPS also induced elevated activation of glia cells (including microglia and astrocytes) and accumulation of pro-inflammatory cytokines in spinal cord. In another experiment, we found that intrathecal injection of PHA-543613, a selective α7 nAchR agonist, attenuated the SPS-evoked allodynia in a dose dependent manner. However, this anti-hyperalgesic effect was blocked by pretreatment with methyllycaconitine (MLA), a selective α7 nAchR antagonist. Further analyses showed that PHA-543613 suppressed SPS-induced spinal glial activation and SPS-elevated spinal pro-inflammatory cytokines, and these were abolished by MLA. Taken together, the present study showed that spinal activation of α7 nAChR by PHA-543613 attenuated mechanical allodynia induced by PTSD-like stress, and the suppression of spinal glial activation may underlie this anti-hyperalgesic effect. Our study demonstrated the therapeutic potential of targeting α7 nAChR in the treatment of PTSD-related chronic pain. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Rapamycin suppresses microglial activation and reduces the development of neuropathic pain after spinal cord injury.

PubMed

Tateda, Satoshi; Kanno, Haruo; Ozawa, Hiroshi; Sekiguchi, Akira; Yahata, Kenichiro; Yamaya, Seiji; Itoi, Eiji

2017-01-01

Rapamycin is an inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway, plays an important role in multiple cellular functions. Our previous study showed rapamycin treatment in acute phase reduced the neural tissue damage and locomotor impairment after spinal cord injury (SCI). However, there has been no study to investigate the therapeutic effect of rapamycin on neuropathic pain after SCI. In this study, we examined whether rapamycin reduces neuropathic pain following SCI in mice. We used a mouse model of thoracic spinal cord contusion injury, and divided the mice into the rapamycin-treated and the vehicle-treated groups. The rapamycin-treated mice were intraperitoneally injected with rapamycin (1 mg/kg) 4 h after SCI. The rapamycin treatment suppressed phosphorylated-p70S6K in the injured spinal cord that indicated inhibition of mTOR. The rapamycin treatment significantly improved not only locomotor function, but also mechanical and thermal hypersensitivity in the hindpaws after SCI. In an immunohistochemical analysis, Iba-1-stained microglia in the lumbar spinal cord was significantly decreased in the rapamycin-treated mice. In addition, the activity of p38 MAPK in the lumbar spinal cord was significantly attenuated by rapamycin treatment. Furthermore, phosphorylated-p38 MAPK-positive microglia was relatively decreased in the rapamycin-treated mice. These results indicated rapamycin administration in acute phase to reduce secondary neural tissue damage can contribute to the suppression of the microglial activation in the lumbar spinal cord and attenuate the development of neuropathic pain after SCI. The present study first demonstrated that rapamycin has significant therapeutic potential to reduce the development of neuropathic pain following SCI. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:93-103, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Reversal of pathological pain through specific spinal GABAA receptor subtypes.

PubMed

Knabl, Julia; Witschi, Robert; Hösl, Katharina; Reinold, Heiko; Zeilhofer, Ulrike B; Ahmadi, Seifollah; Brockhaus, Johannes; Sergejeva, Marina; Hess, Andreas; Brune, Kay; Fritschy, Jean-Marc; Rudolph, Uwe; Möhler, Hanns; Zeilhofer, Hanns Ulrich

2008-01-17

Inflammatory diseases and neuropathic insults are frequently accompanied by severe and debilitating pain, which can become chronic and often unresponsive to conventional analgesic treatment. A loss of synaptic inhibition in the spinal dorsal horn is considered to contribute significantly to this pain pathology. Facilitation of spinal gamma-aminobutyric acid (GABA)ergic neurotransmission through modulation of GABA(A) receptors should be able to compensate for this loss. With the use of GABA(A)-receptor point-mutated knock-in mice in which specific GABA(A) receptor subtypes have been selectively rendered insensitive to benzodiazepine-site ligands, we show here that pronounced analgesia can be achieved by specifically targeting spinal GABA(A) receptors containing the alpha2 and/or alpha3 subunits. We show that their selective activation by the non-sedative ('alpha1-sparing') benzodiazepine-site ligand L-838,417 (ref. 13) is highly effective against inflammatory and neuropathic pain yet devoid of unwanted sedation, motor impairment and tolerance development. L-838,417 not only diminished the nociceptive input to the brain but also reduced the activity of brain areas related to the associative-emotional components of pain, as shown by functional magnetic resonance imaging in rats. These results provide a rational basis for the development of subtype-selective GABAergic drugs for the treatment of chronic pain, which is often refractory to classical analgesics.

Spinal cord stimulation for treatment of meralgia paresthetica.

PubMed

Barna, Steven A; Hu, M Melvin; Buxo, Carlos; Trella, Jason; Cosgrove, G Rees

2005-07-01

Meralgia paresthetica is a clinical syndrome of pain, dysesthesia or both, in the anterolateral thigh. It is associated with an entrapment mononeuropathy of the lateral femoral cutaneous nerve. Diagnosis of meralgia paresthetica is typically made clinically and is based on the characteristic location of pain or dysesthesia, sensory abnormality on exam, and absence of any other neurological abnormality in the leg. The majority of patients with meralgia paresthetica respond well to conservative treatment. To present a case of intractable meralgia paresthetica in which conservative treatment options failed but which was successfully treated with a spinal cord stimulator. A 44-year-old woman presented to the pain clinic with a one-year history of bilateral anterolateral thigh pain. History, physical exam, and diagnostic work-up were consistent with meralgia paresthetica. Multiple medications, physical therapy, and chiropractic therapy were not successful for this patient. In addition, local anesthetic/steroid injection of the lateral femoral cutaneous nerve provided only short-term relief. Ultimately, a spinal cord stimulator was implanted after a successful temporary percutaneous trial. Two months after the implantation, she continued to have 100% pain relief, worked full-time, was physically active, and no longer required any pain medication including opioids. An implanted spinal cord stimulator may be an ideal treatment for intractable meralgia paresthetica after conservative treatments have failed because it is not destructive and can always be explanted without significant permanent adverse effects.

Measuring pain phenomena after spinal cord injury: Development and psychometric properties of the SCI-QOL Pain Interference and Pain Behavior assessment tools.

PubMed

Cohen, Matthew L; Kisala, Pamela A; Dyson-Hudson, Trevor A; Tulsky, David S

2018-05-01

To develop modern patient-reported outcome measures that assess pain interference and pain behavior after spinal cord injury (SCI). Grounded-theory based qualitative item development; large-scale item calibration field-testing; confirmatory factor analyses; graded response model item response theory analyses; statistical linking techniques to transform scores to the Patient Reported Outcome Measurement Information System (PROMIS) metric. Five SCI Model Systems centers and one Department of Veterans Affairs medical center in the United States. Adults with traumatic SCI. N/A. Spinal Cord Injury - Quality of Life (SCI-QOL) Pain Interference item bank, SCI-QOL Pain Interference short form, and SCI-QOL Pain Behavior scale. Seven hundred fifty-seven individuals with traumatic SCI completed 58 items addressing various aspects of pain. Items were then separated by whether they assessed pain interference or pain behavior, and poorly functioning items were removed. Confirmatory factor analyses confirmed that each set of items was unidimensional, and item response theory analyses were used to estimate slopes and thresholds for the items. Ultimately, 7 items (4 from PROMIS) comprised the Pain Behavior scale and 25 items (18 from PROMIS) comprised the Pain Interference item bank. Ten of these 25 items were selected to form the Pain Interference short form. The SCI-QOL Pain Interference item bank and the SCI-QOL Pain Behavior scale demonstrated robust psychometric properties. The Pain Interference item bank is available as a computer adaptive test or short form for research and clinical applications, and scores are transformed to the PROMIS metric.

Attenuation of Persistent Experimental Pancreatitis Pain by a Bradykinin B2 Receptor Antagonist

PubMed Central

Chen, Qingmin; Vera-Portocarrero, Louis P.; Ossipov, Michael H.; Vardanyan, Marina; Lai, Josephine; Porreca, Frank

2017-01-01

Objective The role of bradykinin (BK) receptors in activating and sensitizing peripheral nociceptors is well known. Recently, we showed that spinal dynorphin was pronociceptive through direct or indirect BK receptor activation. Here, we explored the potential role of BK receptors in pain associated with persistent pancreatitis in rats. Methods Experimental pancreatitis and abdominal hypersensitivity were induced by intravenous administrations of dibutyltin dichloride (DBTC). [des-Arg9-Leu8]BK (B1 antagonist) and HOE 140 (B2 antagonist) were given by intraperitoneal or intrathecal injection. Dynorphin antiserum was given intrathecally. Reverse transcription–polymerase chain reaction was used to detect spinal mRNA for BK receptors. Results Dibutyltin dichloride–induced pancreatitis upregulated B1 and B2 mRNA in the thoracic dorsal root ganglion and B2, but not B1, in the pancreas. No changes in spinal B1 or B2 mRNA were observed. Intraperitoneal or intrathecal administration of HOE 140 dose dependently abolished DBTC-induced abdominal hypersensitivity, whereas [des-Arg9-Leu8]BK was without effect by either route of administration. Antiserum to dynorphin (intrathecal) abolished DBTC-induced hypersensitivity. Conclusions These results suggest that blockade of peripheral or spinal BK B2 receptors may be an effective approach for diminishing pain associated with pancreatitis. Moreover, it is suggested that spinal dynorphin may maintain pancreatitis pain through direct or indirect activation of BK B2 receptors in the spinal cord. PMID:20531238

Principles of management of osteometabolic disorders affecting the aging spine.

PubMed

Hadjipavlou, Alexander G; Katonis, Paul G; Tzermiadianos, Michael N; Tsoukas, George M; Sapkas, George

2003-10-01

Osteoporosis is the most common contributing factor of spinal fractures, which characteristically are not generally known to produce spinal cord compression symptoms. Recently, an increasing number of medical reports have implicated osteoporotic fractures as a cause of serious neurological deficit and painful disabling spinal deformities. This has been corroborated by the present authors as well. These complications are only amenable to surgical management, requiring instrumentation. Instrumenting an osteoporotic spine, although a challenging task, can be accomplished if certain guidelines for surgical techniques are respected. Neurological deficits respond equally well to an anterior or posterior decompression, provided this is coupled with multisegmental fixation of the construct. With the steady increase in the elderly population, it is anticipated that the spine surgeon will face serious complications of osteoporotic spines more frequently. With regard to surgery, however, excellent correction of deformities can be achieved, by combining anterior and posterior approaches. Paget's disease of bone (PD) is a non-hormonal osteometabolic disorder and the spine is the second most commonly affected site. About one-third of patients with spinal involvement exhibit symptoms of clinical stenosis. In only 12-24% of patients with PD of the spine is back pain attributed solely to PD, while in the majority of patients, back pain is either arthritic in nature or a combination of a pagetic process and coexisting arthritis. In this context, one must be certain before attributing low back pain to PD exclusively, and antipagetic medical treatment alone may be ineffective. Neural element dysfunction may be attributed to compressive myelopathy by pagetic bone overgrowth, pagetic intraspinal soft tissue overgrowth, ossification of epidural fat, platybasia, spontaneous bleeding, sarcomatous degeneration and vertebral fracture or subluxation. Neural dysfunction can also result from spinal ischemia when blood is diverted by the so-called "arterial steal syndrome". Because the effectiveness of pharmacologic treatment for pagetic spinal stenosis has been clearly demonstrated, surgical decompression should only be instituted after failure of antipagetic medical treatment. Surgery is indicated as a primary treatment when neural compression is secondary to pathologic fractures, dislocations, spontaneous epidural hematoma, syringomyelia, platybasia, or sarcomatous transformation. Five classes of drugs are available for the treatment of PD. Bisphosphonates are the most popular antipagetic drug and several forms have been investigated.

Spinal Cord Diseases

MedlinePlus

... spinal muscular atrophy Symptoms vary but might include pain, numbness, loss of sensation and muscle weakness. These symptoms can occur around the spinal cord, and also in other areas such as your arms and legs. Treatments often include medicines and surgery.

[Spinal cord stimulation (SCS) as a treatment for the spread phenomenon related to complex regional pain syndrome type- I (CRPS-I )].

PubMed

Goto, Shinichi; Taira, Takaomi; Hori, Tomokatsu

2009-09-01

The authors describe an experience of spinal cord stimulation (SCS) in a 30-year-old woman who developed complex regional pain syndrome type-I (CRPS-I) with spread phenomenon. She had received lumbar SCS under a diagnosis of CRPS-I in her left leg for 8 years. She had refractory pain in her right arm for the recent two years. There was no new lesion explaining her refractory pain on physical or radiological examination. Thus, the pain in her right upper arm was considered as spread phenomenon of CRPS-I. Test stimulation with cervical epidural spinal electrode showed good results and the pulse generator was implanted. It is suggested that the symptom of CRPS-I involving spread phenomenon was possibly due to a cortical reorganization. But a certain effect of SCS may be contributing to the favorable results of test stimulation for the treatment of CRPS-I with spread phenomenon in this case.

Control of cancer pain by epidural infusion of morphine.

PubMed

Waterman, N G; Hughes, S; Foster, W S

1991-10-01

Pain that cannot be controlled by traditional oral and parenteral methods in those patients with advanced cancer can be alleviated by spinal administration of narcotics. Epidural and intrathecal infusion with morphine causes analgesia by blocking spinal receptors without significant long-term central nervous, gastrointestinal, and genitourinary system effects. Of the total of 33 patients, epidural catheters inserted in 20 patients then connected by a subcutaneous tunnel to a continuous infusion system. Implanted pumps were used in each of these patients. Because of the cost and limitations of the implanted pumps, epidural catheters were connected, either directly or by subcutaneous reservoirs, to external ambulatory infusion pumps in the remaining 13 patients. Patient assessment by a linear analogue scale to measure pain levels determined that 23 of the 33 total patients (70%) had excellent or good relief of pain. The delivery of spinal administration of narcotics to treat intractable cancer pain in patients is safe. Most importantly, this method of delivery can be used in community hospitals, in outpatient settings, and in home health care programs.

Improvement in pain after lumbar surgery in cancer patients with mechanical radiculopathy.

PubMed

Moliterno, Jennifer; Veselis, Clinton A; Hershey, Michael A; Lis, Eric; Laufer, Ilya; Bilsky, Mark H

2014-10-01

Lumbar metastases can result in spinal instability and mechanical radiculopathy, characterized by radicular pain produced by axial loading. This pain pattern represents a definitive symptom of neoplastic instability and may serve as a reliable indication for surgical stabilization. We examined the results of surgical decompression and fixation in the treatment of mechanical radiculopathy. A retrospective clinical study. An internally maintained spine neurosurgery database was queried between February 2002 and April 2010. Patients were identified and deemed eligible for inclusion in this study based on the presence of all the following: metastatic tumor, lumbar surgery, and lumbar radiculopathy. Visual analog scale (VAS) of pain and Eastern Cooperative Oncology Group (ECOG) status. The Memorial Sloan-Kettering Cancer Center Department of Neurosurgery operative database was queried over an 8-year period to identify all patients with spinal metastases who underwent lumbar surgery. Only patients whose operative indication included mechanical radiculopathy were included. Pre- and postoperative pain was assessed with the VAS of pain, whereas pre- and postoperative performance status was evaluated using the ECOG. Fifty-five patients were included in the cohort. L2 and L3 were the most common levels involved, and most patients underwent multilevel posterior decompression and instrumented fusion. After surgery, 98% of patients reported pain relief. A significant difference between average pre- and postoperative pain scores was found (p<.01). Overall, 41.5% of patients experienced improvement in their ECOG score postoperatively. Mechanical radiculopathy in patients with spinal metastases represents a highly reliable surgical indication. Spinal decompression and fixation is an effective treatment for pain palliation in this patient population. Copyright © 2014 Elsevier Inc. All rights reserved.

A comprehensive yoga programs improves pain, anxiety and depression in chronic low back pain patients more than exercise: an RCT.

PubMed

Tekur, P; Nagarathna, R; Chametcha, S; Hankey, Alex; Nagendra, H R

2012-06-01

Previously, outpatient Yoga programs for patients with chronic low back pain (CLBP) lasting several months have been found to reduce pain, analgesic requirement and disability, and improve spinal mobility. This study evaluated changes in pain, anxiety, depression and spinal mobility for CLBP patients on short-term, residential Yoga and physical exercise programs, including comprehensive yoga lifestyle modifications. A seven day randomized control single blind active study in an residential Holistic Health Centre in Bangalore, India, assigned 80 patients (37 female, 43 male) with CLBP to yoga and physical exercise groups. The Yoga program consisted of specific asanas and pranayamas for back pain, meditation, yogic counselling, and lectures on yoga philosophy. The control group program included physical therapy exercises for back pain, and matching counselling and education sessions. Group×time interactions (p<0.05) and between group differences (p<0.05) were significant in all variables. Both groups' scores on the numerical rating scale for pain reduced significantly, 49% in Yoga (p<0.001, ES=1.62), 17.5% in controls (p=0.005, ES=0.67). State anxiety (STAI) reduced 20.4% (p<0.001, ES=0.72) and trait anxiety 16% (p<0.001, ES=1.09) in the yoga group. Depression (BDI) decreased in both groups, 47% in yoga (p<0.001, ES=0.96,) and 19.9% in controls (p<0.001, ES=0.59). Spinal mobility ('Sit and Reach' instrument) improved in both groups, 50%, in yoga (p<0.001, ES=2.99) and 34.6% in controls (p<0.001, ES=0.81). Seven days intensive residential Yoga program reduces pain, anxiety, and depression, and improves spinal mobility in patients with CLBP more effectively than physiotherapy exercises. Copyright © 2012 Elsevier Ltd. All rights reserved.

Management of neuropathic pain following spinal cord injury: now and in the future.

PubMed

Siddall, P J

2009-05-01

To provide an overview of our current understanding of the problem of neuropathic pain following spinal cord injury (SCI) and to suggest possible therapeutic options in the near future. Original research articles, reviews and book chapters on the subject of pain and SCI. Neuropathic pain following SCI has presented a challenge not only for traditional concepts of how pain occurs but also for more recent conceptualizations. We have made substantial progress in identifying the common types of pain that occur following SCI, determining the prevalence and characteristics of pain, investigating some of the pathophysiological changes in the nervous system that may contribute to the presence of neuropathic SCI pain and examining the effectiveness of some treatments. However major challenges remain. We still need to reach consensus on an SCI pain taxonomy; our understanding of mechanisms and the relative contribution of changes in the periphery, spinal cord and brain is incompletely understood; there are few studies that indicate effective treatment options, particularly for neuropathic SCI pain; and treatment of the biological and psychological contributors to pain is often fragmented. Recent studies suggest the potential usefulness of new treatment approaches such as selective pharmacological agents, application of novel neurostimulation techniques and the use of cognitive approaches to modify the pain experience. Our increasing understanding of the problem combined with the promise of these new approaches offers hope for improved management of neuropathic pain following SCI in the near future.

Effect of Pain Neuroscience Education Combined With Cognition-Targeted Motor Control Training on Chronic Spinal Pain: A Randomized Clinical Trial.

PubMed

Malfliet, Anneleen; Kregel, Jeroen; Coppieters, Iris; De Pauw, Robby; Meeus, Mira; Roussel, Nathalie; Cagnie, Barbara; Danneels, Lieven; Nijs, Jo

2018-04-16

Effective treatments for chronic spinal pain are essential to reduce the related high personal and socioeconomic costs. To compare pain neuroscience education combined with cognition-targeted motor control training with current best-evidence physiotherapy for reducing pain and improving functionality, gray matter morphologic features, and pain cognitions in individuals with chronic spinal pain. Multicenter randomized clinical trial conducted from January 1, 2014, to January 30, 2017, among 120 patients with chronic nonspecific spinal pain in 2 outpatient hospitals with follow-up at 3, 6, and 12 months. Participants were randomized into an experimental group (combined pain neuroscience education and cognition-targeted motor control training) and a control group (combining education on back and neck pain and general exercise therapy). Primary outcomes were pain (pressure pain thresholds, numeric rating scale, and central sensitization inventory) and function (pain disability index and mental health and physical health). There were 22 men and 38 women in the experimental group (mean [SD] age, 39.9 [12.0] years) and 25 men and 35 women in the control group (mean [SD] age, 40.5 [12.9] years). Participants in the experimental group experienced reduced pain (small to medium effect sizes): higher pressure pain thresholds at primary test site at 3 months (estimated marginal [EM] mean, 0.971; 95% CI, -0.028 to 1.970) and reduced central sensitization inventory scores at 6 months (EM mean, -5.684; 95% CI, -10.589 to -0.780) and 12 months (EM mean, -6.053; 95% CI, -10.781 to -1.324). They also experienced improved function (small to medium effect sizes): significant and clinically relevant reduction of disability at 3 months (EM mean, -5.113; 95% CI, -9.994 to -0.232), 6 months (EM mean, -6.351; 95% CI, -11.153 to -1.550), and 12 months (EM mean, -5.779; 95% CI, -10.340 to -1.217); better mental health at 6 months (EM mean, 36.496; 95% CI, 7.998-64.995); and better physical health at 3 months (EM mean, 39.263; 95% CI, 9.644-66.882), 6 months (EM mean, 53.007; 95% CI, 23.805-82.209), and 12 months (EM mean, 32.208; 95% CI, 2.402-62.014). Pain neuroscience education combined with cognition-targeted motor control training appears to be more effective than current best-evidence physiotherapy for improving pain, symptoms of central sensitization, disability, mental and physical functioning, and pain cognitions in individuals with chronic spinal pain. Significant clinical improvements without detectable changes in brain gray matter morphologic features calls into question the relevance of brain gray matter alterations in this population. clinicaltrials.gov Identifier: NCT02098005.

Systematic reviews of physical and rehabilitation medicine Cochrane contents. Part 1. Disabilities due to spinal disorders and pain syndromes in adults.

PubMed

Negrini, S; Imperio, G; Villafañe, J H; Negrini, F; Zaina, F

2013-08-01

This article is the first in a series presenting the strongest published evidence for physical and rehabilitation medicine (PRM) to date coming from the Cochrane Collaboration. The intent of the series is to stimulate ideas for reviews and research in neglected areas of PRM. To systematically review the rehabilitation contents of the Cochrane Collaboration on disabilities due to spinal disorders or pain syndromes in adults. The Cochrane Database of Systematic Reviews was searched at the end of June 2013 for articles relevant for PRM about disabilities resulting from spinal disorders or pain syndromes in adults. Retrieved papers were classified according to the PRM approach: active therapies, which require active participation by patients to achieve treatment goals, and passive treatments, which rely on the application of external forces. The quality of the reviews was checked against the AMSTAR checklist. Reviews on spinal disorders or pain syndromes were found in the Cochrane Back Group (CBG) and in the Pain, Palliative and Supportive Care Group (CPPSCG). Thirty-eight (42.8%) of 89 Cochrane reviews in the CBG and 7 (2.4%) of 293 Cochrane reviews in the CPPSCG were included. All were of high quality (range, 8-11 points out of 11 on the AMSTAR checklist). The contents of the reviews are given in detail. This review presents an overview of the current evidence for PRM in the treatment of disabilities due to spinal disorders or pain syndromes in adults. Within PRM there is ample space for research in the Cochrane Collaboration and for producing original studies (randomized controlled trials [RCTs]). To apply evidence-based clinical practice, clinicians must be familiar with the current best evidence.

Effectiveness of Global Postural Re-education for Treatment of Spinal Disorders: A Meta-analysis.

PubMed

Lomas-Vega, Rafael; Garrido-Jaut, María Victoria; Rus, Alma; Del-Pino-Casado, Rafael

2017-02-01

The aim of this study was to investigate the effects of global postural re-education (GPR) on the treatment of spinal disorders by performing a systematic review and a meta-analysis. MEDLINE, Scopus, and PEDro databases were searched without language or publication date restrictions. Data on pain and function were used to evaluate the effectiveness of GPR. Randomized controlled trials and controlled clinical trials analyzing the effectiveness of GPR on spinal disorders were selected. The standardized mean difference (SMD) and the corresponding 95% confidence interval (95% CI) were calculated. The meta-analysis was performed using the Comprehensive Meta-analysis 3.3 software. Seven randomized controlled trials and 4 controlled clinical trials were included in the meta-analysis. The results showed a medium improvement on pain (SMD = -0.63; 95% CI, -0.43 to -0.83) and function (SMD = -0.48; 95% CI, -0.25 to -0.72) after GPR treatment. The positive effect, which was greater in patients with ankylosing spondylitis followed by low back pain and neck pain, was more significant during the intermediate follow-up than immediately after treatment. This meta-analysis provides reliable evidence that GPR may be an effective method for treating spinal disorders by decreasing pain and improving function.

Quantifying the Nonlinear, Anisotropic Material Response of Spinal Ligaments

NASA Astrophysics Data System (ADS)

Robertson, Daniel J.

Spinal ligaments may be a significant source of chronic back pain, yet they are often disregarded by the clinical community due to a lack of information with regards to their material response, and innervation characteristics. The purpose of this dissertation was to characterize the material response of spinal ligaments and to review their innervation characteristics. Review of relevant literature revealed that all of the major spinal ligaments are innervated. They cause painful sensations when irritated and provide reflexive control of the deep spinal musculature. As such, including the neurologic implications of iatrogenic ligament damage in the evaluation of surgical procedures aimed at relieving back pain will likely result in more effective long-term solutions. The material response of spinal ligaments has not previously been fully quantified due to limitations associated with standard soft tissue testing techniques. The present work presents and validates a novel testing methodology capable of overcoming these limitations. In particular, the anisotropic, inhomogeneous material constitutive properties of the human supraspinous ligament are quantified and methods for determining the response of the other spinal ligaments are presented. In addition, a method for determining the anisotropic, inhomogeneous pre-strain distribution of the spinal ligaments is presented. The multi-axial pre-strain distributions of the human anterior longitudinal ligament, ligamentum flavum and supraspinous ligament were determined using this methodology. Results from this work clearly demonstrate that spinal ligaments are not uniaxial structures, and that finite element models which account for pre-strain and incorporate ligament's complex material properties may provide increased fidelity to the in vivo condition.

Intraoperative direct puncture and embolization (IOPE) using a glue material for spinal cord arteriovenous fistula: a case report.

PubMed

Shin, Hong Kyung; Suh, Dae Chul; Jeon, Sang Ryong

2015-05-01

Spinal arteriovenous fistula (AVF) is treated by embolization or surgery. However, transarterial embolization or surgery is difficult in rare cases when the fistula site is very complicated to access especially as in fistular nidus supplied by posterior and anterior spinal artery. We present the case which was treated with intraoperative direct puncture and embolization (IOPE) using glue material, since the usual transarterial or transvenous neurointerventional approach was difficult to embolize the AVF. A 36-year-old woman presented with progressive leg weakness and pain after a 20-year history of lower back pain. She had pelvic and spinal AVF combined with arteriovenous malformation (AVM). Despite prior treatment of the pelvic lesion with radiotherapy and coil embolization, the spinal lesion persisted and caused repeated subarachnoid hemorrhages. A spinal angiogram revealed a tortuous and long feeder of the AVF which had growing venous sac, as well as AVM. Two embolization trials failed because of the long tortuosity and associated anterior spinal artery. Four months later, drastic leg weakness and pain occurred, and IOPE was performed using a glue material. The subsequent recovery of the patient was rapid. One month later, the use of a strong opioid could be discontinued, and the patient could walk with aid. A follow-up spinal angiogram revealed that the venous sac of the AVF had disappeared. In spinal AVF which is not feasible to access by usual intervention approach and to dissect surgically, IOPE with glue material can be considered for the treatment.

[Pain therapy].

PubMed

Donnadieu, S; Djian, M C

1998-12-12

NEW OPIOID ANALGESICS: Progress in pain reliet has recently been achieved with the introduction of new opioid analgesics such as tramadol and the pediatric preparation of codeine phosphate as well as powerful long-release opioids which can be administered per os, or percutaneously for transdermal fentanyl. CO-ANALGESICS: Other drugs, mainly antidepressants and anti-convulsants, can be usefully combined with analgesics. New serotonin uptake inhibitors and anticonvulsants (gabapentin and lamotrigin) have the advantage of better tolerance. None of these drugs has marketing approval in France for their pain relieving effects. The same is true for clonidine and neostigmine which, after spinal infusion, potentialize opioids and for ketamine which can relieve neuropathy pain by dissociative anesthesia. NEW ANTI-MIGRAINE DRUGS: New drugs have been developed for specific types of pain such as migraine. The new "triptans" are tolerated better than sumatriptan and is reimbursed by the national social security. REFRACTORY NEUROPATHY PAIN: Indications for electrical stimulation techniques conducted in a neurosurgery unit have been identified. Stimulators may be implanted in spinal or supra-spinal localizations. REGULATORY ASPECTS: New legislation has reorganized health care for pain relief in France. The new texts take into consideration personnel training, the health care network and progress in therapeutics.

Radiosurgery for the treatment of spinal lung metastases.

PubMed

Gerszten, Peter C; Burton, Steven A; Belani, Chandra P; Ramalingam, Suresh; Friedland, David M; Ozhasoglu, Cihat; Quinn, Annette E; McCue, Kevin J; Welch, William C

2006-12-01

Spinal metastases are a common source of pain as well as neurologic deficit in patients with lung cancer. Metastases from lung cancer traditionally have been believed to be relatively responsive to radiation therapy. However, conventional external beam radiotherapy lacks the precision to allow delivery of large single-fraction doses of radiation and simultaneously limit the dose to radiosensitive structures such as the spinal cord. The current study evaluated the efficacy of single-fraction radiosurgery for the treatment of spinal lung cancer metastases. In the current prospective cohort evaluation, 87 lung cancer metastases to the spine in 77 patients were treated with a single-fraction radiosurgery technique with a follow-up period of 6 to 40 months (median, 12 months). The indication for radiosurgery treatment was pain in 73 cases, as a primary treatment modality in 7 cases, for radiographic tumor progression in 4 cases, and for progressive neurologic deficit in 3 cases. Tumor volume ranged from 0.2 to 264 cm(3) (mean, 25.7 cm(3)). The maximum tumor dose was maintained at 15 to 25 grays (Gy) (mean, 20 Gy; median, 20 Gy). No radiation-induced toxicity occurred during the follow-up period. Long-term axial and radicular pain improvement occurred in 65 of 73 patients (89%) who were treated primarily for pain. Long-term radiographic tumor control was observed in all patients who underwent radiosurgery as their primary treatment modality or for radiographic tumor progression. Spinal radiosurgery was found to be feasible, safe, and clinically effective for the treatment of spinal metastases from lung cancer. The results of the current study indicate the potential of radiosurgery in the treatment of patients with spinal lung metastases, especially those with solitary sites of spine involvement, to improve long-term palliation. (c) 2006 American Cancer Society.

A prospective double blinded randomized study of anterior cruciate ligament reconstruction with hamstrings tendon and spinal anesthesia with or without femoral nerve block.

PubMed

Astur, Diego Costa; Aleluia, Vinicius; Veronese, Ciro; Astur, Nelson; Oliveira, Saulo Gomes; Arliani, Gustavo Gonçalves; Badra, Ricardo; Kaleka, Camila Cohen; Amaro, Joicemar Tarouco; Cohen, Moisés

2014-10-01

Current literature supports the thought that anesthesia and analgesia administered perioperatively for an anterior cruciate ligament (ACL) reconstruction have a great influence on time to effective rehabilitation during the first week after hospital discharge. The aim of this study is to answer the research question is there a difference in clinical outcomes between the use of a femoral nerve block with spinal anesthesia versus spinal analgesia alone for people undergoing ACL reconstruction? ACL reconstruction with spinal anesthesia and patient sedation (Group one); and spinal anesthesia with patient sedation and an additional femoral nerve block (Group two). Patients were re-evaluated for pain, range of motion (ROM), active contraction of the quadriceps, and a Functional Independence Measure (FIM) scoring scale. Spinal anesthesia with a femoral nerve block demonstrates pain relief 6h after surgery (VAS 0.37; p=0.007). From the third (VAS=4.56; p=0.028) to the seventh (VAS=2.87; p=0.05) days after surgery, this same nerve blockage delivered higher pain scores. Patients had a similar progressive improvement on knee joint range of motion with or without femoral nerve block (p<0.002). Group one and two had 23.75 and 24.29° 6h after surgery and 87.81 and 85.36° of knee flexion after 48h post op. Spinal anesthesia associated with a femoral nerve block had no additional benefits on pain control after the third postoperative day. There were no differences between groups concerning ability for knee flexion and to complete daily activities during postoperative period. Randomized Clinical Trial Level I. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of Localized Cold Therapy on Pain in Postoperative Spinal Fusion Patients: A Randomized Control Trial.

PubMed

Quinlan, Patricia; Davis, Jack; Fields, Kara; Madamba, Pia; Colman, Lisa; Tinca, Daniela; Cannon Drake, Regina

Cold therapy used in the sports medicine settings has been found to be effective in reducing postoperative pain; however, there are limited studies that examine the effect of cold therapy on postoperative pain in patients with posterior lumbar spinal fusion. The purpose of this study was to determine the effects of cold on postoperative spine pain and add to the body of knowledge specific to practical application of cold therapy in the spine surgery setting. Researchers used a two-group randomized control design to evaluate the effects of local cold therapy on postoperative pain and analgesia use after lumbar spinal fusion surgery. The primary outcome was postoperative pain. Secondary outcomes included analgesia use and perceived benefit of cold therapy. The intervention (cold) group had a marginally greater reduction in mean Numerical Rating Scale score across all 12 pain checks (M ± SD = -1.1 ± 0.8 points reduction vs. -1.0 ± 0.8 points reduction, p = .589). On average, the intervention group used less morphine equivalents (M ± SD = 12.6 ± 31.5 vs. 23.7 ± 40.0) than the control group across pain checks seven to 12 (p = .042). This study provides additional evidence to support the use of cold therapy as an adjuvant pain management strategy to optimize pain control and reduce opioid consumption following spine fusion surgical procedures.

Targeting central plasticity: a new direction of finding painkillers.

PubMed

Zhuo, Min

2005-01-01

It is well documented that sensory transmission, including pain, receives endogenous inhibitory modulatory influences at dorsal horn of the spinal cord. Recent results, from behavioral to molecular studies, demonstrate that injury caused plastic changes in forebrain areas. In addition to encoding pain, these supraspinal areas may also affect pain transmission in the spinal cord level by activating "top-down" descending facilitatory systems. In this review, I provide review of evidence related to these new progresses, from human brain imaging to work from genetically mutant mice.

Interrater reliability of the Korean version of the International Spinal Cord Injury Basic Pain Data Set.

PubMed

Kim, H R; Kim, H B; Lee, B S; Ko, H Y; Shin, H I

2014-11-01

To provide a Korean translation of the International Spinal Cord Injury Basic Pain Data Set (ISCIBPDS) and evaluate the interrater reliability of the translated version. Survey of community-dwelling people with spinal cord injury (SCI) in South Korea. The initial translation was performed by two translators with an in-depth knowledge of SCI, and was then checked by another person with a similar background. A total of 115 SCI participants (87 men, 28 women; 48.4±14.1 years) were evaluated using the Korean version of the ISCIBPDS by two different raters. Intraclass correlation coefficient (ICC) or Cohen's kappa (κ) was used for analysis. All 115 participants had at least one pain problem on both surveys. Seventeen (14.8%) participants described their pain as a single pain problem to one rater while reporting the same pain as two or more different pain problems to the other rater. Twenty-two (19.1%) other participants reported their pain problems in a different order of severity on the surveys. The Korean version of the ISCIBPDS had acceptable interrater reliability, except in the 'limit activities (how much do you limit your activities in order to keep your pain from getting worse?)' item (ICC=0.318). Provision of criteria for pain separation may facilitate the consistent application of ISCIBPDS. In addition, the ISCIBPDS, which evaluated pain problems separately, reflected the multiple and complex characteristics of SCI-related pain; this was a strength of this data set.

Spinal cord stimulation: Current applications for treatment of chronic pain.

PubMed

Vannemreddy, Prasad; Slavin, Konstantin V

2011-01-01

Spinal cord stimulation (SCS) is thought to relieve chronic intractable pain by stimulating nerve fibers in the spinal cord. The resulting impulses in the fibers may inhibit the conduction of pain signals to the brain, according to the pain gate theory proposed by Melzack and Wall in 1965 and the sensation of pain is thus blocked. Although SCS may reduce pain, it will not eliminate it. After a period of concern about safety and efficacy, SCS is now regaining popularity among pain specialists for the treatment of chronic pain. The sympatholytic effect of SCS is one of its most interesting therapeutic properties. This effect is considered responsible for the effectiveness of SCS in peripheral ischemia, and at least some cases of complex regional pain syndrome. The sympatholytic effect has also been considered part of the management of other chronic pain states such as failed back surgery syndrome, phantom pain, diabetic neuropathy, and postherpetic neuralgia. In general, SCS is part of an overall treatment strategy and is used only after the more conservative treatments have failed. The concept of SCS has evolved rapidly following the technological advances that have produced leads with multiple contact electrodes and battery systems. The current prevalence of patients with chronic pain requiring treatment other than conventional medical management has significantly increased and so has been the need for SCS. With the cost benefit analysis showing significant support for SCS, it may be appropriate to offer this as an effective alternative treatment for these patients.

Minimally invasive surgical treatment of Bertolotti's Syndrome: case report.

PubMed

Ugokwe, Kene T; Chen, Tsu-Lee; Klineberg, Eric; Steinmetz, Michael P

2008-05-01

This article aims to provide more insight into the presentation, diagnosis, and treatment of Bertolotti's syndrome, which is a rare spinal disorder that is very difficult to recognize and diagnose correctly. The syndrome was first described by Bertolotti in 1917 and affects approximately 4 to 8% of the population. It is characterized by an enlarged transverse process at the most caudal lumbar vertebra with a pseudoarticulation of the transverse process and the sacral ala. It tends to present with low back pain and may be confused with facet and sacroiliac joint disease. In this case report, we describe a 40-year-old man who presented with low back pain and was eventually diagnosed with Bertolotti's syndrome. The correct diagnosis was made based on imaging studies which included computed tomographic scans, plain x-rays, and magnetic resonance imaging scans. The patient experienced temporary relief when the abnormal pseudoarticulation was injected with a cocktail consisting of lidocaine and steroids. In order to minimize the trauma associated with surgical treatment, a minimally invasive approach was chosen to resect the anomalous transverse process with the accompanying pseudoarticulation. The patient did well postoperatively and had 97% resolution of his pain at 6 months after surgery. As with conventional surgical approaches, a complete knowledge of anatomy is required for minimally invasive spine surgery. This case is an example of the expanding utility of minimally invasive approaches in treating spinal disorders.

Protrusion of a rod into the spinal canal 10 years after segmental lumbar spine surgery.

PubMed

Cai, Siyi; Kong, Xiangyi; Yan, Chengrui; Wang, Yipeng; Wan, Xueshuai; Zhang, Jialu; Qiu, Guixing; Yu, Keyi

2017-03-01

The objective of this article is to report an unusual case of a spinal rod that protruded into the spinal canal after lumbar spine surgery.Only 4 cases of spinal rod migration with protrusion into the spinal canal have been reported. This is the first report of a case involving the use of posterior low lumbar segmental instrumentation with a screw-rod system. The left side of the rod gradually migrated and finally protruded into the canal and compressed the cord.A 60-year-old woman presented with pain and numbness of the posterior aspect of the left leg after a long-distance walk. Intermittent claudication became worse, and she developed pain and numbness in the perineal region. An x-ray showed that the left side of a spinal rod among the segmental spinal instruments that had been placed 10 years previously had protruded into the spinal canal.We removed the rod and decompressed the canal at the level of L5-S1. The patient became totally asymptomatic.Rods used as spinal instrumentation have the possibility of protruding into the spinal canal and endangering the nervous system. Long-term follow-up with radiological examinations should be conducted upon completion of spinal operations conducting using instrumentation.

Emerging Role of Spinal Cord TRPV1 in Pain Exacerbation

PubMed Central

Choi, Seung-In; Lim, Ji Yeon; Yoo, Sungjae; Kim, Hyun; Hwang, Sun Wook

2016-01-01

TRPV1 is well known as a sensor ion channel that transduces a potentially harmful environment into electrical depolarization of the peripheral terminal of the nociceptive primary afferents. Although TRPV1 is also expressed in central regions of the nervous system, its roles in the area remain unclear. A series of recent reports on the spinal cord synapses have provided evidence that TRPV1 plays an important role in synaptic transmission in the pain pathway. Particularly, in pathologic pain states, TRPV1 in the central terminal of sensory neurons and interneurons is suggested to commonly contribute to pain exacerbation. These observations may lead to insights regarding novel synaptic mechanisms revealing veiled roles of spinal cord TRPV1 and may offer another opportunity to modulate pathological pain by controlling TRPV1. In this review, we introduce historical perspectives of this view and details of the recent promising results. We also focus on extended issues and unsolved problems to fully understand the role of TRPV1 in pathological pain. Together with recent findings, further efforts for fine analysis of TRPV1's plastic roles in pain synapses at different levels in the central nervous system will promote a better understanding of pathologic pain mechanisms and assist in developing novel analgesic strategies. PMID:26885404

Upregulated TLR3 Promotes Neuropathic Pain by Regulating Autophagy in Rat With L5 Spinal Nerve Ligation Model.

PubMed

Chen, Weijia; Lu, Zhijun

2017-02-01

Microglia, rapidly activated following peripheral nerve injury (PNI), accumulate within the spinal cord and adopt inflammation that contributes to development and maintenance of neuropathic pain. Microglia express functional Toll-like receptors (TLRs), which play pivotal roles in regulating inflammatory processes. However, little is known about the role of TLR3 in regulating neuropathic pain after PNI. Here TLR3 expression and autophagy activation was assayed in dorsal root ganglions and in microglia following PNI by using realtime PCR, western blot and immunohistochemistry. The role of TLR3/autophagy signaling in regulating tactile allodynia was evaluated by assaying paw mechanical withdrawal threshold and cold allodynia after intrathecal administration of Poly (I:C) and 3-methyladenine (3-MA). We found that L5 spinal nerve ligation (SNL) induces the expression of TLR3 in dorsal root ganglions and in primary rat microglia at the mRNA and protein level. Meanwhile, L5 SNL results in an increased activation of autophagy, which contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of Poly (I:C), a TLR3 agonist, significantly increases the activation of microglial autophagy, whereas TLR3 knockdown markedly inhibits L5 SNL-induced microglial autophagy. Poly (I:C) treatment promotes the expression of proinflammatory mediators, whereas 3-MA (a specific inhibitor of autophagy) suppresses Poly (I:C)-induced secretion of proinflammatory cytokines. Autophagy inhibition further inhibits TLR3-mediated mechanical and cold hypersensitivity following SNL. These results suggest that inhibition of TLR3/autophagy signaling contributes to alleviate neurophathic pain triggered by SNL.

Peripheral input and its importance for central sensitization.

PubMed

Baron, Ralf; Hans, Guy; Dickenson, Anthony H

2013-11-01

Many pain states begin with damage to tissue and/or nerves in the periphery, leading to enhanced transmitter release within the spinal cord and central sensitization. Manifestations of this central sensitization are windup and long-term potentiation. Hyperexcitable spinal neurons show reduced thresholds, greater evoked responses, increased receptive field sizes, and ongoing stimulus-independent activity; these changes probably underlie the allodynia, hyperalgesia, and spontaneous pain seen in patients. Central sensitization is maintained by continuing input from the periphery, but also modulated by descending controls, both inhibitory and facilitatory, from the midbrain and brainstem. The projections of sensitized spinal neurons to the brain, in turn, alter the processing of painful messages by higher centers. Several mechanisms contribute to central sensitization. Repetitive activation of primary afferent C fibers leads to a synaptic strengthening of nociceptive transmission. It may also induce facilitation of non-nociceptive Aβ fibers and nociceptive Aδ fibers, giving rise to dynamic mechanical allodynia and mechanical hyperalgesia. In postherpetic neuralgia and complex regional pain syndrome, for example, these symptoms are maintained and modulated by peripheral nociceptive input. Diagnosing central sensitization can be particularly difficult. In addition to the medical history, quantitative sensory testing and functional magnetic resonance imaging may be useful, but diagnostic criteria that include both subjective and objective measures of central augmentation are needed. Mounting evidence indicates that treatment strategies that desensitize the peripheral and central nervous systems are required. These should generally involve a multimodal approach, so that therapies may target the peripheral drivers of central sensitization and/or the central consequences. © 2013 American Neurological Association.

Association of pain, social support and socioeconomic indicators in patients with spinal cord injury in Iran.

PubMed

Khazaeipour, Z; Ahmadipour, E; Rahimi-Movaghar, V; Ahmadipour, F; Vaccaro, A R; Babakhani, B

2017-02-01

Descriptive cross-sectional study. Pain is a prevalent complication of individuals with spinal cord injury (SCI). Our objective was to examine the association between social support, socioeconomic factors and psychosocial factors and pain to develop more effective management strategies. Brain and Spinal Cord Injury Research (BASIR) Center, Tehran University of Medical Sciences, Tehran, Iran. The Persian version of the Brief Pain Inventory was used to measure the pain, and the Multidimensional Scale of Perceived Social Support was used to measure social support through structured face-to-face interviews in SCI individuals. The overall prevalence of pain was 50.7%; 79.3% of individuals had bilateral pain, with lower limbs and back being the most common location. The quality of pain was described as aching (41.4%), tingling (32.9%), pressure (15.7%), coldness (5.7%) and feeling electric shock sensations (4.3%). The frequency of pain in individuals with paraplegia (60.9% vs 45.7%) and incomplete (53.5% vs 52.5%) SCI was higher than with other types of neurological injuries. Patients with a medium level of education had the least pain and those with good economic situation reported higher frequency of having pain (P=0.034). There was no significant relationship between pain and social support. There was a positive correlation between pain and impairment of mood, normal work, relations with other people and lack of sleep (P<0.001). These novel findings will inform the development of strategies to manage pain by improving access to health-care facilities and supplies.

Utilization of mechanical diagnosis and therapy (MDT) for the treatment of lumbar pain in the presence of known lumbar transverse process fractures: a case study

PubMed Central

Elenburg, J. L.; Foley, B. S.; Roberts, K.; Bayliss, A. J.

2016-01-01

Background Spinal fractures are typically considered a contraindication to mechanical diagnosis and therapy (MDT). Objective and importance The purpose of this case study is to illustrate how MDT was used safely and effectively to treat lumbar pain in a patient with multiple lumbar transverse process fractures. Clinical presentation The subject was a 24-year-old female with left L2-5 transverse process fractures, sustained 10 weeks prior in a pedestrian versus motor vehicle accident. Intervention (and technique) After collaboration with her physiatrist, an MDT examination revealed a presentation consistent with the lumbar derangement syndrome. Conclusion After three visits, utilizing patient generated forces with the extension principle of treatment, her pain, Oswestry disability index (ODI) score, and function all improved. PMID:27559276

The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the Neuromodulation Appropriateness Consensus Committee.

PubMed

Deer, Timothy R; Mekhail, Nagy; Provenzano, David; Pope, Jason; Krames, Elliot; Leong, Michael; Levy, Robert M; Abejon, David; Buchser, Eric; Burton, Allen; Buvanendran, Asokumar; Candido, Kenneth; Caraway, David; Cousins, Michael; DeJongste, Michael; Diwan, Sudhir; Eldabe, Sam; Gatzinsky, Kliment; Foreman, Robert D; Hayek, Salim; Kim, Philip; Kinfe, Thomas; Kloth, David; Kumar, Krishna; Rizvi, Syed; Lad, Shivanand P; Liem, Liong; Linderoth, Bengt; Mackey, Sean; McDowell, Gladstone; McRoberts, Porter; Poree, Lawrence; Prager, Joshua; Raso, Lou; Rauck, Richard; Russo, Marc; Simpson, Brian; Slavin, Konstantin; Staats, Peter; Stanton-Hicks, Michael; Verrills, Paul; Wellington, Joshua; Williams, Kayode; North, Richard

2014-08-01

The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications. The NACC used literature reviews, expert opinion, clinical experience, and individual research. Authors consulted the Practice Parameters for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain (2006), systematic reviews (1984 to 2013), and prospective and randomized controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google Scholar. Neurostimulation is relatively safe because of its minimally invasive and reversible characteristics. Comparison with medical management is difficult, as patients considered for neurostimulation have failed conservative management. Unlike alternative therapies, neurostimulation is not associated with medication-related side effects and has enduring effect. Device-related complications are not uncommon; however, the incidence is becoming less frequent as technology progresses and surgical skills improve. Randomized controlled studies support the efficacy of spinal cord stimulation in treating failed back surgery syndrome and complex regional pain syndrome. Similar studies of neurostimulation for peripheral neuropathic pain, postamputation pain, postherpetic neuralgia, and other causes of nerve injury are needed. International guidelines recommend spinal cord stimulation to treat refractory angina; other indications, such as congestive heart failure, are being investigated. Appropriate neurostimulation is safe and effective in some chronic pain conditions. Technological refinements and clinical evidence will continue to expand its use. The NACC seeks to facilitate the efficacy and safety of neurostimulation. © 2014 International Neuromodulation Society.

Spinal cord stimulation for the treatment of chronic back pain patients: 500-Hz vs. 1000-Hz burst stimulation.

PubMed

Van Havenbergh, Tony; Vancamp, Tim; Van Looy, Pieter; Vanneste, Sven; De Ridder, Dirk

2015-01-01

Spinal cord stimulation is a commonly used, safe, and effective procedure applied for medically intractable failed back surgery syndrome, as well as other neuropathic pain syndromes. Recently, a novel stimulation paradigm called burst stimulation has been developed that is paresthesia-free and has a more pronounced suppressive effect on neuropathic pain. Fifteen patients who were being treated with burst spinal cord stimulation for failed back surgery syndrome participated in an open-label trial to verify whether their pain suppression could be further ameliorated by changing the burst pattern. Burst stimulation with packets of five electrical pulses delivered at 500 Hz with 1000-μsec pulse width 40 times per second was changed to burst mode delivering five spikes at 1000 Hz with 500-μsec pulse width 40 times a second. As the amplitudes did not differ between the two groups, the total delivery of current to the spinal cord was not different between the two modes of burst stimulation. Scores on visual analog scales for pain and paresthesia, the Pain Catastrophizing Scale, the Pain Vigilance and Awareness Questionnaire, and the Short Form 36 quality of life measurement were compared between the two modes of burst stimulation. [Correction added on 06 Feb 2015, after first online publication: this paragraph has been revised to signify the comparison of amplitudes between two groups] No statistically significant differences were found between the two modes of stimulation. The results suggest that increasing the frequency from 500 to 1000 Hz while keeping the pulse width constant does not add any extra benefit in suppressing pain. Further studies should verify whether increasing the frequency above 1000 Hz has a similar lack of effect. © 2014 International Neuromodulation Society.

Finite Element Analysis of the Effect of Epidural Adhesions.

PubMed

Lee, Nam; Ji, Gyu Yeul; Yi, Seong; Yoon, Do Heum; Shin, Dong Ah; Kim, Keung Nyun; Ha, Yoon; Oh, Chang Hyun

2016-07-01

It is well documented that epidural adhesion is associated with spinal pain. However, the underlying mechanism of spinal pain generation by epidural adhesion has not yet been elucidated. To elucidate the underlying mechanism of spinal pain generation by epidural adhesion using a two-dimensional (2D) non-linear finite element (FE) analysis. A finite element analysis. A two-dimensional nonlinear FE model of the herniated lumbar disc on L4/5 with epidural adhesion. A two-dimensional nonlinear FE model of the lumbar spine was developed, consisting of intervertebral discs, dura, spinal nerve, and lamina. The annulus fibrosus and nucleus pulpous were modeled as hyperelastic using the Mooney-Rivlin equation. The FE mesh was generated and analyzed using Abaqus (ABAQUS 6.13.; Hibbitt, Karlsson & Sorenson, Inc., Providence, RI, USA). Epidural adhesion was simulated as rough contact, in which no slip occurred once two surfaces were in contact, between the dura mater and posterior annulus fibrosus. The FE model of adhesion showed significant stress concentration in the spinal nerves, especially on the dorsal root ganglion (DRG). The stress concentration was caused by the lack of adaptive displacement between the dura mater and posterior annulus fibrosus. The peak von Mises stress was higher in the epidural adhesion model (Adhesion, 0.67 vs. Control, 0.46). In the control model, adaptive displacement was observed with decreased stress in the spinal nerve and DRG (with adhesion, 2.59 vs. without adhesion, 3.58, P < 0.00). This study used a 2D non-linear FE model, which simplifies the 3D nature of the human intervertebral disc. In addition, this 2D non-linear FE model has not yet been validated. The current study clearly demonstrated that epidural adhesion causes significantly increased stress in the spinal nerves, especially at the DRG. We believe that the increased stress on the spinal nerve might elicit more pain under similar magnitudes of lumbar disc protrusion.

Effect of electroacupuncture on the cervicospinal P2X7 receptor/fractalkine/CX3CR1 signaling pathway in a rat neck-incision pain model.

PubMed

Gao, Y H; Li, C W; Wang, J Y; Tan, L H; Duanmu, C L; Jing, X H; Chang, X R; Liu, J L

2017-06-01

Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation. EA stimulation was applied to bilateral LI18, LI4-PC6, or ST36-GB34. The thermal pain threshold, cervicospinal ATP concentration, expression levels of purinergic P2XR and P2YR subunits mRNAs, and fractalkine, CX3CR1 and p38 MAPK proteins, were detected separately. The neck incision induced strong thermal hyperalgesia and upregulation of spinal ATP within 48 h. No significant change was found in thermal hyperalgesia after a single session of EA intervention. However, a single session of EA dramatically enhanced the neck incision-induced upregulation of ATP and upregulated the expression of P2X7R, which was reversed by two sessions of EA. Two sessions of EA at bilateral LI18 or LI4-PC6 attenuated hyperalgesia significantly, accompanied with downregulation of P2X7R/fractalkine/ CX3CR1 signaling after three sessions of EA. EA stimulation of LI18 or LI4-PC6 alleviates thermal hyperalgesia in neck-incision pain rats, which may be associated with its effects in regulating the neck incision-induced increase of ATP and P2X7R and subsequently suppressing fractalkine/CX3CR1 signaling in the cervical spinal cord.

Management of lumbar spinal stenosis.

PubMed

Lurie, Jon; Tomkins-Lane, Christy

2016-01-04

Lumbar spinal stenosis (LSS) affects more than 200,000 adults in the United States, resulting in substantial pain and disability. It is the most common reason for spinal surgery in patients over 65 years. Lumbar spinal stenosis is a clinical syndrome of pain in the buttocks or lower extremities, with or without back pain. It is associated with reduced space available for the neural and vascular elements of the lumbar spine. The condition is often exacerbated by standing, walking, or lumbar extension and relieved by forward flexion, sitting, or recumbency. Clinical care and research into lumbar spinal stenosis is complicated by the heterogeneity of the condition, the lack of standard criteria for diagnosis and inclusion in studies, and high rates of anatomic stenosis on imaging studies in older people who are completely asymptomatic. The options for non-surgical management include drugs, physiotherapy, spinal injections, lifestyle modification, and multidisciplinary rehabilitation. However, few high quality randomized trials have looked at conservative management. A systematic review concluded that there is insufficient evidence to recommend any specific type of non-surgical treatment. Several different surgical procedures are used to treat patients who do not improve with non-operative therapies. Given that rapid deterioration is rare and that symptoms often wax and wane or gradually improve, surgery is almost always elective and considered only if sufficiently bothersome symptoms persist despite trials of less invasive interventions. Outcomes (leg pain and disability) seem to be better for surgery than for non-operative treatment, but the evidence is heterogeneous and often of limited quality. © BMJ Publishing Group Ltd 2015.

Predicting Postsurgical Satisfaction in Adolescents With Idiopathic Scoliosis: The Role of Presurgical Functioning and Expectations.

PubMed

Sieberg, Christine B; Manganella, Juliana; Manalo, Gem; Simons, Laura E; Hresko, M Timothy

2017-12-01

There is a need to better assess patient satisfaction and surgical outcomes. The purpose of the current study is to identify how preoperative expectations can impact postsurgical satisfaction among youth with adolescent idiopathic scoliosis undergoing spinal fusion surgery. The present study includes patients with adolescent idiopathic scoliosis undergoing spinal fusion surgery enrolled in a prospective, multicentered registry examining postsurgical outcomes. The Scoliosis Research Society Questionnaire-Version 30, which assesses pain, self-image, mental health, and satisfaction with management, along with the Spinal Appearance Questionnaire, which measures surgical expectations was administered to 190 patients before surgery and 1 and 2 years postoperatively. Regression analyses with bootstrapping (with n=5000 bootstrap samples) were conducted with 99% bias-corrected confidence intervals to examine the extent to which preoperative expectations for spinal appearance mediated the relationship between presurgical mental health and pain and 2-year postsurgical satisfaction. Results indicate that preoperative mental health, pain, and expectations are predictive of postsurgical satisfaction. With the shifting health care system, physicians may want to consider patient mental health, pain, and expectations before surgery to optimize satisfaction and ultimately improve clinical care and patient outcomes. Level I-prognostic study.

Comparative short-term effects of two thoracic spinal manipulation techniques in subjects with chronic mechanical neck pain: a randomized controlled trial.

PubMed

Casanova-Méndez, Amaloha; Oliva-Pascual-Vaca, Angel; Rodriguez-Blanco, Cleofás; Heredia-Rizo, Alberto Marcos; Gogorza-Arroitaonandia, Kristobal; Almazán-Campos, Ginés

2014-08-01

Spinal Manipulation (SM) has been purported to decrease pain and improve function in subjects with non-specific neck pain. Previous research has investigated which individuals with non-specific neck pain will be more likely to benefit from SM. It has not yet been proven whether or not the effectiveness of thoracic SM depends on the specific technique being used. This double-blind randomized trial has compared the short-term effects of two thoracic SM maneuvers in subjects with chronic non-specific neck pain. Sixty participants were distributed randomly into two groups. One group received the Dog technique (n = 30), with the subject in supine position, and the other group underwent the Toggle-Recoil technique (n = 30), with the participant lying prone, T4 being the targeted area in both cases. Evaluations were made of self-reported neck pain (Visual Analogue Scale); neck mobility (Cervical Range of Motion); and pressure pain threshold at the cervical and thoracic levels (C4 and T4 spinous process) and over the site described for location of tense bands of the upper trapezius muscle. Measurements were taken before intervention, immediately afterward, and 20 min later. Both maneuvers improved neck mobility and mechanosensitivity and reduced pain in the short term. No major or clinical differences were found between the groups. In the between-groups comparison slightly better results were observed in the Toggle-Recoil group only for cervical extension (p = 0.009), right lateral flexion (p = 0.004) and left rotation (p < 0.05). Copyright © 2014 Elsevier Ltd. All rights reserved.

Involvement of peripheral and spinal tumor necrosis factor α in spinal cord hyperexcitability during knee joint inflammation in rats.

PubMed

König, Christian; Zharsky, Maxim; Möller, Christian; Schaible, Hans-Georg; Ebersberger, Andrea

2014-03-01

Tumor necrosis factor α (TNFα) is produced not only in peripheral tissues, but also in the spinal cord. The purpose of this study was to address the potential of peripheral and spinal TNFα to induce and maintain spinal hyperexcitability, which is a hallmark of pain states in the joints during rheumatoid arthritis and osteoarthritis. In vivo recordings of the responses of spinal cord neurons to nociceptive knee input under normal conditions and in the presence of experimental knee joint inflammation were obtained in anesthetized rats. TNFα, etanercept, or antibodies to TNF receptors were applied to either the knee joint or the spinal cord surface. Injection of TNFα into the knee joint cavity increased the responses of spinal cord neurons to mechanical joint stimulation, and injection of etanercept into the knee joint reduced the inflammation-evoked spinal activity. These spinal effects closely mirrored the induction and reduction of peripheral sensitization. Responses to joint stimulation were also enhanced by spinal application of TNFα, and spinal application of either etanercept or anti-TNF receptor type I significantly attenuated the generation of inflammation-evoked spinal hyperexcitability, which is characterized by widespread pain sensitization beyond the inflamed joint. Spinally applied etanercept did not reduce established hyperexcitability in the acute kaolin/carrageenan model. In antigen-induced arthritis, etanercept decreased spinal responses on day 1, but not on day 3. While peripheral TNFα increases spinal responses to joint stimulation, spinal TNFα supports the generation of the full pattern of spinal hyperexcitability. However, established spinal hyperexcitability may be maintained by downstream mechanisms that are independent of spinal TNFα. Copyright © 2014 by the American College of Rheumatology.

Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors.

PubMed

Olson, William; Abdus-Saboor, Ishmail; Cui, Lian; Burdge, Justin; Raabe, Tobias; Ma, Minghong; Luo, Wenqin

2017-10-12

The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying regional differences in processing nociception, we sparsely traced non-peptidergic nociceptors across the body using a newly generated Mrgprd CreERT2 mouse line. We found that mouse plantar paw skin is also innervated by a low density of Mrgprd + nociceptors, while individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the "enlarged representation" of plantar paw regions in the CNS.

Predictive parameters for the antecedent development of hip pathology associated with long segment fusions to the pelvis for the treatment of adult spinal deformity.

PubMed

Kinon, Merritt D; Nasser, Rani; Nakhla, Jonathan P; Adogwa, Owoicho; Moreno, Jessica R; Harowicz, Michael; Verla, Terence; Yassari, Reza; Bagley, Carlos A

2016-01-01

The surgical treatment of adult scoliosis frequently involves long segment fusions across the lumbosacral joints that redistribute tremendous amounts of force to the remaining mobile spinal segments as well as to the pelvis and hip joints. Whether or not these forces increase the risk of femoral bone pathology remains unknown. The aim of this study is to determine the correlation between long segment spinal fusions to the pelvis and the antecedent development of degenerative hip pathologies as well as what predictive patient characteristics, if any, correlate with their development. A retrospective chart review of all long segment fusions to the pelvis for adult degenerative deformity operated on by the senior author at the Duke Spine Center from February 2008 to March 2014 was undertaken. Enrolment criteria included all available demographic, surgical, and clinical outcome data as well as pre and postoperative hip pathology assessment. All patients had prospectively collected outcome measures and a minimum 2-year follow-up. Multivariable logistic regression analysis was performed comparing the incidence of preoperative hip pain and antecedent postoperative hip pain as a function of age, gender, body mass index (BMI), and number of spinal levels fused. In total, 194 patients were enrolled in this study. Of those, 116 patients (60%) reported no hip pain prior to surgery. Eighty-three patients (71.6%) remained hip pain free, whereas 33 patients (28.5%) developed new postoperative hip pain. Age, gender, and BMI were not significant among those who went on to develop hip pain postoperatively ( P < 0.0651, 0.3491, and 0.1021, respectively). Of the 78 patients with preoperative hip pain, 20 patients (25.6%) continued to have hip pain postoperatively, whereas 58 patients reported improvement in the hip pain after long segment fusion for correction of their deformity, a 74.4% rate of reduction. Age, gender, and BMI were not significant among those who continued to have hip pain postoperatively ( P < 0.4386, 0.4637, and 0.2545, respectively). Number of levels fused was not a significant factor in the development of hip pain in either patient population; patients without preoperative pain who developed pain postoperatively ( P < 0.1407) as well as patients with preoperative pain who continued to have pain postoperatively ( P < 0.0772). This study demonstrates that long segment lumbosacral fusions are not associated with an increase in postoperative hip pathology. Age, gender, BMI, and levels fused do not correlate with the development of postoperative hip pain. The restoration of spinal alignment with long segment fusions may actually decrease the risk of developing femoral bone pathology and have a protective effect on the hip.

Effects of chronic shoulder pain on quality of life and occupational engagement in the population with chronic spinal cord injury: preparing for the best outcomes with occupational therapy.

PubMed

Silvestri, Jennifer

2017-01-01

Purpose To examine the implications of chronic shoulder pain on quality of life and occupational engagement in spinal cord injury (SCI). The Ecology of Human Performance Model and Self-Efficacy Theory will be used to further examine the interplay of shoulder pain, quality of life and engagement in this population. Method Analysis of literature. Results Persons with SCI have a high prevalence of shoulder pain and injury, affecting 37-84% of analysed studies; chronic pain limits occupational engagement and decreases quality of life. Remediation of pain provides improved occupational engagement, functional independence and quality of life in those with high self-efficacy and low depression. Conclusion Shoulder pain is a serious complication following SCI and the Ecology of Human Performance Model and Self-Efficacy Theory can be utilized in conjunction for a framework to evaluate, treat and prevent shoulder pain and its devastating effects on occupational engagement and quality of life in the spinal cord injured population. Thereafter, rehabilitation professionals will have a greater understanding of these interactions to serve as a guide for evaluation and intervention planning to promote optimal occupational engagement through limiting the experiences of occupational injustices for those with SCI and shoulder pain. Implications for Rehabilitation Musculoskeletal pain at the shoulder joint and depression are common complications following spinal cord injury that limit occupational engagement and decrease quality of life. To increase engagement and quality of life in this population, treatments need to address all factors including the under-lying psychosocial instead of task and environment modification alone. The Ecology of Human Performance Model and Self-efficacy Theory are effective frameworks that can be used for evaluation, treatment planning and outcome measurement to maximize occupational engagement and quality of life.

Effects of self-hypnosis training and EMG biofeedback relaxation training on chronic pain in persons with spinal-cord injury.

PubMed

Jensen, Mark P; Barber, Joseph; Romano, Joan M; Hanley, Marisol A; Raichle, Katherine A; Molton, Ivan R; Engel, Joyce M; Osborne, Travis L; Stoelb, Brenda L; Cardenas, Diana D; Patterson, David R

2009-07-01

Thirty-seven adults with spinal-cord injury and chronic pain were randomly assigned to receive 10 sessions of self-hypnosis (HYP) or EMG biofeedback relaxation (BIO) training for pain management. Participants in both treatment conditions reported substantial, but similar, decreases in pain intensity from before to after the treatment sessions. However, participants in the HYP condition, but not the BIO condition, reported statistically significant decreases in daily average pain pre- to posttreatment. These pre- to posttreatment decreases in pain reported by the HYP participants were maintained at 3-month follow-up. Participants in the HYP condition, but not the BIO condition, also reported significant pre- to posttreatment increases in perceived control over pain, but this change was not maintained at the 3-month follow-up.

Transforaminal Percutaneous Endoscopic Discectomy and Foraminoplasty after Lumbar Spinal Fusion Surgery.

PubMed

Wu, Jian-Jun; Chen, Hui-Zhen; Zheng, Changkun

2017-07-01

The most common causes of pain following lumbar spinal fusions are residual herniation, or foraminal fibrosis and foraminal stenosis that is ignored, untreated, or undertreated. The original surgeon may advise his patient that nothing more can be done in his opinion that the nerve was visually decompressed by the original surgery. Post-operative imaging or electrophysiological assessment may be inadequate to explain all the reasons for residual or recurrent symptoms. Treatment of failed lumbar spinal fusions by repeat traditional open revision surgery usually incorporates more extensive decompression causing increased instability and back pain. The authors, having limited their practice to endoscopic surgery over the last 10 years, report on their experience gained during that period to relieve pain by transforaminal percutaneous endoscopic revision of lumbar spinal fusions. To assess the effectiveness of transforaminal percutaneous endoscopic discectomy and foraminoplasty in patients with pain after lumbar spinal fusion. Retrospective study. Inpatient surgery center. Sixteen consecutive patients with pain after lumbar spinal fusions presenting with back and leg pain that had supporting imaging diagnosis of foraminal stenosis and/or residual/recurrent disc herniation, or whose pain complaint was supported by relief from diagnostic and therapeutic injections, were offered percutaneous transforaminal endoscopic discectomy and foraminoplasty over a repeat open procedure. Each patient sought consultation following a transient successful, partially successful or unsuccessful open lumbar spinal fusions treatment for disc herniation or spinal stenosis. Endoscopic foraminoplasty was also performed to either decompress the bony foramen in the case of foraminal stenosis, or to allow for endoscopic visual examination of the affected traversing and exiting nerve roots in the axilla. The average follow-up time was 30.3 months, minimum 12 months. Outcome data at each visit included MacNab criteria, visual analog scale (VAS), and Oswestry Disability Index (ODI). The average leg VAS improved from 9.1 ± 2.0 to 2.0 ± 0.8 (P < 0.005). Ten patients had excellent outcomes, 5 had good outcomes, one had a fair outcome, and none had poor outcomes, according to the MacNab criteria. Fifteen of 16 patients had excellent or good outcomes, for an overall success rate of 93.7%. No patients required reoperation. There were no incidental durotomies, infections, vascular, or visceral injuries. There was one complication, a case of leg numbness caused by dorsal root ganglion injury. The numbness improved after 2 weeks. After 3 months, physical exam showed that the total area of numbness in the legs had decreased. At last follow-up, the patient had no pain, and only a few areas with numbness remained that did not affect the patient's activities of daily living. The patient was relieved to be able to avoid open decompression. This is a retrospective study. The transforaminal endoscopic approach is effective for patients with back or leg pain after lumbar spinal fusions due to residual/recurrent nucleus pulposus and foraminal stenosis. Failed initial index surgery may involve failure to recognize patho-anatomy in the axilla of the foramen housing the traversing and the exiting nerve. The transforaminal endoscopic approach effectively decompresses the foramen and does not further destabilize the spine needing stabilization. It also avoids going through the previous surgical site. Full-endoscopic, foraminal stenosis, recurrent herniation, surgical treatment, fusion.

No Difference in Early Analgesia Between Liposomal Bupivacaine Injection and Intrathecal Morphine After TKA.

PubMed

Barrington, John W; Emerson, Roger H; Lovald, Scott T; Lombardi, Adolph V; Berend, Keith R

2017-01-01

Opioid analgesics have been a standard modality for postoperative pain management after total knee arthroplasty (TKA) but are also associated with increased risk of nausea, pruritus, vomiting, respiratory depression, prolonged ileus, and cognitive dysfunction. There is still a need for a method of anesthesia that can deliver effective long-term postoperative pain relief without incurring the high cost and health burden of opioids and nerve blocks. (1) Is liposomal bupivacaine-based periarticular injection (PAI) more effective than morphine-based spinal anesthesia or ropivacaine-based PAI in controlling postoperative pain after TKA? (2) Do patients treated with liposomal bupivacaine-based PAI experience fewer opioid-related adverse events compared with patients treated with morphine-based spinal anesthesia or ropivacaine-based PAI in controlling postoperative pain after TKA? This multicenter, blind trial randomized 119 patients undergoing TKA with spinal anesthesia to receive spinal anesthesia plus periarticular injection with liposomal bupivacaine (40 patients), spinal anesthesia with bupivacaine plus intrathecal morphine (41 patients) but no liposomal bupivacaine injection, or spinal anesthesia with bupivacaine (38 patients) and no liposomal bupivacaine injection. The two groups that did not receive periarticular liposomal bupivacaine did receive periarticular injection with ropivacaine, and all three groups had ketorolac (30 mg) plus epinephrine (1:1000) in the periarticular injections. Patients in all three groups received identical perioperative multimodal analgesic and antiemetic drugs. All patients were analyzed in the group to which they were randomized and no patients were lost to followup. The primary study endpoints were visual analog score (VAS) for pain and narcotic use during postoperative day 1. Secondary endpoints included side effects associated with narcotic administration during the hospital stay. Mean VAS pain in the liposomal bupivacaine PAI group was lower than that for the ropivacaine PAI group at 6 hours (1.8 ± 2.1 versus 3.3 ± 2.3, p = 0.005, mean difference: 1.5, 95% confidence interval [CI], 0.5-2.5) and 12 hours (1.5 ± 2.0 versus 3.3 ± 2.4, p < 0.001, mean difference: 1.8, 95% CI, 0.8-2.8) after surgery. The morphine spinal group had lower pain compared with the liposomal bupivacaine PAI group at 6 hours (0.9 ± 1.8 versus 1.8 ± 2.1, p = 0.035, mean difference: 1.0, 95% CI, 0.1-1.8), but there was no difference at 12 hours (0.8 ± 1.5 versus 1.5 ± 2.0, p = 0.086, mean difference: 0.7, 95% CI, -0.1 to 1.5). The magnitude of the differences at 6 and 12 hours are near the lower end of minimal clinically important differences reported in the literature, and thus the improvement shown in this study may only represent a small clinical improvement. Both the liposomal bupivacaine group (13% [five of 40]) and the ropivacaine group (5% [two of 38]) had fewer incidents of itching (pruritus) than the spinal morphine group (38% [15 of 41]) (p = 0.001). This prospective multicenter three-arm blind randomized controlled trial showed potentially improved pain control at 6 and 12 hours in the liposomal bupivacaine and intrathecal morphine groups compared with the ropivacaine group at the cost of much higher incidences of pruritus (itching) in the intrathecal morphine group. Based on these results, we prefer the use of PAI with liposomal bupivacaine as an alternative to spinal anesthesia with intrathecal morphine as a result of similar postoperative pain control and the potential for reducing adverse events. Level I, therapeutic study.

Laparoscopic cholecystectomy under spinal anesthesia: comparative study between conventional-dose and low-dose hyperbaric bupivacaine

PubMed Central

Imbelloni, Luiz Eduardo; Sant’Anna, Raphael; Fornasari, Marcos; Fialho, José Carlos

2011-01-01

Background Laparoscopic cholecystectomy has the advantages of causing less postoperative pain and requiring a short hospital stay, and therefore is the treatment of choice for cholelithiasis. This study was designed to compare spinal anesthesia using hyperbaric bupivacaine given as a conventional dose by lumbar puncture or as a low-dose by thoracic puncture. Methods A total of 140 patients with symptomatic gallstone disease were randomized to undergo laparoscopic cholecystectomy with low-pressure CO2 pneumoperitoneum under spinal anesthesia using either conventional lumbar spinal anesthesia (hyperbaric bupivacaine 15 mg and fentanyl 20 mg) or low-dose thoracic spinal anesthesia (hyperbaric bupivacaine 7.5 mg and fentanyl 20 μg). Intraoperative parameters, postoperative pain, complications, recovery time, and patient satisfaction at follow-up were compared between the two treatment groups. Results All procedures were completed under spinal anesthesia, with no cases needing conversion to general anesthesia. Values for time for block to reach the T3 dermatomal level, duration of motor and sensory block, and hypotensive events were significantly lower with low-dose bupivacaine. Postoperative pain was higher for low-dose hyperbaric bupivacaine at 6 and 12 hours. All patients were discharged after 24 hours. Follow-up 1 week postoperatively showed all patients to be satisfied and to be keen advocates of spinal anesthesia. Conclusion Laparoscopic cholecystectomy can be performed successfully under spinal anesthesia. A small dose of hyperbaric bupivacaine 7.5 mg and 20 μg fentanyl provides adequate spinal anesthesia for laparoscopy and, in comparison with hyperbaric bupivacaine 15% and fentanyl 20 μg, causes markedly less hypotension. The low-dose strategy may have an advantage in ambulatory patients because of the earlier recovery of motor and sensory function and earlier discharge. PMID:22915892

Blended-Learning Pain Neuroscience Education for People With Chronic Spinal Pain: Randomized Controlled Multicenter Trial.

PubMed

Malfliet, Anneleen; Kregel, Jeroen; Meeus, Mira; Roussel, Nathalie; Danneels, Lieven; Cagnie, Barbara; Dolphens, Mieke; Nijs, Jo

2018-05-01

Available evidence favors the use of pain neuroscience education (PNE) in patients with chronic pain. However, PNE trials are often limited to small sample sizes and, despite the current digital era, the effects of blended-learning PNE (ie, the combination of online digital media with traditional educational methods) have not yet been investigated. The study objective was to examine whether blended-learning PNE is able to improve disability, catastrophizing, kinesiophobia, and illness perceptions. This study was a 2-center, triple-blind randomized controlled trial (participants, statistician, and outcome assessor were masked). The study took place at university hospitals in Ghent and Brussels, Belgium. Participants were 120 people with nonspecific chronic spinal pain (ie, chronic neck pain and low back pain). The intervention was 3 sessions of PNE or biomedically focused back/neck school education (addressing spinal anatomy and physiology). Measurements were self-report questionnaires (Pain Disability Index, Pain Catastrophizing Scale, Tampa Scale for Kinesiophobia, Illness Perception Questionnaire, and Pain Vigilance and Awareness Questionnaire). None of the treatment groups showed a significant change in the perceived disability (Pain Disability Index) due to pain (mean group difference posteducation: 1.84; 95% CI = -2.80 to 6.47). Significant interaction effects were seen for kinesiophobia and several subscales of the Illness Perception Questionnaire, including negative consequences, cyclical time line, and acute/chronic time line. In-depth analysis revealed that only in the PNE group were these outcomes significantly improved (9% to 17% improvement; 0.37 ≤ Cohen d ≥ 0.86). Effect sizes are small to moderate, which might raise the concern of limited clinical utility; however, changes in kinesiophobia exceed the minimal detectable difference. PNE should not be used as the sole treatment modality but should be combined with other treatment strategies. Blended-learning PNE was able to improve kinesiophobia and illness perceptions in participants with chronic spinal pain. As effect sizes remained small to medium, PNE should not be used as a sole treatment but rather should be used as a key element within a comprehensive active rehabilitation program. Future studies should compare the effects of blended-learning PNE with offline PNE and should consider cost-effectiveness.

Unspecific chronic low back pain – a simple functional classification tested in a case series of patients with spinal deformities

PubMed Central

Weiss, Hans-Rudolf; Werkmann, Mario

2009-01-01

Background Up to now, chronic low back pain without radicular symptoms is not classified and attributed in international literature as being "unspecific". For specific bracing of this patient group we use simple physical tests to predict the brace type the patient is most likely to benefit from. Based on these physical tests we have developed a simple functional classification of "unspecific" low back pain in patients with spinal deformities. Methods Between January 2006 and July 2007 we have tested 130 patients (116 females and 14 males) with spinal deformities (average age 45 years, ranging from 14 years to 69) and chronic unspecific low back pain (pain for > 24 months) along with the indication for brace treatment for chronic unspecific low back pain. Some of the patients had symptoms of spinal claudication (n = 16). The "sagittal realignment test" (SRT) was applied, a lumbar hyperextension test, and the "sagittal delordosation test" (SDT). Additionally 3 female patients with spondylolisthesis were tested, including one female with symptoms of spinal claudication and 2 of these patients were 14 years of age and the other 43yrs old at the time of testing. Results 117 Patients reported significant pain release in the SRT and 13 in the SDT (>/= 2 steps in the Roland & Morris VRS). 3 Patients had no significant pain release in both of the tests (< 2 steps in the Roland & Morris VRS). Pain intensity was high (3,29) before performing the physical tests (VRS-scale 0–5) and low (1,37) while performing the physical test for the whole sample of patients. The differences where highly significant in the Wilcoxon test (z = -3,79; p < 0,0001). In the 16 patients who did not respond to the SRT in the manual investigation we found hypermobility at L5/S1 or a spondylolisthesis at level L5/S1. In the other patients who responded well to the SRT loss of lumbar lordosis was the main issue, a finding which, according to scientific literature, correlates well with low back pain. The 3 patients who did not respond to either test had a fair pain reduction in a generally delordosing brace with an isolated small foam pad inserted at the level of L 2/3, leading to a lordosation at this region. Discussion With the exception of 3 patients (2.3%) a clear distribution to one of the two classes has been possible. 117 patients were supplied successfully with a sagittal realignment test-brace (physio-logic® brace) and 13 with a sagittal delordosing brace (spondylogic® brace). There were patients with scoliosies and hyperkyphosiesbrace). Therefore a clear distribution of the patients from this sample to either chronic postural or chronic instability back pain was possible. In 2.3% a combined chronic low back pain from the findings obtained seems reasonable. Conclusion Chronic unspecific low back pain is possible to clearly be classified physically. This functional classification is necessary to decide on which specific conservative approach (physical therapy, braces) should be used. Other factors than spinal deformities contribute to chronic low back pain. PMID:19222845

Unspecific chronic low back pain - a simple functional classification tested in a case series of patients with spinal deformities.

PubMed

Weiss, Hans-Rudolf; Werkmann, Mario

2009-02-17

Up to now, chronic low back pain without radicular symptoms is not classified and attributed in international literature as being "unspecific". For specific bracing of this patient group we use simple physical tests to predict the brace type the patient is most likely to benefit from. Based on these physical tests we have developed a simple functional classification of "unspecific" low back pain in patients with spinal deformities. Between January 2006 and July 2007 we have tested 130 patients (116 females and 14 males) with spinal deformities (average age 45 years, ranging from 14 years to 69) and chronic unspecific low back pain (pain for > 24 months) along with the indication for brace treatment for chronic unspecific low back pain. Some of the patients had symptoms of spinal claudication (n = 16). The "sagittal realignment test" (SRT) was applied, a lumbar hyperextension test, and the "sagittal delordosation test" (SDT). Additionally 3 female patients with spondylolisthesis were tested, including one female with symptoms of spinal claudication and 2 of these patients were 14 years of age and the other 43yrs old at the time of testing. 117 Patients reported significant pain release in the SRT and 13 in the SDT (> or = 2 steps in the Roland & Morris VRS). 3 Patients had no significant pain release in both of the tests (< 2 steps in the Roland & Morris VRS).Pain intensity was high (3,29) before performing the physical tests (VRS-scale 0-5) and low (1,37) while performing the physical test for the whole sample of patients. The differences where highly significant in the Wilcoxon test (z = -3,79; p < 0,0001).In the 16 patients who did not respond to the SRT in the manual investigation we found hypermobility at L5/S1 or a spondylolisthesis at level L5/S1. In the other patients who responded well to the SRT loss of lumbar lordosis was the main issue, a finding which, according to scientific literature, correlates well with low back pain. The 3 patients who did not respond to either test had a fair pain reduction in a generally delordosing brace with an isolated small foam pad inserted at the level of L 2/3, leading to a lordosation at this region. With the exception of 3 patients (2.3%) a clear distribution to one of the two classes has been possible. 117 patients were supplied successfully with a sagittal realignment test-brace (physio-logic brace) and 13 with a sagittal delordosing brace (spondylogic brace). There were patients with scoliosies and hyperkyphosiesbrace). Therefore a clear distribution of the patients from this sample to either chronic postural or chronic instability back pain was possible. In 2.3% a combined chronic low back pain from the findings obtained seems reasonable. Chronic unspecific low back pain is possible to clearly be classified physically. This functional classification is necessary to decide on which specific conservative approach (physical therapy, braces) should be used.Other factors than spinal deformities contribute to chronic low back pain.

Loss of spinal substance P pain transmission under the condition of LPA1 receptor-mediated neuropathic pain.

PubMed

Inoue, Makoto; Yamaguchi, Asuka; Kawakami, Megumi; Chun, Jerold; Ueda, Hiroshi

2006-08-16

Among various machineries occurring in the experimental neuropathic pain model, there exists the loss of pain transmission through C-fiber neurons as well as the hypersensitivity through A-fibers. The current study reveals that molecular machineries underlying the latter hypersensitivity are derived from the events through LPA1 receptor and its downstream RhoA-activation following peripheral nerve injury. The loss of C-fiber responses, which are mediated by spinal substance P (SP) pain transmission was observed with the nociceptive flexor responses by intraplantar injection of SP in nerve-injured mice. The immunohistochemistry revealed that SP signal in the dorsal horn was markedly reduced in such mice. All these changes were completely abolished in LPA1-/- mice or by the pretreatment with BoNT/C3, a RhoA inhibitor. In addition, the loss of C-fiber responses and the down-regulation of spinal SP signal induced by single intrathecal LPA injection were also abolished in such treatments. All these results suggest that the loss of pain transmission through polymodal C-fiber neurons is also mediated by the LPA1 activation following nerve injury.

Modulating the Delicate Glial-Neuronal Interactions in Neuropathic Pain: Promises and Potential Caveats

PubMed Central

Tiwari, Vinod; Guan, Yun; Raja, Srinivasa N.

2014-01-01

During neuropathic pain, glial cells (mainly astrocytes and microglia) become activated and initiate a series of signaling cascades that modulate pain processing at both spinal and supraspinal levels. It has been generally accepted that glial cell activation contributes to neuropathic pain because glia release proinflammatory cytokines, chemokines, and factors such as calcitonin gene-related peptide, substance P, and glutamate, which are known to facilitate pain signaling. However, recent research has shown that activation of glia also leads to some beneficial outcomes. Glia release anti-inflammatory factors that protect against neurotoxicity and restore normal pain. Accordingly, use of glial inhibitors might compromise the protective functions of glia in addition to suppressing their detrimental effects. With a better understanding of how different conditions affect glial cell activation, we may be able to promote the protective function of glia and pave the way for future development of novel, safe, and effective treatments of neuropathic pain. PMID:24820245

Spinal muscle evaluation in healthy individuals and low-back-pain patients: a literature review.

PubMed

Demoulin, Christophe; Crielaard, Jean-Michel; Vanderthommen, Marc

2007-01-01

This article reviews available techniques for spinal muscle investigation, as well as data on spinal muscles in healthy individuals and in patients with low back pain. In patients with chronic low back pain, medical imaging studies show paraspinal muscle wasting with reductions in cross-sectional surface area and fiber density. In healthy individuals, the paraspinal muscles contain a high proportion of slow-twitch fibers (Type I), reflecting their role in maintaining posture. The proportion of Type I fibers is higher in females, leading to better adaptation to aerobic exertion compared to males. Abnormalities seen in paraspinal muscles from patients with chronic low back pain include marked Type II fiber atrophy, conversion of Type I to Type II fibers, and an increased number of nonspecific abnormalities. Limited data are available from magnetic resonance spectroscopy used to investigate muscle metabolism and from near infrared spectroscopy used to measure oxygen uptake by the paraspinal muscles. Surface electromyography in patients with chronic low back pain shows increased paraspinal muscle fatigability, often with abolition of the flexion-relaxation phenomenon.

Postdural puncture headache and back pain after spinal anesthesia with 27-gauge Quincke and 26-gauge Atraucan needles.

PubMed

Schultz, A M; Ulbing, S; Kaider, A; Lehofer, F

1996-01-01

The purpose of this study was to determine whether the 26-gauge Atraucan needle shows any benefit on the incidence of postdural puncture headache (PDPH) and back pain as compared with the 27-gauge Quincke needle. We investigated 388 patients, 171 men and 217 women, who were receiving spinal anesthesia for subumbilical surgery. We compared spinal anesthesia via the 27-gauge Quincke needle in 202 patients (group Q) and via the 26-gauge Atraucan needle in 186 patients (group A). The incidence of PDPH was 2.97% (6 of 202) in group Q and 2.69% (5 of 186) in group A. The incidence of back pain was 4.95% (10 of 202) in group Q and 5.91% (11 of 186) in group A. There was no statistically significant association of needle type, age, or sex with the incidence of PDPH and back pain. Both needles are associated with very low incidences of PDPH and back pain, which are not affected by which needle is chosen.

Neuraxial analgesia effects on labor progression: facts, fallacies, uncertainties, and the future

PubMed Central

Grant, Erica N.; Tao, Weike; Craig, Margaret; McIntire, Donald; Leveno, Kenneth

2014-01-01

Approximately 60% of women who labor receive some form of neuraxial analgesia, but concerns have been raised regarding whether it negatively impacts the labor and delivery process. In this review, we attempt to clarify what has been established as truths, falsities, and uncertainties regarding the effects of this form of pain relief on labor progression, negative and/or positive. Additionally, although the term “epidural” has become synonymous with neuraxial analgesia, we discuss two other techniques, combined spinal-epidural and continuous spinal analgesia, that are gaining popularity, as well as their effects on labor progression. PMID:25088476

Effects of a three-month therapeutic exercise programme on flexibility in subjects with low back pain.

PubMed

Kuukkanen, T; Mälkiä, E

2000-01-01

Spinal and muscle flexibility have been studied intensively and used clinically as outcome measurements in the rehabilitation of subjects with low back pain. The results of previous studies are contradictory and there is a lack of longitudinal data on the effects of long term therapeutic exercise on flexibility. A controlled experimental study was conducted to determine the effects of progressive therapeutic exercise on spinal and muscle flexibility. Eighty-six chronic low back pain subjects fulfilled the inclusion criteria and were divided into three study groups: (1) intensive training group, (2) home exercise group and (3) control group. The intervention period lasted three months and measurements were performed at both the beginning of the study and immediately after intervention. Follow-up measurements were carried out six and 12 months after baseline. Spinal flexibility was measured with lumbar flexion, extension, spinal lateral flexion and rotation, and muscle flexibility was measured with measurements of erector spinae, hamstring and iliopsoas muscles. Also self-reported outcomes of the Oswestry Index and Borg Scale--Back Pain Intensity were used. Associations between change (pre- to post-treatment) were determined for the dependent variables. The results showed no correlation between flexibility, the Oswestry Index or back pain intensity. After the first three-month period lumbar flexion, extension and spinal rotation decreased among all subjects. Spinal rotation and erector spinae muscle flexibility improved significantly with intensive training. At the nine-month follow-up, erector spine flexibility was still greater than at baseline. Hamstring flexibility increased among the intensive training and home exercise groups from pre- to post-intervention. However, the degree of hamstring flexibility gained during training was subsequently lost following the period without programmed exercise in both training groups. Self-reported outcome variables showed positive changes among the three study groups after the completion of intervention period, but these changes were only able to be maintained during subsequent follow-ups for the intensive training and home exercise groups. The findings suggest that flexibility does not play an important role in coping with chronic low back pain for subjects whose functional limitations are not severe. Also, it appears that the achieved gains in spinal and muscle flexibility may not be able to be maintained without continued exercise.

Intrathecal injection of the peptide myr-NR2B9c attenuates bone cancer pain via perturbing N-methyl-D-aspartate receptor-PSD-95 protein interactions in mice.

PubMed

Liu, Yue; Cui, Xinlong; Sun, Yu-E; Yang, Xuli; Ni, Kun; Zhou, Yu; Ma, Zhengliang; Gu, Xiaoping

2014-06-01

N-methyl-D-aspartate receptor (NMDARs)-dependent central sensitization plays an important role in cancer pain. Binding of NMDAR subunit 2B (NR2B) by postsynaptic density protein-95 (PSD-95) can couple NMDAR activity to intracellular enzymes, such as neuronal nitric oxide synthase (nNOS), facilitate downstream signaling pathways, and modulate NMDAR stability, contributing to synaptic plasticity. In this study, we investigated whether perturbing the specific interaction between spinal NR2B-containing NMDAR and PSD-95, using a peptide-mimetic strategy, could attenuate bone cancer-related pain behaviors. Osteosarcoma cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce progressive bone cancer-related pain behaviors. Western blotting was applied to examine the expression of spinal phospho-Tyr1472 NR2B, nNOS, and PSD-95. We further investigated the effects of intrathecal injection of the mimetic peptide Myr-NR2B9c, which competitively disrupts the interaction between PSD-95 and NR2B, on nociceptive behaviors and on the upregulation of phospho-Tyr1472 NR2B, nNOS, and PSD-95 associated with bone cancer pain in the spinal cord. Inoculation of osteosarcoma cells induced progressive bone cancer pain and resulted in a significant upregulation of phospho-Tyr1472 NR2B, nNOS, and PSD-95. Intrathecal administration of Myr-NR2B9c attenuated bone cancer-evoked mechanical allodynia, thermal hyperalgesia, and reduced spinal phospho-Tyr1472 NR2B, nNOS, and PSD-95 expression. Intrathecal administration of Myr-NR2B9c reduced bone cancer pain. Internalization of spinal NR2B and dissociation NR2B-containing NMDARs activation from downstream nNOS signaling may contribute to the analgesic effects of Myr-NR2B9c. This approach may circumvent the negative consequences associated with blocking NMDARs, and may be a novel strategy for the treatment of bone cancer pain.

Spinal cord stimulation for chronic pain.

PubMed

Mailis-Gagnon, A; Furlan, A D; Sandoval, J A; Taylor, R

2004-01-01

Spinal cord stimulation (SCS) is a form of therapy used to treat certain types of chronic pain. It involves an electrical generator that delivers pulses to a targeted spinal cord area. The leads can be implanted by laminectomy or percutaneously and the source of power is supplied by an implanted battery or by an external radio-frequency transmitter. The exact mechanism of action of SCS is poorly understood. To assess the efficacy and effectiveness of spinal cord stimulation in relieving certain kinds of pain, as well as the complications and adverse effects of this procedure. We searched MEDLINE and EMBASE to September 2003; the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2003); textbooks and reference lists in retrieved articles. We also contacted experts in the field of pain and the main manufacturer of the stimulators. We included trials with a control group, either randomized controlled trials (RCTs) or non-randomized controlled clinical trials (CCTs), that assessed spinal cord stimulation for chronic pain. Two independent reviewers selected the studies, assessed study quality and extracted the data. One of the assessors of methodological quality was blinded to authors, dates and journals. The data were analysed using qualitative methods (best evidence synthesis). Two RCTs (81 patients in total) met our inclusion criteria. One was judged as being of high quality (score of 3 on Jadad scale) and the other of low quality (score of 1 on Jadad scale). One trial included patients with Complex Regional Pain Syndrome Type I (reflex sympathetic dystrophy) and the other patients with Failed Back Surgery Syndrome. The follow-up periods varied from 6 to 12 months. Both studies reported that SCS was effective, however, meta-analysis was not undertaken because of the small number of patients and the heterogeneity of the study population. Although there is limited evidence in favour of SCS for Failed Back Surgery Syndrome and Complex Regional Pain Syndrome Type I, more trials are needed to confirm whether SCS is an effective treatment for certain types of chronic pain. In addition, there needs to be a debate about trial designs that will provide the best evidence for assessing this type of intervention.

Assessment of effectiveness of percutaneous adhesiolysis in managing chronic low back pain secondary to lumbar central spinal canal stenosis.

PubMed

Manchikanti, Laxmaiah; Cash, Kimberly A; McManus, Carla D; Pampati, Vidyasagar

2013-01-01

Chronic persistent low back and lower extremity pain secondary to central spinal stenosis is common and disabling. Lumbar surgical interventions with decompression or fusion are most commonly performed to manage severe spinal stenosis. However, epidural injections are also frequently performed in managing central spinal stenosis. After failure of epidural steroid injections, the next sequential step is percutaneous adhesiolysis and hypertonic saline neurolysis with a targeted delivery. The literature on the effectiveness of percutaneous adhesiolysis in managing central spinal stenosis after failure of epidural injections has not been widely studied. A prospective evaluation. An interventional pain management practice, a specialty referral center, a private practice setting in the United States. To evaluate the effectiveness of percutaneous epidural adhesiolysis in patients with chronic low back and lower extremity pain with lumbar central spinal stenosis. Seventy patients were recruited. The initial phase of the study was randomized, double-blind with a comparison of percutaneous adhesiolysis with caudal epidural injections. The 25 patients from the adhesiolysis group continued with follow-up, along with 45 additional patients, leading to a total of 70 patients. All patients received percutaneous adhesiolysis and appropriate placement of the Racz catheter, followed by an injection of 5 mL of 2% preservative-free lidocaine with subsequent monitoring in the recovery room. In the recovery room, each patient also received 6 mL of 10% hypertonic sodium chloride solution, and 6 mg of non-particulate betamethasone, followed by an injection of 1 mL of sodium chloride solution and removal of the catheter. Multiple outcome measures were utilized including the Numeric Rating Scale (NRS), the Oswestry Disability Index 2.0 (ODI), employment status, and opioid intake with assessment at 3, 6, and 12, 18 and 24 months post treatment. The primary outcome measure was 50% or more improvement in pain scores and ODI scores. Overall, a primary outcome or significant pain relief and functional status improvement of 50% or more was seen in 71% of patients at the end of 2 years. The overall number of procedures over a period of 2 years were 5.7 ± 2.73. The lack of a control group and a prospective design. Significant relief and functional status improvement as seen in 71% of the 70 patients with percutaneous adhesiolysis utilizing local anesthetic steroids and hypertonic sodium chloride solution may be an effective management strategy in patients with chronic function limiting low back and lower extremity pain with central spinal stenosis after failure of conservatie management and fluoroscopically directed epidural injections.

Wen-Luo-Tong Prevents Glial Activation and Nociceptive Sensitization in a Rat Model of Oxaliplatin-Induced Neuropathic Pain.

PubMed

Deng, Bo; Jia, Liqun; Pan, Lin; Song, Aiping; Wang, Yuanyuan; Tan, Huangying; Xiang, Qing; Yu, Lili; Ke, Dandan

2016-01-01

One of the main dose-limiting complications of the chemotherapeutic agent oxaliplatin (OXL) is painful neuropathy. Glial activation and nociceptive sensitization may be responsible for the mechanism of neuropathic pain. The Traditional Chinese Medicine (TCM) Wen-luo-tong (WLT) has been widely used in China to treat chemotherapy induced neuropathic pain. However, there is no study on the effects of WLT on spinal glial activation induced by OXL. In this study, a rat model of OXL-induced chronic neuropathic pain was established and WLT was administrated. Pain behavioral tests and morphometric examination of dorsal root ganglia (DRG) were conducted. Glial fibrillary acidic protein (GFAP) immunostaining was performed, glial activation was evaluated, and the excitatory neurotransmitter substance P (SP) and glial-derived proinflammatory cytokine tumor necrosis factor-α (TNF-α) were analyzed. WLT treatment alleviated OXL-induced mechanical allodynia and mechanical hyperalgesia. Changes in the somatic, nuclear, and nucleolar areas of neurons in DRG were prevented. In the spinal dorsal horn, hypertrophy and activation of GFAP-positive astrocytes were averted, and the level of GFAP mRNA decreased significantly. Additionally, TNF-α mRNA and protein levels decreased. Collectively, these results indicate that WLT reversed both glial activation in the spinal dorsal horn and nociceptive sensitization during OXL-induced chronic neuropathic pain in rats.

A preliminary evaluation of the motivational model of pain self-management in persons with spinal cord injury related pain

PubMed Central

Molton, Ivan R.; Jensen, Mark P.; Nielson, Warren; Cardenas, Diana; Ehde, Dawn M.

2008-01-01

Chronic pain commonly accompanies long-term disabilities such as spinal cord injury (SCI). Research suggests that patient motivation to engage in adaptive pain coping strategies, such as exercise/stretching and task persistence, is an important factor in determining the impact that this pain will have on quality of life. One recently proposed model (the “Motivational Model of Pain Self-Management”) suggests that motivation to manage pain is influenced by two primary variables: beliefs about the importance of engaging in pain self-management (i.e., “perceived importance”) and beliefs about one's own ability to engage in these behaviors (i.e., “self-efficacy”). The purpose of this study was to provide a preliminary test of this model in a sample of 130 adults with SCI who completed a return by mail survey. Measures included a numerical rating scale of pain intensity and the revised version of the Multidimensional Pain Readiness to Change Questionnaire. Mediation analyses were performed using multiple regression. Results suggested that the effects of perceived importance and self-efficacy on exercise behavior were mediated by readiness to engage in exercise, consistent with the proposed model. However, the model could not be established for the outcome of task persistence. Perspective: This study tests a model describing motivation to engage in pain management behaviors (i.e., “readiness to change”) in adults with spinal cord injury. This model could potentially aid clinicians in their conceptualization of the factors that affect patient motivation to manage pain. PMID:18359668

Dimethylarginine dimethylaminohydrolase 1 is involved in spinal nociceptive plasticity.

PubMed

DʼMello, Richard; Sand, Claire A; Pezet, Sophie; Leiper, James M; Gaurilcikaite, Egle; McMahon, Stephen B; Dickenson, Anthony H; Nandi, Manasi

2015-10-01

Activation of neuronal nitric oxide synthase, and consequent production of nitric oxide (NO), contributes to spinal hyperexcitability and enhanced pain sensation. All NOS isoforms are inhibited endogenously by asymmetric dimethylarginine, which itself is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). Inhibition of DDAH can indirectly attenuate NO production by elevating asymmetric dimethylarginine concentrations. Here, we show that the DDAH-1 isoform is constitutively active in the nervous system, specifically in the spinal dorsal horn. DDAH-1 was found to be expressed in sensory neurons within both the dorsal root ganglia and spinal dorsal horn; L-291 (NG-[2-Methoxyethyl]-L-arginine methyl ester), a DDAH-1 inhibitor, reduced NO synthesis in cultured dorsal root ganglia neurons. Spinal application of L-291 decreased N-methyl-D-aspartate-dependent postdischarge and windup of dorsal horn sensory neurons--2 measures of spinal hyperexcitability. Finally, spinal application of L-291 reduced both neuronal and behavioral measures of formalin-induced central sensitization. Thus, DDAH-1 may be a potential therapeutic target in neuronal disorders, such as chronic pain, where elevated NO is a contributing factor.

Spinal Cord Stimulation for the Relief of Pain: Proceedings of a Symposium during the 4th International Congress of the International Neuromodulation Society, September 16-20, 1998, Lucerne, Switzerland.

PubMed

Oakley, J C

1999-07-01

Spinal cord stimulation has become an accepted technique used in the management of chronic neuropathic pain syndromes. However, a number of problematic questions remain unanswered. This introduction states some of these problems and concentrates on the problem of whether low back pain can be relieved by stimulation. This paper introduces subsequent contributions to this symposium, which offer some interesting new techniques, and attempts to answer some of the problems presented.

Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

PubMed Central

Ferguson, Adam R.; Huie, J. Russell; Crown, Eric D.; Baumbauer, Kyle M.; Hook, Michelle A.; Garraway, Sandra M.; Lee, Kuan H.; Hoy, Kevin C.; Grau, James W.

2012-01-01

Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI). Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. A mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. In addition, the lumbar spinal cord can sustain several forms of learning and memory, including limb-position training. However, not all spinal plasticity promotes recovery of function. Central sensitization of nociceptive (pain) pathways in the spinal cord may emerge in response to various noxious inputs, demonstrating that plasticity within the spinal cord may contribute to maladaptive pain states. In this review we discuss interactions between adaptive and maladaptive forms of activity-dependent plasticity in the spinal cord below the level of SCI. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. Prior work from our group has shown that stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after SCI. We review these basic phenomena, how these findings relate to the broader spinal plasticity literature, discuss the cellular and molecular mechanisms, and finally discuss implications of these and other findings for improved rehabilitative therapies after SCI. PMID:23087647

[Controversies about instrumented surgery and pain relief in degenerative lumbar spine pain. Results of scientific evidence].

PubMed

Robaina-Padrón, F J

2007-10-01

Investigation and development of new techniques for intrumented surgery of the spine is not free of conflicts of interest. The influence of financial forces in the development of new technologies an its immediately application to spine surgery, shows the relationship between the published results and the industry support. Even authors who have defend eagerly fusion techniques, it have been demonstrated that them are very much involved in the revision of new articles to be published and in the approval process of new spinal technologies. When we analyze the published results of spine surgery, we must bear in mind what have been call in the "American Stock and Exchange" as "the bubble of spine surgery". The scientific literature doesn't show clear evidence in the cost-benefit studies of most instrumented surgical interventions of the spine compare with the conservative treatments. It has not been yet demonstrated that fusion surgery and disc replacement are better options than the conservative treatment. It's necessary to point out that at present "there are relationships between the industry and back pain, and there is also an industry of the back pain". Nonetheless, the "market of the spine surgery" is growing up because patients are demanding solutions for their back problems. The tide of scientific evidence seams to go against the spinal fusions in the degenerative disc disease, discogenic pain and inespecific back pain. After decades of advances in this field, the results of spinal fusions are mediocre. New epidemiological studies show that "spinal fusion must be accepted as a non proved or experimental method for the treatment of back pain". The surgical literature on spinal fusion published in the last 20 years following the Cochrane's method establish that: 1- this is at least incomplete, not reliable and careless; 2- the instrumentation seems to slightly increase the fusion rate; 3- the instrumentation doesn't improve the clinical results in general, lacking studies in subgroups of patients. We still are needing randomized studies to compare the surgical results with the natural history of the disease, the placebo effect, or the conservative treatment. The European Guidelines for lumbar chronic pain management show a "strong evidence" indicating that complex and demanding spine surgery where different instrumentation is used, is not more effective than a simple, safer and cheaper posterolateral fusion without instrumentation. Recently, the literature published in this field is sending a message to use "minimally invasive techniques", abandon transpedicular fusions and clearly indicating that we must apply the knowledge accumulated at least along the last 20 years based on the scientific evidence. In conclusion, based in recent information, we must recommend the "abandon of the instrumented pathway" in a great number of present indications for degenerative spine surgery, and look for new strategies in the field of rehabilitation and conservative treatments correctly apply, using before the decompressive and instrumented surgery all the interventional and minimally invasive techniques that are presently offer in the field of modem lumbar chronic pain treatment.

Glial contributions to visceral pain: implications for disease etiology and the female predominance of persistent pain

PubMed Central

Dodds, K N; Beckett, E A H; Evans, S F; Grace, P M; Watkins, L R; Hutchinson, M R

2016-01-01

In the central nervous system, bidirectional signaling between glial cells and neurons (‘neuroimmune communication') facilitates the development of persistent pain. Spinal glia can contribute to heightened pain states by a prolonged release of neurokine signals that sensitize adjacent centrally projecting neurons. Although many persistent pain conditions are disproportionately common in females, whether specific neuroimmune mechanisms lead to this increased susceptibility remains unclear. This review summarizes the major known contributions of glia and neuroimmune interactions in pain, which has been determined principally in male rodents and in the context of somatic pain conditions. It is then postulated that studying neuroimmune interactions involved in pain attributed to visceral diseases common to females may offer a more suitable avenue for investigating unique mechanisms involved in female pain. Further, we discuss the potential for primed spinal glia and subsequent neurogenic inflammation as a contributing factor in the development of peripheral inflammation, therefore, representing a predisposing factor for females in developing a high percentage of such persistent pain conditions. PMID:27622932

Changes in neck pain and active range of motion after a single thoracic spine manipulation in subjects presenting with mechanical neck pain: a case series.

PubMed

Fernández-de-las-Peñas, César; Palomeque-del-Cerro, Luis; Rodríguez-Blanco, Cleofás; Gómez-Conesa, Antonia; Miangolarra-Page, Juan C

2007-05-01

Our aim was to report changes in neck pain at rest, active cervical range of motion, and neck pain at end-range of cervical motion after a single thoracic spine manipulation in a case series of patients with mechanical neck pain. Seven patients with mechanical neck pain (2 men, 5 women), 20 to 33 years old, were included. All patients received a single thoracic manipulation by an experienced manipulative therapist. The outcome measures of these cases series were neck pain at rest, as measured by a numerical pain rating scale; active cervical range of motion; and neck pain at the end of each neck motion (eg, flexion or extension). These outcomes were assessed pre treatment, 5 minutes post manipulation, and 48 hours after the intervention. A repeated-measures analysis was made with parametric tests. Within-group effect sizes were calculated using Cohen d coefficients. A significant (P < .001) decrease, with large within-group effect sizes (d > 1), in neck pain at rest were found after the thoracic spinal manipulation. A trend toward an increase in all cervical motions (flexion, extension, right or left lateral flexion, and right or left rotation) and a trend toward a decrease in neck pain at the end of each cervical motion were also found, although differences did not reach the significance (P > .05). Nevertheless, medium to large within-group effect sizes (0.5 < d < 1) were found between preintervention data and both postintervention assessments in both active range of motion and neck pain at the end of each neck motion. The present results demonstrated a clinically significant reduction in pain at rest in subjects with mechanical neck pain immediately and 48 hours following a thoracic manipulation. Although increases in all tested ranges of motion were obtained, none of them reached statistical significance at either posttreatment point. The same was found for pain at the end of range of motion for all tested ranges, with the exception of pain at the end of forward flexion at 48 hours. More than one mechanism likely explains the effects of thoracic spinal manipulation. Future controlled studies comparing spinal manipulation vs spinal mobilization of the thoracic spine are required.

Spinal cord stimulation during the antepartum and intrapartum periods: a case report showing no deleterious effect of conventional paraesthesia producing stimulation.

PubMed

Moussa, Ahmad Abdelhai; Glancz, Laurence; Das, Mausumi; Basu, Surajit

2016-12-01

We report on a 25-year-old woman who used her spinal cord stimulator (SCS), previously inserted for chronic regional pain syndrome (CPRS), to assist with both chronic and pregnancy-related pain management. We describe the therapeutic effect of the stimulator and briefly highlight the issues surrounding the use of SCS during pregnancy.

ERK-GluR1 phosphorylation in trigeminal spinal subnucleus caudalis neurons is involved in pain associated with dry tongue.

PubMed

Nakaya, Yuka; Tsuboi, Yoshiyuki; Okada-Ogawa, Akiko; Shinoda, Masamichi; Kubo, Asako; Chen, Jui Yen; Noma, Noboru; Batbold, Dulguun; Imamura, Yoshiki; Sessle, Barry J; Iwata, Koichi

2016-01-01

Dry mouth is known to cause severe pain in the intraoral structures, and many dry mouth patients have been suffering from intraoral pain. In development of an appropriate treatment, it is crucial to study the mechanisms underlying intraoral pain associated with dry mouth, yet the detailed mechanisms are not fully understood. To evaluate the mechanisms underlying pain related to dry mouth, the dry-tongue rat model was developed. Hence, the mechanical or heat nocifensive reflex, the phosphorylated extracellular signal-regulated kinase and phosphorylated GluR1-IR immunohistochemistries, and the single neuronal activity were examined in the trigeminal spinal subnucleus caudalis of dry-tongue rats. The head-withdrawal reflex threshold to mechanical, but not heat, stimulation of the tongue was significantly decreased on day 7 after tongue drying. The mechanical, but not heat, responses of trigeminal spinal subnucleus caudalis nociceptive neurons were significantly enhanced in dry-tongue rats compared to sham rats on day 7. The number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells was also significantly increased in the trigeminal spinal subnucleus caudalis following noxious stimulation of the tongue in dry-tongue rats compared to sham rats on day 7. The decrement of the mechanical head-withdrawal reflex threshold (HWT) was reversed during intracisternal administration of the mitogen-activated protein kinase kinase 1 inhibitor, PD98059. The trigeminal spinal subnucleus caudalis neuronal activities and the number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells following noxious mechanical stimulation of dried tongue were also significantly decreased following intracisternal administration of PD98059 compared to vehicle-administrated rats. Increased number of the phosphorylated GluR1-IR cells was observed in the trigeminal spinal subnucleus caudalis of dry-tongue rats, and the number of phosphorylated GluR1-IR cells was significantly reduced in PD98059-administrated rats compared to the vehicle-administrated tongue-dry rats. These findings suggest that the pERK-pGluR1 cascade is involved in central sensitization of trigeminal spinal subnucleus caudalis nociceptive neurons, thus resulting in tongue mechanical hyperalgesia associated with tongue drying. © The Author(s) 2016.

Spinal serum-inducible and glucocorticoid-inducible kinase 1 mediates neuropathic pain via kalirin and downstream PSD-95-dependent NR2B phosphorylation in rats.

PubMed

Peng, Hsien-Yu; Chen, Gin-Den; Lai, Cheng-Yuan; Hsieh, Ming-Chun; Lin, Tzer-Bin

2013-03-20

The coupling of the spinal postsynaptic density-95 (PSD-95) with the glutamatergic N-methyl-d-aspartate receptor NR2B subunit and the subsequent NR2B phosphorylation contribute to pain-related plasticity. Increasing evidence reveals that kalirin, a Rho-guanine nucleotide exchange factor, modulates PSD-95-NR2B-dependent neuroplasticity. Our laboratory recently demonstrated that serum-inducible and glucocorticoid-inducible kinase 1 (SGK1) participates in inflammation-associated pain hypersensitivity by modulating spinal glutamatergic neurotransmission. Because kalirin is one of the proteins in PSD that is highly phosphorylated by various kinases, we tested whether kalirin could be a downstream target of spinal SGK1 that participates in neuropathic pain development via regulation of the PSD-95-NR2B coupling-dependent phosphorylation of NR2B. We observed that spinal nerve ligation (SNL, L5) in male Sprague Dawley rats resulted in behavioral allodynia, which was associated with phosphorylated SGK1 (pSGK1), kalirin, and phosphorylated NR2B (pNR2B) expression and an increase in pSGK1-kalirin-PSD-95-pNR2B coprecipitation in the ipsilateral dorsal horn (L4-L5). SNL-enhanced kalirin immunofluorescence was coincident with pSGK1, PSD-95, and pNR2B immunoreactivity. Small-interfering RNA (siRNA) that targeted spinal kalirin mRNA expression (10 μg, 10 μl; i.t.) reduced SNL-induced allodynia, kalirin and pNR2B expression, as well as kalirin-PSD-95 and PSD-95-pNR2B coupling and costaining without affecting SGK1 phosphorylation. Daily administration of GSK-650394 (an SGK1 antagonist; 100 nm, 10 μl, i.t.) not only exhibited effects similar to the kalirin mRNA-targeting siRNA but also attenuated pSGK1-kalirin costaining and SGK1-kalirin coupling. We suggest that nerve injury could induce spinal SGK1 phosphorylation that subsequently interacts with and upregulates kalirin to participate in neuropathic pain development via PSD-95-NR2B coupling-dependent NR2B phosphorylation.

Spinal Cord Infarction in Clinical Neurology: A Review of Characteristics and Long-Term Prognosis in Comparison to Cerebral Infarction.

PubMed

Romi, Fredrik; Naess, Halvor

2016-01-01

Spinal cord stroke is rare accounting for 0.3-1% of all strokes and is classified into upper (cervical) and lower (thoracolumbar) strokes. Patients present with severe deficits but later often show good functional improvement. On admission, younger age, male gender, hypertension, diabetes mellitus and elevated blood glucose indicate more severe spinal cord strokes. Treatment of these risk factors is essential in the acute phase. Biphasic spinal cord strokes are seen in one-fifth of the patients. These present with acute or transient sensory spinal cord deficits often preceded by radiating pain between the shoulders, and should be considered and treated as imminent spinal cord strokes. Spinal cord infarction patients are younger and more often women compared to cerebral infarction patients. Traditional cerebrovascular risk factors are less relevant in spinal cord infarction. Spinal cord infarction patients are more likely to be discharged home and show better improvement after initial treatment compared to cerebral infarction patients. On long-term follow-up, spinal cord infarction patients have lower mortality and higher emotional well-being scores than cerebral infarction patients. Despite more chronic pain, the frequency of re-employment is higher among spinal cord infarction patients compared to cerebral infarction patients who are more often afflicted with cognitive function deficits. © 2016 S. Karger AG, Basel.

Different underlying pain mechanisms despite identical pain characteristics: a case report of a patient with spinal cord injury.

PubMed

Westermann, Andrea; Krumova, Elena K; Pennekamp, Werner; Horch, Christoph; Baron, Ralf; Maier, Christoph

2012-07-01

Pain following spinal cord injury has been classified as nociceptive (musculoskeletal, visceral) or neuropathic (above, at, below level). There is no clear relation between the etiology and reported symptoms. Thus, due to different underlying mechanisms, the treatment is often ineffective. We report on a patient with spinal cord injury with neurological level of injury at T8 suffering from bilateral burning and prickling pain in the T9-11 dermatomes bilaterally (at-level pain), as well as diffusely in both legs from below the torso (below-level pain), accompanied by musculoskeletal low back pain. Bilateral comparison of quantitative sensory testing (QST) and skin biopsy revealed completely different findings in the dermatome T9 despite identical at-level pain characteristics. On the right side, QST revealed a normal sensory profile; the intraepidermal nerve fiber density (IENFD) was reduced, but not as severe as the contralateral side. On the left side there was a severe sensory loss with a stronger reduction of the IENDF, similar to the areas below the neurological level. These findings were significantly related to the treatment results. Pregabalin induced unilateral pain relief only in the area with remaining sensory function, whereas the left-sided at-level pain was unchanged. Thus, 2 different underlying mechanisms leading to bilaterally neuropathic pain with identical symptoms and with different treatment success were demonstrated in a single patient. The at-level pain in areas with remaining sensory function despite IENFD reduction could be relieved by pregabalin. Thus, in an individual case, QST may be helpful to better understand pain-generating mechanisms and to initiate successful treatment. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Clinical effectiveness and cost-effectiveness of treatments for patients with chronic pain.

PubMed

Turk, Dennis C

2002-01-01

Chronic pain is a prevalent and costly problem. This review addresses the question of the clinical effectiveness and cost-effectiveness of the most common treatments for patients with chronic pain. Representative published studies that evaluate the clinical effectiveness of pharmacological treatments, conservative (standard) care, surgery, spinal cord stimulators, implantable drug delivery systems (IDDSs), and pain rehabilitation programs (PRPs) are examined and compared. The cost-effectiveness of these treatment approaches is also considered. Outcome criteria including pain reduction, medication use, health care consumption, functional activities, and closure of disability compensation cases are examined. In addition to clinical effectiveness, the cost-effectiveness of PRPs, conservative care, surgery, spinal cord stimulators, and IDDSs are compared using costs to return a treated patient to work to illustrate the relative expenses for each of these treatments. There are limitations to the success of all the available treatments. The author urges caution in interpreting the results, particularly in comparisons between treatments and across studies, because there are broad differences in the pain syndromes and inclusion criteria used, the drug dosages, comparability of treatments, the definition of "chronic" used, the outcome criteria selected to determine success, and societal differences. None of the currently available treatments eliminates pain for the majority of patients. Pain rehabilitation programs provide comparable reduction in pain to alternative pain treatment modalities, but with significantly better outcomes for medication use, health care utilization, functional activities, return to work, closure of disability claims, and with substantially fewer iatrogenic consequences and adverse events. Surgery, spinal cord stimulators, and IDDSs appear to have substantial benefits on some outcome criteria for carefully selected patients. These modalities are, however, expensive. Pain rehabilitation programs are significantly more cost effective than implantation of spinal cord stimulators, IDDSs, conservative care, and surgery, even for selected patients. Research is needed to identify which patients are most likely to benefit from the available treatments and to study combinations of the available treatments since none of them appear capable of eliminating pain or significantly improving functional outcomes for all treated.

Effects of a wearable type lumbosacral support for low back pain among hospital workers: A randomized controlled trial.

PubMed

Hagiwara, Yoshihiro; Yabe, Yutaka; Yamada, Hiroyuki; Watanabe, Takashi; Kanazawa, Kenji; Koide, Masashi; Sekiguchi, Takuya; Hatano, Hirokazu; Itoi, Eiji

2017-03-28

To examine the effects of a new wearable type of lumbosacral support on low back pain. A total of 121 healthcare workers participated in this study. They were randomly allocated into the experimental and control groups and the former wore the support with signals of compression on the back by poor posture for the first 3 months. The control group remained on a waiting list for the first 3 months. Medical history, musculoskeletal symptoms, feeling in good posture, sleep habits, psychological distress, Roland-Morris Disability Questionnaire, and Somatosensory Amplification Scale (SSAS) were evaluated. The range of motion (ROM) in the shoulder and hip joints as well as spinal alignment were evaluated. Our primary concern was the difference in the change of low back pain measured by visual analog scale (VAS) between the two groups. A total of 54 participants in the experimental and 53 participants in the control groups were analyzed. VAS and SSAS scores as well as lumbar spinal ROM in the experimental group significantly decreased. Low back pain (OR=0.401, 95% CI=0.168-0.954) and neck pain in the experimental group (OR=0.198, 95% CI=0.052-0.748) significantly decreased. The new lumbar support reduced VAS and SSAS scores, lumbar spinal ROM, low back pain, and neck pain. This new type of lumbar support reduced low back pain among healthcare workers.

Sacral epiduroscopic laser decompression for complex regional pain syndrome after lumbar spinal surgery: A case report.

PubMed

Jung, Jae-Wook; Kim, Yong Han; Kim, Hyojoong; Kang, Eunsu; Jo, Hyunji; Ko, Myoung Jin

2018-05-01

CRPS after a lumbar surgery has symptoms that are similar to PSSS. However, standard criteria for distinguishing CRPS from PSSS do not exist. We present a case report of a 31-year-old female with CRPS symptoms after lumbar spinal surgery treated by performing SELD. This patient was referred to our pain clinic for left ankle pain. She received a lumbar discectomy for a herniated lumbar disc (L5/S1) but the pain was aggravated after surgery. The characteristics of the pain were burning, tingling, and cold, and were accompanied by other symptoms such as swelling, color change and mail dystrophy. The patient was diagnosed with CRPS. Medications and interventional therapies were not effective in reducing pain. SELD was performed and severe adhesive inflammation was observed in the L4-S1 epidural space. We performed mechanical adhesiolysis and injected hyalurodinase and dexamethasone near the L5 and S1 root. One month after, a second SELD was performed as same manner. After second SELD, the patient's pain markedly decreased. On the second visit in the outpatient clinic, the patient was absent of pain without any other medications. CRPS like symptoms can appear after lumbar spinal surgery due to adhesion and inflammation in the epidural space. In such cases, SELD can be considered as diagnostic and therapeutic option.

Spinal SIRPα1-SHP2 interaction regulates spinal nerve ligation-induced neuropathic pain via PSD-95-dependent NR2B activation in rats.

PubMed

Peng, Hsien-Yu; Chen, Gin-Den; Lai, Cheng-Yuang; Hsieh, Ming-Chun; Lin, Tzer-Bin

2012-05-01

The fact that neuropathic pain mechanisms are not well understood is a major impediment in the development of effective clinical treatments. We examined whether the interaction between signal regulatory protein alpha 1 (SIRPα1) and Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP2), and the downstream spinal SHP2/postsynaptic density 95 (PSD-95)/N-methyl-d-aspartate receptor NR2B subunit signaling cascade play a role in neuropathic pain. Following spinal nerve ligation (L5), we assessed tactile allodynia using the von Frey filament test and analyzed dorsal horn samples (L4-5) by Western blotting, reverse transcription polymerase chain reaction, coimmunoprecipitation, and immunofluorescence. Nerve ligation induced allodynia, SIRPα1, SHP2, phosphorylated SHP2 (pSHP2), and phosphorylated NR2B (pNR2B) expression, and SHP2-PSD-95, pSHP2-PSD-95, PSD-95-NR2B, and PSD-95-pNR2B coimmunoprecipitation in the ipsilateral dorsal horn. In allodynic rats, injury-induced SHP2 immunoreactivity was localized in the ipsilateral dorsal horn neurons and coincident with PSD-95 and NR2B immunoreactivity. SIRPα1 silencing using small interfering RNA (siRNA; 1, 3, or 5μg/rat for 7days) prevented injury-induced allodynia and the associated changes in protein expression, phosphorylation, and coimmunoprecipitation. Intrathecal administration of NSC-87877 (an SHP2 antagonist; 1, 10, or 100μM/rat) and SIRPα1-neutralizing antibodies (1, 10, or 30μg/rat) suppressed spinal nerve ligation-induced allodynia, spinal SHP2 and NR2B phosphorylation, and SHP2/phosphorylated SHP2-PSD-95 and PSD-95-NR2B/phosphorylated NR2B coprecipitation. SHP2 siRNA led to similar effects as the NSC-87877 and SIRPα1 antibody treatments, except it prevented the allodynia-associated spinal SHP2 expression. In conclusion, our results suggest that a spinal SIRPα1-SHP2 interaction exists that subsequently triggers SHP2/PSD-95/NR2B signaling, thereby playing a role in neuropathic pain development. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Phosphatidylinositol 3-kinase is a key mediator of central sensitization in painful inflammatory conditions

PubMed Central

Pezet, Sophie; Marchand, Fabien; D'Mello, Richard; Grist, John; Clark, Anna K.; Malcangio, Marzia; Dickenson, Anthony H.; Williams, Robert J.; McMahon, Stephen B.

2010-01-01

Here we show that phosphatidylinositol 3-kinase (PI3K) is a key player in the establishment of central sensitization, the spinal cord phenomenon associated with persistent afferent inputs and contributing to chronic pain states. We demonstrated electrophysiologically that PI3K is required for the full expression of spinal neuronal wind-up. In an inflammatory pain model, intrathecal administration of LY294002, a potent PI3K inhibitor, dose-dependently inhibited pain related behavior. This effect was correlated with a reduction of the phosphorylation of extracellular signal-regulated kinase (ERK) and CaMKinase II. In addition, we observed a significant decrease in the phosphorylation of the NMDA receptor subunit NR2B, decreased translocation to the plasma membrane of the GluR1 AMPA receptor subunit in the spinal cord and a reduction of evoked neuronal activity as measured using c-Fos immunohistochemistry. Our study suggests that PI3K is a major factor in the expression of central sensitization after noxious inflammatory stimuli. PMID:18417706

Neuromodulation in Pediatrics: Case Series.

PubMed

Kim, Eugene; Gamble, Sean; Schwartz, Adina; Cucchiaro, Giovanni

2018-05-22

Neuromodulation, particularly intrathecal drug delivery systems and spinal cord stimulators, can be a valuable tool when treating chronic pain in adults. However, there is a paucity of literature regarding its use in pediatrics. and Methods: We present a series of 14 children and adolescents with intractable pain who received a spinal cord stimulator or a pump for the intrathecal delivery of medications between 2010 and 2016 at our institution. During the study period, we placed 10 intrathecal pumps and 4 spinal cord stimulators with an average age of 17 years old. Pain scores significantly improved after the implant (P<0.007) and function improved in 79% of patients. Opioid use was also significantly reduced. Three patients eventually had their device removed due to psychiatric comorbidities. Four patients had complications that were treated without further sequelae. Neuromodulation can offer important options in treating some pediatric chronic pain patients. In-depth knowledge of primary disease and strict patient selection in the context of the patient's social situation is vital to successful treatment.

First-contact care with a medical vs chiropractic provider after consultation with a swiss telemedicine provider: comparison of outcomes, patient satisfaction, and health care costs in spinal, hip, and shoulder pain patients.

PubMed

Houweling, Taco A W; Braga, Andrea V; Hausheer, Thomas; Vogelsang, Marco; Peterson, Cynthia; Humphreys, B Kim

2015-09-01

The purpose of this study was to identify differences in outcomes, patient satisfaction, and related health care costs in spinal, hip, and shoulder pain patients who initiated care with medical doctors (MDs) vs those who initiated care with doctors of chiropractic (DCs) in Switzerland. A retrospective double cohort design was used. A self-administered questionnaire was completed by first-contact care spinal, hip, and shoulder pain patients who, 4 months previously, contacted a Swiss telemedicine provider regarding advice about their complaint. Related health care costs were determined in a subsample of patients by reviewing the claims database of a Swiss insurance provider. The study sample included 403 patients who had seen MDs and 316 patients who had seen DCs as initial health care providers for their complaint. Differences in patient sociodemographic characteristics were found in terms of age, pain location, and mode of onset. Patients initially consulting MDs had significantly less reduction in their numerical pain rating score (difference of 0.32) and were significantly less likely to be satisfied with the care received (odds ratio = 1.79) and the outcome of care (odds ratio = 1.52). No significant differences were found for Patient's Global Impression of Change ratings. Mean costs per patient over 4 months were significantly lower in patients initially consulting DCs (difference of CHF 368; US $368). Spinal, hip, and shoulder pain patients had clinically similar pain relief, greater satisfaction levels, and lower overall cost if they initiated care with DCs, when compared with those who initiated care with MDs. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

Trigeminal nerve injury-induced thrombospondin-4 up-regulation contributes to orofacial neuropathic pain states in a rat model.

PubMed

Li, K-W; Kim, D-S; Zaucke, F; Luo, Z D

2014-04-01

Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause up-regulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve. Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 up-regulation and orofacial behavioural hypersensitivity. Our data indicated that trigeminal nerve injury induced TSP4 up-regulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 up-regulation in Vc/C2 and behavioural hypersensitivity. Our data support that infraorbital nerve injury leads to TSP4 up-regulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states. © 2013 European Pain Federation - EFIC®

Experimental autoimmune prostatitis induces microglial activation in the spinal cord.

PubMed

Wong, Larry; Done, Joseph D; Schaeffer, Anthony J; Thumbikat, Praveen

2015-01-01

The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host's immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain. Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S14-S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain. Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1β, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1β, P2X4R, and BDNF. Our data show that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain. © 2014 Wiley Periodicals, Inc.

Experimental autoimmune prostatitis induces microglial activation in the spinal cord

PubMed Central

Wong, Larry; Done, Joseph D.; Schaeffer, Anthony J.; Thumbikat, Praveen

2014-01-01

Background The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host’s immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain. Methods Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S4–S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain. Results Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1β, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1β, P2X4R, and BDNF. Conclusion Our data shows that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain. PMID:25263093

Spinal CPEB-mtROS-CBP signaling pathway contributes to perineural HIV gp120 with ddC-related neuropathic pain in rats.

PubMed

Iida, Takafumi; Yi, Hyun; Liu, Shue; Huang, Wan; Kanda, Hirotsugu; Lubarsky, David A; Hao, Shuanglin

2016-07-01

Human immunodeficiency virus (HIV) patients treated with nucleoside reverse transcriptase inhibitors (NRTIs), have been known to develop neuropathic pain. While there has been a major shift away from some neurotoxic NRTIs in current antiretroviral therapy, a large number of HIV patients alive today have previously received them, and many have developed painful peripheral neuropathy. The exact mechanisms by which HIV with NRTIs contribute to the development of neuropathic pain are not known. Previous studies suggest that cytoplasmic polyadenylation element-binding protein (CPEB), reactive oxygen species (ROS), and cAMP-response element-binding protein (CREB)-binding protein (CBP), are involved in the neuroimmunological diseases including inflammatory/neuropathic pain. In this study, we investigated the role of CPEB, mitochondrial ROS (mtROS), or CBP in neuropathic pain induced by HIV envelope protein gp120 combined with antiretroviral drug. The application of recombinant gp120 into the sciatic nerve plus systemic ddC (one of NRTIs) induced mechanical allodynia. Knockdown of CPEB or CBP using intrathecal antisense oligodeoxynucleotide (AS-ODN) reduced mechanical allodynia. Intrathecal mitochondrial superoxide scavenger mito-tempol (Mito-T) increased mechanical withdrawal threshold. Knockdown of CPEB using intrathecal AS-ODN, reduced the up-regulated mitochondrial superoxide in the spinal dorsal horn in rats with gp120 combined with ddC. Intrathecal Mito-T lowered the increased expression of CBP in the spinal dorsal horn. Immunostaining studies showed that neuronal CPEB positive cells were co-localized with MitoSox positive profiles, and that MitoSox positive profiles were co-localized with neuronal CBP. Our studies suggest that neuronal CPEB-mtROS-CBP pathway in the spinal dorsal horn, plays an important role in the gp120/ddC-induced neuropathic pain in rats. Copyright © 2016. Published by Elsevier Inc.

Does cervical lordosis change after spinal manipulation for non-specific neck pain? A prospective cohort study.

PubMed

Shilton, Michael; Branney, Jonathan; de Vries, Bas Penning; Breen, Alan C

2015-01-01

The association between cervical lordosis (sagittal alignment) and neck pain is controversial. Further, it is unclear whether spinal manipulative therapy can change cervical lordosis. This study aimed to determine whether cervical lordosis changes after a course of spinal manipulation for non-specific neck pain. Posterior tangents of C2 and C6 were drawn on the lateral cervical fluoroscopic images of 29 patients with subacute/chronic non-specific neck pain and 30 healthy volunteers matched for age and gender, recruited August 2011 to April 2013. The resultant angle was measured using 'Image J' digital geometric software. The intra-observer repeatability (measurement error and reliability) and intra-subject repeatability (minimum detectable change (MDC) over 4 weeks) were determined in healthy volunteers. A comparison of cervical lordosis was made between patients and healthy volunteers at baseline. Change in lordosis between baseline and 4-week follow-up was determined in patients receiving spinal manipulation. Intra-observer measurement error for cervical lordosis was acceptable (SEM 3.6°) and reliability was substantial ICC 0.98, 95 % CI 0.962-0991). The intra-subject MDC however, was large (13.5°). There was no significant difference between lordotic angles in patients and healthy volunteers (p = 0.16). The mean cervical lordotic increase over 4 weeks in patients was 2.1° (9.2) which was not significant (p = 0.12). This study found no difference in cervical lordosis (sagittal alignment) between patients with mild non-specific neck pain and matched healthy volunteers. Furthermore, there was no significant change in cervical lordosis in patients after 4 weeks of cervical spinal manipulation.

Activation of spinal and supraspinal cannabinoid-1 receptors lead to antinociception in a rat model of neuropathic spinal cord injury pain

PubMed Central

Hama, Aldric; Sagen, Jacqueline

2011-01-01

Activation of CNS cannabinoid subtype-1 (CB1) receptors has been shown to mediate the antinociceptive and other effects of systemically administered CB receptor agonists. The endogenous peptide CB receptor ligand hemopressin (HE) has previously demonstrated an antinociceptive effect in rats with a hind paw inflammation, without exhibiting characteristic CB1 receptor-mediated side-effects. The current study evaluated the effect of intrathecal (i.t.) and intracerebroventricular (i.c.v.) injection of HE in a rat model of neuropathic spinal cord injury (SCI) pain. The non-subtype selective CB receptor agonist WIN 55,212-2 was also centrally administered in SCI rats as a comparator. Four weeks following an acute compression of the mid-thoracic spinal cord, rats displayed markedly decreased hind paw withdrawal thresholds, indicative of below-level neuropathic pain. Central administration of WIN 55,212-2 significantly increased withdrawal thresholds, whereas HE did not. Hemopressin has been reported to block CB1 receptors in vitro, similar to the CB1 receptor antagonist rimonabant. Pretreatment with rimonabant completely blocked the antinociceptive effect of centrally administered WIN 55,212-2, but pretreatment with HE did not. While the data confirm that activation of either supraspinal or spinal CB1 receptors leads to significant antinociception in SCI rats, the current data do not support an antinociceptive effect from an acute blockade of central CB1 receptors, HE’s putative antinociceptive mechanism, in neuropathic SCI rats. Although such a mechanism could be useful in other models of pain with a significant inflammatory component, the current data indicate that activation of CB1 receptors is needed to ameliorate neuropathic SCI pain. PMID:21813113

Granulocyte-colony–stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis

PubMed Central

Basso, Lilian; Lapointe, Tamia K.; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D.; Kurrasch, Deborah M.; Altier, Christophe

2017-01-01

Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony–stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF–induced visceral pain in vivo. Finally, administration of G-CSF–neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron–microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain. PMID:28973941

Granulocyte-colony-stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis.

PubMed

Basso, Lilian; Lapointe, Tamia K; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D; Kurrasch, Deborah M; Altier, Christophe

2017-10-17

Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony-stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF-induced visceral pain in vivo. Finally, administration of G-CSF-neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron-microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain.

An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain From Spinal Cord Injury and Disease.

PubMed

Wilsey, Barth; Marcotte, Thomas D; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

2016-09-01

Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, most of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta 9-THC on 3 separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was used to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model showed a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (eg, good drug effect, feeling high, etc) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all P < .0004). Psychoactive and subjective effects were dose-dependent. Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. Because the 2 active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. A crossover, randomized, placebo-controlled human laboratory experiment involving administration of vaporized cannabis was performed in patients with neuropathic pain related to spinal cord injury and disease. This study supports consideration of future research that would include longer duration studies over weeks to months to evaluate the efficacy of medicinal cannabis in patients with central neuropathic pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Back pain in space and post-flight spine injury: Mechanisms and countermeasure development

NASA Astrophysics Data System (ADS)

Sayson, Jojo V.; Lotz, Jeffrey; Parazynski, Scott; Hargens, Alan R.

2013-05-01

During spaceflight many astronauts experience moderate to severe lumbar pain and deconditioning of paraspinal muscles. There is also a significant incidence of herniated nucleus pulposus (HNP) in astronauts post-flight being most prevalent in cervical discs. Relief of in-flight lumbar back pain is facilitated by assuming a knee-to-chest position. The pathogenesis of lumbar back pain during spaceflight is most likely discogenic and somatic referred (from the sinuvertebral nerves) due to supra-physiologic swelling of the lumbar intervertebral discs (IVDs) due to removal of gravitational compressive loads in microgravity. The knee-to-chest position may reduce lumbar back pain by redistributing stresses through compressive loading to the IVDs, possibly reducing disc volume by fluid outflow across IVD endplates. IVD stress redistribution may reduce Type IV mechanoreceptor nerve impulse propagation in the annulus fibrosus and vertebral endplate resulting in centrally mediated pain inhibition during spinal flexion. Countermeasures for lumbar back pain may include in-flight use of: (1) an axial compression harness to prevent excessive IVD expansion and spinal column elongation; (2) the use of an adjustable pulley exercise developed to prevent atrophy of spine muscle stabilisers; and (3) other exercises that provide Earth-like annular stress with low-load repetitive active spine rotation movements. The overall objective of these countermeasures is to promote IVD health and to prevent degenerative changes that may lead to HNPs post-flight. In response to "NASA's Critical Path Roadmap Risks and Questions" regarding disc injury and higher incidence of HNPs after space flight (Integrated Research Plan Gap-B4), future studies will incorporate pre- and post-flight imaging of International Space Station long-duration crew members to investigate mechanisms of lumbar back pain as well as degeneration and damage to spinal structures. Quantitative results on morphological, biochemical, metabolic, and kinematic spinal changes in the lumbar spine may aid further development of countermeasures to prevent lumbar back pain in microgravity and reduce the incidence of HNPs post-flight.

Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain

PubMed Central

Kostich, Walter; Hamman, Brian D.; Li, Yu-Wen; Naidu, Sreenivasulu; Dandapani, Kumaran; Feng, Jianlin; Easton, Amy; Bourin, Clotilde; Baker, Kevin; Allen, Jason; Savelieva, Katerina; Louis, Justin V.; Dokania, Manoj; Elavazhagan, Saravanan; Vattikundala, Pradeep; Sharma, Vivek; Das, Manish Lal; Shankar, Ganesh; Kumar, Anoop; Holenarsipur, Vinay K.; Gulianello, Michael; Molski, Ted; Brown, Jeffrey M.; Lewis, Martin; Huang, Yanling; Lu, Yifeng; Pieschl, Rick; O’Malley, Kevin; Lippy, Jonathan; Nouraldeen, Amr; Lanthorn, Thomas H.; Ye, Guilan; Wilson, Alan; Balakrishnan, Anand; Denton, Rex; Grace, James E.; Lentz, Kimberley A.; Santone, Kenneth S.; Bi, Yingzhi; Main, Alan; Swaffield, Jon; Carson, Ken; Mandlekar, Sandhya; Vikramadithyan, Reeba K.; Nara, Susheel J.; Dzierba, Carolyn; Bronson, Joanne; Macor, John E.; Zaczek, Robert; Westphal, Ryan; Kiss, Laszlo; Bristow, Linda; Conway, Charles M.

2016-01-01

To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the adapter protein-2 associated kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase I formalin), but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL). Based on these findings, potent, small-molecule inhibitors of AAK1 were identified. Studies in mice showed that one such inhibitor, LP-935509, caused a reduced pain response in phase II formalin and reversed fully established pain behavior following the SNL procedure. Further studies showed that the inhibitor also reduced evoked pain responses in the rat chronic constriction injury (CCI) model and the rat streptozotocin model of diabetic peripheral neuropathy. Using a nonbrain-penetrant AAK1 inhibitor and local administration of an AAK1 inhibitor, the relevant pool of AAK1 for antineuropathic action was found to be in the spinal cord. Consistent with these results, AAK1 inhibitors dose-dependently reduced the increased spontaneous neural activity in the spinal cord caused by CCI and blocked the development of windup induced by repeated electrical stimulation of the paw. The mechanism of AAK1 antinociception was further investigated with inhibitors of α2 adrenergic and opioid receptors. These studies showed that α2 adrenergic receptor inhibitors, but not opioid receptor inhibitors, not only prevented AAK1 inhibitor antineuropathic action in behavioral assays, but also blocked the AAK1 inhibitor–induced reduction in spinal neural activity in the rat CCI model. Hence, AAK1 inhibitors are a novel therapeutic approach to neuropathic pain with activity in animal models that is mechanistically linked (behaviorally and electrophysiologically) to α2 adrenergic signaling, a pathway known to be antinociceptive in humans. PMID:27411717

Use of Spinal Cord Diffusion Tensor Imaging to Quantify Neural Ablation and Evaluate Outcome after Percutaneous Cordotomy for Intractable Cancer Pain

PubMed Central

Vedantam, Aditya; Hou, Ping; Chi, T. Linda; Dougherty, Patrick M.; Hess, Kenneth R.; Viswanathan, Ashwin

2017-01-01

Background Up to 20% of patients experience only partial pain relief after percutaneous cordotomy for cancer pain. Objective To determine whether diffusion tensor imaging (DTI) can quantify neural ablation and help evaluate early postoperative outcomes after cordotomy. Methods Patients undergoing percutaneous CT-guided cordotomy for intractable cancer pain were prospectively studied. Pre- and postoperative assessment was made using the visual analog scale (VAS) on pain and the pain severity scores of the Brief Pain Inventory Short Form. On postoperative day 1, DTI images of the high cervical spinal cord were obtained. DTI metrics were correlated with the number of ablations as well as early postoperative pain outcomes. Results Seven patients (4 male, mean age 53.8 ± 4.6 years) were studied. Fractional anisotropy of the hemicord was significantly lower on the side of the lesion as compared to the contralateral side (0.54 ± 0.03 vs. 0.63 ± 0.03, p < 0.001). Mean diffusivity correlated with the improvement in the VAS score at 1 week (r = 0.88, 95% CI = 0.34–1.00, p = 0.008), as well as the change in pain severity scores at 1 week (r = 0.99, 95% CI = 0.82–1.00, p < 0.001). Conclusion DTI metrics are sensitive to the number of ablations as well as early improvement in pain scores after cordotomy. DTI of the cervical spinal cord is a potential biomarker of neural ablation after percutaneous cordotomy for intractable cancer pain. PMID:28088799

Effect of estrogen on morphine- and oxycodone-induced antinociception in a female femur bone cancer pain model.

PubMed

Ono, Hiroko; Nakamura, Atsushi; Kanemasa, Toshiyuki; Sakaguchi, Gaku; Shinohara, Shunji

2016-02-15

Although estrous cycle has been reported to influence antiociceptive effect of morphine in several pain conditions, its effect on cancer pain is not well established. We investigated the effect of estrogen on morphine antinociception using a bone cancer pain model and compared its potency with that of oxycodone. Female mice were ovariectomized (OVX) for preparation of a femur bone cancer pain (FBC) model. β-estradiol was subcutaneously (s.c.) administered and antinociceptive effects of opioids was assessed using the von Frey monofilament test. Although morphine (5-20mg/kg, s.c.) did have significant antinociceptive effects in the FBC-OVX group, its effects in the FBC-OVX+β-estradiol (OVX+E) group was limited. Oxycodone (1-5mg/kg, s.c.) exhibited significant effects in both groups. Expression changes in opioid-related genes (μ-, κ-, δ-opioid receptors, prodynorphin, proenkephalin, proopiomelanocortin) in the spinal and supraspinal sites were examined among the sham-OVX, sham-OVX+E, FBC-OVX, and FBC-OVX+E groups by in situ hybridization. These studies detected a significant increase in prodynorphin in the spinal dorsal horn of the FBC-OVX+E group. Spinal injection of a dynorphin-A antibody to FBC-OVX+E mice restored antinociception of morphine. In conclusion, we detected a differential effect of estrogen on morphine- and oxycodone-induced antinociception in a female FBC model. The effect of morphine was limited with estrogen exposure, which may be due to estrogen- and pain-mediated spinal expression of dynorphin-A. Copyright © 2016 Elsevier B.V. All rights reserved.

The afferent pathways of discogenic low-back pain. Evaluation of L2 spinal nerve infiltration.

PubMed

Nakamura, S I; Takahashi, K; Takahashi, Y; Yamagata, M; Moriya, H

1996-07-01

The afferent pathways of discogenic low-back pain have not been fully investigated. We hypothesised that this pain was transmitted mainly by sympathetic afferent fibres in the L2 nerve root, and in 33 patients we used selective local anaesthesia of this nerve. Low-back pain disappeared or significantly decreased in all patients after the injection. Needle insertion provoked pain which radiated to the low back in 23 patients and the area of skin hypoalgesia produced included the area of pre-existing pain in all but one. None of the nine patients with related sciatica had relief of that component of their symptoms. Our findings show that the main afferent pathways of pain from the lower intervertebral discs are through the L2 spinal nerve root, presumably via sympathetic afferents from the sinuvertebral nerves. Discogenic low-back pain should be regarded as a visceral pain in respect of its neural pathways. Infiltration of the L2 nerve is a useful diagnostic test and also has some therapeutic value.

Striatal-enriched protein tyrosine phosphatase modulates nociception: evidence from genetic deletion and pharmacological inhibition

PubMed Central

Azkona, Garikoitz; Saavedra, Ana; Aira, Zigor; Aluja, David; Xifró, Xavier; Baguley, Tyler; Alberch, Jordi; Ellman, Jonathan A.; Lombroso, Paul J.; Azkue, Jon J.; Pérez-Navarro, Esther

2016-01-01

The information from nociceptors is processed in the dorsal horn of the spinal cord by complex circuits involving excitatory and inhibitory interneurons. It is well documented that GluN2B and ERK1/2 phosphorylation contributes to central sensitization. Striatal-enriched protein tyrosine phosphatase (STEP) dephosphorylates GluN2B and ERK1/2, promoting internalization of GluN2B and inactivation of ERK1/2. The activity of STEP was modulated by genetic (STEP knockout mice) and pharmacological (recently synthesized STEP inhibitor, TC-2153) approaches. STEP61 protein levels in the lumbar spinal cord were determined in male and female mice of different ages. Inflammatory pain was induced by complete Freund’s adjuvant injection. Behavioral tests, immunoblotting, and electrophysiology were used to analyze the effect of STEP on nociception. Our results show that both genetic deletion and pharmacological inhibition of STEP induced thermal hyperalgesia and mechanical allodynia, which were accompanied by increased pGluN2BTyr1472 and pERK1/2Thr202/Tyr204 levels in the lumbar spinal cord. Striatal-enriched protein tyrosine phosphatase heterozygous and knockout mice presented a similar phenotype. Furthermore, electrophysiological experiments showed that TC-2153 increased C fiber-evoked spinal field potentials. Interestingly, we found that STEP61 protein levels in the lumbar spinal cord inversely correlated with thermal hyperalgesia associated with age and female gender in mice. Consistently, STEP knockout mice failed to show age-related thermal hyperalgesia, although gender-related differences were preserved. Moreover, in a model of inflammatory pain, hyperalgesia was associated with increased phosphorylation-mediated STEP61 inactivation and increased pGluN2BTyr1472 and pERK1/2Thr202/Tyr204 levels in the lumbar spinal cord. Collectively, the present results underscore an important role of spinal STEP activity in the modulation of nociception. PMID:26270590

Transcutaneous electrical nerve stimulation attenuates postsurgical allodynia and suppresses spinal substance P and proinflammatory cytokine release in rats.

PubMed

Chen, Yu-Wen; Tzeng, Jann-Inn; Lin, Min-Fei; Hung, Ching-Hsia; Wang, Jhi-Joung

2015-01-01

Transcutaneous electrical nerve stimulation (TENS) is often used for management of chronic pain. The purpose of this study was to investigate whether TENS altered postincisional allodynia, substance P, and proinflammatory cytokines in a rat model of skin-muscle incision and retraction (SMIR). This was an experimental study. High-frequency (100-Hz) TENS therapy began on postoperative day 3 and was administered for 20 minutes daily to SMIR-operated rats by self-adhesive electrodes delivered to skin innervated via the ipsilateral dorsal rami of lumbar spinal nerves L1-L6 for the next 27 days. The expressions of substance P, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1β) in the spinal cord and mechanical sensitivity to von Frey stimuli (4g and 10g) were evaluated. The SMIR-operated rats displayed a marked hypersensitivity to von Frey stimuli on postoperative day 3. In contrast to the SMIR-operated rats, SMIR-operated rats after TENS administration showed a quick recovery of mechanical hypersensitivity. On postoperative days 3, 16, and 30, SMIR-operated rats exhibited an upregulation of substance P and cytokines (TNF-α, IL-6, and IL-1β) in the spinal cord, whereas SMIR-operated rats after TENS therapy inhibited that upregulation. By contrast, the placebo TENS following SMIR surgery did not alter mechanical hypersensitivity and the levels of spinal substance P, TNF-α, IL-6, and IL-1β. The experimental data are limited to animal models and cannot be generalized to postoperative pain in humans. The results revealed that TENS attenuates prolonged postoperative allodynia following SMIR surgery. Increased levels of spinal substance P and proinflammatory cytokines, activated after SMIR surgery, are important in the processing of persistent postsurgical allodynia. The protective effect of TENS may be related to the suppression of spinal substance P and proinflammatory cytokines in SMIR-operated rats. © 2015 American Physical Therapy Association.

Factors Leading to Persistent Postsurgical Pain in Adolescents Undergoing Spinal Fusion: An Integrative Literature Review.

PubMed

Perry, Mallory; Starkweather, Angela; Baumbauer, Kyle; Young, Erin

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity among children and adolescents and the most frequent reason for corrective spinal fusion (SF). Of the children and adolescents who undergo SF, a significant number will experience persistent postoperative pain (PPP). This integrative literature review was conducted to identify and synthesize perioperative factors that may contribute to risk of developing PPP. Articles which addressed PPP within the last 10years and primary research on postoperative pain outcomes in adolescents after SF were selected for review. 15 articles which met eligibility criteria were included. Preoperative pain intensity was the most significant factor identified in the development of PPP and increased postoperative pain. Social function and psychological factors also have role in the development of PPP. There were no theoretical models or frameworks for evaluating PPP incidence in adolescent with AIS after SF. Perioperative factors such as, preoperative pain, correction magnitude, pain coping, anxiety and social functioning are vital to understanding a child's risk of PPP following SF. There is a need for theoretically-based studies to assess PPP among children and adolescents with AIS after SF surgery. The Biobehavioral Pain Network (BPN) model was proposed, to encompass biological, social and psychological domains which may be responsible for incidence of PPP in children undergoing SF. Such a model can be used to systematically develop and evaluate personalized postoperative pain management strategies for this patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative multifactorial analysis of the effects of idiopathic adolescent scoliosis and Scheuermann kyphosis on the self-perceived health status of adolescents treated with brace.

PubMed

Korovessis, Panagiotis; Zacharatos, Spyridon; Koureas, Georgios; Megas, Panagiotis

2007-04-01

Bracing is the most effective non-operative treatment for mild progressive spinal deformities in adolescence but it has shown a considerable impact on several aspects of adolescents' functioning. This cross-sectional study investigated the self-perceived health status of adolescents with the two most common deformities, treated with body orthosis. Seventy-nine adolescents with spinal deformities (idiopathic adolescent scoliosis, thoracic Scheuermann kyphosis) and 62 adolescents without spinal deformities were asked to complete the Quality of Life profile for Spine Deformities Instrument. This study showed that adolescents with deformities are significantly less likely to have back pain in training than controls, but more likely to have difficulty in forward bending, and in the most common daily activities while in brace. These individuals claim they wake up because of back pain and feel quite nervous with the external appearance of their body. These patients face often problems with their relations with friends, while they reported difficulties in getting up from bed and sleep at night more often than their counterparts without deformities. As they grow older, patients feel increasing ashamed of their body, as they are more concerned about the future effect of the deformity on their body. As the bracing time increases, patients have much more probability than controls to get low back pain. Girls with deformity have a higher probability than boys to get low back pain while working in the house and while training. Individuals with larger spinal curvatures have more difficulties in bending and increased incidence of back pain than their counterparts with smaller curvatures. Psychological reasons associated mainly with relations at school and back pain are the main causes for low compliance in adolescents with spinal deformities treated with body orthosis. Careful instructions for all individuals who will undergo brace therapy, psychological support for all patients who develop psychological reactions and physical training particularly for older girls should be recommended to increase bracing compliance.

Comparative multifactorial analysis of the effects of idiopathic adolescent scoliosis and Scheuermann kyphosis on the self-perceived health status of adolescents treated with brace

PubMed Central

Zacharatos, Spyridon; Koureas, Georgios; Megas, Panagiotis

2006-01-01

Bracing is the most effective non-operative treatment for mild progressive spinal deformities in adolescence but it has shown a considerable impact on several aspects of adolescents’ functioning. This cross-sectional study investigated the self-perceived health status of adolescents with the two most common deformities, treated with body orthosis. Seventy-nine adolescents with spinal deformities (idiopathic adolescent scoliosis, thoracic Scheuermann kyphosis) and 62 adolescents without spinal deformities were asked to complete the Quality of Life profile for Spine Deformities Instrument. This study showed that adolescents with deformities are significantly less likely to have back pain in training than controls, but more likely to have difficulty in forward bending, and in the most common daily activities while in brace. These individuals claim they wake up because of back pain and feel quite nervous with the external appearance of their body. These patients face often problems with their relations with friends, while they reported difficulties in getting up from bed and sleep at night more often than their counterparts without deformities. As they grow older, patients feel increasing ashamed of their body, as they are more concerned about the future effect of the deformity on their body. As the bracing time increases, patients have much more probability than controls to get low back pain. Girls with deformity have a higher probability than boys to get low back pain while working in the house and while training. Individuals with larger spinal curvatures have more difficulties in bending and increased incidence of back pain than their counterparts with smaller curvatures. Psychological reasons associated mainly with relations at school and back pain are the main causes for low compliance in adolescents with spinal deformities treated with body orthosis. Careful instructions for all individuals who will undergo brace therapy, psychological support for all patients who develop psychological reactions and physical training particularly for older girls should be recommended to increase bracing compliance. PMID:16953447

Therapeutic relevance of ozone therapy in degenerative diseases: Focus on diabetes and spinal pain.

PubMed

Braidy, Nady; Izadi, Morteza; Sureda, Antoni; Jonaidi-Jafari, Nematollah; Banki, Abdolali; Nabavi, Seyed F; Nabavi, Seyed M

2018-04-01

Ozone, one of the most important air pollutants, is a triatomic molecule containing three atoms of oxygen that results in an unstable form due to its mesomeric structure. It has been well-known that ozone has potent ability to oxidize organic compounds and can induce respiratory irritation. Although ozone has deleterious effects, many therapeutic effects have also been suggested. Since last few decades, the therapeutic potential of ozone has gained much attention through its strong capacity to induce controlled and moderated oxidative stress when administered in precise therapeutic doses. A plethora of scientific evidence showed that the activation of hypoxia inducible factor-1α (HIF-1a), nuclear factor of activated T-cells (NFAT), nuclear factor-erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE), and activated protein-1 (AP-1) pathways are the main molecular mechanisms underlying the therapeutic effects of ozone therapy. Activation of these molecular pathways leads to up-regulation of endogenous antioxidant systems, activation of immune functions as well as suppression of inflammatory processes, which is important for correcting oxidative stress in diabetes and spinal pain. The present study intended to review critically the available scientific evidence concerning the beneficial properties of ozone therapy for treatment of diabetic complications and spinal pain. It finds benefit for integrating the therapy with ozone into pharmacological procedures, instead of a substitutive or additional option to therapy. © 2017 Wiley Periodicals, Inc.

Stimulation of spinal dorsal horn β2-adrenergic receptor ameliorates neuropathic mechanical hypersensitivity through a reduction of phosphorylation of microglial p38 MAP kinase and astrocytic c-jun N-terminal kinase.

PubMed

Zhang, Fang Fang; Morioka, Norimitsu; Abe, Hiromi; Fujii, Shiori; Miyauchi, Kazuki; Nakamura, Yoki; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

2016-12-01

The noradrenaline-adrenergic system has a crucial role in controlling nociceptive transduction at the spinal level. While α-adrenergic receptors are known to regulate nociceptive neurotransmitter release at the spinal presynaptic level, it is not entirely clear whether β-adrenergic receptors are involved in controlling pain transduction at the spinal level as well. The current study elucidated a role of β-adrenergic receptors in neuropathic pain in mice following a partial sciatic nerve ligation (PSNL). In addition, the cellular and intracellular signaling cascade induced by β-adrenergic receptors in neuropathic mice was elaborated. Intrathecal injection of isoproterenol (1 nmol), a nonselective β-adrenergic receptor agonist, briefly ameliorated hind paw mechanical hypersensitivity of PSNL mice. Isoproterenol's antinociceptive effect was mediated through β2-adrenergic receptors since pretreatment with ICI118551, a selective β2-adrenergic receptor antagonist, but not with CGP20712A, a selective β1-adrenergic receptor antagonist, significantly attenuated isoproterenol's effect. Furthermore, intrathecal treatment with a selective β2-adrenergic receptor agonist, terbutaline, but not a selective β1-adrenergic receptor agonist, dobutamine, also significantly ameliorated neuropathic pain. Fourteen days after PSNL, increased phosphorylation of both p38 Mitogen-activated protein kinase (MAPK) in microglia and c-jun N-terminal kinase (JNK) in astrocytes of ipsilateral spinal dorsal horn were observed. Phosphorylation of both microglial p38 MAPK and astrocytic JNK were downregulated by stimulation of the β2-adrenergic receptor. Together, these results suggest that spinal β2-adrenergic receptor have an inhibitory role in neuropathic nociceptive transduction at the spinal level through a downregulation of glial activity, perhaps through modulation of MAP kinases phosphorylation. Thus, targeting of β2-adrenergic receptors could be an effective therapeutic strategy in treating neuropathic pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Altered spinal microRNA-146a and the microRNA-183 cluster contribute to osteoarthritic pain in knee joints.

PubMed

Li, Xin; Kroin, Jeffrey S; Kc, Ranjan; Gibson, Gary; Chen, Di; Corbett, Grant T; Pahan, Kalipada; Fayyaz, Sana; Kim, Jae-Sung; van Wijnen, Andre J; Suh, Joon; Kim, Su-Gwan; Im, Hee-Jeong

2013-12-01

The objective of this study was to examine whether altered expression of microRNAs in central nervous system components is pathologically linked to chronic knee joint pain in osteoarthritis. A surgical animal model for knee joint OA was generated by medial meniscus transection in rats followed by behavioral pain tests. Relationships between pathological changes in knee joint and development of chronic joint pain were examined by histology and imaging analyses. Alterations in microRNAs associated with OA-evoked pain sensation were determined in bilateral lumbar dorsal root ganglia (DRG) and the spinal dorsal horn by microRNA array followed by individual microRNA analyses. Gain- and loss-of-function studies of selected microRNAs (miR-146a and miR-183 cluster) were conducted to identify target pain mediators regulated by these selective microRNAs in glial cells. The ipsilateral hind leg displayed significantly increased hyperalgesia after 4 weeks of surgery, and sensitivity was sustained for the remainder of the 8-week experimental period (F = 341, p < 0.001). The development of OA-induced chronic pain was correlated with pathological changes in the knee joints as assessed by histological and imaging analyses. MicroRNA analyses showed that miR-146a and the miR-183 cluster were markedly reduced in the sensory neurons in DRG (L4/L5) and spinal cord from animals experiencing knee joint OA pain. The downregulation of miR-146a and/or the miR-183 cluster in the central compartments (DRG and spinal cord) are closely associated with the upregulation of inflammatory pain mediators. The corroboration between decreases in these signature microRNAs and their specific target pain mediators were further confirmed by gain- and loss-of-function analyses in glia, the major cellular component of the central nervous system (CNS). MicroRNA therapy using miR-146a and the miR-183 cluster could be powerful therapeutic intervention for OA in alleviating joint pain and concomitantly regenerating peripheral knee joint cartilage. © 2013 American Society for Bone and Mineral Research.

The effect of exercise frequency on neuropathic pain and pain-related cellular reactions in the spinal cord and midbrain in a rat sciatic nerve injury model

PubMed Central

Sumizono, Megumi; Otsuka, Shotaro; Terashi, Takuto; Nakanishi, Kazuki; Ueda, Koki; Takada, Seiya; Kikuchi, Kiyoshi

2018-01-01

Background Exercise regimens are established methods that can relieve neuropathic pain. However, the relationship between frequency and intensity of exercise and multiple cellular responses of exercise-induced alleviation of neuropathic pain is still unclear. We examined the influence of exercise frequency on neuropathic pain and the intracellular responses in a sciatic nerve chronic constriction injury (CCI) model. Materials and methods Rats were assigned to four groups as follows: CCI and high-frequency exercise (HFE group), CCI and low-frequency exercise (LFE group), CCI and no exercise (No-Ex group), and naive animals (control group). Rats ran on a treadmill, at a speed of 20 m/min, for 30 min, for 5 (HFE) or 3 (LFE) days a week, for a total of 5 weeks. The 50% withdrawal threshold was evaluated for mechanical sensitivity. The activation of glial cells (microglia and astrocytes), expression of brain-derived neurotrophic factor (BDNF) and μ-opioid receptor in the spinal dorsal horn and endogenous opioid in the midbrain were examined using immunohistochemistry. Opioid receptor antagonists (naloxone) were administered using intraperitoneal injection. Results The development of neuropathic pain was related to the activation of glial cells, increased BDNF expression, and downregulation of the μ-opioid receptor in the ipsilateral spinal dorsal horn. In the No-Ex group, neuropathic pain showed the highest level of mechanical hypersensitivity at 2 weeks, which improved slightly until 5 weeks after CCI. In both exercise groups, the alleviation of neuropathic pain was accelerated through the regulation of glial activation, BDNF expression, and the endogenous opioid system. The expression of BDNF and endogenous opioid in relation to exercise-induced alleviation of neuropathic pain differed in the HFE and LFE groups. The effects of exercise-induced alleviation of mechanical hypersensitivity were reversed by the administration of naloxone. Conclusion The LFE and HFE program reduced neuropathic pain. Our findings indicated that aerobic exercise-induced alleviated neuropathic pain through the regulation of glial cell activation, expression of BDNF in the ipsilateral spinal dorsal horn, and the endogenous opioid system. PMID:29445295

Content validity of manual spinal palpatory exams - A systematic review

PubMed Central

Najm, Wadie I; Seffinger, Michael A; Mishra, Shiraz I; Dickerson, Vivian M; Adams, Alan; Reinsch, Sibylle; Murphy, Linda S; Goodman, Arnold F

2003-01-01

Background Many health care professionals use spinal palpatory exams as a primary and well-accepted part of the evaluation of spinal pathology. However, few studies have explored the validity of spinal palpatory exams. To evaluate the status of the current scientific evidence, we conducted a systematic review to assess the content validity of spinal palpatory tests used to identify spinal neuro-musculoskeletal dysfunction. Methods Review of eleven databases and a hand search of peer-reviewed literature, published between 1965–2002, was undertaken. Two blinded reviewers abstracted pertinent data from the retrieved papers, using a specially developed quality-scoring instrument. Five papers met the inclusion/exclusion criteria. Results Three of the five papers included in the review explored the content validity of motion tests. Two of these papers focused on identifying the level of fixation (decreased mobility) and one focused on range of motion. All three studies used a mechanical model as a reference standard. Two of the five papers included in the review explored the validity of pain assessment using the visual analogue scale or the subjects' own report as reference standards. Overall the sensitivity of studies looking at range of motion tests and pain varied greatly. Poor sensitivity was reported for range of motion studies regardless of the examiner's experience. A slightly better sensitivity (82%) was reported in one study that examined cervical pain. Conclusions The lack of acceptable reference standards may have contributed to the weak sensitivity findings. Given the importance of spinal palpatory tests as part of the spinal evaluation and treatment plan, effort is required by all involved disciplines to create well-designed and implemented studies in this area. PMID:12734016

Neuroleptic-induced "painful legs and moving toes" syndrome: successful treatment with clonazepam and baclofen.

PubMed

Sandyk, R

1990-12-01

The syndrome of "painful legs and moving toes" is characterised by spontaneous causalgic pain in the lower extremities associated with peculiar involuntary movements of the toes and feet. It has been observed after a variety of lesions affecting the posterior nerve roots, the spinal ganglia and the peripheral nerves. The pathophysiology of the syndrome is unknown. I report a patient who developed the syndrome during treatment for schizophrenia with the antipsychotic agent molindone hydrochloride. The patient's response to the combination of clonazepam and baclofen suggests that the pathophysiology of the "painful legs and moving toes" may be linked to impairment of spinal serotonergic and GABA functions.

Driving Safety after Spinal Surgery: A Systematic Review

PubMed Central

Alkhalili, Kenan; Hannallah, Jack; Ibeche, Bashar; Bajammal, Sohail; Baco, Abdul Moeen

2017-01-01

This study aimed to assess driving reaction times (DRTs) after spinal surgery to establish a timeframe for safe resumption of driving by the patient postoperatively. The MEDLINE and Google Scholar databases were analyzed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) Statement for clinical studies that investigated changes in DRTs following cervical and lumbar spinal surgery. Changes in DRTs and patients' clinical presentation, pathology, anatomical level affected, number of spinal levels involved, type of intervention, pain level, and driving skills were assessed. The literature search identified 12 studies that investigated postoperative DRTs. Six studies met the inclusion criteria; five studies assessed changes in DRT after lumbar spine surgery and two studies after cervical spina surgery. The spinal procedures were selective nerve root block, anterior cervical discectomy and fusion, and lumbar fusion and/ordecompression. DRTs exhibited variable responses to spinal surgery and depended on the patients' clinical presentation, spinal level involved, and type of procedure performed. The evidence regarding the patients' ability to resume safe driving after spinal surgery is scarce. Normalization of DRT or a return of DRT to pre-spinal intervention level is a widely accepted indicator for safe driving, with variable levels of statistical significance owing to multiple confounding factors. Considerations of the type of spinal intervention, pain level, opioid consumption, and cognitive function should be factored in the assessment of a patient's ability to safely resume driving. PMID:28443178

Driving Safety after Spinal Surgery: A Systematic Review.

PubMed

Alhammoud, Abduljabbar; Alkhalili, Kenan; Hannallah, Jack; Ibeche, Bashar; Bajammal, Sohail; Baco, Abdul Moeen

2017-04-01

This study aimed to assess driving reaction times (DRTs) after spinal surgery to establish a timeframe for safe resumption of driving by the patient postoperatively. The MEDLINE and Google Scholar databases were analyzed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) Statement for clinical studies that investigated changes in DRTs following cervical and lumbar spinal surgery. Changes in DRTs and patients' clinical presentation, pathology, anatomical level affected, number of spinal levels involved, type of intervention, pain level, and driving skills were assessed. The literature search identified 12 studies that investigated postoperative DRTs. Six studies met the inclusion criteria; five studies assessed changes in DRT after lumbar spine surgery and two studies after cervical spina surgery. The spinal procedures were selective nerve root block, anterior cervical discectomy and fusion, and lumbar fusion and/ordecompression. DRTs exhibited variable responses to spinal surgery and depended on the patients' clinical presentation, spinal level involved, and type of procedure performed. The evidence regarding the patients' ability to resume safe driving after spinal surgery is scarce. Normalization of DRT or a return of DRT to pre-spinal intervention level is a widely accepted indicator for safe driving, with variable levels of statistical significance owing to multiple confounding factors. Considerations of the type of spinal intervention, pain level, opioid consumption, and cognitive function should be factored in the assessment of a patient's ability to safely resume driving.

Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction

PubMed Central

Chen, Jeremy Tsung-chieh; Guo, Da; Campanelli, Dario; Frattini, Flavia; Mayer, Florian; Zhou, Luming; Kuner, Rohini; Heppenstall, Paul A.; Knipper, Marlies; Hu, Jing

2014-01-01

The gate control theory proposes the importance of both pre- and post-synaptic inhibition in processing pain signal in the spinal cord. However, although postsynaptic disinhibition caused by brain-derived neurotrophic factor (BDNF) has been proved as a crucial mechanism underlying neuropathic pain, the function of presynaptic inhibition in acute and neuropathic pain remains elusive. Here we show that a transient shift in the reversal potential (EGABA) together with a decline in the conductance of presynaptic GABAA receptor result in a reduction of presynaptic inhibition after nerve injury. BDNF mimics, whereas blockade of BDNF signalling reverses, the alteration in GABAA receptor function and the neuropathic pain syndrome. Finally, genetic disruption of presynaptic inhibition leads to spontaneous development of behavioural hypersensitivity, which cannot be further sensitized by nerve lesions or BDNF. Our results reveal a novel effect of BDNF on presynaptic GABAergic inhibition after nerve injury and may represent new strategy for treating neuropathic pain. PMID:25354791

Nitric oxide synthase and soluble guanylate cyclase are involved in spinal cord wind-up activity of monoarthritic, but not of normal rats.

PubMed

Laurido, Claudio; Hernández, Alejandro; Constandil, Luis; Pelissier, Teresa

2003-11-27

While increasing evidence points to a role for the nitric oxide (NO)/cyclic guanosine 3,5-monophosphate (GMPc) cascade in hyperalgesia and allodynia, participation of the NO/GMPc pathway in synaptic processing in the spinal cord, i.e. wind-up activity, is less clear. We studied the effects of intrathecal administration of Nomega-nitro-L-arginine methyl ester (L-NAME) and methylene blue, inhibitors of NO synthase and guanylate cyclase respectively, on wind-up activity developed in a C-fiber reflex response paradigm. 5, 10 and 20 microg i.t. of L-NAME or methylene blue did not modify spinal wind-up in normal rats, while a dose-dependent inhibition of wind-up was observed in monoarthritic rats. Results suggest that the NO/GMPc pathway plays a non-significant role in wind-up activity evoked in normal animals, while it may be essential in chronic pain processing.

The effects of religion and spirituality on postoperative pain, hemodynamic functioning and anxiety after cesarean section.

PubMed

Beiranvand, Siavash; Noparast, Morteza; Eslamizade, Nasrin; Saeedikia, Saeed

2014-01-01

Spiritual elements play an important role in the recovery process from acute postoperative pain. This study was conducted to assess the effect of pray meditation on postoperative pain reduction and physiologic responds among muslim patients who underwent cesarean surgery under spinal anesthesia. This double-blinded randomized clinical trial study was conducted among muslim patients who underwent cesarean surgery under spinal anesthesia during 2011-2013 at tertiary regional and teaching hospital in Lorestan, Iran. The patients were randomly divided into interventional group (n=80) and control group (n=80). For about 20 minutes using a disposable phone mentioned and listened to pray meditation "Ya man esmoho davaa va zekroho shafa, Allahomma salle ala mohammad va ale mohammad" in interventional group and phone off in control group. Before and during pray meditation, 30, 60 minutes, 3 and 6 hours after pray meditation pain intensity, blood pressure, heart rate and respiratory rate were measured. No statistically significant improvement in pain score was found before and during pray meditation, 30, 60 minutes after pray meditation (P>0.05). Statistically significant improvement in pain score was found at 3 and 6 hours after pray meditation than control group (1.5 ± 0.3 vs. 3 ± 1.3, P=0.030) and (1.3 ± 0.8 vs. 3 ± 1.1, P=0.003). However, there was no significant difference in the physiological responses (systolic and diastolic blood pressure, respiration, and heart rate) any time between the groups. Religion and spirituality intervention such as pray meditation could be used as one of non-pharmacological pain management techniques for reducing pain after cesarean surgery. Also, Pray meditation provides less postoperative nausea and vomiting (PONV) and more relaxation.

Pyrrolidine dithiocarbamate inhibits superoxide anion-induced pain and inflammation in the paw skin and spinal cord by targeting NF-κB and oxidative stress.

PubMed

Pinho-Ribeiro, Felipe A; Fattori, Victor; Zarpelon, Ana C; Borghi, Sergio M; Staurengo-Ferrari, Larissa; Carvalho, Thacyana T; Alves-Filho, Jose C; Cunha, Fernando Q; Cunha, Thiago M; Casagrande, Rubia; Verri, Waldiceu A

2016-06-01

We evaluated the effect of pyrrolidine dithiocarbamate (PDTC) in superoxide anion-induced inflammatory pain. Male Swiss mice were treated with PDTC and stimulated with an intraplantar or intraperitoneal injection of potassium superoxide, a superoxide anion donor. Subcutaneous PDTC treatment attenuated mechanical hyperalgesia, thermal hyperalgesia, paw oedema and leukocyte recruitment (neutrophils and macrophages). Intraplantar injection of superoxide anion activated NF-κB and increased cytokine production (IL-1β, TNF-α and IL-10) and oxidative stress (nitrite and lipid peroxidation levels) at the primary inflammatory foci and in the spinal cord (L4-L6). PDTC treatment inhibited superoxide anion-induced NF-κB activation, cytokine production and oxidative stress in the paw and spinal cord. Furthermore, intrathecal administration of PDTC successfully inhibited superoxide anion-induced mechanical hyperalgesia, thermal hyperalgesia and inflammatory response in peripheral foci (paw). These results suggest that peripheral stimulus with superoxide anion activates the local and spinal cord oxidative- and NF-κB-dependent inflammatory nociceptive mechanisms. PDTC targets these events, therefore, inhibiting superoxide anion-induced inflammatory pain in mice.

Correction of Grade 2 Spondylolisthesis Following a Non-Surgical Structural Spinal Rehabilitation Protocol Using Lumbar Traction: A Case Study and Selective Review of Literature

PubMed Central

Fedorchuk, Curtis; Lightstone, Douglas F; McRae, Christi; Kaczor, Derek

2017-01-01

Objective Discuss the use of non-surgical spinal rehabilitation protocol in the case of a 69-year-old female with a grade 2 spondylolisthesis. A selective literature review and discussion are provided. Clinical Features A 69-year-old female presented with moderate low back pain (7/10 pain) and severe leg cramping (7/10 pain). Initial lateral lumbar x-ray revealed a grade 2 spondylolisthesis at L4-L5 measuring 13.3 mm. Interventions and Outcomes The patient completed 60 sessions of Mirror Image® spinal exercises, adjustments, and traction over 45 weeks. Post-treatment lateral lumbar x-ray showed a decrease in translation of L4-L5 from 13.3 mm to 2.4 mm, within normal limits. Conclusions This case provides the first documented evidence of a non-surgical or chiropractic treatment, specifically Chiropractic BioPhysics®, protocols of lumbar spondylolisthesis where spinal alignment was corrected. Additional research is needed to investigate the clinical implications and treatment methods. PMID:29299090

Reducing pain with genetic amniocentesis-A randomized trial of subfreezing versus room temperature needles.

PubMed

Wax, Joseph R; Pinette, Michael G; Carpenter, Molly; Chard, Renée; Blackstone, Jacquelyn; Cartin, Angelina

2005-10-01

To determine whether pain associated with second trimester genetic amniocentesis is decreased by using subfreezing rather than room temperature needles. Subjects were randomized to a -14 degrees C or room temperature (20-22 degrees C) 22-gauge spinal needle. Patients, blinded to allocation, recorded anticipated and actual pain before and after the procedure, respectively, using a 0-10 visual analog scale with 0 = no pain and 10 = excruciating pain. Thirty-three subjects were randomized to room temperature and 29 subjects to subfreezing needles. Anticipated pain was similar in room temperature, 5.1 +/- 1.7, and subfreezing groups, 4.9 +/- 2.0, respectively (p = 0.6). Actual pain was also similar in the room temperature, 3.6 +/- 2.0, and subfreezing groups, 2.8 +/- 2.0, respectively (p = 0.14). Similar numbers of subjects in the room temperature and subfreezing groups reported less actual pain (20 vs. 18), greater actual pain (4 vs. 4) or no difference in pain (9 vs. 5) than anticipated (p = 0.6). A subfreezing 22-gauge spinal needle does not decrease perceived pain associated with second trimester genetic amniocentesis.

Clinical presentation and manual therapy for upper quadrant musculoskeletal conditions

PubMed Central

Isabel de-la-Llave-Rincón, Ana; Puentedura, Emilio J; Fernández-de-las-Peñas, César

2011-01-01

In recent years, increased knowledge of the pathogenesis of upper quadrant pain syndromes has translated to better management strategies. Recent studies have demonstrated evidence of peripheral and central sensitization mechanisms in different local pain syndromes of the upper quadrant such as idiopathic neck pain, lateral epicondylalgia, whiplash-associated disorders, shoulder impingement, and carpal tunnel syndrome. Therefore, a treatment-based classification approach where subjects receive matched interventions has been developed and, it has been found that these patients experience better outcomes than those receiving non-matched interventions. There is evidence suggesting that the cervical and thoracic spine is involved in upper quadrant pain. Spinal manipulation has been found to be effective for patients with elbow pain, neck pain, or cervicobrachial pain. Additionally, it is known that spinal manipulative therapy exerts neurophysiological effects that can activate pain modulation mechanisms. This paper exposes some manual therapies for upper quadrant pain syndromes, based on a nociceptive pain rationale for modulating central nervous system including trigger point therapy, dry needling, mobilization or manipulation, and cognitive pain approaches. PMID:23115473

Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone

PubMed Central

Hutchinson, Mark R.; Zhang, Yingning; Brown, Kimberley; Coats, Benjamen D.; Shridhar, Mitesh; Sholar, Paige W.; Patel, Sonica J.; Crysdale, Nicole Y.; Harrison, Jacqueline A.; Maier, Steven F.; Rice, Kenner C.; Watkins, Linda R.

2008-01-01

Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll-like receptor 4 (TLR4) may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury (CCI). Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived from lipopolysaccharide. Additionally, (+)-naltrexone, (+)-naloxone, and (-))-naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293-TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI-induced microglial activation by (+)-naloxone and (-))-naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron-to-glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists (+)-naloxone and (-))-naloxone can each fully reverse established neuropathic pain upon multi-day administration. This finding with (+)-naloxone is of potential clinical relevance. This is because (+)-naloxone is an antagonist that is inactive at the (-))-opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that (+)-opioid antagonists such as (+)-naloxone may be useful clinically to suppress glial activation, yet (-))-opioid agonists suppress pain. PMID:18662331

Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain.

PubMed

Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H; Porreca, Frank

2017-12-01

Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats. By contrast, GBP microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP, and elicited NAc DA release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on wide-dynamic-range neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous GBP-induced CPP and NAc DA release but failed to block its inhibition of tactile allodynia. Gabapentin, therefore, can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity, and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from nonopioid analgesics, GBP requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain-motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of GBP's analgesic effects in patients.

Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain

PubMed Central

Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H.; Porreca, Frank

2017-01-01

Gabapentin is a first-line therapy for neuropathic pain but its mechanisms and sites of action remain uncertain. We investigated gabapentin-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal gabapentin reversed evoked mechanical hypersensitivity, produced conditioned place preference (CPP) and dopamine release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal gabapentin also significantly inhibited dorsal horn wide dynamic range (WDR) neuronal responses to a range of evoked stimuli in SNL rats. In contrast, gabapentin microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP and elicited NAc dopamine release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on WDR neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous gabapentin-induced CPP and NAc dopamine release but failed to block its inhibition of tactile allodynia. Gabapentin therefore can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from non-opioid analgesics, gabapentin requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of gabapentin’s analgesic effects in patients. PMID:28832395

Herpes zoster sciatica mimicking lumbar canal stenosis: a case report.

PubMed

Koda, Masao; Mannoji, Chikato; Oikawa, Makiko; Murakami, Masazumi; Okamoto, Yuzuru; Kon, Tamiyo; Okawa, Akihiko; Ikeda, Osamu; Yamazaki, Masashi; Furuya, Takeo

2015-07-29

Symptom of herpes zoster is sometimes difficult to distinguish from sciatica induced by spinal diseases, including lumbar disc herniation and spinal canal stenosis. Here we report a case of sciatica mimicking lumbar canal stenosis. A 74-year-old Chinese male patient visited our hospital for left-sided sciatic pain upon standing or walking for 5 min of approximately 1 month's duration. At the first visit to our hospital, there were no skin lesions. A magnetic resonance imaging showed spinal canal stenosis between the 4th and 5th lumbar spine. Thus, we diagnosed the patient with sciatica induced by spinal canal stenosis. We considered decompression surgery for the stenosis of 4th and 5th lumbar spine because conservative therapy failed to relieve the patient's symptom. At that time, the patient complained of a skin rash involving his left foot for several days. A vesicular rash and erythema were observed on the dorsal and plantar surfaces of the great toe and lateral malleolus. The patient was diagnosed with herpes zoster in the left 5th lumbar spinal nerve area based on clinical findings, including the characteristics of the pain and vesicular rash and erythema in the 5th lumbar spinal dermatome. The patient was treated with famciclovir (1,500 mg/day) and non-steroidal anti-inflammatory drugs. After 1 week of medication, the skin rash resolved and pain relief was obtained. In conclusion, spinal surgeons should keep in mind herpes zoster infection as one of the possible differential diagnoses of sciatica, even if there is no typical skin rash.

Combined spinal epidural anesthesia for laparoscopic appendectomy in adults: A case series

PubMed Central

Mane, Rajesh S.; Patil, Manjunath C.; Kedareshvara, K. S.; Sanikop, C. S.

2012-01-01

Background: Laparoscopy is one of the most common surgical procedures and is the procedure of choice for most of the elective abdominal surgeries performed preferably under endotracheal general anesthesia. Technical advances in the field of laparoscopy have helped to reduce surgical trauma and discomfort, reduce anesthetic requirement resulting in shortened hospital stay. Recently, regional anaesthetic techniques have been found beneficial, especially in patients at a high risk to receive general anesthesia. Herewith we present a case series of laparoscopic appendectomy in eight American Society of Anaesthesiologists (ASA) I and II patients performed under spinal-epidural anaesthesia. Methods: Eight ASA Grade I and II adult patients undergoing elective Laparoscopic appendectomy received Combined Spinal Epidural Anaesthesia. Spinal Anaesthesia was performed at L2-L3 interspace using 2 ml of 0.5% (10 mg) hyperbaric Bupivacaine mixed with 0.5ml (25 micrograms) of Fentanyl. Epidural catheter was inserted at T10-T11 interspace for inadequate spinal anaesthesia and postoperative pain relief. Perioperative events and operative difficulty were studied. Systemic drugs were administered if patients complained of shoulder pain, abdominal discomfort, nausea or hypotension. Results: Spinal anaesthesia was adequate for surgery with no operative difficulty in all the patients. Intraoperatively, two patients experienced right shoulder pain and received Fentanyl, one patient was given Midazolam for anxiety and two were given Ephedrine for hypotension. The postoperative period was uneventful. Conclusion: Spinal anaesthesia with Hyperbaric Bupivacaine and Fentanyl is adequate and safe for elective laparoscopic appendectomy in healthy patients but careful evaluation of the method is needed particularly in compromised cardio respiratory conditions. PMID:22412773

Predominant Leg Pain Is Associated With Better Surgical Outcomes in Degenerative Spondylolisthesis and Spinal Stenosis: Results from the Spine Patient Outcomes Research Trial (SPORT)

PubMed Central

Pearson, Adam; Blood, Emily; Lurie, Jon; Abdu, William; Sengupta, Dilip; Frymoyer, John W.; Weinstein, James

2010-01-01

Study Design As-treated analysis of the Spine Patient Outcomes Research Trial (SPORT). Objective To compare baseline characteristics and surgical and nonoperative outcomes in degenerative spondylolisthesis (DS) and spinal stenosis (SpS) patients stratified by predominant pain location (i.e. leg vs. back). Summary of Background Data Evidence suggests that degenerative spondylolisthesis (DS) and spinal stenosis (SpS) patients with predominant leg pain may have better surgical outcomes than patients with predominant low back pain (LBP). Methods The DS cohort included 591 patients (62% underwent surgery), and the SpS cohort included 615 patients (62% underwent surgery). Patients were classified as leg pain predominant, LBP predominant or having equal pain according to baseline pain scores. Baseline characteristics were compared between the three predominant pain location groups within each diagnostic category, and changes in surgical and nonoperative outcome scores were compared through two years. Longitudinal regression models including baseline covariates were used to control for confounders. Results Among DS patients at baseline, 34% had predominant leg pain, 26% had predominant LBP, and 40% had equal pain. Similarly, 32% of SpS patients had predominant leg pain, 26% had predominant LBP, and 42% had equal pain. DS and SpS patients with predominant leg pain had baseline scores indicative of less severe symptoms. Leg pain predominant DS and SpS patients treated surgically improved significantly more than LBP predominant patients on all primary outcome measures at one and two years. Surgical outcomes for the equal pain groups were intermediate to those of the predominant leg pain and LBP groups. The differences in nonoperative outcomes were less consistent. Conclusions Predominant leg pain patients improved significantly more with surgery than predominant LBP patients. However, predominant LBP patients still improved significantly more with surgery than with nonoperative treatment. PMID:21124260

Perturbing NR2B-PSD-95 interaction relieves neuropathic pain by inactivating CaMKII-CREB signaling.

PubMed

Xu, Fangxia; Zhao, Xin; Liu, Lin; Song, Jia; Zhu, Yingjun; Chu, Shuaishuai; Shao, Xueming; Li, Xiuxiu; Ma, Zhengliang; Gu, Xiaoping

2017-09-06

Neuropathic pain is characterized by central sensitization. The interaction between N-methyl-D-aspartate receptors (NMDARs) and postsynaptic density protein-95 (PSD-95) plays a major role in central sensitization. Here, we aimed to investigate the analgesic effect of disruption of the interaction between NMDAR and PSD-95. Chronic dorsal root ganglia compression model rats were used to mimic sciatica. Thermal hyperalgesia and mechanical allodynia were evaluated. The expression of spinal phospho-NR2B, PSD-95, calcium/calmodulin-dependent protein kinase II (CaMKII), and cAMP response element binding protein (CREB) was measured using western blotting. A mimetic peptide Myr-NR2B9c was injected intrathecally to disrupt the interaction between PSD-95 and NR2B and detected by coimmunoprecipitation. Chronic dorsal root ganglia compression surgery induced thermal hyperalgesia and mechanical allodynia, and upregulated pain-related proteins such as phospho-NR2B, PSD-95, CaMKII, and CREB expressions in the spinal cord. Myr-NR2B9c disrupted the interaction between NR2B-containing NMDARs and PSD-95 in the spinal cord. Intrathecal administration of Myr-NR2B9c attenuated neuropathic pain behaviors and downregulated the expressions of phospho-NR2B, PSD-95, CaMKII, and CREB in the spinal cord. The present study indicates that dissociation of NR2B-containing NMDARs from PSD-95 inactivates CaMKII and CREB signaling and relieves pain.

The effectiveness of a back school program in lowerlimb amputees: a randomized controlled study.

PubMed

Anaforoğlu, Bahar; Erbahçeci, Fatih; Aksekili, Mehmet Atıf Erol

2016-06-23

A few studies have been carried out in lower limb amputees (LLAs) and they examined the incidence of and reasons for low back pain. The aim of this study was to assess the effectiveness of a back school program in LLAs with mechanical low back pain (MLBP). Forty male unilateral transfemoral amputees with MLBP were randomly allocated into two groups. A back school program was applied to Group 1 over 2 weeks. A booklet for home use was given to each participant in Group 2. Pain was assessed using a visual analogue scale. Spinal flexibility measurements were obtained. For the assessment of back pain-related disability, the Oswestry Disability Index was used. Patients were assessed at baseline, at month 1, and at month 3. At the month 1 assessment, a reduction in pain intensity and disability, and increase in spinal flexibility measurements were detected in Group 1 only (P < 0.05). At the month 3 assessment, there were improvements in all measured parameters in both groups(P < 0.05). Group 1 had better results in all parameters compared with Group 2. The back school program, combined with an exercise program, decreased pain and disability and improved the spinal flexibility significantly in LLAs with MLBP.

Spinal interleukin-10 therapy to treat peripheral neuropathic pain.

PubMed

Milligan, Erin D; Penzkover, Kathryn R; Soderquist, Ryan G; Mahoney, Melissa J

2012-01-01

  Current research indicates that chronic peripheral neuropathic pain includes a role for glia and the actions of proinflammatory factors. This review briefly discusses the glial and cytokine responses that occur following peripheral nerve damage in support of utilizing anti-inflammatory cytokine interleukin-10 (IL-10) therapy to suppress chronic peripheral neuropathic pain. SPINAL NONVIRAL INTERLEUKIN-10 GENE THERAPY:  IL-10 is one of the most powerful endogenous counter-regulators of proinflammatory cytokine function that acts in the nervous system. Subarachnoid (intrathecal) spinal injection of the gene encoding IL-10 delivered by nonviral vectors has several advantages over virally mediated gene transfer methods and leads to profound pain relief in several animal models. NONVIRAL GENE DELIVERY:  Lastly, data are reviewed that nonviral deoxyribonucleic acid (DNA) encapsulated by a biologically safe copolymer, poly(lactic-co-glycolic) acid (PLGA), thought to protect DNA, leads to significantly improved therapeutic gene transfer in animal models, which additionally and significantly extends pain relief.   The impact of these early studies exploring anti-inflammatory genes emphasizes the exceptional therapeutic potential of new biocompatible intrathecal nonviral gene delivery approaches such as PLGA microparticles. Ultimately, ongoing expression of therapeutic genes is a viable option to treat chronic neuropathic pain in the clinic. © 2012 International Neuromodulation Society.

Formalin-induced behavioural hypersensitivity and neuronal hyperexcitability are mediated by rapid protein synthesis at the spinal level

PubMed Central

Asante, Curtis O; Wallace, Victoria C; Dickenson, Anthony H

2009-01-01

Background The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation whose action can be inhibited by the drug rapamycin. Forms of long-term plasticity require protein synthesis and evidence indicates that mRNA in dendrites, axon terminals and cell bodies is essential for long-term synaptic plasticity. Specific to pain, shifts in pain thresholds and responsiveness are an expression of neuronal plasticity and this likely contributes to persistent pain. We investigated this by inhibiting the activity of mTOR with rapamycin at the spinal level, of rats that were subjected to the formalin test, using both behavioural and electrophysiological techniques. Results For in vivo electrophysiology, Sprague Dawley rats were fully anaesthetised and single-unit extracellular recordings were obtained from lamina V wide dynamic range (WDR) dorsal horn spinal neurones at the region where input is received from the hind paw. Neuronal responses from naive rats showed that rapamycin-sensitive pathways were important in nociceptive-specific C-fibre mediated transmission onto WDR neurones as well mechanically-evoked responses since rapamycin was effective in attenuating these measures. Formalin solution was injected into the hind paw prior to which, rapamycin or vehicle was applied directly onto the exposed spinal cord. When rapamycin was applied to the spinal cord prior to hind paw formalin injection, there was a significant attenuation of the prolonged second phase of the formalin test, which comprises continuing afferent input to the spinal cord, neuronal hyperexcitability and an activated descending facilitatory drive from the brainstem acting on spinal neurones. In accordance with electrophysiological data, behavioural studies showed that rapamycin attenuated behavioural hypersensitivity elicited by formalin injection into the hind paw. Conclusion We conclude that mTOR has a role in maintaining persistent pain states via mRNA translation and thus protein synthesis. We hypothesise that mTOR may be activated by excitatory neurotransmitter release acting on sensory afferent terminals as well as dorsal horn spinal neurones, which may be further amplified by descending facilitatory systems originating from higher centres in the brain. PMID:19500426

Secondary health conditions in persons with spinal cord injury: a longitudinal study from one to five years post-discharge.

PubMed

Adriaansen, Jacinthe J E; Post, Marcel W M; de Groot, Sonja; van Asbeck, Floris W A; Stolwijk-Swüste, Janneke M; Tepper, Marga; Lindeman, Eline

2013-11-01

To assess the occurrence of secondary health conditions and their potential risk factors in persons with spinal cord injury from 1 to 5 years after discharge from initial inpatient rehabilitation. Multicentre longitudinal study. A total of 139 wheelchair-dependent persons with spinal cord injury. The occurrence of secondary health conditions and their potential risk factors were assessed in a clinical interview with a rehabilitation physician at 1 and 5 years after discharge from inpatient rehabilitation and by a telephone interview 2 years after discharge. Self-report questionnaires were used for the assessment of musculoskeletal and neuropathic pain. Neuropathic pain (83.7-92.1%), musculoskeletal pain (62.3-87.1%) and urinary tract infection (56.5-58.9%) were the most frequently reported secondary health conditions. The occurrence of several secondary health conditions was higher among women and individuals with a complete lesion, tetraplegia, and with a higher body mass index. Secondary health conditions are common in the first years post-discharge following spinal cord injury, and their course seems to be relatively stable. These results emphasize the number of health issues that must be considered during post-injury care of persons with spinal cord injury living in the community, and the importance of a well-coordinated interdisciplinary approach from specialized rehabilitation centres.

Sphingosine kinase 2-deficiency mediated changes in spinal pain processing.

PubMed

Canlas, Jastrow; Holt, Phillip; Carroll, Alexander; Rix, Shane; Ryan, Paul; Davies, Lorena; Matusica, Dusan; Pitson, Stuart M; Jessup, Claire F; Gibbins, Ian L; Haberberger, Rainer V

2015-01-01

Chronic pain is one of the most burdensome health issues facing the planet (as costly as diabetes and cancer combined), and in desperate need for new diagnostic targets leading to better therapies. The bioactive lipid sphingosine 1-phosphate (S1P) and its receptors have recently been shown to modulate nociceptive signaling at the level of peripheral nociceptors and central neurons. However, the exact role of S1P generating enzymes, in particular sphingosine kinase 2 (Sphk2), in nociception remains unknown. We found that both sphingosine kinases, Sphk1 and Sphk2, were expressed in spinal cord (SC) with higher levels of Sphk2 mRNA compared to Sphk1. All three Sphk2 mRNA-isoforms were present with the Sphk2.1 mRNA showing the highest relative expression. Mice deficient in Sphk2 (Sphk2(-/-)) showed in contrast to mice deficient in Sphk1 (Sphk1(-/-)) substantially lower spinal S1P levels compared to wild-type C57BL/6 mice. In the formalin model of acute peripheral inflammatory pain, Sphk2(-/-) mice showed facilitation of nociceptive transmission during the late response, whereas responses to early acute pain, and the number of c-Fos immunoreactive dorsal horn neurons were not different between Sphk2(-/-) and wild-type mice. Chronic peripheral inflammation (CPI) caused a bilateral increase in mechanical sensitivity in Sphk2(-/-) mice. Additionally, CPI increased the relative mRNA expression of P2X4 receptor, brain-derived neurotrophic factor and inducible nitric oxide synthase in the ipsilateral SC of wild-type but not Sphk2(-/-) mice. Similarly, Sphk2(-/-) mice showed in contrast to wild-type no CPI-dependent increase in areas of the dorsal horn immunoreactive for the microglia marker Iba-1 and the astrocyte marker Glial fibrillary acidic protein (GFAP). Our results suggest that the tightly regulated cell signaling enzyme Sphk2 may be a key component for facilitation of nociceptive circuits in the CNS leading to central sensitization and pain memory formation.

Effects of dexmedetomidine infusion during spinal anesthesia on hemodynamics and sedation

PubMed Central

Tarıkçı Kılıç, Ebru; Aydın, Gaye

2018-01-01

ABSTRACT Background: We evaluated the effects of intravenous dexmedetomidine during spinal anesthesia on hemodynamics, respiratory rate, oxygen saturation, sedpain, and compared them with those of saline infusion. Sixty American Society of Anesthesiologists physical status I and II cases were randomly divided into two groups. Patients were connected to the monitor after premedication, and spinal anesthesia was administered. Sensory and motor blockades were assessed using pinprick test and Bromage scale, respectively. Group I received dexmedetomidine infusion and Group II received saline infusion. Throughout the infusion process, hemodynamic data, respiratory rate, oxygen saturation, sedation, pain, Bromage score, amnesia, bispectral index, and side effects were recorded. Postoperative hemodynamic measurements, oxygen saturation, sedation, pain scores were obtained. Sedation and pain were evaluated using the Ramsay and visual analog scales, respectively. Analgesics were administered in cases with high scores on the visual analog scale. Postoperative analgesic consumption, side effects, treatments were recorded. No significant differences were found between the groups with respect to oxygen saturation, respiratory rate, pain, and side effects in the intraoperative period. Time to onset of sensorial block, maximum sensorial block, onset of motor block, and maximum motor block; bispectral index values; and apex heartbeat until 80 min of infusion, systolic arterial blood pressure until 90 min, and diastolic arterial blood pressure until 50 min were lower, whereas amnesia and sedation levels were higher in dexmedetomidine group. Postoperative pain and analgesic requirement were not different. Apex heartbeat at 15 min and systolic arterial blood pressure at 30 min were lower and sedation scores were higher in the dexmedetomidine infusion group. We demonstrated dexmedetomidine infusion had a hemodynamic depressant effect intraoperatively whereas it had no significant effect on peripheral oxygen saturation, respiratory rate, visual analog scale scores, and side effects. Dexmedetomidine infusion enhanced motor and sensory blockade quality and induced amnesia and sedation. PMID:29457538

Malignant spinal cord compression in cancer patients may be mimicked by a primary spinal cord tumour.

PubMed

Mohammadianpanah, M; Vasei, M; Mosalaei, A; Omidvari, S; Ahmadloo, N

2006-12-01

Although it is quite rare, second primary neoplasms in cancer patients may present with the signs and symptoms of malignant spinal cord compression. Primary spinal cord tumours in the cancer patients may be deceptive and considered as the recurrent first cancer. Therefore, it should be precisely differentiated and appropriately managed. We report such a case of intramedullary ependymoma of the cervical spinal cord mimicking metatstatic recurrent lymphoma and causing cord compression. A 50-year-old man developed intramedullary ependymoma of the cervical spinal cord 1.5 years following chemoradiation for Waldeyer's ring lymphoma. He presented with a 2-month history of neck pain, progressive upper- and lower-extremity numbness and weakness, and bowel and bladder dysfunction. Magnetic resonance imaging revealed an intramedullary expansive lesion extending from C4 to C6 levels of the cervical spinal cord. The clinical and radiological findings were suggestive of malignant process. A comprehensive investigation failed to detect another site of disease. He underwent operation, and the tumour was subtotally resected. The patient's neurological deficits improved subsequently. The development of the intramedullary ependymoma following treating lymphoma has not been reported. We describe the clinical, radiological and pathological findings of this case and review the literature.

Central glucocorticoid receptors regulate the upregulation of spinal cannabinoid-1 receptors after peripheral nerve injury in rats.

PubMed

Wang, Shuxing; Lim, Grewo; Mao, Ji; Sung, Backil; Yang, Liling; Mao, Jianren

2007-09-01

Previous studies have shown that peripheral nerve injury upregulated both glucocorticoid receptors (GR) and cannabinoid-1 receptors (CB1R) within the spinal cord dorsal horn in rats. However, the relationship between the expression of spinal GR and CB1R after nerve injury remains unclear. Here, we examined the hypothesis that the upregulation of spinal CB1R induced by chronic constriction nerve injury (CCI) in rats would be regulated by spinal GR. CCI induced the upregulation of spinal CB1R primarily within the ipsilateral spinal cord dorsal horn as revealed by Western blot and immunohistochemistry. The expression of CB1R in CCI rats was substantially attenuated by intrathecal treatment with either the GR antagonist RU38486 or a GR antisense oligonucleotide given twice daily for postoperative day 1-6, whereas the expression of spinal CB1R was enhanced following intrathecal administration of a GR sense oligonucleotide twice daily for postoperative day 1-6. Furthermore, the upregulation of spinal CB1R after nerve injury was prevented in adrenalectomized rats, which was at least partially restored with the intrathecal administration of an exogenous GR agonist dexamethasone, indicating that corticosteroids (endogenous GR agonists) were critical to spinal GR actions. Since the development of neuropathic pain behaviors in CCI rats was attenuated by either RU38486 or a GR antisense oligonucleotide, these results suggest that CB1R is a downstream target for spinal GR actions contributory to the mechanisms of neuropathic pain.

Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson's Disease

PubMed Central

Wang, Bing; Chen, Li-Hua

2016-01-01

In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain. PMID:27747105

The influence of shoulder pain on functional limitation, perceived health, and depressive mood in patients with traumatic paraplegia

PubMed Central

Wang, Jia-Chi; Chan, Rai-Chi; Tsai, Yun-An; Huang, Wen-Cheng; Cheng, Henrich; Wu, Han-Lin

2015-01-01

Objective To assess whether functional activity, perceived health, and depressive symptoms differ between individuals with traumatic paraplegia with and without shoulder pain. Design Cross sectional and comparative investigation using the unified questionnaire. Setting Neural Regeneration and Repair Division unit of Taipei Veterans General Hospital in Taiwan. Participants Seventy-six patients with paraplegia (23 with and 53 without shoulder pain) who had experienced spinal cord injury at American Spinal Injury Association Impairment Scale T2 to T12 neurologic level (at least 6 months previously). Outcome measures Spinal Cord Independence Measure (SCIM), a single item from the Medical Outcomes Study 36-Item Short-Form Health Survey, and Patient Health Questionnaire-9 (PHQ-9) depression scale. Results Shoulder pain was prevalent in 30% patients. Patients with shoulder pain had significantly worse perceived health and greater depressive symptoms than those without. No significant difference was found in functional ability between groups. Greater shoulder pain intensity was related to higher depressive scores (r = 0.278, P = 0.017) and lower self-perceived health scores (r = −0.433, P < 0.001) but not SCIM scores (P = 0.342). Conclusion Although shoulder pain was unrelated to functional limitation, it was associated with lower perceived health and higher depressive mood levels. PMID:25296991

Sigma-1 Receptor Antagonist BD1047 Reduces Mechanical Allodynia in a Rat Model of Bone Cancer Pain through the Inhibition of Spinal NR1 Phosphorylation and Microglia Activation

PubMed Central

Zhu, Shanshan; Wang, Chenchen; Han, Yuan; Song, Chao; Hu, Xueming; Liu, Yannan

2015-01-01

Previous studies have demonstrated that sigma-1 receptor plays important roles in the induction phase of rodent neuropathic pain; however, whether it is involved in bone cancer pain (BCP) and the underlying mechanisms remain elusive. The aim of this study was to examine the potential role of the spinal sigma-1 receptor in the development of bone cancer pain. Walker 256 mammary gland carcinoma cells were implanted into the intramedullary space of the right tibia of Sprague-Dawley rats to induce ongoing bone cancer-related pain behaviors; our findings indicated that, on days 7, 10, 14, and 21 after operation, the expression of sigma-1 receptor in the spinal cord was higher in BCP rats compared to the sham rats. Furthermore, intrathecal injection of 120 nmol of sigma-1 receptor antagonist BD1047 on days 5, 6, and 7 after operation attenuated mechanical allodynia as well as the associated induction of c-Fos and activation of microglial cells, NR1, and the subsequent Ca2+-dependent signals of BCP rats. These results suggest that sigma-1 receptor is involved in the development of bone cancer pain and that targeting sigma-1 receptor may be a new strategy for the treatment of bone cancer pain. PMID:26696751

Shoulder pain after caesarean section: comparison between general and spinal anaesthesia.

PubMed

Zirak, N; Soltani, G; Hafizi, L; Mashayekhi, Z; Kashani, I

2012-05-01

This study investigated shoulder pain as a maternal complication after caesarean section (CS), evaluation of its prevalence and comparison between spinal anaesthesia (SA) and general anaesthesia (GA) groups. A total of 200 women as CS candidates were allocated into two equal groups; SA and GA. The total prevalence of shoulder pain was 39.45%. The two groups were matched according to demographic data. However, the incidence of shoulder pain in the GA group was more than that in the SA group (p =0.004). Shoulder pain in the right shoulder in the GA group was more prevalent than the left shoulder (p <0.001). Moderate severity of shoulder pain was significantly more in the GA group (p =0.000), while in the SA group, the mild severity was significant (p <0.001). Our study revealed that the incidence of shoulder pain after CS is significant. Moreover, shoulder pain was significantly more common in the GA group than the SA group.

Constitutive cyclooxygenase-2 is involved in central nociceptive processes in humans

PubMed Central

Martin, Frédéric; Fletcher, Dominique; Chauvin, Marcel; Bouhassira, Didier

2007-01-01

Background Prostaglandins play a major role in inflammation and pain. They are synthesised by the two cyclooxygenase (COX) isoforms: COX-1, which is expressed constitutively in many cell types and COX-2, which is induced at the site of inflammation. However, unlike peripheral tissues, COX-2 is expressed constitutively in the central nervous system and may play a role in nociceptive processes. The present study aimed to investigate the role of constitutive COX-2 in the spinal transmission of nociceptive signals in humans. Methods We used 12 healthy volunteers to compare the effects of the specific COX-2 inhibitor sodium parecoxib (1 mg/kg) or placebo, administered intravenously in a double-blind and cross-over fashion, on the electrophysiological recordings of the nociceptive flexion (RIII) reflex. The RIII reflex is an objective psychophysiological index of the spinal transmission of nociceptive signals and was recorded from the biceps femoris after electrical stimulation of the sural nerve. Two experiments, seven days apart, were carried out on each volunteer. On each experimental day, the effects of parecoxib or placebo were tested on: 1) the RIII reflex threshold, 2) the stimulus-response curves of the reflex up to the tolerance threshold (frequency of stimulation: 0.1 Hz); 3) the progressive increase of the reflex and pain sensations (i.e. “wind-up” phenomenon) induced by a series of 15 stimulations at a frequency of 1 Hz (intensity 20% above RIII threshold). Results Parecoxib, but not placebo, significantly reduced the slope of the stimulus-response curve, suggesting a reduction in the gain of the spinal transmision of nociceptive signals. By contrast, the “wind-up” phenomenon was not significantly altered after administration of parecoxib or placebo. Conclusions Our study shows that constitutive COX-2 modulates spinal nociceptive processes and that the anti-inflammatory and antinociceptive actions of COX-2 inhibitors are not necessarily related. PMID:17457134

Intrathecal curcumin attenuates pain hypersensitivity and decreases spinal neuroinflammation in rat model of monoarthritis.

PubMed

Chen, Jun-Jie; Dai, Lin; Zhao, Lin-Xia; Zhu, Xiang; Cao, Su; Gao, Yong-Jing

2015-05-19

Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. Neuroinflammation has been recognized to play an important role in the pathogenesis of various diseases in the central nervous system. Here we investigated the anti-nociceptive and anti-neuroinflammatory effect of curcumin on arthritic pain in rats. We found that repeated oral treatment with curcumin, either before or after complete Freund's adjuvant (CFA) injection, dose-dependently attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, but had no effect on joint edema. Repeated intrathecal injection of curcumin reversed CFA-induced pain hypersensitivity. Furthermore, such a curcumin treatment reduced CFA-induced activation of glial cells and production of inflammatory mediators [interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and monocyte inflammatory protein-1 (MIP-1α)] in the spinal cord. Curcumin also decreased lipopolysaccharide-induced production of IL-1β, tumor necrosis factor-α, MCP-1, and MIP-1α in cultured astrocytes and microglia. Our results suggest that intrathecal curcumin attenuates arthritic pain by inhibiting glial activation and the production of inflammatory mediators in the spinal cord, suggesting a new application of curcumin for the treatment of arthritic pain.

Intrathecal curcumin attenuates pain hypersensitivity and decreases spinal neuroinflammation in rat model of monoarthritis

PubMed Central

Chen, Jun-Jie; Dai, Lin; Zhao, Lin-Xia; Zhu, Xiang; Cao, Su; Gao, Yong-Jing

2015-01-01

Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. Neuroinflammation has been recognized to play an important role in the pathogenesis of various diseases in the central nervous system. Here we investigated the anti-nociceptive and anti-neuroinflammatory effect of curcumin on arthritic pain in rats. We found that repeated oral treatment with curcumin, either before or after complete Freund’s adjuvant (CFA) injection, dose-dependently attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, but had no effect on joint edema. Repeated intrathecal injection of curcumin reversed CFA-induced pain hypersensitivity. Furthermore, such a curcumin treatment reduced CFA-induced activation of glial cells and production of inflammatory mediators [interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and monocyte inflammatory protein-1 (MIP-1α)] in the spinal cord. Curcumin also decreased lipopolysaccharide-induced production of IL-1β, tumor necrosis factor-α, MCP-1, and MIP-1α in cultured astrocytes and microglia. Our results suggest that intrathecal curcumin attenuates arthritic pain by inhibiting glial activation and the production of inflammatory mediators in the spinal cord, suggesting a new application of curcumin for the treatment of arthritic pain. PMID:25988362

Rehabilitation of low back pain patients. A review.

PubMed

Revel, M

1995-01-01

Numerous methods have been developed for the rehabilitation of low back pain patients, including spinal flexion and extension exercises, lumbar spine locking in an intermediate position, enhancement of spinal and pelvic proprioceptive sensibility, swimming pool therapy, back schools, and functional restoration. Each seeks to achieve a goal assumed to be central to the prevention of a first or recurrent episode of low back pain. Goals include short-term pain relief, an improved ability to achieve self-sedation, abdominal and lumbar muscle strengthening, increased hip and lumbar spine mobility, improved lumbar and pelvic proprioceptive sensibility, intervertebral joint stabilization, lumbar posture modification and improved general fitness. Less than 30 studies meeting widely accepted validity and applicability criteria for therapeutic trials have addressed the clinical efficacy of rehabilitation in low back pain patients. Most studies of the back school approach have found no benefit. Spinal flexion and extension exercise programs have yielded short-lived improvements, with no differences across methods. There is evidence that functional restoration programs based on graded activity may provide long-term benefits including better social and occupational outcomes. We have evaluated the physical therapy methods most commonly taught to and used by physical therapists in France.

Central Pain Syndrome

MedlinePlus

... cord. This syndrome can be caused by stroke, multiple sclerosis, tumors, epilepsy, brain or spinal cord trauma, or ... cord. This syndrome can be caused by stroke, multiple sclerosis, tumors, epilepsy, brain or spinal cord trauma, or ...

Pain outcomes after surgery in patients with intramedullary spinal cord cavernous malformations.

PubMed

Deutsch, Harel

2010-09-01

The objective of the study was to quantify the improvement in pain levels for patients who have undergone surgery for intramedullary spinal cord cavernous malformations (SCCMs). The author reviewed medical records of patients who underwent surgery for an intramedullary SCCM between 2003 and 2010. Numerical pain scores (range 0-10) were recorded preoperatively and at follow-up. The follow-up period exceeded 1 year. Neurological status and subjective outcomes were assessed. Each patient underwent follow-up MR imaging. Five patients were identified with SCCMs who underwent surgery: 4 with thoracic and 1 with cervical lesions. Patients had been conservatively managed for an average of 5 years prior to surgery, and none had a history of acute hemorrhage or neurological deterioration during the observation period. The primary indication for surgery in each patient was pain, although 4 of 5 patients had some evidence of myelopathy on examination. Pain improved from a mean preoperative score of 8.6 to mean score of 2.0 (p < 0.01) at 1 month. Pain scores then increased to 3.7 (p < 0.01) at 1 year. All patients had some improvement in pain. No new motor weakness was noted, but all patients had increased symptoms of posterior-column dysfunction and numbness after surgery. Spinal cord intramedullary cavernous malformations are increasingly being diagnosed early with patients presenting with mostly pain symptoms. Removal of the lesion is reliably associated with improvement in pain scores but often the pain improvement is transient. While long-term worsening of pain scores occurs, at 1-year follow-up, patients reported pain scores were improved over preoperative scores. In all patients some degree of postoperative posterior-column dysfunction was present. Some of the immediate pain relief may be due to analgesia related to the myelotomy of newly described posterior column pain pathways. In patients with severe pain, surgery to remove SCCMs reduced the overall pain level at 1 year.

Spinal Ceramide and Neuronal Apoptosis in Morphine Antinociceptive Tolerance

PubMed Central

Bryant, Leesa; Doyle, Tim; Chen, Zhoumo; Cuzzocrea, Salvatore; Masini, Emanuela; Vinci, M. Cristina; Esposito, Emanuela; Mazzon, Emanuela; Petrusca, Daniela Nicoleta; Petrache, Irina; Salvemini, Daniela

2009-01-01

Opiates, like morphine, are the most effective analgesics for treating acute and chronic severe pain, but their use is limited by the development of analgesic tolerance and hypersensitivity to innocuous and noxious stimuli. Because opioids are a mainstay of pain management, restoring their efficacy has great clinical importance. We have recently demonstrated that spinal ceramide, a sphingolipid signaling molecule plays a central role in the development of morphine antinociceptive tolerance. We now report that ceramide up-regulation in dorsal horn tissues in response to chronic morphine administration is associated with significant neuronal apoptosis. Inhibition of ceramide biosynthesis attenuated both the increase in neuronal apoptosis and the development of antinociceptive tolerance. These findings indicate that spinal ceramide upregulation is a key pro-apoptotic event that occurs upstream of the development of morphine antinociceptive tolerance and support the rationale for development of inhibitors of ceramide biosynthesis as adjuncts to opiates for the management of chronic pain. PMID:19631718

Assessment of Effectiveness of Percutaneous Adhesiolysis in Managing Chronic Low Back Pain Secondary to Lumbar Central Spinal Canal Stenosis

PubMed Central

Manchikanti, Laxmaiah; Cash, Kimberly A.; McManus, Carla D.; Pampati, Vidyasagar

2013-01-01

Background: Chronic persistent low back and lower extremity pain secondary to central spinal stenosis is common and disabling. Lumbar surgical interventions with decompression or fusion are most commonly performed to manage severe spinal stenosis. However, epidural injections are also frequently performed in managing central spinal stenosis. After failure of epidural steroid injections, the next sequential step is percutaneous adhesiolysis and hypertonic saline neurolysis with a targeted delivery. The literature on the effectiveness of percutaneous adhesiolysis in managing central spinal stenosis after failure of epidural injections has not been widely studied. Study Design: A prospective evaluation. Setting: An interventional pain management practice, a specialty referral center, a private practice setting in the United States. Objective: To evaluate the effectiveness of percutaneous epidural adhesiolysis in patients with chronic low back and lower extremity pain with lumbar central spinal stenosis. Methods: Seventy patients were recruited. The initial phase of the study was randomized, double-blind with a comparison of percutaneous adhesiolysis with caudal epidural injections. The 25 patients from the adhesiolysis group continued with follow-up, along with 45 additional patients, leading to a total of 70 patients. All patients received percutaneous adhesiolysis and appropriate placement of the Racz catheter, followed by an injection of 5 mL of 2% preservative-free lidocaine with subsequent monitoring in the recovery room. In the recovery room, each patient also received 6 mL of 10% hypertonic sodium chloride solution, and 6 mg of non-particulate betamethasone, followed by an injection of 1 mL of sodium chloride solution and removal of the catheter. Outcomes Assessment: Multiple outcome measures were utilized including the Numeric Rating Scale (NRS), the Oswestry Disability Index 2.0 (ODI), employment status, and opioid intake with assessment at 3, 6, and 12, 18 and 24 months post treatment. The primary outcome measure was 50% or more improvement in pain scores and ODI scores. Results: Overall, a primary outcome or significant pain relief and functional status improvement of 50% or more was seen in 71% of patients at the end of 2 years. The overall number of procedures over a period of 2 years were 5.7 ± 2.73. Limitations: The lack of a control group and a prospective design. Conclusions: Significant relief and functional status improvement as seen in 71% of the 70 patients with percutaneous adhesiolysis utilizing local anesthetic steroids and hypertonic sodium chloride solution may be an effective management strategy in patients with chronic function limiting low back and lower extremity pain with central spinal stenosis after failure of conservatie management and fluoroscopically directed epidural injections. PMID:23289005

Relationship between spinal morphology and function and adolescent non-specific back pain: A cross-sectional study.

PubMed

Feng, Qiang; Jiang, Chongmin; Zhou, Yu; Huang, Yun; Zhang, Ming

2017-01-01

Non-specific back pain has become a public health problem affecting adolescent health. To examine the relationships between abnormalities in spinal morphology and non-specific back pain among adolescents. Cross-sectional study. Junior and senior high schools. Participants were screened using a questionnaire regarding back pain. Students in the pain group (n= 273, 121 boys and 152 girls) reported experiencing upper and/or lower back pain within the previous month, and those who did not report pain were assigned to the group without pain (n= 127, 63 boys and 64 girls). Participants who had experienced acute upper and/or lower back injuries within the previous month or received a definitive diagnose of disease were excluded. The SpinalMouse® was used to measure the thoracic kyphosis angle (TKA), lumbar lordosis angle (LLA), sacrum/hip angle (SA), and incline angle (INA) in both the standing position and sitting position. The SpinalMouse® also was used to measure the sacral, thoracic, and lumbar range of motion (ROM) in the fully flexed position and fully extended position in the sagittal plane. The thoracic and lumbar ROM in left/right lateral flexion was recorded. The Matthiass test was used to assess changes in the measured angles upon loading. Among junior high school students, 47.0% of boys and 53% of girls had an abnormal TKA. Among senior high school students, 52.6% of boys and 46.99% of girls had an abnormal TKA. The incidence of LLA abnormality was significantly higher among junior high boys than girls (p< 0.05), as was the incidence of hypolordosis (p< 0.05). Significantly fewer senior high boys than girls had a normal LLA value (p< 0.05). An excessive TKA (p< 0.05, odds ratio = 1.236) and limited lumbar ROM (p< 0.01, odds ratio = 0.975) were correlated with back pain in adolescents. The incidences of TKA and LLA abnormality are high among Chinese adolescents, and an excessive TKA and insufficient total lumbar ROM may be risk factors for non-specific back pain in adolescents.

Persistent pain after spinal cord injury is maintained by primary afferent activity.

PubMed

Yang, Qing; Wu, Zizhen; Hadden, Julia K; Odem, Max A; Zuo, Yan; Crook, Robyn J; Frost, Jeffrey A; Walters, Edgar T

2014-08-06

Chronic pain caused by insults to the CNS (central neuropathic pain) is widely assumed to be maintained exclusively by central mechanisms. However, chronic hyperexcitablility occurs in primary nociceptors after spinal cord injury (SCI), suggesting that SCI pain also depends upon continuing activity of peripheral sensory neurons. The present study in rats (Rattus norvegicus) found persistent upregulation after SCI of protein, but not mRNA, for a voltage-gated Na(+) channel, Nav1.8, that is expressed almost exclusively in primary afferent neurons. Selectively knocking down Nav1.8 after SCI suppressed spontaneous activity in dissociated dorsal root ganglion neurons, reversed hypersensitivity of hindlimb withdrawal reflexes, and reduced ongoing pain assessed by a conditioned place preference test. These results show that activity in primary afferent neurons contributes to ongoing SCI pain. Copyright © 2014 the authors 0270-6474/14/3410765-05$15.00/0.

The association of age, pain, and fatigue with physical functioning and depressive symptoms in persons with spinal cord injury.

PubMed

Alschuler, Kevin N; Jensen, Mark P; Sullivan-Singh, Sarah J; Borson, Soo; Smith, Amanda E; Molton, Ivan R

2013-09-01

To describe the relationship of pain and fatigue with physical and psychological functioning in adults with spinal cord injury (SCI). Cross-sectional survey. Community-based survey. Convenience sample of individuals with SCI. Not applicable. Physical functioning (Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Functioning item bank items), depression (Patient Health Questionnaire-9 (PHQ-9)), pain severity (0-10 Numerical Rating Scale (NRS)), and fatigue (0-10 NRS). Pain and fatigue were independently associated with depression, but only pain was associated with physical functioning. Additionally, depression was more severe among middle-aged participants relative to younger or older participants. Physical functioning declined with increasing age, as well as with higher level of injury. The findings support the need for continued development of effective treatments for both pain and fatigue in order to prevent and mitigate the negative effects these symptoms can have on functioning.

Incidental intrathecal injection of meglumine diatrizoate.

PubMed

Masjedi, Mansour; Khosravi, Abbas; Sabetian, Golnar; Rahmanian, Mohammad Reza

2014-05-01

Myelograghy is a process of instilling contrast medium to the subarachnoid space for evaluating the spinal column by radiography. There are various contrast solutions for different radiographic studies but not all of them are suitable for spinal column evaluation. Our patient was a 60-year-old man who developed severe pain, tonic clonic convulsions and cardiopulmonary arrest after intrathecal injection of 14 mL of meglumine diatrizoate during an elective myelography procedure. Many of these cases would die or suffer from permanent sequelae if appropriate treatment is not received. Our subject recovered completely without any sequelae after receiving appropriate treatment in a multidisciplinary intensive care unit.

"The Jackson Table Is a Pain in the…": A Qualitative Study of Providers' Perception Toward a Spinal Surgery Table.

PubMed

Asiedu, Gladys B; Lowndes, Bethany R; Huddleston, Paul M; Hallbeck, Susan

2018-03-01

The aim of this study was to define health care providers' perceptions toward prone patient positioning for spine surgery using the Jackson Table, which has not been hitherto explored. We analyzed open-ended questionnaire data and interviews conducted with the spine surgical team regarding the current process of spinal positioning/repositioning using the Jackson Table. Participants were asked to provide an open-ended explanation as to whether they think the current process of spinal positioning/repositioning is safe for the staff or patients. Follow-up qualitative interviews were conducted with 11 of the participants to gain an in-depth understanding of the challenges and safety issues related to prone patient positioning. Data analysis resulted in 6 main categories: general challenges with patient positioning, role-specific challenges, challenges with the Jackson Table and the "sandwich" mechanism, safety concerns for patients, safety concerns for the medical staff, and recommendations for best practices. This study is relevant to everyday practice for spinal surgical team members and advances our understanding of how surgical teams qualitatively view the current process of patient positioning for spinal surgery. Providers recommended best practices for using the Jackson Table, which can be achieved through standardized practice for transfer of patients, educational tools, and checklists for equipment before patient transfer and positioning. This research has identified several important practice opportunities for improving provider and patient safety in spine surgery.

[The spa and health resort- based treatment of back pain syndrome in the adolescents presenting with juvenile idiopathic scoliosis].

PubMed

Kravtsova, E Yu; Murav'ev, S V; Kravtsov, Yu I

The relevance of the problem arises from the lack of substantiation for the inclusion of transcutaneous spinal direct current stimulation (tSDCS) in the comprehensive spa and health resort-based treatment of back pain syndrome in the adolescents presenting with juvenile idiopathic scoliosis. The objective of the present study was to demonstrate the effectiveness of transcutaneous spinal direct current stimulation for the comprehensive spa and health resort-based treatment of back pain syndrome in the adolescents presenting with juvenile idiopathic scoliosis. A total of 18 patients with scoliosis forming the study group 1 received the traditional comprehensive spa and health resort-based treatment. The course of transcutaneous spinal direct current stimulation was prescribed to 38 other patients (comprising group 2) in addition to the standard procedures. Another control group was comprised of 15 practically healthy adolescents having no signs of spinal deformations. The visual analog scale for pain, the McGill questionnaire, the scale for the assessment of the situational and personal uneasiness levels (Spilberger Ch.D., Khanin Yu.L.), and the Beck and Tsung depression scales were used, beside the routine clinical methods. Statistical data processing was carried out with the use of the Statistica 6.0 software package. In the group of patients treated with the use of transcutaneous spinal direct current stimulation, regression of pain syndrome was well apparent. In the boys with the severity of pain estimated at 2 points based on the visual analog scale who received the standard course of the spa and health resort-based treatment, the pain rank index and the index of the number of the selected descriptors decreased significantly but nonetheless remained higher than in the patients treated by means of tSDCS as a component of the combined therapy (p=0.039). Simultaneously, the significantly lower level of situational (Q1=25.00; Me=36.50; Q3=45.00; p=0.036) and personal (Q1=26.00; Me=36.50; Q3=44.00; p=0.07) anxiety was observed in the group of girls in comparison with the group of those given only the standard course of the spa and health resort-based treatment. In addition, the level of trait anxiety in the female patients treated with the use of tSDCS was lower than in the girls of the control group (Q1=46.00; Me=49.00; Q3=51.5; p=0.001). In the boys undergoing the course the of tSDCS treatment, the levels of trait anxiety (Q1=29.00 ; Me=37.00 ; Q3=42.00; p=0.021) and depression estimated from the Tsung scale (Q1=2.85; Me=3.00; Q3=3.60; p=0.014) and the cognitive-affective scale of Beck (Q1=0.50; Me=2.00; Q3=5.50; p=0.041) were significantly lower than in the boys of the control group. The level of depression based on the Tsung scale was significantly lower (p=0.020) in the boys and after the standard spa and health resort-based treatment (Q1=2.50; Me=2.90; Q3=3.60) was comparable with that in the boys of the control group (Q1=4.00; Me=4.60; Q3=4.80). The present study has demonstrated the expediency of inclusion of a course of transcutaneous spinal direct current stimulation in the programs of the combined spa and health resort-based treatment for the adolescents presenting with scoliosis.

Effectiveness of Iyengar yoga in treating spinal (back and neck) pain: A systematic review

PubMed Central

Crow, Edith Meszaros; Jeannot, Emilien; Trewhela, Alison

2015-01-01

Considerable amount of money spent in health care is used for treatments of lifestyle related, chronic health conditions, which come from behaviors that contribute to morbidity and mortality of the population. Back and neck pain are two of the most common musculoskeletal problems in modern society that have significant cost in health care. Yoga, as a branch of complementary alternative medicine, has emerged and is showing to be an effective treatment against nonspecific spinal pain. Recent studies have shown positive outcome of yoga in general on reducing pain and functional disability of the spine. The objective of this study is to conduct a systematic review of the existing research within Iyengar yoga method and its effectiveness on relieving back and neck pain (defined as spinal pain). Database research form the following sources (Cochrane library, NCBI PubMed, the Clinical Trial Registry of the Indian Council of Medical Research, Google Scholar, EMBASE, CINAHL, and PsychINFO) demonstrated inclusion and exclusion criteria that selected only Iyengar yoga interventions, which in turn, identified six randomized control trials dedicated to compare the effectiveness of yoga for back and neck pain versus other care. The difference between the groups on the postintervention pain or functional disability intensity assessment was, in all six studies, favoring the yoga group, which projected a decrease in back and neck pain. Overall six studies with 570 patients showed, that Iyengar yoga is an effective means for both back and neck pain in comparison to control groups. This systematic review found strong evidence for short-term effectiveness, but little evidence for long-term effectiveness of yoga for chronic spine pain in the patient-centered outcomes. PMID:25558128

Effectiveness of transcranial direct current stimulation and visual illusion on neuropathic pain in spinal cord injury

PubMed Central

Kumru, Hatice; Pelayo, Raul; Vidal, Joan; Tormos, Josep Maria; Fregni, Felipe; Navarro, Xavier; Pascual-Leone, Alvaro

2010-01-01

The aim of this study was to evaluate the analgesic effect of transcranial direct current stimulation of the motor cortex and techniques of visual illusion, applied isolated or combined, in patients with neuropathic pain following spinal cord injury. In a sham controlled, double-blind, parallel group design, 39 patients were randomized into four groups receiving transcranial direct current stimulation with walking visual illusion or with control illusion and sham stimulation with visual illusion or with control illusion. For transcranial direct current stimulation, the anode was placed over the primary motor cortex. Each patient received ten treatment sessions during two consecutive weeks. Clinical assessment was performed before, after the last day of treatment, after 2 and 4 weeks follow-up and after 12 weeks. Clinical assessment included overall pain intensity perception, Neuropathic Pain Symptom Inventory and Brief Pain Inventory. The combination of transcranial direct current stimulation and visual illusion reduced the intensity of neuropathic pain significantly more than any of the single interventions. Patients receiving transcranial direct current stimulation and visual illusion experienced a significant improvement in all pain subtypes, while patients in the transcranial direct current stimulation group showed improvement in continuous and paroxysmal pain, and those in the visual illusion group improved only in continuous pain and dysaesthesias. At 12 weeks after treatment, the combined treatment group still presented significant improvement on the overall pain intensity perception, whereas no improvements were reported in the other three groups. Our results demonstrate that transcranial direct current stimulation and visual illusion can be effective in the management of neuropathic pain following spinal cord injury, with minimal side effects and with good tolerability. PMID:20685806

Neurostimulation for the treatment of axial back pain: a review of mechanisms, techniques, outcomes, and future advances.

PubMed

Deer, Timothy; Pope, Jason; Hayek, Salim; Narouze, Samer; Patil, Parag; Foreman, Robert; Sharan, Ashwini; Levy, Robert

2014-10-01

The use of spinal cord stimulation (SCS) is well established in the treatment of neuropathic pain. This procedure has been approved in the United States for neuropathic pain of the trunk and limbs from various conditions. International use is variable based on governmental policy. Most studies showing efficacy have focused on pain primarily in the limbs for such conditions as complex regional pain syndrome (CRPS), sciatica, radiculitis, ischemic limb pain, and peripheral neuropathy. Data on success in neuropathic pain of the trunk and particularly of the axial back are limited. New understanding about the targets of neuromodulation and their treatment with novel neurostimulation approaches has led to a new dawn of enthusiasm for spinal cord stimulation for axial low back pain. The authors review mechanisms, current and future targets, techniques, and their outcomes for treating axial back pain with neurostimulation. The paper discusses many newer methods and targets that may substantially improve results for the treatment of this patient group. The continuing evolution of technology and new data may well change these recommendations over time and regular updates of this manuscript will be critical moving forward. Improved technology and a better understanding of the goals of stimulation have led to a new ability to stimulate the axial low back and increase the effectiveness of these therapies to reduce pain. New paddle lead constructs, percutaneous paddle lead introduction, and other new technologies have led to an increased number of potential candidates for spinal cord stimulation. Optimizing the application of neurostimulation for chronic axial back pain will depend upon answering questions relating to patient selection, implantation technique, and stimulation parameters. © 2014 International Neuromodulation Society.

Neck pain

MedlinePlus

... injuries, such as vertebral fractures, whiplash, blood vessel injury, and even paralysis. Other causes include: Medical conditions, such as fibromyalgia Cervical arthritis or spondylosis Ruptured disk Small fractures to the spine from osteoporosis Spinal stenosis (narrowing of the spinal ...

Rostral ventromedial medulla control of spinal sensory processing in normal and pathophysiological states.

PubMed

Bee, L A; Dickenson, A H

2007-07-13

Complex networks of pathways project from various structures in the brain to modulate spinal processing of sensory input in a top-down fashion. The rostral ventromedial medulla (RVM) in the brainstem is one major final common output of this endogenous modulatory system and is involved in the relay of sensory information between the spinal cord and brain. The net output of descending neurons that exert inhibitory and facilitatory effects will determine whether neuronal activity in the spinal cord is increased or decreased. By pharmacologically blocking RVM activity with the local anesthetic lignocaine, and then measuring evoked responses of dorsal horn neurons to a range of applied peripheral stimuli, our aim was to determine the prevailing descending influence operating in normal anesthetized animals and animals with experimental neuropathic pain. The injection of 0.8 microl 2% lignocaine into the RVM caused a reduction in deep dorsal horn neuronal responses to electrical and natural stimuli in 64% of normal animals and in 81% of spinal-nerve-ligated (SNL) animals. In normal animals, responses to noxious input were predominantly reduced, while in SNL animals, reductions in spinal cord activity induced by intra-RVM lignocaine further included responses to non-noxious stimuli. This suggests that in terms of activity at least, if not number, descending facilitations are the predominant RVM influence that impacts the spinal cord in normal animals. Moreover, the increase in the proportion of neurons showing a post-lignocaine reduction in dorsal horn activity in SNL rats suggests that the strength of these facilitatory influences increases after neuropathy. This predominant inhibitory spinal effect following the injection of lignocaine into the RVM may be due to blockade of facilitatory On cells.

Cervical radiculopathy: a systematic review on treatment by spinal manipulation and measurement with the Neck Disability Index

PubMed Central

Rodine, Robert J.; Vernon, Howard

2012-01-01

Cervical radiculopathy (CR), while less common than conditions with neck pain alone, can be a significant cause of neck pain and disability; thus the determination of adequate treatment options for patients is essential. Currently, inadequate scientific literature restricts specific conservative management recommendations for CR. Despite a paucity of evidence for high-velocity low-amplitude (HVLA) spinal manipulation in the treatment for CR, this strategy has been frequently labeled as contraindicated. Scientific support for appropriate outcome measures for CR is equally deficient. While more scientific data is needed to draw firm conclusions, the present review suggests that spinal manipulation may be cautiously considered as a therapeutic option for patients suffering from CR. With respect to outcome measures, the Neck Disability Index appears well-suited for spinal manipulative treatment of CR. PMID:22457538

Sudden post-traumatic sciatica caused by a thoracic spinal meningioma.

PubMed

Mariniello, Giuseppe; Malacario, Francesca; Dones, Flavia; Severino, Rocco; Ugga, Lorenzo; Russo, Camilla; Elefante, Andrea; Maiuri, Francesco

2016-10-01

Spinal meningiomas usually present with slowly progressive symptoms of cord and root compression, while a sudden clinical onset is very rare. A 35-year-old previously symptom-free woman presented sudden right sciatica and weakness of her right leg following a fall with impact to her left foot. A neurological examination showed paresis of the right quadriceps, tibial and sural muscles, increased bilateral knee and ankle reflexes and positive Babinski sign. Magnetic resonance imaging (MRI) revealed the presence of a spinal T11 meningioma in the left postero-lateral compartment of the spinal canal; at this level, the spinal cord was displaced to the contralateral side with the conus in the normal position. At surgery, a meningioma with dural attachment of the left postero-lateral dural surface was removed. The intervention resulted in rapid remission of both pain and neurological deficits. Spinal meningiomas may exceptionally present with sudden pain and neurological deficits as result of tumour bleeding or post-traumatic injury of the already compressed nervous structures, both in normal patients and in those with conus displacement or tethered cord. In this case, the traumatic impact of the left foot was transmitted to the spine, resulting in stretching of the already compressed cord and of the contralateral lombosacral roots. This case suggests that low thoracic cord compression should be suspected in patients with post-traumatic radicular leg pain with normal lumbar spine MRI. © The Author(s) 2016.

Mechanical hypersensitivity, sympathetic sprouting, and glial activation are attenuated by local injection of corticosteroid near the lumbar ganglion in a rat model of neuropathic pain.

PubMed

Li, Jing-Yi; Xie, Wenrui; Strong, Judith A; Guo, Qu-Lian; Zhang, Jun-Ming

2011-01-01

Inflammatory responses in the lumbar dorsal root ganglion (DRG) play a key role in pathologic pain states. Systemic administration of a common anti-inflammatory corticosteroid, triamcinolone acetonide (TA), reduces sympathetic sprouting, mechanical pain behavior, spontaneous bursting activity, and cytokine and nerve growth factor production in the DRG. We hypothesized that systemic TA effects are primarily due to local effects on the DRG. Male Sprague-Dawley rats were divided into 4 groups: SNL (tight ligation and transection of spinal nerves) and normal with and without a single dose of TA injectable suspension slowly injected onto the surface of DRG and surrounding region at the time of SNL or sham surgery. Mechanical threshold was tested on postoperative days 1, 3, 5, and 7. Immunohistochemical staining examined tyrosine hydroxylase and glial fibrillary acidic protein in DRG and CD11B antibody (OX-42) in spinal cord. Local TA treatment attenuated mechanical sensitivity, reduced sympathetic sprouting in the DRG, and decreased satellite glia activation in the DRG and microglia activation in the spinal cord after SNL. A single injection of corticosteroid in the vicinity of the axotomized DRG can mimic many effects of systemic TA, mitigating behavioral and cellular abnormalities induced by spinal nerve ligation. This provides a further rationale for the use of localized steroid injections clinically and provides further support for the idea that localized inflammation at the level of the DRG is an important component of the spinal nerve ligation model, commonly classified as neuropathic pain model.

Lumbar Muscle Cross-Sectional Areas Do Not Predict Clinical Outcomes in Adults With Spinal Stenosis: A Longitudinal Study.

PubMed

Gellhorn, Alfred C; Suri, Pradeep; Rundell, Sean D; Olafsen, Nathan; Carlson, M Jake; Johnson, Steve; Fry, Adrielle; Annaswamy, Thiru M; Gilligan, Christopher; Comstock, Bryan; Heagerty, Patrick; Friedly, Janna; Jarvik, Jeffrey G

2017-06-01

Minimal longitudinal data exist regarding the role of lumbar musculature in predicting back pain and function. In cross-sectional study designs, there is often atrophy of the segmental multifidus muscle in subjects with low back pain compared with matched controls. However, the cross-sectional design of these studies prevents drawing conclusions regarding whether lumbar muscle characteristics predict or modify future back pain or function. The primary objective of this study is to determine whether the cross-sectional area (CSA) of lumbar muscles predict functional status or back pain at 6- or 12-month follow-up in older adults with spinal degeneration. The secondary objective is to evaluate whether these muscle characteristics improve outcome prediction above and beyond the prognostic information conferred by demographic and psychosocial variables. Secondary analysis of a randomized controlled trial. A total of 209 adults aged 50 years and older with clinical and radiographic spinal stenosis from the Lumbar Epidural steroid injection for Spinal Stenosis (LESS) trial. Using baseline magnetic resonance images, we calculated CSAs of the lumbar multifidus, psoas, and quadratus lumborum muscles using a standardized protocol by manually tracing the borders of each of the muscles. The relationship between lumbar muscle CSAs and baseline measures was assessed with Pearson or Spearman correlation coefficients. The relationship between lumbar muscle characteristics and 6- and 12-month Roland Morris Disability Questionnaire (RDQ) and back pain Numeric Rating Scale (NRS) responses was further evaluated with multivariate linear regression. A hierarchical approach to the regression was performed: a basic model with factors of conceptual importance including age, gender, BMI, and baseline RDQ score formed the first step. The second and third steps evaluated whether psychosocial variables or muscle measures conferred additional prognostic information to the basic model. Function as measured by the RDQ and back pain as measured by the NRS at 6- and 12-month follow-up. Lumbar muscle CSA was not a significant predictor of 6- or 12-month RDQ or pain score in multivariate analyses. Cross-sectional areas of lumbar muscles do not predict function or pain at medium- and long-term follow-up in adults with lumbar spinal stenosis. III. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Functional Organization of Cutaneous and Muscle Afferent Synapses onto Immature Spinal Lamina I Projection Neurons

PubMed Central

Li, Jie

2017-01-01

It is well established that sensory afferents innervating muscle are more effective at inducing hyperexcitability within spinal cord circuits compared with skin afferents, which likely contributes to the higher prevalence of chronic musculoskeletal pain compared with pain of cutaneous origin. However, the mechanisms underlying these differences in central nociceptive signaling remain incompletely understood, as nothing is known about how superficial dorsal horn neurons process sensory input from muscle versus skin at the synaptic level. Using a novel ex vivo spinal cord preparation, here we identify the functional organization of muscle and cutaneous afferent synapses onto immature rat lamina I spino-parabrachial neurons, which serve as a major source of nociceptive transmission to the brain. Stimulation of the gastrocnemius nerve and sural nerve revealed significant convergence of muscle and cutaneous afferent synaptic input onto individual projection neurons. Muscle afferents displayed a higher probability of glutamate release, although short-term synaptic plasticity was similar between the groups. Importantly, muscle afferent synapses exhibited greater relative expression of Ca2+-permeable AMPARs compared with cutaneous inputs. In addition, the prevalence and magnitude of spike timing-dependent long-term potentiation were significantly higher at muscle afferent synapses, where it required Ca2+-permeable AMPAR activation. Collectively, these results provide the first evidence for afferent-specific properties of glutamatergic transmission within the superficial dorsal horn. A larger propensity for activity-dependent strengthening at muscle afferent synapses onto developing spinal projection neurons could contribute to the enhanced ability of these sensory inputs to sensitize central nociceptive networks and thereby evoke persistent pain in children following injury. SIGNIFICANCE STATEMENT The neurobiological mechanisms underlying the high prevalence of chronic musculoskeletal pain remain poorly understood, in part because little is known about why sensory neurons innervating muscle appear more capable of sensitizing nociceptive pathways in the CNS compared with skin afferents. The present study identifies, for the first time, the functional properties of muscle and cutaneous afferent synapses onto immature lamina I projection neurons, which convey nociceptive information to the brain. Despite many similarities, an enhanced relative expression of Ca2+-permeable AMPA receptors at muscle afferent synapses drives greater LTP following repetitive stimulation. A preferential ability of the dorsal horn synaptic network to amplify nociceptive input arising from muscle is predicted to favor the generation of musculoskeletal pain following injury. PMID:28069928

Chronic spontaneous lumbar epidural hematoma simulating extradural spinal tumor: a case report.

PubMed

Matsui, Hiroki; Imagama, Shiro; Ito, Zenya; Ando, Kei; Hirano, Kenichi; Tauchi, Ryoji; Muramoto, Akio; Matsumoto, Tomohiro; Ishiguro, Naoki

2014-02-01

Spinal epidural hematoma (SEH) is an uncommon disorder, and chronic SEHs are rarer than acute SEHs. However, there is few reported involving the bone change of the vertebral body in chronic SEHs. We present a case report of lumbar epidural hematoma that required differentiation from extramedullary spinal tumors by a long process because the CT scan revealed scalloping of the vertebral body and review the relevant literature. A 78-year-old man had experienced a gradual onset of low back pain and excruciating pain in both legs. Lumbar MRI on T1-weighted images revealed a space-occupying lesion with a hyperintense signal relative to the spinal cord with no enhancement on gadolinium adminisration. Meanwhile, T2-weighted images revealed a heterogeneous intensity change, accompanying a central area of hyperintense signals with a hypointense peripheral border at the L4 vertebra. Moreover, the CT scan demonstrated scalloping of the posterior wall of the L4 vertebral body which is generally suspected as the CT finding of spainal tumor. During the epidural space exploration, we found a dark red-colored mass surrounded by a capsular layer, which was fibrous and adhered to the flavum and dura mater. Microscopic histological examination of the resected mass revealed a mixture of the relatively new hematoma and the hematoma that was moving into the connective tissue. Accordingly, the hematoma was diagnosed as chronic SEH. The particular MRI findings of chronic SEHs are helpful for making accurate preoperative diagnoses of this pathology.

IL4-10 Fusion Protein Is a Novel Drug to Treat Persistent Inflammatory Pain.

PubMed

Eijkelkamp, Niels; Steen-Louws, Cristine; Hartgring, Sarita A Y; Willemen, Hanneke L D M; Prado, Judith; Lafeber, Floris P J G; Heijnen, Cobi J; Hack, C E; van Roon, Joel A G; Kavelaars, Annemieke

2016-07-13

Chronic pain is a major clinical problem that is difficult to treat and requires novel therapies. Although most pain therapies primarily target neurons, neuroinflammatory processes characterized by spinal cord and dorsal root ganglion production of proinflammatory cytokines play an important role in persistent pain states and represent potential therapeutic targets. Anti-inflammatory cytokines are attractive candidates to regulate aberrant neuroinflammatory processes, but the therapeutic potential of these cytokines as stand-alone drugs is limited. Their optimal function requires concerted actions with other regulatory cytokines, and their relatively small size causes rapid clearance. To overcome these limitations, we developed a fusion protein of the anti-inflammatory cytokines interleukin 4 (IL4) and IL10. The IL4-10 fusion protein is a 70 kDa glycosylated dimeric protein that retains the functional activity of both cytokine moieties. Intrathecal administration of IL4-10 dose-dependently inhibited persistent inflammatory pain in mice: three IL4-10 injections induced full resolution of inflammatory pain in two different mouse models of persistent inflammatory pain. Both cytokine moieties were required for optimal effects. The IL4-10 fusion protein was more effective than the individual cytokines or IL4 plus IL10 combination therapy and also inhibited allodynia in a mouse model of neuropathic pain. Mechanistically, IL4-10 inhibited the activity of glial cells and reduced spinal cord and dorsal root ganglion cytokine levels without affecting paw inflammation. In conclusion, we developed a novel fusion protein with improved efficacy to treat pain, compared with wild-type anti-inflammatory cytokines. The IL4-10 fusion protein has potential as a treatment for persistent inflammatory pain. The treatment of chronic pain is a major clinical and societal challenge. Current therapies to treat persistent pain states are limited and often cause major side effects. Therefore, novel analgesic treatments are urgently needed. In search of a novel drug to treat chronic pain, we developed a fusion protein consisting of two prototypic regulatory cytokines, interleukin 4 (IL4) and IL10. The work presented in this manuscript shows that this IL4-10 fusion protein overcomes some major therapeutic limitations of pain treatment with individual cytokines. The IL4-10 fusion protein induces full resolution of persistent inflammatory pain in two different mouse models. These novel findings are significant, as they highlight the IL4-10 fusion protein as a long-needed potential new drug to stop persistent pain states. Copyright © 2016 the authors 0270-6474/16/367353-11$15.00/0.

IL4-10 Fusion Protein Is a Novel Drug to Treat Persistent Inflammatory Pain

PubMed Central

Steen-Louws, Cristine; Hartgring, Sarita A. Y.; Willemen, Hanneke L. D. M.; Prado, Judith; Lafeber, Floris P. J. G.; Heijnen, Cobi J.; Hack, C. E.; van Roon, Joel A. G.; Kavelaars, Annemieke

2016-01-01

Chronic pain is a major clinical problem that is difficult to treat and requires novel therapies. Although most pain therapies primarily target neurons, neuroinflammatory processes characterized by spinal cord and dorsal root ganglion production of proinflammatory cytokines play an important role in persistent pain states and represent potential therapeutic targets. Anti-inflammatory cytokines are attractive candidates to regulate aberrant neuroinflammatory processes, but the therapeutic potential of these cytokines as stand-alone drugs is limited. Their optimal function requires concerted actions with other regulatory cytokines, and their relatively small size causes rapid clearance. To overcome these limitations, we developed a fusion protein of the anti-inflammatory cytokines interleukin 4 (IL4) and IL10. The IL4-10 fusion protein is a 70 kDa glycosylated dimeric protein that retains the functional activity of both cytokine moieties. Intrathecal administration of IL4-10 dose-dependently inhibited persistent inflammatory pain in mice: three IL4-10 injections induced full resolution of inflammatory pain in two different mouse models of persistent inflammatory pain. Both cytokine moieties were required for optimal effects. The IL4-10 fusion protein was more effective than the individual cytokines or IL4 plus IL10 combination therapy and also inhibited allodynia in a mouse model of neuropathic pain. Mechanistically, IL4-10 inhibited the activity of glial cells and reduced spinal cord and dorsal root ganglion cytokine levels without affecting paw inflammation. In conclusion, we developed a novel fusion protein with improved efficacy to treat pain, compared with wild-type anti-inflammatory cytokines. The IL4-10 fusion protein has potential as a treatment for persistent inflammatory pain. SIGNIFICANCE STATEMENT The treatment of chronic pain is a major clinical and societal challenge. Current therapies to treat persistent pain states are limited and often cause major side effects. Therefore, novel analgesic treatments are urgently needed. In search of a novel drug to treat chronic pain, we developed a fusion protein consisting of two prototypic regulatory cytokines, interleukin 4 (IL4) and IL10. The work presented in this manuscript shows that this IL4-10 fusion protein overcomes some major therapeutic limitations of pain treatment with individual cytokines. The IL4-10 fusion protein induces full resolution of persistent inflammatory pain in two different mouse models. These novel findings are significant, as they highlight the IL4-10 fusion protein as a long-needed potential new drug to stop persistent pain states. PMID:27413147

Cost-effectiveness of manual therapy for the management of musculoskeletal conditions: a systematic review and narrative synthesis of evidence from randomized controlled trials.

PubMed

Tsertsvadze, Alexander; Clar, Christine; Court, Rachel; Clarke, Aileen; Mistry, Hema; Sutcliffe, Paul

2014-01-01

The purpose of this study was to systematically review trial-based economic evaluations of manual therapy relative to other alternative interventions used for the management of musculoskeletal conditions. A comprehensive literature search was undertaken in major medical, health-related, science and health economic electronic databases. Twenty-five publications were included (11 trial-based economic evaluations). The studies compared cost-effectiveness and/or cost-utility of manual therapy interventions to other treatment alternatives in reducing pain (spinal, shoulder, ankle). Manual therapy techniques (e.g., osteopathic spinal manipulation, physiotherapy manipulation and mobilization techniques, and chiropractic manipulation with or without other treatments) were more cost-effective than usual general practitioner (GP) care alone or with exercise, spinal stabilization, GP advice, advice to remain active, or brief pain management for improving low back and shoulder pain/disability. Chiropractic manipulation was found to be less costly and more effective than alternative treatment compared with either physiotherapy or GP care in improving neck pain. Preliminary evidence from this review shows some economic advantage of manual therapy relative to other interventions used for the management of musculoskeletal conditions, indicating that some manual therapy techniques may be more cost-effective than usual GP care, spinal stabilization, GP advice, advice to remain active, or brief pain management for improving low back and shoulder pain/disability. However, at present, there is a paucity of evidence on the cost-effectiveness and/or cost-utility evaluations for manual therapy interventions. Further improvements in the methodological conduct and reporting quality of economic evaluations of manual therapy are warranted in order to facilitate adequate evidence-based decisions among policy makers, health care practitioners, and patients. Copyright © 2014 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

Postoperative dysesthesia in lumbar three-column resection osteotomies.

PubMed

Zhang, Zhengfeng; Wang, Honggang; Zheng, Wenjie

2016-08-01

Three-column lumbar spinal resection osteotomies including pedicle subtraction osteotomy (PSO), vertebral column resection (VCR), and total en bloc spondylectomy (TES) can potentially lead to dorsal root ganglion (DRG) injury which may cause postoperative dysesthesia (POD). The purpose of retrospective study was to describe the uncommon complication of POD in lumbar spinal resection osteotomies. Between January 2009 and December 2013, 64 patients were treated with lumbar three-column spinal resection osteotomies (PSO, n = 31; VCR, n = 29; TES, n = 4) in investigator group. POD was defined as dysesthetic pain or burning dysesthesia at a proper DRG innervated region, whether spontaneous or evoked. Non-steroidal antiinflammatory drugs, central none-opioid analgesic agent, neuropathic pain drugs and/or intervertebral foramen block were selectively used to treat POD. There were 5 cases of POD (5/64, 7.8 %), which consisted of 1 patient in PSO (1/31, 3.2 %), 3 patients in PVCR (3/29, 10.3 %), and 1 patient in TES (1/4, 25 %). After the treatment by drugs administration plus DRG block, all patients presented pain relief with duration from 8 to 38 days. A gradual pain moving to distal end of a proper DRG innervated region was found as the beginning of end. Although POD is a unique and rare complication and maybe misdiagnosed as nerve root injury in lumbar spinal resection osteotomies, combination drug therapy and DRG block have an effective result of pain relief. The appearance of a gradual pain moving to distal end of a proper DRG innervated region during recovering may be used as a sign for the good prognosis.

Combined spinal and general anesthesia vs general anesthesia for robotic sacrocervicopexy: a randomized controlled trial.

PubMed

Segal, Dror; Awad, Nibal; Nasir, Hawash; Mustafa, Susana; Lowenstein, Lior

2014-03-01

Gynecologic laparoscopic surgery is frequently accompanied by early postoperative pain. This study assessed the effect of combined general and spinal anesthesia on postoperative pain score, analgesic use, and patient satisfaction following robotic surgeries. This was a randomized controlled trial. Thirty-eight consecutive women who underwent robotic surgeries for pelvic organ prolapse (sacrocolpopexy with or without subtotal hysterectomy) were randomly assigned to receive general anesthesia (control group, n = 20) or combined general with spinal anesthesia (study group, n = 18). Pain scores were assessed at rest and while coughing using a visual analog scale (VAS) 0-10. Dosage of analgesic medication consumption was retrieved from patients' charts. There were no statistically significant differences between the two groups with respect to demographic data and intraoperative hemodynamic parameters. In the postanesthesia care unit (PACU) mean total IV morphine and meperidine dosages were significantly lower for the study than the control group (0.33 vs 7.59 mg, 1.39 vs 27.89 mg, respectively, P < 0.003, <0.001, respectively). In addition, a significantly lower percentage of patients belonging to the study group demanded analgesic medications while in the PACU (33 vs 53 %, P = 0.042). Pain scores in the PACU and during postoperative day 1 were significantly lower in the study group than in the control group (delta VAS 1.9 vs 3.0, P = 0.04). Satisfaction with pain treatment among both patients and nurses was significantly higher in the study group. Reported levels of pain and analgesic use during the first 24 h following robotic gynecologic surgery were significantly lower following general and spinal anesthesia compared to general anesthesia alone.

Dexamethasone added to local lidocaine for infiltration along the spinal-epidural needle pathway decreases incidence and severity of backache after gynecological surgery.

PubMed

Gao, Wei; Ren, Yi; Cui, Guang Xiao

2015-03-18

The aim of this study was to evaluate the effect of dexamethasone added to local lidocaine infiltration on incidence and severity of backache after combined spinal-epidural anesthesia for gynecological surgery. We randomly allocated 160 patients to receive either local lidocaine infiltration along the pathway of the spinal-epidural needle (Group L) or local dexamethasone and lidocaine infiltration (Group DL). The incidence and scores for back pain were evaluated on the first, second, and third day (acute lumbago) and first, second, and sixth month (chronic lumbago) after surgery. Fentanyl consumption for management of back pain was recorded. The incidence of acute, subacute, and chronic back pain was significantly lower in the DL group than the L group (P<0.05 for all comparisons). The VAS score for back pain on the first and second day and first and second month, were significantly lower in the DL group than the L group (P=0.0028, P=0.017; P<0.001, both), but there were no significant differences on the third day and sixth month. Fentanyl consumption in the first 3 postoperative days was significantly lower in the DL group than in the L group (P<0.001). The incidence of back pain during the first, second, and sixth month in patients who did not have preoperative lumbago were significantly lower in the DL group than in the L group (P<0.001, both). Addition of dexamethasone to local lidocaine infiltration effectively decreases the incidence and severity of back pain after combined spinal-epidural anesthesia implemented for gynecological surgery.

Stereotactic Radiosurgery for the Treatment of Primary and Metastatic Spinal Sarcomas

PubMed Central

Balagamwala, Ehsan H.; Angelov, Lilyana; Suh, John H.; Djemil, Toufik; Magnelli, Anthony; Qi, Peng; Zhuang, Tingliang; Godley, Andrew

2016-01-01

Purpose: Despite advancements in local and systemic therapy, metastasis remains common in the natural history of sarcomas. Unfortunately, such metastases are the most significant source of morbidity and mortality in this heterogeneous disease. As a classically radioresistant histology, stereotactic radiosurgery has emerged to control spinal sarcomas and provide palliation. However, there is a lack of data regarding pain relief and relapse following stereotactic radiosurgery. Methods: We queried a retrospective institutional database of patients who underwent spine stereotactic radiosurgery for primary and metastatic sarcomas. The primary outcome was pain relief following stereotactic radiosurgery. Secondary outcomes included progression of pain, radiographic failure, and development of toxicities following treatment. Results: Forty treatment sites were eligible for inclusion; the median prescription dose was 16 Gy in a single fraction. Median time to radiographic failure was 14 months. At 6 and 12 months, radiographic control was 63% and 51%, respectively. Among patients presenting with pain, median time to pain relief was 1 month. Actuarial pain relief at 6 months was 82%. Median time to pain progression was 10 months; at 12 months, actuarial pain progression was 51%. Following multivariate analysis, presence of neurologic deficit at consult (hazard ratio: 2.48, P < .01) and presence of extraspinal bone metastases (hazard ratio: 2.83, P < .01) were associated with pain relief. Greater pain at consult (hazard ratio: 1.92, P < .01), prior radiotherapy (hazard ratio: 4.65, P = .02), and greater number of irradiated vertebral levels were associated with pain progression. Conclusions: Local treatment of spinal sarcomas has remained a challenge for decades, with poor rates of local control and limited pain relief following conventional radiotherapy. In this series, pain relief was achieved in 82% of treatments at 6 months, with half of patients experiencing pain progression by 12 months. Given minimal toxicity and suboptimal pain control at 12 months, dose escalation beyond 16 Gy is warranted. PMID:27074915

The Transition of Acute Postoperative Pain to Chronic Pain: An Integrative Overview of Research on Mechanisms.

PubMed

Chapman, C Richard; Vierck, Charles J

2017-04-01

The nature of the transition from acute to chronic pain still eludes explanation, but chronic pain resulting from surgery provides a natural experiment that invites clinical epidemiological investigation and basic scientific inquiry into the mechanisms of this transition. The primary purpose of this article is to review current knowledge and hypotheses on the transition from acute to persistent postsurgical pain, summarizing literature on clinical epidemiological studies of persistent postsurgical pain development, as well as basic neurophysiological studies targeting mechanisms in the periphery, spinal cord, and brain. The second purpose of this article is to integrate theory, information, and causal reasoning in these areas. Conceptual mapping reveals 5 classes of hypotheses pertaining to pain. These propose that chronic pain results from: 1) persistent noxious signaling in the periphery; 2) enduring maladaptive neuroplastic changes at the spinal dorsal horn and/or higher central nervous system structures reflecting a multiplicity of factors, including peripherally released neurotrophic factors and interactions between neurons and microglia; 3) compromised inhibitory modulation of noxious signaling in medullary-spinal pathways; 4) descending facilitatory modulation; and 5) maladaptive brain remodeling in function, structure, and connectivity. The third purpose of this article is to identify barriers to progress and review opportunities for advancing the field. This review reveals a need for a concerted, strategic effort toward integrating clinical epidemiology, basic science research, and current theory about pain mechanisms to hasten progress toward understanding, managing, and preventing persistent postsurgical pain. The development of chronic pain after surgery is a major clinical problem that provides an opportunity to study the transition from acute to chronic pain at epidemiologic and basic science levels. Strategic, coordinated, multidisciplinary research efforts targeting mechanisms of pain chronification can to help minimize or eliminate persistent postsurgical pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Spinal gap junctions: potential involvement in pain facilitation.

PubMed

Spataro, Leah E; Sloane, Evan M; Milligan, Erin D; Wieseler-Frank, Julie; Schoeniger, Diana; Jekich, Brian M; Barrientos, Ruth M; Maier, Steven F; Watkins, Linda R

2004-09-01

Glia are now recognized as important contributors in pathological pain creation and maintenance. Spinal cord glia exhibit extensive gap junctional connectivity, raising the possibility that glia are involved in the contralateral spread of excitation resulting in mirror image pain. In the present experiments, the gap junction decoupler carbenoxolone was administered intrathecally after induction of neuropathic pain in response to sciatic nerve inflammation (sciatic inflammatory neuropathy) or partial nerve injury (chronic constriction injury). In both neuropathic pain models, a low dose of carbenoxolone reversed mirror image mechanical allodynia, while leaving ipsilateral mechanical allodynia unaffected. Ipsilateral thermal hyperalgesia was briefly attenuated. Critically, blockade of mechanical allodynia and thermal hyperalgesia was not observed in response to intrathecal glycyrrhizic acid, a compound similar to carbenoxolone in all respects but it does not decouple gap junctions. Thus, blockade of mechanical allodynia and thermal hyperalgesia by carbenoxolone does appear to reflect an effect on gap junctions. Examination of carbenoxolone's effects on intrathecal human immunodeficiency virus type 1 gp120 showed that blockade of pain facilitation might result, at least in part, via suppression of interleukin-1 and, in turn, interleukin-6. These data provide the first suggestion that spread of excitation via gap junctions might contribute importantly to inflammatory and traumatic neuropathic pain. The current studies provide evidence for involvement of gap junctions in spinal cord pain facilitation. Intrathecal carbenoxolone, a gap junction decoupler, reversed neuropathy-induced mirror image pain and intrathecal gp120-induced allodynia. In addition, it decreased gp120-induced proinflammatory cytokines. This suggests gap junction activation might lead to proinflammatory cytokine release by distantly activated glia.

Rostral Ventral Medulla Cholinergic Mechanism in Pain-Induced Analgesia

PubMed Central

Gear, Robert W.; Levine, Jon D.

2009-01-01

The ascending nociceptive control (ANC), a novel spinostriatal pain modulation pathway, mediates a form of pain-induced analgesia referred to as noxious stimulus-induced antinociception (NSIA). ANC includes specific spinal cord mechanisms as well as circuitry in nucleus accumbens, a major component of the ventral striatum. Here, using the trigeminal jaw-opening reflex (JOR) in the rat as a nociceptive assay, we show that microinjection of the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine into the rostral ventral medulla (RVM) blocks NSIA, implicating RVM as a potentially important link between ANC and the PAG – RVM – spinal descending pain modulation system. A circuit connecting nucleus accumbens to the RVM is proposed as a novel striato-RVM pathway. PMID:19699268

Spinal surgery - cervical - series (image)

MedlinePlus

... problems include: pain that interferes with daily activities neck pain that extends (radiates) to the shoulder or arm ... done while the patient is deep asleep and pain-free (general anesthesia). For the neck (cervical spine), an incision may be made either in ...

Spinal kinematics during smartphone texting - A comparison between young adults with and without chronic neck-shoulder pain.

PubMed

Xie, Yan Fei; Szeto, Grace; Madeleine, Pascal; Tsang, Sharon

2018-04-01

To advance our understanding about the association between smartphone use and chronic neck-shoulder pain, the objective of this study was to compare spinal kinematics between different text-entry methods in smartphone users with and without chronic neck-shoulder pain. Symptomatic (n = 19) and healthy participants (n = 18) were recruited and they performed three tasks: texting on a smartphone with one hand, with two hands, and typing on a desktop computer. Three-dimensional kinematics were examined in the cervical, thoracic and lumbar regions for each task. This study suggests that altered kinematics may be associated with pain since significantly increased angles of cervical right side flexion during smartphone texting and greater postural changes in cervical rotation were found during all text-entry tasks in the symptomatic group. Two-handed texting was associated with increased cervical flexion while one-handed texting was correlated with an asymmetric neck posture, indicating both text-entry methods are not favorable in terms of spinal postures. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation and Management of SCI-Associated Pain.

PubMed

Saulino, Michael; Averna, Justin F

2016-09-01

Traumatic spinal cord injury (SCI) is a devastating neurological condition. Treatment of SCI-related pain is challenging for the treating physician, as normal neural pathways are disrupted. Patients with SCI consistently rate pain as one of the most difficult problems associated with their injury. SCI-related pain can be refractory and complete relief is often not possible. The multidimensional nature of SCI-related pain affects the neural system including autonomic nervous system deregulation and can alter metabolic and biochemical processes throughout the body. Co-morbid psychological illnesses such as depression and adjustment disorder are seen in a significant percentage of patients. Despite a better understanding of the underlying pain mechanisms and advances in procedural, pharmacologic, and non-pharmacologic therapies, treatment of pain after SCI remains elusive. This manuscript reviews the current evidence-based evaluation and management of the SCI patient with the overarching goal of providing appropriate and effective management of their pain. In particular, additional well-designed studies are needed to help elucidate effective treatments for SCI-related neuropathic pain in an effort to help provide these patients with better management of their pain and improve their quality of life.

An algorithmic programming approach for back pain symptoms in failed back surgery syndrome using spinal cord stimulation with a multicolumn surgically implanted epidural lead: a multicenter international prospective study.

PubMed

Rigoard, Philippe; Jacques, Line; Delmotte, Alexandre; Poon, Katherine; Munson, Russell; Monlezun, Olivier; Roulaud, Manuel; Prevost, Audrey; Guetarni, Farid; Bataille, Benoit; Kumar, Krishna

2015-03-01

Many studies have demonstrated the efficacy and the medical/economic value of epidural spinal cord stimulation for the treatment of "failed back surgery syndrome" (FBSS). However, the back pain component of FBSS has been recalcitrant. Recent clinical trials have suggested that multicolumn surgically implanted leads combined with enhanced programming capabilities in the newer implantable pulse generators demonstrate the ability to treat the back pain component of FBSS. The objective of our present international multicentre study is to prospectively evaluate these findings in a larger population. We conducted a prospective, nonrandomized, observational study on 76 patients with refractory FBSS, consecutively implanted with multicolumn spinal cord stimulation (SCS) between 2008 and 2011 in three neurosurgical pain management centers (Poitiers, France; Montréal, Canada; and Regina, Canada). The primary objective of this study was to prospectively analyze the effect of multicolumn lead programming on paresthesia coverage for the back pain region in these patients. The secondary objective was to assess the analgesic efficacy of this technique on the global and back pain components. Paresthesia could be induced in the lower extremities in the majority of patients with at least one of the configurations tested. Bilateral low back paresthesia was induced in 53.5% of patients, while unilateral low back paresthesia was induced in 78.9% of patients. Multicolumn configurations were statistically more effective than monocolumn configurations for all anatomic regions studied. At 6 months, 75.4% of patients receiving multicolumn stimulation (n = 57) obtained at least a 30% improvement of the back pain VAS score, while 42.1% of patients obtained at least a 50% improvement of the back pain VAS score. This study confirms the hypothesis that multicolumn SCS should be considered as an important tool in the treatment of radicular and axial pain in FBSS patients. The efficacy of this modality is based on a rigorous patient selection process, access to new generation lead technologies, but most importantly an algorithmic programming approach for optimal stimulation and electrical field shaping. With over 40 million potential programming combinations associated with 16 contact leads to achieve paresthesia coverage, optimal stimulation is often missed as either the patient or the clinician become exhausted or overwhelmed during the course of therapy programming and optimization session. © 2014 World Institute of Pain.

The Glt1 glutamate receptor mediates the establishment and perpetuation of chronic visceral pain in an animal model of stress-induced bladder hyperalgesia.

PubMed

Ackerman, A Lenore; Jellison, Forrest C; Lee, Una J; Bradesi, Sylvie; Rodríguez, Larissa V

2016-04-01

Psychological stress exacerbates interstitial cystitis/bladder pain syndrome (IC/BPS), a lower urinary tract pain disorder characterized by increased urinary frequency and bladder pain. Glutamate (Glu) is the primary excitatory neurotransmitter modulating nociceptive networks. Glt1, an astrocytic transporter responsible for Glu clearance, is critical in pain signaling termination. We sought to examine the role of Glt1 in stress-induced bladder hyperalgesia and urinary frequency. In a model of stress-induced bladder hyperalgesia with high construct validity to human IC/BPS, female Wistar-Kyoto (WKY) rats were subjected to 10-day water avoidance stress (WAS). Referred hyperalgesia and tactile allodynia were assessed after WAS with von Frey filaments. After behavioral testing, we assessed Glt1 expression in the spinal cord by immunoblotting. We also examined the influence of dihydrokainate (DHK) and ceftriaxone (CTX), which downregulate and upregulate Glt1, respectively, on pain development. Rats exposed to WAS demonstrated increased voiding frequency, increased colonic motility, anxiety-like behaviors, and enhanced visceral hyperalgesia and tactile allodynia. This behavioral phenotype correlated with decreases in spinal Glt1 expression. Exogenous Glt1 downregulation by DHK resulted in hyperalgesia similar to that following WAS. Exogenous Glt1 upregulation via intraperitoneal CTX injection inhibited the development of and reversed preexisting pain and voiding dysfunction induced by WAS. Repeated psychological stress results in voiding dysfunction and hyperalgesia that correlate with altered central nervous system glutamate processing. Manipulation of Glu handling altered the allodynia developing after psychological stress, implicating Glu neurotransmission in the pathophysiology of bladder hyperalgesia in the WAS model of IC/BPS. Copyright © 2016 the American Physiological Society.

Visceral Pain: The Neurophysiological Mechanism

PubMed Central

Sengupta, Jyoti N.

2011-01-01

The mechanism of visceral pain is still less understood compared with that of somatic pain. This is primarily due to the diverse nature of visceral pain compounded by multiple factors such as sexual dimorphism, psychological stress, genetic trait, and the nature of predisposed disease. Due to multiple contributing factors there is an enormous challenge to develop animal models that ideally mimic the exact disease condition. In spite of that, it is well recognized that visceral hypersensitivity can occur due to (1) sensitization of primary sensory afferents innervating the viscera, (2) hyperexcitability of spinal ascending neurons (central sensitization) receiving synaptic input from the viscera, and (3) dysregulation of descending pathways that modulate spinal nociceptive transmission. Depending on the type of stimulus condition, different neural pathways are involved in chronic pain. In early-life psychological stress such as maternal separation, chronic pain occurs later in life due to dysregulation of the hypothalamic–pituitary–adrenal axis and significant increase in corticotrophin releasing factor (CRF) secretion. In contrast, in early-life inflammatory conditions such as colitis and cystitis, there is dysregulation of the descending opioidergic system that results excessive pain perception (i.e., visceral hyperalgesia). Functional bowel disorders and chronic pelvic pain represent unexplained pain that is not associated with identifiable organic diseases. Often pain overlaps between two organs and approximately 35% of patients with chronic pelvic pain showed significant improvement when treated for functional bowel disorders. Animal studies have documented that two main components such as (1) dichotomy of primary afferent fibers innervating two pelvic organs and (2) common convergence of two afferent fibers onto a spinal dorsal horn are contributing factors for organ-to-organ pain overlap. With reports emerging about the varieties of peptide molecules involved in the pathological conditions of visceral pain, it is expected that better therapy will be achieved relatively soon to manage chronic visceral pain. PMID:19655104

Relief from Back Pain Through Postural Adjustment: a Controlled Clinical Trial of the Immediate Effects of Muscular Chains Therapy (MCT).

PubMed

Rosario, Jose L

2014-09-01

Back pain can be one of the most common health problems, causing suffering, disabilities, and financial losses. Postural models for pain treatment state that poor posture alters the joint position and causes pain, such as back pain. Muscular Chain Therapy (MCT) is a technique that is used to treat posture pathologies, among others. The aim of the present study was to assess the efficiency of a single session of Muscular Chain Therapy (MCT) on complaints of undiagnosed musculoskeletal spinal pain. Physical therapy clinic of the University of Center-West (Guarapuava, Brazil). 100 subjects, aged between 20 and 39 years, with complaints of spinal musculoskeletal pain. Randomized controlled trial. The participants were randomly assigned by a non-care provider into two groups: The MCT Group that received Muscular Chain Treatment and the Control Group that received a placebo treatment of 15 minutes turned off ultrasound therapy. All volunteers were assessed before and after treatment using an analog pain scale. A score of 0 indicated no pain and 10 was the maximum degree of pain on the scale. Degree of pain measured by analog scale. The chi-square goodness of fit test was used to compare gender distribution among groups displayed a p value = .25. Subject age had differences analyzed using the unpaired t test (p = .44). Pain assessment for treatment and placebo control groups was analyzed using a paired t test and unpaired t test. The paired t test was used for intragroup before/after treatment comparison (MCT p = .00001; Control Group p = .0001). The unpaired t test was used for comparing the difference of the pain level before and after treatment between groups (p = .0001). A priori statistical significance was set a p = .05. It is possible to conclude that one MCT session is an effective treatment of undiagnosed spinal musculoskeletal pain.

Workshop: The Technical Requirements for Image-Guided Therapy (Focus: Spinal Cord and Spinal Column)

DTIC Science & Technology

2000-02-01

degenerative disease, spondylosis , ligamental ossification, fractures, tumors, and other causes. Compression is a painful condition that may require...series of 7000 patients who underwent lumbar disk surgery, Long indicates three reasons for failed surgery: 1. Failure of the patient to meet the...validated outcomes measures in the lumbar area, is used for a 70-year-old patient with osteoarthritis of the knees and low back pain as well as problems

Management of chronic spinal cord dysfunction.

PubMed

Abrams, Gary M; Ganguly, Karunesh

2015-02-01

Both acute and chronic spinal cord disorders present multisystem management problems to the clinician. This article highlights key issues associated with chronic spinal cord dysfunction. Advances in symptomatic management for chronic spinal cord dysfunction include use of botulinum toxin to manage detrusor hyperreflexia, pregabalin for management of neuropathic pain, and intensive locomotor training for improved walking ability in incomplete spinal cord injuries. The care of spinal cord dysfunction has advanced significantly over the past 2 decades. Management and treatment of neurologic and non-neurologic complications of chronic myelopathies ensure that each patient will be able to maximize their functional independence and quality of life.

Fisetin exerts antihyperalgesic effect in a mouse model of neuropathic pain: engagement of spinal serotonergic system

PubMed Central

Zhao, Xin; Wang, Chuang; Cui, Wu-Geng; Ma, Qing; Zhou, Wen-Hua

2015-01-01

Fisetin, a natural flavonoid, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential antinociceptive efficacies of fisetin against neuropathic pain and explore mechanism(s). We subjected mice to chronic constriction injury (CCI) by loosely ligating the sciatic nerves, and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic fisetin treatment (5, 15 or 45 mg/kg, p.o.) ameliorated thermal hyperalgesia (but not mechanical allodynia) in CCI mice, concomitant with escalated levels of spinal monoamines and suppressed monoamine oxidase (MAO)-A activity. The antihyperalgesic action of fisetin was abolished by chemical depletion of spinal serotonin (5-HT) but potentiated by co-treatment with 5-HTP, a precursor of 5-HT. Moreover, intraperitoneal (i.p.) or intrathecal (i.t.) co-treatment with 5-HT7 receptor antagonist SB-258719 completely abrogated fisetin's antihyperalgesia. These findings confirm that chronic fisetin treatment exerts antinociceptive effect on thermal hyperalgesia in neuropathic mice, with spinal serotonergic system (coupled with 5-HT7) being critically involved. Of special benefit, fisetin attenuated co-morbidly behavioral symptoms of depression and anxiety (evaluated in forced swim test, novelty suppressed feeding test and light-dark test) evoked by neuropathic pain. PMID:25761874

Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment. Part VI: Lumbar Spinal Stenosis.

PubMed

Fritz, Julie M; Rundell, Sean D; Dougherty, Paul; Gentili, Angela; Kochersberger, Gary; Morone, Natalia E; Naga Raja, Srinivasa; Rodriguez, Eric; Rossi, Michelle I; Shega, Joseph; Sowa, Gwendolyn; Weiner, Debra K

2016-03-01

. To present the sixth in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. This article focuses on the evaluation and management of lumbar spinal stenosis (LSS), the most common condition for which older adults undergo spinal surgery. . The evaluation and treatment algorithm, a table articulating the rationale for the individual algorithm components, and stepped-care drug recommendations were developed using a modified Delphi approach. The Principal Investigator, a five-member content expert panel and a nine-member primary care panel were involved in the iterative development of these materials. The illustrative clinical case was taken from the clinical practice of a contributor's colleague (SR). . We present an algorithm and supportive materials to help guide the care of older adults with LSS, a condition that occurs not uncommonly in those with CLBP. The case illustrates the importance of function-focused management and a rational approach to conservative care. . Lumbar spinal stenosis exists not uncommonly in older adults with CLBP and management often can be accomplished without surgery. Treatment should address all conditions in addition to LSS contributing to pain and disability. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Tramadol and propentofylline coadministration exerted synergistic effects on rat spinal nerve ligation-induced neuropathic pain.

PubMed

Zhang, Jin; Wu, Dan; Xie, Cheng; Wang, Huan; Wang, Wei; Zhang, Hui; Liu, Rui; Xu, Li-Xian; Mei, Xiao-Peng

2013-01-01

Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system.

Tramadol and Propentofylline Coadministration Exerted Synergistic Effects on Rat Spinal Nerve Ligation-Induced Neuropathic Pain

PubMed Central

Wang, Huan; Wang, Wei; Zhang, Hui; Liu, Rui; Xu, Li-Xian; Mei, Xiao-Peng

2013-01-01

Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system. PMID:24009718

Lower back and neck pain among dentistry students: a cross-sectional study in dentistry students in Northern Greece.

PubMed

Samoladas, Efthimios; Barmpagianni, Christina; Papadopoulos, Dimitrios V; Gelalis, Ioannis D

2018-03-28

Dentistry students and dentists comprise a unique group of professionals, whose everyday professional activity requires long hours of standing and working in a position considered unhealthy for the lower back and neck. Our aim was to explore the factors involved in the appearance of low back and neck pain in dentistry students as well as the impact of the pain on the students' professional and everyday activities. A questionnaire was given to all dentistry students of the 4th and 5th year of our university. The questionnaire included 43 questions regarding demographic data, history (spinal injury, other comorbidities), daily activities (exercise, smoking, alcohol and caffeine consumption, use of cell phone), professional activities (length and type of dental work), pattern and intensity of pain, and personal pain evaluation. A statistical analysis of the gathered data was performed. All students having suffered a spinal trauma or indicating any other comorbidity that could cause severe pain of the spine were excluded from the study. Fifty-five students (21 male, 34 female) were included. Our data showed that increased alcohol consumption and prolonged use of cell phone were connected to increased levels of pain. The students reported that the most frequent onset of pain was 1 h after starting to work in a standing position, while the majority believed that their working habits were involved in the appearance and the intensity of neck and low-back pain. Our findings indicate that among dentistry students appears to be a causative relationship between their professional activities and the experienced spinal pain. These findings may be useful in a possible future restructuring of the educational program in dental schools, as well as in improving the ergonomics of dentistry working units.

Pain correlates with germline mutation in schwannomatosis.

PubMed

Jordan, Justin T; Smith, Miriam J; Walker, James A; Erdin, Serkan; Talkowski, Michael E; Merker, Vanessa L; Ramesh, Vijaya; Cai, Wenli; Harris, Gordon J; Bredella, Miriam A; Seijo, Marlon; Suuberg, Alessandra; Gusella, James F; Plotkin, Scott R

2018-02-01

Schwannomatosis has been linked to germline mutations in the SMARCB1 and LZTR1 genes, and is frequently associated with pain.In a cohort study, we assessed the mutation status of 37 patients with clinically diagnosed schwannomatosis and compared to clinical data, whole body MRI (WBMRI), visual analog pain scale, and Short Form 36 (SF-36) bodily pain subscale.We identified a germline mutation in LZTR1 in 5 patients (13.5%) and SMARCB1 in 15 patients (40.5%), but found no germline mutation in 17 patients (45.9%). Peripheral schwannomas were detected in 3 LZTR1-mutant (60%) and 10 SMARCB1-mutant subjects (66.7%). Among those with peripheral tumors, the median tumor number was 4 in the LZTR1 group (median total body tumor volume 30 cc) and 10 in the SMARCB1 group (median volume 85cc), (P=.2915 for tumor number and P = .2289 for volume). mutation was associated with an increased prevalence of spinal schwannomas (100% vs 41%, P = .0197). The median pain score was 3.9/10 in the LZTR1 group and 0.5/10 in the SMARCB1 group (P = .0414), and SF-36 pain-associated quality of life was significantly worse in the LZTR1 group (P = .0106). Pain scores correlated with total body tumor volume (rho = 0.32471, P = .0499), but not with number of tumors (rho = 0.23065, P = .1696).We found no significant difference in quantitative tumor burden between mutational groups, but spinal schwannomas were more common in LZTR1-mutant patients. Pain was significantly higher in LZTR1-mutant than in SMARCB1-mutant patients, though spinal tumor location did not significantly correlate with pain. This suggests a possible genetic association with schwannomatosis-associated pain.