[Complex regional pain syndrome (CRPS) : An update].

PubMed

Dimova, V; Birklein, F

2018-04-17

The acute phase of complex regional pain syndrome (CRPS) is pathophysiologically characterized by an activation of the immune system and its associated inflammatory response. During the course of CRPS, central nervous symptoms like mechanical hyperalgesia, loss of sensation, and body perception disorders develop. Psychological factors such as pain-related anxiety and traumatic events might have a negative effect on the treatment outcome. While the visible inflammatory symptoms improve, the pain often persists. A stage adapted, targeted treatment could improve the prognosis. Effective multidisciplinary treatment includes the following: pharmacotherapy with steroids, bisphosphonates, or dimethylsulfoxide cream (acute phase), and antineuropathic analgesics (all phases); physiotherapy and behavioral therapy for pain-related anxiety and avoidance of movement; and interventional treatment like spinal cord or dorsal root ganglion stimulation if noninvasive options failed.

Post-conditioning experience with acute or chronic inflammatory pain reduces contextual fear conditioning in the rat

PubMed Central

Johnston, Ian N.; Maier, Steven F.; Rudy, Jerry W.; Watkins, Linda R.

2017-01-01

There is evidence that pain can impact cognitive function in people. The present study evaluated whether Pavlovian fear conditioning in rats would be reduced if conditioning were followed by persistent inflammatory pain induced by a subcutaneous injection of dilute formalin or complete Freund's adjuvant (CFA) on the dorsal lumbar surface of the back. Formalin-induced pain specifically impaired contextual fear conditioning but not auditory cue conditioning (Experiment 1A). Moreover, formalin pain only impaired contextual fear conditioning if it was initiated within 1 h of conditioning and did not have a significant effect if initiated 2, 8 or 32 h after (Experiments 1A and 1B). Experiment 2 showed that formalin pain initiated after a session of context pre-exposure reduced the ability of that pre-exposure to facilitate contextual fear when the rat was limited to a brief exposure to the context during conditioning. Similar impairments in context- but not CS-fear conditioning were also observed if the rats received an immediate post-conditioning injection with CFA (Experiment 3). Finally, we confirmed that formalin and CFA injected s.c. on the back induced pain-indicative behaviours, hyperalgesia and allodynia with a similar timecourse to intraplantar injections (Experiment 4). These results suggest that persistent pain impairs learning in a hippocampus-dependent task, and may disrupt processes that encode experiences into long-term memory. PMID:21920390

Preventing the development of chronic pain after orthopaedic surgery with preventive multimodal analgesic techniques.

PubMed

Reuben, Scott S; Buvanendran, Asokumar

2007-06-01

The prevalences of complex regional pain syndrome, phantom limb pain, chronic donor-site pain, and persistent pain following total joint arthroplasty are alarmingly high. Central nervous system plasticity that occurs in response to tissue injury may contribute to the development of persistent postoperative pain. Many researchers have focused on methods to prevent central neuroplastic changes from occurring through the utilization of preemptive or preventive multimodal analgesic techniques. Multimodal analgesia allows a reduction in the doses of individual drugs for postoperative pain and thus a lower prevalence of opioid-related adverse events. The rationale for this strategy is the achievement of sufficient analgesia due to the additive effects of, or the synergistic effects between, different analgesics. Effective multimodal analgesic techniques include the use of nonsteroidal anti-inflammatory drugs, local anesthetics, alpha-2 agonists, ketamine, alpha(2)-delta ligands, and opioids.

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

Sleep Deprivation and Recovery Sleep Prior to a Noxious Inflammatory Insult Influence Characteristics and Duration of Pain.

PubMed

Vanini, Giancarlo

2016-01-01

Insufficient sleep and chronic pain are public health epidemics. Sleep loss worsens pain and predicts the development of chronic pain. Whether previous, acute sleep loss and recovery sleep determine pain levels and duration remains poorly understood. This study tested whether acute sleep deprivation and recovery sleep prior to formalin injection alter post-injection pain levels and duration. Male Sprague-Dawley rats (n = 48) underwent sleep deprivation or ad libitum sleep for 9 hours. Thereafter, rats received a subcutaneous injection of formalin or saline into a hind paw. In the recovery sleep group, rats were allowed 24 h between sleep deprivation and the injection of formalin. Mechanical and thermal nociception were assessed using the von Frey test and Hargreaves' method. Nociceptive measures were performed at 1, 3, 7, 10, 14, 17 and 21 days post-injection. Formalin caused bilateral mechanical hypersensitivity (allodynia) that persisted for up to 21 days post-injection. Sleep deprivation significantly enhanced bilateral allodynia. There was a synergistic interaction when sleep deprivation preceded a formalin injection. Rats allowed a recovery sleep period prior to formalin injection developed allodynia only in the injected limb, with higher mechanical thresholds (less allodynia) and a shorter recovery period. There were no persistent changes in thermal nociception. The data suggest that acute sleep loss preceding an inflammatory insult enhances pain and can contribute to chronic pain. The results encourage studies in a model of surgical pain to test whether enhancing sleep reduces pain levels and duration. © 2016 Associated Professional Sleep Societies, LLC.

Relationship between levels of neuropeptide Substance P in periodontal disease and chronic pain: a literature review.

PubMed

de Avila, Erica Dorigatti; de Molon, Rafael Scaf; de Godoi Gonçalves, Daniela Aparecida; Camparis, Cinara Maria

2014-05-01

The aim of the current review was to investigate the relationship between levels of neuropeptide Substance P in periodontal disease and chronic pain. Substance P is a neuropeptide that is directly related with pain. In periodontal disease, it is expressed during the inflammatory process, and is one of the factors responsible for bone resorption. Studies have shown that Substance P levels are highest in the gingival crevicular fluid from sites with active periodontal disease and bone loss. The persistence of these substances could be sufficient to stimulate neurogenic inflammation in susceptible tissues, and cause pain. The scientific literature shows that Substance P expressed during periodontal disease can be a risk factor for patients with systemic inflammatory pathologies, such as chronic arthritis or rheumatoid arthritis. Additional research is needed to confirm the participation of this substance in the origin of some types of chronic pain. © 2014 Wiley Publishing Asia Pty Ltd.

Depression of home cage wheel running is an objective measure of spontaneous morphine withdrawal in rats with and without persistent pain

PubMed Central

Kandasamy, Ram; Lee, Andrea T.; Morgan, Michael M.

2017-01-01

Opioid withdrawal in humans is often subtle and almost always spontaneous. In contrast, most preclinical studies precipitate withdrawal by administration of an opioid receptor antagonist such as naloxone. These animal studies rely on measurement of physiological symptoms (e.g., wet dog shakes) in the period immediately following naloxone administration. To more closely model the human condition, we tested the hypothesis that depression of home cage wheel running will provide an objective method to measure the magnitude and duration of spontaneous morphine withdrawal. Rats were allowed access to a running wheel in their home cage for 8 days prior to implantation of two 75 mg morphine or placebo pellets. The pellets were removed 3 or 5 days later to induce spontaneous withdrawal. In normal pain-free rats, removal of the morphine pellets depressed wheel running for 48 hours compared to rats that had placebo pellets removed. Morphine withdrawal-induced depression of wheel running was greatly enhanced in rats with persistent inflammatory pain induced by injection of Complete Freund’s Adjuvant (CFA) into the hindpaw. Removal of the morphine pellets following 3 days of treatment depressed wheel running in these rats for over 6 days. These data demonstrate that home cage wheel running provides an objective and more clinically relevant method to assess spontaneous morphine withdrawal compared to precipitated withdrawal in laboratory rats. Moreover, the enhanced withdrawal in rats with persistent inflammatory pain suggests that pain patients may be especially susceptible to opioid withdrawal. PMID:28366799

A novel model of inflammatory pain in human skin involving topical application of sodium lauryl sulfate.

PubMed

Petersen, L J; Lyngholm, A M; Arendt-Nielsen, L

2010-09-01

Sodium lauryl sulfate (SLS) is a known irritant. It releases pro-inflammatory mediators considered pivotal in inflammatory pain. The sensory effects of SLS in the skin remain largely unexplored. In this study, SLS was evaluated for its effect on skin sensory functions. Eight healthy subjects were recruited for this study. Skin sites were randomized to topical SLS 0.25, 0.5, 1, 2% and vehicle for 24 h. Topical capsaicin 1% was applied for 30 min at 24 h after SLS application. Assessments included laser Doppler imaging of local vasodilation and flare reactions, rating of spontaneous pain, assessment of primary thermal and tactile hyperalgesia, and determination of secondary dynamic and static hyperalgesia. SLS induced significant and dose-dependent local inflammation and primary hyperalgesia to tactile and thermal stimulation at 24 h after application, with SLS 2% treatment eliciting results comparable to those observed following treatment with capsaicin 1%. SLS induced no spontaneous pain, small areas of flare, and minimal secondary hyperalgesia. The primary hyperalgesia vanished within 2-3 days, whereas the skin inflammation persisted and was only partly normalized by Day 6. SLS induces profound perturbations of skin sensory functions lasting 2-3 days. SLS-induced inflammation may be a useful model for studying the mechanisms of inflammatory pain.

Serum C-reactive protein levels predict regional brain responses to noxious cold stimulation of the hand in chronic whiplash associated disorders.

PubMed

Sterling, Michele; Head, Jessica; Cabot, Peter J; Farrell, Michael

2016-04-01

Whiplash Associated Disorders (WAD) are a costly health burden. The condition is characterised by sensory disturbances such as widespread hyperalgesia likely indicative of central hyperexcitability. Recently elevated levels of pro-inflammatory biomarkers have also found in acute and chronic WAD. The aim of this cross-sectional study was to investigate the relationship between inflammatory biomarkers and pain processing in people with persistent whiplash associated disorders (WAD). Twenty one participants with chronic whiplash (>3 months) were recruited. Venous blood samples were collected and assays performed for C-reactive protein (CRP) and TNF-α. Blood oxygen level-dependent (BOLD) contrast images of the brain were acquired with a Siemens 1.5T MRI scanner during repeated 24s stimulus blocks of innocuous or painful stimuli (thumbnail pressure and cold stimulation of dorsum of hand) separated by 36s inter-stimulus intervals. Stimulus intensities used during scanning were at the level of participants' thresholds for moderate pain. Parameter estimates representing BOLD signal increases during painful events from each participant were tested for associations with inflammatory biomarkers. Clinically relevant levels of CRP and TNF-α were found in 33% and 38% of participants. Levels of CRP showed a positive correlation with levels of cold pain activation in brain regions including the anterior insula, posterior parietal cortex, caudate and thalamus (p corrected <0.05). Levels of TNF-α were not related to activation levels during either noxious pressure or cold. Pressure pain activations also did not show a relationship with CRP levels. Shared variance between inflammation and increased levels of regional pain-related activation in people with persistent whiplash symptoms is apparent for cold, but not pressure stimuli. The results highlight cold pain processing as an important aspect of whiplash chronicity, although the implications of this modality-specific effect are not readily apparent. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Tmem100 is a regulator of TRPA1-TRPV1 complex and contributes to persistent pain

PubMed Central

Weng, Hao-Jui; Patel, Kush N.; Jeske, Nathaniel A.; Bierbower, Sonya M.; Zou, Wangyuan; Tiwari, Vinod; Zheng, Qin; Tang, Zongxiang; Mo, Gary C.H.; Wang, Yan; Geng, Yixun; Zhang, Jin; Guan, Yun; Akopian, Armen; Dong, Xinzhong

2014-01-01

SUMMARY TRPA1 and TRPV1 are crucial pain mediators, but how their interaction contributes to persistent pain is unknown. Here, we identify Tmem100 as a potentiating modulator of TRPA1-V1 complexes. Tmem100 is co-expressed and forms a complex with TRPA1 and TRPV1 in DRG neurons. Tmem100-deficient mice show a reduction in inflammatory mechanical hyperalgesia and TRPA1- but not TRPV1-mediated pain. Single-channel recording in a heterologous system reveals that Tmem100 selectively potentiates TRPA1 activity in a TRPV1-dependent manner. Mechanistically, Tmem100 weakens the association of TRPA1 and TRPV1, thereby releasing the inhibition of TRPA1 by TRPV1. A Tmem100 mutant, Tmem100-3Q, exerts the opposite effect, i.e., it enhances the association of TRPA1 and TRPV1 and strongly inhibits TRPA1. Strikingly, a cell-permeable peptide (CPP) containing the C-terminal sequence of Tmem100-3Q mimics its effect and inhibits persistent pain. Our study unveils a context-dependent modulation of the TRPA1-V1 complex, and Tmem100-3Q CPP is a promising pain therapy. PMID:25640077

Chemokine (c-c motif) receptor 2 mediates mechanical and cold hypersensitivity in sickle cell disease mice.

PubMed

Sadler, Katelyn E; Zappia, Katherine J; O'Hara, Crystal L; Langer, Sarah N; Weyer, Andy D; Hillery, Cheryl A; Stucky, Cheryl L

2018-04-23

Approximately one third of individuals with sickle cell disease (SCD) develop chronic pain. This debilitating pain is inadequately treated because the underlying mechanisms driving the pain are poorly understood. In addition to persistent pain, SCD patients are also in a tonically pro-inflammatory state. Previous studies have revealed that there are elevated plasma levels of many inflammatory mediators including chemokine (c-c motif) ligand 2 (CCL2) in individuals with SCD. Using a transgenic mouse model of SCD, we investigated the contributions of CCL2 signaling to SCD-related pain. Inhibition of the chemokine receptor 2 (CCR2), but not CCR4, alleviated the behavioral mechanical and cold hypersensitivity in SCD. Further, acute CCR2 blockade reversed both the behavioral and the in vitro responsiveness of sensory neurons to an agonist of TRPV1, a neuronal ion channel previously implicated in SCD pain. These results provide insight into the immune-mediated regulation of hypersensitivity in SCD and could inform future development of analgesics or therapeutic measures to prevent chronic pain.

Understanding Neuropathic Corneal Pain-Gaps and Current Therapeutic Approaches

PubMed Central

Goyal, Sunali; Hamrah, Pedram

2017-01-01

The richly innervated corneal tissue is one of the most powerful pain generator in the body. Corneal neuropathic pain results from dysfunctional nerves causing perceptions such as burning, stinging, eye-ache and pain. Various inflammatory diseases, neurological diseases, and surgical interventions can be the underlying cause of corneal neuropathic pain. Recent efforts have been made by the scientific community to elucidate the pathophysiology and neurobiology of pain resulting from initially protective physiological reflexes, to a more persistent chronic state. The goal of this clinical review is to briefly summarize the pathophysiology of neuropathic corneal pain, describe how to systematically approach the diagnosis of these patients, and finally summarizing our experience with current therapeutic approaches for the treatment of corneal neuropathic pain. PMID:26959131

Elevated [11C]-D-Deprenyl Uptake in Chronic Whiplash Associated Disorder Suggests Persistent Musculoskeletal Inflammation

PubMed Central

Linnman, Clas; Appel, Lieuwe; Fredrikson, Mats; Gordh, Torsten; Söderlund, Anne; Långström, Bengt; Engler, Henry

2011-01-01

There are few diagnostic tools for chronic musculoskeletal pain as structural imaging methods seldom reveal pathological alterations. This is especially true for Whiplash Associated Disorder, for which physical signs of persistent injuries to the neck have yet to be established. Here, we sought to visualize inflammatory processes in the neck region by means Positron Emission Tomography using the tracer 11C-D-deprenyl, a potential marker for inflammation. Twenty-two patients with enduring pain after a rear impact car accident (Whiplash Associated Disorder grade II) and 14 healthy controls were investigated. Patients displayed significantly elevated tracer uptake in the neck, particularly in regions around the spineous process of the second cervical vertebra. This suggests that whiplash patients have signs of local persistent peripheral tissue inflammation, which may potentially serve as a diagnostic biomarker. The present investigation demonstrates that painful processes in the periphery can be objectively visualized and quantified with PET and that 11C-D-deprenyl is a promising tracer for these purposes. PMID:21541010

Effects of Simvastatin Beyond Dyslipidemia: Exploring Its Antinociceptive Action in an Animal Model of Complex Regional Pain Syndrome-Type I

PubMed Central

Vieira, Graziela; Cavalli, Juliana; Gonçalves, Elaine C. D.; Gonçalves, Tainara R.; Laurindo, Larissa R.; Cola, Maíra; Dutra, Rafael C.

2017-01-01

Simvastatin is a lipid-lowering agent that blocks the production of cholesterol through inhibition of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. In addition, recent evidence has suggested its anti-inflammatory and antinociceptive actions during inflammatory and pain disorders. Herein, we investigated the effects of simvastatin in an animal model of complex regional pain syndrome-type I, and its underlying mechanisms. Chronic post-ischemia pain (CPIP) was induced by ischemia and reperfusion (IR) injury of the left hind paw. Our findings showed that simvastatin inhibited mechanical hyperalgesia induced by CPIP model in single and repeated treatment schedules, respectively; however simvastatin did not alter inflammatory signs during CPIP model. The mechanisms underlying those actions are related to modulation of transient receptor potential (TRP) channels, especially TRMP8. Moreover, simvastatin oral treatment was able to reduce the nociception induced by acidified saline [an acid-sensing ion channels (ASICs) activator] and bradykinin (BK) stimulus, but not by TRPA1, TRPV1 or prostaglandin-E2 (PGE2). Relevantly, the antinociceptive effects of simvastatin did not seem to be associated with modulation of the descending pain circuits, especially noradrenergic, serotoninergic and dopaminergic systems. These results indicate that simvastatin consistently inhibits mechanical hyperalgesia during neuropathic and inflammatory disorders, possibly by modulating the ascending pain signaling (TRPM8/ASIC/BK pathways expressed in the primary sensory neuron). Thus, simvastatin open-up new standpoint in the development of innovative analgesic drugs for treatment of persistent pain, including CRPS-I. PMID:28928655

A 41-Year-Old Patient with a Rare Cause of Severe Abdominal Sepsis Misdiagnosed as PID.

PubMed

Mikuscheva, Anastasia; Becker, David; Thompson-Fawcett, Mark

2018-01-01

Infectious pelvic inflammatory disease is a common condition and a frequent cause of abdominal pain in a young female patient. In a patient who has not completed family planning, the diagnosis is often made with a low threshold and treatment started on a low suspicion of diagnosis to avoid a negative impact on fertility. Here, we present a case of a 41-year-old woman who was misdiagnosed with infectious pelvic inflammatory disease and treated ineffectively with antibiotics when the underlying condition of her persistent abdominal pain was a midgut neuroendocrine tumor that had caused bowel perforation and formation of an abscess in the pouch of Douglas.

A 41-Year-Old Patient with a Rare Cause of Severe Abdominal Sepsis Misdiagnosed as PID

PubMed Central

Becker, David; Thompson-Fawcett, Mark

2018-01-01

Infectious pelvic inflammatory disease is a common condition and a frequent cause of abdominal pain in a young female patient. In a patient who has not completed family planning, the diagnosis is often made with a low threshold and treatment started on a low suspicion of diagnosis to avoid a negative impact on fertility. Here, we present a case of a 41-year-old woman who was misdiagnosed with infectious pelvic inflammatory disease and treated ineffectively with antibiotics when the underlying condition of her persistent abdominal pain was a midgut neuroendocrine tumor that had caused bowel perforation and formation of an abscess in the pouch of Douglas. PMID:29850363

Critical role for Epac1 in inflammatory pain controlled by GRK2-mediated phosphorylation of Epac1.

PubMed

Singhmar, Pooja; Huo, XiaoJiao; Eijkelkamp, Niels; Berciano, Susana Rojo; Baameur, Faiza; Mei, Fang C; Zhu, Yingmin; Cheng, Xiaodong; Hawke, David; Mayor, Federico; Murga, Cristina; Heijnen, Cobi J; Kavelaars, Annemieke

2016-03-15

cAMP signaling plays a key role in regulating pain sensitivity. Here, we uncover a previously unidentified molecular mechanism in which direct phosphorylation of the exchange protein directly activated by cAMP 1 (EPAC1) by G protein kinase 2 (GRK2) suppresses Epac1-to-Rap1 signaling, thereby inhibiting persistent inflammatory pain. Epac1(-/-) mice are protected against inflammatory hyperalgesia in the complete Freund's adjuvant (CFA) model. Moreover, the Epac-specific inhibitor ESI-09 inhibits established CFA-induced mechanical hyperalgesia without affecting normal mechanical sensitivity. At the mechanistic level, CFA increased activity of the Epac target Rap1 in dorsal root ganglia of WT, but not of Epac1(-/-), mice. Using sensory neuron-specific overexpression of GRK2 or its kinase-dead mutant in vivo, we demonstrate that GRK2 inhibits CFA-induced hyperalgesia in a kinase activity-dependent manner. In vitro, GRK2 inhibits Epac1-to-Rap1 signaling by phosphorylation of Epac1 at Ser-108 in the Disheveled/Egl-10/pleckstrin domain. This phosphorylation event inhibits agonist-induced translocation of Epac1 to the plasma membrane, thereby reducing Rap1 activation. Finally, we show that GRK2 inhibits Epac1-mediated sensitization of the mechanosensor Piezo2 and that Piezo2 contributes to inflammatory mechanical hyperalgesia. Collectively, these findings identify a key role of Epac1 in chronic inflammatory pain and a molecular mechanism for controlling Epac1 activity and chronic pain through phosphorylation of Epac1 at Ser-108. Importantly, using the Epac inhibitor ESI-09, we validate Epac1 as a potential therapeutic target for chronic pain.

Transient receptor potential ankyrin 1 mediates chronic pancreatitis pain in mice.

PubMed

Cattaruzza, Fiore; Johnson, Cali; Leggit, Alan; Grady, Eileen; Schenk, A Katrin; Cevikbas, Ferda; Cedron, Wendy; Bondada, Sandhya; Kirkwood, Rebekah; Malone, Brian; Steinhoff, Martin; Bunnett, Nigel; Kirkwood, Kimberly S

2013-06-01

Chronic pancreatitis (CP) is a devastating disease characterized by persistent and uncontrolled abdominal pain. Our lack of understanding is partially due to the lack of experimental models that mimic the human disease and also to the lack of validated behavioral measures of visceral pain. The ligand-gated cation channel transient receptor potential ankyrin 1 (TRPA1) mediates inflammation and pain in early experimental pancreatitis. It is unknown if TRPA1 causes fibrosis and sustained pancreatic pain. We induced CP by injecting the chemical agent trinitrobenzene sulfonic acid (TNBS), which causes severe acute pancreatitis, into the pancreatic duct of C57BL/6 trpa1(+/+) and trpa1(-/-) mice. Chronic inflammatory changes and pain behaviors were assessed after 2-3 wk. TNBS injection caused marked pancreatic fibrosis with increased collagen-staining intensity, atrophy, fatty replacement, monocyte infiltration, and pancreatic stellate cell activation, and these changes were reflected by increased histological damage scores. TNBS-injected animals showed mechanical hypersensitivity during von Frey filament probing of the abdomen, decreased daily voluntary wheel-running activity, and increased immobility scores during open-field testing. Pancreatic TNBS also reduced the threshold to hindpaw withdrawal to von Frey filament probing, suggesting central sensitization. Inflammatory changes and pain indexes were significantly reduced in trpa1(-/-) mice. In conclusion, we have characterized in mice a model of CP that resembles the human condition, with marked histological changes and behavioral measures of pain. We have demonstrated, using novel and objective pain measurements, that TRPA1 mediates inflammation and visceral hypersensitivity in CP and could be a therapeutic target for the treatment of sustained inflammatory abdominal pain.

Hippocampal activation of microglia may underlie the shared neurobiology of comorbid posttraumatic stress disorder and chronic pain.

PubMed

Sun, Rao; Zhang, Zuoxia; Lei, Yishan; Liu, Yue; Lu, Cui'e; Rong, Hui; Sun, Yu'e; Zhang, Wei; Ma, Zhengliang; Gu, Xiaoping

2016-01-01

The high comorbidity rates of posttraumatic stress disorder and chronic pain have been widely reported, but the underlying mechanisms remain unclear. Emerging evidence suggested that an excess of inflammatory immune activities in the hippocampus involved in the progression of both posttraumatic stress disorder and chronic pain. Considering that microglia are substrates underlying the initiation and propagation of the neuroimmune response, we hypothesized that stress-induced activation of hippocampal microglia may contribute to the pathogenesis of posttraumatic stress disorder-pain comorbidity. We showed that rats exposed to single prolonged stress, an established posttraumatic stress disorder model, exhibited persistent mechanical allodynia and anxiety-like behavior, which were accompanied by increased activation of microglia and secretion of pro-inflammatory cytokines in the hippocampus. Correlation analyses showed that hippocampal activation of microglia was significantly correlated with mechanical allodynia and anxiety-like behavior. Our data also showed that both intraperitoneal and intra-hippocampal injection of minocycline suppressed single prolonged stress-induced microglia activation and inflammatory cytokines accumulation in the hippocampus, and attenuated both single prolonged stress-induced mechanical allodynia and anxiety-like behavior. Taken together, the present study suggests that stress-induced microglia activation in the hippocampus may serve as a critical mechanistic link in the comorbid relationship between posttraumatic stress disorder and chronic pain. The novel concept introduces the possibility of cotreating chronic pain and posttraumatic stress disorder. © The Author(s) 2016.

Additive Antinociceptive Effects of a Combination of Vitamin C and Vitamin E after Peripheral Nerve Injury

PubMed Central

Lu, Ruirui; Kallenborn-Gerhardt, Wiebke; Geisslinger, Gerd; Schmidtko, Achim

2011-01-01

Accumulating evidence indicates that increased generation of reactive oxygen species (ROS) contributes to the development of exaggerated pain hypersensitivity during persistent pain. In the present study, we investigated the antinociceptive efficacy of the antioxidants vitamin C and vitamin E in mouse models of inflammatory and neuropathic pain. We show that systemic administration of a combination of vitamins C and E inhibited the early behavioral responses to formalin injection and the neuropathic pain behavior after peripheral nerve injury, but not the inflammatory pain behavior induced by Complete Freund's Adjuvant. In contrast, vitamin C or vitamin E given alone failed to affect the nociceptive behavior in all tested models. The attenuated neuropathic pain behavior induced by the vitamin C and E combination was paralleled by a reduced p38 phosphorylation in the spinal cord and in dorsal root ganglia, and was also observed after intrathecal injection of the vitamins. Moreover, the vitamin C and E combination ameliorated the allodynia induced by an intrathecally delivered ROS donor. Our results suggest that administration of vitamins C and E in combination may exert synergistic antinociceptive effects, and further indicate that ROS essentially contribute to nociceptive processing in special pain states. PMID:22195029

[Arthritis of the atlanto-axial joint with inflammatory neck pain as a primary manifestation of seronegative rheumatoid arthritis].

PubMed

Haeusler, U; Dybowski, F; Wittkaemper, T A; Kisters, K; Godolias, G; Braun, J

2010-09-01

A 68-year-old woman with known degenerative joint disease suffered from increasing neck pain. Physical examination revealed painfully restricted movement of the cervical spine. Erythrocyte sedimentation rate and C-reactive protein were increased. Tests for rheumatoid factors, antinuclear, anti-citrullinated protein and anti-neutrophil cytoplasmic antibody were negative. Cervical spine x-ray showed osteochondrosis with partially bridging spondylosis at C5/C6, but there was no atlanto-axial dislocation. Magnetic resonance imaging (MRI) revealed bone marrow edema and hyperintensity of the odontoid process, but there were no indications of fissures or fracture lines. These findings indicated seronegative rheumatoid arthritis, with predominantly active atlanto-axial arthritis. After methotrexate and prednisolone had been administered the symptoms improved rapidly and inflammatory parameters returned to normal. Three months later no atlanto-axial arthritis was seen at MRI. Rheumatoid arthritis involving the atlanto-axial region should be considered in patients with persisting neck pain and signs of inflammation. Copyright Georg Thieme Verlag KG Stuttgart . New York.

Dyssynergic defecation: a treatable cause of persistent symptoms when inflammatory bowel disease is in remission.

PubMed

Perera, Lilani P; Ananthakrishnan, Ashwin N; Guilday, Corinne; Remshak, Kristin; Zadvornova, Yelena; Naik, Amar S; Stein, Daniel J; Massey, Benson T

2013-12-01

Introduction of biologic agents in inflammatory bowel disease (IBD) has increased the likelihood of disease remission. Despite resolution of active inflammation, a subset of IBD patients report persistent defecatory symptoms. To evaluate a group of patients with inflammatory bowel disease with suspected functional defecatory disorders, by use of anorectal manometric testing and subsequent biofeedback therapy. A group of IBD patients with persistent defecatory problems despite clinical improvement were included in this study. These patients had no evidence of left-sided disease. Endoscopic and radiographic study findings and timing in relation to the manometry study were recorded. Anorectal manometry was performed by the standard protocol and included rectal sensory assessment, ability to expel a balloon, and pressure dynamics with simulated defecation. Thirty IBD patients (Crohn's 23 patients; ulcerative colitis six patients) presented with defecatory disorders including constipation (67%) increased stooling (10%), and rectal urgency and/or incontinence and rectal pain (6%). All but one patient had anorectal manometric criteria of dyssynergia (presence of anismus motor pattern and inability to expel the balloon). Of the patients who completed biofeedback therapy, 30% had a clinically significant (≥7-point) improvement in SIBDQ score, with a reduction in health-care utilization after a six-month period (p=0.02). Despite remission, some inflammatory bowel disease patients have persistent defecatory symptoms. Defecatory symptoms may not be predictive of an underlying inflammatory disorder. Lack of inflammatory activity and absence of left-sided disease should prompt investigation of functional disorders. Anorectal manometric testing and biofeedback therapy for patients with a diagnosis of dyssynergia may be a useful therapy.

Osteoid osteoma: diagnosis and treatment.

PubMed

Papathanassiou, Zafiria G; Megas, Panagiotis; Petsas, Theodore; Papachristou, Dionisios J; Nilas, John; Siablis, Dimitrios

2008-11-01

Treatment of small but painful osteoid osteomas was traditionally based on either prolonged medication or resection. In the era of rapidly evolving minimally invasive techniques, reluctance has been posed against surgical interventions mostly due to their relatively high rates of recurrence, complications, or persistent pain. Nonetheless, incomplete pain control and intolerance to anti-inflammatory drugs unfavorably affect prognosis. The objective of this article is to explore the nature and clinical presentation of osteoid osteomas, discuss their imaging and histological features, review available data regarding surgical and percutaneous methods for addressing these lesions and comment on their feasibility, safety, and efficacy.

Postinflammatory visceral sensitivity and pain mechanisms.

PubMed

Vergnolle, N

2008-05-01

The inflammatory reaction is normally tightly regulated, and as soon as the original insult has been cleared, a resolution phase starts that aims at leading the tissues back to a normal physiological state. However, after intestinal inflammation, a number of patients develop postinflammatory hypersensitivity symptoms, which can be defined as an excessive sensitivity to gut nociceptive stimulation. The pain experienced by those patients has been largely studied in the context of postinfectious intestinal diseases. The mechanisms of postinflammatory persistent visceral pain involve peripheral and central neuroplastic changes, low-grade chronic inflammation that sensitizes visceral afferent pathways and sensitization of non-neuronal resident cells of the gut. Several molecular determinants such as neurokinins, serotonin, proteases and voltage-gated ion channels seem to play a significant role in the control of postinflammatory visceral sensation. This review tries to give insights into the mechanisms of persistent visceral pain following the resolution of intestinal inflammation and tries to identify what needs to be done to further advance the field of postinflammatory hypersensitivity clinical management.

Evolutionary considerations in the development of chronic pelvic pain.

PubMed

Jarrell, John; Arendt-Nielsen, Lars

2016-08-01

Chronic pelvic pain is common among women of reproductive age and is associated with significant morbidity and comorbidities. In this Viewpoint, we explore the evolutionary cause of pelvic pain and summarize evidence that supports a menstruation-related evolutionary cause of chronic visceral pelvic pain: (1) lifetime menstruation has increased; (2) severe dysmenorrhea is common in the chronic pelvic pain population, particularly among those with pain sensitization; and (3) a potential biological mechanism can be identified. Thus, chronic pelvic pain may arise from the mismatch between the slow pace of biological evolution in our bodies and the relatively rapid pace of cultural changes that have resulted in increased menstrual frequency due to earlier menarche, later mortality, and lower fecundity. One possible mechanism that explains the development of persistent pain from repeated episodes of intermittent pain is hyperalgesic priming, a physiological process defined as a long-lasting latent hyperresponsiveness of nociceptors to inflammatory mediators after an inflammatory or neuropathic insult. The repetitive severely painful menstrual episodes may play such a role. From an evolutionary perspective the relatively rapid increase in lifetime menstruation experience in contemporary society may contribute to a mismatch between lifetime menstruation and the physiological pain processes, leading to a maladaptive state of chronic visceral pelvic pain. Our current physiology does not conform to current human needs. Copyright © 2016 Elsevier Inc. All rights reserved.

Persistent pain in the older adult: what should we do now in light of the 2009 American geriatrics society clinical practice guideline?

PubMed

Katz, James D; Shah, Tina

2009-12-01

The recent publication of revised guidelines for the management of persistent pain in the older adult (American Geriatric Society, 2009) has posed a dilemma for clinicians. In essence, these revised guidelines now downplay the use of nonsteroidal anti-inflammatory drugs (NSAIDs) relative to prior year's recommendations. The strong recommendation for caution when employing NSAIDs is because of the numerous, well-documented, potential adverse effects including renal failure, stroke, hypertension, heart failure exacerbations, and gastrointestinal complications. Nevertheless, physicians still have a substantial arsenal for combating chronic pain due to such conditions as degenerative arthritis and back problems. Options for intervention include physical therapy, topical nonsteroidals, capsaicin, topical lidocaine, intra-articular therapies, and judicious use of narcotics. In the future, cyclooxygenase-inhibiting nitric oxide-donating drugs may represent a technical improvement in the toxicity profile of traditional NSAIDs.

AMPAkines have novel analgesic properties in rat models of persistent neuropathic and inflammatory pain.

PubMed

Le, Alexander M; Lee, Michelle; Su, Chen; Zou, Anthony; Wang, Jing

2014-11-01

Novel analgesics that do not suppress the respiratory drive are urgently needed. Glutamate signaling through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors plays important roles in central pain circuits. AMPAkines augment AMPA receptor function and have been shown to stimulate the respiratory drive to oppose opioid-induced hypoventilation. However, their role in chronic pain states remains unknown. The authors studied AMPAkines (CX546 and CX516) in rat spared nerve injury (SNI) model of neuropathic pain and Complete Freund's Adjuvant (CFA) model of inflammatory pain. They measured the effect of AMPAkines on mechanical and cold allodynia. They also evaluated their effect on depressive symptoms of pain using the forced swim test, as time of immobility on this test has been used as a measure for behavioral despair, a feature of depression. The authors found that CX546, compared with dimethyl sulfoxide (DMSO) control, reduced both mechanical and sensory allodynia in SNI (DMSO group, n = 9; CX546 group, n = 11) and CFA models (both DMSO and CX546 groups, n = 9). They found that CX546, compared with control, also reduced depressive symptoms of pain by decreasing immobility on the forced swim test in both SNI (both DMSO and CX546 groups, n = 8) and CFA models (both DMSO and CX546 groups, n = 10). Finally, they found that CX516, compared with control, also reduced mechanical and cold allodynia in the SNI model (both DMSO and CX516 groups, n = 10). AMPAkines alleviate pain hypersensitivity as well as depression-like behavior associated with long-lasting nerve injury and inflammatory insult.

ISSLS PRIZE IN CLINICAL SCIENCE 2018: longitudinal analysis of inflammatory, psychological, and sleep-related factors following an acute low back pain episode-the good, the bad, and the ugly.

PubMed

Klyne, David M; Barbe, Mary F; van den Hoorn, Wolbert; Hodges, Paul W

2018-04-01

Prospective longitudinal study. To determine whether systemic cytokines and C-reactive protein (CRP) during an acute episode of low back pain (LBP) differ between individuals who did and did not recover by 6 months and to identify sub-groups based on patterns of inflammatory, psychological, and sleep features associated with recovery/non-recovery. Systemic inflammation is observed in chronic LBP and may contribute to the transition from acute to persistent LBP. Longitudinal studies are required to determine whether changes present early or develop over time. Psychological and/or sleep-related factors may be related. Individuals within 2 weeks of onset of acute LBP (N = 109) and pain-free controls (N = 55) provided blood for assessment of CRP, tumor necrosis factor (TNF), interleukin-6 (IL-6) and interleukin-1β, and completed questionnaires related to pain, disability, sleep, and psychological status. LBP participants repeated measurements at 6 months. Biomarkers were compared between LBP and control participants at baseline, and in longitudinal (baseline/6 months) analysis, between unrecovered (≥pain and disability), partially recovered (reduced pain and/or disability) and recovered (no pain and disability) participants at 6 months. We assessed baseline patterns of inflammatory, psychological, sleep, and pain data using hierarchical clustering and related the clusters to recovery (% change in pain) at 6 months. CRP was higher in acute LBP than controls at baseline. In LBP, baseline CRP was higher in the recovered than non-recovered groups. Conversely, TNF was higher at both time-points in the non-recovered than recovered groups. Two sub-groups were identified that associated with more ("inflammatory/poor sleep") or less ("high TNF/depression") recovery. This is the first evidence of a relationship between an "acute-phase" systemic inflammatory response and recovery at 6 months. High inflammation (CRP/IL-6) was associated with good recovery, but specific elevation of TNF, along with depressive symptoms, was associated with bad recovery. Depression and TNF may have a two-way relationship. These slides can be retrieved under Electronic Supplementary Material.

Slack channels expressed in sensory neurons control neuropathic pain in mice.

PubMed

Lu, Ruirui; Bausch, Anne E; Kallenborn-Gerhardt, Wiebke; Stoetzer, Carsten; Debruin, Natasja; Ruth, Peter; Geisslinger, Gerd; Leffler, Andreas; Lukowski, Robert; Schmidtko, Achim

2015-01-21

Slack (Slo2.2) is a sodium-activated potassium channel that regulates neuronal firing activities and patterns. Previous studies identified Slack in sensory neurons, but its contribution to acute and chronic pain in vivo remains elusive. Here we generated global and sensory neuron-specific Slack mutant mice and analyzed their behavior in various animal models of pain. Global ablation of Slack led to increased hypersensitivity in models of neuropathic pain, whereas the behavior in models of inflammatory and acute nociceptive pain was normal. Neuropathic pain behaviors were also exaggerated after ablation of Slack selectively in sensory neurons. Notably, the Slack opener loxapine ameliorated persisting neuropathic pain behaviors. In conclusion, Slack selectively controls the sensory input in neuropathic pain states, suggesting that modulating its activity might represent a novel strategy for management of neuropathic pain. Copyright © 2015 the authors 0270-6474/15/351125-11$15.00/0.

Widespread pain reliever profile of a flower extract of Tanacetum parthenium.

PubMed

Di Cesare Mannelli, Lorenzo; Tenci, Barbara; Zanardelli, Matteo; Maidecchi, Anna; Lugli, Andrea; Mattoli, Luisa; Ghelardini, Carla

2015-07-15

Tanacetum parthenium L., commonly called Feverfew, is known for anti-inflammatory and anti-migraine properties. Aimed to individuate new therapeutical strategies to control acute and persistent pain induced by different origins we tested two hydroalcoholic extracts obtained from Feverfew flowers and leaves, respectively. Extracts were characterized according to the European Pharmacopoeia monograph. Both the extracts were tested after acute per os administration in the dose range 30-1000 mg kg(-1). The anti-nociceptive properties were evaluated by the Writhing test in mice. The number of abdominal contractions was dose dependently reduced by the flower extract. It reduced mechanical hypersensitivity (Paw pressure test) related to the acute inflammatory phase induced by carrageenan similarly to diclofenac and ibuprofen. In the osteoarthritis model induced by intra articular injection of monoiodoacetate (MIA) the flower extract significantly increased the pain threshold peaking 30 min after treatment. Moreover, it was effective in the chronic constriction injury model of neuropathic pain showing activity similar to the anti-epileptic drug gabapentin. The flower extract activity was confirmed in rat models of chemotherapy-induced neuropathic pain. The mechanical hypersensitivity induced by repeated treatments with the anticancer drug oxaliplatin and with the antiviral dideoxycytidine was significantly reduced after a single injection of Feverfew flower extract. The leaf extract showed lesser efficacy and potency and it was devoid of any effect in carrageenan-, MIA- and chemotherapy-induced pain. The present Feverfew flower extract behaves as a potent pain reliever in acute, inflammatory, articular and neuropathic pain. It appears as a natural strategy potentially suitable for the treatment of different kinds of pain. Copyright © 2015 Elsevier GmbH. All rights reserved.

Assessment of Diverse Biological Indicators in Gulf War Illness: Are They Replicable Are They Related

DTIC Science & Technology

2015-10-01

that includes physical and neuropsychological evaluations, neuroimaging (MRI, fMRI , DTI), adrenal function tests, and diverse immune, inflammatory...characterized by a profile of concurrent symptoms that typically includes persistent headaches, memory and cognitive difficulties, widespread pain, unexplained...includes physical examinations, neuroimaging (MRI volumetric assessments, fMRI , diffusion tensor imaging), neuropsychological evaluations, assessment

Lymphogranuloma Venereum-Serovar L2b Presenting With Painful Genital Ulceration: An Emerging Clinical Presentation?

PubMed

Haber, Roger; Maatouk, Ismaël; de Barbeyrac, Bertille; Bagot, Martine; Janier, Michel; Fouéré, Sébastien

2017-05-01

These 5 cases of atypical inflammatory lymphogranula venereum (LGV) serovar L2b presenting initially with edema and persistent painful ulceration illustrate that clinical manifestations of LGV in the current outbreak in men who have sex with men reflect the influence of both the serovars virulence and the host immune system and are not confined to proctitis. L2b serovar could have a particular high virulence profile, and the need for awareness of LGV as a cause of genital ulceration is crucial.

Evidence for brain glial activation in chronic pain patients.

PubMed

Loggia, Marco L; Chonde, Daniel B; Akeju, Oluwaseun; Arabasz, Grae; Catana, Ciprian; Edwards, Robert R; Hill, Elena; Hsu, Shirley; Izquierdo-Garcia, David; Ji, Ru-Rong; Riley, Misha; Wasan, Ajay D; Zürcher, Nicole R; Albrecht, Daniel S; Vangel, Mark G; Rosen, Bruce R; Napadow, Vitaly; Hooker, Jacob M

2015-03-01

Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand (11)C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for (11)C-PBR28, nine patient-control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29-63 for patients and 28-65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Current alternatives in the surgical treatment of chronic pancreatitis--a review article].

PubMed

Kat'uchová, Jana; Radonak, Jozef

2011-01-01

Chronic pancreatitis is characterized as an inflammatory process affecting the pancreas that causes progressive destruction of the gland and fibrosis, with subsequent endocrine and exocrine insufficiency. The most common cause of chronic pancreatitis is alcohol use in combination with nicotine. Manifestations are persistent or recurrent painful attacks. The only parameter of successful treatment of chronic pancreatitis is a relieve from long-lasting pain and improvement of the quality of life. Surgical treatment options include drainage operations on the pancreas, pancreatic resection or a combination of both. With optimal surgical treatment performed and good patient's compliance, operations for chronic pancreatitis have low number of post-operative complications and relatively good long-term results. The continued consumption of alcohol and drugs bring about worse outcomes, sometimes even a complete failure of therapy. Chronic pancreatitis also has considerable socio-economic consequences. Due to the persisting pain and frequent hospitalization it can lead to long-term disability and early retirement predominantly in young patients.

Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury

PubMed Central

Ai, Zisheng; Zheng, Yongjun

2016-01-01

Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation. PMID:26872020

Pain management in rheumatology research, training, and practice.

PubMed

Borenstein, David G; Hassett, Afton L; Pisetsky, David

2017-01-01

The Pain Management Task Force of the American College of Rheumatology published a report in 2010 highlighting pain management as a fundamental aspect of clinical practice, training and research. In the interim, the consideration of pain as a focus of attention of rheumatologists and rheumatology health professionals has become even more challenging than in 2010 because of the epidemic of opiate addiction and overdose death. The characterisation of categories of pain by mechanism (e.g., inflammation, joint degeneration, abnormalities of central pain processing) can help guide treatment. However, such categorisation can overlook the overlap of these processes and their interaction to create mixed pain states. Further complicating the assessment of pain, outcome measures in rheumatic disease often assess the degree of pain indirectly while concentrating on the quantification of inflammation. Non-inflammatory pain often persists despite treatment, highlighting the need for alternative analgesic therapies. Recommended therapies include acetaminophen, nonsteroidal anti-inflammatory drugs, and stimulators of the pain inhibitory pathway. Each of these non-opioid therapies has incomplete efficacy and potential toxicities that can limit their utility. Non-pharmacologic therapies can show efficacy that rivals or surpasses pharmacologic therapies in the control of pain and improving function in a variety of rheumatic disorders including chronic low back pain and fibromyalgia. A limitation of the use of these therapies is inadequate training and appreciation of their benefits. Furthermore, the supply of trained practitioners to provide non-pharmacological care and support patient efforts for self-management is often limited. Together, these considerations suggest the importance of a renewed effort to implement task force recommendations.

Trigeminal Inflammatory Compression (TIC) Injury Induces Chronic Facial Pain and Susceptibility to Anxiety-Related Behaviors

PubMed Central

Lyons, Danielle N.; Kniffin, Tracey C.; Zhang, Liping; Danaher, Robert J.; Miller, Craig S.; Bocanegra, Jose L.; Carlson, Charles R.; Westlund, Karin N.

2015-01-01

Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week 8 post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury which resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model’s chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model. PMID:25818051

Mu opioid receptors on primary afferent nav1.8 neurons contribute to opiate-induced analgesia: insight from conditional knockout mice.

PubMed

Weibel, Raphaël; Reiss, David; Karchewski, Laurie; Gardon, Olivier; Matifas, Audrey; Filliol, Dominique; Becker, Jérôme A J; Wood, John N; Kieffer, Brigitte L; Gaveriaux-Ruff, Claire

2013-01-01

Opiates are powerful drugs to treat severe pain, and act via mu opioid receptors distributed throughout the nervous system. Their clinical use is hampered by centrally-mediated adverse effects, including nausea or respiratory depression. Here we used a genetic approach to investigate the potential of peripheral mu opioid receptors as targets for pain treatment. We generated conditional knockout (cKO) mice in which mu opioid receptors are deleted specifically in primary afferent Nav1.8-positive neurons. Mutant animals were compared to controls for acute nociception, inflammatory pain, opiate-induced analgesia and constipation. There was a 76% decrease of mu receptor-positive neurons and a 60% reduction of mu-receptor mRNA in dorsal root ganglia of cKO mice. Mutant mice showed normal responses to heat, mechanical, visceral and chemical stimuli, as well as unchanged morphine antinociception and tolerance to antinociception in models of acute pain. Inflammatory pain developed similarly in cKO and controls mice after Complete Freund's Adjuvant. In the inflammation model, however, opiate-induced (morphine, fentanyl and loperamide) analgesia was reduced in mutant mice as compared to controls, and abolished at low doses. Morphine-induced constipation remained intact in cKO mice. We therefore genetically demonstrate for the first time that mu opioid receptors partly mediate opiate analgesia at the level of Nav1.8-positive sensory neurons. In our study, this mechanism operates under conditions of inflammatory pain, but not nociception. Previous pharmacology suggests that peripheral opiates may be clinically useful, and our data further demonstrate that Nav1.8 neuron-associated mu opioid receptors are feasible targets to alleviate some forms of persistent pain.

Mu Opioid Receptors on Primary Afferent Nav1.8 Neurons Contribute to Opiate-Induced Analgesia: Insight from Conditional Knockout Mice

PubMed Central

Karchewski, Laurie; Gardon, Olivier; Matifas, Audrey; Filliol, Dominique; Becker, Jérôme A. J.; Wood, John N.; Kieffer, Brigitte L.; Gaveriaux-Ruff, Claire

2013-01-01

Opiates are powerful drugs to treat severe pain, and act via mu opioid receptors distributed throughout the nervous system. Their clinical use is hampered by centrally-mediated adverse effects, including nausea or respiratory depression. Here we used a genetic approach to investigate the potential of peripheral mu opioid receptors as targets for pain treatment. We generated conditional knockout (cKO) mice in which mu opioid receptors are deleted specifically in primary afferent Nav1.8-positive neurons. Mutant animals were compared to controls for acute nociception, inflammatory pain, opiate-induced analgesia and constipation. There was a 76% decrease of mu receptor-positive neurons and a 60% reduction of mu-receptor mRNA in dorsal root ganglia of cKO mice. Mutant mice showed normal responses to heat, mechanical, visceral and chemical stimuli, as well as unchanged morphine antinociception and tolerance to antinociception in models of acute pain. Inflammatory pain developed similarly in cKO and controls mice after Complete Freund’s Adjuvant. In the inflammation model, however, opiate-induced (morphine, fentanyl and loperamide) analgesia was reduced in mutant mice as compared to controls, and abolished at low doses. Morphine-induced constipation remained intact in cKO mice. We therefore genetically demonstrate for the first time that mu opioid receptors partly mediate opiate analgesia at the level of Nav1.8-positive sensory neurons. In our study, this mechanism operates under conditions of inflammatory pain, but not nociception. Previous pharmacology suggests that peripheral opiates may be clinically useful, and our data further demonstrate that Nav1.8 neuron-associated mu opioid receptors are feasible targets to alleviate some forms of persistent pain. PMID:24069332

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.

Purification and function of two analgesic and anti-inflammatory peptides from coelomic fluid of the earthworm, Eisenia foetida.

PubMed

Li, Chunlong; Chen, Mengrou; Li, Xiaojie; Yang, Meifeng; Wang, Ying; Yang, Xinwang

2017-03-01

The potential application of anti-inflammatory and analgesic compounds in medication and therapeutic care have become of increasing interest. We purified and characterized two novel analgesic and anti-inflammatory peptides, VQ-5 and AQ-5, from the coelomic fluid of the earthworm (Eisenia foetida). Their primary structures were determined as VSSVQ and AMADQ, respectively. Both peptides, especially AQ-5, exhibited analgesic activity in mouse models of persistent neuropathic pain and inflammation. AQ-5 also inhibited tumor necrosis factor alpha and cyclooxygenase-2 production. The mitogen-activated protein kinase signaling pathway, which is involved in analgesic and anti-inflammatory functions, was inhibited by AQ-5. Thus, the analgesic and anti-inflammatory effects of these peptides, especially AQ-5, demonstrated their potential as candidates for the development of novel analgesic medicines. Copyright © 2017 Elsevier Inc. All rights reserved.

Intraarticularly-Injected Mesenchymal Stem Cells Stimulate Anti-Inflammatory Molecules and Inhibit Pain Related Protein and Chondrolytic Enzymes in a Monoiodoacetate-Induced Rat Arthritis Model

PubMed Central

Ichiseki, Toru; Shimasaki, Miyako; Ueda, Yoshimichi; Tsuchiya, Masanobu; Souma, Daisuke; Kaneuji, Ayumi; Kawahara, Norio

2018-01-01

Persistent inflammation is well known to promote the progression of arthropathy. mesenchymal stem cells (MSCs) have been shown to possess anti-inflammatory properties and tissue differentiation potency. Although the experience so far with the intraarticular administration of mesenchymal stem cell (MSC) to induce cartilage regeneration has been disappointing, MSC implantation is now being attempted using various surgical techniques. Meanwhile, prevention of osteoarthritis (OA) progression and pain control remain important components of the treatment of early-stage OA. We prepared a shoulder arthritis model by injecting monoiodoacetate (MIA) into a rat shoulder, and then investigated the intraarticular administration of MSC from the aspects of the cartilage protective effect associated with their anti-inflammatory property and inhibitory effect on central sensitization of pain. When MIA was administered in this rat shoulder arthritis model, anti-Calcitonin Gene Related Peptide (CGRP) was expressed in the joint and C5 spinal dorsal horn. Moreover, expression of A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), a marker of joint cartilage injury, was similarly elevated following MIA administration. When MSC were injected intraarticularly after MIA, the expression of CGRP in the spinal dorsal horn was significantly deceased, indicating suppression of the central sensitization of pain. The expression of ADAMTS 5 in joint cartilage was also significantly inhibited by MSC administration. In contrast, a significant increase in the expression of TNF-α stimulated gene/protein 6 (TSG-6), an anti-inflammatory and cartilage protective factor shown to be produced and secreted by MSC intraarticularly, was found to extend to the cartilage tissue following MSC administration. In this way, the intraarticular injection of MSC inhibited the central sensitization of pain and increased the expression of the anti-inflammatory and cartilage protective factor TSG-6. As the least invasive conservative strategies possible are desirable in the actual clinical setting, the intraarticular administration of MSC, which appears to be effective for the treatment of pain and cartilage protection in early-stage arthritis, may achieve these aims. PMID:29315262

Trigeminal Inflammatory Compression (TIC) injury induces chronic facial pain and susceptibility to anxiety-related behaviors.

PubMed

Lyons, D N; Kniffin, T C; Zhang, L P; Danaher, R J; Miller, C S; Bocanegra, J L; Carlson, C R; Westlund, K N

2015-06-04

Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week eight post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model's chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Epiregulin and EGFR interactions are involved in pain processing

PubMed Central

Martin, Loren J.; Smith, Shad B.; Khoutorsky, Arkady; Magnussen, Claire A.; Samoshkin, Alexander; Sorge, Robert E.; Cho, Chulmin; Yosefpour, Noosha; Sivaselvachandran, Sivaani; Tohyama, Sarasa; Cole, Tiffany; Khuong, Thang M.; Mir, Ellen; Gibson, Dustin G.; Wieskopf, Jeffrey S.; Sotocinal, Susana G.; Austin, Jean Sebastien; Meloto, Carolina B.; Gitt, Joseph H.; Sonenberg, Nahum; Greenspan, Joel D.; Fillingim, Roger B.; Slade, Gary D.; Knott, Charles; Dubner, Ronald; Nackley, Andrea G.; Ribeiro-da-Silva, Alfredo; Neely, G. Gregory; Maixner, William; Zaykin, Dmitri V.; Mogil, Jeffrey S.; Diatchenko, Luda

2017-01-01

The EGFR belongs to the well-studied ErbB family of receptor tyrosine kinases. EGFR is activated by numerous endogenous ligands that promote cellular growth, proliferation, and tissue regeneration. In the present study, we have demonstrated a role for EGFR and its natural ligand, epiregulin (EREG), in pain processing. We show that inhibition of EGFR with clinically available compounds strongly reduced nocifensive behavior in mouse models of inflammatory and chronic pain. EREG-mediated activation of EGFR enhanced nociception through a mechanism involving the PI3K/AKT/mTOR pathway and matrix metalloproteinase-9. Moreover, EREG application potentiated capsaicin-induced calcium influx in a subset of sensory neurons. Both the EGFR and EREG genes displayed a genetic association with the development of chronic pain in several clinical cohorts of temporomandibular disorder. Thus, EGFR and EREG may be suitable therapeutic targets for persistent pain conditions. PMID:28783046

Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury.

PubMed

Fairbanks, C A; Schreiber, K L; Brewer, K L; Yu, C G; Stone, L S; Kitto, K F; Nguyen, H O; Grocholski, B M; Shoeman, D W; Kehl, L J; Regunathan, S; Reis, D J; Yezierski, R P; Wilcox, G L

2000-09-12

Antagonists of glutamate receptors of the N-methyl-d-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in brain and spinal cord, has both NMDAR antagonist and NOS inhibitor activities. We report here that AG, exogenously administered to rodents, decreased hyperalgesia accompanying inflammation, normalized the mechanical hypersensitivity (allodynia/hyperalgesia) produced by chemical or mechanical nerve injury, and reduced autotomy-like behavior and lesion size after excitotoxic spinal cord injury. AG produced these effects in the absence of antinociceptive effects in acute pain tests. Endogenous AG also was detected in rodent lumbosacral spinal cord in concentrations similar to those previously detected in brain. The evidence suggests a unique antiplasticity and neuroprotective role for AG in processes underlying persistent pain and neuronal injury.

In Vitro and In Vivo Characterization of the New Analgesic Combination Beta-Caryophyllene and Docosahexaenoic Acid

PubMed Central

Fiorenzani, Paolo; Lamponi, Stefania; Magnani, Agnese; Ceccarelli, Ilaria; Aloisi, Anna Maria

2014-01-01

Beta-caryophyllene (BCP) and docosahexaenoic acid (DHA) are components of several plants with documented anti-inflammatory and analgesic effects in animal pain models. In the present study, in vitro and in vivo tests were carried out to evaluate their effects, alone or in combination, during long-lasting administration in a model of persistent pain. IR spectra of the two compounds were obtained to determine their chemical stability and then in vitro toxicity was evaluated in fibroblasts and astrocytes. In the in vivo tests, the analgesic effects of BCP and BCP+DHA were determined in male rats subjected to a model of persistent recurrent pain (three repetitions of the formalin test once a week) to mimic recurrent pain. Both substances were administered per os in almond oil for 2 weeks. Gonadal hormones were determined at the end of the tests to evaluate treatment-induced effects on their levels. BCP changed fibroblast and astrocyte survival in a dose-dependent manner and the effect was counteracted by DHA coadministration. In the in vivo tests, pain responses were significantly decreased in the BCP and BCP+DHA groups with respect to OIL after 1 and 2 weeks of treatment. Estradiol and testosterone levels were increased only in the BCP group. In conclusion, BCP alone or at lower concentration in combination with DHA was efficacious in modulating pain, showing a clear analgesic activity. PMID:25097659

The gut-brain interaction in opioid tolerance.

PubMed

Akbarali, Hamid I; Dewey, William L

2017-12-01

The prevailing opioid crisis has necessitated the need to understand mechanisms leading to addiction and tolerance, the major contributors to overdose and death and to develop strategies for developing drugs for pain treatment that lack abuse liability and side-effects. Opioids are commonly used for treatment of pain and symptoms of inflammatory bowel disease. The significant effect of opioids in the gut, both acute and chronic, includes persistent constipation and paradoxically may also worsen pain symptoms. Recent work has suggested a significant role of the gastrointestinal microbiome in behavioral responses to opioids, including the development of tolerance to its pain-relieving effects. In this review, we present current concepts of gut-brain interaction in analgesic tolerance to opioids and suggest that peripheral mechanisms emanating from the gut can profoundly affect central control of opioid function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Arthroscopic Synovectomy of Wrist in Rheumatoid Arthritis.

PubMed

Shim, Jae Woo; Park, Min Jong

2017-11-01

Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting multiple joints. Wrist involvement is common. Patients with persistent symptoms despite medical management are candidates for surgery. Synovectomy can provide pain relief and functional improvement for rheumatoid wrist. Arthroscopic synovectomy is a safe and reliable method, with minimal postoperative morbidity. This article reviews the role, technique, and results of arthroscopic synovectomy in the rheumatoid wrist. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictors of positive 18F-FDG PET/CT-scan for large vessel vasculitis in patients with persistent polymyalgia rheumatica.

PubMed

Prieto-Peña, Diana; Martínez-Rodríguez, Isabel; Loricera, Javier; Banzo, Ignacio; Calderón-Goercke, Mónica; Calvo-Río, Vanesa; González-Vela, Carmen; Corrales, Alfonso; Castañeda, Santos; Blanco, Ricardo; Hernández, José L; González-Gay, Miguel Á

2018-05-18

Polymyalgia rheumatica (PMR) is often the presenting manifestation of giant cell arteritis (GCA). Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan often discloses the presence of large vessel vasculitis (LVV) in PMR patients. We aimed to identify predictive factors of a positive PET/CT scan for LVV in patients classified as having isolated PMR according to well-established criteria. A set of consecutive patients with PMR from a single hospital were assessed. All of them underwent PET/CT scan between January 2010 and February 2018 based on clinical considerations. Patients with PMR associated to other diseases, including those with cranial features of GCA, were excluded. The remaining patients were categorized in classic PMR (if fulfilled the 2012 EULAR/ACR classification criteria at disease diagnosis; n = 84) or atypical PMR (who did not fulfill these criteria; n = 16). Only information on patients with classic PMR was assessed. The mean age of the 84 patients (51 women) with classic PMR was 71.4 ± 9.2 years. A PET/CT scan was positive in 51 (60.7%). Persistence of classic PMR symptoms was the most common reason to perform a PET/CT scan. Nevertheless, patients with positive PET/CT scan often had unusual symptoms. The best set of predictors of a positive PET/CT scan were bilateral diffuse lower limb pain (OR = 8.8, 95% CI: 1.7-46.3; p = 0.01), pelvic girdle pain (OR = 4.9, 95% CI: 1.50-16.53; p = 0.01) and inflammatory low back pain (OR = 4.7, 95% CI: 1.03-21.5; p = 0.04). Inflammatory low back pain, pelvic girdle and diffuse lower limb pain are predictors of positive PET/CT scan for LVV in PMR. Copyright © 2018 Elsevier Inc. All rights reserved.

Mechanisms Mediating Vibration-induced Chronic Musculoskeletal Pain Analyzed in the Rat

PubMed Central

Dina, Olayinka A.; Joseph, Elizabeth K.; Levine, Jon D.; Green, Paul G.

2009-01-01

While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and re-exposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60–80 Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to a pro-inflammatory cytokine or re-exposure to vibration. Exposure of a hind limb to vibration produced mechanical hyperalgesia measured in the gastrocnemius muscle of the exposed hind limb, which persisted for ~2 weeks. When nociceptive thresholds had returned to baseline, exposure to a pro-inflammatory cytokine or re-exposure to vibration produced markedly prolonged hyperalgesia. The chronic prolongation of vibration- and cytokine-hyperalgesia induced by vibration was prevented by spinal intrathecal injection of oligodeoxynucleotide (ODN) antisense to protein kinase Cε, a second messenger in nociceptors implicated in the induction and maintenance of chronic pain. Vibration-induced hyperalgesia was inhibited by spinal intrathecal administration of ODN antisense to receptors for the type-1 tumor necrosis factor-α (TNFα) receptor. Finally, in TNFα-pretreated muscle, subsequent vibration-induced hyperalgesia was markedly prolonged. Perspective These studies establish a model of vibration-induced acute and chronic musculoskeletal pain, and identify the proinflammatory cytokine TNFα and the second messenger PKCε as targets against which therapies might be directed to prevent and/or treat this common and very debilitating chronic pain syndrome. PMID:19962353

Pain management in older adults.

PubMed

Tracy, Bridget; Sean Morrison, R

2013-11-01

Chronic pain is prevalent among older adults but is underrecognized and undertreated. The approach to pain assessment and management in older adults requires an understanding of the physiology of aging, validated assessment tools, and common pain presentations among older adults. To identify the overall principles of pain management in older adults with a specific focus on common painful conditions and approaches to pharmacologic treatment. We searched PubMed for common pain presentations in older adults with heart failure, end-stage renal disease, dementia, frailty, and cancer. We also reviewed guidelines for pain management. Our review encompassed 2 guidelines, 10 original studies, and 22 review articles published from 2000 to the present. This review does not discuss nonpharmacologic treatments of pain. Clinical guidelines support the use of opioids in persistent nonmalignant pain. Opioids should be used in patients with moderate or severe pain or pain not otherwise controlled but with careful attention to potential toxic effects and half-life. In addition, clinical practice guidelines recommend use of oral nonsteroidal anti-inflammatory drugs with extreme caution and for defined, limited periods. An understanding of the basics of pain pathophysiology, assessment, pharmacologic management, and a familiarity with common pain presentations will allow clinicians to effectively manage pain for older adults. © 2013 Elsevier HS Journals, Inc. All rights reserved.

Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury

PubMed Central

Fairbanks, Carolyn A.; Schreiber, Kristin L.; Brewer, Kori L.; Yu, Chen-Guang; Stone, Laura S.; Kitto, Kelley F.; Nguyen, H. Oanh; Grocholski, Brent M.; Shoeman, Don W.; Kehl, Lois J.; Regunathan, Soundararajan; Reis, Donald J.; Yezierski, Robert P.; Wilcox, George L.

2000-01-01

Antagonists of glutamate receptors of the N-methyl-d-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in brain and spinal cord, has both NMDAR antagonist and NOS inhibitor activities. We report here that AG, exogenously administered to rodents, decreased hyperalgesia accompanying inflammation, normalized the mechanical hypersensitivity (allodynia/hyperalgesia) produced by chemical or mechanical nerve injury, and reduced autotomy-like behavior and lesion size after excitotoxic spinal cord injury. AG produced these effects in the absence of antinociceptive effects in acute pain tests. Endogenous AG also was detected in rodent lumbosacral spinal cord in concentrations similar to those previously detected in brain. The evidence suggests a unique antiplasticity and neuroprotective role for AG in processes underlying persistent pain and neuronal injury. PMID:10984543

Unusual case of acute appendicitis with left upper quadrant abdominal pain.

PubMed

Tawk, Charbel M; Zgheib, Rana R; Mehanna, Seba

2012-01-01

Acute appendicitis is one of the most frequent causes of surgical abdominal pain presenting to the Emergency Department. The diagnosis is confirmed by a set of clinical signs, blood tests and imaging. The typical presentation consists of periumbilical pain radiating to the right lower quadrant with peritoneal reaction on palpation (Mac Burney). In this article, we report a case of acute appendicitis presenting with a left upper quadrant pain due to intestinal malrotation and we describe the radiologic findings on computed tomography. With an Alvarado score of 4 and a nonconclusive abdominal U/S, the diagnosis of acute appendicitis was a long shot. Persistence of pain and increasing inflammatory parameters in her blood exams pushed the medical team to further investigate and a CT scan revealed intestinal malrotation with acute appendicitis. An examining physician should not be mislead by the atypical presentation of acute appendicitis and should bear in mind the diagnosis to avoid serious complications. Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Edema: a silent but important factor.

PubMed

Villeco, June P

2012-01-01

Edema is a normal response to injury. Even the smallest injury is associated with some inflammation, and initial edema is part of the normal inflammatory process. However, edema becomes a concern when it persists beyond the inflammatory phase. Once we have progressed into the rebuilding, or fibroplastic phase of healing, edema will delay healing and contribute to complications such as pain and stiffness. Early prevention and management to prevent this progression are therefore critical. This article discusses edema in relation to stages of healing and presents the research behind techniques available to the clinician to manage localized extracellular upper extremity edema in the patient with an intact lymphatic system. Copyright © 2012 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Persistent arm pain is distinct from persistent breast pain following breast cancer surgery.

PubMed

Langford, Dale J; Paul, Steven M; West, Claudia; Abrams, Gary; Elboim, Charles; Levine, Jon D; Hamolsky, Deborah; Luce, Judith A; Kober, Kord M; Neuhaus, John M; Cooper, Bruce A; Aouizerat, Bradley E; Miaskowski, Christine

2014-12-01

Persistent pain following breast cancer surgery is well documented. However, it is not well characterized in terms of the anatomic site affected (ie, breast, arm). In 2 separate growth mixture modeling analyses, we identified subgroups of women (N = 398) with distinct breast pain and arm pain trajectories. The fact that these latent classes differed by anatomic site, types of tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. The purposes of this companion study were to identify demographic and clinical characteristics that differed between the 2 arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection sites, pain qualities, pain interference, and hand and arm function, as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the moderate arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and axillary lymph node dissection site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility. For persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

Defining the neurotoxin derived illness chronic ciguatera using markers of chronic systemic inflammatory disturbances: a case/control study.

PubMed

Shoemaker, Ritchie C; House, Dennis; Ryan, James C

2010-01-01

Ciguatoxins are extremely potent neurotoxins, produced by tropical marine dinoflagellates, that persistently enter into our food web. Over 100,000 people annually experience acute ciguatera poisoning from consuming toxic fish. Roughly 5% of these victims will develop chronic ciguatera (CC), a widespread, multisymptom, multisystem, chronic illness that can last tens of years. CC is marked by disproportionate disability and non-specific refractory symptoms such as fatigue, cognitive deficits and pain, and is suggestive of other illnesses. Its unknown pathophysiology makes both diagnosis and treatment difficult. We wanted to compare objective parameters of visual contrast sensitivity testing, measures of innate immune response and genetic markers in cases to controls to assess the potential for the presence of persistent inflammatory parameters that are demonstrated in other biotoxin associated illnesses at a single specialty clinic. Using 59 CC cases and 59 controls we present in retrospective review, in all cases, abnormalities in immune responses paralleling the chronic systemic inflammatory response syndrome seen in several other chronic diseases. This study defines a preliminary case definition using medical history, total symptoms, visual contrast sensitivity, HLA DR genotype analysis, reduction of regulatory neuropeptides VIP and MSH, and multiple measures of inflammatory immune response, especially C4a and TGFβ1, thereby providing a basis for identification and targeted therapy. CC provides a model for chronic human illness associated with initiation of inflammatory responses by biologically produced neurotoxins. Copyright © 2010 Elsevier Inc. All rights reserved.

PERSISTENT ARM PAIN IS DISTINCT FROM PERSISTENT BREAST PAIN FOLLOWING BREAST CANCER SURGERY

PubMed Central

Langford, Dale J.; Paul, Steven M.; West, Claudia; Abrams, Gary; Elboim, Charles; Levine, Jon D.; Hamolsky, Deborah; Luce, Judith A.; Kober, Kord M.; Neuhaus, John M.; Cooper, Bruce A.; Aouizerat, Bradley E.; Miaskowski, Christine

2014-01-01

Persistent pain following breast cancer surgery is well-documented. However, it is not well characterized in terms of the anatomic site effected (i.e., breast, arm). In two separate growth mixture modeling analyses, we identified subgroups of women (n=398) with distinct breast pain and arm pain trajectories. Based on the fact that these latent classes differed by anatomic site, types if tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. Purposes of this companion study were to identify demographic and clinical characteristics that differed between the two arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection (ALND) sites, pain qualities, pain interference, and hand and arm function; as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the Moderate Arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and ALND site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility. Perspective: For persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women. PMID:25439319

Development, sensibility, and reliability of the Toronto Axial Spondyloarthritis Questionnaire in inflammatory bowel disease.

PubMed

Alnaqbi, Khalid A; Touma, Zahi; Passalent, Laura; Johnson, Sindhu R; Tomlinson, George A; Carty, Adele; Inman, Robert D

2013-10-01

There is an unacceptable delay in the diagnosis of axial spondyloarthritis (axSpA) in its early stages among patients at high risk, in particular those with inflammatory bowel disease (IBD). Our objectives were to develop a sensible and reliable questionnaire to identify undetected axSpA among patients with IBD. Literature was reviewed for item generation in the Toronto axSpA Questionnaire on IBD (TASQ-IBD). Sensibility of the questionnaire was assessed among healthcare professionals and patients. This assessment was related to purpose and framework (clinical function, clinical justification, and clinical applicability), face validity, comprehensiveness [oligo-variability (limiting the questionnaire to important items) and transparency], replicability, content validity, and feasibility. The test-retest reliability study was administered to 77 patients with established IBD and axSpA. Kappa agreement coefficients and absolute agreement were calculated for items. Three domains included IBD, inflammatory back symptoms, and extraaxial features. The entry criterion required a patient to have IBD and back pain or stiffness that ever persisted for ≥ 3 months. Iterative sensibility assessment involved 16 items and a diagram of the back. Kappa coefficients ranged from 0.81-1.00 for each item. Absolute agreement across all items ranged from 91% to 100%. TASQ-IBD is a newly developed, sensible, and reliable case-finding questionnaire to be administered to patients with IBD who have ever had chronic back pain or stiffness persisting for ≥ 3 months. It should facilitate identification and timely referral of patients with IBD to rheumatologists and minimize the delay in diagnosis of axSpA. Consequently, it should assess the prevalence of axSpA in IBD.

Antihypernociceptive and antioxidant effects of Petersianthus macrocarpus stem bark extracts in rats with complete Freund's adjuvant-induced persistent inflammatory pain.

PubMed

Bomba, Francis Desire Tatsinkou; Wandji, Bibiane Aimée; Fofié, Christian Kuete; Kamanyi, Albert; Nguelefack, Télesphore Benoit

2017-03-14

Background Petersianthus macrocarpus (P. Beauv.) Liben (Lecythidaceae) is a plant used in Cameroonian folk medicine to cure ailments such as inflammation and pain. Previous work showed that aqueous (AEPM) and methanol (MEPM) extracts from the stem bark of P. macrocarpus possess acute analgesic activities. The present study evaluates whether the same extracts could inhibit persistent hyperalgesia induced by complete Freund's adjuvant (CFA) in rats. Methods Inflammatory pain was induced by intraplantar injection of CFA into the left hind paw of Wistar rats. AEPM and MEPM were administered either acutely or chronically by the oral route at the doses of 100 and 200 mg/kg/day. The mechanical hyperalgesia was tested using an analgesimeter, while the locomotion activity at the end of experiment was evaluated with an open-field device. Nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) contents were assayed in the brain and spinal cord of rats subjected to 14 days chronic treatment. Results AEPM and MEPM at both doses significantly (p<0.001) inhibited the acute and chronic mechanical hyperalgesia induced by CFA. Although not significant, both extracts increased the mobility of CFA-injected animals. AEPM significantly (p<0.01) reduced the level of nitrate at 100 mg/kg, MDA at 200 mg/kg and significantly (p<0.05) increased the SOD in the spinal cord. MEPM significantly increased the SOD content and reduced the MDA concentration in the brain but had no effect on the nitrate. Conclusions AEPM and MEPM exhibit acute and chronic antihyperalgesic activities. In addition, both extracts possess antioxidant properties that might strengthen their chronic antihyperalgesic effects.

Persistent breast pain among women with histories of breast conserving surgery for breast cancer compared to women without histories of breast surgery or cancer

PubMed Central

Edmond, Sara N.; Shelby, Rebecca A.; Keefe, Francis J.; Fisher, Hannah M.; Schmidt, John; Soo, Mary Scott; Skinner, Celette Sugg; Ahrendt, Gretchen M.; Manculich, Jessica; Sumkin, Jules H.; Zuley, Margarita L.; Bovbjerg, Dana H.

2016-01-01

Objectives This study compared persistent breast pain among women who received breast-conserving surgery for breast cancer and women without a history of breast cancer. Methods Breast cancer survivors (n=200) were recruited at their first post-surgical surveillance mammogram (6-15 months post-surgery). Women without a breast cancer history (n=150) were recruited at the time of a routine screening mammogram. All women completed measures of breast pain, pain interference with daily activities and intimacy, worry about breast pain, anxiety symptoms, and depression symptoms. Demographic and medical information were also collected. Results Persistent breast pain (duration ≥ 6 months) was reported by 46.5% of breast cancer survivors and 12.7% of women without a breast cancer history (p<0.05). Breast cancer survivors also had significantly higher rates of clinically significant persistent breast pain (pain intensity score ≥3/10), as well as higher average breast pain intensity and unpleasantness scores. Breast cancer survivors with persistent breast pain had significantly higher levels of depressive symptoms, as well as pain worry and interference, compared to survivors without persistent breast pain or women without a breast cancer history. Anxiety symptoms were significantly higher in breast cancer survivors with persistent breast pain compared to women without a breast cancer history. Discussion Results indicate that persistent breast pain negatively impacts women with a history of breast conserving cancer surgery compared to women without that history. Strategies to ameliorate persistent breast pain and to improve adjustment among women with persistent breast pain should be explored for incorporation into standard care for breast cancer survivors. PMID:27922843

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.

Atypical presentation of macrophagic myofasciitis 10 years post vaccination.

PubMed

Ryan, Aisling M; Bermingham, Niamh; Harrington, Hugh J; Keohane, Catherine

2006-12-01

Macrophagic myofasciitis (MMF) is an uncommon inflammatory disorder of muscle believed to be due to persistence of vaccine-derived aluminium hydroxide at the site of injection. The condition is characterised by diffuse myalgias, arthralgia and fatigue. We describe a patient with histologically confirmed MMF whose presentation was atypical with left chest and upper limb pain beginning more than 10 years post vaccination. Treatment with steroids led to symptomatic improvement. Although rare, clinicians should consider MMF in cases of atypical myalgia.

Bioactive dietary peptides and amino acids in inflammatory bowel disease.

PubMed

Zhang, Hua; Hu, Chien-An A; Kovacs-Nolan, Jennifer; Mine, Yoshinori

2015-10-01

Inflammatory bowel disease (IBD), most commonly ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammation of the gastrointestinal tract. Patients affected with IBD experience symptoms including abdominal pain, persistent diarrhea, rectal bleeding, and weight loss. There is no cure for IBD; thus treatments typically focus on preventing complications, inducing and maintaining remission, and improving quality of life. During IBD, dysregulation of the intestinal immune system leads to increased production of pro-inflammatory cytokines, such as TNF-α and IL-6, and recruitment of activated immune cells to the intestine, causing tissue damage and perpetuating the inflammatory response. Recent biological therapies targeting specific inflammatory cytokines or pathways, in particular TNF-α, have shown promise, but not all patients respond to treatment, and some individuals become intolerant to treatment over time. Dietary peptides and amino acids (AAs) have been shown to modulate intestinal immune functions and influence inflammatory responses, and may be useful as alternative or ancillary treatments in IBD. This review focuses on dietary interventions for IBD treatment, in particular the role of dietary peptides and AAs in reducing inflammation, oxidative stress, and apoptosis in the gut, as well as recent advances in the cellular mechanisms responsible for their anti-inflammatory activity.

[Mirror therapy for inflammatory rheumatic pain: Potentials and limitations].

PubMed

Bekrater-Bodmann, R

2015-11-01

Mirror therapy reduces chronic pain and might also be suitable for the treatment of inflammatory rheumatic pain. On the basis of the relevant literature this article a) characterizes the universal alterations in body perception and body representation in chronic pain, b) describes the potential mechanisms underlying mirror therapy and c) discusses the chances of success of mirror therapy for the treatment of inflammatory rheumatic pain. Literature search on the effectiveness and mechanisms of mirror therapy and derived procedures for the potential treatment of pain in inflammatory rheumatic disorders. There is evidence that mirror therapy can alleviate chronic pain experiences by correcting the accompanying distorted body perception as well as body representation by multimodal sensory stimulation. As there is probably a similar distortion in persons with chronic pain related to inflammatory rheumatic disorders, mirror therapy might also have positive effects in this field; however, the accompanying characteristics of these disorders, such as motor impairment and motor-evoked pain, may complicate the implementation of this kind of treatment. Mirror therapy represents an intervention with few side effects and might have positive effects on the experience of chronic pain in patients with inflammatory rheumatic disorders. Further clinical research is required in order to evaluate the potential of mirror therapy and associated interventional methods for the treatment of inflammatory rheumatic pain.

Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain.

PubMed

Inage, Kazuhide; Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

2016-08-01

Retrospective study. To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain.

Role of interleukin-1beta and tumor necrosis factor-alpha-dependent expression of cyclooxygenase-2 mRNA in thermal hyperalgesia induced by chronic inflammation in mice.

PubMed

Narita, M; Shimamura, M; Imai, S; Kubota, C; Yajima, Y; Takagi, T; Shiokawa, M; Inoue, T; Suzuki, M; Suzuki, T

2008-03-18

The present study investigated whether the endogenous pro-inflammatory cytokines [interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha)]-dependent expression of cyclooxygenase-2 (COX-2) mRNA within the spinal cord could be involved in the development of chronic inflammatory pain-like behaviors in mice. We demonstrated that the expression of COX-2 mRNA on the ipsilateral side of the spinal cord was significantly increased 6 h and 3 days after intraplantar injection of complete Freund's adjuvant (CFA), compared with the expression in saline-treated mice. In addition, the chronic pain-like behaviors following CFA injection were markedly suppressed by repeated intrathecal (i.t.) pre-treatment with the COX-2 inhibitor etodolac, but not with the COX-1 inhibitor mofezolac. The cytosolic level of the activated form of nuclear factor-kappa B (NF-kappaB), which is a major contributor to the induction of COX-2, on the ipsilateral side of the mouse spinal cord was also increased compared with that in the saline-treated mice. The key finding in the present study was that a single i.t. injection with either IL-1beta or TNF-alpha induced a marked increase in spinal COX-2 mRNA and persistent thermal hyperalgesia in mice. Furthermore, CFA-induced hypersensitivity to inflammatory pain was significantly reduced by repeated i.t. pre-injection of the recombinant Fc chimera of IL-1 receptor I or soluble TNF receptor I, which sequesters endogenous IL-1beta or TNF-alpha, respectively. In contrast, the expression of spinal COX-2 mRNA in CFA-treated mice was similar to that in saline-treated mice at 7 days after CFA injection. The present findings strongly indicate the early intrathecal use of the COX-2 inhibitor for the relief of chronic inflammatory pain. Furthermore, together with the result in a previous study that pro-inflammatory cytokines lead to stimulation of a NF-kappaB-dependent transcriptional pathway, these findings suggest that a spinal cytokine/NF-kappaB/COX-2 pathway may play an important role in the development, but not maintenance, of chronic pain following peripheral tissue inflammation.

Diabetes is associated with persistent pain after hip and knee replacement

PubMed Central

Rajamäki, Tuomas J; Jämsen, Esa; Puolakka, Pia A; Nevalainen, Pasi I; Moilanen, Teemu

2015-01-01

Background and purpose In some patients, for unknown reasons pain persists after joint replacement, especially in the knee. We determined the prevalence of persistent pain following primary hip or knee replacement and its association with disorders of glucose metabolism, metabolic syndrome (MetS), and obesity. Patients and methods The incidence of pain in the operated joint was surveyed 1–2 years after primary hip replacement (74 patients (4 bilateral)) or primary knee replacement (119 patients (19 bilateral)) in 193 osteoarthritis patients who had participated in a prospective study on perioperative hyperglycemia. Of the 155 patients who completed the survey, 21 had undergone further joint replacement surgery during the follow-up and were excluded, leaving 134 patients for analysis. Persistent pain was defined as daily pain in the operated joint that had lasted over 3 months. Factors associated with persistent pain were evaluated using binary logistic regression with adjustment for age, sex, and operated joint. Results 49 of the134 patients (37%) had a painful joint and 18 of them (14%) had persistent pain. A greater proportion of knee patients than hip patients had a painful joint (46% vs. 24%; p = 0.01) and persistent pain (20% vs. 4%; p = 0.007). Previously diagnosed diabetes was strongly associated with persistent pain (5/19 vs. 13/115 in those without; adjusted OR = 8, 95% CI: 2–38) whereas MetS and obesity were not. However, severely obese patients (BMI ≥ 35) had a painful joint (but not persistent pain) more often than patients with BMI < 30 (14/21 vs. 18/71; adjusted OR = 5, 95% CI: 2–15). Interpretation Previously diagnosed diabetes is a risk factor for persistent pain in the operated joint 1–2 years after primary hip or knee replacement. PMID:25953426

Frequency, Impact, and Predictors of Persistent Pain Following Root Canal Treatment: A National Dental PBRN Study

PubMed Central

Nixdorf, Donald R.; Law, Alan S.; Lindquist, Kimberly; Reams, Gregory J.; Cole, Emery; Kanter, Keith; Nguyen, Ruby H.N.; Harris, D. Robert

2015-01-01

Root canal treatment (RCT) is commonly performed surgery and persistent pain is known to occur, but little is known about how these patients are affected by this pain. While biopsychosocial mechanisms are thought to be associated with the development of such pain, similar to persistent pain following surgery in other body sites, little is known about the baseline predictors for persistent pain. We assessed the frequency of persistent pain 6 months following RCT, measured the impact this pain had on patients, and determined predictive factors for persistent tooth pain in a multi-center prospective cohort study conducted within the National Dental Practice-Based Research Network. Of 708 patients enrolled, 651 (91.9%) provided follow-up data, with 65 (10.0%) meeting criteria for pain 6 months following RCT. On average, these patients reported their pain as mild to moderate in intensity, present for about 10 days in the preceding month, and minimally interfered with daily activities. After adjusting for type of dental practitioner and patient age, gender and household income, pain duration over the week prior to RCT significantly increased the risk of developing persistent pain (odds ratio [OR]=1.19 per 1 day increase in pain duration, 95% confidence interval [CI]: 1.07–1.33), whereas optimism about the procedure reduced the risk (OR=0.39, 95% CI: 0.22–0.67). Our data suggest that persistent pain following RCT is fairly common, but generally does not have a large impact on those experiencing it. Furthermore, patient age and gender did not predict persistent pain, while pre-operative pain duration and the patient’s expectation did. PMID:26335907

[A case of short-lasting unilateral neuralgiform headache with conjunctival injection and tearing triggered by mumps meningitis in a patient with recurrent primary stabbing headache].

PubMed

Unai, Yuki; Sato, Kenta

2018-03-28

A 32-year-old man with a 16-year history of recurrent primary stabbing headache was admitted to our hospital, owing to mumps meningitis. On day 2 of admission, he began experiencing episodes of unbearable intermittent stabbing pain, each lasting few seconds, with conjunctival injection and tearing, on the temporal side of the left orbit. We suspected trigeminal autonomic cephalgias, and administered non-steroidal anti-inflammatory drugs (NSAIDs), oxygen, and sumatriptan; however, the pain episodes persisted. Subsequently, after the start of intravenous lidocaine administration, the pain episodes stopped. We diagnosed a short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), triggered by mumps meningitis. This is a valuable case report, involving a patient with a history of primary stabbing headache who was diagnosed with SUNCT triggered by mumps meningitis.

Association of pain catastrophizing with the incidence and severity of acute and persistent perineal pain after natural childbirth: longitudinal cohort study.

PubMed

Soares, Anne Danielle Santos; Couceiro, Tânia Cursino de Menezes; Lima, Luciana Cavalcanti; Flores, Fernanda Lobo Lago; Alcoforado, Eusa Maria Belarmino; Filho, Roberto de Oliveira Couceiro

2013-01-01

Vaginal birth delivery may result in acute and persistent perineal pain postpartum. This study evaluated the association between catastrophizing, a phenomenon of poor psychological adjustment to pain leading the individual to magnify the painful experience making it more intense, and the incidence and severity of perineal pain and its relationship to perineal trauma. Cohort study conducted with pregnant women in labor. We used the pain catastrophizing scale during hospitalization and assessed the degree of perineal lesion and pain severity in the first 24 hours and after 8 weeks of delivery using a numerical pain scale. We evaluated 55 women, with acute pain reported by 69.1%, moderate/severe pain by 36.3%, and persistent pain by 14.5%. Catastrophizing mean score was 2.15 ± 1.24. Catastrophizing patients showed a 2.90 relative risk (RR) for perineal pain (95% CI: 1.08-7.75) and RR: 1.31 for developing persistent perineal pain (95% CI: 1.05-1.64). They also showed a RR: 2.2 for developing acute and severe perineal pain (95% CI: 1.11-4.33). The incidence of acute and persistent perineal pain after vaginal delivery is high. Catastrophizing pregnant women are at increased risk for developing acute and persistent perineal pain, as well as severe pain. Perineal trauma increased the risk of persistent perineal pain. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Negative beliefs about low back pain are associated with persistent high intensity low back pain.

PubMed

Ng, Sin Ki; Cicuttini, Flavia M; Wang, Yuanyuan; Wluka, Anita E; Fitzgibbon, Bernadette; Urquhart, Donna M

2017-08-01

While previous cross-sectional studies have found that negative beliefs about low back pain are associated with pain intensity, the relationship between back beliefs and persistent low back pain is not well understood. This cohort study aimed to examine the role of back beliefs in persistent low back pain in community-based individuals. A hundred and ninety-two participants from a previous musculoskeletal health study were invited to take part in a two-year follow-up study. Beliefs about back pain were assessed by the Back Beliefs Questionnaire (BBQ) at baseline and low back pain intensity was measured by the Chronic Pain Grade Questionnaire at baseline and follow-up. Of the 150 respondents (78.1%), 16 (10.7%) reported persistent high intensity low back pain, 12 (8.0%) developed high intensity low back pain, in 16 (10.7%) their high intensity low back pain resolved and 106 (70.7%) experienced no high intensity low back pain. While participants were generally positive about low back pain (BBQ mean (SD) = 30.2 (6.4)), those with persistent high intensity pain reported greater negativity (BBQ mean (SD) = 22.6 (4.9)). Negative beliefs about back pain were associated with persistent high intensity low back pain after adjusting for confounders (M (SE) = 23.5 (1.6) vs. >30.1 (1.7), p < .001). This study found negative back beliefs were associated with persistent high intensity low back pain over 2 years in community-based individuals. While further longitudinal studies are required, these findings suggest that targeting beliefs in programs designed to treat and prevent persistent high intensity low back pain may be important.

Peripheral substance P and neurokinin-1 receptors have a role in inflammatory and neuropathic orofacial pain models.

PubMed

Teodoro, Fernanda C; Tronco Júnior, Marcos F; Zampronio, Aleksander R; Martini, Alessandra C; Rae, Giles A; Chichorro, Juliana G

2013-06-01

There is accumulating evidence that substance P released from peripheral sensory neurons participates in inflammatory and neuropathic pain. In this study it was investigated the ability of substance P to induce orofacial nociception and thermal and mechanical hyperalgesia, as well as the role of NK1 receptors on models of orofacial inflammatory and neuropathic pain. Substance P injected into the upper lip at 1, 10 and 100 μg/50 μL failed to induce nociceptive behavior. Also, substance P (0.1-10 μg/50 μL) injected into the upper lip did not evoke orofacial cold hyperalgesia and when injected at 1 μg/50 μL did not induce mechanical hyperalgesia. However, substance P at this latter dose induced orofacial heat hyperalgesia, which was reduced by the pre-treatment of rats with a non-peptide NK1 receptor antagonist (SR140333B, 3mg/kg). Systemic treatment with SR140333B (3 mg/kg) also reduced carrageenan-induced heat hyperalgesia, but did not exert any influence on carrageenan-induced cold hyperalgesia. Blockade of NK1 receptors with SR140333B also reduced by about 50% both phases of the formalin response evaluated in the orofacial region. Moreover, heat, but not cold or mechanical, hyperalgesia induced by constriction of the infraorbital nerve, a model of trigeminal neuropathic pain, was abolished by pretreatment with SR140333B. Considering that substance P was peripherally injected (i.e. upper lip) and the NK1 antagonist used lacks the ability to cross the blood-brain-barrier, our results demonstrate that the peripheral SP/NK1 system participates in the heat hyperalgesia associated with inflammation or nerve injury and in the persistent pain evoked by formalin in the orofacial region. Copyright © 2012 Elsevier Ltd. All rights reserved.

Epigenetic regulation of persistent pain

PubMed Central

Bai, Guang; Ren, Ke; Dubner, Ronald

2014-01-01

Persistent or chronic pain is tightly associated with various environmental changes and linked to abnormal gene expression within cells processing nociceptive signaling. Epigenetic regulation governs gene expression in response to environmental cues. Recent animal model and clinical studies indicate that epigenetic regulation plays an important role in the development/maintenance of persistent pain and, possibly the transition of acute pain to chronic pain, thus shedding light in a direction for development of new therapeutics for persistent pain. PMID:24948399

A novel inhibitor of active protein kinase G attenuates chronic inflammatory and osteoarthritic pain.

PubMed

Sung, Ying-Ju; Sofoluke, Nelson; Nkamany, Mary; Deng, Shixian; Xie, Yuli; Greenwood, Jeremy; Farid, Ramy; Landry, Donald W; Ambron, Richard T

2017-05-01

Activating PKG-1α induces a long-term hyperexcitability (LTH) in nociceptive neurons. Since the LTH correlates directly with chronic pain in many animal models, we tested the hypothesis that inhibiting PKG-1α would attenuate LTH-mediated pain. We first synthesized and characterized compound N46 (N-((3R,4R)-4-(4-(2-fluoro-3-methoxy-6-propoxybenzoyl)benzamido)pyrrolidin-3-yl)-1H-indazole-5-carboxamide). N46 inhibits PKG-1α with an IC50 of 7.5 nmol, was highly selective when tested against a panel of 274 kinases, and tissue distribution studies indicate that it does not enter the CNS. To evaluate its antinociceptive potential, we used 2 animal models in which the pain involves both activated PKG-1α and LTH. Injecting complete Freund's adjuvant (CFA) into the rat hind paw causes a thermal hyperalgesia that was significantly attenuated 24 hours after a single intravenous injection of N46. Next, we used a rat model of osteoarthritic knee joint pain and found that a single intra-articular injection of N46 alleviated the pain 14 days after the pain was established and the relief lasted for 7 days. Thermal hyperalgesia and osteoarthritic pain are also associated with the activation of the capsaicin-activated transient receptor protein vanilloid-1 (TRPV1) channel. We show that capsaicin activates PKG-1α in nerves and that a subcutaneous delivery of N46 attenuated the mechanical and thermal hypersensitivity elicited by exposure to capsaicin. Thus, PKG-1α appears to be downstream of the transient receptor protein vanilloid-1. Our studies provide proof of concept in animal models that a PKG-1α antagonist has a powerful antinociceptive effect on persistent, already existing inflammatory pain. They further suggest that N46 is a valid chemotype for the further development of such antagonists.

Predictors of the transition from acute to persistent musculoskeletal pain in children and adolescents: a prospective study

PubMed Central

Holley, Amy Lewandowski; Wilson, Anna C.; Palermo, Tonya M.

2016-01-01

Strategies directed at the prevention of disabling pain have been suggested as a public health priority, making early identification of youth at risk for poor outcomes critical. At present limited information is available to predict which youth presenting with acute pain are at risk for persistence. The aims of this prospective longitudinal study were to identify biopsychosocial factors in the acute period that predict the transition to persistent pain in youth with new-onset musculoskeletal (MSK) pain complaints. Participants were 88 children and adolescents (age 10–17 years) presenting to the emergency department (n=47) or orthopedic clinic (n=41) for evaluation of a new MSK pain complaint (< 1 month duration). Youth presented for two study visits (T1 = <1 month post pain onset; T2 = 4 month follow-up) during which they completed questionnaires (assessing pain characteristics, psychological factors, sleep quality) and participated in a lab task assessing conditioned pain modulation (CPM). Regression analyses tested T1 predictors of longitudinal pain outcomes (pain persistence, pain-related disability, quality of life). Results revealed approximately 35% of youth had persistent pain at 4-month follow-up, with persistent pain predicted by poorer CPM and female sex. Higher depressive symptoms at T1 were associated with higher pain-related disability and poorer quality of life at T2. Findings highlight the roles of depressive symptoms and pain modulation in longitudinally predicting pain persistence in treatment-seeking youth with acute MSK pain, and suggest potential mechanisms in the transition from acute to chronic MSK pain in children and adolescents. PMID:28151835

Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain

PubMed Central

Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

2016-01-01

Study Design Retrospective study. Purpose To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Overview of Literature Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Methods Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. Results No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). Conclusions Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain. PMID:27559448

Inflammatory Pain Promotes Increased Opioid Self-Administration: Role of Dysregulated Ventral Tegmental Area μ Opioid Receptors

PubMed Central

Hipólito, Lucia; Wilson-Poe, Adrianne; Campos-Jurado, Yolanda; Zhong, Elaine; Gonzalez-Romero, Jose; Virag, Laszlo; Whittington, Robert; Comer, Sandra D.; Carlton, Susan M.; Walker, Brendan M.; Bruchas, Michael R.

2015-01-01

Pain management in opioid abusers engenders ethical and practical difficulties for clinicians, often resulting in pain mismanagement. Although chronic opioid administration may alter pain states, the presence of pain itself may alter the propensity to self-administer opioids, and previous history of drug abuse comorbid with chronic pain promotes higher rates of opioid misuse. Here, we tested the hypothesis that inflammatory pain leads to increased heroin self-administration resulting from altered mu opioid receptor (MOR) regulation of mesolimbic dopamine (DA) transmission. To this end, the complete Freund's adjuvant (CFA) model of inflammation was used to assess the neurochemical and functional changes induced by inflammatory pain on MOR-mediated mesolimbic DA transmission and on rat intravenous heroin self-administration under fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. In the presence of inflammatory pain, heroin intake under an FR schedule was increased for high, but attenuated for low, heroin doses with concomitant alterations in mesolimbic MOR function suggested by DA microdialysis. Consistent with the reduction in low dose FR heroin self-administration, inflammatory pain reduced motivation for a low dose of heroin, as measured by responding under a PR schedule of reinforcement, an effect dissociable from high heroin dose PR responding. Together, these results identify a connection between inflammatory pain and loss of MOR function in the mesolimbic dopaminergic pathway that increases intake of high doses of heroin. These findings suggest that pain-induced loss of MOR function in the mesolimbic pathway may promote opioid dose escalation and contribute to opioid abuse-associated phenotypes. SIGNIFICANCE STATEMENT This study provides critical new insights that show that inflammatory pain alters heroin intake through a desensitization of MORs located within the VTA. These findings expand our knowledge of the interactions between inflammatory pain and opioid abuse liability, and should help to facilitate the development of novel and safer opioid-based strategies for treating chronic pain. PMID:26338332

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

Current advances in orthodontic pain

PubMed Central

Long, Hu; Wang, Yan; Jian, Fan; Liao, Li-Na; Yang, Xin; Lai, Wen-Li

2016-01-01

Orthodontic pain is an inflammatory pain that is initiated by orthodontic force-induced vascular occlusion followed by a cascade of inflammatory responses, including vascular changes, the recruitment of inflammatory and immune cells, and the release of neurogenic and pro-inflammatory mediators. Ultimately, endogenous analgesic mechanisms check the inflammatory response and the sensation of pain subsides. The orthodontic pain signal, once received by periodontal sensory endings, reaches the sensory cortex for pain perception through three-order neurons: the trigeminal neuron at the trigeminal ganglia, the trigeminal nucleus caudalis at the medulla oblongata and the ventroposterior nucleus at the thalamus. Many brain areas participate in the emotion, cognition and memory of orthodontic pain, including the insular cortex, amygdala, hippocampus, locus coeruleus and hypothalamus. A built-in analgesic neural pathway—periaqueductal grey and dorsal raphe—has an important role in alleviating orthodontic pain. Currently, several treatment modalities have been applied for the relief of orthodontic pain, including pharmacological, mechanical and behavioural approaches and low-level laser therapy. The effectiveness of nonsteroidal anti-inflammatory drugs for pain relief has been validated, but its effects on tooth movement are controversial. However, more studies are needed to verify the effectiveness of other modalities. Furthermore, gene therapy is a novel, viable and promising modality for alleviating orthodontic pain in the future. PMID:27341389

Fatigue, Pain, Anxiety and Depression in Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

PubMed

Merkies, Ingemar S J; Kieseier, Bernd C

2016-01-01

In the clinical evaluation of patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), scant attention is paid to symptoms such as fatigue, pain and anxiety/depression. We aimed at addressing seminal studies that focused on the burden of these symptoms and their impact on quality of life (QoL) in these conditions. Fatigue, pain, and anxiety/depression are increasingly being recognized in patients with GBS and CIDP, although their pathophysiological provenance remains unknown. Fatigue and pain are significant in terms of prevalence and intensity, may be a presenting symptom, and can persist for years after apparent functional recovery, suggesting residual injury. Anxiety/depression has also been examined although studies are limited. Despite their negative impact on QoL, the long-term dynamics of these symptoms in patients with GBS and particularly CIDP receiving therapy in routine clinical practice have not been systematically evaluated. Such observations formed the basis for the ongoing (GAMEDIS) studies evaluating the effect of Gamunex on fatigue and depression in patients with CIDP, of which some preliminary data are presented. Strength and sensory deficits are the main areas of focus in patients with GBS and CIDP, but they do not explain the total reduction in QoL, suggesting the possible role of other complaints. A more comprehensive approach to patient care demands that factors such as pain, fatigue and anxiety/depression receive greater attention. The non-interventional GAMEDIS studies are expected to provide valuable insight into the long-term effectiveness of Gamunex in everyday practice. © 2016 S. Karger AG, Basel.

Comparison of Low Back Pain Recovery and Persistence: A Descriptive Study of Characteristics at Pain Onset.

PubMed

Starkweather, Angela R; Lyon, Debra E; Kinser, Patricia; Heineman, Amy; Sturgill, Jamie L; Deng, Xiaoyan; Siangphoe, Umaporn; Elswick, R K; Greenspan, Joel; Dorsey, Susan G

2016-07-01

Persistent low back pain is a significant problem worldwide. Early identification and treatment of individuals at high risk for persistent low back pain have been suggested as strategies to decrease the rate of disability associated with this condition. To examine and compare demographic, pain-related, psychological, and somatosensory characteristics in a cohort of participants with acute low back pain who later went on to experience persistent low back pain or whose pain resolved within the first 6 weeks after initial onset. A descriptive study was conducted among men and women 18-50 years of age who had an acute episode of low back pain. Study questionnaires were administered to collect demographic information and measures of pain, coping, reactivity, mood, work history and satisfaction, and disability. A standardized protocol of quantitative sensory testing was performed on each participant at the painful area of their low back and at a remote site on their arm. The sample consisted of 48 participants, of whom 19 went on to develop persistent low back pain and 29 resolved. Compared to the resolved group, the persistent low back pain group was significantly older and had a lower level of educational attainment, a higher body mass index, and higher mean "least" pain score on the Brief Pain Inventory-Short Form. Significantly higher thermal detection thresholds at the painful and remote sites as well as signs of central sensitivity differentiated the persistent pain group from the resolved group during the acute stage of low back pain. © The Author(s) 2016.

Role of Stress and Smoking as Modifiable Risk Factors for Nonpersistent and Persistent Back Pain in Women.

PubMed

Schmelzer, Amy C; Salt, Elizabeth; Wiggins, Amanda; Crofford, Leslie J; Bush, Heather; Mannino, David M

2016-03-01

The purpose of this study was to examine the association between smoking and stress with nonpersistent and persistent back pain. Participants included 3703 women who took part in the Kentucky Women's Health Registry in 2008 and 2011. Multivariate logistic regression modeling was used to examine whether smoking status and stress levels were predictive of nonpersistent and persistent back pain, controlling for sociodemographic characteristics. Stress level was associated with both nonpersistent and persistent back pain, whereas smoking was associated with only persistent back pain. Current smokers were 1.5 times more likely to report persistent back pain compared with never smokers, controlling for age, race, body mass index, educational attainment, and employment status. Women experiencing large or overwhelming amounts of stress were 1.8 times more likely to have nonpersistent back pain and 1.6 times more likely to report persistent back pain, compared with women experiencing small amounts of stress. This study further substantiates the findings of prior research that describes a significant relationship between back pain, stress, and smoking. Understanding the role of modifiable risk factors (ie, smoking and stress) and their impact on back pain provides an opportunity to offer a comprehensive and tailored treatment plan.

A new technique to treat facet joint pain with pulsed radiofrequency.

PubMed

Schianchi, Pietro Martino

2015-02-01

Facet joint pain affects 5% to 15% of the population with low back pain and the prevalence increases with age due to progression of arthritis. While conservative treatments are often unsuccessful, the scientific evidence on minimally invasive therapies such as intra-articular steroid infiltration and continuous and pulsed radiofrequency (PRF) of the medial branches is contradictory. Since PRF has recently been reported to successfully treat joint pain, a new application of this method is proposed for facetogenic lumbar pain via an intra-articular subcapsular approach. Here we reported two cases with successful treatment. A 71-year-old patient presented because of persisting pain in the left gluteal region radiating to the lateral thigh and calf when standing. Anti-inflammatory drugs produced only short-lasting insufficient relief. A 52-year-old employee was admitted in June 2012 because of axial lower lumbar pain with intermittent diffuse radiation to the right lower extremity that worsened during walking and lying down despite receiving analgesics and physiotherapy. A new approach to treat lumbar facet joint pain with PRF is simple to perform and without serious complications. In view of the good long-lasting results obtained with the two reported cases, randomized control trials are necessary to validate this new approach.

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.

COX2 in CNS neural cells mediates mechanical inflammatory pain hypersensitivity in mice

PubMed Central

Vardeh, Daniel; Wang, Dairong; Costigan, Michael; Lazarus, Michael; Saper, Clifford B.; Woolf, Clifford J.; FitzGerald, Garret A.; Samad, Tarek A.

2009-01-01

A cardinal feature of peripheral inflammation is pain. The most common way of managing inflammatory pain is to use nonsteroidal antiinflammatory agents (NSAIDs) that reduce prostanoid production, for example, selective inhibitors of COX2. Prostaglandins produced after induction of COX2 in immune cells in inflamed tissue contribute both to the inflammation itself and to pain hypersensitivity, acting on peripheral terminals of nociceptors. COX2 is also induced after peripheral inflammation in neurons in the CNS, where it aids in developing a central component of inflammatory pain hypersensitivity by increasing neuronal excitation and reducing inhibition. We engineered mice with conditional deletion of Cox2 in neurons and glial cells to determine the relative contribution of peripheral and central COX2 to inflammatory pain hypersensitivity. In these mice, basal nociceptive pain was unchanged, as was the extent of peripheral inflammation, inflammatory thermal pain hypersensitivity, and fever induced by lipopolysaccharide. By contrast, peripheral inflammation–induced COX2 expression in the spinal cord was reduced, and mechanical hypersensitivity after both peripheral soft tissue and periarticular inflammation was abolished. Mechanical pain is a major symptom of most inflammatory conditions, such as postoperative pain and arthritis, and induction of COX2 in neural cells in the CNS seems to contribute to this. PMID:19127021

VGLUT2-dependent glutamatergic transmission in primary afferents is required for intact nociception in both acute and persistent pain modalities.

PubMed

Rogoz, Katarzyna; Lagerström, Malin C; Dufour, Sylvie; Kullander, Klas

2012-07-01

Glutamate is an essential transmitter in pain pathways. However, its broad usage in the central and peripheral nervous system prevents us from designing efficient glutamate-based pain therapies without causing harmful side effects. The discovery of vesicular glutamate transporters (VGLUT1-3) has been a crucial step in describing specific glutamatergic neuronal subpopulations and glutamate-dependent pain pathways. To assess the role of VGLUT2-mediated glutamatergic contribution to pain transmission from the entire primary sensory population, we crossed our Vglut2(f/f) line with the Ht-Pa-Cre line. Such Vglut2-deficient mice showed significantly decreased, but not completely absent, acute nociceptive responses. The animals were less prone to develop an inflammatory-related state of pain and were, in the partial sciatic nerve ligation chronic pain model, much less hypersensitive to mechanical stimuli and did not develop cold allodynia or heat hyperalgesia. To take advantage of this neuropathic pain-resistant model, we analyzed Vglut2-dependent transcriptional changes in the dorsal spinal cord after nerve injury, which revealed several novel candidate target genes potentially relevant for the development of neuropathic pain therapeutics. Taken together, we conclude that VGLUT2 is a major mediator of nociception in primary afferents, implying that glutamate is the key somatosensory neurotransmitter. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Empyema necessitans in a six-month-old girl.

PubMed

Goussard, P; Gie, Robert; Janson, Jacques; Andronikou, Savvas

2018-05-23

Empyema necessitans is a rare complication of acute bacterial pneumonia, especially in children. It is a complication of empyema characterised by the extension of pus from the pleural cavity into the thoracic wall to form a mass of purulent fluid in the adjacent soft tissue. An inflammatory chest wall mass following pneumonia caused by Streptococcus pneumonia in a six-month-old infant is reported. The case emphasises that children presenting with persistent fever and a painful chest wall mass following pneumonia should be investigated immediately as there might be an urgent need for surgery.

Efficacy and safety of oxymetazoline cream 1.0% for treatment of persistent facial erythema associated with rosacea: Findings from the 52-week open label REVEAL trial.

PubMed

Draelos, Zoe Diana; Gold, Michael H; Weiss, Robert A; Baumann, Leslie; Grekin, Steven K; Robinson, Deanne Mraz; Kempers, Steven E; Alvandi, Nancy; Weng, Emily; Berk, David R; Ahluwalia, Gurpreet

2018-06-01

Limited treatments are available for persistent erythema of rosacea. To examine the long-term safety and efficacy of oxymetazoline cream 1.0% in patients with rosacea with moderate-to-severe persistent erythema. Patients applied oxymetazoline once daily for 52 weeks. Safety assessments included treatment-emergent adverse events (TEAEs), skin blanching, inflammatory lesion counts, telangiectasia, disease severity, and rebound effect. Efficacy was assessed by the Clinician Erythema Assessment and Subject Self-Assessment composite score at 3 and 6 hours after the dose on day 1 and at weeks 4, 26, and 52. Among 440 patients, 8.2% reported treatment-related TEAEs; the most common were application-site dermatitis, paresthesia, pain, and pruritus. The rate of discontinuation due to adverse events (mostly application-site TEAEs) was 3.2%. No clinically meaningful changes were observed in skin blanching, inflammatory lesions, or telangiectasia. At week 52, 36.7%, and 43.4% of patients achieved a 2-grade or greater composite improvement from baseline in both Clinician Erythema Assessment and Subject Self-Assessment 3 and 6 hours after a dose, respectively. Less than 1% of patients experienced a rebound effect following treatment cessation. A vehicle-control group was not included. This long-term study demonstrated sustained safety, tolerability, and efficacy of oxymetazoline for moderate-to-severe persistent erythema of rosacea. Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Maintenance of Pain in Children With Functional Abdominal Pain.

PubMed

Czyzewski, Danita I; Self, Mariella M; Williams, Amy E; Weidler, Erica M; Blatz, Allison M; Shulman, Robert J

2016-03-01

A significant proportion of children with functional abdominal pain develop chronic pain. Identifying clinical characteristics predicting pain persistence is important in targeting interventions. We examined whether child anxiety and/or pain-stooling relations were related to maintenance of abdominal pain frequency and compared the predictive value of 3 methods for assessing pain-stooling relations (ie, diary, parent report, child report). Seventy-six children (7-10 years old at baseline) who presented for medical treatment of functional abdominal pain were followed up 18 to 24 months later. Baseline anxiety and abdominal pain-stooling relations based on pain and stooling diaries and child- and parent questionnaires were examined in relationship to the persistence of abdominal pain frequency. Children's baseline anxiety was not related to persistence of pain frequency. Children who, however, displayed irritable bowel syndrome (IBS) symptoms at baseline maintained pain frequency at follow-up, whereas in children in whom there was no relationship between pain and stooling, pain frequency decreased. Pain and stool diaries and parent report of pain-stooling relations were predictive of pain persistence but child-report questionnaires were not. The presence of IBS symptoms in school-age children with functional abdominal pain appears to predict persistence of abdominal pain over time, whereas anxiety does not. Prospective pain and stooling diaries and parent report of IBS symptoms were predictors of pain maintenance, but child report of symptoms was not.

Pain and pharmacologic pain management in long-stay nursing home residents.

PubMed

Hunnicutt, Jacob N; Ulbricht, Christine M; Tjia, Jennifer; Lapane, Kate L

2017-06-01

Previous studies estimate that >40% of long-stay nursing home (NH) residents experience persistent pain, with 20% of residents in pain receiving no analgesics. Strengthened NH surveyor guidance and improved pain measures on the Minimum Data Set 3.0 were introduced in March 2009 and October 2010, respectively. This study aimed to provide estimates after the important initiatives of (1) prevalence and correlates of persistent pain; and (2) prevalence and correlates of untreated or undertreated persistent pain. We identified 1,387,405 long-stay residents in U.S. NHs between 2011 and 2012 with 2 Minimum Data Set assessments 90 days apart. Pain was categorized as persistent (pain on both assessments), intermittent (pain on either assessment), or none. Pharmacologic pain management was classified as untreated pain (no scheduled or as needed medications received) or potentially undertreated (no scheduled received). Modified Poisson models adjusting for resident clustering within NHs provided adjusted prevalence ratios (APRs) estimates and 95% confidence intervals (CIs). The prevalence of persistent and intermittent pain was 19.5% and 19.2%, respectively, but varied substantially by age, sex, race and ethnicity, cognitive impairment, and cancer. Of residents in persistent pain, 6.4% and 32.0% were untreated and undertreated, respectively. Racial and ethnic minorities (non-Hispanic blacks vs whites, APR = 1.19, 95% CI: 1.13-1.25) and severely cognitively impaired residents (severe vs no/mild APR = 1.51, 95% CI: 1.44-1.57) had an increased prevalence of untreated and undertreated pain. One in 5 NH residents has persistent pain. Although this estimate is greatly improved, many residents may be undertreated. The disturbing disparities in untreated and undertreated pain need to be addressed.

Chronic Pain in Inflammatory Arthritis: Mechanisms, Metrology, and Emerging Targets—A Focus on the JAK-STAT Pathway

PubMed Central

Salaffi, Fausto; Giacobazzi, Giovanni

2018-01-01

Chronic pain is nowadays considered not only the mainstay symptom of rheumatic diseases but also “a disease itself.” Pain is a multidimensional phenomenon, and in inflammatory arthritis, it derives from multiple mechanisms, involving both synovitis (release of a great number of cytokines) and peripheral and central pain-processing mechanisms (sensitization). In the last years, the JAK-STAT pathway has been recognized as a pivotal component both in the inflammatory process and in pain amplification in the central nervous system. This paper provides a summary on pain in inflammatory arthritis, from pathogenesis to clinimetric instruments and treatment, with a focus on the JAK-STAT pathway. PMID:29623147

Persistent post-surgical pain and experimental pain sensitivity in the Tromsø study: comorbid pain matters.

PubMed

Johansen, Aslak; Schirmer, Henrik; Stubhaug, Audun; Nielsen, Christopher S

2014-02-01

In a large survey incorporating medical examination (N=12,981), information on chronic pain and surgery was collected, and sensitivity to different pain modalities was tested. Tolerance to the cold pressor test was analysed with survival statistics for 10,486 individuals, perceived cold pressor pain intensity was calculated for 10,367 individuals, heat pain threshold was assessed for 4,054 individuals, and pressure pain sensitivity for 4,689 individuals. Persistent post-surgical pain, defined by self-report, was associated with lower cold pressor tolerance (sex-adjusted hazard ratio=1.34, 95% confidence interval=1.08-1.66), but not when adjusting for other chronic pain. Other experimental pain modalities did not differentiate between individuals with or without post-surgical pain. Of the individuals with chronic pain (N=3352), 6.2% indicated surgery as a cause, although only 0.5% indicated surgery as the only cause. The associations found between persistent post-surgical pain and cold pressor tolerance is largely explained by the co-existence of chronic pain from other causes. We conclude that most cases of persistent post-surgical pain are coexistent with other chronic pain, and that, in an unselected post-surgical population, persistent post-surgical pain is not significantly associated with pain sensitivity when controlling for comorbid pain from other causes. A low prevalence of self-reported persistent pain from surgery attenuates statistically significant associations. We hypothesize that general chronic pain is associated with central changes in pain processing as expressed by reduced tolerance for the cold pressor test. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Toll-like Receptor 4 and Comorbid Pain in Interstitial Cystitis/Bladder Pain Syndrome: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Study

PubMed Central

Schrepf, Andrew; Bradley, Catherine S.; O'Donnell, Michael; Luo, Yi; Harte, Steven E.; Kreder, Karl; Lutgendorf, Susan

2015-01-01

Background Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a condition characterized by pelvic pain and urinary symptoms. Some IC/BPS patients have pain confined to the pelvic region, while others suffer widespread pain. Inflammatory processes have previously been linked to pelvic pain in IC/BPS, but their association with widespread pain in IC/BPS has not been characterized. Methods Sixty-six women meeting criteria for IC/BPS completed self-report measures of pain as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP), collected 3 days of saliva for cortisol assays, and provided blood samples. Peripheral blood mononuclear cells (PBMCs) were stimulated with Toll-Like Receptor (TLR) 2 and 4 agonists and cytokines were measured in supernatant; IL-6 was also measured in plasma. Associations between inflammatory variables and the likelihood of endorsing extra-pelvic pain, or the presence of a comorbid syndrome, were tested by logistic regression and General Linear Models, respectively. A subset of patients (n=32) completed Quantitative Sensory Testing. Results A one standard deviation increase in TLR-4 inflammatory response was associated with a 1.59 greater likelihood of endorsing extra-pelvic pain (p = .019). Participants with comorbid syndromes also had higher inflammatory responses to TLR-4 stimulation in PBMCs (p = .016). Lower pressure pain thresholds were marginally associated with higher TLR-4 inflammatory responses (p = .062), and significantly associated with higher IL-6 in plasma (p = .031). Conclusions TLR-4 inflammatory responses in PBMCs are a marker of widespread pain in IC/BPS, and should be explored in other conditions characterized by medically unexplained pain. PMID:25771510

Ultralow Dose of Naloxone as an Adjuvant to Intrathecal Morphine Infusion Improves Perceived Quality of Sleep but Fails to Alter Persistent Pain

PubMed Central

Lundborg, Christopher; Bjersing, Jan; Dahm, Peter; Hansson, Elisabeth; Biber, Björn

2015-01-01

Introduction: This randomized, cross-over, double-blind, controlled study of continuous intrathecal morphine administration in patients with severe, long-term pain addresses whether the supplementation of low doses of naloxone in this setting is associated with beneficial clinical effects. Methods: All of the study subjects (n=11) provided informed consent and were recruited from a subset of patients who were already undergoing long-term treatment with continuous intrathecal morphine because of difficult-to-treat pain. The patients were (in a randomized order) also given intrathecal naloxone (40 ng/24 h or 400 ng/24 h). As control, the patients’ ordinary dose of morphine without any additions was used. The pain (Numeric Rating Scale, NRS) during activity, perceived quality of sleep, level of activity, and quality of life as well as the levels of several proinflammatory and anti-inflammatory cytokines in the blood were assessed. The prestudy pain (NRS during activity) in the study group ranged from 3 to 10. Results: A total of 64% of the subjects reported improved quality of sleep during treatment with naloxone at a dose of 40 ng per 24 hours as compared with 9% with sham treatment (P=0.024). Although not statistically significant, pain was reduced by 2 NRS steps or more during supplemental treatment with naloxone in 36% of subjects when using the 40 ng per 24 hours dose and in 18% of the subjects when using naloxone 400 ng per 24 hours dose. The corresponding percentage among patients receiving unaltered treatment was 27%. Conclusions: To conclude, the addition of an ultralow dose of intrathecal naloxone (40 ng/24 h) to intrathecal morphine infusion in patients with severe, persistent pain improved perceived quality of sleep. We were not able to show any statistically significant effects of naloxone on pain relief, level of activity, or quality of life. PMID:25629634

Language and the pain experience.

PubMed

Wilson, Dianne; Williams, Marie; Butler, David

2009-03-01

People in persistent pain have been reported to pay increased attention to specific words or descriptors of pain. The amount of attention paid to pain or cues for pain (such as pain descriptors), has been shown to be a major factor in the modulation of persistent pain. This relationship suggests the possibility that language may have a role both in understanding and managing the persistent pain experience. The aim of this paper is to describe current models of neuromatrices for pain and language, consider the role of attention in persistent pain states and highlight discrepancies, in previous studies based on the McGill Pain Questionnaire (MPQ), of the role of attention on pain descriptors. The existence of a pain neuromatrix originally proposed by Melzack (1990) has been supported by emerging technologies. Similar technologies have recently allowed identification of multiple areas of involvement for the processing of auditory input and the construction of language. As with the construction of pain, this neuromatrix for speech and language may intersect with neural systems for broader cognitive functions such as attention, memory and emotion. A systematic search was undertaken to identify experimental or review studies, which specifically investigated the role of attention on pain descriptors (as cues for pain) in persistent pain patients. A total of 99 articles were retrieved from six databases, with 66 articles meeting the inclusion criteria. After duplicated articles were eliminated, the remaining 41 articles were reviewed in order to support a link between persistent pain, pain descriptors and attention. This review revealed a diverse range of specific pain descriptors, the majority of which were derived from the MPQ. Increased attention to pain descriptors was consistently reported to be associated with emotional state as well as being a significant factor in maintaining persistent pain. However, attempts to investigate the attentional bias of specific pain descriptors highlighted discrepancies between the studies. As well as the diversity of pain descriptors used in studies, they were inconsistently categorized into domains of pain. A lack of consistent bias towards certain pain descriptors was observed, and may be explained simply by the fact that the words provided are not those which subjects themselves would use. These findings suggest that the multidimensional and individual nature of the persistent pain experience may not be adequately explained by pain questionnaires such as the MPQ. Personalized pain descriptors may communicate the pain experience more appropriately, but may also contribute to an increased sensitivity of cortical pain processing areas by capturing increased attention for that individual. The language used as part of communication between therapists and people with persistent pain may provide an, as yet, unexplored adjunct strategy in management. Copyright (c) 2008 John Wiley & Sons, Ltd.

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

[Phosphorylation of protein kinase C in cerebrospinal fluid-contacting nucleus modulates the inflammatory pain in rats].

PubMed

Zhou, Fang; Wang, Jia-You; Tian, En-Qi; Zhang, Li-Cai

2015-12-25

The present study was aimed to investigate the role of cerebrospinal fluid-contacting nucleus (CSF-CN) neurons in modulation of inflammatory pain and underlying mechanism. The inflammatory pain model was made by subcutaneous injection of the complete Freund's adjuvant (CFA) into the left hind paw of rats. The phosphorylation level of PKC (p-PKC) was examined by Western blot. Thermal withdrawal latency (TWL) of the rats was measured to assess inflammatory pain. The results showed that, compared with the sham controls, the inflammatory pain model rats showed shortened TWL on day 1, 3, and 7 after CFA injection, as well as increased level of p-PKC in CSF-CN neurons at 24 h after CFA injection. The administration of GF109203X, a PKC inhibitor, into lateral ventricle decreased the level of p-PKC protein expression and increased TWL in the model rats. These results suggest that blocking the PKC pathway in CSF-CN neurons may be an effective way to reduce or eliminate the inflammatory pain.

Factors associated with and impact of pain persistence in Asian patients with depression: a 3-month, prospective observational study.

PubMed

Novick, Diego; Montgomery, William; Aguado, Jaume; Peng, Xiaomei; Haro, Josep Maria

2017-03-01

We investigated the depression outcomes and the factors associated with pain persistence in Asian patients treated for major depressive disorder (MDD). This observational study enrolled 909 Asian adult inpatients and outpatients. The presence or absence of painful physical symptoms and severity of depression were assessed at baseline and after three months of treatment. Factors associated with pain persistence and outcome of depression were investigated using regression methods. Of the 909 patients enrolled, 684 were included in the analysis and evaluated at three months. Of them, 335 (49%) had no pain at baseline nor follow up, 198 (29%) at baseline but not at follow up and 151 (22%) in both assessments. Pain more frequently persisted in patients who were divorced/widowed/separated, with >1 comorbidity, aged <40 years, with previous MDD episodes, taking pain medications, and with greater depression severity. At three months, response/remission were 84%/73% in the no pain group, 83%/63% in the remitted pain group and 46%/25% in the persistent pain group (differences all p < .0001; all bivariate comparisons were statistically significant with p < .05 except response between no pain and remitted pain). Persistent pain was also associated with less improvement in quality of life and health state. Pain should be taken into account when diagnosing MDD and when tailoring therapy.

Limbus Vertebra Presenting with Inflammatory Low Back Pain: A Case Report

PubMed Central

Özdemir, Tayfun; Öz, Hande Ece

2016-01-01

Limbus vertebra is a condition characterized by marginal interosseous herniation of the nucleus pulposus, and causes non specific symptoms like low back pain, back pain, muscle spasms and radiculopathy. It is frequently confused with vertebral fracture, infection, schmorl nodule or tumour because it has not a spesific symptom. It usually causes mechanical low back pain rather than inflammatory low back pain. We reported a patient presented with inflammatory low back pain and diagnosed with anterior limbus vertebra because it is rare and the patient has atypical clinical presentation. PMID:27134989

Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement

PubMed Central

Goodman, S. B.; Gibon, E.; Pajarinen, J.; Lin, T.-H.; Keeney, M.; Ren, P.-G.; Nich, C.; Yao, Z.; Egashira, K.; Yang, F.; Konttinen, Y. T.

2014-01-01

Wear particles and by-products from joint replacements and other orthopaedic implants may result in a local chronic inflammatory and foreign body reaction. This may lead to persistent synovitis resulting in joint pain and swelling, periprosthetic osteolysis, implant loosening and pathologic fracture. Strategies to modulate the adverse effects of wear debris may improve the function and longevity of joint replacements and other orthopaedic implants, potentially delaying or avoiding complex revision surgical procedures. Three novel biological strategies to mitigate the chronic inflammatory reaction to orthopaedic wear particles are reported. These include (i) interference with systemic macrophage trafficking to the local implant site, (ii) modulation of macrophages from an M1 (pro-inflammatory) to an M2 (anti-inflammatory, pro-tissue healing) phenotype in the periprosthetic tissues, and (iii) local inhibition of the transcription factor nuclear factor kappa B (NF-κB) by delivery of an NF-κB decoy oligodeoxynucleotide, thereby interfering with the production of pro-inflammatory mediators. These three approaches have been shown to be viable strategies for mitigating the undesirable effects of wear particles in preclinical studies. Targeted local delivery of specific biologics may potentially extend the lifetime of orthopaedic implants. PMID:24478281

Maintenance of Pain in Children with Functional Abdominal Pain

PubMed Central

Czyzewski, Danita I.; Self, Mariella M.; Williams, Amy E.; Weidler, Erica M.; Blatz, Allison M.; Shulman, Robert J.

2015-01-01

Objectives A significant proportion of children with functional abdominal pain develop chronic pain. Identifying clinical characteristics predicting pain persistence is important in targeting interventions. We examined whether child anxiety and/or pain-stooling relations were related to maintenance of abdominal pain frequency and compared the predictive value of three methods for assessing pain-stooling relations (i.e., diary, parent report, child report). Methods Seventy-six children (7–10-years-old at baseline) who presented for medical treatment of functional abdominal pain were followed up 18–24 months later. Baseline anxiety and abdominal pain-stooling relations based on pain and stooling diaries and child- and parent-questionnaires were examined in relationship to the persistence of abdominal pain frequency. Results Children’s baseline anxiety was not related to persistence of pain frequency. However, children who displayed irritable bowel syndrome (IBS) symptoms at baseline maintained pain frequency at follow-up, whereas in children in whom there was no relationship between pain and stooling, pain frequency decreased. Pain and stool diaries and parent report of pain-stooling relations were predictive of pain persistence but child-report questionnaires were not. Conclusions The presence of IBS symptoms in school age children with functional abdominal pain appears to predict persistence of abdominal pain over time, while anxiety does not. Prospective pain and stooling diaries and parent report of IBS symptoms were predictors of pain maintenance, but child report of symptoms was not. PMID:26301615

Light-emitting diode therapy reduces persistent inflammatory pain: Role of interleukin 10 and antioxidant enzymes.

PubMed

Martins, D F; Turnes, B L; Cidral-Filho, F J; Bobinski, F; Rosas, R F; Danielski, L G; Petronilho, F; Santos, A R S

2016-06-02

During the last decades, the use of light-emitting diode therapy (LEDT) has increased significantly for the treatment of wound healing, analgesia and inflammatory processes. Nevertheless, scientific data on the mechanisms responsible for the therapeutic effect of LEDT are still insufficient. Thus, this study investigated the analgesic, anti-inflammatory and anti-oxidative effect of LEDT in the model of chronic inflammatory hyperalgesia. Mice injected with Complete Freund's Adjuvant (CFA) underwent behavioral, i.e. mechanical and hot hyperalgesia; determination of cytokine levels (tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-10), oxidative stress markers (protein carbonyls and thiobarbituric acid reactive species (TBARS)) and antioxidant enzymes (catalase (CAT) and superoxide dismutase (SOD)). Additionally, mice were pretreated with either naloxone or fucoidin and mechanical hyperalgesia was assessed. LEDT inhibited mechanical and thermal hyperalgesia induced by CFA injection. LEDT did not reduce paw edema, neither influenced the levels of TNF-α and IL1-β; although it increased the levels of IL-10. LEDT significantly prevented TBARS increase in both acute and chronic phases post-CFA injection; whereas protein carbonyl levels were reduced only in the acute phase. LEDT induced an increase in both SOD and CAT activity, with effects observable in the acute but not in the chronic. And finally, pre-administration of naloxone or fucoidin prevented LEDT analgesic effect. These data contribute to the understanding of the neurobiological mechanisms involved in the therapeutic effect of LEDT as well as provides additional support for its use in the treatment of painful conditions of inflammatory etiology. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Glutamate-evoked jaw muscle pain as a model of persistent myofascial TMD pain?

PubMed Central

Castrillon, Eduardo E.; Cairns, Brian E.; Ernberg, Malin; Wang, Kelun; Sessle, Barry; Arendt-Nielsen, Lars; Svensson, Peter

2008-01-01

Objective Compare pain-related measures and psychosocial variables between glutamate-evoked jaw muscle pain in healthy subjects (HS) and patients with persistent myofascial temporomandibular disorder (TMD) pain. Design 47 female HS and 10 female patients with persistent myofascial TMD pain participated. The HS received an injection of glutamate into the masseter muscle to model persistent myofascial TMD pain. Participants filled out a coping strategies questionnaire (CSQ), the symptom checklist 90 (SCL-90) and McGill Pain Questionnaire (MPQ). Pain intensity was assessed on an electronic visual analog scale (VAS). Pain-drawing areas, Numerical Rating Scale (NRS) scores of unpleasantness, pressure pain thresholds (PPT) and tolerance (PPTOL) were measured. Unpaired t-tests and correlation tests were used for analyses. Results The groups were significantly different when comparing the CSQ scores of control, decrease, diverting attention, increase of behavioral activities and somatization. The peak VAS pain, NRS of unpleasantness and MPQ scores were not significantly different between groups, but PPT and PPTOL were significantly lower in the TMD patients. Significant positive correlations were found in the TMD patients between peak VAS pain and CSQ catastrophizing score and SCL-90 somatization. The scores of PPTs and PPTOLs, in patients showed positive correlations with CSQ reinterpreting pain sensations scores and PPTs correlated with CSQ praying/hoping scores. Conclusions Glutamate-evoked pain responses in HS and persistent myofascial TMD pain have similar sensory-discriminative and affective-unpleasantness components but differ in psycho-social features. This study suggests that experimental designs based on glutamate injection into muscle can provide an appropriate model for elucidating persistent myofascial pain conditions. PMID:18313028

Acetaminophen and non-steroidal anti-inflammatory drugs interact with morphine and tramadol analgesia for the treatment of neuropathic pain in rats.

PubMed

Shinozaki, Tomonari; Yamada, Toshihiko; Nonaka, Takahiro; Yamamoto, Tatsuo

2015-06-01

Although non-steroidal anti-inflammatory drugs and acetaminophen have no proven efficacy against neuropathic pain, they are frequently prescribed for neuropathic pain patients. We examined whether the combination of opioids (tramadol and morphine) with indomethacin or acetaminophen produce favorable effects on neuropathic pain and compared the efficacy for neuropathic pain with that for inflammatory pain. The carrageenan model was used as the inflammatory pain model while the tibial neuroma transposition (TNT) model was used as the neuropathic pain model. The tibial nerve is transected in the TNT model, with the tibial nerve stump then transpositioned to the lateral aspect of the hindlimb. Neuropathic pain (mechanical allodynia and neuroma pain) is observed after TNT injury. Drugs were administered orally. In the carrageenan model, all drugs produced anti-allodynic effects and all drug combinations, but not tramadol + indomethacin combination, produced synergistic anti-allodynic effects. In the TNT model, tramadol and morphine, but not acetaminophen and indomethacin, produced anti-neuropathic pain effects. In the combination, with the exception of morphine + acetaminophen combination, both acetaminophen and indomethacin reduced the 50% effective dose (ED50) of tramadol and morphine as compared with the ED50s for the single drug study in the TNT model. The ED50s of tramadol and morphine in the carrageenan combination test were not statistically significantly different from the ED50s in the TNT model combination study. The combination of opioids with indomethacin or acetaminophen produced a synergistic analgesic effect both in inflammatory and neuropathic pain with some exceptions. The efficacy of these combinations for neuropathic pain was not different from that for inflammatory pain.

[Menstruation, inflammation and comorbidities: implications for woman health].

PubMed

Graziottin, A; Zanello, P P

2015-02-01

Menstruation is the genital sign of systemic endocrine events. Heterogeneity of perimenstrual symptoms is associated with levels of inflammation, triggered by the fall of estrogens at genital and systemic level. Aim of the review is to concisely analyze the evidence on: 1) genital and systemic endocrine and inflammatory events associated with periods and perimenstrual symptoms; 2) rationale of intervention to reduce their intensity and impact on women's lives. This review of the literature, selected with a clinical perspective, supports the inflammatory basis of the menstrual event, triggered by the estrogens' and progesterone' fall. Moreover, the review analyzes the endocrine and inflammatory basis of perimenstrual pelvic and extrapelvic symptoms such as: menstrual pain, menstrual irregularities, premenstrual syndrome, gastrointestinal symptoms, catamenial headache, depression, perimenstrual myalgia, joint pain, allergies and asthma, heavy menstrual bleeding, associated ironless anemia, brain and behavioral consequences. Inflammation, with increase of cytokines and other markers, is modulated by the degranulation of mast cells at the basal level of the endometrium, in the blood, in all the organs where mast-cell are already activated from local pathologies and within the brain. The shift of inflammation from physiological to a pathologic intensity increases the severity of perimenstrual symptoms. Symptoms persist, moderately attenuated, also during the hormone free interval (HFI) in contraception. The HFI reduction from seven to two days significantly reduces menstrual inflammation and associated symptoms.

Association Between Persistent Pain and Memory Decline and Dementia in a Longitudinal Cohort of Elders.

PubMed

Whitlock, Elizabeth L; Diaz-Ramirez, L Grisell; Glymour, M Maria; Boscardin, W John; Covinsky, Kenneth E; Smith, Alexander K

2017-08-01

Chronic pain is common among the elderly and is associated with cognitive deficits in cross-sectional studies; the population-level association between chronic pain and longitudinal cognition is unknown. To determine the population-level association between persistent pain, which may reflect chronic pain, and subsequent cognitive decline. Cohort study with biennial interviews of 10 065 community-dwelling older adults in the nationally representative Health and Retirement Study who were 62 years or older in 2000 and answered pain and cognition questions in both 1998 and 2000. Data analysis was conducted between June 24 and October 31, 2016. "Persistent pain," defined as a participant reporting that he or she was often troubled with moderate or severe pain in both the 1998 and 2000 interviews. Coprimary outcomes were composite memory score and dementia probability, estimated by combining neuropsychological test results and informant and proxy interviews, which were tracked from 2000 through 2012. Linear mixed-effects models, with random slope and intercept for each participant, were used to estimate the association of persistent pain with slope of the subsequent cognitive trajectory, adjusting for demographic characteristics and comorbidities measures in 2000 and applying sampling weights to represent the 2000 US population. We hypothesized that persistent pain would predict accelerated memory decline and increased probability of dementia. To quantify the impact of persistent pain on functional independence, we combined our primary results with information on the association between memory and ability to manage medications and finances independently. Of the 10 065 eligible HRS sample members, 60% were female, and median baseline age was 73 years (interquartile range, 67-78 years). At baseline, persistent pain affected 10.9% of participants and was associated with worse depressive symptoms and more limitations in activities of daily living. After covariate adjustment, persistent pain was associated with 9.2% (95% CI, 2.8%-15.0%) more rapid memory decline compared with those without persistent pain. After 10 years, this accelerated memory decline implied a 15.9% higher relative risk of inability to manage medications and an 11.8% higher relative risk of inability to manage finances independently. Adjusted dementia probability increased 7.7% faster (95% CI, 0.55%-14.2%); after 10 years, this translates to an absolute 2.2% increase in dementia probability for those with persistent pain. Persistent pain was associated with accelerated memory decline and increased probability of dementia.

Rationale for early versus late intervention with arthroscopy for treatment of inflammatory/degenerative temporomandibular joint disorders.

PubMed

Israel, Howard A; Behrman, David A; Friedman, Joel M; Silberstein, Jennifer

2010-11-01

The goal of this study was to determine if there were differences in outcomes of arthroscopic surgery in patients with inflammatory/degenerative temporomandibular joint (TMJ) disease who underwent early surgical intervention versus late surgical intervention. The study population included 44 consecutive patients who met the criteria for TMJ operative arthroscopy who were divided into early and late intervention groups. The time between the onset of symptoms and the performance of arthroscopy was used to determine entry into the early versus late intervention group. All groups were evaluated for changes in preoperative versus postoperative pain levels based on visual analog scale (VAS) scores and maximum interincisal opening distance. Statistical analyses included the Student t test to determine if there were significant differences between preoperative and postoperative assessments in the early and late intervention groups. The mean time between onset of symptoms in the early intervention group (21 patients) was 5.4 months compared with 33 months in the late intervention group (23 patients). All patient groups had statistically significant decreases in pain and improvement in maximum interincisal opening distance after arthroscopy. The early intervention group had a mean decrease in VAS pain scores of 5.14 compared with the late intervention group with a mean decrease in VAS pain scores of 2.84, and this difference was significant (P = .012). The early intervention group had a mean increase in maximum interincisal opening of 12.38 mm compared with the late intervention group with a mean increase of 7.70. Although statistical significance was not achieved for increases in maximum interincisal opening between the early and late intervention groups (P = .089), the difference between the 2 groups was suggestive of a trend. There were no surgical complications for either group; however, 2 patients in the late intervention group developed persistent chronic neuropathic pain, requiring pain management. TMJ arthroscopy reliably decreased pain and increased the maximum interincisal opening distance in the early and late intervention groups. The early intervention group had better surgical outcomes than the late intervention group. Arthroscopic surgery should be considered early in the management of patients with inflammatory/degenerative TMJ disease. Copyright © 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Overview of persistent pain in older adults.

PubMed

Molton, Ivan R; Terrill, Alexandra L

2014-01-01

With the shifting age demographics of the U.S. population, more psychologists will be asked to provide clinical services to older adults. Given the high prevalence of persistent pain in aging, in many cases this will mean providing empirically supported interventions for pain and the interference it creates. The purpose of this review is to provide a broad overview of the scope and impact of persistent pain in older people and to discuss mechanisms by which persistent geriatric pain can lead to suffering and disability. We consider the unique context of pain in older adulthood and review differences between older and younger people in terms of pain perception, the social network, beliefs about pain, pain-related coping, and adherence to pain medication. Finally, we discuss special issues affecting pain management in older adults, including dementia, polypharmacy, and barriers to accessing adequate pain care. This review also highlights a need for greater provider training in pain management to meet the needs of a changing U.S. population. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Risk factors for the onset and persistence of neck pain in undergraduate students: 1-year prospective cohort study.

PubMed

Kanchanomai, Siriluck; Janwantanakul, Prawit; Pensri, Praneet; Jiamjarasrangsi, Wiroj

2011-07-15

Although neck pain is common in young adulthood, studies on predictive factors for its onset and persistence are scarce. It is therefore important to identify possible risk factors among young adults so as to prevent the development of neck pain later in life. A prospective study was carried out in healthy undergraduate students. At baseline, a self-administered questionnaire and standardized physical examination were used to collect data on biopsychosocial factors. At 3, 6, 9, and 12 months thereafter, follow-up data were collected on the incidence of neck pain. Those who reported neck pain on ≥ 2 consecutive follow-ups were categorized as having persistent neck pain. Two regression models were built to analyze risk factors for the onset and persistence of neck pain. Among the recruited sample of 684 students, 46% reported the onset of neck pain between baseline and 1-year follow-up, of whom 33% reported persistent neck pain. The onset of neck pain was associated with computer screen position not being level with the eyes and mouse position being self-rated as suitable. Factors that predicted persistence of neck pain were position of the keyboard being too high, use of computer for entertainment < 70% of total computer usage time, and students being in the second year of their studies. Neck pain is quite common among undergraduate students. This study found very few proposed risk factors that predicted onset and persistence of neck pain. The future health of undergraduate students deserves consideration. However, there is still much uncertainty about factors leading to neck pain and more research is needed on this topic.

Risk factors for the onset and persistence of neck pain in undergraduate students: 1-year prospective cohort study

PubMed Central

2011-01-01

Background Although neck pain is common in young adulthood, studies on predictive factors for its onset and persistence are scarce. It is therefore important to identify possible risk factors among young adults so as to prevent the development of neck pain later in life. Methods A prospective study was carried out in healthy undergraduate students. At baseline, a self-administered questionnaire and standardized physical examination were used to collect data on biopsychosocial factors. At 3, 6, 9, and 12 months thereafter, follow-up data were collected on the incidence of neck pain. Those who reported neck pain on ≥ 2 consecutive follow-ups were categorized as having persistent neck pain. Two regression models were built to analyze risk factors for the onset and persistence of neck pain. Results Among the recruited sample of 684 students, 46% reported the onset of neck pain between baseline and 1-year follow-up, of whom 33% reported persistent neck pain. The onset of neck pain was associated with computer screen position not being level with the eyes and mouse position being self-rated as suitable. Factors that predicted persistence of neck pain were position of the keyboard being too high, use of computer for entertainment < 70% of total computer usage time, and students being in the second year of their studies. Conclusion Neck pain is quite common among undergraduate students. This study found very few proposed risk factors that predicted onset and persistence of neck pain. The future health of undergraduate students deserves consideration. However, there is still much uncertainty about factors leading to neck pain and more research is needed on this topic. PMID:21756362

Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases

PubMed Central

2017-01-01

Microglial cells are responsible for immune surveillance within the CNS. They respond to noxious stimuli by releasing inflammatory mediators and mounting an effective inflammatory response. This is followed by release of anti-inflammatory mediators and resolution of the inflammatory response. Alterations to this delicate process may lead to tissue damage, neuroinflammation, and neurodegeneration. Chronic pain, such as inflammatory or neuropathic pain, is accompanied by neuroimmune activation, and the role of glial cells in the initiation and maintenance of chronic pain has been the subject of increasing research over the last two decades. Neuropeptides are small amino acidic molecules with the ability to regulate neuronal activity and thereby affect various functions such as thermoregulation, reproductive behavior, food and water intake, and circadian rhythms. Neuropeptides can also affect inflammatory responses and pain sensitivity by modulating the activity of glial cells. The last decade has witnessed growing interest in the study of microglial activation and its modulation by neuropeptides in the hope of developing new therapeutics for treating neurodegenerative diseases and chronic pain. This review summarizes the current literature on the way in which several neuropeptides modulate microglial activity and response to tissue damage and how this modulation may affect pain sensitivity. PMID:28154473

Persistent Pain Quality as a Novel Approach to Assessing Risk for Disability in Community-Dwelling Elders with Chronic Pain.

PubMed

Thakral, Manu; Shi, Ling; Foust, Janice B; Patel, Kushang V; Shmerling, Robert H; Bean, Jonathan F; Leveille, Suzanne G

2018-06-18

This study aims to test whether persistent pain quality is associated with incident or worsening disability in four domains: mobility, ADL and IADL difficulty and physical performance. From the MOBILIZE Boston Study, a population-based cohort of adults aged ≥70 years, we studied participants with chronic pain who endorsed at least one pain quality descriptor (N=398) and completed baseline and 18-month assessments. Pain quality was assessed using an adapted short-form McGill Pain Questionnaire with 20 pain quality descriptors in 3 categories: sensory, cognitive/affective, neuropathic. Persistence was defined as endorsing the same category at baseline and 18 months. Self-reported outcomes included mobility, ADL, and IADL difficulty. Physical performance was assessed using the Short Physical Performance Battery. After adjusting for baseline pain severity and other covariates, individuals with 3 persistent categories had a greater risk of developing new or worsening IADL difficulty relative to those with 1 persistent category (RR 2.69, 95% CI 1.34, 7.79). Similar results were observed for ADL difficulty (RR 5.83, 95% CI 1.32, 25.85) but no differences were noted in risk for mobility difficulty. There was no significant linear trend in physical performance over 18 months according to number of persistent categories (p=0.68). Elders with persistent pain quality experienced a higher risk of developing new or worsening IADL and ADL disability with each additional category but not mobility difficulty or poorer physical performance. Longitudinal assessment of pain quality could be useful in determining risk for global disability among elders with chronic pain.

Neuropathic pain in the orofacial region: The role of pain history. A retrospective study.

PubMed

Dieb, W; Moreau, N; Chemla, I; Descroix, V; Boucher, Y

2017-06-01

Orofacial neuropathic pain is often difficult to treat, mostly because of still unclear underlying mechanisms. The occurrence of such neuropathic pain varies depending on different factors, of which preexisting preoperative pain seems to be of high importance. The aim of this study was thus to test the hypothesis that prior history of pain could indeed be considered a risk factor for the development of orofacial neuropathic pain in the same region. The study was performed in the dental department of the Groupe Hospitalier Pitié-Salpêtrière (GHPS) in Paris, France. We investigated the presence of prior inflammatory pain before development of orofacial neuropathic pain in 56 patients. For each patient file, the following items were collected: age, gender; medical history; diagnosis; description of the pain (at time of consultation); presence or absence of prior dental treatment; date and type of dental treatment received. 41 patients (73%) of orofacial neuropathic pain patients had a history of pain compatible with an inflammatory condition; 4% (n=2) did not report any prior pain and 23% (n=13) could not remember. Among the patients with documented history of pain prior to neuropathy, 88% (n=36) received surgical treatment; 61%, (n=25) endodontic treatment and 22%, (n=9) restorative treatment. All eventually received endodontic treatment or tooth extraction. These dental treatments are compatible with the hypothesis of prior inflammatory pain in these patients. These results support the hypothesis that prior inflammatory pain could favor the development of orofacial neuropathic pain. Prevention and treatment of inflammatory trigeminal pain may therefore play a key role in preventing future neuropathic pain development. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Nonoperative Management of Cervical Radiculopathy.

PubMed

Childress, Marc A; Becker, Blair A

2016-05-01

Cervical radiculopathy describes pain in one or both of the upper extremities, often in the setting of neck pain, secondary to compression or irritation of nerve roots in the cervical spine. It can be accompanied by motor, sensory, or reflex deficits and is most prevalent in persons 50 to 54 years of age. Cervical radiculopathy most often stems from degenerative disease in the cervical spine. The most common examination findings are painful neck movements and muscle spasm. Diminished deep tendon reflexes, particularly of the triceps, are the most common neurologic finding. The Spurling test, shoulder abduction test, and upper limb tension test can be used to confirm the diagnosis. Imaging is not required unless there is a history of trauma, persistent symptoms, or red flags for malignancy, myelopathy, or abscess. Electrodiagnostic testing is not needed if the diagnosis is clear, but has clinical utility when peripheral neuropathy of the upper extremity is a likely alternate diagnosis. Patients should be reassured that most cases will resolve regardless of the type of treatment. Nonoperative treatment includes physical therapy involving strengthening, stretching, and potentially traction, as well as nonsteroidal anti-inflammatory drugs, muscle relaxants, and massage. Epidural steroid injections may be helpful but have higher risks of serious complications. In patients with red flag symptoms or persistent symptoms after four to six weeks of treatment, magnetic resonance imaging can identify pathology amenable to epidural steroid injections or surgery.

Early revisions of the Femoro-Patella Vialla joint replacement.

PubMed

Williams, D P; Pandit, H G; Athanasou, N A; Murray, D W; Gibbons, C L M H

2013-06-01

The aim of this study was to review the early outcome of the Femoro-Patella Vialla (FPV) joint replacement. A total of 48 consecutive FPVs were implanted between December 2007 and June 2011. Case-note analysis was performed to evaluate the indications, operative histology, operative findings, post-operative complications and reasons for revision. The mean age of the patients was 63.3 years (48.2 to 81.0) and the mean follow-up was 25.0 months (6.1 to 48.9). Revision was performed in seven (14.6%) at a mean of 21.7 months, and there was one re-revision. Persistent pain was observed in three further patients who remain unrevised. The reasons for revision were pain due to progressive tibiofemoral disease in five, inflammatory arthritis in one, and patellar fracture following trauma in one. No failures were related to the implant or the technique. Trochlear dysplasia was associated with a significantly lower rate of revision (5.9% vs 35.7%, p = 0.017) and a lower incidence of revision or persistent pain (11.8% vs 42.9%, p = 0.045). Focal patellofemoral osteoarthritis secondary to trochlear dysplasia should be considered the best indication for patellofemoral replacement. Standardised radiological imaging, with MRI to exclude overt tibiofemoral disease should be part of the pre-operative assessment, especially for the non-dysplastic knee.

A machine-learned analysis of human gene polymorphisms modulating persisting pain points at major roles of neuroimmune processes.

PubMed

Kringel, Dario; Lippmann, Catharina; Parnham, Michael J; Kalso, Eija; Ultsch, Alfred; Lötsch, Jörn

2018-06-19

Human genetic research has implicated functional variants of more than one hundred genes in the modulation of persisting pain. Artificial intelligence and machine learning techniques may combine this knowledge with results of genetic research gathered in any context, which permits the identification of the key biological processes involved in chronic sensitization to pain. Based on published evidence, a set of 110 genes carrying variants reported to be associated with modulation of the clinical phenotype of persisting pain in eight different clinical settings was submitted to unsupervised machine-learning aimed at functional clustering. Subsequently, a mathematically supported subset of genes, comprising those most consistently involved in persisting pain, was analyzed by means of computational functional genomics in the Gene Ontology knowledgebase. Clustering of genes with evidence for a modulation of persisting pain elucidated a functionally heterogeneous set. The situation cleared when the focus was narrowed to a genetic modulation consistently observed throughout several clinical settings. On this basis, two groups of biological processes, the immune system and nitric oxide signaling, emerged as major players in sensitization to persisting pain, which is biologically highly plausible and in agreement with other lines of pain research. The present computational functional genomics-based approach provided a computational systems-biology perspective on chronic sensitization to pain. Human genetic control of persisting pain points to the immune system as a source of potential future targets for drugs directed against persisting pain. Contemporary machine-learned methods provide innovative approaches to knowledge discovery from previous evidence. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Retrospective evaluation of the effectiveness of radiotherapy in patients with plantar fascitis (heel spurs).

PubMed

Kędzierawski, Piotr; Stando, Rafał; Macek, Paweł

2017-01-01

The aim of the study was the evaluation of the effectiveness of radiotherapy in patients with the feet pain caused by heel spurs. Treatment options for patients reporting these symptoms include use of suitable orthopedic footwear, the use of general or topical non-steroidal anti-inflammatory drugs or steroids, physiotherapy, manual therapy, shock wave or appropriate surgical procedures. Radiotherapy is one of the method used in patients with chronic pain syndrome. The material consisted of 47 patients treated in Radiotherapy Department at the Holycross Cancer Center. The time of follow-up ranged from 1 to 129 months. After treatment patients were observed. During the first follow-up visit a complete relief of symptoms was observed in 37 patients, and the pain was felt by 10 patients for 4 months after the treatment. One patient was re-irradiated 6 months after treatment because of persistent pain. At 16 and 17 months after the onset of treatment, pain was reported by two patients. These patients were re-irradiated. One patient had recurrence of pain 48 months after completion of radiation. After the second irradiation the pain was relieved. The remaining patients, with the exception of two, experienced remission of pain, which has been documented. Tolerance of the treatment was very good. No complications of radiation were observed. Radiotherapy remains an attractive treatment for patients with inflammation of the heel fascia.

Advances in the diagnosis and management of neck pain.

PubMed

Cohen, Steven P; Hooten, W Michael

2017-08-14

Neck pain imposes a considerable personal and socioeconomic burden-it is one of the top five chronic pain conditions in terms of prevalence and years lost to disability-yet it receives a fraction of the research funding given to low back pain. Although most acute episodes resolve spontaneously, more than a third of affected people still have low grade symptoms or recurrences more than one year later, with genetics and psychosocial factors being risk factors for persistence. Nearly half of people with chronic neck pain have mixed neuropathic-nociceptive symptoms or predominantly neuropathic symptoms. Few clinical trials are dedicated solely to neck pain. Muscle relaxants and non-steroidal anti-inflammatory drugs are effective for acute neck pain, and clinical practice is mostly guided by the results of studies performed for other chronic pain conditions. Among complementary and alternative treatments, the strongest evidence is for exercise, with weaker evidence supporting massage, acupuncture, yoga, and spinal manipulation in different contexts. For cervical radiculopathy and facet arthropathy, weak evidence supports epidural steroid injections and radiofrequency denervation, respectively. Surgery is more effective than conservative treatment in the short term but not in the long term for most of these patients, and clinical observation is a reasonable strategy before surgery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Prediction of Persistent Musculoskeletal Pain at 12 Months: A Secondary Analysis of the Optimal Screening for Prediction of Referral and Outcome (OSPRO) Validation Cohort Study.

PubMed

Beneciuk, Jason M; Lentz, Trevor A; He, Ying; Wu, Samuel S; George, Steven Z

2018-05-01

Musculoskeletal pain is a societal epidemic because it is highly prevalent and a leading contributor to disability; however, physical therapists are still challenged when predicting which patients are at high risk for persistent symptoms. The objectives of this study were to identify patient characteristics predictive of persistent musculoskeletal pain 12 months following physical therapist care and to determine the influence of anatomical region. The design included a secondary analysis of a cohort study. Participants ranged in age from 18 to 65 years, had a primary report of knee, shoulder, back, or neck pain, were receiving physical therapy, and were enrolled in the Orthopedic Physical Therapy Investigative Network (OPT-IN) Optimal Screening for Prediction of Referral and Outcome (OSPRO) validation cohort study. Candidate predictor variables included demographic and clinical characteristics, comorbidities, and OSPRO Review of Systems (OSPRO-ROS) and OSPRO Yellow Flag (OSPRO-YF) tool scores. Persistent musculoskeletal pain was assessed by self-report responses to questions on the duration of pain and activity limitation. Logistic regression was used for completed cases to identify predictors of persistent pain at 12 months in full and parsimonious models. Follow-up assessment at 12 months was performed for 63.4% of participants (279/440). Participants with persistent pain at 12 months (n = 101; 36.2%) had more comorbidities, higher numerical pain rating scale scores, and higher OSPRO-ROS and OSPRO-YF tool scores at baseline than those without persistent pain, and the findings were independent of anatomical region. The number of comorbidities (odds ratio [OR] range = 0.30-0.46), numerical pain rating scale scores (OR at baseline = 1.44-1.75; OR at 4 weeks = 1.37-1.39), and OSPRO-ROS (plus additional items) scores (OR = 1.33-1.54) were predictors in full and parsimonious models. Convenience sampling was used, with a follow-up rate at 12 months (63.4%) that was lower than anticipated, and an operational definition for chronic low back pain was applied to persistent musculoskeletal pain in other body regions. The OSPRO-ROS tool may be used to improve the prediction of persistent musculoskeletal pain at 12 months in conjunction with comorbidities and pain intensity (baseline and 4 weeks). These are potentially important findings because persistent pain was not commonly evaluated in previous screening studies; however, it is a relevant outcome in an era of front-line nonpharmacological pain management.

Nociceptive Response to L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats.

PubMed

Nascimento, G C; Bariotto-Dos-Santos, K; Leite-Panissi, C R A; Del-Bel, E A; Bortolanza, M

2018-04-02

Non-motor symptoms are increasingly identified to present clinical and diagnostic importance for Parkinson's disease (PD). The multifactorial origin of pain in PD makes this symptom of great complexity. The dopamine precursor, L-DOPA (L-3,4-dihydroxyphenylalanine), the classic therapy for PD, seems to be effective in pain threshold; however, there are no studies correlating L-DOPA-induced dyskinesia (LID) and nociception development in experimental Parkinsonism. Here, we first investigated nociceptive responses in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease to a hind paw-induced persistent inflammation. Further, the effect of L-DOPA on nociception behavior at different times of treatment was investigated. Pain threshold was determined using von Frey and Hot Plate/Tail Flick tests. Dyskinesia was measured by abnormal involuntary movements (AIMs) induced by L-DOPA administration. This data is consistent to show that 6-OHDA-lesioned rats had reduced nociceptive thresholds compared to non-lesioned rats. Additionally, when these rats were exposed to a persistent inflammatory challenge, we observed increased hypernociceptive responses, namely hyperalgesia. L-DOPA treatment alleviated pain responses on days 1 and 7 of treatment, but not on day 15. During that period, we observed an inverse relationship between LID and nociception threshold in these rats, with a high LID rate corresponding to a reduced nociception threshold. Interestingly, pain responses resulting from CFA-induced inflammation were significantly enhanced during established dyskinesia. These data suggest a pro-algesic effect of L-DOPA-induced dyskinesia, which is confirmed by the correlation founded here between AIMs and nociceptive indexes. In conclusion, our results are consistent with the notion that central dopaminergic mechanism is directly involved in nociceptive responses in Parkinsonism condition.

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.

Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on inflammatory and neuropathic pain in mice.

PubMed

Marabese, I; de Novellis, V; Palazzo, E; Scafuro, M A; Vita, D; Rossi, F; Maione, S

2007-02-01

In this study, the effect of (S)-3,4-dicarboxyphenylglycine (DCPG), a selective mGlu8 receptor agonist, has been investigated in inflammatory and neuropathic pain models in order to elucidate the role of mGlu8 receptor in modulating pain perception. Inflammatory pain was induced by the peripheral injection of formalin or carrageenan in awake mice. Systemic administration of (S)-3,4-DCPG, performed 15 min before formalin, decreased both early and delayed nociceptive responses of the formalin test. When this treatment was carried out 15 min after the peripheral injection of formalin it still reduced the late hyperalgesic phase. Similarly, systemic (S)-3,4-DCPG reduced carrageenan-induced thermal hyperalgesia and mechanical allodynia when administered 15 min before carrageenan, but no effect on pain behaviour was observed when (S)-3,4-DCPG was given after the development of carrageenan-induced inflammatory pain. When microinjected into the lateral PAG (RS)-alpha-methylserine-O-phoshate (MSOP), a group III receptor antagonist, antagonised the analgesic effect induced by systemic administration of (S)-3,4-DCPG in both of the inflammatory pain models. Intra-lateral PAG (S)-3,4-DCPG reduced pain behaviour when administered 10 min before formalin or carrageenan; both the effects were blocked by intra-lateral PAG MSOP. (S)-3,4-DCPG was ineffective in alleviating thermal hyperalgesia and mechanical allodynia 7 days after the chronic constriction injury of the sciatic nerve, whereas it proved effective 3 days after surgery. Taken together these results suggest that stimulation of mGlu8 receptors relieve formalin and carrageenan-induced hyperalgesia in inflammatory pain, whereas it would seem less effective in established inflammatory or neuropathic pain.

Predictors of persistent pain after total knee arthroplasty: a systematic review and meta-analysis.

PubMed

Lewis, G N; Rice, D A; McNair, P J; Kluger, M

2015-04-01

Several studies have identified clinical, psychosocial, patient characteristic, and perioperative variables that are associated with persistent postsurgical pain; however, the relative effect of these variables has yet to be quantified. The aim of the study was to provide a systematic review and meta-analysis of predictor variables associated with persistent pain after total knee arthroplasty (TKA). Included studies were required to measure predictor variables prior to or at the time of surgery, include a pain outcome measure at least 3 months post-TKA, and include a statistical analysis of the effect of the predictor variable(s) on the outcome measure. Counts were undertaken of the number of times each predictor was analysed and the number of times it was found to have a significant relationship with persistent pain. Separate meta-analyses were performed to determine the effect size of each predictor on persistent pain. Outcomes from studies implementing uni- and multivariable statistical models were analysed separately. Thirty-two studies involving almost 30 000 patients were included in the review. Preoperative pain was the predictor that most commonly demonstrated a significant relationship with persistent pain across uni- and multivariable analyses. In the meta-analyses of data from univariate models, the largest effect sizes were found for: other pain sites, catastrophizing, and depression. For data from multivariate models, significant effects were evident for: catastrophizing, preoperative pain, mental health, and comorbidities. Catastrophizing, mental health, preoperative knee pain, and pain at other sites are the strongest independent predictors of persistent pain after TKA. © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Long-Term Effects of Neonatal Pain and Stress on Reactivity of the Nociceptive System.

PubMed

Butkevich, I P; Mikhailenko, V A

2016-10-01

The influence of inflammatory pain and/or weaning stress at different terms of neonatal development on functional activity of the nociceptive system during adulthood was studied in rats. Repeated stress in 1-2-day-old rat pups (a premature baby model) enhanced pain sensitivity to peripheral inflammation in both males and females. Repeated inflammatory pain experienced by male pups aged 1-2 or 7-8 days (models of preterm and full-term baby), even in presence of mother, enhanced pain behavior under conditions of repeated inflammatory pain in adulthood. Pain sensitivity in adult animals before (hot plate test) and after formation of the inflammatory focus (formalin test) depended on the age when the animals were subjected to the injury, type of exposure, and on animal sex. The priority data obtained by us will help to understand the mechanisms of long-term effects of early injuries and are important for pediatricians and neonatologists.

A systematic review of early prognostic factors for persistent pain following acute orthopedic trauma

PubMed Central

Clay, Fiona J; Watson, Wendy L; Newstead, Stuart V; McClure, Roderick J

2012-01-01

BACKGROUND: Acute orthopedic trauma contributes substantially to the global burden of disease. OBJECTIVES: The present systematic review aimed to summarize the current knowledge concerning prognostic factors for the presence of persistent pain, pain severity and pain-related disability following acute orthopedic trauma involving a spectrum of pathologies to working-age adults. METHODS: The Ovid MEDLINE and EMBASE databases were searched for level II prognostic studies published between January 1996 and October 2010. Studies that were longitudinal and reported results with multivariate analyses appropriate for prognostic studies were included. Studies that addressed two specific injury types that have been the subject of previous reviews, namely, injuries to the spinal column and amputations, were excluded. RESULTS: The searches yielded 992 studies; 10 studies met the inclusion criteria and were rated for methodological quality. Seventeen factors were considered in more than one cohort. There was strong evidence supporting the association of female sex, older age, high pain intensity, preinjury anxiety or depression, and fewer years of education with persistent pain outcomes. There was moderate evidence supporting the association between postinjury depression or anxiety with persistent pain, and that injury severity was not a risk factor for ongoing pain. CONCLUSION: Many individuals experience persistent pain following acute trauma. Due to the lack of studies, the use of different constructs to measure the same factor and the methodological limitations associated with many of the studies, the present review was only able to reliably identify a limited set of factors that predicted persistent pain. Recommendations for the conduct of future methodologically rigorous studies of persistent pain are provided. PMID:22518366

Sigma-1 receptor and inflammatory pain.

PubMed

Gris, Georgia; Cobos, Enrique José; Zamanillo, Daniel; Portillo-Salido, Enrique

2015-06-01

The sigma-1 receptor (Sig-1R) is a unique ligand-regulated molecular chaperone that interacts with several protein targets such as G protein-coupled receptors and ion channels to modulate their activity. Sig-1R is located in areas of the central and peripheral nervous system that are key to pain control. Previous preclinical studies have suggested a potential therapeutic use of Sig-1R antagonists for the management of neuropathic pain. Recent studies using pharmacological and genetic tools have explored the role of Sig-1R in inflammatory pain conditions. Mice lacking the Sig-1R have shown different patterns of phenotypic responses to inflammatory injury. Systemic or peripheral administration of several Sig-1R antagonists, including the selective Sig-1R antagonist S1RA, inhibited both mechanical and thermal hypersensitivity in several preclinical models of inflammatory pain. These recent studies are summarized in the present commentary. Central and peripheral pharmacological blockade of Sig-1R could be an effective option to treat inflammatory pain.

Analgesic Effect of Xenon in Rat Model of Inflammatory Pain.

PubMed

Kukushkin, M L; Igon'kina, S I; Potapov, S V; Potapov, A V

2017-02-01

The analgesic effects of inert gas xenon were examined on rats. The formalin model of inflammatory pain, tail-flick test, and hot-plate test revealed the antinociceptive effects of subanesthetizing doses of inhalation anesthetic xenon. Inhalation of 50/50 xenon/oxygen mixture moderated the nociceptive responses during acute and tonic phases of inflammatory pain.

Preventing Chronic Pain following Acute Pain: Risk Factors, Preventive Strategies, and their Efficacy

PubMed Central

McGreevy, Kai; Bottros, Michael M.; Raja, Srinivasa N.

2011-01-01

Chronic pain is the leading cause of disability in the United States. The transition from acute to persistent pain is thought to arise from maladaptive neuroplastic mechanisms involving three intertwined processes, peripheral sensitization, central sensitization, and descending modulation. Strategies aimed at preventing persistent pain may target such processes. Models for studying preventive strategies include persistent post-surgical pain (PPP), persistent post-trauma pain (PTP) and post-herpetic neuralgia (PHN). Such entities allow a more defined acute onset of tissue injury after which study of the long-term effects is more easily examined. In this review, we examine the pathophysiology, epidemiology, risk factors, and treatment strategies for the prevention of chronic pain using these models. Both pharmacological and interventional approaches are described, as well as a discussion of preventive strategies on the horizon. PMID:22102847

Spine Conditions: Mechanical and Inflammatory Low Back Pain.

PubMed

Ledford, Christopher

2017-10-01

Mechanical low back pain (LBP) is an injury or derangement of an anatomic structure in the low back. When evaluating patients with LBP, clinicians should maintain clinical suspicion for vertebral fracture, cancer, and cauda equina syndrome. Management includes patient education focused on exercise, massage, and behavioral approaches such as cognitive behavioral therapy. Acupuncture can be an effective alternative and specific herbal supplements may provide short-term pain relief. The prognosis for patients with mechanical LBP is good. Inflammatory LBP is pain resulting from a systemic inflammatory condition, often referred to as axial spondyloarthritis. Ankylosing spondylitis is chronic inflammatory LBP characterized by early onset (mean age 24 years), with a higher prevalence in men. Five clinical parameters can help identify inflammatory LBP: improvement with exercise, pain at night, insidious onset, onset at younger than 40 years, and no improvement with rest. Management of inflammatory LBP typically includes nonsteroidal anti-inflammatory drugs and structured exercise programs, with emphasis on the involvement of a rheumatology subspecialist. Spondyloarthritis is associated with other rheumatic or autoimmune conditions, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. These should be considered when evaluating patients with inflammatory LBP. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Targeted nanoparticles that mimic immune cells in pain control inducing analgesic and anti-inflammatory actions: a potential novel treatment of acute and chronic pain condition.

PubMed

Hua, Susan; Cabot, Peter J

2013-01-01

The peripheral immune-derived opioid analgesic pathway has been well established as a novel target in the clinical pain management of a number of painful pathologies, including acute inflammatory pain, neuropathic pain, and rheumatoid arthritis. Our objective was to engineer targeted nanoparticles that mimic immune cells in peripheral pain control to deliver opioids, in particular loperamide HCl, specifically to peripheral opioid receptors to induce analgesic and anti-inflammatory actions for use in painful inflammatory conditions. This peripheral analgesic system is devoid of central opioid mediated side effects (e.g., respiratory depression, sedation, dependence, tolerance). A randomized, double blind, controlled animal trial. Thirty-six adult male Wistar rats (200 - 250 g) were randomly divided into 6 groups: loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, naloxone methiodide + loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, loperamide HCl-encapsulated liposomes, empty anti-ICAM-1 immunoliposomes, empty liposomes, and loperamide solution. Animals received an intraplantar injection of 150 μL Complete Freund's Adjuvant (CFA) into the right hindpaw and experiments were performed 5 days post-CFA injection, which corresponded to the peak inflammatory response. All formulations were administered intravenously via tail vein injection. The dose administered was 200 μL, which equated to 0.8 mg of loperamide HCl for the loperamide HCl treatment groups (sub-therapeutic dose). Naloxone methiodide (1 mg/kg) was administered via intraplantar injection, 15 minutes prior to loperamide-encapsulated anti-ICAM-1 immunoliposomes. An investigator blinded to the treatment administered assessed the time course of the antinociceptive and anti-inflammatory effects using a paw pressure analgesiometer and plethysmometer, respectively. Biodistribution studies were performed 5 days post-CFA injection with anti-ICAM-1 immunoliposomes and control liposomes via tail vein injection using liquid scintillation counting (LSC). Administration of liposomes loaded with loperamide HCl, and conjugated with antibody to intercellular adhesion molecule-1 (anti-ICAM-1), exerted analgesic and anti-inflammatory effects exclusively in peripheral painful inflamed tissue. These targeted nanoparticles produced highly significant analgesic and anti-inflammatory effects over the 48 hour time course studied following intravenous administration in rats with Complete Freund's Adjuvant-induced inflammation of the paw. All control groups showed no significant antinociceptive or anti-inflammatory effects. Our biodistribution study demonstrated specific localization of the targeted nanoparticles to peripheral inflammatory tissue and no significant uptake into the brain. In vivo studies were performed in the well-established rodent model of acute inflammatory pain. We are currently studying this approach in chronic pain models known to have clinical activation of the peripheral immune-derived opioid response. The study presents a novel approach of opioid delivery specifically to injured tissues for pain control. The study also highlights a novel anti-inflammatory role for peripheral opioid targeting, which is of clinical relevance. The potential also exists for the modification of these targeted nanoparticles with other therapeutic compounds for use in other painful conditions.

Identification of a vesicular ATP release inhibitor for the treatment of neuropathic and inflammatory pain.

PubMed

Kato, Yuri; Hiasa, Miki; Ichikawa, Reiko; Hasuzawa, Nao; Kadowaki, Atsushi; Iwatsuki, Ken; Shima, Kazuhiro; Endo, Yasuo; Kitahara, Yoshiro; Inoue, Tsuyoshi; Nomura, Masatoshi; Omote, Hiroshi; Moriyama, Yoshinori; Miyaji, Takaaki

2017-07-18

Despite the high incidence of neuropathic and inflammatory pain worldwide, effective drugs with few side effects are currently unavailable for the treatment of chronic pain. Recently, researchers have proposed that inhibitors of purinergic chemical transmission, which plays a key role in the pathological pain response, may allow for targeted treatment of pathological neuropathic and inflammatory pain. However, such therapeutic analgesic agents have yet to be developed. In the present study, we demonstrated that clodronate, a first-generation bisphosphonate with comparatively fewer side effects than traditional treatments, significantly attenuates neuropathic and inflammatory pain unrelated to bone abnormalities via inhibition of vesicular nucleotide transporter (VNUT), a key molecule for the initiation of purinergic chemical transmission. In vitro analyses indicated that clodronate inhibits VNUT at a half-maximal inhibitory concentration of 15.6 nM without affecting other vesicular neurotransmitter transporters, acting as an allosteric modulator through competition with Cl - A low concentration of clodronate impaired vesicular ATP release from neurons, microglia, and immune cells. In vivo analyses revealed that clodronate is more effective than other therapeutic agents in attenuating neuropathic and inflammatory pain, as well as the accompanying inflammation, in wild-type but not VNUT -/- mice, without affecting basal nociception. These findings indicate that clodronate may represent a unique treatment strategy for chronic neuropathic and inflammatory pain via inhibition of vesicular ATP release.

Adherence Monitoring with Chronic Opioid Therapy for Persistent Pain: A Biopsychosocial-spiritual Approach to Mitigate Risk

PubMed Central

Matteliano, Deborah; St. Marie, Barbara J.; Oliver, June

2013-01-01

Opioids represent a mainstay in the pharmacological management of persistent pain. While these drugs are intended to support improved comfort and function, the inherent risk of abuse or addiction must be considered in the delivery of care. The experience of living with persistent pain often includes depression, fear, loss, and anxiety, leading to feelings of hopelessness, helplessness, and spiritual crisis. Collectively, these factors represent an increased risk for all patients, particularly those with a past history of substance abuse or addiction. This companion article to the American Society for Pain Management Nursing (ASPMN) Position Statement on Pain Management in Patients with Substance Use Disorders (2012) focuses on the intersection of persistent pain, SUD, and chronic opioid therapy and the clinical implications of monitoring adherence with safe use of opioids for those with persistent pain. This paper presents an approach to the comprehensive assessment of persons with persistent pain when receiving opioid therapy by presenting an expansion of the biopsychosocial model to now include spiritual factors associated with pain and SUD, thus formulating a biopsychosocial-spiritual approach to mitigate risk. Key principles are provided for adherence monitoring using the biopsychosocial-spiritual assessment model developed by the authors as a means of promoting sensitive and respectful care. PMID:24602442

Persistent pain and comorbidity among Operation Enduring Freedom/Operation Iraqi Freedom/operation New Dawn veterans.

PubMed

Higgins, Diana M; Kerns, Robert D; Brandt, Cynthia A; Haskell, Sally G; Bathulapalli, Harini; Gilliam, Wesley; Goulet, Joseph L

2014-05-01

Chronic pain is a significant concern for the Veterans Health Administration (VHA), with chronic pain conditions among those most frequently reported by Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF)/Operation New Dawn (OND) veterans. The current study examined VHA electronic medical record data to examine variation in demographics and high prevalence and high impact medical and mental health conditions in order to characterize the differences between patients with persistent pain and no pain. A conservative operational definition of chronic or "persistent pain" based on multiple indicators of pain (i.e., pain intensity ratings, prescription opioids, pain clinic visits, International Classification of Diseases, Ninth Revision codes) was employed. Analyses included the entire roster of longitudinal clinical data on OEF/OIF/OND veterans who used VHA care to compare those with persistent pain with those with no clinical evidence of pain. Results of logistic regression models suggest that sex, race, education, military variables, body mass index (BMI), traumatic brain injury (TBI), and mental health conditions, but not age, reliably discriminate the two groups. Those with persistent pain were more likely to be Black, female, on active duty, enlisted, Army service members, have a high school education or less, and have diagnoses of mood disorders, post-traumatic stress disorder, substance use disorders, anxiety disorders, TBI, and have a BMI consistent with overweight and obesity. The operational definition of chronic pain used in this study may have research implications for examining predictors of incident and chronic pain. These data have important clinical implications in that addressing comorbid conditions of persistent pain may improve adaptive coping and functioning in these patients. Wiley Periodicals, Inc.

Adherence monitoring with chronic opioid therapy for persistent pain: a biopsychosocial-spiritual approach to mitigate risk.

PubMed

Matteliano, Deborah; St Marie, Barbara J; Oliver, June; Coggins, Candace

2014-03-01

Opioids represent a mainstay in the pharmacologic management of persistent pain. Although these drugs are intended to support improved comfort and function, the inherent risk of abuse or addiction must be considered in the delivery of care. The experience of living with persistent pain often includes depression, fear, loss, and anxiety, leading to feelings of hopelessness, helplessness, and spiritual crisis. Collectively, these factors represent an increased risk for all patients, particularly those with a history of substance abuse or addiction. This companion article to the American Society for Pain Management Nursing "Position Statement on Pain Management in Patients with Substance Use Disorders" (2012) focuses on the intersection of persistent pain, substance use disorder (SUD), and chronic opioid therapy and the clinical implications of monitoring adherence with safe use of opioids for those with persistent pain. This paper presents an approach to the comprehensive assessment of persons with persistent pain when receiving opioid therapy by presenting an expansion of the biopsychosocial model to include spiritual factors associated with pain and SUD, thus formulating a biopsychosocial-spiritual approach to mitigate risk. Key principles are provided for adherence monitoring using the biopsychosocial-spiritual assessment model developed by the authors as a means of promoting sensitive and respectful care. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Treatment with Sulforaphane Produces Antinociception and Improves Morphine Effects during Inflammatory Pain in Mice.

PubMed

Redondo, Alejandro; Chamorro, Pablo Aníbal Ferreira; Riego, Gabriela; Leánez, Sergi; Pol, Olga

2017-12-01

The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) exerts potent antioxidative and anti-inflammatory effects; however, its participation in the modulation of chronic inflammatory pain and on the antinociceptive effects of μ -opioid receptor (MOR) agonists has not been evaluated. We investigated whether the induction of Nrf2 could alleviate chronic inflammatory pain and augment the analgesic effects of morphine and mechanisms implicated. In male C57BL/6 mice with inflammatory pain induced by complete Freund's adjuvant (CFA) subplantarly administered, we assessed: 1) antinociceptive actions of the administration of 5 and 10 mg/kg of a Nrf2 activator, sulforaphane (SFN); and 2) effects of SFN on the antinociceptive actions of morphine and on protein levels of Nrf2, heme oxygenase 1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1) enzymes, microglial activation and inducible nitric oxide synthase (NOS2) overexpression, as well as on mitogen-activated protein kinase (MAPK) and MOR expression in the spinal cord and paw of animals with inflammatory pain. Results showed that treatment with SFN inhibited allodynia and hyperalgesia induced by CFA and increased the local antinociceptive actions of morphine. This treatment also augmented the expression of Nrf2, HO-1, NQO1, and MOR, and inhibited NOS2 and CD11b/c overexpression and MAPK phosphorylation induced by inflammation. Thus, this study shows that the induction of Nrf2 might inhibit inflammatory pain and enhance the analgesic effects of morphine by inhibiting oxidative stress and inflammatory responses induced by peripheral inflammation. This study suggests the administration of SFN alone and in combination with morphine are potential new ways of treating chronic inflammatory pain. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

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

Neuropathic pain in experimental autoimmune neuritis is associated with altered electrophysiological properties of nociceptive DRG neurons.

PubMed

Taha, Omneya; Opitz, Thoralf; Mueller, Marcus; Pitsch, Julika; Becker, Albert; Evert, Bernd Oliver; Beck, Heinz; Jeub, Monika

2017-11-01

Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy characterized by rapidly progressive paresis and sensory disturbances. Moderate to severe and often intractable neuropathic pain is a common symptom of GBS, but its underlying mechanisms are unknown. Pathology of GBS is classically attributed to demyelination of large, myelinated peripheral fibers. However, there is increasing evidence that neuropathic pain in GBS is associated with impaired function of small, unmyelinated, nociceptive fibers. We therefore examined the functional properties of small DRG neurons, the somata of nociceptive fibers, in a rat model of GBS (experimental autoimmune neuritis=EAN). EAN rats developed behavioral signs of neuropathic pain. This was accompanied by a significant shortening of action potentials due to a more rapid repolarization and an increase in repetitive firing in a subgroup of capsaicin-responsive DRG neurons. Na + current measurements revealed a significant increase of the fast TTX-sensitive current and a reduction of the persistent TTX-sensitive current component. These changes of Na + currents may account for the significant decrease in AP duration leading to an overall increase in excitability and are therefore possibly directly linked to pathological pain behavior. Thus, like in other animal models of neuropathic and inflammatory pain, Na + channels seem to be crucially involved in the pathology of GBS and may constitute promising targets for pain modulating pharmaceuticals. Copyright © 2017 Elsevier Inc. All rights reserved.

The Impact of Persistent Pain on Working Memory and Learning

ERIC Educational Resources Information Center

Smith, Alexander; Ayres, Paul

2014-01-01

The study reviewed the evidence that persistent pain has the capacity to interrupt and consume working memory resources. It was argued that individuals with persistent pain essentially operate within a compromised neurocognitive paradigm of limited working memory resources that impairs task performance. Using cognitive load theory as a theoretical…

Are ultrasound features at the first metatarsophalangeal joint associated with clinically-assessed pain and function? A study of people with gout, asymptomatic hyperuricaemia and normouricaemia.

PubMed

Stewart, Sarah; Dalbeth, Nicola; Vandal, Alain C; Allen, Bruce; Miranda, Rhian; Rome, Keith

2017-01-01

The first metatatarsophalangeal joint (1st MTP joint) is a common location for sonographic evidence of urate deposition in people with gout and asymptomatic hyperuricaemia. However, it is unclear whether these are related to clinically-assessed pain and function. This study aimed to determine the association between ultrasound features and clinical characteristics of the 1st MTP joint in people with gout, asymptomatic hyperuricaemia and age- and sex-matched normouricaemic individuals. Twenty-three people with gout, 29 with asymptomatic hyperuricaemia and 34 with normouricaemia participated in a cross-sectional study. No participant had clinical evidence of acute inflammatory arthritis at the time of assessment. Four sonographic features at the 1st MTP joint were analysed: double contour sign, tophus, bone erosion and synovitis. Clinical characteristics included in the analysis were 1st MTP joint pain, overall foot pain and disability, 1st MTP joint temperature, 1st MTP joint range of motion and gait velocity. Statistical analyses adjusted for the diagnostic group of the participant. After accounting for the diagnostic group, double contour sign was associated with higher foot pain and disability scores ( P  < 0.001). Ultrasound tophus was associated with higher foot pain and disability scores ( P  < 0.001), increased temperature ( P  = 0.005), and reduced walking velocity ( P  = 0.001). No associations were observed between ultrasound synovitis or erosion and the clinical characteristics. Ultrasound features of urate crystal deposition, rather than soft tissue inflammation or bone erosion, are associated with clinical measures of foot-related functional impairment and disability even in the absence of clinical evidence of current acute inflammatory arthritis. This association persisted regardless of the diagnosis of the participant as having gout or asymptomatic hyperuricaemia.

Effects of fluoxetine on changes of pain sensitivity in chronic stress model rats.

PubMed

Lian, Yan-Na; Chang, Jin-Long; Lu, Qi; Wang, Yi; Zhang, Ying; Zhang, Feng-Min

2017-06-09

Exposure to stress could facilitate or inhibit pain responses (stress-induced hyperalgesia or hypoalgesia, respectively). Fluoxetine is a selective serotonin (5-HT) reuptake inhibitor antidepressant. There have been contradictory reports on whether fluoxetine produces antinociceptive effects. The purpose of this study was to elucidate changes in pain sensitivity after chronic stress exposure, and the effects of fluoxetine on these changes. We measured thermal, mechanical, and formalin-induced acute and inflammatory pain by using the tail-flick, von Frey, and formalin tests respectively. The results showed that rats exposed to chronic stress exhibited thermal and formalin-induced acute and inflammatory hypoalgesia and transient mechanical hyperalgesia. Furthermore, fluoxetine promoted hypoalgesia in thermal and inflammatory pain and induced mechanical hyperalgesia. Our results indicate that the 5-HT system could be involved in hypoalgesia of thermal and inflammatory pain and induce transient mechanical hyperalgesia after stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Rab7-a novel redox target that modulates inflammatory pain processing.

PubMed

Kallenborn-Gerhardt, Wiebke; Möser, Christine V; Lorenz, Jana E; Steger, Mirco; Heidler, Juliana; Scheving, Reynir; Petersen, Jonas; Kennel, Lea; Flauaus, Cathrin; Lu, Ruirui; Edinger, Aimee L; Tegeder, Irmgard; Geisslinger, Gerd; Heide, Heinrich; Wittig, Ilka; Schmidtko, Achim

2017-07-01

Chronic pain is accompanied by production of reactive oxygen species (ROS) in various cells that are important for nociceptive processing. Recent data indicate that ROS can trigger specific redox-dependent signaling processes, but the molecular targets of ROS signaling in the nociceptive system remain largely elusive. Here, we performed a proteome screen for pain-dependent redox regulation using an OxICAT approach, thereby identifying the small GTPase Rab7 as a redox-modified target during inflammatory pain in mice. Prevention of Rab7 oxidation by replacement of the redox-sensing thiols modulates its GTPase activity. Immunofluorescence studies revealed Rab7 expression to be enriched in central terminals of sensory neurons. Knockout mice lacking Rab7 in sensory neurons showed normal responses to noxious thermal and mechanical stimuli; however, their pain behavior during inflammatory pain and in response to ROS donors was reduced. The data suggest that redox-dependent changes in Rab7 activity modulate inflammatory pain sensitivity.

The influence of self-reported leisure time physical activity and the body mass index on recovery from persistent back pain among men and women: a population-based cohort study.

PubMed

Bohman, Tony; Alfredsson, Lars; Hallqvist, Johan; Vingård, Eva; Skillgate, Eva

2013-04-25

There is limited knowledge about leisure time physical activity and the body mass index (BMI) as prognostic factors for recovery from persistent back pain. The aim of this study was to assess the influence of leisure time physical activity and BMI on recovery from persistent back pain among men and women in a general population. The study population (n=1836) in this longitudinal cohort study consisted of participants reporting persistent back pain in the baseline questionnaire in 2002-2003. Data on leisure time physical activity, BMI and potential confounders were also collected at baseline. Information on recovery from persistent back pain (no back pain periods ≥ 7 days during the last 5 years) was obtained from the follow-up questionnaire in 2007. Log-binomial models were applied to calculate Risk Ratios with 95 percent Confidence Intervals (CI) comparing physically active and normal weight groups versus sedentary and overweight groups. Compared to a sedentary leisure time, all measured levels of leisure time physical activity were associated with a greater chance of recovery from persistent back pain among women. The adjusted Risk Ratios was 1.46 (95% CI: 1.06, 2.01) for low leisure time physical activity, 1.51 (95% CI: 1.02, 2.23) for moderate leisure time physical activity, and 1.67 (95% CI: 1.08, 2.58) for high leisure time physical activity. There were no indications that leisure time physical activity influenced recovery among men, or that BMI was associated with recovery from persistent back pain either among men or among women. Regular leisure time physical activity seems to improve recovery from persistent back pain among women.

"When I feel the worst pain, I look like shit" - body image concerns in persistent pain.

PubMed

Sündermann, Oliver; Rydberg, Karin; Linder, Ludwig; Linton, Steven James

2018-04-17

Persistent pain is a pervasive condition that is often associated with a distorted body image. Most research into pain and body image investigated neural or physiological correlates (e.g. phantom limb pain), and much less is known about the psychological experience of body image changes in response to pain such as appearance concerns. The aim was to examine body image concerns in people with persistent pain, in particular appearance concerns and related coping behaviours and appearance-related emotions such as anger and shame. Design was cross-sectional and data was collected through in-depth semi-structured interviews with people suffering from persistent musculoskeletal pain (n=7; six females; age=19-56), and analysed with inductive thematic analysis (TA). Two main themes were identified: "Relationship to the painful body" and "Dissatisfaction with the body", each containing three subthemes, along with the side-theme "Appearance concerns affected by pain and mood". All participants reported appearance concerns, predominantly about their weight and related coping behaviours such as avoidance of mirrors, exercising or dieting and pain-induced mood changes that were associated with a negative body image. People with persistent pain report appearance concerns, often related to pain-induced negative mood changes, and reduced functioning. It remains unclear to what extent attitudes towards the body change over time in accordance with pain. A wider concept of body image is required, including the perception of reduced functioning, related appraisals (e.g. "I look weak and old") and appearance investment.

Persistent of Neck/Shoulder Pain among Computer Office Workers with Specific Attention to Pain Expectation, Somatization Tendency, and Beliefs.

PubMed

Sadeghian, Farideh; Raei, Mehdi; Amiri, Mohammad

2014-09-01

Neck and shoulder pains are the prevalent complaints among computer office workers. The purpose of this study was to assess the relationship of somatization tendency, expectation of pain, mental health and beliefs about causation of pain with persistence of neck/shoulder pains among computer office workers. This research is a kind of prospective cohort study with 1-year follow-up. It has done among all eligible computer office workers of Shahroud universities (n = 182) in 2008-2009 and 1-year later. Data were collected using the Cultural and Psychosocial Influences on Disability questionnaire. Multiple logistic regression analysis was used to analyze the data through SPSS (P < 0.05). At the baseline 100 (54.9%) of participants reported neck/shoulder pains and at follow-up 34.3% of them reported persistence pains. Significant relationships were found between persistence of neck/shoulder pains and negative expectation about pain in next 1-year P = 0.002, (odds ratio [OR] =8.3, 95% confidence interval [CI]: 2.1-32.9) and somatization tendency P = 0.01, (OR = 6.5, 95% CI: 1.6-27.4). Pain expectation and somatization tendency recognized as associated risk factors of persistent neck/shoulder pain among computer operators. This confirmed some other similar studies on work-related musculoskeletal disorders in Europe countries in recent years.

The impact of anxiety and catastrophizing on interleukin-6 responses to acute painful stress

PubMed Central

Lazaridou, Asimina; Martel, Marc O; Cahalan, Christine M; Cornelius, Marise C; Franceschelli, Olivia; Campbell, Claudia M; Haythornthwaite, Jennifer A; Smith, Michael; Riley, Joseph; Edwards, Robert R

2018-01-01

Objective To examine the influence of anxiety and pain-related catastrophizing on the time course of acute interleukin-6 (IL-6) responses to standardized noxious stimulation among patients with chronic pain. Methods Data were collected from 48 participants in the following demographically matched groups: patients with chronic pain (n=36) and healthy controls (n=12). Participants underwent a series of Quantitative Sensory Testing (QST) procedures assessing responses to mechanical and thermal stimuli during two separate visits, in a randomized order. One visit consisted of standard, moderately painful QST procedures, while the other visit involved nonpainful analogs to these testing procedures. Blood samples were taken at baseline, and then for up to 2 hours after QST in order to study the time course of IL-6 responses. Results Results of multilevel analyses revealed that IL-6 responses increased across assessment time points in both visits (p<0.001). While patients with chronic pain and healthy controls did not differ in the magnitude of IL-6 responses, psychological factors influenced IL-6 trajectories only in the chronic pain group. Among patients, increases in catastrophizing over the course of the QST session were associated with elevated IL-6 responses only during the painful QST session (p<0.05). When controlling for anxiety, results indicated that the main multilevel model among patients remained significant (p<0.05). Conclusion Under specific conditions (eg, application of a painful stressor), catastrophizing may be associated with amplified proinflammatory responses in patients with persistent pain. These findings suggest that psychosocial interventions that reduce negative pain-related cognitions may benefit patients’ inflammatory profiles. PMID:29636630

Acetaminophen Reduces acute and persistent incisional pain after hysterectomy.

PubMed

Koyuncu, Onur; Hakimoglu, Sedat; Ugur, Mustafa; Akkurt, Cagla; Turhanoglu, Selim; Sessler, Daniel; Turan, Alparslan

2018-05-15

Acetaminophen is effective for acute surgical pain, but whether it reduces persistent incision pain remains unknown. We tested the primary hypothesis that patients given perioperative acetaminophen have less incisional pain three months after surgery. Our secondary hypotheses were that patients randomized to acetaminophen have less postoperative pain and analgesic consumption, and better functional recovery at three months. 140 patients having abdominal hysterectomy were randomly assigned to: 1)intravenous acetaminophen (4 g/day for 72 postoperative hours); or, 2) saline placebo. The primary outcome was incisional pain visual analog scale (VAS) at three months after surgery. The secondary outcomes were (1, 2) postoperative VAS scores while laying and sitting and (3) total patient-controlled intravenous tramadol consumption during the initial 24 hours, (4) DN4 questionnaires and (5) SF-12 at three months after surgery. The persistent incisional pain scores at three months were significantly lower in acetaminophen (median [Q1, Q3]: 0 [0, 0]) as compared with saline group (0 [0, 1]) (P = 0.002). Specifically, 89%, 9%, and 2% of acetaminophen patients with VAS pain score at three months of 0, 1, and 2 or more, as compared with 66%, 23%, and 10% in the saline group (odds ratio: 2.19 (95% CI: 1.33, 3.59), P = 0.002). Secondly, postoperative pain scores both laying and sitting were significantly lower in the acetaminophen group. Acetaminophen group had significantly better DN4 score and mental health related but not physical health related quality of life. Our results suggest that acetaminophen reduces the risk and intensity of persistent incisional pain. However, there are other mechanisms by which acetaminophen might reduce persistent pain. Anesthesia, acetaminophen, Persistent surgical pain, Postoperative acute pain.

Effects of sevoflurane on carrageenan- and fentanyl-induced pain hypersensitivity in Sprague-Dawley rats.

PubMed

Richebé, Philippe; Rivalan, Bertrand; Rivat, Cyril; Laulin, Jean-Paul; Janvier, Gérard; Maurette, Pierre; Simonnet, Guy

2009-02-01

Opioids are widely used for anesthesia but paradoxically induce postoperative pain hypersensitivity via N-methyl-D: -aspartate (NMDA) receptor modulation. Sevoflurane effects on opioid-induced hyperalgesia have not been yet evaluated in vivo. Nevertheless, some experimental in vitro studies reported anti-NMDA receptor properties for sevoflurane. The aim of this study was to evaluate sevoflurane effects on fentanyl-induced hyperalgesia in opioid-naive rats and in rats with inflammatory pain. Sevoflurane effects on hyperalgesia were evaluated in Sprague-Dawley rats: opioid-naive rats, rats treated with fentanyl (4 x 60 microg kg(-1)) and rats with inflammatory pain (carrageenan) treated with fentanyl (4 x 60 microg kg(-1)). On day zero, subcutaneous fentanyl injections were administered and inflammatory pain was induced with one carrageenan injection in one hind paw. Rats were exposed to low concentrations of sevoflurane (1.0 or 1.5%) on day zero prior to fentanyl injections and inflammatory pain induction, and for the duration of the fentanyl analgesic effect. The nociceptive threshold (Randall-Selitto test) was evaluated daily for 7 days. On day seven, naloxone was injected and the nociceptive threshold was assessed 5 min later. In rats without inflammatory pain but treated with fentanyl on day zero, sevoflurane 1.0% reversed the early (day zero) and long-lasting (day zero to day three) hyperalgesia classically described after high-doses of fentanyl (P < 0.05). This sevoflurane concentration antagonized the hyperalgesia induced by naloxone on day seven (P = 0.33). In a second experiment in rats with inflammatory pain, exposure to low concentrations of sevoflurane (1.0 and 1.5%) did not reduce fentanyl-induced hyperalgesia (P > 0.05), but nevertheless antagonized the naloxone induced hyperalgesia on day seven (P = 0.061). Relatively low sevoflurane concentrations (1.0%) reverse fentanyl-induced hyperalgesia in rats without inflammatory pain. Nevertheless, the lack of effect of sevoflurane concentrations of 1.0% and 1.5% to oppose hyperalgesia following high-dose fentanyl and inflammatory pain suggests that sevoflurane anti-hyperalgesic properties are weak.

Investigating the Modality and Redundancy Effects for Learners with Persistent Pain

ERIC Educational Resources Information Center

Smith, Alexander; Ayres, Paul

2016-01-01

Two experiments were conducted to investigate how individuals with persistent pain would respond to instructional materials designed to promote the modality and redundancy effects. It was predicted that persistent pain would reduce the positive impact of narrated text due to reduced working memory capacity. One hundred thirty-seven full-time…

The role of TRPV1 in different subtypes of dorsal root ganglion neurons in rat chronic inflammatory nociception induced by complete Freund's adjuvant

PubMed Central

Yu, Lu; Yang, Fei; Luo, Hao; Liu, Feng-Yu; Han, Ji-Sheng; Xing, Guo-Gang; Wan, You

2008-01-01

Background The present study aims to investigate the role of transient receptor potential vanilloid 1 (TRPV1) in dorsal root ganglion (DRG) neurons in chronic pain including thermal hyperalgesia and mechanical allodynia. Chronic inflammatory nociception of rats was produced by intraplantar injection of complete Freund's adjuvant (CFA) and data was collected until day 28 following injection. Results Thermal hyperalgesia was evident from day 1 to day 28 with peak at day 7, while mechanical allodynia persisted from day 1 to day 14 and was greatest at day 7. Intrathecal administration of AMG 9810 at day 7, a selective TRPV1 antagonist, significantly reduced thermal hyperalgesia and mechanical allodynia. TRPV1 expression in DRG detected by Western blotting was increased relative to baseline throughout the observation period. Double labeling of TRPV1 with neuronal marker neurofilament 200 (NF200), calcitonin gene-related peptide (CGRP) or isolectin B4 (IB4) was used to distinguish different subtypes of DRG neurons. TRPV1 expression was increased in the medium-sized myelinated A fiber (NF200 positive) neurons and in small non-peptidergic (IB4 positive) neurons from day 1 to day 14 and was increased in small peptidergic (CGRP positive) neurons from day 1 to day 28. Conclusion TRPV1 expression increases in all three types of DRG neurons after CFA injection and plays a role in CFA-induced chronic inflammatory pain including thermal hyperalgesia and mechanical allodynia. PMID:19055783

Idiopathic ophthalmodynia and idiopathic rhinalgia: two topographic facial pain syndromes.

PubMed

Pareja, Juan A; Cuadrado, María L; Porta-Etessam, Jesús; Fernández-de-las-Peñas, César; Gili, Pablo; Caminero, Ana B; Cebrián, José L

2010-09-01

To describe 2 topographic facial pain conditions with the pain clearly localized in the eye (idiopathic ophthalmodynia) or in the nose (idiopathic rhinalgia), and to propose their distinction from persistent idiopathic facial pain. Persistent idiopathic facial pain, burning mouth syndrome, atypical odontalgia, and facial arthromyalgia are idiopathic facial pain syndromes that have been separated according to topographical criteria. Still, some other facial pain syndromes might have been veiled under the broad term of persistent idiopathic facial pain. Through a 10-year period we have studied all patients referred to our neurological clinic because of facial pain of unknown etiology that might deviate from all well-characterized facial pain syndromes. In a group of patients we have identified 2 consistent clinical pictures with pain precisely located either in the eye (n=11) or in the nose (n=7). Clinical features resembled those of other localized idiopathic facial syndromes, the key differences relying on the topographic distribution of the pain. Both idiopathic ophthalmodynia and idiopathic rhinalgia seem specific pain syndromes with a distinctive location, and may deserve a nosologic status just as other focal pain syndromes of the face. Whether all such focal syndromes are topographic variants of persistent idiopathic facial pain or independent disorders remains a controversial issue.

Anti-hypernociceptive properties of agmatine in persistent inflammatory and neuropathic models of pain in mice.

PubMed

Paszcuk, Ana Flávia; Gadotti, Vinicius M; Tibola, Daiane; Quintão, Nara L M; Rodrigues, Ana Lúcia S; Calixto, João B; Santos, Adair R S

2007-07-23

The present study examined the anti-hypernociceptive effects of agmatine (AGM) in acute and chronic models of behavioural pain in mice. Agmatine (30 mg/kg, i.p. 30 min early), produced time-dependent inhibition of mechanical hypernociception induced by Complete Freund's Adjuvant (CFA) injected in the mice paw (inhibition of 52+/-7%) after 4 h. Given chronically (twice a day) during 10 days, AGM significantly reversed the mechanical hypernociception caused by CFA (inhibition of 43+/-6% to 67+/-5%). Moreover, AGM also significantly reduced the mechanical hypernociception caused by partial sciatic nerve ligation (PSNL) during 6 h, with inhibition of 81+/-8%. In thermal hypernociception (cold stimuli) caused by PSNL the antinociceptive effect of AGM was prolonged by 4 h with inhibition of 97+/-3% observed 1 h after the treatment. Nevertheless, AGM failed to inhibit the paw oedema caused by CFA and the myeloperoxidase enzyme activity. Of note, AGM (10-100 mg/kg, i.p., 30 min before) also elicited a pronounced inhibition of the biting response induced by TNF-alpha and IL-1beta in mice, with mean ID(50) values of 61.3 mg/kg (47.7-78.6 mg/kg) and 30.4 mg/kg (18.6-49.8 mg/kg) and inhibitions of 75+/-5% and 66+/-6%, respectively. Together, present and previous findings show that AGM given systemically is effective in inhibiting mechanical and thermal hypernociception present in chronic inflammatory processes caused by CFA and also the neuropathic pain caused by PSNL.

Long-term pain prevalence and health-related quality of life outcomes for patients enrolled in a ketamine versus morphine for prehospital traumatic pain randomised controlled trial.

PubMed

Jennings, Paul A; Cameron, Peter; Bernard, Stephen; Walker, Tony; Jolley, Damien; Fitzgerald, Mark; Masci, Kevin

2014-10-01

Improved early pain control may affect the longer-term prevalence of persistent pain. In a previous randomised, controlled trial, we found that the administration of ketamine on hospital arrival decreased pain scores to a greater extent than morphine alone in patients with prehospital traumatic pain. In this follow-up study, we sought to determine the prevalence of persistent pain and whether there were differences in patients who received ketamine or morphine. This study was a long-term follow-up study of the prehospital, prospective, randomised, controlled, open-label study comparing ketamine with morphine in patients with trauma and a verbal pain score of >5 after 5 mg intravenous morphine. Patients were followed-up by telephone 6-12 months after enrollment, and a questionnaire including the SF-36 (V.2) health-related quality of life survey and the Verbal Numerical Rating Scale for pain was administered. A total of 97/135 (72%) patients were able to be followed-up 6-12 months after enrollment between July 2008 and July 2010. Overall, 44/97 (45%) participants reported persistent pain related to their injury, with 3/97 (3%) reporting persistent severe pain. The prevalence of persistent pain was the same between study groups (22/50 (44%) for the ketamine group vs 22/47 (46%) for the morphine group). There was no difference in the SF-36 scores between study arms. There is a high incidence of persistent pain after traumatic injury, even in patients with relatively minor severity of injury. Although decreased pain scores at hospital arrival are achieved with ketamine compared with morphine, this difference does not affect the prevalence of persistent pain or health-related quality of life 6 months after injury. Further larger studies are required to confirm this finding. Australian and New Zealand Clinical Trials Registry (ACTRN12607000441415). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Interacting influences of gender and chronic pain status on parasympathetically mediated heart rate variability in adolescents and young adults.

PubMed

Walker, Lynn S; Stone, Amanda L; Smith, Craig A; Bruehl, Stephen; Garber, Judy; Puzanovova, Martina; Diedrich, André

2017-08-01

Considerable research links chronic pain to autonomic nervous system (ANS) dysfunction, specifically low heart rate variability (HRV) mediated by reduced parasympathetic activity. However, little is known about factors that influence ANS function in chronic pain. The ANS is the primary pathway for brain-gut communication, making it of particular interest in gastrointestinal disorders, such as irritable bowel syndrome, characterized by functional abdominal pain (FAP). We evaluated the relation of sex, pain severity, and psychological stress to ANS function in adolescents/young adults from a database of pediatric FAP and control participants enrolled 8 years earlier in a prospective study of pain. At follow-up in adolescence/young adulthood (Mean age = 19.46, SD = 3.48), we classified participants as Pain-Remit (n = 130), Pain-Persist (n = 96), and pain-free controls (n = 123). We recorded electrocardiogram data at rest and during laboratory stressors. Results demonstrated significantly lower HRV in Pain-Persist females compared with Pain-Remit females, female controls, and all males regardless of pain category. Spectral analysis of electrocardiogram showed that Pain-Persist females had reduced power in the high frequency domain of cardiac activity, ie, reduced parasympathetic "braking" of sympathetic activity, both at rest and during stress. Pain-Remit females exhibited levels of autonomic imbalance intermediate between those of females with persistent FAP and all other participants. Parasympathetically mediated low HRV in young women with persistent FAP may reflect a peripheral mechanism (eg, gut dysfunction) or a central nervous system mechanism (eg, pain amplification or poor emotion self-regulation) involving prolonged sympathetic activation.

Is exercise effective for the management of neck pain and associated disorders or whiplash-associated disorders? A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

PubMed

Southerst, Danielle; Nordin, Margareta C; Côté, Pierre; Shearer, Heather M; Varatharajan, Sharanya; Yu, Hainan; Wong, Jessica J; Sutton, Deborah A; Randhawa, Kristi A; van der Velde, Gabrielle M; Mior, Silvano A; Carroll, Linda J; Jacobs, Craig L; Taylor-Vaisey, Anne L

2016-12-01

In 2008, the Neck Pain Task Force (NPTF) recommended exercise for the management of neck pain and whiplash-associated disorders (WAD). However, no evidence was available on the effectiveness of exercise for Grade III neck pain or WAD. Moreover, limited evidence was available to contrast the effectiveness of various types of exercises. To update the findings of the NPTF on the effectiveness of exercise for the management of neck pain and WAD grades I to III. Systematic review and best evidence synthesis. Studies comparing the effectiveness of exercise to other conservative interventions or no intervention. Outcomes of interest included self-rated recovery, functional recovery, pain intensity, health-related quality of life, psychological outcomes, and/or adverse events. We searched eight electronic databases from 2000 to 2013. Eligible studies were critically appraised using the Scottish Intercollegiate Guidelines Network criteria. The results of scientifically admissible studies were synthesized following best-evidence synthesis principles. We retrieved 4,761 articles, and 21 randomized controlled trials (RCTs) were critically appraised. Ten RCTs were scientifically admissible: nine investigated neck pain and one addressed WAD. For the management of recent neck pain Grade I/II, unsupervised range-of-motion exercises, nonsteroidal anti-inflammatory drugs and acetaminophen, or manual therapy lead to similar outcomes. For recent neck pain Grade III, supervised graded strengthening is more effective than advice but leads to similar short-term outcomes as a cervical collar. For persistent neck pain and WAD Grade I/II, supervised qigong and combined strengthening, range-of-motion, and flexibility exercises are more effective than wait list. Additionally, supervised Iyengar yoga is more effective than home exercise. Finally, supervised high-dose strengthening is not superior to home exercises or advice. We found evidence that supervised qigong, Iyengar yoga, and combined programs including strengthening, range of motion, and flexibility are effective for the management of persistent neck pain. We did not find evidence that one supervised exercise program is superior to another. Overall, most studies reported small effect sizes suggesting that a small clinical effect can be expected with the use of exercise alone. Copyright © 2014 Elsevier Inc. All rights reserved.

Diagnosis and Management of Vertebral Compression Fractures.

PubMed

McCarthy, Jason; Davis, Amy

2016-07-01

Vertebral compression fractures (VCFs) are the most common complication of osteoporosis, affecting more than 700,000 Americans annually. Fracture risk increases with age, with four in 10 white women older than 50 years experiencing a hip, spine, or vertebral fracture in their lifetime. VCFs can lead to chronic pain, disfigurement, height loss, impaired activities of daily living, increased risk of pressure sores, pneumonia, and psychological distress. Patients with an acute VCF may report abrupt onset of back pain with position changes, coughing, sneezing, or lifting. Physical examination findings are often normal, but can demonstrate kyphosis and midline spine tenderness. More than two-thirds of patients are asymptomatic and diagnosed incidentally on plain radiography. Acute VCFs may be treated with analgesics such as acetaminophen, nonsteroidal anti-inflammatory drugs, narcotics, and calcitonin. Physicians must be mindful of medication adverse effects in older patients. Other conservative therapeutic options include limited bed rest, bracing, physical therapy, nerve root blocks, and epidural injections. Percutaneous vertebral augmentation, including vertebroplasty and kyphoplasty, is controversial, but can be considered in patients with inadequate pain relief with nonsurgical care or when persistent pain substantially affects quality of life. Family physicians can help prevent vertebral fractures through management of risk factors and the treatment of osteoporosis.

From acute to persistent low back pain: a longitudinal investigation of somatosensory changes using quantitative sensory testing—an exploratory study

PubMed Central

Marcuzzi, Anna; Wrigley, Paul J.; Dean, Catherine M.; Graham, Petra L.; Hush, Julia M.

2018-01-01

Abstract Introduction: Chronic low back pain (LBP) is commonly associated with generalised pain hypersensitivity. It is suggested that such somatosensory alterations are important determinants for the transition to persistent pain from an acute episode of LBP. Although cross-sectional research investigating somatosensory function in the acute stage is developing, no longitudinal studies designed to evaluate temporal changes have been published. Objectives: This exploratory study aimed to investigate the temporal development of somatosensory changes from the acute stage of LBP to up to 4 months from onset. Methods: Twenty-five people with acute LBP (<3 weeks' duration) and 48 pain-free controls were prospectively assessed at baseline using quantitative sensory testing with the assessor blinded to group allocation, and again at 2 and 4 months. Psychological variables were concurrently assessed. People with acute LBP were classified based on their average pain severity over the previous week at 4 months as recovered (≤1/10 numeric rating scale) or persistent (≥2/10 numeric rating scale) LBP. Results: In the persistent LBP group, (1) there was a significant decrease in pressure pain threshold between 2 and 4 months (P < 0.013), and at 4 months, pressure pain threshold was significantly different from the recovered LBP group (P < 0.001); (2) a trend towards increased temporal summation was found at 2 months and 4 months, at which point it exceeded 2 SDs beyond the pain-free control reference value. Pain-related psychological variables were significantly higher in those with persistent LBP compared with the recovered LBP group at all time points (P < 0.05). Conclusion: Changes in mechanical pain sensitivity occurring in the subacute stage warrant further longitudinal evaluation to better understand the role of somatosensory changes in the development of persistent LBP. Pain-related cognitions at baseline distinguished persistent from the recovered LBP groups, emphasizing the importance of concurrent evaluation of psychological contributors in acute LBP. PMID:29756087

From acute to persistent low back pain: a longitudinal investigation of somatosensory changes using quantitative sensory testing-an exploratory study.

PubMed

Marcuzzi, Anna; Wrigley, Paul J; Dean, Catherine M; Graham, Petra L; Hush, Julia M

2018-03-01

Chronic low back pain (LBP) is commonly associated with generalised pain hypersensitivity. It is suggested that such somatosensory alterations are important determinants for the transition to persistent pain from an acute episode of LBP. Although cross-sectional research investigating somatosensory function in the acute stage is developing, no longitudinal studies designed to evaluate temporal changes have been published. This exploratory study aimed to investigate the temporal development of somatosensory changes from the acute stage of LBP to up to 4 months from onset. Twenty-five people with acute LBP (<3 weeks' duration) and 48 pain-free controls were prospectively assessed at baseline using quantitative sensory testing with the assessor blinded to group allocation, and again at 2 and 4 months. Psychological variables were concurrently assessed. People with acute LBP were classified based on their average pain severity over the previous week at 4 months as recovered (≤1/10 numeric rating scale) or persistent (≥2/10 numeric rating scale) LBP. In the persistent LBP group, (1) there was a significant decrease in pressure pain threshold between 2 and 4 months ( P < 0.013), and at 4 months, pressure pain threshold was significantly different from the recovered LBP group ( P < 0.001); (2) a trend towards increased temporal summation was found at 2 months and 4 months, at which point it exceeded 2 SDs beyond the pain-free control reference value. Pain-related psychological variables were significantly higher in those with persistent LBP compared with the recovered LBP group at all time points ( P < 0.05). Changes in mechanical pain sensitivity occurring in the subacute stage warrant further longitudinal evaluation to better understand the role of somatosensory changes in the development of persistent LBP. Pain-related cognitions at baseline distinguished persistent from the recovered LBP groups, emphasizing the importance of concurrent evaluation of psychological contributors in acute LBP.

Semimembranosus Tendinopathy

PubMed Central

Bylund, William E.; de Weber, Kevin

2010-01-01

Context: Semimembranosus tendinopathy (SMT) is an uncommon cause of chronic knee pain that is rarely described in the medical literature and may be underdiagnosed or inadequately treated owing to a lack of understanding of the condition. Evidence Acquisition: A search of the entire PubMed (MEDLINE) database using the terms knee pain semimembranosus and knee tendinitis semimembranosus, returned only 5 references about SMT—4 case series and 1 case report—and several relevant anatomical or imaging references. Results: The incidence of SMT is unknown in the athletic population and is probably more common in older patients. The usual presentation for SMT is aching posteromedial knee pain. Physical examination can usually localize the area of tenderness to the distal semimembranosus tendon or its insertion on the medial proximal tibia. In unclear cases, bone scan, magnetic resonance imaging, or ultrasound may distinguish SMT from other causes of posteromedial knee pain. Treatment should begin with relative rest, ice, nonsteroidal anti-inflammatory drugs, and rehabilitative exercise. In the minority of cases that persist greater than 3 months, a corticosteroid injection at the tendon insertion site may be effective. Surgery to reroute and reattach the tendon is rarely needed but may be effective. Conclusion: SMT is an uncommon cause of knee pain, but timely diagnosis can lead to effective treatments. PMID:23015963

Vascular Permeability and Remodelling Coincide with Inflammatory and Reparative Processes after Joint Bleeding in Factor VIII-Deficient Mice.

PubMed

Cooke, Esther J; Zhou, Jenny Y; Wyseure, Tine; Joshi, Shweta; Bhat, Vikas; Durden, Donald L; Mosnier, Laurent O; Drygalski, Annette von

2018-06-01

Vascular remodelling is a prominent feature of haemophilic arthropathy (HA) that may underlie re-bleeding, yet the nature of vascular changes and underlying mechanisms remain largely unknown. Here, we aimed to characterize synovial vascular remodelling and vessel integrity after haemarthrosis, as well as temporal changes in inflammatory and tissue-reparative pathways. Thirty acutely painful joints in patients with haemophilia (PWH) were imaged by musculoskeletal ultrasound with Power Doppler (MSKUS/PD) to detect vascular abnormalities and bloody effusions. Nineteen out of 30 painful joint episodes in PWH were associated with haemarthrosis, and abnormal vascular perfusion was unique to bleeding joints. A model of induced haemarthrosis in factor VIII (FVIII)-deficient mice was used for histological assessment of vascular remodelling (α-smooth muscle actin [αSMA] expression), and monitoring of in vivo vascular perfusion and permeability by MSKUS/PD and albumin extravasation, respectively. Inflammatory (M1) and reparative (M2) macrophage markers were quantified in murine synovium over a 10-week time course by real-time polymerase chain reaction. The abnormal vascular perfusion observed in PWH was recapitulated in FVIII-deficient mice after induced haemarthrosis. Neovascularization and increased vessel permeability were apparent 2 weeks post-bleed in FVIII-deficient mice, after a transient elevation of inflammatory macrophage M1 markers. These vascular changes subsided by week 4, while vascular remodelling, evidenced by architectural changes and pronounced αSMA expression, persisted alongside a reparative macrophage M2 response. In conclusion, haemarthrosis leads to transient inflammation coupled with neovascularization and associated vascular permeability, while subsequent tissue repair mechanisms coincide with vascular remodelling. Together, these vascular changes may promote re-bleeding and HA progression. Schattauer GmbH Stuttgart.

Pain and Emotion: A Biopsychosocial Review of Recent Research

PubMed Central

Lumley, Mark A.; Cohen, Jay L.; Borszcz, George S.; Cano, Annmarie; Radcliffe, Alison M.; Porter, Laura S.; Schubiner, Howard; Keefe, Francis J.

2011-01-01

Objective and Method Research on emotion and pain has burgeoned. We review the last decade’s literature, focusing on links between emotional processes and persistent pain. Results Neurobiological research documents the neural processes that distinguish affective from sensory pain dimensions, link emotion and pain, and generate central nervous system pain sensitization. Psychological research demonstrates that greater pain is related to emotional stress and limited emotional awareness, expression, and processing. Social research shows the potential importance of emotional communication, empathy, attachment, and rejection. Conclusions Emotions are integral to the conceptualization, assessment, and treatment of persistent pain. Research should clarify when to eliminate or attenuate negative emotions, and when to access, experience, and express them. Theory and practice should integrate emotion into cognitive-behavioral models of persistent pain. PMID:21647882

Coping with persistent pain: a comparison of persistent pain sufferers in a specialty pain clinic and in a family practice clinic.

PubMed

Crook, J; Tunks, E; Kalaher, S; Roberts, J

1988-08-01

Coping has been defined as an effort to manage external and internal demands and conflicts that tax or exceed a person's resources. This paper examines the types of coping strategies used by two groups of persistent pain sufferers: one from a family practice clinic and the other from a specialty pain clinic. The relationship between the use of different types of coping strategies and adjustment was determined. The two study groups of persistent pain sufferers differed significantly from each other on many of the indices developed to tap adjustment but did not differ on any of the Billings and Moos original categories of coping strategies. When a factor analysis of coping items was performed, 5 valid clusters relevant to the chronic pain patient samples were determined. The factor the authors entitled 'adversarialness' with the qualities of dysphoric withdrawal, avoidant behavior and catastrophizing was found to explain adjustment defined by several indices. The authors conclude that it may be important to help persistent pain sufferers to alter their attitudes and behavior that tend toward catastrophizing, avoidance and withdrawal, rather than simply concentrate on trying to teach them techniques for 'coping with stress.'

Inverse relationship of interleukin-6 and mast cells in children with inflammatory and non-inflammatory abdominal pain phenotypes

PubMed Central

Henderson, Wendy A; Shankar, Ravi; Taylor, Tara J; Del Valle-Pinero, Arseima Y; Kleiner, David E; Kim, Kevin H; Youssef, Nader N

2012-01-01

AIM: To investigate interleukin-6 (IL-6), mast cells, enterochromaffin cells, 5-hydroxytryptamine, and substance P in the gastrointestinal mucosa of children with abdominal pain. METHODS: Formalin-fixed paraffin-embedded gastrointestinal biopsy blocks from patients (n = 48) with non-inflammatory bowel disease (irritable bowel syndrome and functional abdominal pain) and inflammatory bowel disease were sectioned and stained for IL-6, mast cells, enterochromaffin cells, 5-hydroxytryptamine, and substance P. All children had chronic abdominal pain as part of their presenting symptoms. Biopsy phenotype was confirmed by a pathologist, blinded to patient information. Descriptive statistics, chi-square, and independent sample t tests were used to compare differences between the inflammatory and non-inflammatory groups. RESULTS: The cohort (n = 48), mean age 11.9 years (SD = 2.9), 54.2% females, 90% Caucasian, was comprised of a non-inflammatory (n = 26) and an inflammatory (n = 22) phenotype. There was a significant negative correlation between substance P expression and mast cell count (P = 0.05, r = -0.373). Substance P was found to be expressed more often in female patient biopsies and more intensely in the upper gastrointestinal mucosa as compared to the lower mucosa. There were significantly increased gastrointestinal mucosal immunoreactivity to IL-6 (P = 0.004) in the inflammatory phenotype compared to non-inflammatory. Additionally, we found significantly increased mast cells (P = 0.049) in the mucosa of the non-inflammatory phenotype compared to the inflammatory group. This difference was particularly noted in the lower colon biopsies. CONCLUSION: The findings of this study yield preliminary evidence in identifying biomarkers of undiagnosed abdominal pain in children and may suggest candidate genes for future evaluation. PMID:23516176

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.

Predictors of persistent pain after breast cancer surgery: a systematic review and meta-analysis of observational studies

PubMed Central

Wang, Li; Guyatt, Gordon H.; Kennedy, Sean A.; Romerosa, Beatriz; Kwon, Henry Y.; Kaushal, Alka; Chang, Yaping; Craigie, Samantha; de Almeida, Carlos P.B.; Couban, Rachel J.; Parascandalo, Shawn R.; Izhar, Zain; Reid, Susan; Khan, James S.; McGillion, Michael; Busse, Jason W.

2016-01-01

Background: Persistent pain after breast cancer surgery affects up to 60% of patients. Early identification of those at higher risk could help inform optimal management. We conducted a systematic review and meta-analysis of observational studies to explore factors associated with persistent pain among women who have undergone surgery for breast cancer. Methods: We searched the MEDLINE, Embase, CINAHL and PsycINFO databases from inception to Mar. 12, 2015, to identify cohort or case–control studies that explored the association between risk factors and persistent pain (lasting ≥ 2 mo) after breast cancer surgery. We pooled estimates of association using random-effects models, when possible, for all independent variables reported by more than 1 study. We reported relative measures of association as pooled odds ratios (ORs) and absolute measures of association as the absolute risk increase. Results: Thirty studies, involving a total of 19 813 patients, reported the association of 77 independent variables with persistent pain. High-quality evidence showed increased odds of persistent pain with younger age (OR for every 10-yr decrement 1.36, 95% confidence interval [CI] 1.24–1.48), radiotherapy (OR 1.35, 95% CI 1.16–1.57), axillary lymph node dissection (OR 2.41, 95% CI 1.73–3.35) and greater acute postoperative pain (OR for every 1 cm on a 10-cm visual analogue scale 1.16, 95% CI 1.03–1.30). Moderate-quality evidence suggested an association with the presence of preoperative pain (OR 1.29, 95% CI 1.01–1.64). Given the 30% risk of pain in the absence of risk factors, the absolute risk increase corresponding to these ORs ranged from 3% (acute postoperative pain) to 21% (axillary lymph node dissection). High-quality evidence showed no association with body mass index, type of breast surgery, chemotherapy or endocrine therapy. Interpretation: Development of persistent pain after breast cancer surgery was associated with younger age, radiotherapy, axillary lymph node dissection, greater acute postoperative pain and preoperative pain. Axillary lymph node dissection provides the only high-yield target for a modifiable risk factor to prevent the development of persistent pain after breast cancer surgery. PMID:27402075

Gabapentin Effects on PKC-ERK1/2 Signaling in the Spinal Cord of Rats with Formalin-Induced Visceral Inflammatory Pain

PubMed Central

Li, Mei-yi; Fong, Peter; Zhang, Ji-guo; Zhang, Can-wen; Gong, Ke-rui; Yang, Ming-feng; Niu, Jing-zhong; Ji, Xun-ming; Lv, Guo-wei

2015-01-01

Currently, the clinical management of visceral pain remains unsatisfactory for many patients suffering from this disease. While preliminary animal studies have suggested the effectiveness of gabapentin in successfully treating visceral pain, the mechanism underlying its analgesic effect remains unclear. Evidence from other studies has demonstrated the involvement of protein kinase C (PKC) and extracellular signal-regulated kinase1/2 (ERK1/2) in the pathogenesis of visceral inflammatory pain. In this study, we tested the hypothesis that gabapentin produces analgesia for visceral inflammatory pain through its inhibitory effect on the PKC-ERK1/2 signaling pathway. Intracolonic injections of formalin were performed in rats to produce colitis pain. Our results showed that visceral pain behaviors in these rats decreased after intraperitoneal injection of gabapentin. These behaviors were also reduced by intrathecal injections of the PKC inhibitor, H-7, and the ERK1/2 inhibitor, PD98059. Neuronal firing of wide dynamic range neurons in L6–S1 of the rat spinal cord dorsal horn were significantly increased after intracolonic injection of formalin. This increased firing rate was inhibited by intraperitoneal injection of gabapentin and both the individual and combined intrathecal application of H-7 and PD98059. Western blot analysis also revealed that PKC membrane translocation and ERK1/2 phosphorylation increased significantly following formalin injection, confirming the recruitment of PKC and ERK1/2 during visceral inflammatory pain. These effects were also significantly reduced by intraperitoneal injection of gabapentin. Therefore, we concluded that the analgesic effect of gabapentin on visceral inflammatory pain is mediated through suppression of PKC and ERK1/2 signaling pathways. Furthermore, we found that the PKC inhibitor, H-7, significantly diminished ERK1/2 phosphorylation levels, implicating the involvement of PKC and ERK1/2 in the same signaling pathway. Thus, our results suggest a novel mechanism of gabapentin-mediated analgesia for visceral inflammatory pain through a PKC-ERK1/2 signaling pathway that may be a future therapeutic target for the treatment of visceral inflammatory pain. PMID:26512901

Breaking the cycle: extending the persistent pain cycle diagram using an affective pictorial metaphor.

PubMed

Stones, Catherine; Cole, Frances

2014-01-01

The persistent pain cycle diagram is a common feature of pain management literature. but how is it designed and is it fulfilling its potential in terms of providing information to motivate behavioral change? This article examines on-line persistent pain diagrams and critically discusses their purpose and design approach. By using broad information design theories by Karabeg and particular approaches to dialogic visual communications in business, this article argues the need for motivational as well as cognitive diagrams. It also outlines the design of a new persistent pain cycle that is currently being used with chronic pain patients in NHS Bradford, UK. This new cycle adopts and then visually extends an established verbal metaphor within acceptance and commitment therapy (ACT) in an attempt to increase the motivational aspects of the vicious circle diagram format.

Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism.

PubMed

Wigerblad, Gustaf; Bas, Duygu B; Fernades-Cerqueira, Cátia; Krishnamurthy, Akilan; Nandakumar, Kutty Selva; Rogoz, Katarzyna; Kato, Jungo; Sandor, Katalin; Su, Jie; Jimenez-Andrade, Juan Miguel; Finn, Anja; Bersellini Farinotti, Alex; Amara, Khaled; Lundberg, Karin; Holmdahl, Rikard; Jakobsson, Per-Johan; Malmström, Vivianne; Catrina, Anca I; Klareskog, Lars; Svensson, Camilla I

2016-04-01

An interesting and so far unexplained feature of chronic pain in autoimmune disease is the frequent disconnect between pain and inflammation. This is illustrated well in rheumatoid arthritis (RA) where pain in joints (arthralgia) may precede joint inflammation and persist even after successful anti-inflammatory treatment. In the present study, we have addressed the possibility that autoantibodies against citrullinated proteins (ACPA), present in RA, may be directly responsible for the induction of pain, independent of inflammation. Antibodies purified from human patients with RA, healthy donors and murinised monoclonal ACPA were injected into mice. Pain-like behaviour was monitored for up to 28 days, and tissues were analysed for signs of pathology. Mouse osteoclasts were cultured and stimulated with antibodies, and supernatants analysed for release of factors. Mice were treated with CXCR1/2 (interleukin (IL) 8 receptor) antagonist reparixin. Mice injected with either human or murinised ACPA developed long-lasting pronounced pain-like behaviour in the absence of inflammation, while non-ACPA IgG from patients with RA or control monoclonal IgG were without pronociceptive effect. This effect was coupled to ACPA-mediated activation of osteoclasts and release of the nociceptive chemokine CXCL1 (analogue to human IL-8). ACPA-induced pain-like behaviour was reversed with reparixin. The data suggest that CXCL1/IL-8, released from osteoclasts in an autoantibody-dependent manner, produces pain by activating sensory neurons. The identification of this new pain pathway may open new avenues for pain treatment in RA and also in other painful diseases associated with autoantibody production and/or osteoclast activation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism

PubMed Central

Wigerblad, Gustaf; Bas, Duygu B; Fernades-Cerqueira, Cátia; Krishnamurthy, Akilan; Rogoz, Katarzyna; Kato, Jungo; Sandor, Katalin; Su, Jie; Jimenez–Andrade, Juan Miguel; Finn, Anja; Bersellini Farinotti, Alex; Amara, Khaled; Lundberg, Karin; Holmdahl, Rikard; Jakobsson, Per-Johan; Malmström, Vivianne; Catrina, Anca I; Klareskog, Lars; Svensson, Camilla I

2016-01-01

Objective An interesting and so far unexplained feature of chronic pain in autoimmune disease is the frequent disconnect between pain and inflammation. This is illustrated well in rheumatoid arthritis (RA) where pain in joints (arthralgia) may precede joint inflammation and persist even after successful anti-inflammatory treatment. In the present study, we have addressed the possibility that autoantibodies against citrullinated proteins (ACPA), present in RA, may be directly responsible for the induction of pain, independent of inflammation. Methods Antibodies purified from human patients with RA, healthy donors and murinised monoclonal ACPA were injected into mice. Pain-like behaviour was monitored for up to 28 days, and tissues were analysed for signs of pathology. Mouse osteoclasts were cultured and stimulated with antibodies, and supernatants analysed for release of factors. Mice were treated with CXCR1/2 (interleukin (IL) 8 receptor) antagonist reparixin. Results Mice injected with either human or murinised ACPA developed long-lasting pronounced pain-like behaviour in the absence of inflammation, while non-ACPA IgG from patients with RA or control monoclonal IgG were without pronociceptive effect. This effect was coupled to ACPA-mediated activation of osteoclasts and release of the nociceptive chemokine CXCL1 (analogue to human IL-8). ACPA-induced pain-like behaviour was reversed with reparixin. Conclusions The data suggest that CXCL1/IL-8, released from osteoclasts in an autoantibody-dependent manner, produces pain by activating sensory neurons. The identification of this new pain pathway may open new avenues for pain treatment in RA and also in other painful diseases associated with autoantibody production and/or osteoclast activation. PMID:26613766

Altered Cortical Responsiveness to Pain Stimuli after High Frequency Electrical Stimulation of the Skin in Patients with Persistent Pain after Inguinal Hernia Repair

PubMed Central

van den Broeke, Emanuel N.; Koeslag, Lonneke; Arendsen, Laura J.; Nienhuijs, Simon W.; Rosman, Camiel; van Rijn, Clementina M.; Wilder-Smith, Oliver H. G.; van Goor, Harry

2013-01-01

Background High Frequency electrical Stimulation (HFS) of the skin induces enhanced brain responsiveness expressed as enhanced Event-Related Potential (ERP) N1 amplitude to stimuli applied to the surrounding unconditioned skin in healthy volunteers. The aim of the present study was to investigate whether this enhanced ERP N1 amplitude could be a potential marker for altered cortical sensory processing in patients with persistent pain after surgery. Materials and Methods Nineteen male patients; 9 with and 10 without persistent pain after inguinal hernia repair received HFS. Before, directly after and thirty minutes after HFS evoked potentials and the subjective pain intensity were measured in response to electric pain stimuli applied to the surrounding unconditioned skin. Results The results show that, thirty minutes after HFS, the ERP N1 amplitude observed at the conditioned arm was statistically significantly larger than the amplitude at the control arm across all patients. No statistically significant differences were observed regarding ERP N1 amplitude between patients with and without persistent pain. However, thirty minutes after HFS we did observe statistically significant differences of P2 amplitude at the conditioned arm between the two groups. The P2 amplitude decreased in comparison to baseline in the group of patients with pain. Conclusion The ERP N1 effect, induced after HFS, was not different between patients with vs. without persistent pain. The decreasing P2 amplitude was not observed in the patients without pain and also not in the previous healthy volunteer study and thus might be a marker for altered cortical sensory processing in patients with persistent pain after surgery. PMID:24376568

Development and Initial Validation of the Activity Patterns Scale in Patients With Chronic Pain.

PubMed

Esteve, Rosa; Ramírez-Maestre, Carmen; Peters, Madelon L; Serrano-Ibáñez, Elena R; Ruíz-Párraga, Gema T; López-Martínez, Alicia E

2016-04-01

Several self-report measures were used to identify 6 activity patterns in chronic pain patients: pain avoidance, activity avoidance, task-contingent persistence, excessive persistence, pain-contingent persistence, and pacing. Instruments for assessing pacing should include 3 pacing behaviors (breaking tasks into smaller tasks, taking frequent short rests, slowing down), each of which relate to a single goal (increasing activity levels, conserving energy for valued activities, and reducing pain). This article presents the Activity Patterns Scale (APS), which assesses these 6 activity patterns. Study 1 included 291 participants with chronic pain, and tested 3 structures using confirmatory factor analyses. The structure with the best fit had 8 factors corresponding to the hypothesized scales. High correlations in the expected direction were found between the APS subscales and the "Patterns of Activity Measure-Pain." Study 2 included 111 patients with chronic pain, and aimed at examining the association between the APS subscales and adjustment to pain. It was found that that activity avoidance was associated with daily functioning and impairment. Negative affect was positively associated with activity avoidance and excessive persistence, and negatively associated with task-contingent persistence, which was also positively associated with positive affect. This study showed that the APS is a valid and reliable instrument for clinical practice and research. This article presents a valid and reliable instrument to assess activity patterns in patients with chronic pain. The findings suggest that avoidance, persistence, and pacing are multidimensional constructs. Distinguishing between these dimensions sheds light on previous contradictory results and has direct clinical implications regarding recommending the most advisable activity patterns. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

The role of slow and persistent TTX-resistant sodium currents in acute tumor necrosis factor-α-mediated increase in nociceptors excitability

PubMed Central

Gudes, Sagi; Barkai, Omer; Caspi, Yaki; Katz, Ben; Lev, Shaya

2014-01-01

Tetrodotoxin-resistant (TTX-r) sodium channels are key players in determining the input-output properties of peripheral nociceptive neurons. Changes in gating kinetics or in expression levels of these channels by proinflammatory mediators are likely to cause the hyperexcitability of nociceptive neurons and pain hypersensitivity observed during inflammation. Proinflammatory mediator, tumor necrosis factor-α (TNF-α), is secreted during inflammation and is associated with the early onset, as well as long-lasting, inflammation-mediated increase in excitability of peripheral nociceptive neurons. Here we studied the underlying mechanisms of the rapid component of TNF-α-mediated nociceptive hyperexcitability and acute pain hypersensitivity. We showed that TNF-α leads to rapid onset, cyclooxygenase-independent pain hypersensitivity in adult rats. Furthermore, TNF-α rapidly and substantially increases nociceptive excitability in vitro, by decreasing action potential threshold, increasing neuronal gain and decreasing accommodation. We extended on previous studies entailing p38 MAPK-dependent increase in TTX-r sodium currents by showing that TNF-α via p38 MAPK leads to increased availability of TTX-r sodium channels by partial relief of voltage dependence of their slow inactivation, thereby contributing to increase in neuronal gain. Moreover, we showed that TNF-α also in a p38 MAPK-dependent manner increases persistent TTX-r current by shifting the voltage dependence of activation to a hyperpolarized direction, thus producing an increase in inward current at functionally critical subthreshold voltages. Our results suggest that rapid modulation of the gating of TTX-r sodium channels plays a major role in the mediated nociceptive hyperexcitability of TNF-α during acute inflammation and may lead to development of effective treatments for inflammatory pain, without modulating the inflammation-induced healing processes. PMID:25355965

TNF and granulocyte macrophage-colony stimulating factor interdependence mediates inflammation via CCL17

PubMed Central

Cook, Andrew D.; Khiew, Hsu-Wei; Christensen, Anne D.; Fleetwood, Andrew J.; Lacey, Derek C.; Smith, Julia E.; Förster, Irmgard

2018-01-01

TNF and granulocyte macrophage-colony stimulating factor (GM-CSF) have proinflammatory activity and both contribute, for example, to rheumatoid arthritis pathogenesis. We previously identified a new GM-CSF→JMJD3 demethylase→interferon regulatory factor 4 (IRF4)→CCL17 pathway that is active in monocytes/macrophages in vitro and important for inflammatory pain, as well as for arthritic pain and disease. Here we provide evidence for a nexus between TNF and this pathway, and for TNF and GM-CSF interdependency. We report that the initiation of zymosan-induced inflammatory pain and zymosan-induced arthritic pain and disease are TNF dependent. Once arthritic pain and disease are established, blockade of GM-CSF or CCL17, but not of TNF, is still able to ameliorate them. TNF is required for GM-CSF–driven inflammatory pain and for initiation of GM-CSF–driven arthritic pain and disease, but not once they are established. TNF-driven inflammatory pain and TNF-driven arthritic pain and disease are dependent on GM-CSF and mechanistically require the same downstream pathway involving GM-CSF→CCL17 formation via JMJD3-regulated IRF4 production, indicating that GM-CSF and CCL17 can mediate some of the proinflammatory and algesic actions of TNF. Given we found that TNF appears important only early in arthritic pain and disease progression, targeting a downstream mediator, such as CCL17, which appears to act throughout the course of disease, could be effective at ameliorating chronic inflammatory conditions where TNF is implicated. PMID:29563337

Transient physical and psychosocial activities increase the risk of nonpersistent and persistent low back pain: a case-crossover study with 12 months follow-up.

PubMed

Machado, Gustavo C; Ferreira, Paulo H; Maher, Chris G; Latimer, Jane; Steffens, Daniel; Koes, Bart W; Li, Qiang; Ferreira, Manuela L

2016-12-01

A previous study has shown that transient physical and psychosocial activities increased the risk of developing low back pain. However, the link between these factors in triggering nonpersistent or persistent episodes remains unclear. We aimed to investigate the association of transient exposures to physical and psychosocial activities with the development of nonpersistent or persistent low back pain. This was a case-crossover study with 12 months follow-up. We included 999 consecutive participants seeking care for a sudden onset of low back pain. Development of low back pain was the outcome measure. At baseline, participants reported transient exposures to 12 predefined activities over the 4 days preceding pain onset. After 12 months, participants were asked whether they had recovered and the date of recovery. Exposures in the 2-hour period preceding pain onset (case window) were compared with the 2-hour period, 24 hours before pain onset (control window) in a case-crossover design for all participants. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CI), and interaction analyses were used to compare estimates of nonpersistent (i.e., <6 weeks duration) and persistent cases. This study received funding from Australia's National Health and Medical Research Council (APP1003608). There were 832 participants (83%) who completed the 12 months follow-up successfully. Of these, 430 participants had nonpersistent low back pain (<6 weeks duration), whereas 352 reported persistent symptoms (≥6 weeks duration). Exposure to several transient activities, such as manual tasks involving heavy loads, awkward postures, live people or animals, moderate or vigorous physical activity, and being fatigued or tired during a task or activity, significantly increased the risk of both nonpersistent and persistent low back pain, with ORs ranging from 2.9 to 11.7. Overall, the risk of developing a persistent or a nonpersistent episode of low back pain associated with the included physical factors did not differ significantly. Our results revealed that previously identified triggers contribute equally to the development of both nonpersistent and persistent low back pain. Future prevention strategies should focus on controlling exposure to these triggers as they have the potential to decrease the burden associated with both acute and chronic low back pain. Copyright © 2016 Elsevier Inc. All rights reserved.

Cogan's syndrome mimicking acute Lyme arthritis.

PubMed

Schwegmann, J P; Enzenauer, R J

1995-05-01

A pediatric case of Cogan's syndrome mimicking acute Lyme arthritis is described. A 12-year-old black boy was admitted to the pediatric service for presumed right knee septic arthritis. Symptoms included acute pain and swelling with decreased range-of-motion. Although the patient's right knee symptoms and positive Lyme serology were consistent with a diagnosis of Lyme arthritis, the presence of sensorineural hearing loss and interstitial keratitis with inflammatory arthritis suggested a diagnosis of Cogan's syndrome. Subsequent Western blot analysis was negative for Borrelia burgdorferi antigens. The patient had dramatic clinical improvement of musculoskeletal and ophthalmologic complaints shortly after receiving high-dose corticosteroids, although residual sensorineural hearing loss persisted.

A self-regulation perspective on avoidance and persistence behavior in chronic pain: new theories, new challenges?

PubMed

Van Damme, Stefaan; Kindermans, Hanne

2015-02-01

Behavioral factors such as avoidance and persistence have received massive theoretical and empirical attention in the attempts to explain chronic pain and disability. The determinants of these pain behaviors remain, however, poorly understood. We propose a self-regulation perspective to increase our understanding of pain-related avoidance and persistence. A narrative review. We identified several theoretical views that may help explaining avoidance and persistence behavior, and organized these views around 4 concepts central in self-regulation theories: (1) identity, (2) affective-motivational orientation, (3) goal cognitions, and (4) coping. The review shows that each of these self-regulation perspectives allows for a broadened view in which pain behaviors are not simply considered passive consequences of fear, but proactive strategies to regulate the self when challenged by pain. Several implications and challenges arising from this review are discussed. In particular, a self-regulation perspective does not consider avoidance and persistence behavior to be intrinsically adaptive or maladaptive, but argues that their effects on disability and well-being rather depend on the goals underlying these behaviors. Such view would require a shift in how avoidance and persistence behavior are assessed and approached in clinical interventions.

Effects of neonatal pain, stress and their interrelation on pain sensitivity in later life in male rats.

PubMed

Butkevich, Irina P; Mikhailenko, Viktor A; Vershinina, Elena A; Aloisi, Anna Maria

2016-08-31

Neonatal pain and stress induce long-term changes in pain sensitivity. Therefore their interrelation is a topical subject of clinical and basic research. The present study investigated the effects of inflammatory peripheral pain and stress of maternal deprivation (MD)-isolation in 1-2- and 7-8-day-old Wistar rats (P1,2 and P7,8 respectively, ages comparable to preterm and full-term human babies) on basal pain and pain sensitivity in conditions of inflammatory pain (formalin test) during adolescence. The neonatal impacts were: pain (formalin injection, FOR in the paw), stress (a short 60-min MD), or pain+stress combination (FOR+MD), and appropriate controls. We found that stress of short-term maternal deprivation-isolation and inflammatory pain on P1,2 and P7,8 significantly increased the vulnerability of the nociceptive system to inflammatory pain. Maternal deprivation-isolation on P1,2 as compared with a similar impact on P7,8 had a greater effect on pain sensitivity of the adolescent rats, but the influence of early pain was independent of the injury age. Only adolescent rats with an early combination of pain and maternal deprivation-isolation showed hypoalgesia in the hot plate (HP) test. However licking duration (reflecting pain sensitivity) in these rats did not exceed licking duration in animals exposed only to maternal deprivation-isolation or pain. This study adds new data to the growing body of work demonstrating that early noxious impacts have long-term consequences for the functional activity of the nociceptive system. Our new findings may help to understand the impact of pain and maternal separation in the neonatal intensive care unit.

[Tendinopathy in rheumatic diseases].

PubMed

Henniger, M; Rehart, S

2017-03-01

Involvement of tendons and tendon sheaths is frequently found in the most common inflammatory systemic diseases, rheumatoid arthritis and spondyloarthritis. In rheumatoid arthritis tendon manifestations occur as tenosynovitis, with swelling and pain of the tendons mainly on the hands and feet. In spondyloarthritis the involvement of tendons presents as enthesitis with pain and swelling directly at the attachment points of tendons to the bony structures and more commonly in the lower extremities. Pathological alterations of tendons can be normally visualized by sonography and only sometimes with magnetic resonance imaging (MRI) or scintigraphy. Furthermore, it is important for diagnostics and effective therapy to detect all joints involved by means of clinical, sonographic and radiological examination as well as laboratory parameters of inflammation, antibody serology (e.g. anti-CCP antibodies) and HLA-B27. The histopathological alterations of tendinopathy in rheumatic diseases differ from degenerative/posttraumatic tendinopathy in their expression of the changes; however, a clear differentiation of the different rheumatic inflammatory systemic diseases is histopathologically not possible. Therapeutically, systemic medication is the most important part of treatment in rheumatic diseases. Local therapeutic measures can be employed in the treatment of tenosynovitis and enthesitis. In the case of failure or lack of efficacy of the medication and conservative therapy, tenosynovectomy is performed for persistent tenosynovitis and reconstructive surgical procedures are necessary for tendon ruptures.

Patient evaluation and general treatment planning.

PubMed

Fechtel, Scot Gerald

2006-05-01

Treating pain patients is difficult. The usual problems encountered in providing coherent and effective treatment for any chronic medical illness are compounded in painful conditions by time, society's choices, and the cultural role of the patient. Effective treatment of these patients depends on the persistence of the clinician. We must persist in requiring a complete history to understand the patient and his or her problem. We must persist in performing a thorough physical examination to uncover sufficient under-standing of the patient's physiology. We must persist in developing a comprehensive treatment plan to cover all of the intervening concerns. We must persist in following the patient in the clinic to make sure that the plan is completed and that complications that arise are dealt with efficiently. This can lead to considerable satisfaction and frustration. There remain many unanswered questions in the evaluation of pain patients and of pain itself. How accurate is physical examination in providing information about a given patient that is relevant to treating pain? Can physical examination reliably elicit a nociceptive focus for a specific individual's chronic pain experience? Is all long-term pain a smorgasbord of nociceptive, central sensitization, and neuromodulatory mechanisms? Can acute pain be more consistently aborted to minimize the development of chronic pain? Over the next few years, as our expanding knowledge of neuropharmacology, neurophysiology, and pain modulation in the CNS combines with better understanding of pain psychology and sociology, we clinicians will expect to have happier and more productive patients.

Anthropogenic Radio-Frequency Electromagnetic Fields Elicit Neuropathic Pain in an Amputation Model

PubMed Central

Jones, Erick; Romero-Ortega, Mario

2016-01-01

Anecdotal and clinical reports have suggested that radio-frequency electromagnetic fields (RF EMFs) may serve as a trigger for neuropathic pain. However, these reports have been widely disregarded, as the epidemiological effects of electromagnetic fields have not been systematically proven, and are highly controversial. Here, we demonstrate that anthropogenic RF EMFs elicit post-neurotomy pain in a tibial neuroma transposition model. Behavioral assays indicate a persistent and significant pain response to RF EMFs when compared to SHAM surgery groups. Laser thermometry revealed a transient skin temperature increase during stimulation. Furthermore, immunofluorescence revealed an increased expression of temperature sensitive cation channels (TRPV4) in the neuroma bulb, suggesting that RF EMF-induced pain may be due to cytokine-mediated channel dysregulation and hypersensitization, leading to thermal allodynia. Additional behavioral assays were performed using an infrared heating lamp in place of the RF stimulus. While thermally-induced pain responses were observed, the response frequency and progression did not recapitulate the RF EMF effects. In vitro calcium imaging experiments demonstrated that our RF EMF stimulus is sufficient to directly contribute to the depolarization of dissociated sensory neurons. Furthermore, the perfusion of inflammatory cytokine TNF-α resulted in a significantly higher percentage of active sensory neurons during RF EMF stimulation. These results substantiate patient reports of RF EMF-pain, in the case of peripheral nerve injury, while confirming the public and scientific consensus that anthropogenic RF EMFs engender no adverse sensory effects in the general population. PMID:26760033

Probing the Effects and Mechanisms of Electroacupuncture at Ipsilateral or Contralateral ST36-ST37 Acupoints on CFA-induced Inflammatory Pain.

PubMed

Lu, Kung-Wen; Hsu, Chao-Kuei; Hsieh, Ching-Liang; Yang, Jun; Lin, Yi-Wen

2016-02-24

Transient receptor potential vanilloid 1 (TRPV1) and associated signaling pathways have been reported to be increased in inflammatory pain signaling. There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). EA can reliably attenuate the increase of TRPV1 in mouse inflammatory pain models with unclear signaling mechanisms. Moreover, the difference in the clinical therapeutic effects between using the contralateral and ipsilateral acupoints has been rarely studied. We found that inflammatory pain, which was induced by injecting the complete Freund's adjuvant (CFA), (2.14 ± 0.1, p < 0.05, n = 8) can be alleviated after EA treatment at either ipsilateral (3.91 ± 0.21, p < 0.05, n = 8) or contralateral acupoints (3.79 ± 0.25, p < 0.05, n = 8). EA may also reduce nociceptive Nav sodium currents in dorsal root ganglion (DRG) neurons. The expression of TRPV1 and associated signaling pathways notably increased after the CFA injection; this expression can be further attenuated significantly in EA treatment. TRPV1 and associated signaling pathways can be prevented in TRPV1 knockout mice, suggesting that TRPV1 knockout mice are resistant to inflammatory pain. Through this study, we have increased the understanding of the mechanism that both ipsilateral and contralateral EA might alter TRPV1 and associated signaling pathways to reduce inflammatory pain.

The Antinociceptive and Antiinflammatory Properties of 3-furan-2-yl-N-p-tolyl-acrylamide, a Positive Allosteric Modulator of α7 Nicotinic Acetylcholine Receptors in Mice

PubMed Central

Bagdas, Deniz; Targowska-Duda, Katarzyna M.; López, Jhon J.; Perez, Edwin G.; Arias, Hugo R.; Damaj, M. Imad

2016-01-01

BACKGROUND Positive allosteric modulators (PAMs) facilitate endogenous neurotransmission and/or enhance the efficacy of agonists without directly acting on the orthosteric binding sites. In this regard, selective α7 nicotinic acetylcholine receptor type II PAMs display antinociceptive activity in rodent chronic inflammatory and neuropathic pain models. This study investigates whether 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a new putative α7-selective type II PAM, attenuates experimental inflammatory and neuropathic pains in mice. METHODS We tested the activity of PAM-2 after intraperitoneal administration in 3 pain assays: the carrageenan-induced inflammatory pain, the complete Freund adjuvant induced inflammatory pain, and the chronic constriction injury–induced neuropathic pain in mice. We also tested whether PAM-2 enhanced the effects of the selective α7 agonist choline in the mouse carrageenan test given intrathecally. Because the experience of pain has both sensory and affective dimensions, we also evaluated the effects of PAM-2 on acetic acid–induced aversion by using the conditioned place aversion test. RESULTS We observed that systemic administration of PAM-2 significantly reversed mechanical allodynia and thermal hyperalgesia in inflammatory and neuropathic pain models in a dose- and time-dependent manner without motor impairment. In addition, by attenuating the paw edema in inflammatory models, PAM-2 showed antiinflammatory properties. The antinociceptive effect of PAM-2 was inhibited by the selective competitive antagonist methyllycaconitine, indicating that the effect is mediated by α7 nicotinic acetylcholine receptors. Furthermore, PAM-2 enhanced the antiallodynic and antiinflammatory effects of choline, a selective α7 agonist, in the mouse carrageenan test. PAM-2 was also effective in reducing acetic acid induced aversion in the conditioned place aversion assay. CONCLUSIONS These findings suggest that the administration of PAM-2, a new α7-selective type II PAM, reduces the neuropathic and inflammatory pain sensory and affective behaviors in the mouse. Thus, this drug may have therapeutic applications in the treatment and management of chronic pain. PMID:26280585

Localized Sympathectomy Reduces Mechanical Hypersensitivity by Restoring Normal Immune Homeostasis in Rat Models of Inflammatory Pain

PubMed Central

Xie, Wenrui; Chen, Sisi; Strong, Judith A.; Li, Ai-Ling; Lewkowich, Ian P.

2016-01-01

Some forms of chronic pain are maintained or enhanced by activity in the sympathetic nervous system (SNS), but attempts to model this have yielded conflicting findings. The SNS has both pro- and anti-inflammatory effects on immunity, confounding the interpretation of experiments using global sympathectomy methods. We performed a “microsympathectomy” by cutting the ipsilateral gray rami where they entered the spinal nerves near the L4 and L5 DRG. This led to profound sustained reductions in pain behaviors induced by local DRG inflammation (a rat model of low back pain) and by a peripheral paw inflammation model. Effects of microsympathectomy were evident within one day, making it unlikely that blocking sympathetic sprouting in the local DRGs or hindpaw was the sole mechanism. Prior microsympathectomy greatly reduced hyperexcitability of sensory neurons induced by local DRG inflammation observed 4 d later. Microsympathectomy reduced local inflammation and macrophage density in the affected tissues (as indicated by paw swelling and histochemical staining). Cytokine profiling in locally inflamed DRG showed increases in pro-inflammatory Type 1 cytokines and decreases in the Type 2 cytokines present at baseline, changes that were mitigated by microsympathectomy. Microsympathectomy was also effective in reducing established pain behaviors in the local DRG inflammation model. We conclude that the effect of sympathetic fibers in the L4/L5 gray rami in these models is pro-inflammatory. This raises the possibility that therapeutic interventions targeting gray rami might be useful in some chronic inflammatory pain conditions. SIGNIFICANCE STATEMENT Sympathetic blockade is used for many pain conditions, but preclinical studies show both pro- and anti-nociceptive effects. The sympathetic nervous system also has both pro- and anti-inflammatory effects on immune tissues and cells. We examined effects of a very localized sympathectomy. By cutting the gray rami to the spinal nerves near the lumbar sensory ganglia, we avoided widespread sympathetic denervation. This procedure profoundly reduced mechanical pain behaviors induced by a back pain model and a model of peripheral inflammatory pain. One possible mechanism was reduction of inflammation in the sympathetically denervated regions. This raises the possibility that therapeutic interventions targeting gray rami might be useful in some inflammatory conditions. PMID:27535916

Society of Behavioral Medicine (SBM) position statement: improving access to psychosocial care for individuals with persistent pain: supporting the National Pain Strategy's call for interdisciplinary pain care.

PubMed

Janke, E Amy; Cheatle, Martin; Keefe, Francis J; Dhingra, Lara

2018-03-01

Policy makers have articulated a need for clear, evidence-based guidance to help inform pain policy. Persistent pain is common, expensive, and debilitating, and requires comprehensive assessment and treatment planning. Recently released opioid prescribing guidelines by the CDC (2016) emphasize the importance of using nonopioid therapies before considering opioid treatment for those without a malignant illness. The National Pain Strategy (2016) underscores the importance of comprehensive, interdisciplinary pain care. Unfortunately, despite persuasive evidence supporting the efficacy of psychosocial approaches, these interventions are inaccessible to the majority of Americans. Psychosocial approaches to pain management should be available for all individuals with persistent pain and in all health care settings and contexts as part of the comprehensive, interdisciplinary approach to pain care as outlined in the National Pain Strategy. To achieve this, we must prioritize reimbursement of evidence-based psychosocial approaches for pain assessment and management and improve provider training and competencies to implement these approaches.

SNPs in PTGS2 and LTA Predict Pain and Quality of Life in Long Term Lung Cancer Survivors

PubMed Central

Rausch, Sarah M.; Gonzalez, Brian D.; Clark, Matthew M.; Patten, Christi; Felten, Sara; Liu, Heshan; Li, Yafei; Sloan, Jeff; Yang, Ping

2015-01-01

PURPOSE Lung cancer survivors report the lowest quality of life relative to other cancer survivors. Pain is one of the most devastating, persistent, and incapacitating symptoms for lung cancer survivors. Prevalence rates vary with 80–100% of survivors experiencing cancer pain and healthcare costs are five times higher in cancer survivors with uncontrolled pain. Cancer pain often has a considerable impact on quality of life among cancer patients and cancer survivors. Therefore, early identification, and treatment is important. Although recent studies have suggested a relationship between single nucleotide polymorphisms (SNPs) in several cytokine and inflammation genes with cancer prognosis, associations with cancer pain are not clear. Therefore, the primary aim of this study was to identify SNPs related to pain in long term lung cancer survivors. PATIENTS AND METHODS Participants were enrolled in the Mayo Clinic Lung Cancer Cohort upon diagnosis of their lung cancer. 1149 Caucasian lung cancer survivors, (440 surviving < 3 years; 354 surviving 3–5 years; and 355 surviving> 5 years) completed study questionnaires and had genetic samples available. Ten SNPS from PTGS2 and LTA genes were selected based on the serum literature. Outcomes included pain, and quality of life as measured by the SF-8. RESULTS Of the 10 SNPs evaluated in LTA and PTGS2 genes, 3 were associated with pain severity (rs5277; rs1799964), social function (rs5277) and mental health (rs5275). These results suggested both specificity and consistency of these inflammatory gene SNPs in predicting pain severity in long term lung cancer survivors. CONCLUSION These results provide support for genetic predisposition to pain severity and may aid in identification of lung cancer survivors at high risk for morbidity and poor QOL. PMID:22464751

Standard analgesics reverse burrowing deficits in a rat CCI model of neuropathic pain, but not in models of type 1 and type 2 diabetes-induced neuropathic pain.

PubMed

Rutten, Kris; Gould, Stacey A; Bryden, Luke; Doods, Henri; Christoph, Thomas; Pekcec, Anton

2018-09-17

Burrowing is a rodent behavior validated as a robust and reproducible outcome measure to infer the global effect of pain in several inflammatory pain models. However, less is known about the effect of analgesics on burrowing in neuropathic pain models and no studies have determined burrowing performance in models of diabetes-associated neuropathic pain. To compare the sensitivity of the burrowing assay in different neuropathic pain models: mononeuropathic pain and diabetic polyneuropathy. Burrowing performance was determined by the amount of substrate left in a hollow tube by rats with chronic constriction injury (CCI). In addition, burrowing performance, locomotion and pain development was assessed in the Zucker diabetic fatty (ZDF) rat model, resembling type-2 diabetes. Efficacy of clinically-active reference drugs (opioids, gabapentin and/or pregabalin) were investigated in these models. Burrowing behavior was additionally assessed in a second model, induced by streptozotocin (STZ) treatment, resembling type-1 diabetes. In the CCI model, moderate but consistent burrowing deficits were observed that persisted over a period of ≥20 days. Systemic administration of morphine, pregabalin and gabapentin reversed this deficit. In contrast, none of the reference drugs improved marked burrowing deficits detected in ZDF rats, and pregabalin did not reverse severe burrowing deficits observed in STZ rats. Burrowing performance cannot necessarily be used as pain-related readout across pain models and largely depends on the model used, at least in models of neuropathy. Specifically, analgesic drug effects might be masked by general diabetes-associated alteration of the animals' well-being, resulting in false negative outcomes. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Detection of systemic inflammation in severely impaired chronic pain patients, and effects of a CBT-ACT-based multi-modal pain rehabilitation program.

PubMed

Hysing, E-B; Smith, L; Thulin, M; Karlsten, R; Gordh, T

2017-12-29

Aims A few previous studies indicate an ongoing of low-grade systemic inflammation in chronic pain patients (CPP) [1, 2]. In the present study we investigated the plasma inflammatory profile in severely impaired chronic pain patients. In addition we studied if there were any alterations in inflammation patterns at one-year follow up, after the patients had taken part in a CBT-ACT based 4 weeks in-hospital pain rehabilitation program (PRP). Methods Blood samples were collected from 52 well characterized chronic pain patients. Plasma from matched healthy blood donors were used as controls. At one year after the treatment program, 28 of the patients were available for follow up. Instead of only analyzing single inflammation-related substances, we used a new multiplex panel enabling the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines (Proseek Inflammation, Olink, Uppsala, Sweden). Multivariate statistics were used for analysis. Results Clear signs of increased inflammatory activity were detected in the pain patients. Accepting a false discovery rate (FDR) of 5%, there were significant differences in 43 of the 92 inflammatory biomarkers. The expression of 8 biomarkers were 4 times higher in patients compared to controls. Three biomarkers, CXCL5, SIRT2, AXIN1 were more than 8 times higher. The conventional marker for inflammation, CRP, did not differ. Of the 28 patients available for follow up one year after the intervention, all showed lower levels of the inflammatory biomarker initially raised. Conclusions The results indicate that CPP suffer from a low grade of chronic systemic inflammation, not detectable by CRP analysis. This may have implications for the general pain hypersensitivity, and other symptoms, often described in this group of patients. We conclude that inflammatory plasma proteins may be measureable molecular markers to distinguishes CPP from pain free controls, and that a CBT-ACT pain rehab program seem to decrease this inflammatory activity.

What do we mean by "older adults' persistent pain self-management"? A concept analysis.

PubMed

Stewart, Carrie; Schofield, Pat; Elliott, Alison M; Torrance, Nicola; Leveille, Suzanne

2014-02-01

No standard definition exists for the concept "persistent pain self-management" or how it should be defined in relation to older adults. Poorly defined concepts can result in misunderstandings in the clinical setting and can hinder research through difficulties identifying or measuring the concept. To ascertain attributes, referents, antecedents, and consequences of the concept older adults' persistent pain self-management and develop a theoretical definition. Rodgers evolutionary model of concept analysis was used to systematically analyze articles from the academic and grey literature (N = 45). Data were extracted using standardized extraction forms and analyzed using thematic analysis. This concept was discussed in three ways: as an intervention, in reference to everyday behaviors, and as an outcome. Five defining attributes were identified: multidimensional process, personal development, active individuals, symptom response, and symptom control. Patients' perceived need and ability to manage pain with support from others is necessary for pain self-management to occur. Numerous physical, psychological, and social health consequences were identified. A theoretical definition is discussed. Our findings have clarified existing use and understanding regarding the concept of older adults' persistent pain self-management. We have identified three areas for future development: refinement of the attributes of this concept within the context of older adults, an exploration of how providers can overcome difficulties supporting older adults' persistent pain self-management, and a clarification of the overall theoretical framework of older adults' persistent pain self-management. Wiley Periodicals, Inc.

Analgesic effect of the neuropeptide cortistatin in murine models of arthritic inflammatory pain.

PubMed

Morell, Maria; Souza-Moreira, Luciana; Caro, Marta; O'Valle, Francisco; Forte-Lago, Irene; de Lecea, Luis; Gonzalez-Rey, Elena; Delgado, Mario

2013-05-01

To investigate the role of the antiinflammatory neuropeptide cortistatin in chronic pain evoked by joint inflammation. Thermal and mechanical hyperalgesia was evoked in mouse knee joints by intraplantar injection of tumor necrosis factor α and intraarticular infusion of Freund's complete adjuvant, and the analgesic effects of cortistatin, administered centrally, peripherally, and systemically, were assessed. In addition, the effects of cortistatin on the production of nociceptive peptides and the activation of pain signaling were assayed in dorsal root ganglion cultures and in inflammatory pain models. The role of endogenous cortistatin in pain sensitization and perpetuation of chronic inflammatory states was evaluated in cortistatin-deficient mice. Finally, the effect of noxious/inflammatory stimuli in the production of cortistatin by the peripheral nociceptive system was assayed in vitro and in vivo. Expression of cortistatin was observed in peptidergic nociceptors of the peripheral nociceptive system, and endogenous cortistatin was found to participate in the tuning of pain sensitization, especially in pathologic inflammatory conditions. Results showed that cortistatin acted both peripherally and centrally to reduce the tactile allodynia and heat hyperalgesia evoked by arthritis and peripheral tissue inflammation in mice, via mechanisms that were independent of its antiinflammatory action. These mechanisms involved direct action on nociceptive neurons and regulation of central sensitization. The analgesic effects of cortistatin in murine arthritic pain were linked to binding of the neuropeptide to somatostatin and ghrelin receptors, activation of the G protein subunit Gαi , impairment of ERK signaling, and decreased production of calcitonin gene-related peptide in primary nociceptors. These findings indicate that cortistatin is an antiinflammatory factor with potent analgesic effects that may offer a new approach to pain therapy in pathologic inflammatory states, including osteoarthritis and rheumatoid arthritis. Copyright © 2013 by the American College of Rheumatology.

Combining biofeedback and Narrative Exposure Therapy for persistent pain and PTSD in refugees: a pilot study

PubMed Central

Morina, Naser; Maier, Thomas; Bryant, Richard; Knaevelsrud, Christine; Wittmann, Lutz; Rufer, Michael; Schnyder, Ulrich; Müller, Julia

2012-01-01

Objective Many traumatised refugees suffer from both persistent pain and posttraumatic stress disorder (PTSD). To date, no specific guidelines exist for treatment of this group of patients. This paper presents data on a pilot treatment study conducted with 15 traumatised refugees with persistent pain and PTSD. Methods Participants received 10 sessions of pain-focused treatment with biofeedback (BF) followed by 10 sessions of Narrative Exposure Therapy (NET). Structured interviews and standardised questionnaires were used to assess symptoms of pain intensity, pain disability, PTSD and quality of life directly before and after treatment and at 3 months follow-up. Results Following the combined intervention, participants showed a significant reduction in both pain and PTSD symptoms, as well as improved quality of life. Additionally, biofeedback increased motivation for subsequent trauma-focused therapy, which in turn was related to larger PTSD treatment gains. Conclusion This pilot study provides initial evidence that combining BF and NET is safe, acceptable, and feasible in patients with co-morbid persistent pain and PTSD. PMID:22893834

Antinociceptive and Anti-Inflammatory Effects of Octacosanol from the Leaves of Sabicea grisea var. grisea in Mice

PubMed Central

de Oliveira, Anderson Marques; Conserva, Lucia M.; de Souza Ferro, Jamylle N.; de Almeida Brito, Fabíola; Lyra Lemos, Rosângela P.; Barreto, Emiliano

2012-01-01

Sabicea species are used in the Amazon for treatment of fever and malaria, which suggests that its chemical constituents may have some effect on pain and inflammation. Phytochemical analysis of the hexane fraction obtained from the crude ethanol extract from Sabicea grisea var. grisea Cham. & Schltdl (Rubiaceae), an endemic plant in Brazil, resulted in the isolation of octacosanol. This study investigated the antinociceptive and anti-inflammatory effects of the octacosanol in different experimental models. The crude ethanolic extract and hexane fraction obtained from the leaves of S. grisea produced an inhibition of acetic acid-induced pain. Moreover, octacosanol isolated from the hexane fraction produced a significant inhibition of pain response elicited by acetic acid. Pre-treatment with yohimbine, an alpha 2-adrenergic receptor antagonist, notably reversed the antinociceptive activity induced by octacosanol in the abdominal constriction test. Furthermore, mice treated with octacosanol did not exhibit any behavioral alteration during the hot plate and rota-rod tests, indicating non-participation of the supraspinal components in the modulation of pain by octacosanol with no motor abnormality. In the formalin test, octacosanol did not inhibit the licking time in first phase (neurogenic pain), but significantly inhibited the licking time in second phase (inflammatory pain) of mice. The anti-inflammatory effect of octacosanol was evaluated using carrageenan-induced pleurisy. The octacosanol significantly reduced the total leukocyte count and neutrophils influx, as well as TNF-α levels in the carrageenan-induced pleurisy. This study revealed that the mechanism responsible for the antinociceptive and anti-inflammatory effects of the octacosanol appears to be partly associated with an inhibition of alpha 2-adrenergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, these results demonstrated that the octacosanol from the leaves of S. grisea possesses antinociceptive and anti-inflammatory activities, which could be of relevance for the pharmacological control of pain and inflammatory processes. PMID:22408410

Anti-nociceptive and anti-inflammatory actions of sulforaphane in chronic constriction injury-induced neuropathic pain mice.

PubMed

Wang, Cheng; Wang, Congpin

2017-02-01

Neuropathic pain is still considered as incurable disease as current therapies are not ideal in terms of efficacy and tolerability. It is imperative to search for novel drugs to obtain better treatments. Sulforaphane (SFN), a derivative of glucoraphanin present in cruciferous vegetables, exhibits therapeutic effects on inflammation-related diseases. Since inflammation plays an important role in regulating chronic pain, in the present study, we investigated anti-nociceptive effects of SFN and its underlying mechanisms in a neuropathic pain mouse model, sciatic nerve chronic constriction injury (CCI). SFN (0.1-100 mg/kg) was injected intraperitoneally for 7 days when pain behaviors, including mechanical allodynia and thermal hyperalgesia, reached to the maximum in CCI mice. We observed that SFN dose-dependently attenuated CCI-induced pain behavioral hypersensitivity, accompanied by reduction in pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and upregulation of an anti-inflammatory cytokine (IL-10). Moreover, SFN counteracted CCI enhancement of COX2 and iNOS in injured nerves, two key enzymes implicated in inflammation and neuropathic pain. Furthermore, pretreatment of naloxone, an antagonist of opioid receptors, significantly blocked SFN attenuation of behavioral hypersensitivity without affecting SFN modulation of inflammatory cytokines in CCI mice. Interestingly, CCI-induced increase in µ-opioid receptors in injured sciatic nerves was further increased by SFN treatment. Taken together, SFN has both anti-nociceptive and anti-inflammatory actions.

Young people's experiences of persistent musculoskeletal pain, needs, gaps and perceptions about the role of digital technologies to support their co-care: a qualitative study

PubMed Central

Jordan, Joanne E; Chua, Jason; Schütze, Robert; Wark, John D

2016-01-01

Objective To investigate young people's experiences of persistent musculoskeletal pain, including care needs and current service gaps as well as perceptions about the role of digital technologies to support their co-care. Methods A qualitative study employing two independent data collection modes: in-depth individual semistructured interviews and focus groups. Setting Community settings throughout Australia. Participants Participants were included if they had experienced persistent musculoskeletal pain of >3-month duration with an average of ≥3 on the visual analogue scale over the preceding 3 months, including non-specific conditions (eg, low back pain) and specific conditions (eg, juvenile idiopathic arthritis and other systemic arthritides), with/without pre-existing or current diagnosed mental health conditions. 23 young people (87.0% women; mean (SD) age: 20.8 (2.4) years) from across 6 Australian jurisdictions participated. Almost two-thirds of participants with persistent musculoskeletal pain reported comorbid mental health conditions. Main outcome measures Inductive and deductive approaches to analyse and derive key themes from verbatim transcripts. Results Participants described their daily experiences of living with persistent musculoskeletal pain, their fears and the challenges imposed by the invisibility of pain, and the two-way relationship between their pain and mental well-being. A lack of relevant and accessible information and resources tailored to young people's unique needs, integrated and youth-relevant healthcare services and adequately skilled healthcare practitioners were identified as key care gaps. Participants strongly advocated for the use of digital technologies to improve access to age-appropriate resources and support for co-care. Conclusions Young people living with persistent musculoskeletal pain described the absence of age-appropriate pain services and clearly articulated their perceptions on the role of, and opportunities provided by, digital technologies to connect with and support improved pain healthcare. Innovative and digitally-enabled models of pain care are likely to be helpful for this group. PMID:27940635

Painful neurotrophins and their role in visceral pain.

PubMed

López-Pérez, Ana E; Nurgali, Kulmira; Abalo, Raquel

2018-04-01

Beyond their well-known role in embryonic development of the central and peripheral nervous system, neurotrophins, particularly nerve growth factor and brain-derived neurotrophic factor, exert an essential role in pain production and sensitization. This has mainly been studied within the framework of somatic pain, and even antibodies (tanezumab and fasinumab) have recently been developed for their use in chronic somatic painful conditions, such as osteoarthritis or low back pain. However, data suggest that neurotrophins also exert an important role in the occurrence of visceral pain and visceral sensitization. Visceral pain is a distressing symptom that prompts many consultations and is typically encountered in both 'organic' (generally inflammatory) and 'functional' (displaying no obvious structural changes in routine clinical evaluations) disorders of the gut, such as inflammatory bowel disease and irritable bowel syndrome, respectively. The present review provides a summary of neurotrophins as a molecular family and their role in pain in general and addresses recent investigations of the involvement of nerve growth factor and brain-derived neurotrophic factor in visceral pain, particularly that associated with inflammatory bowel disease and irritable bowel syndrome.

Predicting persistent disabling low back pain in general practice: a prospective cohort study

PubMed Central

Jones, Gareth T; Johnson, Ruth E; Wiles, Nicola J; Chaddock, Carol; Potter, Richard G; Roberts, Chris; Symmons, Deborah PM; Macfarlane, Gary J

2006-01-01

Background Patients may adopt active and/or passive coping strategies in response to pain. However, it is not known whether these strategies may also precede the onset of chronic symptoms and, if so, whether they are independent predictors of prognosis. Aim To examine, in patients with low back pain in general practice, the prognostic value of active and passive coping styles, in the context of baseline levels of pain, disability and pain duration. Design of study Prospective cohort study. Setting Nine general practices in north west England. Method Patients consulting their GP with a new episode of low back pain were recruited to the study. Information on coping styles, pain severity, disability, duration, and a brief history of other chronic pain symptoms was recorded using a self-completion postal questionnaire. Participants were then sent a follow-up questionnaire, 3 months after their initial consultation, to assess the occurrence of low back pain. The primary outcome was persistent disabling low back pain, that is, low back pain at 3-month follow-up self-rated as ≥20 mm on a 100 mm visual analogue scale, and ≥5 on the Roland and Morris Disability Questionnaire. Results A total of 974 patients took part in the baseline survey, of whom 922 (95%) completed a follow-up questionnaire; 363 individuals (39%) reported persistent disabling pain at follow-up. Persons who reported high levels of passive coping experienced a threefold increase in the risk of persistent disabling low back pain (relative risk [RR] = 3.0; 95% confidence interval [CI] = 2.3 to 4.0). In contrast, active coping was associated with neither an increase nor a decrease in the risk of a poor prognosis. After adjusting for baseline pain severity, disability, and other measures of pain and pain history, persons who reported a high passive coping score were still at 50% increased risk of a poor outcome (RR = 1.5; 95% CI = 1.1 to 2.0). Conclusion Patients who report passive coping strategies experience a significant increase in the risk of persistent symptoms. Further, this risk persists after controlling for initial pain severity and disability. The identification of this low back pain subgroup may help target future treatments to those at greatest risk of a poor outcome. PMID:16638248

Persistent ulnar-sided wrist pain after treatment of triquetral dorsal chip fracture: six cases related to triangular fibrocartilage complex injury.

PubMed

Lee, Seoung-joon; Rathod, Chasanal Mohan; Park, Kwang-Won; Hwang, Jin-Ho

2012-05-01

Persistent ulnar-sided wrist pain after treatment of triquetral dorsal chip fracture even after union is a matter of concern. There could be various reasons for this persistent pain like arthritis, instability, fractures and non-union. We correlate our findings of physical examination and wrist arthroscopy as triangular fibrocartilage complex injury to be one of the causes of this persistent pain. Six subjects who had persistent ulnocarpal joint pain and tenderness after triquetral dorsal chip fracture, despite 2 months of conservative treatment, were subjected to physical tests. If the physical examination yields positive results, then magnetic resonance imaging followed by arthroscopic treatment was performed. The six patients were then evaluated using the visual analogue scale, the Mayo modified wrist score, and the grip strength test. Triangular fibrocartilage complex (TFCC) injury was observed in all six cases and partial TFCC resection and synovectomy were performed. Analysis of the visual analogue scale, Mayo modified wrist score, and grip strength test data revealed statistically significant improvements (P < 0.05). In addition to several causes reported in the published literature, TFCC injury can be a cause of persistent ulnar pain after treatment of triquetral dorsal chip fracture. Arthroscopic partial TFCC resection can be considered to be a suitable treatment for such cases.

Knockdown of sodium channel NaV1.6 blocks mechanical pain and abnormal bursting activity of afferent neurons in inflamed sensory ganglia

PubMed Central

Xie, Wenrui; Strong, Judith A.; Ye, Ling; Mao, Ju-Xian; Zhang, Jun-Ming

2013-01-01

Inflammatory processes in the sensory ganglia contribute to many forms of chronic pain. We previously showed that local inflammation of the lumbar sensory ganglia rapidly leads to prolonged mechanical pain behaviors and high levels of spontaneous bursting activity in myelinated cells. Abnormal spontaneous activity of sensory neurons occurs early in many preclinical pain models, and initiates many other pathological changes, but its molecular basis is not well understood. The sodium channel isoform NaV1.6 can underlie repetitive firing and excitatory persistent and resurgent currents. We used in vivo knockdown of this channel via local injection of siRNA to examine its role in chronic pain following local inflammation of the rat lumbar sensory ganglia. In normal DRG, quantitative PCR showed that cells capable of firing repetitively had significantly higher relative expression of NaV1.6. In inflamed DRG, spontaneously active bursting cells expressed high levels of NaV1.6′ immunoreactivity. In vivo knockdown of NaV1.6 locally in the lumbar DRG at the time of DRG inflammation completely blocked development of pain behaviors and abnormal spontaneous activity, while having only minor effects on unmyelinated C-cells. Current research on isoform-specific sodium channel blockers for chronic pain is largely focused on NaV1.8, because it is present primarily in unmyelinated C fiber nociceptors, or on NaV1.7, because lack of this channel causes congenital indifference to pain. However, the results suggest that NaV1.6 may be a useful therapeutic target for chronic pain, and that some pain conditions may be primarily mediated by myelinated A-fiber sensory neurons. PMID:23622763

New insights into the impact of neuro-inflammation in rheumatoid arthritis

PubMed Central

Fuggle, Nicholas R.; Howe, Franklyn A.; Allen, Rachel L.; Sofat, Nidhi

2014-01-01

Rheumatoid arthritis (RA) is considered to be, in many respects, an archetypal autoimmune disease that causes activation of pro-inflammatory pathways resulting in joint and systemic inflammation. RA remains a major clinical problem with the development of several new therapies targeted at cytokine inhibition in recent years. In RA, biologic therapies targeted at inhibition of tumor necrosis factor alpha (TNFα) have been shown to reduce joint inflammation, limit erosive change, reduce disability and improve quality of life. The cytokine TNFα has a central role in systemic RA inflammation and has also been shown to have pro-inflammatory effects in the brain. Emerging data suggests there is an important bidirectional communication between the brain and immune system in inflammatory conditions like RA. Recent work has shown how TNF inhibitor therapy in people with RA is protective for Alzheimer's disease. Functional MRI studies to measure brain activation in people with RA to stimulus by finger joint compression, have also shown that those who responded to TNF inhibition showed a significantly greater activation volume in thalamic, limbic, and associative areas of the brain than non-responders. Infections are the main risk of therapies with biologic drugs and infections have been shown to be related to disease flares in RA. Recent basic science data has also emerged suggesting that bacterial components including lipopolysaccharide induce pain by directly activating sensory neurons that modulate inflammation, a previously unsuspected role for the nervous system in host-pathogen interactions. In this review, we discuss the current evidence for neuro-inflammation as an important factor that impacts on disease persistence and pain in RA. PMID:25414636

Persistent axial neck pain after cervical disc arthroplasty: a radiographic analysis.

PubMed

Wagner, Scott C; Formby, Peter M; Kang, Daniel G; Van Blarcum, Gregory S; Cody, John P; Tracey, Robert W; Lehman, Ronald A

2016-07-01

There is very little literature examining optimal radiographic parameters for placement of cervical disc arthroplasty (CDA), nor is there substantial evidence evaluating the relationship between persistent postoperative neck pain and radiographic outcomes. We set out to perform a single-center evaluation of the radiographic outcomes, including associated complications, of CDA. This is a retrospective review. Two hundred eighty-five consecutive patients undergoing CDA were included in the review. The outcome measures were radiological parameters (preoperative facet arthrosis, disc height, CDA placement in sagittal and coronal planes, heterotopic ossification [HO] formation, etc.) and patient outcomes (persistent pain, recurrent pain, new-onset pain, etc.). We performed a retrospective review of all patients from a single military tertiary medical center from August 2008 to August 2012 undergoing CDA. Preoperative, immediate postoperative, and final follow-up films were evaluated. The clinical outcomes and complications associated with the procedure were also examined. The average radiographic follow-up was 13.5 months and the rate of persistent axial neck pain was 17.2%. For patients with persistent neck pain, the rate of HO formation per level studied was 22.6%, whereas the rate was significantly lower for patients without neck pain (11.7%, p=.03). There was no significant association between the severity of HO and the presence of neck pain. Patients with a preoperative diagnosis of cervicalgia, compared to those without cervicalgia, were significantly more likely to experience continued neck pain postoperatively (28.6% vs. 13.1%, p=.01). There were no differences in preoperative facet arthrosis, pre- or postoperative disc height, segmental range of motion, or placement of the device relative to the posterior edge of the vertebral body.However, patients with implants more centered between the uncovertebral joints were more likely to experience posterior neck pain (p=.03). We found that posterior axial neck pain is relatively frequent after CDA, and patients with persistent neck pain were significantly more likely to have preoperative cervicalgia and develop HO postoperatively. We also found that patients with implants that were placed off-centered were less likely to also complain of neck pain, although the reasons for this finding remain unclear. Published by Elsevier Inc.

Adolescents' experience of complex persistent pain.

PubMed

Sørensen, Kari; Christiansen, Bjørg

2017-04-01

Persistent (chronic) pain is a common phenomenon in adolescents. When young people are referred to a pain clinic, they usually have amplified pain signals, with pain syndromes of unconfirmed ethology, such as fibromyalgia and complex regional pain syndrome (CRPS). Pain is complex and seems to be related to a combination of illness, injury, psychological distress, and environmental factors. These young people are found to have higher levels of distress, anxiety, sleep disturbance, and lower mood than their peers and may be in danger of entering adulthood with mental and physical problems. In order to understand the complexity of persistent pain in adolescents, there seems to be a need for further qualitative research into their lived experiences. The aim of this study was to explore adolescents' experiences of complex persistent pain and its impact on everyday life. The study has an exploratory design with individual in-depth interviews with six youths aged 12-19, recruited from a pain clinic at a main referral hospital in Norway. A narrative approach allowed the informants to give voice to their experiences concerning complex persistent pain. A hermeneutic analysis was used, where the research question was the basis for a reflective interpretation. Three main themes were identified: (1) a life with pain and unpleasant bodily expressions; (2) an altered emotional wellbeing; and (3) the struggle to keep up with everyday life. The pain was experienced as extremely strong, emerging from a minor injury or without any obvious causation, and not always being recognised by healthcare providers. The pain intensity increased as the suffering got worse, and the sensation was hard to describe with words. Parts of their body could change in appearance, and some described having pain-attacks or fainting. The feeling of anxiety was strongly connected to the pain. Despair and uncertainty contributed to physical disability, major sleep problems, school absence, and withdrawal from leisure activities. Their parents were supportive, but sometimes more emotionally affected than themselves. The adolescents described how they strived for normality and to not become an outsider. Being met with necessary facilitation from school was important, as well as keeping up with friends. These adolescents had all been treated by an interdisciplinary pain team, and stated that they had an optimistic view of the future, despite still having some symptoms. The study provides new insights into adolescents' own experiences of complex persistent pain occurring unexpectedly, developing dramatically over time, and influencing all parts of their everyday lives. The adolescents entered vicious cycles, with despair and decreased physical and social functioning, with the risk of isolation and role-loss. However, these young people seem to have a strong motivation to strive for normalcy. These findings may encourage healthcare providers to perceive adolescents' persistent pain through the lenses of a biopsychosocial approach. We suggest that further research into adolescents with persistent pain should include longitudinal studies of quality of life and gender perspectives. Copyright © 2017 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Effects of a self-guided, web-based activity programme for patients with persistent musculoskeletal pain in primary healthcare: A randomized controlled trial.

PubMed

Calner, T; Nordin, C; Eriksson, M K; Nyberg, L; Gard, G; Michaelson, P

2017-07-01

Web-based interventions for pain management are increasingly used with possible benefits, but never used in addition to multimodal rehabilitation (MMR). MMR is recommended treatment for persistent pain in Sweden. The aim was to evaluate the effects of a self-guided, web-based programme added to MMR for work ability, pain, disability and health-related quality of life. We included 99 participants with persistent musculoskeletal pain in a randomized study with two intervention arms: (1) MMR and web-based intervention, and (2) MMR. Data was collected at baseline, 4 and 12 months. Outcome measures were work ability, working percentage, average pain intensity, pain-related disability, and health-related quality of life. There were no significant effects of adding the web-based intervention to MMR regarding any of the outcome variables. This trial provides no support for adding a self-guided, web-based activity programme to MMR for patients with persistent musculoskeletal pain. The comprehensive self-guided, web-based programme for activity, Web-BCPA, added to multimodal treatment in primary health care had no effect on work ability, pain, disability or health-related quality of life. Future web-based interventions should be tailored to patients' individual needs and expectations. © 2017 European Pain Federation - EFIC®.

Probing the Effects and Mechanisms of Electroacupuncture at Ipsilateral or Contralateral ST36–ST37 Acupoints on CFA-induced Inflammatory Pain

PubMed Central

Lu, Kung-Wen; Hsu, Chao-Kuei; Hsieh, Ching-Liang; Yang, Jun; Lin, Yi-Wen

2016-01-01

Transient receptor potential vanilloid 1 (TRPV1) and associated signaling pathways have been reported to be increased in inflammatory pain signaling. There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). EA can reliably attenuate the increase of TRPV1 in mouse inflammatory pain models with unclear signaling mechanisms. Moreover, the difference in the clinical therapeutic effects between using the contralateral and ipsilateral acupoints has been rarely studied. We found that inflammatory pain, which was induced by injecting the complete Freund’s adjuvant (CFA), (2.14 ± 0.1, p < 0.05, n = 8) can be alleviated after EA treatment at either ipsilateral (3.91 ± 0.21, p < 0.05, n = 8) or contralateral acupoints (3.79 ± 0.25, p < 0.05, n = 8). EA may also reduce nociceptive Nav sodium currents in dorsal root ganglion (DRG) neurons. The expression of TRPV1 and associated signaling pathways notably increased after the CFA injection; this expression can be further attenuated significantly in EA treatment. TRPV1 and associated signaling pathways can be prevented in TRPV1 knockout mice, suggesting that TRPV1 knockout mice are resistant to inflammatory pain. Through this study, we have increased the understanding of the mechanism that both ipsilateral and contralateral EA might alter TRPV1 and associated signaling pathways to reduce inflammatory pain. PMID:26906464

The association of persistent pain with out-patient addiction treatment outcomes and service utilization.

PubMed

Caldeiro, Ryan M; Malte, Carol A; Calsyn, Donald A; Baer, John S; Nichol, Paul; Kivlahan, Daniel R; Saxon, Andrew J

2008-12-01

To estimate the prevalence of persistent pain among veterans in out-patient addiction treatment and examine associated addiction treatment outcomes and medical and psychiatric service use. Analysis of data from a prospective randomized controlled trial comparing on-site versus referral primary care of veterans with substance dependence (n = 582), excluding opioid dependence who had at least one follow-up interview during the 12-month study period in a Veterans Affairs (VA) out-patient addiction treatment center. Pain status was classified as persistent (pain was rated moderate to very severe at all time-points), low (pain was rated none to mild at all time-points) or intermittent (all others). Main outcome measures were addiction treatment retention, addiction severity index (ASI) alcohol and drug composite scores, VA service utilization and treatment costs. A total of 33.2% of veterans reported persistent pain and 47.3% reported intermittent pain. All groups benefited from addiction treatment, but veterans with persistent pain were in treatment for an estimated 35.1 fewer days [95% confidence interval (CI) = -64.1, -6.1, P = 0.018], less likely to be abstinent from alcohol or drugs at 12 months [odds ratio (OR)(adj) = 0.52; 95% CI = 0.30,0.89; P = 0.018], had worse ASI alcohol composite scores at 12 months (beta(adj) = 0.09; 95% CI = 0.02,0.15; P = 0.007), were more likely to be medically hospitalized (OR(adj) = 2.70; 95% CI = 1.02,7.13; P = 0.046) and had higher total service costs compared to those with low pain ($17 766 versus $13 261, P = 0.012). Persistent pain is common among veterans in out-patient addiction treatment and is associated with poorer rates of abstinence, worse alcohol use severity and greater service utilization and costs than those with low pain.

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.

Evaluation of the incidence and risk factors associated with persistent frequency in interstitial cystitis/bladder pain syndrome and the efficacy of antimuscarinic treatment.

PubMed

Kim, Aram; Hoe, Kyeong-Ok; Shin, Jung Hyun; Choo, Myung-Soo

2017-09-01

To investigate the incidence and risk factors associated with persistent urinary frequency, and to evaluate the efficacy of antimuscarinic treatment. Interstitial cystitis/bladder pain syndrome (IC/BPS) patients complaining of persistent urinary frequency despite improved pain were evaluated. Before initial conventional treatment, each patient completed a voiding diary and symptom questionnaires. After conventional treatment, patients were divided according to the presence of pain and frequency. Improved pain was defined as lesser than 3 points in visual analogue scale, and persistent urinary frequency as >10 times/d. Risk factors for persistent frequency were identified through multivariate analysis. The efficacy of antimuscarinic treatment was assessed by the mean change of frequency. Of 171 IC/BPS patients treated with conventional therapy, 132 had improved pain after 3 months, but 72 had persistent frequency (72 of 132, 54.5%). Patients with persistent frequency had lower voided volume (p=0.008), lower maximal flow rate (p<0.001), lower maximal bladder capacity (p=0.003), and more frequent micturition (p<0.001) at baseline compared to those with improved frequency. Patients who took antimuscarinic agents showed slightly decreased urinary frequency, from 14.6 times/d to 13.5 times/d (p=0.438) after 3 months of medication. No patients showed more than a 20% decrease in frequency with antimuscarinics. About half of the patients with IC/BPS showed persistent frequency, with poor voiding function identified as a risk factor; antimuscarinic treatment was not effective in these patients.

Selective peripheral nerve resection for treatment of persistent pain around the knee joint after total knee arthroplasty.

PubMed

Zhong, Guangjun; Liang, Zhu; Kan, Jiang; Muheremu, Aikeremujiang

2018-01-01

Objective This study was performed to determine the efficacy of selective peripheral nerve resection for treatment of persistent neuropathic pain after total knee arthroplasty (TKA). Methods Patients who underwent TKA in our department from January 2013 to July 2016 and experienced persistent pain around the knee joint after TKA were retrospectively included in the current study. Sixty patients were divided into experimental and control groups according the treatment they received. The treatment effect was evaluated by the Hospital for Special Surgery (HSS) knee score and visual analog scale (VAS) pain score preoperatively and at 1, 2, 3, 6, and 12 months postoperatively. Results The HSS knee scores were higher in both groups after than before the treatment, and HSS knee scores were significantly higher in the experimental group than in the control group. The VAS pain scores were lower in both groups after than before the treatment, and VAS pain scores were significantly lower in the experimental group than in the control group. Conclusions Selective peripheral nerve resection is an effective treatment method for persistent neuropathic pain after TKA.

Preliminary evidence of a blunted anti-inflammatory response to exhaustive exercise in fibromyalgia

PubMed Central

Torgrimson-Ojerio, Britta; Ross, Rebecca L.; Dieckman, Nathaniel F.; Avery, Stephanie; Bennett, Robert M.; Jones, Kim D.; Guarino, Anthony J.; Wood, Lisa J.

2014-01-01

Exercise intolerance, as evidenced by a worsening of pain, fatigue, and stiffness after novel exertion, is a key feature of fibromyalgia (FM). In this pilot study, we investigate whether; insufficient muscle repair processes and impaired anti-inflammatory mechanisms result in an exaggerated pro-inflammatory cytokine response to exhaustive exercise, and consequently a worsening of muscle pain, stiffness and fatigue in the days post-exercise. We measured changes in muscle pain and tenderness, fatigue, stiffness, and serum levels of neuroendocrine and inflammatory cytokine markers in 20 women with FM and 16 healthy controls (HCs) before and after exhaustive treadmill exercise. Compared to HCs, FM participants failed to mount the expected anti-inflammatory response to exercise and experienced a worsening of symptoms post-exercise. However, changes in post-exertional symptoms were not mediated by post-exertional changes in pro-inflammatory cytokine levels. Implications of these findings are discussed. PMID:25457842

Central Sensitization and Neuropathic Features of Ongoing Pain in a Rat Model of Advanced Osteoarthritis.

PubMed

Havelin, Joshua; Imbert, Ian; Cormier, Jennifer; Allen, Joshua; Porreca, Frank; King, Tamara

2016-03-01

Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain and a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present study, palpation of the ipsilateral hind limb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced expression of the early oncogene, FOS, in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways using a microinjection of lidocaine within the rostral ventromedial medulla induced conditioned place preference selectively in rats treated with the high dose of MIA. Conditioned place preference to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, intraperitoneally at -30 minutes). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID-resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that might guide drug discovery for treatment of advanced OA pain without the need for joint replacement. Difficulty in managing advanced OA pain often results in joint replacement therapy in these patients. Improved understanding of mechanisms driving NSAID-resistant ongoing OA pain might facilitate development of alternatives to joint replacement therapy. Our findings suggest that central sensitization and neuropathic features contribute to NSAID-resistant ongoing OA joint pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Using emergency department-based inception cohorts to determine genetic characteristics associated with long term patient outcomes after motor vehicle collision: methodology of the CRASH study.

PubMed

Platts-Mills, Timothy F; Ballina, Lauren; Bortsov, Andrey V; Soward, April; Swor, Robert A; Jones, Jeffrey S; Lee, David C; Peak, David A; Domeier, Robert M; Rathlev, Niels K; Hendry, Phyllis L; McLean, Samuel A

2011-09-26

Persistent musculoskeletal pain and psychological sequelae following minor motor vehicle collision (MVC) are common problems with a large economic cost. Prospective studies of pain following MVC have demonstrated that demographic characteristics, including female gender and low education level, and psychological characteristics, including high pre-collision anxiety, are independent predictors of persistent pain. These results have contributed to the psychological and social components of a biopsychosocial model of post-MVC pain pathogenesis, but the biological contributors to the model remain poorly defined. Recent experimental studies indicate that genetic variations in adrenergic system function influence the vulnerability to post-traumatic pain, but no studies have examined the contribution of genetic factors to existing predictive models of vulnerability to persistent pain. The Project CRASH study is a federally supported, multicenter, prospective study designed to determine whether variations in genes affecting synaptic catecholamine levels and alpha and beta adrenergic receptor function augment social and psychological factors in a predictive model of persistent musculoskeletal pain and posttraumatic stress disorder (PTSD) following minor MVC. The Project CRASH study will assess pain, pain interference and PTSD symptoms at 6 weeks, 6 months, and 1 year in approximately 1,000 patients enrolled from 8 Emergency Departments in four states with no-fault accident laws. The results from this study will provide insights into the pathophysiology of persistent pain and PTSD following MVC and may serve to improve the ability of clinicians and researchers to identify individuals at high risk for adverse outcomes following minor MVC.

Macrophage-specific nanotechnology-driven CD163 overexpression in human macrophages results in an M2 phenotype under inflammatory conditions.

PubMed

Alvarado-Vazquez, Perla Abigail; Bernal, Laura; Paige, Candler A; Grosick, Rachel L; Moracho Vilrriales, Carolina; Ferreira, David Wilson; Ulecia-Morón, Cristina; Romero-Sandoval, E Alfonso

2017-08-01

M1 macrophages release proinflammatory factors during inflammation. They transit to an M2 phenotype and release anti-inflammatory factors to resolve inflammation. An imbalance in the transition from M1 to M2 phenotype in macrophages contributes to the development of persistent inflammation. CD163, a member of the scavenger receptor cysteine-rich family, is an M2 macrophage marker. The functional role of CD163 during the resolution of inflammation is not completely known. We postulate that CD163 contributes to the transition from M1 to M2 phenotype in macrophages. We induced CD163 gene in THP-1 and primary human macrophages using polyethylenimine nanoparticles grafted with a mannose ligand (Man-PEI). This nanoparticle specifically targets cells of monocytic origin via mannose receptors. Cells were challenged with a single or a double stimulation of lipopolysaccharide (LPS). A CD163 or empty plasmid was complexed with Man-PEI nanoparticles for cell transfections. Quantitative RT-PCR, immunocytochemistry, and ELISAs were used for molecular assessments. CD163-overexpressing macrophages displayed reduced levels of tumor necrosis factor-alpha (TNF)-α and monocytes chemoattractant protein (MCP)-1 after a single stimulation with LPS. Following a double stimulation paradigm, CD163-overexpressing macrophages showed an increase of interleukin (IL)-10 and IL-1ra and a reduction of MCP-1. This anti-inflammatory phenotype was partially blocked by an anti-CD163 antibody (effects on IL-10 and IL-1ra). A decrease in the release of TNF-α, IL-1β, and IL-6 was observed in CD163-overexpressing human primary macrophages. The release of IL-6 was blocked by an anti-CD163 antibody in the CD163-overexpressing group. Our data show that the induction of the CD163 gene in human macrophages under inflammatory conditions produces changes in cytokine secretion in favor of an anti-inflammatory phenotype. Targeting macrophages to induce CD163 using cell-directed nanotechnology is an attractive and practical approach for inflammatory conditions that could lead to persistent pain, i.e. major surgeries, burns, rheumatoid arthritis, etc. Copyright © 2017 Elsevier GmbH. All rights reserved.

The role of the blood-brain barrier in the development and treatment of migraine and other pain disorders.

PubMed

DosSantos, Marcos F; Holanda-Afonso, Rosenilde C; Lima, Rodrigo L; DaSilva, Alexandre F; Moura-Neto, Vivaldo

2014-01-01

The function of the blood-brain barrier (BBB) related to chronic pain has been explored for its classical role in regulating the transcellular and paracellular transport, thus controlling the flow of drugs that act at the central nervous system, such as opioid analgesics (e.g., morphine) and non-steroidal anti-inflammatory drugs. Nonetheless, recent studies have raised the possibility that changes in the BBB permeability might be associated with chronic pain. For instance, changes in the relative amounts of occludin isoforms, resulting in significant increases in the BBB permeability, have been demonstrated after inflammatory hyperalgesia. Furthermore, inflammatory pain produces structural changes in the P-glycoprotein, the major efflux transporter at the BBB. One possible explanation for these findings is the action of substances typically released at the site of peripheral injuries that could lead to changes in the brain endothelial permeability, including substance P, calcitonin gene-related peptide, and interleukin-1 beta. Interestingly, inflammatory pain also results in microglial activation, which potentiates the BBB damage. In fact, astrocytes and microglia play a critical role in maintaining the BBB integrity and the activation of those cells is considered a key mechanism underlying chronic pain. Despite the recent advances in the understanding of BBB function in pain development as well as its interference in the efficacy of analgesic drugs, there remain unknowns regarding the molecular mechanisms involved in this process. In this review, we explore the connection between the BBB as well as the blood-spinal cord barrier and blood-nerve barrier, and pain, focusing on cellular and molecular mechanisms of BBB permeabilization induced by inflammatory or neuropathic pain and migraine.

The role of the blood–brain barrier in the development and treatment of migraine and other pain disorders

PubMed Central

DosSantos, Marcos F.; Holanda-Afonso, Rosenilde C.; Lima, Rodrigo L.; DaSilva, Alexandre F.; Moura-Neto, Vivaldo

2014-01-01

The function of the blood–brain barrier (BBB) related to chronic pain has been explored for its classical role in regulating the transcellular and paracellular transport, thus controlling the flow of drugs that act at the central nervous system, such as opioid analgesics (e.g., morphine) and non-steroidal anti-inflammatory drugs. Nonetheless, recent studies have raised the possibility that changes in the BBB permeability might be associated with chronic pain. For instance, changes in the relative amounts of occludin isoforms, resulting in significant increases in the BBB permeability, have been demonstrated after inflammatory hyperalgesia. Furthermore, inflammatory pain produces structural changes in the P-glycoprotein, the major efflux transporter at the BBB. One possible explanation for these findings is the action of substances typically released at the site of peripheral injuries that could lead to changes in the brain endothelial permeability, including substance P, calcitonin gene-related peptide, and interleukin-1 beta. Interestingly, inflammatory pain also results in microglial activation, which potentiates the BBB damage. In fact, astrocytes and microglia play a critical role in maintaining the BBB integrity and the activation of those cells is considered a key mechanism underlying chronic pain. Despite the recent advances in the understanding of BBB function in pain development as well as its interference in the efficacy of analgesic drugs, there remain unknowns regarding the molecular mechanisms involved in this process. In this review, we explore the connection between the BBB as well as the blood–spinal cord barrier and blood–nerve barrier, and pain, focusing on cellular and molecular mechanisms of BBB permeabilization induced by inflammatory or neuropathic pain and migraine. PMID:25339863

Role of sodium ferulate in the nociceptive sensory facilitation of neuropathic pain injury mediated by P2X(3) receptor.

PubMed

Zhang, Aixia; Xu, Changshui; Liang, Shangdong; Gao, Yun; Li, Guilin; Wei, Jie; Wan, Fang; Liu, Shuangmei; Lin, Jiari

2008-12-01

Neuropathic pain usually is persistent and no effective treatment. ATP plays an important role in the initiation of pain. P2X(3) receptors are localized in the dorsal root ganglion (DRG) neurons and activated by extracellular ATP. Sodium ferulate (SF) is an active principle from Chinese herbal medicine and has anti-inflammatory activities. This study observed the effects of SF on the nociceptive facilitation of the primary sensory afferent after chronic constriction injury (CCI) mediated by P2X(3) receptor. In this study, the content of ATP in DRG neurons was measured by high-performance liquid chromatography (HPLC). P2X(3) agonist-activated currents in DRG neurons was recorded by the whole-cell patch-clamp skill. The expression of P2X(3) mRNA in DRG neurons was analyzed by in situ hybridization. The ATP content of DRG was increased after CCI. In CCI rats treated with SF, the content of ATP in DRG neurons was reduced. SF decreased the increment of P2X(3) agonist-activated currents and P2X(3) mRNA expression in DRG neurons during CCI. SF may inhibit the initiation of pain and primary afferent sensitization mediated by P2X(3) receptor during CCI.

A retrospective study on persistent pain after childbirth in the Netherlands

PubMed Central

Bijl, Rianne C; Freeman, Liv M; Weijenborg, Philomeen TM; Middeldorp, Johanna M; Dahan, Albert; van Dorp, Eveline LA

2016-01-01

Reported prevalence rates of persistent postpartum pain (PPP) range from less than 1% to almost 20%. The aim of this study was to examine the prevalence of PPP in a Dutch cohort and to evaluate a possible causal role for specific risk factors on the development of chronic pain after childbirth. A questionnaire was sent to 960 postpartum women approximately 2 years after delivery. Primary outcome was pain that arose from childbirth at follow-up, and secondary outcomes included quality of life (QoL) and Hospital Anxiety and Depression Scale scores. Tested risk factors included mode of labor analgesia, history of negative effect, history of chronic pain, delivery route, parity, and ethnicity. A total of 495 (51.6%) women participated. At a mean time of 2.3 postpartum years, 7.3% of women reported any pain and 6.1% reported significant pain related to the delivery. Compared to spontaneous delivery, cesarean delivery provided protection against persistent pain (odds ratio, 0.12; 95% CI, 0.01–0.63, P<0.05). None of the other risk factors, including remifentanil use for labor pain, were of influence on the prevalence of persistent pain. Women with PPP experienced greater negative effects and had lower QoL scores compared to women without pain. In this cohort of Dutch patients, PPP is a serious problem with a great impact on the physical and mental health of women. PMID:26834496

An evaluation of the antinociceptive effects of Phα1β, a neurotoxin from the spider Phoneutria nigriventer, and ω-conotoxin MVIIA, a cone snail Conus magus toxin, in rat model of inflammatory and neuropathic pain.

PubMed

de Souza, Alessandra Hubner; Castro, Célio J; Rigo, Flavia Karine; de Oliveira, Sara Marchesan; Gomez, Renato Santiago; Diniz, Danuza Montijo; Borges, Marcia Helena; Cordeiro, Marta Nascimento; Silva, Marco Aurélio Romano; Ferreira, Juliano; Gomez, Marcus Vinicius

2013-01-01

Voltage-sensitive calcium channels (VSCCs) underlie cell excitability and are involved in the mechanisms that generate and maintain neuropathic and inflammatory pain. We evaluated in rats the effects of two VSCC blockers, ω-conotoxin MVIIA and Phα1β, in models of inflammatory and neuropathic pain induced with complete Freund's adjuvant (CFA) and chronic constrictive injury (CCI), respectively. We also evaluated the effects of the toxins on capsaicin-induced Ca(2+) influx in dorsal root ganglion (DRG) neurons obtained from rats exposed to both models of pain. A single intrathecal injection of Phα1β reversibly inhibits CFA and CCI-induced mechanical hyperalgesia longer than a single injection of ω-conotoxin MVIIA. Phα1β and MVIIA also inhibited capsaicin-induced Ca(2+) influx in DRG neurons. The inhibitory effect of Phα1β on capsaicin-induced calcium transients in DRG neurons was greater in the CFA model of pain, while the inhibitory effect of ω-conotoxin MVIIA was greater in the CCI model. The management of chronic inflammatory and neuropathic pain is still a major challenge for clinicians. Phα1β, a reversible inhibitor of VSCCs with a preference for N-type Ca(2+) channels, has potential as a novel therapeutic agent for inflammatory and neuropathic pain. Clinical studies are necessary to establish the role of Phα1β in the treatment of chronic pain.

Overlap between functional abdominal pain disorders and organic diseases in children.

PubMed

Langshaw, A H; Rosen, J M; Pensabene, L; Borrelli, O; Salvatore, S; Thapar, N; Concolino, D; Saps, M

2018-04-02

Functional abdominal pain disorders are highly prevalent in children. These disorders can be present in isolation or combined with organic diseases, such as celiac disease and inflammatory bowel diseases. Intestinal inflammation (infectious and non-infectious) predisposes children to the development of visceral hypersensitivity that can manifest as functional abdominal pain disorders, including irritable bowel syndrome. The new onset of irritable bowel syndrome symptoms in a patient with an underlying organic disease, such as inflammatory bowel disease, is clinically challenging, given that the same symptomatology may represent a flare-up of the inflammatory bowel disease or an overlapping functional abdominal pain disorder. Similarly, irritable bowel syndrome symptoms in a child previously diagnosed with celiac disease may occur due to poorly controlled celiac disease or the overlap with a functional abdominal pain disorder. There is little research on the overlap of functional abdominal disorders with organic diseases in children. Studies suggest that the overlap between functional abdominal pain disorders and inflammatory bowel disease is more common in adults than in children. The causes for these differences in prevalence are unknown. Only a handful of studies have been published on the overlap between celiac disease and functional abdominal pain disorders in children. The present article provides a review of the literature on the overlap between celiac disease, inflammatory bowel disease, and functional abdominal pain disorders in children and establish comparisons with studies conducted on adults. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Is the Whipple procedure harmful for long-term outcome in treatment of chronic pancreatitis? 15-years follow-up comparing the outcome after pylorus-preserving pancreatoduodenectomy and Frey procedure in chronic pancreatitis.

PubMed

Bachmann, Kai; Tomkoetter, Lena; Kutup, Asad; Erbes, Johannes; Vashist, Yogesh; Mann, Oliver; Bockhorn, Maximilian; Izbicki, Jakob R

2013-11-01

The aim of this study was to report on 15-year long-term results of a randomized controlled trial comparing extended drainage procedure (Frey) and classical resectional procedure [pylorus-preserving pancreatoduodenectomy (PD)] in patients with chronic pancreatitis. Chronic pancreatitis is a common inflammatory disease with a prevalence of 10 to 30 cases per 100,000 inhabitants. It is characterized by the progressive conversion of pancreatic parenchyma to fibrous tissue. Different surgical procedures are used in treatment of persistent pain. Sixty-four patients suffering from chronic pancreatitis with inflammatory mass in the pancreatic head were randomly assigned in 2 treatment groups (PD, n = 32) and (Frey, n = 32). The perioperative course of the randomized controlled trial and the 7 years follow-up have been previously published. All participating patients were contacted with a standardized, validated questionnaire (EORTC QLQ C30) to evaluate the long-term survival, quality-of-life pain, and exocrine and endocrine function. In the 15-year long-term follow-up, the pain control was good and comparable between both groups, but the quality of life was better after Frey procedure in regard of the physical status [PD: 100 (0-100) vs PD: 60 (0-100) (P = 0.011)]. No significant differences in terms of the Pain Score were detected between both groups [PD: 7 (0-100) vs Frey 4 (0-100) P = 0.258]. Seven patients after Frey OP and 6 patients after PD were free of pain. Analyzing the postoperative overall survival, a higher long-term mortality was found after PD (53%) than that found after Frey procedure (30%) resulting in a longer mean survival (14.5 ± 0.8 vs 11.3 ± 0.8 years; P = 0.037). No correlation between endocrine or exocrine pancreatic function and pain was found, whereas continuous alcohol consumption was associated with poorer outcome regarding quality of life (P < 0.001) and pain score (P < 0.001). PD and Frey procedure provide good and permanent pain relief and improvement of the quality of life in long-term follow-up. In addition, a longer survival was found after the organ sparing resection. Together with better short-term results, the organ-sparing procedure seems to be favorable in treatment of chronic pancreatitis.

Cellular, molecular, and epigenetic mechanisms in non-associative conditioning: implications for pain and memory.

PubMed

Rahn, Elizabeth J; Guzman-Karlsson, Mikael C; David Sweatt, J

2013-10-01

Sensitization is a form of non-associative conditioning in which amplification of behavioral responses can occur following presentation of an aversive or noxious stimulus. Understanding the cellular and molecular underpinnings of sensitization has been an overarching theme spanning the field of learning and memory as well as that of pain research. In this review we examine how sensitization, both in the context of learning as well as pain processing, shares evolutionarily conserved behavioral, cellular/synaptic, and epigenetic mechanisms across phyla. First, we characterize the behavioral phenomenon of sensitization both in invertebrates and vertebrates. Particular emphasis is placed on long-term sensitization (LTS) of withdrawal reflexes in Aplysia following aversive stimulation or injury, although additional invertebrate models are also covered. In the context of vertebrates, sensitization of mammalian hyperarousal in a model of post-traumatic stress disorder (PTSD), as well as mammalian models of inflammatory and neuropathic pain is characterized. Second, we investigate the cellular and synaptic mechanisms underlying these behaviors. We focus our discussion on serotonin-mediated long-term facilitation (LTF) and axotomy-mediated long-term hyperexcitability (LTH) in reduced Aplysia systems, as well as mammalian spinal plasticity mechanisms of central sensitization. Third, we explore recent evidence implicating epigenetic mechanisms in learning- and pain-related sensitization. This review illustrates the fundamental and functional overlay of the learning and memory field with the pain field which argues for homologous persistent plasticity mechanisms in response to sensitizing stimuli or injury across phyla. Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical stimulation of the lateral hypothalamus by carbachol attenuated the formalin-induced pain behaviors in rats.

PubMed

Ezzatpanah, Somayeh; Babapour, Vahab; Sadeghi, Bahman; Haghparast, Abbas

2015-02-01

Electrical and chemical stimulation of the lateral hypothalamus (LH) produces analgesia. Previous studies emphasized the importance of LH in the modulation of nociceptive behaviors in the acute pain models. In the current study, for the first time, we examined the effect of direct chemical stimulation of the LH with cholinergic receptor agonist, carbachol, on pain-related behaviors in the formalin test as a model of persistent inflammatory pain. Forty-eight adult male Wistar rats were implanted unilaterally with cannula into the LH. Four doses of carbachol (62.5, 125, 250 and 500 nM/0.5 μl saline) were microinjected into the LH just 5 min before the formalin test. Vehicle group received 0.5 μl saline into the LH. Pain-related behaviors were quantified and monitored in 5-min blocks for 60 min test period. Average nociceptive scores and area under the curve (AUC) as raw pain scores × time by the linear trapezoidal method were used for the statistical analyses. One important finding of our study was that carbachol blocks the nociceptive responses in both phases of formalin-induced nociception in a dose-dependent manner. Altogether, the percentage decrease of AUC values calculated for treatment groups, compared to the control group, was more significant in the late phase than the early phase. These findings suggest that LH modulates formalin-induced nociception through spinal and/or supraspinal sites. Copyright © 2014 Elsevier Inc. All rights reserved.

Disruption of δ-opioid receptor phosphorylation at threonine 161 attenuates morphine tolerance in rats with CFA-induced inflammatory hypersensitivity.

PubMed

Chen, Hai-Jing; Xie, Wei-Yan; Hu, Fang; Zhang, Ying; Wang, Jun; Wang, Yun

2012-04-01

Our previous study identified Threonine 161 (Thr-161), located in the second intracellular loop of the δ-opioid receptor (DOR), as the only consensus phosphorylation site for cyclin-dependent kinase 5 (Cdk5). The aim of this study was to assess the function of DOR phosphorylation by Cdk5 in complete Freund's adjuvant (CFA)-induced inflammatory pain and morphine tolerance. Dorsal root ganglion (DRG) neurons of rats with CFA-induced inflammatory pain were acutely dissociated and the biotinylation method was used to explore the membrane localization of phosphorylated DOR at Thr-161 (pThr-161-DOR), and paw withdrawal latency was measured after intrathecal delivery of drugs or Tat-peptide, using a radiant heat stimulator in rats with CFA-induced inflammatory pain. Both the total amount and the surface localization of pThr-161-DOR were significantly enhanced in the ipsilateral DRG following CFA injection. Intrathecal delivery of the engineered Tat fusion-interefering peptide corresponding to the second intracellular loop of DOR (Tat-DOR-2L) increased inflammatory hypersensitivity, and inhibited DOR- but not µ-opioid receptor-mediated spinal analgesia in CFA-treated rats. However, intrathecal delivery of Tat-DOR-2L postponed morphine antinociceptive tolerance in rats with CFA-induced inflammatory pain. Phosphorylation of DOR at Thr-161 by Cdk5 attenuates hypersensitivity and potentiates morphine tolerance in rats with CFA-induced inflammatory pain, while disruption of the phosphorylation of DOR at Thr-161 attenuates morphine tolerance.

Incidence and impact of painful exacerbations in a cohort with post-treatment persistent endodontic lesions.

PubMed

Yu, Victoria Soo Hoon; Messer, Harold H; Yee, Robert; Shen, Liang

2012-01-01

Painful exacerbations of persistent periapical lesions have unknown incidence and impact on quality of life. This study examined the incidence and impact of painful exacerbations and evaluated potential predictive factors of pain associated with root-filled teeth with persistent lesions after root canal treatment. Patients from a university hospital clinic were screened to identify root-filled teeth with periapical lesions at time of treatment and not resolved at least 4 years later. A clinical and radiographic examination and questionnaire survey were conducted. Patient and treatment characteristics and details of pain experience were studied. Statistical analysis was carried out by using SPSS (version 18). One hundred twenty-seven patients with 185 persistent lesions were recruited. Median age of patients at recruitment was 56 years (range, 21-82 years). Median time since treatment was 5 years (range, 4-38 years). Overall incidence of flare-up (requiring an unscheduled dental visit) was only 5.8% 20 years after treatment. Less severe pain was more frequent, with a combined incidence of 45% pain at 20 years after treatment. Female patients (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.2-6.0; P < .05), treatment involving a mandibular molar or maxillary premolar (OR, 3.7; 95% CI, 1.6-8.6; P < .05), and preoperative pain (OR, 2.9; 95% CI, 1.3-6.7; P < .05) were significantly associated with pain after treatment. The most commonly affected activities during painful exacerbations were eating and tooth brushing, with minimal impact on daily living. The risk of flare-up among persistent lesions was very low. A lower degree of pain was more common, but generally with minimal impact on daily activities. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

The analgesic effects of oxytocin in the peripheral and central nervous system.

PubMed

Xin, Qing; Bai, Bo; Liu, Wenyan

2017-02-01

Pain is a ubiquitously unpleasant feeling among humans as well as many animal species often caused by actual and potential tissue damage. However, it is absolutely crucial for our survival in many ways. Acute pain can signal the presence of danger or life-threatenting events, which help escape noxious stimuli. By contrast, when pain becomes chronic or persistent, it becomes an encumbrance and exerts deleterious effects to the body and mind, often co-occured with anxiety and depression. Additionaly, chronic pain is more or less an economic burden for the patients because it requires immediate medical treatments and seriously hinders pepople in their work. To date, there has been a lack of breakthrough progress in the pain field, despite huge gains in basic science knowledge obtained using animal models, it is still difficult to develop many new clinically effective analgesic drugs to control pain with long-term effectiveness. Opioids and nonsteroidal anti-inflammatory drugs were introduced for pain management more than a century ago. Those drugs do have proven efficacy in the treatment of pain but the use of them are also significantly limited due to the multiple serious adverse effects (e.g., drug resistance, addiction and gastrointestinal bleeding). In the field of pain relief and treatment, there is a strong impetus to develop and establish novel analgesics that must be safer and more effective to offer significant pain relief for a wide variety of painful conditions. Preliminary evidence suggests that oxytocin might be the ideal candidate as a target for reducing the severity of pain. In this review, we present a summary of the total literature related to the effects of oxytocin on pain modulation in both animals and humans. Better understanding the fundamental physiopharmacology of the actions of oxytocin in pain may highlight novel mechanisms associated with analgesia. Copyright © 2017 Elsevier Ltd. All rights reserved.

LATERAL EPICONDYLITIS OF THE ELBOW

PubMed Central

Cohen, Marcio; da Rocha Motta Filho, Geraldo

2015-01-01

Lateral epicondylitis, also known as tennis elbow, is a common condition that is estimated to affect 1% to 3% of the population. The word epicondylitis suggests inflammation, although histological analysis on the tissue fails to show any inflammatory process. The structure most commonly affected is the origin of the tendon of the extensor carpi radialis brevis and the mechanism of injury is associated with overloading. Nonsurgical treatment is the preferred method, and this includes rest, physiotherapy, cortisone infiltration, platelet-rich plasma injections and use of specific immobilization. Surgical treatment is recommended when functional disability and pain persist. Both the open and the arthroscopic surgical technique with resection of the degenerated tendon tissue present good results in the literature. PMID:27047843

The roles of special proresolving mediators in pain relief.

PubMed

Zhang, Lan-Yu; Jia, Ming-Rui; Sun, Tao

2018-02-08

The resolution of acute inflammation, once thought to be a passive process, is now recognized as an active one. The productions of endogenous special proresolving mediators (SPMs) are involved in this process. SPMs, including lipoxins, resolvins, protectins, and maresins, are endogenous lipid mediators generated from ω-6 arachidonic acid or ω-3 poly-unsaturated fatty acids during the resolution phase of acute inflammation. They have potent anti-inflammatory and proresolving actions in various inflammatory disorders. Due to the potent proresolving and anti-inflammatory effects, SPMs are also used for pain relief. This review focuses on the mechanisms by which SPMs act on their respective G-protein-coupled receptors in immune cells and nerve cells to normalize pain via regulating inflammatory mediators, transient receptor potential ion channels, and central sensitization. SPMs may offer novel therapeutic approaches for preventing and treating pain conditions associated with inflammation.

DDD-028: a potent potential non-opioid, non-cannabinoid analgesic for neuropathic and inflammatory pain.

PubMed

Rajagopalan, Parthasarathi; Tracey, Heather; Chen, Zhoumou; Bandyopadhyaya, Acintya; Veeraraghavan, Sridhar; Rajagopalan, Desikan R; Salvemini, Daniela; McPhee, Ian; Viswanadha, Srikant; Rajagopalan, Raghavan

2014-07-15

DDD-028 (4), a novel pentacyclic pyridoindolobenzazepine derivative was evaluated in vitro for receptor binding affinity and in vivo for analgesic activity using rodent models of neuropathic and inflammatory pain. DDD-028 does not bind to opioid, cannabinoid, dopamine, or histamine receptors. DDD-028 is very active even at the low oral dose of 1-5 mg/kg in both neuropathic, (spinal nerve ligation and chronic constriction injury) and inflammatory (Complete Freund's Adjuvant Induced) models of pain. DDD-028 appears to be about 6-fold more potent than pregabalin and indomethacin. Visual observation of all the animals used in these studies indicated that DDD-028 is well tolerated without any sedation. Thus, DDD-028 seems to be a promising candidate for the treatment of neuropathic and inflammatory pain without the possible side effects or abuse potential associated with opioid or cannabinoid activities. Copyright © 2014 Elsevier Ltd. All rights reserved.

The efficacy of oral non-steroidal anti-inflammatory drugs for rotator cuff tendinopathy: a systematic review and meta-analysis.

PubMed

Boudreault, Jennifer; Desmeules, François; Roy, Jean-Sébastien; Dionne, Clermont; Frémont, Pierre; Macdermid, Joy C

2014-04-01

To conduct a systematic review and meta-analysis on the efficacy of oral non-steroidal anti-inflammatory drugs for rotator cuff tendinopathy. Systematic review. A literature search was conducted in 4 databases for randomized controlled trials published until 05/2013, comparing the efficacy of oral anti-inflammatory drugs to any other intervention. Studies characteristics were extracted using a standardized form and the methodological quality was evaluated. Results were summarized qualitatively or quantitatively. The mean methodological score of the 12 included studies was 53.6 ± 8.8%. The majority of studies included acute cases and were underpowered to detect differences in adverse events. Compared to a placebo, oral non-steroidal anti-inflammatory drugs were found to provide short-term pain relief (pooled mean difference: -2.69; 95% confidence interval: -1.96 to -3.41) but not function. Oral anti-inflammatory- drugs and corticosteroids injections have similar short-term efficacy in terms of pain reduction as well as in function (pooled standardized mean difference: 0.09; 95% confidence interval: -0.25 to 0.44). Low to moderate grade evidence exists regarding the efficacy of non-steroidal anti-inflammatory drugs for rotator cuff tendinopathy. Oral anti-inflammatory drugs are effective in reducing short-term pain but not function. In terms of pain and function, oral anti-inflammatory drugs in the short term are as effective as corticosteroid injections.

An Online Cross-Sectional Comparison of Women With Symptoms of Persistent Genital Arousal, Painful Persistent Genital Arousal, and Chronic Vulvar Pain.

PubMed

Jackowich, Robyn A; Pink, Leah; Gordon, Allan; Poirier, Évéline; Pukall, Caroline F

2018-04-01

Persistent genital arousal disorder (PGAD) is an understudied condition characterized by unwanted physiologic genital arousal in the absence of subjective sexual arousal. Markos and Dinsmore (Int J STD AIDS 2013;24:852-858) theorized that PGAD shares a number of similarities with vulvodynia (unexplained chronic vulvar pain [CVP]), including symptom characteristics and comorbidities. To compare medical histories, symptom characteristics, pain characteristics, and daily functioning among women with persistent genital pain (PGA) (n = 42), painful PGA (n = 37), and CVP (n = 42) symptoms. An online cross-sectional survey was conducted from October 2015 through April 2016. Self-report measures of symptoms, diagnosed medical conditions, pain characteristics (McGill Pain Questionnaire), catastrophizing (Pain Catastrophizing Scale), and daily functioning (Functional Status Questionnaire) were collected. All 3 groups reported similar medical diagnoses and high frequencies of other chronic pelvic pain conditions. Women in all 3 groups reported comparable ages at symptom onset and timing of symptom expression (ie, constant vs intermittent). Women in the 2 PGA groups reported significantly greater feelings of helplessness than women in the CVP group. Women in the painful PGA and CVP groups endorsed significantly more sensory terms to describe their symptoms compared with women in the PGA group, whereas women in the painful PGA group reported significantly more affective terms to describe their symptoms compared with women in the CVP group. Women in the 2 PGA groups reported that their symptoms interfered significantly with most areas of daily functioning. Given the similarities between PGA and CVP symptoms, women with PGA may benefit from similar assessment, treatment, and research approaches. Limitations of the present study include its sole use of self-report measures; the presence of PGA or CVP symptoms was not confirmed by clinical assessment. However, the anonymous design of the online survey could have resulted in a larger and more diverse sample. The results of this study provide some initial support for the conceptualization of persistent genital arousal as a subtype of genital paresthesias/discomfort. These results also further highlight the negative impact that PGA symptoms have on many domains of daily living and the need for further research on this distressing condition. Jackowich RA, Pink L, Gordon A, et al. An Online Cross-Sectional Comparison of Women With Symptoms of Persistent Genital Arousal, Painful Persistent Genital Arousal, and Chronic Vulvar Pain. J Sex Med 2018;15:558-567. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Protective Effects of Sinomenine on CFA-Induced Inflammatory Pain in Rats.

PubMed

Yuan, Yan; Zhang, Yongjun; He, Xiaofeng; Fan, Shengdeng

2018-04-05

BACKGROUND The purpose of this study was to investigate the effects of sinomenine (SIN) on CFA-induced inflammatory pain in rats, and to explore the underlying molecular mechanisms. MATERIAL AND METHODS To determine the potential influences of SIN in the pathogenesis of inflammatory pain, an inflammatory pain (IP) mouse model was established and rats were treated with SIN (30 mg/kg). Behavioral tests were used to assess the MWT and TWL of the rats. ELISA assay was used to detect the level of inflammation cytokines. Western blotting and qRT-PCR were carried out to measure the related protein and mRNA expression level, respectively. RESULTS We found that the MWT and TWL of the CFA-treated rats were markedly lower than that of the control rats, and they were significantly increased by SIN administration. The results suggest that IP rats had higher levels of TNF-α, IL-1β and IL-6 compared with the control rats. SIN administration decreased the levels of TNF-α, IL-1β, and IL-6. In addition, we found that p-p65 and p-p38 expression notably decreased after SIN treatment in IP rats. Moreover, the results showed that SIN inhibited Cox-2 and PGE2 expression in IP rats. CONCLUSIONS The data indicate that SIN had a protective role in inflammatory pain through repressing inflammatory mediators via preventing the p38MAPK-NF-κB pathway.

Illness perceptions in the context of differing work participation outcomes: exploring the influence of significant others in persistent back pain

PubMed Central

2013-01-01

Background Previous research has demonstrated that the significant others of individuals with persistent back pain may have important influences on work participation outcomes. The aim of this study was to extend previous research by including individuals who have remained in work despite persistent back pain in addition to those who had become incapacitated for work, along with their significant others. The purpose of this research was to explore whether the illness beliefs of significant others differed depending on their relative’s working status, and to make some preliminary identification of how significant others may facilitate or hinder work participation for those with persistent back pain. Methods Interviews structured around the Illness Perception Questionnaire (chronic pain version) were conducted with back pain patients recruited from a hospital pain management clinic along with their significant others. Some patients had remained in work despite their back pain; others had ceased employment. Data were analysed using template analysis. Results There were clear differences between beliefs about, and reported responses to, back pain symptoms amongst the significant others of individuals who had remained in employment compared with the significant others of those who had ceased work. Three overarching themes emerged: perceived consequences of back pain, specific nature of employment and the impact of back pain on patient identity. Conclusions Significant others of employed individuals with back pain focused on the extent to which activity could still be undertaken despite back pain symptoms. Individuals out of work due to persistent back pain apparently self-limited their activity and were supported in their beliefs and behaviours by their significant others. To justify incapacity due to back pain, this group had seemingly become entrenched in a position whereby it was crucial that the individual with back pain was perceived as completely disabled. We suggest that significant others are clearly important, and potentially detrimental, sources of support to individuals with back pain. The inclusion of significant others in vocational rehabilitation programmes could potentially be a valuable way of mobilising readily accessible resources in a way that supports optimal functioning. PMID:23363454

Recurrent Fever, Anemia, Arthralgia, and Genu Varum as Late Manifestations of Congenital Syphilis.

PubMed

Quaresma, Liliana; Gonçalves, Juan; Estanqueiro, Paula; Salgado, Manuel

2015-12-01

We report an unusual case of recurrent fever, inflammatory knee pain, genu varum, persistent anemia, and high erythrocyte sedimentation rate in a 28-month-old boy as late manifestations of congenital syphilis (CS). Despite standard penicillin treatment at the end of the first month of life, it recurred later in life, more than once. In the first relapse, manifested by a likely gumma lesion, the prior penicillin treatment plus a negative venereal disease research laboratory result unduly led to exclusion of CS. A second treatment with penicillin led to complete clinical resolution. Although rare, bow legs, recurrent fever, anemia, and inflammatory arthralgias may be manifestations of late CS. Congenital syphilis should be considered throughout early childhood, especially if history of syphilis infection is present. A negative venereal disease research laboratory result does not exclude late syphilis, present in nearly 30% of these patients. The possibility of atypical symptoms of this "great masquerader" should always be borne in mind.

Role of orexin-2 receptors in the nucleus accumbens in antinociception induced by carbachol stimulation of the lateral hypothalamus in formalin test.

PubMed

Yazdi, Fatemeh; Jahangirvand, Mahboubeh; Ezzatpanah, Somayeh; Haghparast, Abbas

2016-08-01

Orexins, which are mainly produced by orexin-expressing neurons in the lateral hypothalamus (LH), play an important role in pain modulation. Previously, it has been established that the nucleus accumbens (NAc) is involved in the modulation of formalin-induced nociceptive responses, a model of tonic pain. In this study, the role of intra-accumbal orexin-2 receptors (OX2rs) in the mediation of formalin-induced pain was investigated. A volume of 0.5 μl of 10, 20, and 40 nmol/l solutions of TCS OX2 29, an OX2r antagonist, were unilaterally microinjected into the NAc 5 min before an intra-LH carbachol microinjection (0.5 μl of 250 nmol/l solution). After 5 min, animals received a subcutaneous injection of formalin 2.5% (50 μl) into the hind paw. Pain-related behaviors were assessed at 5 min intervals during a 60-min test period. The findings showed that TCS OX2 29 administration dose dependently blocked carbachol-induced antinociception during both phases of formalin-induced pain. The antianalgesic effect of TCS OX2 29 was greater during the late phase compared with the early phase. These observations suggest that the NAc, as a part of a descending pain-modulatory circuitry, partially mediates LH-induced analgesia in the formalin test through recruitment of OX2rs. This makes the orexinergic system a good potential therapeutic target in the control of persistent inflammatory pain.

Young people's experiences of persistent musculoskeletal pain, needs, gaps and perceptions about the role of digital technologies to support their co-care: a qualitative study.

PubMed

Slater, Helen; Jordan, Joanne E; Chua, Jason; Schütze, Robert; Wark, John D; Briggs, Andrew M

2016-12-09

To investigate young people's experiences of persistent musculoskeletal pain, including care needs and current service gaps as well as perceptions about the role of digital technologies to support their co-care. A qualitative study employing two independent data collection modes: in-depth individual semistructured interviews and focus groups. Community settings throughout Australia. Participants were included if they had experienced persistent musculoskeletal pain of >3-month duration with an average of ≥3 on the visual analogue scale over the preceding 3 months, including non-specific conditions (eg, low back pain) and specific conditions (eg, juvenile idiopathic arthritis and other systemic arthritides), with/without pre-existing or current diagnosed mental health conditions. 23 young people (87.0% women; mean (SD) age: 20.8 (2.4) years) from across 6 Australian jurisdictions participated. Almost two-thirds of participants with persistent musculoskeletal pain reported comorbid mental health conditions. Inductive and deductive approaches to analyse and derive key themes from verbatim transcripts. Participants described their daily experiences of living with persistent musculoskeletal pain, their fears and the challenges imposed by the invisibility of pain, and the two-way relationship between their pain and mental well-being. A lack of relevant and accessible information and resources tailored to young people's unique needs, integrated and youth-relevant healthcare services and adequately skilled healthcare practitioners were identified as key care gaps. Participants strongly advocated for the use of digital technologies to improve access to age-appropriate resources and support for co-care. Young people living with persistent musculoskeletal pain described the absence of age-appropriate pain services and clearly articulated their perceptions on the role of, and opportunities provided by, digital technologies to connect with and support improved pain healthcare. Innovative and digitally-enabled models of pain care are likely to be helpful for this group. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A human trial of HSV mediated gene transfer for the treatment of chronic pain

PubMed Central

Wolfe, Darren; Mata, Marina; Fink, David J.

2009-01-01

Gene transfer to the dorsal root ganglion using replication defective herpes simplex virus (HSV)-based vectors reduces pain related behaviors in rodent models of inflammatory pain, neuropathic pain, and pain caused by cancer in bone. HSV vectors engineered to produce inhibitory neurotransmitters including the delta opioid agonist peptide enkephalin, the mu opioid agonist peptide endomorphin-2 and glutamic acid decarboxylase (GAD) to effect the release of gamma amino butyric acid (GABA) act to inhibit nociceptive neurotransmission at the first synapse between primary nociceptive and second-order neuron in the dorsal horn of spinal cord. HSV vectors engineered to release anti-inflammatory peptides including interleukin (IL)-4, IL-10 and the p55 soluble tumor necrosis factor α (TNFα) receptor reduce neuroimmune activation in the spinal dorsal horn. The path leading from preclinical animal studies to the ongoing phase 1 human trial of the enkephalin-producing vector in patients with pain from cancer, and plans for an efficacy trial with an opioid producing vector in inflammatory pain and an efficacy trial with a GAD producing vector in diabetic neuropathic pain are outlined. PMID:19242524

Perioperative psychotherapy for persistent post-surgical pain and physical impairment: a meta-analysis of randomised trials.

PubMed

Wang, L; Chang, Y; Kennedy, S A; Hong, P J; Chow, N; Couban, R J; McCabe, R E; Bieling, P J; Busse, J W

2018-06-01

Persistent post-surgical pain affects 10-80% of individuals after common operations, and is more common among patients with psychological factors such as depression, anxiety, or catastrophising. We conducted a systematic review and meta-analysis of randomised, controlled trials to evaluate the efficacy of perioperative psychotherapy for persistent post-surgical pain and physical impairment. Paired independent reviewers identified studies, extracted data, and assessed risk of bias. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence. Our search of five electronic databases, up to September 1, 2016, found 15 trials (2220 patients) that were eligible for review. For both persistent post-surgical pain and physical impairment, perioperative education was ineffective, while active psychotherapy suggested a benefit (test of interaction P=0.01 for both outcomes). Moderate quality evidence showed that active perioperative psychotherapy (cognitive-behaviour therapy, relaxation therapy, or both) significantly reduced persistent post-surgical pain [weighted mean difference (WMD) -1.06 cm on a 10 cm visual analogue scale for pain, 95% confidence interval (CI) -1.56 to -0.55 cm; risk difference (RD) for achieving no more than mild pain (≤3 cm) 14%, 95% CI 8-21%] and physical impairment [WMD -9.87% on the 0-100% Oswestry Disability Index, 95% CI -13.42 to -6.32%, RD for achieving no more than mild disability (≤20%) 21%, 95% CI 13-29%]. Perioperative cognitive behavioural therapy and relaxation therapy are effective for reducing persistent pain and physical impairment after surgery. Future studies should explore targeted psychotherapy for surgical patients at higher risk for poor outcome. PROSPERO CRD42016047335. Copyright © 2017. Published by Elsevier Ltd.

Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.

PubMed

Xiao, Xing; Zhao, Xiao-Tao; Xu, Ling-Chi; Yue, Lu-Peng; Liu, Feng-Yu; Cai, Jie; Liao, Fei-Fei; Kong, Jin-Ge; Xing, Guo-Gang; Yi, Ming; Wan, You

2015-04-01

Transient receptor potential vanilloid 1 (TRPV1) receptors are expressed in nociceptive neurons of rat dorsal root ganglions (DRGs) and mediate inflammatory pain. Nonspecific inhibition of protein-tyrosine phosphatases (PTPs) increases the tyrosine phosphorylation of TRPV1 and sensitizes TRPV1. However, less is known about tyrosine phosphorylation's implication in inflammatory pain, compared with that of serine/threonine phosphorylation. Src homology 2 domain-containing tyrosine phosphatase 1 (Shp-1) is a key phosphatase dephosphorylating TRPV1. In this study, we reported that Shp-1 colocalized with and bound to TRPV1 in nociceptive DRG neurons. Shp-1 inhibitors, including sodium stibogluconate and PTP inhibitor III, sensitized TRPV1 in cultured DRG neurons. In naive rats, intrathecal injection of Shp-1 inhibitors increased both TRPV1 and tyrosine-phosphorylated TRPV1 in DRGs and induced thermal hyperalgesia, which was abolished by pretreatment with TRPV1 antagonists capsazepine, BCTC, or AMG9810. Complete Freund's adjuvant (CFA)-induced inflammatory pain in rats significantly increased the expression of Shp-1, TRPV1, and tyrosine-phosphorylated TRPV1, as well as the colocalization of Shp-1 and TRPV1 in DRGs. Intrathecal injection of sodium stibogluconate aggravated CFA-induced inflammatory pain, whereas Shp-1 overexpression in DRG neurons alleviated it. These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.

A case of systemic lupus erythematosus presenting as bilateral avascular necrosis of femur.

PubMed

Adikari, Madura; Gunawardane, Aloka; Illangantilaka, Sachithra; Atukorale, Himantha; Rubasinghe, Jeevanie

2016-08-05

Avascular necrosis occur as a result of diverse etiology. Chronic inflammatory conditions such as systemic lupus erythematosus considered as a recognize cause. Many cases were reported in systemic lupus erythematosus after treating with corticosteroids. We report a case of a corticosteroid naïve patient presented as bilateral avascular necrosis of femoral head and later progressed to a case of systemic lupus erythematosus. A 26 year old lady presented with right sided hip pain and diagnosed as avascular necrosis of the femoral head. After 6 months she presented a similar pain in left hip, which revealed avascular necrosis of left femoral head as well. A probable cause for her clinical presentation could not be found after extensive clinical and laboratory evaluation. Patient reported high erythrocyte sedimentation rate persistently, and over the next few years progressed as a case of systemic lupus erythematosus. Above case illustrated avascular necrosis could be an early musculoskeletal manifestation of systemic lupus erythematosus even in the absence of corticosteroid administration.

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.

Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats

PubMed Central

2013-01-01

Background Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund’s Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Methods Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. Results CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1/2 and COX-2, and over-production of PGE2 induced by CFA, were suppressed by TENS administration. Conclusions TENS may be an effective therapy in controlling inflammatory pain induced by CFA. Its analgesic effect may be associated with the inhibition of activation of the spinal ERK1/2-COX-2 pathway. PMID:23768044

Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats.

PubMed

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

2013-06-15

Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund's Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1/2 and COX-2, and over-production of PGE2 induced by CFA, were suppressed by TENS administration. TENS may be an effective therapy in controlling inflammatory pain induced by CFA. Its analgesic effect may be associated with the inhibition of activation of the spinal ERK1/2-COX-2 pathway.

Does progestin-only contraceptive use after pregnancy affect recovery from pelvic girdle pain? A prospective population study

PubMed Central

Owe, Katrine Mari; Nordeng, Hedvig Marie Egeland; Engdahl, Bo Lars; Kristiansson, Per; Vangen, Siri; Eberhard-Gran, Malin

2017-01-01

Objective To estimate associations of progestin-only contraceptives with persistent pelvic girdle pain 18 months after delivery. Methods Prospective population based cohort study during the years 2003–2011. We included 20,493 women enrolled in the Norwegian Mother and Child Cohort Study who reported pelvic girdle pain in pregnancy week 30. Data were obtained by 3 self-administered questionnaires and the exposure was obtained by linkage to the Prescription Database of Norway. The outcome was pelvic girdle pain 18 months after delivery. Results Pelvic girdle pain 18 months after delivery was reported by 9.7% (957/9830) of women with dispense of a progestin-only contraceptive and by 10.5% (1114/10,663) of women without dispense (adjusted odds ratio 0.93; 95% CI 0.84–1.02). In sub-analyses, long duration of exposure to a progestin intrauterine device or progestin-only oral contraceptives was associated with reduced odds of persistent pelvic girdle pain (Ptrend = 0.021 and Ptrend = 0.005). Conversely, long duration of exposure to progestin injections and/or a progestin implant was associated with modest increased odds of persistent pelvic girdle pain (Ptrend = 0.046). Early timing of progestin-only contraceptive dispense following delivery (≤3 months) was not significantly associated with persistent pelvic girdle pain. Conclusions Our findings suggest a small beneficial effect of progestin intrauterine devices and progestin-only oral contraceptives on recovery from pelvic girdle pain. We cannot completely rule out an opposing adverse effect of exposure to progestin injections and/or progestin implants. However, the modest increased odds of persistent pelvic girdle pain among these users could be a result of unmeasured confounding. PMID:28892506

Does progestin-only contraceptive use after pregnancy affect recovery from pelvic girdle pain? A prospective population study.

PubMed

Bjelland, Elisabeth Krefting; Owe, Katrine Mari; Nordeng, Hedvig Marie Egeland; Engdahl, Bo Lars; Kristiansson, Per; Vangen, Siri; Eberhard-Gran, Malin

2017-01-01

To estimate associations of progestin-only contraceptives with persistent pelvic girdle pain 18 months after delivery. Prospective population based cohort study during the years 2003-2011. We included 20,493 women enrolled in the Norwegian Mother and Child Cohort Study who reported pelvic girdle pain in pregnancy week 30. Data were obtained by 3 self-administered questionnaires and the exposure was obtained by linkage to the Prescription Database of Norway. The outcome was pelvic girdle pain 18 months after delivery. Pelvic girdle pain 18 months after delivery was reported by 9.7% (957/9830) of women with dispense of a progestin-only contraceptive and by 10.5% (1114/10,663) of women without dispense (adjusted odds ratio 0.93; 95% CI 0.84-1.02). In sub-analyses, long duration of exposure to a progestin intrauterine device or progestin-only oral contraceptives was associated with reduced odds of persistent pelvic girdle pain (Ptrend = 0.021 and Ptrend = 0.005). Conversely, long duration of exposure to progestin injections and/or a progestin implant was associated with modest increased odds of persistent pelvic girdle pain (Ptrend = 0.046). Early timing of progestin-only contraceptive dispense following delivery (≤3 months) was not significantly associated with persistent pelvic girdle pain. Our findings suggest a small beneficial effect of progestin intrauterine devices and progestin-only oral contraceptives on recovery from pelvic girdle pain. We cannot completely rule out an opposing adverse effect of exposure to progestin injections and/or progestin implants. However, the modest increased odds of persistent pelvic girdle pain among these users could be a result of unmeasured confounding.

Audit of postoperative pain management after open thoracotomy and the incidence of chronic postthoracotomy pain in more than 500 patients at a tertiary center.

PubMed

Niraj, G; Kelkar, A; Kaushik, Vipul; Tang, Yee; Fleet, Danny; Tait, Frances; Mcmillan, Theresa; Rathinam, Sridhar

2017-02-01

To evaluate the quality of postoperative pain relief during the first 3 days after surgery and to evaluate with the incidence of persistent pain at 6 months after surgery. Retrospective single-center audit. University hospital. Five hundred four patients who underwent thoracotomy. Review of patient records, questionnaire, and telephone review. Of the 364 survivors, 306 were contacted. Five or more episodes of severe pain (numerical rating scale >6/10 at rest or movement) during the first 72 hours after surgery occurred in 133 patients. Persistent postsurgical pain at 6 months was present in 82% (109/133) of these patients. Patient satisfaction with acute postoperative pain management was excellent (36%), good (43%), and fair or poor (21%).The incidence of postthoracotomy pain was 56% (mild 32%, moderate 18%, and severe 6%). Poorly controlled acute postoperative pain correlated with persistent postsurgical pain at 6 months. In view of such a high incidence in thoracotomy patients, preventative strategies assume great significance. Copyright © 2016 Elsevier Inc. All rights reserved.

Meralgia Paresthetica

MedlinePlus

... in which pain is persistent or severe, surgical intervention may be indicated. × Treatment Treatment for meralgia paresthetica ... in which pain is persistent or severe, surgical intervention may be indicated. View Full Treatment Information Definition ...

Transient decrease in nociceptor GRK2 expression produces long–term enhancement in inflammatory pain

PubMed Central

Ferrari, Luiz F.; Bogen, Oliver; Alessandri–Haber, Nicole; Levine, Emma; Gear, Robert W.; Levine, Jon D.

2012-01-01

In heterozygous mice, attenuation of G-protein-coupled receptor kinase 2 (GRK2) level in nociceptors is associated with enhanced and prolonged inflammatory hyperalgesia. To further elucidate the role of GRK2 in nociceptor function we reversibly decreased GRK2 expression using intrathecal antisense oligodeoxynucleotide (AS-ODN). GRK2 AS-ODN administration led to an enhanced and prolonged hyperalgesia induced by prostaglandin E 2, epinephrine and carrageenan. Morover, this effect persisted unattenuated 2 weeks after the last dose of antisense, well after GRK2 protein recovered, suggesting that transient attenuation of GRK2 produced neuroplastic changes in nociceptor function. Unlike hyperalgesic priming induced by transient attenuation of GRK2 produced neuroplastic changes in nociceptor function. Unlike hyperalgesic priming induced by transient activation of protein kinase C epsilon (PKCε), (Aley et al., 2000, Parada et al., 2003b), the enhanced and prolonged hyperalgesia following attenuation of GRK2 is PKCε- and cytoplasmic polyadenylation element binding protein (CPEB)-independent and is protein kinase A (PKA)- and Src tyrosine kinase (Src)-dependent. Finally, rats treated with GRK2 AS-ODN exhibited enhanced and prolonged hyperalgesia induced by direct activation of second messengers, adenyl cyclase, Epac or PKA, suggesting changes downstream of G-protein-coupled receptors. Because inflammation can produce a decrease in GRK2, such a mechanism could help explain a predilection to develop chronic pain, after resolution of acute inflammation. PMID:22796071

Lumbar Facet Joint Compressive Injury Induces Lasting Changes in Local Structure, Nociceptive Scores, and Inflammatory Mediators in a Novel Rat Model

PubMed Central

Henry, James L.; Yashpal, Kiran; Vernon, Howard; Kim, Jaesung; Im, Hee-Jeong

2012-01-01

Objective. To develop a novel animal model of persisting lumbar facet joint pain. Methods. Sprague Dawley rats were anaesthetized and the right lumbar (L5/L6) facet joint was exposed and compressed to ~1 mm with modified clamps applied for three minutes; sham-operated and naïve animals were used as control groups. After five days, animals were tested for hind-paw sensitivity using von Frey filaments and axial deep tissue sensitivity by algometer on assigned days up to 28 days. Animals were sacrificed at selected times for histological and biochemical analysis. Results. Histological sections revealed site-specific loss of cartilage in model animals only. Tactile hypersensitivity was observed for the ipsi- and contralateral paws lasting 28 days. The threshold at which deep tissue pressure just elicited vocalization was obtained at three lumbar levels; sensitivity at L1 > L3/4 > L6. Biochemical analyses revealed increases in proinflammatory cytokines, especially TNF-α, IL-1α, and IL-1β. Conclusions. These data suggest that compression of a facet joint induces a novel model of local cartilage loss accompanied by increased sensitivity to mechanical stimuli and by increases in inflammatory mediators. This new model may be useful for studies on mechanisms and treatment of lumbar facet joint pain and osteoarthritis. PMID:22966427

MicroRNA-16 Alleviates Inflammatory Pain by Targeting Ras-Related Protein 23 (RAB23) and Inhibiting p38 MAPK Activation.

PubMed

Chen, Wenjin; Guo, Shengdong; Wang, Shenggang

2016-10-22

BACKGROUND The purpose of our study was to determine the functional role of microRNA (miR)-16 in chronic inflammatory pain and to disclose its underlying molecular mechanism. MATERIAL AND METHODS Inflammatory pain was induced by injection of complete Freund's adjuvant (CFA) to Wistar rats. The pWPXL-miR-16, PcDNA3.1- Ras-related protein (RAB23), and/or SB203580 were delivered intrathecally to the rats. Behavioral tests were detected at 0 h, 4 h, 1 d, 4 d, 7 d, and 14 d after CFA injection. After behavioral tests, L4-L6 dorsal spinal cord were obtained and the levels of miR-16, RAB23, and phosphorylation of p38 (p-p38) were evaluated by quantitative real-time PCR (qRT-PCR). In addition, luciferase reporter assay was performed to explore whether RAB23 was a target of miR-16, and qRT-PCR and Western blotting were used to confirm the regulation between RAB23 and miR-16. RESULTS The level of miR-16 was significantly decreased in the CFA-induced inflammatory pain. Intrathecal injection of miR-16 alleviates pain response and raised pain threshold. The level of RAB23 was significantly increased in the pain model, and intrathecal injection of RAB23 aggravated pain response. Luciferase reporter assay confirmed that RAB23 was a direct target of miR-16, and RAB23 was negatively regulated by miR-16. In addition, we found that simultaneous administration of SB203580 and miR-16 further alleviates pain response compared to only administration of miR-16. CONCLUSIONS Our findings suggest that miR-16 relieves chronic inflammatory pain by targeting RAB23 and inhibiting p38 MAPK activation.

Internet-mediated physiotherapy and pain coping skills training for people with persistent knee pain (IMPACT - knee pain): a randomised controlled trial protocol.

PubMed

Dobson, Fiona; Hinman, Rana S; French, Simon; Rini, Christine; Keefe, Francis; Nelligan, Rachel; Abbott, J Haxby; Bryant, Christina; Staples, Margaret P; Dalwood, Andrew; Bennell, Kim L

2014-08-13

Persistent knee pain in people over 50 years of age is often attributable to knee osteoarthritis (OA), a common joint condition that causes physical and psychological dysfunction. Exercise and pain coping skills training (PCST) can help reduce the impact of persistent knee pain, however, access to health professionals who deliver these services can be challenging. With increasing access to the Internet, remotely delivered Internet-based treatment approaches may provide alternatives for healthcare delivery. This pragmatic randomised controlled trial will investigate whether an Internet-delivered intervention that combines PCST and physiotherapist-guided exercise (PCST + Ex) is more effective than online educational material (educational control) in people with persistent knee pain. We will recruit 148 people over 50 years of age with self-reported persistent knee pain consistent with knee OA from the Australian community. Following completion of baseline questionnaires, participants will be randomly allocated to access a 3-month intervention of either (i) online educational material, or (ii) the same online material plus an 8-module (once per week) Internet-based PCST program and seven Internet-delivered physiotherapy sessions with a home exercise programs to be performed 3 times per week. Outcomes will be measured at baseline, 3 months and 9 months with the primary time point at 3 months. Primary outcomes are average knee pain on walking (11-point numeric rating scale) and self-reported physical function (Western Ontario and McMaster Universities Osteoarthritis Index subscale). Secondary outcomes include additional measures of knee pain, health-related quality-of-life, perceived global change in symptoms, and potential moderators and mediators of outcomes including self-efficacy for pain management and function, pain coping attempts and pain catastrophising. Other measures of adherence, adverse events, harms, use of health services/co-interventions, and process measures including appropriateness and satisfaction of the intervention, will be collected at 3, 6 and 9 months. The findings will help determine the effectiveness and acceptability of Internet access to a combination of interventions that are known to be beneficial to people with persistent knee pain. This study has the potential to guide clinical practice towards innovative modes of healthcare provision. Australian New Zealand Clinical Trials Registry reference: ACTRN12614000243617.

Differential effects of subcutaneous electrical stimulation (SQS) and transcutaneous electrical nerve stimulation (TENS) in rodent models of chronic neuropathic or inflammatory pain.

PubMed

Vera-Portocarrero, Louis P; Cordero, Toni; Billstrom, Tina; Swearingen, Kim; Wacnik, Paul W; Johanek, Lisa M

2013-01-01

Electrical stimulation has been used for many years for the treatment of pain. Present-day research demonstrates that stimulation targets and parameters impact the induction of specific pain-modulating mechanisms. New targets are increasingly being investigated clinically, but the scientific rationale for a particular target is often not well established. This present study compares the behavioral effects of targeting peripheral axons by electrode placement in the subcutaneous space vs. electrode placement on the surface of the skin in a rodent model. Rodent models of inflammatory and neuropathic pain were used to investigate subcutaneous electrical stimulation (SQS) vs. transcutaneous electrical nerve stimulation (TENS). Electrical parameters and relative location of the leads were held constant under each condition. SQS had cumulative antihypersensitivity effects in both inflammatory and neuropathic pain rodent models, with significant inhibition of mechanical hypersensitivity observed on days 3-4 of treatment. In contrast, reduction of thermal hyperalgesia in the inflammatory model was observed during the first four days of treatment with SQS, and reduction of cold allodynia in the neuropathic pain model was seen only on the first day with SQS. TENS was effective in the inflammation model, and in agreement with previous studies, tolerance developed to the antihypersensitivity effects of TENS. With the exception of a reversal of cold hypersensitivity on day 1 of testing, TENS did not reveal significant analgesic effects in the neuropathic pain rodent model. The results presented show that TENS and SQS have different effects that could point to unique biologic mechanisms underlying the analgesic effect of each therapy. Furthermore, this study is the first to demonstrate in an animal model that SQS attenuates neuropathic and inflammatory-induced pain behaviors. © 2013 Medtronic, Inc.

VIPER: Chronic Pain after Amputation: Inflammatory Mechanisms, Novel Analgesic Pathways, and Improved Patient Safety

DTIC Science & Technology

2016-10-01

inflammatory mediators. Pro-inflammatory mediators including TNF-α, TNF-β, IL-8, ICAM-1, Tie2, CRP, and SAA were elevated in patients with chronic residual limb...IL-12, TNF-β, PIGF, Tie2, SAA and ICAM-1), and inversely with concentrations of the anti-inflammatory mediator IL-13, as well as IL-2 and Eotaxin-3...catastrophizing and residual limb pain intensity were partially mediated by TNF-α, TNF- β, SAA , and ICAM-1 levels. Results suggest that chronic post

Evaluation of analgesic and anti-inflammatory activity of a combination of tramadol-ibuprofen in experimental animals.

PubMed

Suthakaran, Chidambarann; Kayalvizhi, Muniyagounder K; Nithya, Karnam; Raja, Thozhudalangudy Ar

2017-01-01

Pain is the major concern of patients attending dental clinics, and satisfactory pain relief has always been difficult to achieve. Since the pathophysiology of pain is a complex, central and peripheral nervous system process, combined analgesic regimens with different mechanisms of action as a multimodal approach are becoming popular among the clinicians and dentists. The aim of the present study was to evaluate the analgesic and anti-inflammatory activity of ibuprofen and tramadol when used alone or in combination in animal models of pain and inflammation. The animals were divided into six groups with six animals in each group. Analgesic activity was assessed by hot plate method in rats and by acetic acid-induced writhing test in mice. Paw edema model in rats after induction with 0.1 mL of 1% carrageenan was used to assess the anti-inflammatory activity. Analysis of variance followed by Tukey's honestly significant difference post hoc test was used for statistical analysis. Combined use of tramadol and ibuprofen provided enhanced analgesic and anti-inflammatory effects in animal models of pain and inflammation.

Evaluation of acute pelvic pain in women.

PubMed

Kruszka, Paul S; Kruszka, Stephen J

2010-07-15

Diagnosis of pelvic pain in women can be challenging because many symptoms and signs are insensitive and nonspecific. As the first priority, urgent life-threatening conditions (e.g., ectopic pregnancy, appendicitis, ruptured ovarian cyst) and fertility-threatening conditions (e.g., pelvic inflammatory disease, ovarian torsion) must be considered. A careful history focusing on pain characteristics, review of systems, and gynecologic, sexual, and social history, in addition to physical examination helps narrow the differential diagnosis. The most common urgent causes of pelvic pain are pelvic inflammatory disease, ruptured ovarian cyst, and appendicitis; however, many other diagnoses in the differential may mimic these conditions, and imaging is often needed. Transvaginal ultrasonography should be the initial imaging test because of its sensitivities across most etiologies and its lack of radiation exposure. A high index of suspicion should be maintained for pelvic inflammatory disease when other etiologies are ruled out, because the presentation is variable and the prevalence is high. Multiple studies have shown that 20 to 50 percent of women presenting with pelvic pain have pelvic inflammatory disease. Adolescents and pregnant and postpartum women require unique considerations.

Peroxisome proliferator-activated receptor agonists modulate neuropathic pain: a link to chemokines?

PubMed Central

Freitag, Caroline M.; Miller, Richard J.

2014-01-01

Chronic pain presents a widespread and intractable medical problem. While numerous pharmaceuticals are used to treat chronic pain, drugs that are safe for extended use and highly effective at treating the most severe pain do not yet exist. Chronic pain resulting from nervous system injury (neuropathic pain) is common in conditions ranging from multiple sclerosis to HIV-1 infection to type II diabetes. Inflammation caused by neuropathy is believed to contribute to the generation and maintenance of neuropathic pain. Chemokines are key inflammatory mediators, several of which (MCP-1, RANTES, MIP-1α, fractalkine, SDF-1 among others) have been linked to chronic, neuropathic pain in both human conditions and animal models. The important roles chemokines play in inflammation and pain make them an attractive therapeutic target. Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors known for their roles in metabolism. Recent research has revealed that PPARs also play a role in inflammatory gene repression. PPAR agonists have wide-ranging effects including inhibition of chemokine expression and pain behavior reduction in animal models. Experimental evidence suggests a connection between the pain ameliorating effects of PPAR agonists and suppression of inflammatory gene expression, including chemokines. In early clinical research, one PPARα agonist, palmitoylethanolamide (PEA), shows promise in relieving chronic pain. If this link can be better established, PPAR agonists may represent a new drug therapy for neuropathic pain. PMID:25191225

Acid-sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain.

PubMed

Fu, Hui; Fang, Peng; Zhou, Hai-Yun; Zhou, Jun; Yu, Xiao-Wei; Ni, Ming; Zheng, Jie-Yan; Jin, You; Chen, Jian-Guo; Wang, Fang; Hu, Zhuang-Li

2016-02-01

Orofacial pain is a common clinical symptom that is accompanied by tooth pain, migraine and gingivitis. Accumulating evidence suggests that acid-sensing ion channels (ASICs), especially ASIC3, can profoundly affect the physiological properties of nociception in peripheral sensory neurons. The aim of this study is to examine the contribution of ASICs in trigeminal ganglion (TG) neurons to orofacial inflammatory pain. A Western blot (WB), immunofluorescence assay of labelled trigeminal ganglion neurons, orofacial formalin test, cell preparation and electrophysiological experiments are performed. This study demonstrated that ASIC1, ASIC2a and ASIC3 are highly expressed in TG neurons innervating the orofacial region of rats. The amplitude of ASIC currents in these neurons increased 119.72% (for ASIC1-like current) and 230.59% (for ASIC3-like current) in the formalin-induced orofacial inflammatory pain model. In addition, WB and immunofluorescence assay demonstrated a significantly augmented expression of ASICs in orofacial TG neurons during orofacial inflammation compared with the control group. The relative protein density of ASIC1, ASIC2a and ASIC3 also increased 58.82 ± 8.92%, 45.30 ± 11.42% and 55.32 ± 14.71%, respectively, compared with the control group. Furthermore, pharmacological blockade of ASICs and genetic deletion of ASIC1 attenuated the inflammation response. These findings indicate that peripheral inflammation can induce the upregulation of ASICs in TG neurons, causing orofacial inflammatory pain. Additionally, the specific inhibitor of ASICs may have a significant analgesic effect on orofacial inflammatory pain. © 2016 John Wiley & Sons Australia, Ltd.

Trajectories of acute low back pain: a latent class growth analysis.

PubMed

Downie, Aron S; Hancock, Mark J; Rzewuska, Magdalena; Williams, Christopher M; Lin, Chung-Wei Christine; Maher, Christopher G

2016-01-01

Characterising the clinical course of back pain by mean pain scores over time may not adequately reflect the complexity of the clinical course of acute low back pain. We analysed pain scores over 12 weeks for 1585 patients with acute low back pain presenting to primary care to identify distinct pain trajectory groups and baseline patient characteristics associated with membership of each cluster. This was a secondary analysis of the PACE trial that evaluated paracetamol for acute low back pain. Latent class growth analysis determined a 5 cluster model, which comprised 567 (35.8%) patients who recovered by week 2 (cluster 1, rapid pain recovery); 543 (34.3%) patients who recovered by week 12 (cluster 2, pain recovery by week 12); 222 (14.0%) patients whose pain reduced but did not recover (cluster 3, incomplete pain recovery); 167 (10.5%) patients whose pain initially decreased but then increased by week 12 (cluster 4, fluctuating pain); and 86 (5.4%) patients who experienced high-level pain for the whole 12 weeks (cluster 5, persistent high pain). Patients with longer pain duration were more likely to experience delayed recovery or nonrecovery. Belief in greater risk of persistence was associated with nonrecovery, but not delayed recovery. Higher pain intensity, longer duration, and workers' compensation were associated with persistent high pain, whereas older age and increased number of episodes were associated with fluctuating pain. Identification of discrete pain trajectory groups offers the potential to better manage acute low back pain.

Homology-guided mutational analysis reveals the functional requirements for antinociceptive specificity of collapsin response mediator protein 2-derived peptides.

PubMed

Moutal, Aubin; Li, Wennan; Wang, Yue; Ju, Weina; Luo, Shizhen; Cai, Song; François-Moutal, Liberty; Perez-Miller, Samantha; Hu, Jackie; Dustrude, Erik T; Vanderah, Todd W; Gokhale, Vijay; Khanna, May; Khanna, Rajesh

2017-02-05

N-type voltage-gated calcium (Ca v 2.2) channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Although Ca v 2.2 channel antagonists are recommended as first-line treatment for neuropathic pain, calcium-current blocking gabapentinoids inadequately alleviate chronic pain symptoms and often exhibit numerous side effects. Collapsin response mediator protein 2 (CRMP2) targets Ca v 2.2 channels to the sensory neuron membrane and allosterically modulates their function. A 15-amino-acid peptide (CBD3), derived from CRMP2, disrupts the functional protein-protein interaction between CRMP2 and Ca v 2.2 channels to inhibit calcium influx, transmitter release and acute, inflammatory and neuropathic pain. Here, we have mapped the minimal domain of CBD3 necessary for its antinociceptive potential. Truncated as well as homology-guided mutant versions of CBD3 were generated and assessed using depolarization-evoked calcium influx in rat dorsal root ganglion neurons, binding between CRMP2 and Ca v 2.2 channels, whole-cell voltage clamp electrophysiology and behavioural effects in two models of experimental pain: post-surgical pain and HIV-induced sensory neuropathy induced by the viral glycoprotein 120. The first six amino acids within CBD3 accounted for all in vitro activity and antinociception. Spinal administration of a prototypical peptide (TAT-CBD3-L5M) reversed pain behaviours. Homology-guided mutational analyses of these six amino acids identified at least two residues, Ala1 and Arg4, as being critical for antinociception in two pain models. These results identify an antinociceptive scaffold core in CBD3 that can be used for development of low MW mimetics of CBD3. © 2017 The British Pharmacological Society.

Preliminary evidence of a blunted anti-inflammatory response to exhaustive exercise in fibromyalgia.

PubMed

Torgrimson-Ojerio, Britta; Ross, Rebecca L; Dieckmann, Nathan F; Avery, Stephanie; Bennett, Robert M; Jones, Kim D; Guarino, Anthony J; Wood, Lisa J

2014-12-15

Exercise intolerance, as evidenced by a worsening of pain, fatigue, and stiffness after novel exertion, is a key feature of fibromyalgia (FM). In this pilot study, we investigate whether; insufficient muscle repair processes and impaired anti-inflammatory mechanisms result in an exaggerated pro-inflammatory cytokine response to exhaustive exercise, and consequently a worsening of muscle pain, stiffness and fatigue in the days post-exercise. We measured changes in muscle pain and tenderness, fatigue, stiffness, and serum levels of neuroendocrine and inflammatory cytokine markers in 20 women with FM and 16 healthy controls (HCs) before and after exhaustive treadmill exercise. Compared to HCs, FM participants failed to mount the expected anti-inflammatory response to exercise and experienced a worsening of symptoms post-exercise. However, changes in post-exertional symptoms were not mediated by post-exertional changes in pro-inflammatory cytokine levels. Implications of these findings are discussed. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Inflammatory Asthma Phenotype Discrimination Using an Electronic Nose Breath Analyzer.

PubMed

Plaza, V; Crespo, A; Giner, J; Merino, J L; Ramos-Barbón, D; Mateus, E F; Torrego, A; Cosio, B G; Agustí, A; Sibila, O

2015-01-01

Patients with persistent asthma have different inflammatory phenotypes. The electronic nose is a new technology capable of distinguishing volatile organic compound (VOC) breath-prints in exhaled breath. The aim of the study was to investigate the capacity of electronic nose breath-print analysis to discriminate between different inflammatory asthma phenotypes (eosinophilic, neutrophilic, paucigranulocytic) determined by induced sputum in patients with persistent asthma. Fifty-two patients with persistent asthma were consecutively included in a cross-sectional proof-of-concept study. Inflammatory asthma phenotypes (eosinophilic, neutrophilic and paucigranulocytic) were recognized by inflammatory cell counts in induced sputum. VOC breath-prints were analyzed using the electronic nose Cyranose 320 and assessed by discriminant analysis on principal component reduction, resulting in cross-validated accuracy values. Receiver operating characteristic (ROC) curves were calculated. VOC breath-prints were different in eosinophilic asthmatics compared with both neutrophilic asthmatics (accuracy 73%; P=.008; area under ROC, 0.92) and paucigranulocytic asthmatics (accuracy 74%; P=.004; area under ROC, 0.79). Likewise, neutrophilic and paucigranulocytic breath-prints were also different (accuracy 89%; P=.001; area under ROC, 0.88). An electronic nose can discriminate inflammatory phenotypes in patients with persistent asthma in a regular clinical setting. ClinicalTrials.gov identifier: NCT02026336.

Biological Stress Systems, Adverse Life Events, and the Improvement of Chronic Multisite Musculoskeletal Pain Across a 6-Year Follow-Up.

PubMed

Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; de Geus, Eco J C N; Dekker, Joost; Penninx, Brenda W J H

2017-02-01

Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1) function of biological stress systems, 2) adverse life events, and 3) their combination predict the improvement of chronic multisite musculoskeletal pain. Subjects of the Netherlands Study of Depression and Anxiety (NESDA) with chronic multisite musculoskeletal pain at baseline (N = 665) were followed-up 2, 4, and 6 years later. The Chronic Pain Grade Questionnaire was used to determine improvement (not meeting the criteria) of chronic multisite musculoskeletal pain at follow-up. Baseline assessment of biological stress systems included function of hypothalamic-pituitary-adrenal axis (1-hour cortisol awakening response, evening level, and post dexamethasone level), the immune system (basal and lipopolysaccharide-stimulated inflammatory markers), the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, and respiratory sinus arrhythmia). The number of adverse life events were assessed at baseline and 2-year follow-up using the List of Threatening Events Questionnaire. We showed that hypothalamic-pituitary-adrenal axis, immune system, and autonomic nervous system functioning and adverse life events were not associated with the improvement of chronic multisite musculoskeletal pain, either as a main effect or in interaction. This longitudinal study could not confirm that biological stress system dysfunction and adverse life events affect the course of chronic multisite musculoskeletal pain. Biological stress systems and adverse life events are not associated with the improvement of chronic multisite musculoskeletal pain over 6 years of follow-up. Other determinants should thus be considered in future research to identify in which persons pain symptoms will improve. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Optimism, Positive and Negative Affect, and Goal Adjustment Strategies: Their Relationship to Activity Patterns in Patients with Chronic Musculoskeletal Pain.

PubMed

Esteve, Rosa; López-Martínez, Alicia E; Peters, Madelon L; Serrano-Ibáñez, Elena R; Ruiz-Párraga, Gema T; Ramírez-Maestre, Carmen

2018-01-01

Activity patterns are the product of pain and of the self-regulation of current goals in the context of pain. The aim of this study was to investigate the association between goal management strategies and activity patterns while taking into account the role of optimism/pessimism and positive/negative affect. Two hundred and thirty-seven patients with chronic musculoskeletal pain filled out questionnaires on optimism, positive and negative affect, pain intensity, and the activity patterns they employed in dealing with their pain. Questionnaires were also administered to assess their general goal management strategies: goal persistence, flexible goal adjustment, and disengagement and reengagement with goals. Structural equation modelling showed that higher levels of optimism were related to persistence, flexible goal management, and commitment to new goals. These strategies were associated with higher positive affect, persistence in finishing tasks despite pain, and infrequent avoidance behaviour in the presence or anticipation of pain. The strategies used by the patients with chronic musculoskeletal pain to manage their life goals are related to their activity patterns.

Conditioned medium from persistently RSV-infected macrophages alters transcriptional profile and inflammatory response of non-infected macrophages.

PubMed

Rivera-Toledo, Evelyn; Salido-Guadarrama, Iván; Rodríguez-Dorantes, Mauricio; Torres-González, Laura; Santiago-Olivares, Carlos; Gómez, Beatriz

2017-02-15

Cells susceptible to persistent viral infections undergo important changes in their biological functions as a consequence of the expression of viral gene products that are capable of altering the gene expression profile of the host cell. Previously, we reported that persistence of the RSV genome in a mouse macrophage cell line induces important alterations in cell homeostasis, including constitutive expression of IFN-β and other pro-inflammatory cytokines. Here, we postulated that changes in the homeostasis of non-infected macrophages could be induced by soluble factors secreted by persistently RSV- infected macrophages. To test this hypothesis, non-infected mouse macrophages were treated with conditioned medium (CM) collected from cultures of persistently RSV-infected macrophages. Total RNA was extracted and a microarray-based gene expression analysis was performed. Non-infected macrophages, treated under similar conditions with CM obtained from cultures of non-infected macrophages, were used as a control to establish differential gene expression between the two conditions. Results showed that CM from the persistently RSV-infected cultures altered expression of a total of 95 genes in non-infected macrophages, resulting in an antiviral gene-transcription profile along with inhibition of the inflammatory response, since some inflammatory genes were down-regulated, including Nlrp3 and Il-1 β, both related to the inflammasome pathway. However, down-regulation of Nlrp3 and Il-1 β was reversible upon acute RSV infection. Additionally, we observed that the inflammatory response, evaluated by secreted IL-1 β, a final product of the inflammasome activity, was enhanced during acute RSV infection in macrophages treated with CM from persistently RSV-infected cultures, compared to that in macrophages treated with the control CM. This suggests that soluble factors secreted during RSV persistence may induce an exacerbated inflammatory response in non-infected cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Dysfunctional stress responses in chronic pain.

PubMed

Woda, Alain; Picard, Pascale; Dutheil, Frédéric

2016-09-01

Many dysfunctional and chronic pain conditions overlap. This review describes the different modes of chronic deregulation of the adaptive response to stress which may be a common factor for these conditions. Several types of dysfunction can be identified within the hypothalamo-pituitary-adrenal axis: basal hypercortisolism, hyper-reactivity, basal hypocortisolism and hypo-reactivity. Neuroactive steroid synthesis is another component of the adaptive response to stress. Dehydroepiandrosterone (DHEA) and its sulfated form DHEA-S, and progesterone and its derivatives are synthetized in cutaneous, nervous, and adipose cells. They are neuroactive factors that act locally. They may have a role in the localization of the symptoms and their levels can vary both in the central nervous system and in the periphery. Persistent changes in neuroactive steroid levels or precursors can induce localized neurodegeneration. The autonomic nervous system is another component of the stress response. Its dysfunction in chronic stress responses can be expressed by decreased basal parasympathethic activity, increased basal sympathetic activity or sympathetic hyporeactivity to a stressful stimulus. The immune and genetic systems also participate. The helper-T cells Th1 secrete pro-inflammatory cytokines such as IL-1-β, IL-2, IL-6, IL-8, IL-12, IFN-γ, and TNF-α, whereas Th2 secrete anti-inflammatory cytokines: IL-4, IL-10, IGF-10, IL-13. Chronic deregulation of the Th1/Th2 balance can occur in favor of anti- or pro-inflammatory direction, locally or systemically. Individual vulnerability to stress can be due to environmental factors but can also be genetically influenced. Genetic polymorphisms and epigenetics are the main keys to understanding the influence of genetics on the response of individuals to constraints. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rationale and design of a pilot study examining Acceptance and Commitment Therapy for persistent pain in an integrated primary care clinic.

PubMed

Kanzler, Kathryn E; Robinson, Patricia J; McGeary, Donald D; Mintz, Jim; Potter, Jennifer Sharpe; Muñante, Mariana; Lopez, Eliot J; Dougherty, Donald M; Hale, Willie J; Velligan, Dawn I

2018-03-01

Most of the 100 million Americans with persistent pain are treated in primary care clinics, but evidence-based psychosocial approaches targeting pain-related disability are not usually provided in these settings. This manuscript describes the rationale and methods for a protocol to pilot test the feasibility and effectiveness of Acceptance and Commitment Therapy (ACT), an evidence-based psychological treatment for persistent pain, delivered by a Behavioral Health Consultant in primary care. Eligible patients are identified through electronic health record registries and invited to participate via secure messaging, letters and a follow-up phone call. Participants are also recruited with advertising and clinician referral. Patients agreeing to participate are consented and complete initial assessments, with a target of 60 participants. Randomization is stratified based on pain severity with participants assigned to either ACT or Enhanced Treatment as Usual (E-TAU). ACT participants receive one standardized Behavioral Health Consultation visit followed by three ACT-based group visits and one group booster visit. All patients attend six assessment visits, during which the E-TAU patients are provided with educational pain management handouts based on standard cognitive behavioral treatment of pain. The study aims to determine feasibility and effectiveness of brief ACT for persistent pain delivered by an integrated behavioral health clinician in primary care from pre- to post-treatment, and to examine mechanisms of change in ACT participants. This study, in a "real-world" setting, will lay groundwork for a larger trial. If effective, it could improve treatment methods and quality of life for patients with persistent pain using a scalable approach. Copyright © 2018 Elsevier Inc. All rights reserved.

Anti-inflammatory and antinociceptive activities of azadirachtin in mice.

PubMed

Soares, Darly G; Godin, Adriana M; Menezes, Raquel R; Nogueira, Rafaela D; Brito, Ana Mercy S; Melo, Ivo S F; Coura, Giovanna Maria E; Souza, Danielle G; Amaral, Flávio A; Paulino, Tony P; Coelho, Márcio M; Machado, Renes R

2014-06-01

Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti-inflammatory and antinociceptive properties. However, the activities of azadirachtin, a limonoid and the major bioactive compound found in the extracts, have been poorly investigated in animal models. In the present study, we investigated the effects induced by azadirachtin in experimental models of pain and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue growth induced by subcutaneous cotton pellet implantation were used to investigate the anti-inflammatory activity of azadirachtin in mice. Zymosan-induced writhing and hot plate tests were employed to evaluate the antinociceptive activity. To explore putative mechanisms of action, the level of tumor necrosis factor-α in inflammatory tissue was measured and the effect induced by opioidergic and serotonergic antagonists was evaluated. Previous per os (p. o.) administration of azadirachtin (120 mg/kg) significantly reduced the acute paw edema induced by carrageenan. However, the concomitant increase of the paw concentration of tumor necrosis factor-α induced by this inflammatory stimulus was not reduced by azadirachtin. In addition to inhibiting the acute paw edema induced by carrageenan, azadirachtin (6, 60, and 120 mg/kg) inhibited the proliferative phase of the inflammatory response, as demonstrated by the reduced formation of fibrovascular tissue growth. Azadirachtin (120 mg/kg) also inhibited the nociceptive response in models of nociceptive (hot plate) and inflammatory (writhing induced by zymosan) pain. The activity of azadirachtin (120 mg/kg) in the model of nociceptive pain was attenuated by a nonselective opioid antagonist, naltrexone (10 mg/kg, i. p.), but not by a nonselective serotonergic antagonist, cyproheptadine. In conclusion, this study demonstrates the activity of azadirachtin in experimental models of nociceptive and inflammatory pain, and also in models of acute and chronic inflammation. Finally, multiple mechanisms, including the inhibition of the production of inflammatory mediators and activation of endogenous opioid pathways, may mediate azadirachtin activities in experimental models of inflammation and pain. Georg Thieme Verlag KG Stuttgart · New York.

Anti-nociceptive effects of Tanshinone IIA (TIIA) in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain.

PubMed

Sun, Shukai; Yin, Yue; Yin, Xin; Cao, Fale; Luo, Daoshu; Zhang, Ting; Li, Yunqing; Ni, Longxing

2012-09-01

Inflammatory pain is an important clinical symptom. The levels of extracellular signal-regulated kinases (ERKs) and the levels of cytokines such as interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) play important roles in inflammatory pain. Tanshinone IIA (TIIA) is an important component of Danshen, a traditional Chinese medicine that has been commonly used to treat cardiovascular disease. In this study, we investigated the potential anti-inflammatory nociceptive effects of TIIA on complete Freund's adjuvant (CFA)-induced inflammation and inflammatory pain in rats. The effects of TIIA on CFA-induced thermal and mechanical hypersensitivity were investigated using behavioral tests. The levels of ERKs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transient receptor potential vanilloid 1 (TRPV1) in the fifth segment of the lumbar spinal cord (L5) ganglia were detected by Western blot, and the levels of mRNA and protein production of IL1-β, IL-6 and TNF-α were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA). In this study, we found that TIIA attenuates the development of CFA-induced mechanical and thermal hypersensitivity. In addition, p-ERK and NF-κB expression levels were inhibited by TIIA, and the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced. Finally, we found that the expression level of TRPV1 was significantly decreased after TIIA injection. This study demonstrated that TIIA has significant anti-nociceptive effects in a rat model of CFA-induced inflammatory pain. TIIA can inhibit the activation of ERK signaling pathways and the expression of pro-inflammatory cytokines. These results suggest that TIIA may be a potential anti-inflammatory and anti-nociceptive drug. Copyright © 2012 Elsevier Inc. All rights reserved.

The peripheral administration of a nitric oxide donor potentiates the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice.

PubMed

Hervera, Arnau; Leánez, Sergi; Negrete, Roger; Pol, Olga

2009-10-01

Several works reveal that nitric oxide could enhance the peripheral antinociception induced by opioids during acute inflammation. Nonetheless, the role of nitric oxide in the local antinociceptive effects of delta-opioid receptor (DOR) agonists during chronic peripheral inflammation is not known. The aim of this study is to evaluate whether nitric oxide would enhance the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice. Chronic inflammatory pain was induced by the subplantar administration of complete Freund's adjuvant (CFA; 30 microl) and thermal hyperalgesia assessed by plantar test. In C57BL/6J mice, we evaluated the local antinociceptive effects of a DOR agonist, [D-Pen2,5]-enkephalin (DPDPE) and a nitric oxide donor, DETA NONOate DETA/NO 2,2'-(hydroxynitrosohydrazino) Bis-Ethanamine (NOC-18) alone or combined (DPDPE plus NOC-18) at 1, 4, 7, and 10 days after CFA injection. The reversibility of the peripheral antinociceptive effects of DPDPE, alone or combined with NOC-18, was assessed with the local administration of selective (naltrindole) and non-selective (naloxone methiodide) DOR antagonists. The local administration of DPDPE or NOC-18 alone dose-dependently inhibited the thermal hyperalgesia induced by peripheral inflammation. Moreover, the co-administration of NOC-18 with DPDPE significantly increased the antinociceptive effects produced by DPDPE from 1 to 10 days of CFA-induced inflammatory pain (P < 0.05). These effects were completely blocked by naltrindole and naloxone methiodide. Our results demonstrate that nitric oxide might enhance the local antinociceptive effects of a DOR agonist during chronic inflammatory pain by interaction with peripheral DOR, representing a useful strategy for an efficient antinociceptive treatment of peripheral inflammatory pain.

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

Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria

PubMed Central

Yu, Yanbao; Zielinski, Martin D.; Rolfe, Melanie A.; Kuntz, Melissa M.; Nelson, Heidi; Nelson, Karen E.

2015-01-01

Differential diagnosis of asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) is based on the presence of diverse symptoms, including fever (≥38.5°C), rigors, malaise, lethargy, flank pain, hematuria, suprapubic discomfort, dysuria, and urgent or frequent urination. There is consensus in the medical community that ASB warrants antibiotic treatment only for patients undergoing urological procedures that lead to mucosal bleeding, catheterized individuals whose ASB persists for more than 48 h after catheter removal, and pregnant women. Pyuria is associated with UTI and implicates host immune responses via release of antibacterial effectors and phagocytosis of pathogens by neutrophils. Such responses are not sufficiently described for ASB. Metaproteomic methods were used here to identify the pathogens and evaluate molecular evidence of distinct immune responses in cases of ASB compared to UTI in elderly patients who were hospitalized upon injury. Neutrophil-driven inflammatory responses to invading bacteria were not discernible in most patients diagnosed with ASB compared to those with UTI. In contrast, proteomic urine analysis for trauma patients with no evidence of bacteriuria, including those who suffered mucosal injuries via urethral catheterization, rarely showed evidence of neutrophil infiltration. The same enzymes contributing to the synthesis of leukotrienes LTB4 and LTC4, mediators of inflammation and pain, were found in the UTI and ASB cohorts. These data support the notion that the pathways mediating inflammation and pain in most elderly patients with ASB are not quantitatively different from those seen in most elderly patients with UTI and warrant larger clinical studies to assess whether a common antibiotic treatment strategy for elderly ASB and UTI patients is justified. PMID:26238715

Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria.

PubMed

Yu, Yanbao; Zielinski, Martin D; Rolfe, Melanie A; Kuntz, Melissa M; Nelson, Heidi; Nelson, Karen E; Pieper, Rembert

2015-10-01

Differential diagnosis of asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) is based on the presence of diverse symptoms, including fever (≥38.5°C), rigors, malaise, lethargy, flank pain, hematuria, suprapubic discomfort, dysuria, and urgent or frequent urination. There is consensus in the medical community that ASB warrants antibiotic treatment only for patients undergoing urological procedures that lead to mucosal bleeding, catheterized individuals whose ASB persists for more than 48 h after catheter removal, and pregnant women. Pyuria is associated with UTI and implicates host immune responses via release of antibacterial effectors and phagocytosis of pathogens by neutrophils. Such responses are not sufficiently described for ASB. Metaproteomic methods were used here to identify the pathogens and evaluate molecular evidence of distinct immune responses in cases of ASB compared to UTI in elderly patients who were hospitalized upon injury. Neutrophil-driven inflammatory responses to invading bacteria were not discernible in most patients diagnosed with ASB compared to those with UTI. In contrast, proteomic urine analysis for trauma patients with no evidence of bacteriuria, including those who suffered mucosal injuries via urethral catheterization, rarely showed evidence of neutrophil infiltration. The same enzymes contributing to the synthesis of leukotrienes LTB4 and LTC4, mediators of inflammation and pain, were found in the UTI and ASB cohorts. These data support the notion that the pathways mediating inflammation and pain in most elderly patients with ASB are not quantitatively different from those seen in most elderly patients with UTI and warrant larger clinical studies to assess whether a common antibiotic treatment strategy for elderly ASB and UTI patients is justified. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Ineffective and prolonged apical contraction is associated with chest pain and ischaemia in apical hypertrophic cardiomyopathy.

PubMed

Stephenson, Edward; Monney, Pierre; Pugliese, Francesca; Malcolmson, James; Petersen, Steffen E; Knight, Charles; Mills, Peter; Wragg, Andrew; O'Mahony, Constantinos; Sekhri, Neha; Mohiddin, Saidi A

2018-01-15

To investigate the hypothesis that persistence of apical contraction into diastole is linked to reduced myocardial perfusion and chest pain. Apical hypertrophic cardiomyopathy (HCM) is defined by left ventricular (LV) hypertrophy predominantly of the apex. Hyperdynamic contractility resulting in obliteration of the apical cavity is often present. Apical HCM can lead to drug-refractory chest pain. We retrospectively studied 126 subjects; 76 with apical HCM and 50 controls (31 with asymmetrical septal hypertrophy (ASH) and 19 with non-cardiac chest pain and culprit free angiograms and structurally normal hearts). Perfusion cardiac magnetic resonance imaging (CMR) scans were assessed for myocardial perfusion reserve index (MPRi), late gadolinium enhancement (LGE), LV volumes (muscle and cavity) and regional contractile persistence (apex, mid and basal LV). In apical HCM, apical MPRi was lower than in normal and ASH controls (p<0.05). In apical HCM, duration of contractile persistence was associated with lower MPRi (p<0.01) and chest pain (p<0.05). In multivariate regression, contractile persistence was independently associated with chest pain (p<0.01) and reduced MPRi (p<0.001). In apical HCM, regional contractile persistence is associated with impaired myocardial perfusion and chest pain. As apical myocardium makes limited contributions to stroke volume, apical contractility is also largely ineffective. Interventions to reduce apical contraction and/or muscle mass are potential therapies for improving symptoms without reducing cardiac output. Copyright © 2017 Elsevier B.V. All rights reserved.

Antinociceptive effects of radon inhalation on formalin-induced inflammatory pain in mice.

PubMed

Yamato, Keiko; Kataoka, Takahiro; Nishiyama, Yuichi; Taguchi, Takehito; Yamaoka, Kiyonori

2013-04-01

Radon therapy is clinically useful for the treatment of inflammatory diseases. The mechanisms of pain relief remain to be fully elucidated. In this study, we investigated the antinociceptive effects of radon inhalation in a mouse model of formalin-induced inflammatory pain. Immediately, after radon inhalation at a concentration of background level (ca. 19 Bq/m(3)), 1,000 or 2,000 Bq/m(3) for 24 h, 1.35 % formalin (0.5 % formaldehyde in saline, 20 μl) was subcutaneously injected into the hind paw of mice, and we measured licking response time. Radon inhalation inhibited the second phase of response in formalin test. Formalin administration induced nociception and increased tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) levels in serum and leukocyte migration in paws. Concurrently, formalin injection decreased antioxidative functions. Radon inhalation produced antinociceptive effects, i.e., lowered serum TNF-α and NO levels, and restored antioxidative functions. The results showed that radon inhalation inhibited formalin-induced inflammatory pain.

Reduction of chronic abdominal pain in patients with inflammatory bowel disease through transcranial direct current stimulation: a randomized controlled trial.

PubMed

Volz, Magdalena S; Farmer, Annabelle; Siegmund, Britta

2016-02-01

Inflammatory bowel disease (IBD) is frequently associated with chronic abdominal pain (CAP). Transcranial direct current stimulation (tDCS) has been proven to reduce chronic pain. This study aimed to investigate the effects of tDCS in patients with CAP due to IBD. This randomized, sham-controlled, double blind, parallel-designed study included 20 patients with either Crohn disease or ulcerative colitis with CAP (≥3/10 on the visual analog scale (VAS) in 3/6 months). Anodal or sham tDCS was applied over the primary motor cortex for 5 consecutive days (2 mA, 20 minutes). Assessments included VAS, pressure pain threshold, inflammatory markers, and questionnaires on quality of life, functional and disease specific symptoms (Irritable Bowel Syndrome-Severity Scoring System [IBS-SSS]), disease activity, and pain catastrophizing. Follow-up data were collected 1 week after the end of the stimulation. Statistical analyses were performed using analysis of variance and t tests. There was a significant reduction of abdominal pain in the anodal tDCS group compared with sham tDCS. This effect was evident in changes in VAS and pressure pain threshold on the left and right sides of the abdomen. In addition, 1 week after stimulation, pain reduction remained significantly decreased in the right side of the abdomen. There was also a significant reduction in scores on pain catastrophizing and on IBS-SSS when comparing both groups. Inflammatory markers and disease activity did not differ significantly between groups throughout the experiment. Transcranial direct current stimulation proved to be an effective and clinically relevant therapeutic strategy for CAP in IBD. The analgesic effects observed are unrelated to inflammation and disease activity, which emphasizes central pain mechanisms in CAP.

Management of Clostridium difficile Infection in Inflammatory Bowel Disease: Expert Review from the Clinical Practice Updates Committee of the AGA Institute.

PubMed

Khanna, Sahil; Shin, Andrea; Kelly, Ciarán P

2017-02-01

The purpose of this expert review is to synthesize the existing evidence on the management of Clostridium difficile infection in patients with underlying inflammatory bowel disease. The evidence reviewed in this article is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. This review is a summary of expert opinion in the field without a formal systematic review of evidence. Best Practice Advice 1: Clinicians should test patients who present with a flare of underlying inflammatory bowel disease for Clostridium difficile infection. Best Practice Advice 2: Clinicians should screen for recurrent C difficile infection if diarrhea or other symptoms of colitis persist or return after antibiotic treatment for C difficile infection. Best Practice Advice 3: Clinicians should consider treating C difficile infection in inflammatory bowel disease patients with vancomycin instead of metronidazole. Best Practice Advice 4: Clinicians strongly should consider hospitalization for close monitoring and aggressive management for inflammatory bowel disease patients with C difficile infection who have profuse diarrhea, severe abdominal pain, a markedly increased peripheral blood leukocyte count, or other evidence of sepsis. Best Practice Advice 5: Clinicians may postpone escalation of steroids and other immunosuppression agents during acute C difficile infection until therapy for C difficile infection has been initiated. However, the decision to withhold or continue immunosuppression in inflammatory bowel disease patients with C difficile infection should be individualized because there is insufficient existing robust literature on which to develop firm recommendations. Best Practice Advice 6: Clinicians should offer a referral for fecal microbiota transplantation to inflammatory bowel disease patients with recurrent C difficile infection. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

[Aseptic cutaneous breast abscesses associated with ulcerative colitis].

PubMed

Sallé de Chou, C; Ortonne, N; Hivelin, M; Wolkenstein, P; Chosidow, O; Valeyrie-Allanore, L

2016-02-01

Inflammatory bowel diseases are associated with a broad range of cutaneous lesions. Herein we report the first case of aseptic skin abscesses associated with ulcerative colitis. Since March 2008, a 40-year-old woman presented with bilateral mammary abscesses, relapsing despite repeated antibiotic treatment. She was followed for ulcerative colitis diagnosed in 2011 by means of a rectal biopsy. Despite four surgical procedures, there was no improvement in her mammary abscesses and bilateral mastectomy was then proposed because of the persistent symptoms. Her general state of health remained stable. Clinically, there were bilateral inflammatory nodes with fistulae and pus. These lesions were extremely painful. Mild inflammatory syndrome was noted, but the immunological tests revealed nothing of note. Bacteriological, parasitological and mycological tests on biopsy specimens were negative. Histological examination of a surgical biopsy revealed lymphoplasmacytic infiltration of the dermis and subcutis with altered polymorphonuclear cells and epithelioid granuloma. The CT-scan showed no other remote lesions. The final diagnosis was cutaneous aseptic abscess syndrome associated with ulcerative colitis. Colchicine 1mg/day was initiated and resulted in regression of the skin lesions, with complete remission at one year of follow-up. Aseptic abscess syndrome must be considered in the event of recurrent aseptic cutaneous abscesses which may be associated with inflammatory bowel disease. Surgery should be avoided and treatment should be based on suitable drug therapy. Copyright © 2016. Published by Elsevier Masson SAS.

[The persistent sciatic artery aneurysm. A rare and painful buttock mass].

PubMed

Alliez, A; Gay, A-M; Prost, C; Legre, R

2013-08-01

The persistent sciatic artery is a rare cause of painful buttock mass with L5-S1 radicular signs. A 56-year-old man presents a right painful buttock mass with L5-S1 radicular symptoms for 3 years. The surgical exploration found a pulsatile vascular mass like a persistent sciatic artery aneurysm. This vascular pathology is a misunderstood embryogenesis anomaly. The treatment aims to avoid serious complications. This pathology must be known from plastic surgeon. Copyright © 2013 Elsevier Masson SAS. 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

Coexistence of Ankylosing Spondylitis and Klinefelter's Syndrome

PubMed Central

Kobak, Şenol; Yalçin, Murat; Karadeniz, Muamer; Oncel, Guray

2013-01-01

Ankylosing spondylitis is a chronic inflammatory disease characterized by inflammatory lower back pain and morning stiffness and accompanied by spine and sacroiliac joint involvement. Klinefelter's syndrome is a genetic condition that only affects males. Affected males have an extra X chromosome. This paper reports a 30-years-old male on followup with the diagnosis of Klinefelters syndrome. The patient admitted with complaints of inflammatory lower back, and neck pain and morning stiffness and was diagnosed with ankylosing spondylitis. Nonsteroidal anti-inflammatory drug and salazopyrine treatment resulted in significant regression in his complaints. PMID:23762731

Coexistence of Ankylosing Spondylitis and Klinefelter's Syndrome.

PubMed

Kobak, Senol; Yalçin, Murat; Karadeniz, Muamer; Oncel, Guray

2013-01-01

Ankylosing spondylitis is a chronic inflammatory disease characterized by inflammatory lower back pain and morning stiffness and accompanied by spine and sacroiliac joint involvement. Klinefelter's syndrome is a genetic condition that only affects males. Affected males have an extra X chromosome. This paper reports a 30-years-old male on followup with the diagnosis of Klinefelters syndrome. The patient admitted with complaints of inflammatory lower back, and neck pain and morning stiffness and was diagnosed with ankylosing spondylitis. Nonsteroidal anti-inflammatory drug and salazopyrine treatment resulted in significant regression in his complaints.

Kaempferol, a dietary flavonoid, ameliorates acute inflammatory and nociceptive symptoms in gastritis, pancreatitis, and abdominal pain.

PubMed

Kim, Shi Hyoung; Park, Jae Gwang; Sung, Gi-Ho; Yang, Sungjae; Yang, Woo Seok; Kim, Eunji; Kim, Jun Ho; Ha, Van Thai; Kim, Han Gyung; Yi, Young-Su; Kim, Ji Hye; Baek, Kwang-Soo; Sung, Nak Yoon; Lee, Mi-nam; Kim, Jong-Hoon; Cho, Jae Youl

2015-07-01

Kaempferol (KF) is the most abundant polyphenol in tea, fruits, vegetables, and beans. However, little is known about its in vivo anti-inflammatory efficacy and mechanisms of action. To study these, several acute mouse inflammatory and nociceptive models, including gastritis, pancreatitis, and abdominal pain were employed. Kaempferol was shown to attenuate the expansion of inflammatory lesions seen in ethanol (EtOH)/HCl- and aspirin-induced gastritis, LPS/caerulein (CA) triggered pancreatitis, and acetic acid-induced writhing. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Intervertebral Foramen Injection of Ozone Relieves Mechanical Allodynia and Enhances Analgesic Effect of Gabapentin in Animal Model of Neuropathic Pain.

PubMed

Luo, Wen-Jun; Yang, Fan; Yang, Fei; Sun, Wei; Zheng, Wei; Wang, Xiao-Liang; Wu, Fang-Fang; Wang, Jiang-Lin; Wang, Jia-Shuang; Guan, Su-Min; Chen, Jun

2017-07-01

In a 5-year follow-up study in a hospital in southern China, it was shown that intervertebral foramen (IVF) injection of ozone at the involved segmental levels could significantly alleviate paroxysmal spontaneous pain and mechanical allodynia in patients with chronic, intractable postherpetic neuralgia (PHN) and improve the quality of life. However, so far no proof-of-concept studies in animals have been available. This study was designed to investigate whether IVF ozone has an analgesic effect on animal models of neuropathic and inflammatory pain. Experimental trial in rats. Institute for Biomedical Sciences of Pain. By IVF injection, a volume of 50 µl containing 30 µg/mL ozone-oxygen mixture or 50 µl air was carried out on male Sprague-Dawley rats of naïve, inflammatory pain states produced by injections of either bee venom or complete Freud's adjuvant, and neuropathic pain state produced by spared nerve injury, respectively. The effects of IVF ozone on pain-related behaviors were evaluated for 2 weeks or one month. Then combined use of gabapentin (100 mg/1 kg body weight) with IVF ozone was evaluated in rats with neuropathic pain by intraperitoneal administration 5 days after the ozone treatment. Finally, the analgesic effects of another 4 drugs, AMD3100 (a CXCR4 antagonist), A-803467 (a selective Nav1.8 blocker), rapamycin (the mTOR inhibitor), and MGCD0103 (a selective histone deacetylase inhibitor) were evaluated for long term through IVF injection, respectively. (1) IVF injection of ozone at L4-5 was only effective in suppression of mechanical allodynia in rats with neuropathic pain but not with inflammatory pain; (2) the analgesic effects of IVF ozone lasted much longer (> 14 days) than other selective molecular target drugs (< 48 hours) inhibiting or antagonizing at Nav1.8 (A-803467), CXCR4 (AMD3100), mTOR (rapamycin), and histone deacetylase (MGCD0103); (3) combined use of systemic gabapentin and IVF ozone produced a synergistic analgesic effect in rats with neuropathic pain. Evaluation of the possible analgesic effects of the intraplantar injection of ozone was not performed. In the present study, we provided a line of evidence for the first time that IVF injection of ozone selectively relieved neuropathic pain but not inflammatory pain, and enhanced the analgesic effect of gabapentin. Chronic pain, neuropathic pain, inflammatory pain, ozone therapy, interventional therapy, gabapentin, spared nerve injury, bee venom, complete Freud's adjuvant.

The microbiome of the oral mucosa in irritable bowel syndrome

PubMed Central

Fourie, Nicolaas H.; Wang, Dan; Abey, Sarah K.; Sherwin, LeeAnne B.; Joseph, Paule V.; Rahim-Williams, Bridgett; Ferguson, Eric G.; Henderson, Wendy A.

2016-01-01

abstract Irritable bowel syndrome (IBS) is a poorly understood disorder characterized by persistent symptoms, including visceral pain. Studies have demonstrated oral microbiome differences in inflammatory bowel diseases suggesting the potential of the oral microbiome in the study of non-oral conditions. In this exploratory study we examine whether differences exist in the oral microbiome of IBS participants and healthy controls, and whether the oral microbiome relates to symptom severity. The oral buccal mucosal microbiome of 38 participants was characterized using PhyloChip microarrays. The severity of visceral pain was assessed by orally administering a gastrointestinal test solution. Participants self-reported their induced visceral pain. Pain severity was highest in IBS participants (P = 0.0002), particularly IBS-overweight participants (P = 0.02), and was robustly correlated to the abundance of 60 OTUs, 4 genera, 5 families and 4 orders of bacteria (r2 > 0.4, P < 0.001). IBS-overweight participants showed decreased richness in the phylum Bacteroidetes (P = 0.007) and the genus Bacillus (P = 0.008). Analysis of β-diversity found significant separation of the IBS-overweight group (P < 0.05). Our oral microbial results are concordant with described fecal and colonic microbiome-IBS and -weight associations. Having IBS and being overweight, rather than IBS-subtypes, was the most important factor in describing the severity of visceral pain and variation in the microbiome. Pain severity was strongly correlated to the abundance of many taxa, suggesting the potential of the oral microbiome in diagnosis and patient phenotyping. The oral microbiome has potential as a source of microbial information in IBS. PMID:26963804

Vinpocetine Reduces Carrageenan-Induced Inflammatory Hyperalgesia in Mice by Inhibiting Oxidative Stress, Cytokine Production and NF-κB Activation in the Paw and Spinal Cord

PubMed Central

Ruiz-Miyazawa, Kenji W.; Zarpelon, Ana C.; Pinho-Ribeiro, Felipe A.; Pavão-de-Souza, Gabriela F.; Casagrande, Rubia; Verri, Waldiceu A.

2015-01-01

Vinpocetine is a safe nootropic agent used for neurological and cerebrovascular diseases. The anti-inflammatory activity of vinpocetine has been shown in cell based assays and animal models, leading to suggestions as to its utility in analgesia. However, the mechanisms regarding its efficacy in inflammatory pain treatment are still not completely understood. Herein, the analgesic effect of vinpocetine and its anti-inflammatory and antioxidant mechanisms were addressed in murine inflammatory pain models. Firstly, we investigated the protective effects of vinpocetine in overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone (PBQ) and formalin. The intraplantar injection of carrageenan was then used to induce inflammatory hyperalgesia. Mechanical and thermal hyperalgesia were evaluated using the electronic von Frey and the hot plate tests, respectively, with neutrophil recruitment to the paw assessed by a myeloperoxidase activity assay. A number of factors were assessed, both peripherally and in the spinal cord, including: antioxidant capacity, reduced glutathione (GSH) levels, superoxide anion, tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels, as well as nuclear factor kappa B (NF-κB) activation. Vinpocetine inhibited the overt pain-like behavior induced by acetic acid, PBQ and formalin (at both phases), as well as the carrageenan-induced mechanical and thermal hyperalgesia and associated neutrophil recruitment. Both peripherally and in the spinal cord, vinpocetine also inhibited: antioxidant capacity and GSH depletion; increased superoxide anion; IL-1β and TNF-α levels; and NF-κB activation. As such, vinpocetine significantly reduces inflammatory pain by targeting oxidative stress, cytokine production and NF-κB activation at both peripheral and spinal cord levels. PMID:25822523

Vinpocetine reduces carrageenan-induced inflammatory hyperalgesia in mice by inhibiting oxidative stress, cytokine production and NF-κB activation in the paw and spinal cord.

PubMed

Ruiz-Miyazawa, Kenji W; Zarpelon, Ana C; Pinho-Ribeiro, Felipe A; Pavão-de-Souza, Gabriela F; Casagrande, Rubia; Verri, Waldiceu A

2015-01-01

Vinpocetine is a safe nootropic agent used for neurological and cerebrovascular diseases. The anti-inflammatory activity of vinpocetine has been shown in cell based assays and animal models, leading to suggestions as to its utility in analgesia. However, the mechanisms regarding its efficacy in inflammatory pain treatment are still not completely understood. Herein, the analgesic effect of vinpocetine and its anti-inflammatory and antioxidant mechanisms were addressed in murine inflammatory pain models. Firstly, we investigated the protective effects of vinpocetine in overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone (PBQ) and formalin. The intraplantar injection of carrageenan was then used to induce inflammatory hyperalgesia. Mechanical and thermal hyperalgesia were evaluated using the electronic von Frey and the hot plate tests, respectively, with neutrophil recruitment to the paw assessed by a myeloperoxidase activity assay. A number of factors were assessed, both peripherally and in the spinal cord, including: antioxidant capacity, reduced glutathione (GSH) levels, superoxide anion, tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels, as well as nuclear factor kappa B (NF-κB) activation. Vinpocetine inhibited the overt pain-like behavior induced by acetic acid, PBQ and formalin (at both phases), as well as the carrageenan-induced mechanical and thermal hyperalgesia and associated neutrophil recruitment. Both peripherally and in the spinal cord, vinpocetine also inhibited: antioxidant capacity and GSH depletion; increased superoxide anion; IL-1β and TNF-α levels; and NF-κB activation. As such, vinpocetine significantly reduces inflammatory pain by targeting oxidative stress, cytokine production and NF-κB activation at both peripheral and spinal cord levels.

Endogenous opioids released during non-nociceptive environmental stress induce latent pain sensitization Via a NMDA-dependent process.

PubMed

Le Roy, Chloé; Laboureyras, Emilie; Gavello-Baudy, Stéphanie; Chateauraynaud, Jérémy; Laulin, Jean-Paul; Simonnet, Guy

2011-10-01

Although stress induces analgesia, there is evidence that stressful events may exacerbate pain syndromes. Here, we studied the effects of 1 to 3 prestressful events (days 0, 2, and 7), such as non-nociceptive environmental stress, on inflammatory hyperalgesia induced by a carrageenan injection (day 14) in 1 rat hind paw. Changes in nociceptive threshold were evaluated by the paw pressure vocalization test. The higher the number of stress sessions presented to the rats, the greater was the inflammatory hyperalgesia. Blockade of opioid receptors by naltrexone before each stress inhibited stress-induced analgesia and suppressed the exaggerated inflammatory hyperalgesia. Stressed versus nonstressed animals could be discriminated by their response to a fentanyl ultra-low dose (fULD), that produced hyperalgesia or analgesia, respectively. This pharmacological test permitted the prediction of the pain vulnerability level of prestressed rats because fULD analgesic or hyperalgesic indices were positively correlated with inflammatory hyperalgesic indices (r(2) = .84). In prestressed rats, fULD-induced hyperalgesia and the exaggerated inflammatory hyperalgesia were prevented NMDA receptor antagonists. This study provides some preclinical evidence that pain intensity is not only the result of nociceptive input level but is also dependent on the individual history, especially prior life stress events associated with endogenous opioid release. Based on these preclinical data, it would be of clinical interest to evaluate whether prior stressful events may also affect further pain sensation in humans. Moreover, this preclinical model could be a good tool for evaluating new therapeutic strategies for relieving pain hypersensitivity. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Effects of insomnia disorder and knee osteoarthritis on resting and pain-evoked inflammatory markers.

PubMed

Quartana, Phillip J; Finan, Patrick H; Page, Gayle G; Smith, Michael T

2015-07-01

Osteoarthritis is the most prevalent arthritic condition. Systemic inflammatory cytokines appear to have an important role in the onset and maintenance of the disease. Sleep disturbances are prevalent in osteoarthritis and associated with alterations in systemic inflammatory cytokines, suggesting a common pathophysiology across these conditions. A comparative investigation of the effects of insomnia disorder and osteoarthritis on pain-evoked cytokine responses has yet to be undertaken. We examined the influence of symptomatic knee osteoarthritis and insomnia disorder on resting C-reactive protein (CRP), interleukin (IL)-6, and IL-10 levels, and pain-evoked IL-6 and IL-10 responses. Participants were N=117 older adults (mean age=59.7years; 61.8% women) rigorously evaluated for knee osteoarthritis and insomnia disorder using established diagnostic guidelines. Results revealed no association of osteoarthritis or insomnia disorder with CRP. Resting IL-6 was greater in osteoarthritis participants versus those without osteoarthritis, although this association was largely attributable to BMI. IL-10 was highest among participants with osteoarthritis or insomnia disorder. Growth curve modeling revealed that participants with insomnia disorder had greater pain-evoked IL-6 responses than participants without insomnia disorder or osteoarthritis. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Moreover, our findings provide evidence for amplified pain-evoked pro-inflammatory cytokine reactivity among older adults with clinically diagnosed insomnia disorder, even after controlling for individual differences in BMI and age. Additional research will be required determine whether an amplified pain-related cytokine response contributes to OA, and possibly other age-related disease, associated with insomnia disorder. Published by Elsevier Inc.

Efficacy of a Subacromial Corticosteroid Injection for Persistent Pain After Arthroscopic Rotator Cuff Repair.

PubMed

Shin, Sang-Jin; Do, Nam-Hoon; Lee, Juyeob; Ko, Young-Won

2016-09-01

Corticosteroid injections have been widely used for reducing shoulder pain. However, catastrophic complications induced by corticosteroid such as infections and tendon degeneration have made surgeons hesitant to use a corticosteroid injection as a pain control modality, especially during the postoperative recovery phase. To determine the effectiveness and safety of a subacromial corticosteroid injection for persistent pain control during the recovery period and to analyze the factors causing persistent pain after arthroscopic rotator cuff repair. Cohort study; Level of evidence, 3. A total of 458 patients who underwent arthroscopic rotator cuff repair were included in this study. Patient-specific parameters, tear size and pattern, and pain intensity were reviewed. Seventy-two patients were administered a postoperative subacromial corticosteroid injection under ultrasound guidance. The corticosteroid injection was administered to patients who awakened overnight because of constant severe shoulder pain or whose pain was exacerbated at the time of rehabilitation exercises within 8 weeks after surgery. Pain intensity, patient satisfaction, and functional outcomes using the American Shoulder and Elbow Surgeons (ASES) and Constant scores were compared between the patients with and without a subacromial corticosteroid injection. The retear rate was evaluated with magnetic resonance imaging at 6 months postoperatively. In patients with an injection, the mean (±SD) visual analog scale for pain (pVAS) score was 7.7 ± 1.2 at the time of the injection. This significantly decreased to 2.3 ± 1.4 at the end of the first month after the injection, demonstrating a 70.2% reduction in pain (P < .01). At 3 months after the injection, the mean pVAS score was 1.2 ± 1.8. Functional outcomes at final follow-up showed no significant differences between patients with and without an injection (ASES score: 90.1 ± 14.6 with injection, 91.9 ± 8.2 without injection [P = .91]; Constant score: 89.1 ± 12.9 with injection, 84.5 ± 13.0 without injection [P = .17]). Patients with an injection showed no significant increase in the retear rate (6.8% with injection, 18.4% without injection; P = .06). According to the tear pattern, L-shaped rotator cuff tears (41.8%) showed a higher occurrence of severe postoperative persistent pain. Preoperative shoulder stiffness was revealed as a predisposing factor for persistent pain (odds ratio, 0.2; P = .04). A subacromial corticosteroid injection can be considered as a useful and safe modality for the treatment of patients having severe persistent pain during the recovery phase after arthroscopic rotator cuff repair. © 2016 The Author(s).

The public neglect of rheumatic diseases: insights from analyses of attendees in a musculoskeletal disease awareness activity

PubMed Central

Machold, Klaus P; Köller, Marcus D; Pflugbeil, Stephan; Zimmermann, Christof; Wagner, Ernst; Stuby, Ulrike; Aletaha, Daniel; Stamm, Tanja A; Mayrhofer, Franz; Dunky, Attila; Hermann, Josef; Ilias, Wilfried; Smolen, Josef S

2007-01-01

Objectives To obtain data on the care received by individuals counselled during a public health awareness campaign on painful musculoskeletal conditions (MSC). Methods Easy non‐formal access to rheumatologists/pain specialists was offered using a mobile unit (Rheuma‐Bus) at widely accessible sites. Clients were asked to assess their severity of pain using a 100 mm visual analogue scale (VAS). Age, gender, disease duration, diagnosis if known, current and previous treatment as well as tentative diagnoses assigned and recommendations given to each individual by the counselling physicians were recorded. Results Average (SD) VAS pain rating was 59 (20.6) mm. Approximately 40% of clients had never consulted a physician for their condition before, but had lower pain scores than those who had seen a physician. Patients with inflammatory MSC had higher pain scores than those with non‐inflammatory conditions. More than 2% of the clients had a newly detected inflammatory rheumatic disease. Conclusions Many individuals having painful MSC seek medical help only when a very high threshold of pain is reached. Even while under treatment, the high mean pain scores suggest neglect of MSC that are not adequately recognised as important contributors to disability and decreased quality of life. PMID:17204565

Clinical characteristics of importance to outcome in patients with axial spondyloarthritis: protocol for a prospective descriptive and exploratory cohort study.

PubMed

Andreasen, Rikke Asmussen; Kristensen, Lars Erik; Ellingsen, Torkell; Christensen, Robin; Baraliakos, Xenofon; Wied, Jimmi; Aalykke, Claus; Ulstrup, Thomas; Schiøttz-Christensen, Berit; Horn, Hans Christian; Emamifar, Amir; Duerlund, Bent; Fischer, Lars; Hansen, Inger Marie Jensen

2017-07-10

Spondyloarthritis (SpA) is a heterogeneous spectrum of rheumatic diseases with either predominantly axial inflammatory symptoms of the spine and sacroiliac joints or predominantly peripheral arthritis. The two main entities of axial SpA (axSpA) are ankylosing spondylitis or non-radiographic axSpA (nr-axSpA). Tumour necrosis factor-α inhibitors have revolutionised the treatment of patients with axSpA who failed to respond to non-steroidal anti-inflammatory drugs and physical therapy. Chronic pain is common in patients with SpA and may still persist despite the lack of signs of inflammation. This has led researchers to hypothesise that central pain sensitisation may play a role in the generation of chronic pain in SpA. The painDETECT Questionnaire (PDQ) is a screening tool developed to detect neuropathic pain components. The primary objective is to explore the prognostic value of the PDQ regarding treatment response in patients with axSpA 3 months after initiating a biological agent. Secondary aim is to evaluate the impact of extra-articular manifestations, comorbidities and patient-reported outcomes and elucidate if these factors influence treatment response. We will include 60 participants (≥18 years of age) diagnosed with axSpA independent of main entity, who initiate or switch treatment of a biologic. Data will be collected at baseline and at endpoint following Danish clinical practice (≥3 months) of treatment with biologics. We will explore whether the PDQ and other phenotypical patient characteristics are prognostically important for response to biological therapy according to established response criteria like 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (50%) and Ankylosing Spondylitis Disease Activity Score. The study is approved by the Region of Southern Denmark's Ethics committee (S-20160094) and has been designed in cooperation with patient representatives. The study is registered at clinicaltrials.gov (NCT02948608, pre-results). Dissemination will occur through publication(s) in international peer-reviewed journal(s). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Potential involvement of μ-opioid receptor dysregulation on the reduced antinociception of morphine in the inflammatory pain state in mice.

PubMed

Aoki, Yuta; Mizoguchi, Hirokazu; Watanabe, Chizuko; Takeda, Kumiko; Sakurada, Tsukasa; Sakurada, Shinobu

2014-01-01

The antinociceptive effect of morphine in the inflammatory pain state was described in the von Frey filament test using the complete Freund's adjuvant (CFA)-induced mouse inflammatory pain model. After an i.pl. injection of CFA, mechanical allodynia was observed in the ipsilateral paw. The antinociceptive effect of morphine injected s.c. and i.t. against mechanical allodynia was reduced bilaterally at 1 day and 4 days after the CFA pretreatment. The expression level of mRNA for μ-opioid receptors at 1 day after the CFA pretreatment was reduced bilaterally in the lumbar spinal cord and dorsal root ganglion (DRG). In contrast, the protein level of μ-opioid receptors at 1 day after CFA pretreatment was decreased in the ipsilateral side in the DRG but not the lumbar spinal cord. Single or repeated i.t. pretreatment with the protein kinase Cα (PKCα) inhibitor Ro-32-0432 completely restored the reduced morphine antinociception in the contralateral paw but only partially restored it in the ipsilateral paw in the inflammatory pain state. In conclusion, reduced morphine antinociception against mechanical allodynia in the inflammatory pain state is mainly mediated via a decrease in μ-opioid receptors in the ipsilateral side and via the desensitization of μ-opioid receptors in the contralateral side by PKCα-induced phosphorylation.

Cortex glial cells activation, associated with lowered mechanical thresholds and motor dysfunction, persists into adulthood after neonatal pain.

PubMed

Sanada, Luciana Sayuri; Sato, Karina Laurenti; Machado, Nathalia Leilane Berto; Carmo, Elisabete de Cássia do; Sluka, Kathleen A; Fazan, Valeria Paula Sassoli

2014-06-01

We investigated if changes in glial activity in cortical areas that process nociceptive stimuli persisted in adult rats after neonatal injury. Neonatal pain was induced by repetitive needle prickling on the right paw, twice per day for 15 days starting at birth. Wistar rats received either neonatal pain or tactile stimulation and were tested behaviorally for mechanical withdrawal thresholds of the paws and gait alterations, after 15 (P15) or 180 (P180) days of life. Brains from rats on P15 and P180 were immunostained for glial markers (GFAP, MCP-1, OX-42) and the following cortical areas were analyzed for immunoreactivity density: prefrontal, anterior insular, anterior cingulated, somatosensory and motor cortices. Withdrawal thresholds of the stimulated paw remained decreased on P180 after neonatal pain when compared to controls. Neonatal pain animals showed increased density for both GFAP and MCP-1 staining, but not for OX-42, in all investigated cortical areas on both experimental times (P15 and P180). Painful stimuli in the neonatal period produced pain behaviors immediately after injury that persisted in adult life, and was accompanied by increase in the glial markers density in cortical areas that process and interpret pain. Thus, long-lasting changes in cortical glial activity could be, at least in part, responsible for the persistent hyperalgesia in adult rats that suffered from neonatal pain. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

Acute versus chronic phase mechanisms in a rat model of CRPS.

PubMed

Wei, Tzuping; Guo, Tian-Zhi; Li, Wen-Wu; Kingery, Wade S; Clark, John David

2016-01-19

Tibia fracture followed by cast immobilization in rats evokes nociceptive, vascular, epidermal, and bone changes resembling complex regional pain syndrome (CRPS). In most cases, CRPS has three stages. Over time, this acute picture, allodynia, warmth, and edema observed at 4 weeks, gives way to a cold, dystrophic but still painful limb. In the acute phase (at 4 weeks post fracture), cutaneous immunological and NK1-receptor signaling mechanisms underlying CRPS have been discovered; however, the mechanisms responsible for the chronic phase are still unknown. The purpose of this study is to understand the mechanisms responsible for the chronic phases of CRPS (at 16 weeks post fracture) at both the peripheral and central levels. We used rat tibial fracture/cast immobilization model of CRPS to study molecular, vascular, and nociceptive changes at 4 and 16 weeks post fracture. Immunoassays and Western blotting were carried out to monitor changes in inflammatory response and NK1-receptor signaling in the skin and spinal cord. Skin temperature and thickness were measured to elucidate vascular changes, whereas von Frey testing and unweighting were carried out to study nociceptive changes. All data were analyzed by one-way analysis of variance (ANOVA) followed by Neuman-Keuls multiple comparison test to compare among all cohorts. In the acute phase (at 4 weeks post fracture), hindpaw allodynia, unweighting, warmth, edema, and/or epidermal thickening were observed among 90 % fracture rats, though by 16 weeks (chronic phase), only the nociceptive changes persisted. The expression of the neuropeptide signaling molecule substance P (SP), NK1 receptor, inflammatory mediators TNFα, IL-1β, and IL-6 and nerve growth factor (NGF) were elevated at 4 weeks in sciatic nerve and/or skin, returning to normal levels by 16 weeks post fracture. The systemic administration of a peripherally restricted IL-1 receptor antagonist (anakinra) or of anti-NGF inhibited nociceptive behaviors at 4 weeks but not 16 weeks. However, spinal levels of NK1 receptor, TNFα, IL-1β, and NGF were elevated at 4 and 16 weeks, and intrathecal injection of an NK1-receptor antagonist (LY303870), anakinra, or anti-NGF each reduced nociceptive behaviors at both 4 and 16 weeks. These results demonstrate that tibia fracture and immobilization cause peripheral changes in neuropeptide signaling and inflammatory mediator production acutely, but central spinal changes may be more important for the persistent nociceptive changes in this CRPS model.

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

The Effects of Inflammatory Tooth Pain on Anxiety in Adult Male Rats

PubMed Central

Raoof, Maryam; Ebrahimnejad, Hamed; Abbasnejad, Mehdi; Amirkhosravi, Ladan; Raoof, Ramin; Esmaeili Mahani, Saeed; Ramazani, Mohsen; Shokouhinejad, Noushin; Khoshkhounejad, Mehrfam

2016-01-01

Introduction: This study aimed to examine the effects of induced inflammatory tooth pain on anxiety level in adult male rats. Methods: The mandibular incisors of 56 adult male rats were cut off and prefabricated crowns were fixed on the teeth. Formalin and capsaicin were injected intradentally to induce inflammatory tooth pain. Diazepam treated group received diazepam 30 minutes before intradental injection. The anxiety-related behavior was evaluated with elevated plus maze test. Results: Intradental application of chemical noxious stimuli, capsaicin and formalin, significantly affected nociceptive behaviors (P<0.001). Capsaicin (P<0.001) and formalin (P<0.01) significantly increased the anxiety levels in rats by decrease in the duration of time spent in open arm and increase in the duration of time spent in closed arm. Rats that received capsaicin made fewer open arm entries compared to the control animals (P<0.05). Capsaicin (P<0.001) and formalin (P<0.01) treated rats showed more stretch attend postures compared to the control and sham operated animals. In diazepampretreated rats, capsaicin induced algesic effect was prevented (P<0.001). Conclusion: Inflammatory pulpal pain has anxiogenic effect on rats, whereas diazepam premedication showed both anxiolytic and pain reducing effects. PMID:27563419

Predicting the pain continuum after adolescent idiopathic scoliosis surgery: A prospective cohort study

PubMed Central

Chidambaran, V.; Ding, L.; Moore, D.L.; Spruance, K.; Cudilo, E.M.; Pilipenko, V.; Hossain, M.; Sturm, P.; Kashikar-Zuck, S.; Martin, L.J.; Sadhasivam, S.

2017-01-01

Background Chronic postsurgical pain (CPSP) affects half a million children annually in the United States, with dire socioeconomic consequences, including long-term disability into adulthood. The few studies of CPSP in children are limited by sample size, follow-up duration, non-homogeneity of surgical procedure and factors evaluated. Methods In a prospective study of 144 adolescents undergoing a single major surgery (spine fusion), we evaluated demographic, perioperative, surgical and psychosocial factors as predictors of a continuum of postsurgical pain: immediate, pain maintenance at 2–3 months (chronic pain/CP) and persistence of pain a year (persistent pain/PP) after surgery. Results We found an incidence of 37.8% and 41.8% for CP and PP. CP and acute pain were both significant predictors for developing PP (p-value <0.001 and 0.003). Preoperative pain and higher postoperative opioid requirement was significantly associated with CP (p = 0.015, p = 0.002), while Childhood Anxiety Sensitivity Index (p = 0.002) and surgical duration (p = 0.014) predicted PP. The final regression models had reasonable predictive accuracy (c-statistic of 0.73 and 0.83 for CP and PP, respectively). Anxiety scores and catastrophizing for child and parent were found to be significantly correlated (p = 0.005, p = 0.013 respectively). Pain trajectories revealed that 65% of patients who developed PP reported CP and high pain trends; however, 33% of those who developed PP could not be identified using solely pain criteria. Conclusion Persistent postsurgical pain in children is a significant problem. It can be predicted in part by combinations of psychological and clinical variables, which may provide evidence-based measures to prevent development of CPSP in the future. Significance In a homogeneous cohort of adolescents undergoing spine fusion, we report a high incidence of persistent postsurgical pain (41.8%) predicted by child anxiety, perioperative pain, and surgical duration. Our results stress timely preventive and therapeutic strategies. PMID:28346762

Predictors of Persistent Axial Neck Pain After Cervical Laminoplasty.

PubMed

Kimura, Atsushi; Shiraishi, Yasuyuki; Inoue, Hirokazu; Endo, Teruaki; Takeshita, Katsushi

2018-01-01

Retrospective analysis of prospective data. The aim of this study was to reveal baseline predictors of persistent postlaminoplasty neck pain. Axial neck pain is one of the most common complications after cervical laminoplasty; however, baseline predictors of persistent postlaminoplasty neck pain are unclear. We analyzed data from 156 patients who completed a 2-year follow-up after double-door laminoplasty for degenerative cervical myelopathy. Patients rated the average intensity of axial neck pain in the last month using an 11-point numerical rating scale preoperatively and at the 2-year follow-up. The dependent variable was the presence of moderate-to-severe neck pain (numerical rating scale ≥4) at the 2-year follow-up. The independent variables included patient characteristics, baseline radiological parameters, surgical variables, baseline axial neck pain intensity, and baseline functions, which were measured by the Japanese Orthopaedic Association score and the Short Form-36 survey (SF-36). Logistic regression analysis was performed to identify independent predictors of moderate-to-severe neck pain after laminoplasty. At the 2-year follow-up, 51 patients (32%) had moderate-to-severe neck pain, and 106 patients (68%) had no or mild pain. Univariate analysis revealed that the ratio of cervical anterolisthesis, ratio of current smoking, baseline neck pain intensity, and baseline SF-36 Mental Component Summary differed significantly between the groups. Multivariate logistic regression analysis showed that independent predictors of moderate-to-severe neck pain at the 2-year follow-up include the presence of anterolisthesis, current smoking, moderate-to-severe baseline neck pain, and lower SF-36 Mental Component Summary. The presence of anterolisthesis and moderate-to-severe baseline neck pain were also associated with significantly poorer physical function after surgery. The presence of anterolisthesis was associated not only with the highest odds ratio of persistent neck pain but also with significantly poorer functional outcomes. Indications for cervical laminoplasty should be carefully determined in patients with cervical anterolisthesis. 4.

Effect of surgical castration with or without oral meloxicam on the acute inflammatory response in yearling beef bulls

USDA-ARS?s Scientific Manuscript database

Pain management and welfare are increasingly prevalent concerns within animal agriculture and oral analgesics may alleviate the pain associated with castration. This study was conducted to elucidate the effects of surgical castration on the acute inflammatory response and immunomodulation and whethe...

Effect of surgical castration with or without oral meloxicam on the acute inflammatory response in yearling beef bulls

USDA-ARS?s Scientific Manuscript database

Pain management and welfare are increasingly prevalent concerns within animal agriculture. Analgesics may alleviate pain and inflammation associated with castration of beef cattle. This study was conducted to elucidate the effects of surgical castration on the acute inflammatory response and immunom...

Effect of surgical castration with or without meloxicam on the acute inflammatory response in yearling beef bulls

USDA-ARS?s Scientific Manuscript database

Pain management and welfare are increasingly prevalent concerns within animal agriculture and oral analgesics may alleviate the pain associated with castration. This study was conducted to elucidate the effects of surgical castration on the acute inflammatory response and immunomodulation and whethe...

Potamotrygon motoro stingray venom induces both neurogenic and inflammatory pain behavior in rodents.

PubMed

Kimura, L F; Santos-Neto, M; Barbaro, K C; Picolo, G

2018-05-25

Freshwater stingray accidents cause an immediate, intense, and unrelieved pain which is followed by edema, erythema and necrosis formation. Treatment for stingray envenomation is based on administration of analgesic, antipyretic and anti-inflammatory drugs. Concerning pain control, it is prescribed to immerse punctured limb on hot water to alleviate pain. There are no studies demonstrating specific targets on which stingray venom acts to promote pain. Therefore, the aim of this work was to investigate some mechanisms of Potamotrygon motoro venom (PmV) that contribute to nociception induction. Evaluating spontaneous pain behavior in mice injected i.pl. with PmV, it was seen that PmV induced both neurogenic and inflammatory pain. PmV also induced hyperalgesia in both mice and rats, evaluated through electronic von Frey and rat paw pressure test, respectively. Partial inhibition of hyperalgesia was observed in mice treated with cromolyn or promethazine, which indicated that mast cell and histamine via H1 receptor participate in the inflammatory pain. To search for some targets involved in PmVinduced hyperalgesia, the participation of TRPV1, calcium channels, neurokinins, CGRP, and norepinephrine, was evaluated in rats. It was seen that PmV-induced hyperalgesia occurs with the participation of neurokinins, mainly via NK1 receptor, CGRP, and calcium influx, through both P/Q and L-type voltage-dependent calcium channels, besides TRPV1 activation. The data presented herein indicate that PmV causes hyperalgesia in rodents which is dependent on the participation of several neuroinflammatory mediators. Copyright © 2018 Elsevier Ltd. All rights reserved.

Anti-inflammatory and anti-hypersensitive effects of the crude extract, fractions and triterpenes obtained from Chrysophyllum cainito leaves in mice.

PubMed

Meira, Nicole Anzanelo; Klein, Luiz Carlos; Rocha, Lilian W; Quintal, Zhelmy Martin; Monache, Franco Delle; Cechinel Filho, Valdir; Quintão, Nara Lins Meira

2014-02-03

Chrysophyllum cainito, popularly known as "star apple", caimito, "abiu-roxo" or "abiu-do-Pará", is a tree of about 25m in height. Besides its culinary use, it is also used in folk medicine for the treatment of diabetes mellitus and several inflammatory diseases. The crude methanolic extract (CME) was submitted to phytochemical studies for obtaining fractions and isolated compounds. They were monitored by thin-layer-chromatography (TLC). The biological activity was evaluated in mice using the carrageenan-induced mechanical hypersensitivity and paw oedema. Biochemical assays, such as myeloperoxidase (MPO) and activity and cytokines levels quantification, were carried out to analyse the involvement of neutrophil migration and IL-1β and TNFα production. Some adverse effects were investigated using the open-field and rota-rod tests, and it was also measured the rectal temperature. This study demonstrates, for the first time, the anti-hypersensitivity and anti-inflammatory effects of CME, fractions and two isolated triterpenes obtained from the leaves of Chrysophyllum cainito on carrageenan-induced hypersensitivity and paw-oedema. The mice treated with CME or chloroform fraction (CHCl3) presented reduction in mechanical hypersensitivity. The effect of the CME seemed to be partially related to the anti-inflammatory activity, as the paw-oedema and MPO activity were also significantly inhibited. The isolated compound Lup-20(29)-en-3β-O-hexanoate demonstrated more reduction of the hypersensitivity than 3β-Lup-20(29)-en-3-yl acetate, suggesting that this molecule might be partially responsible for the biological effects obtained with CME and CHCl3 fractions. Finally, animals treated with CME and CHCl3 did not present changes in locomotor activity, motor performance or body temperature. Our data demonstrates, for the first time, that the crude extract, fractions and pure compounds obtained from the Chrysophyllum cainito leaves possess important anti-hypersensitive properties against inflammatory pain in mice. The mechanisms through which Chrysophyllum cainito exerts its anti-hypersensitive actions are still unclear, and require further investigation; however, this could well constitute a new and attractive alternative for the management of persistent inflammatory and neuropathic pain in humans. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Investigation of the central and peripheral analgesic and anti-inflammatory activity of Draksharishta an Indian Ayurvedic formulation

PubMed Central

Kabir, Ashraf-ul; Samad, Mehdi Bin; D′Costa, Ninadh Malrina; Hannan, Juardar Mohammad

2012-01-01

Rationale: Draksharishta (DRK) is an Ayurvedic formulation approved by the “National formulary of Ayurvedic Medicine 2011”, of Bangladesh. It is widely available in the Bangladeshi market as an effective preparation to treat lumbago, sciatia and arthritic pain of joints. But there are very scientific evidences available to support their common uses. Objectives: Our present studies make an attempt toward identifying probable antinociceptive and anti-inflammatory effect and its mechanisms of DRK. Findings: DRK, at three doses, (10 mL/kg, 20 mL/kg, and 40 mL/kg) showed no involvement of the CNS in antinociceptive activity of the test drug. Both Carrageenan-induced paw edema and acetic acid writhing tests gave significant results (P < 0.05), indicating possible peripheral analgesic and anti-inflammatory action. Formalin-induced paw- licking test showed that DRK had significant effect in suppressing inflammatory pain (P < 0.05) but not neurogenic pain. Conclusions: Hence our study shows anti-inflammatory and peripheral analgesic action for DRK. PMID:24826047

Pharmacological Approaches for the Management of Persistent Pain in Older Adults: What Nurses Need to Know.

PubMed

Guerriero, Fabio; Bolier, Ruth; Van Cleave, Janet H; Reid, M Cary

2016-12-01

HOW TO OBTAIN CONTACT HOURS BY READING THIS ARTICLE INSTRUCTIONS 1.4 contact hours will be awarded by Villanova University College of Nursing upon successful completion of this activity. A contact hour is a unit of measurement that denotes 60 minutes of an organized learning activity. This is a learner-based activity. Villanova University College of Nursing does not require submission of your answers to the quiz. A contact hour certificate will be awarded once you register, pay the registration fee, and complete the evaluation form online at http://goo.gl/gMfXaf. To obtain contact hours you must: 1. Read the article, "Pharmacological Approaches for the Management of Persistent Pain in Older Adults: What Nurses Need to Know" found on pages 49-57, carefully noting any tables and other illustrative materials that are included to enhance your knowledge and understanding of the content. Be sure to keep track of the amount of time (number of minutes) you spend reading the article and completing the quiz. 2. Read and answer each question on the quiz. After completing all of the questions, compare your answers to those provided within this issue. If you have incorrect answers, return to the article for further study. 3. Go to the Villanova website listed above to register for contact hour credit. You will be asked to provide your name; contact information; and a VISA, MasterCard, or Discover card number for payment of the $20.00 fee. Once you complete the online evaluation, a certificate will be automatically generated. This activity is valid for continuing education credit until November 30, 2019. CONTACT HOURS This activity is co-provided by Villanova University College of Nursing and SLACK Incorporated. Villanova University College of Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. ACTIVITY OBJECTIVES 1. Describe age-related barriers to pain assessment and key aspects of the assessment process. 2. Identify benefits and risks associated with commonly prescribed analgesic medications for the treatment of later life pain. DISCLOSURE STATEMENT Neither the planners nor the authors have any conflicts of interest to disclose. The current article addresses pharmacological treatment issues regarding the management of persistent pain in later life, which is a worldwide problem associated with substantial disability. Recommendations from guidelines were reviewed and data are presented regarding the benefits and risks of commonly prescribed analgesic medications. The evidence base supports a stepwise approach with acetaminophen as first-line therapy for mild-to-moderate pain. Oral nonsteroidal anti-inflammatory drugs are not recommended for long-term use. In properly selected older patients, opioid drugs should be considered if pain is not adequately controlled. Careful surveillance to monitor for benefits and harms of therapy is critical, given that advancing age increases risk for adverse effects. Key aspects of the pain care process that nurses routinely engage in are covered, including conducting pain assessments prior to initiating therapy, addressing barriers to effective pain care, educating patients and family members about the importance of reducing pain, discussing treatment-related risks and benefits, and formulating strategies to monitor for treatment outcomes. Finally, a case is presented to illustrate issues that arise in the care of affected patients. [Journal of Gerontological Nursing, 42(12), 49-57.]. Copyright 2016, SLACK Incorporated.

Lack of analgesia by oral standardized cannabis extract on acute inflammatory pain and hyperalgesia in volunteers.

PubMed

Kraft, Birgit; Frickey, Nathalie A; Kaufmann, Rainer M; Reif, Marcus; Frey, Richard; Gustorff, Burkhard; Kress, Hans G

2008-07-01

Cannabinoid-induced analgesia was shown in animal studies of acute inflammatory and neuropathic pain. In humans, controlled clinical trials with Delta-tetrahydrocannabinol or other cannabinoids demonstrated analgesic efficacy in chronic pain syndromes, whereas the data in acute pain were less conclusive. Therefore, the aim of this study was to investigate the effects of oral cannabis extract in two different human models of acute inflammatory pain and hyperalgesia. The authors conducted a double-blind, crossover study in 18 healthy female volunteers. Capsules containing Delta-tetrahydrocannabinol-standardized cannabis extract or active placebo were orally administered. A circular sunburn spot was induced at one upper leg. Heat and electrical pain thresholds were determined at the erythema, the area of secondary hyperalgesia, and the contralateral leg. Intradermal capsaicin-evoked pain and areas of flare and secondary hyperalgesia were measured. Primary outcome parameters were heat pain thresholds in the sunburn erythema and the capsaicin-evoked area of secondary hyperalgesia. Secondary measures were electrical pain thresholds, sunburn-induced secondary hyperalgesia, and capsaicin-induced pain. Cannabis extract did not affect heat pain thresholds in the sunburn model. Electrical thresholds (250 Hz) were significantly lower compared with baseline and placebo. In the capsaicin model, the area of secondary hyperalgesia, flare, and spontaneous pain were not altered. To conclude, no analgesic or antihyperalgesic activity of cannabis extract was found in the experiments. Moreover, the results even point to the development of a hyperalgesic state under cannabinoids. Together with previous data, the current results suggest that cannabinoids are not effective analgesics for the treatment of acute nociceptive pain in humans.

Conditioned Pain Modulation and Situational Pain Catastrophizing as Preoperative Predictors of Pain following Chest Wall Surgery: A Prospective Observational Cohort Study

PubMed Central

Grosen, Kasper; Vase, Lene; Pilegaard, Hans K.; Pfeiffer-Jensen, Mogens; Drewes, Asbjørn M.

2014-01-01

Background Variability in patients' postoperative pain experience and response to treatment challenges effective pain management. Variability in pain reflects individual differences in inhibitory pain modulation and psychological sensitivity, which in turn may be clinically relevant for the disposition to acquire pain. The aim of this study was to investigate the effects of conditioned pain modulation and situational pain catastrophizing on postoperative pain and pain persistency. Methods Preoperatively, 42 healthy males undergoing funnel chest surgery completed the Spielberger's State-Trait Anxiety Inventory and Beck's Depression Inventory before undergoing a sequential conditioned pain modulation paradigm. Subsequently, the Pain Catastrophizing Scale was introduced and patients were instructed to reference the conditioning pain while answering. Ratings of movement-evoked pain and consumption of morphine equivalents were obtained during postoperative days 2–5. Pain was reevaluated at six months postoperatively. Results Patients reporting persistent pain at six months follow-up (n = 15) were not significantly different from pain-free patients (n = 16) concerning preoperative conditioned pain modulation response (Z = 1.0, P = 0.3) or level of catastrophizing (Z = 0.4, P = 1.0). In the acute postoperative phase, situational pain catastrophizing predicted movement-evoked pain, independently of anxiety and depression (β = 1.0, P = 0.007) whereas conditioned pain modulation predicted morphine consumption (β = −0.005, P = 0.001). Conclusions Preoperative conditioned pain modulation and situational pain catastrophizing were not associated with the development of persistent postoperative pain following funnel chest repair. Secondary outcome analyses indicated that conditioned pain modulation predicted morphine consumption and situational pain catastrophizing predicted movement-evoked pain intensity in the acute postoperative phase. These findings may have important implications for developing strategies to treat or prevent acute postoperative pain in selected patients. Pain may be predicted and the malfunctioning pain inhibition mechanism as tested with CPM may be treated with suitable drugs augmenting descending inhibition. PMID:24587268

Thyroiditis: an integrated approach.

PubMed

Sweeney, Lori B; Stewart, Christopher; Gaitonde, David Y

2014-09-15

Thyroiditis is a general term that encompasses several clinical disorders characterized by inflammation of the thyroid gland. The most common is Hashimoto thyroiditis; patients typically present with a nontender goiter, hypothyroidism, and an elevated thyroid peroxidase antibody level. Treatment with levothyroxine ameliorates the hypothyroidism and may reduce goiter size. Postpartum thyroiditis is transient or persistent thyroid dysfunction that occurs within one year of childbirth, miscarriage, or medical abortion. Release of preformed thyroid hormone into the bloodstream may result in hyperthyroidism. This may be followed by transient or permanent hypothyroidism as a result of depletion of thyroid hormone stores and destruction of thyroid hormone-producing cells. Patients should be monitored for changes in thyroid function. Beta blockers can treat symptoms in the initial hyperthyroid phase; in the subsequent hypothyroid phase, levothyroxine should be considered in women with a serum thyroid-stimulating hormone level greater than 10 mIU per L, or in women with a thyroid-stimulating hormone level of 4 to 10 mIU per L who are symptomatic or desire fertility. Subacute thyroiditis is a transient thyrotoxic state characterized by anterior neck pain, suppressed thyroid-stimulating hormone, and low radioactive iodine uptake on thyroid scanning. Many cases of subacute thyroiditis follow an upper respiratory viral illness, which is thought to trigger an inflammatory destruction of thyroid follicles. In most cases, the thyroid gland spontaneously resumes normal thyroid hormone production after several months. Treatment with high-dose acetylsalicylic acid or nonsteroidal anti-inflammatory drugs is directed toward relief of thyroid pain.

Maintenance of pain in children with functional abdominal pain

USDA-ARS?s Scientific Manuscript database

A significant proportion of children with functional abdominal pain develop chronic pain. Identifying clinical characteristics predicting pain persistence is important in targeting interventions. We examined whether child anxiety and/or pain-stooling relations were related to maintenance of abdomina...

Neuropathic pain, depressive symptoms, and C-reactive protein in sciatica patients.

PubMed

Uher, Tomas; Bob, Petr

2013-03-01

There is evidence that neuropathic pain component in low back pain (LBP) patients is associated with higher ratings of comorbidities such as depression and anxiety disorders. In line with current findings, the purpose of this clinical study is to examine a hypothesis regarding a relationship of neuropathic pain component, depression, and other psychopathological symptoms in a specific group of LBP patients with sciatica pain. With respect to findings that depression is related to inflammatory changes, and inflammatory mediators may play a role in neuropathic pain generation, we have assessed also serum C-reactive protein (CRP). Results of the present study show that increased neuropathic pain component in sciatica patients is associated with elevated levels of depression, anxiety, alexithymia, and serum CRP levels. In conclusion, results of this study indicate that CRP levels in sciatica patients are closely associated with neuropathic pain.

Persistent Postoperative Pain after Cardiac Surgery: Incidence, Characterization, Associated Factors and its impact in Quality of Life.

PubMed

Guimarães-Pereira, Luís; Farinha, Filomena; Azevedo, Luís; Abelha, Fernando; Castro-Lopes, José

2016-10-01

Cardiac surgery (CS) ranks among the most frequently performed interventions worldwide and persistent postoperative pain (PPP) has been recognized as a relevant clinical outcome in this context. We aimed to evaluate its incidence, characteristics, associated factors and patient's quality of life (QoL). Observational prospective study conducted in patients undergoing CS in a tertiary university hospital. PPP was defined as persistent pain after surgery with higher than 3 months' duration, after excluding other causes of pain. We used a set of questionnaires for data collection: Pain Catastrophizing Scale, Duke Health Profile, Brief Pain Inventory Short Form, McGill Pain Questionnaire Short Form, Douleur Neuropathique en 4 Questions and standardized questions regarding pain periodicity. A total of 288 patients have completed the study and 43% presented PPP assessed at 3 months (PPP3M); out of which 84% were not under any treatment. PPP patients reported significantly lower QoL, and a neuropathic pain (NP) component was present in 50% of them. Younger age, female gender, higher body mass index, catastrophizing, coronary artery bypass graft, osteoarthritis, history of previous surgery (excluding sternotomy) and moderate to severe acute postoperative pain were independent predictors of PPP3M. This is the first study comprehensively describing PPP after CS and identifying NP in half of them. Our results support the important role that PPP plays after CS in considering its interference in patients' daily life and their lower QoL, which deserves the attention of health care professionals in order to improve prevention, assessment and treatment of these patients. WHAT DOES THIS STUDY ADD?: This study comprehensively describes persistent postoperative pain (PPP) after cardiac surgery (CS) and identifies neuropathic pain (NP) in half of them. Our results support the important role that PPP plays after CS in considering its interference in patients' daily life and their lower quality of life. © 2016 European Pain Federation - EFIC®

Disturbed body perception, reduced sleep, and kinesiophobia in subjects with pregnancy-related persistent lumbopelvic pain and moderate levels of disability: An exploratory study.

PubMed

Beales, Darren; Lutz, Alison; Thompson, Judith; Wand, Benedict Martin; O'Sullivan, Peter

2016-02-01

For a small but significant group, pregnancy-related lumbopelvic pain may become persistent. While multiple factors may contribute to disability in this group, previous studies have not investigated sleep impairments, body perception or mindfulness as potential factors associated with disability post-partum. To compare women experiencing no pain post-pregnancy with those experiencing pregnancy-related persistent lumbopelvic pain (either low- or high-level disability) across multiple biopsychosocial domains. Cross-sectional. Participants completed questionnaires for thorough profiling of factors thought to be important in pregnancy-related lumbopelvic pain. Specific measures were the Urinary Distress Inventory, Medical Outcomes Study Sleep Scale, Back Beliefs Questionnaire, Tampa Scale for Kinesiophobia, Depression Anxiety Stress Scale, Coping Strategies Questionnaire, Pain Catastrophising Scale, The Fremantle Back Awareness Questionnaire and the Mindful Attention Awareness Scale. Women where categorised into three groups; pain free (n = 26), mild disability (n = 12) and moderate disability (n = 12) (based on Oswestry Disability Index scores). Non-parametric group comparisons were used to compare groups across the profiling variables. Differences were identified for kinesiophobia (p = 0.03), body perception (p = 0.02), sleep quantity (p < 0.01) and sleep adequacy (p = 0.02). Generally subjects in the moderate disability group had more negative findings for these variables. Disturbances in body-perception, sleep and elevated kinesiophobia were found in pregnancy-related lumbopelvic pain subjects with moderate disability, factors previously linked to persistent low back pain. The cross-sectional nature of this study does not allow for identification of directional pathways between factors. The results support the consideration of these factors in the assessment and management of pregnancy-related lumbopelvic pain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intrathecal clonidine and bupivacaine have synergistic analgesia for acute thermally or inflammatory-induced pain in rats.

PubMed

Nishiyama, Tomoki; Hanaoka, Kazuo

2004-04-01

We investigated the interaction between spinally administered bupivacaine and clonidine using an animal model of acute and inflammatory pain. Rats implanted with lumbar intrathecal catheters were injected intrathecally with saline (control), bupivacaine (1 to 100 microg), or clonidine (0.1 to 3 microg) and tested for their responses to thermal stimulation to the tail (tail flick test) and subcutaneous formalin injection into the hindpaw (formalin test). The effects of the combination of bupivacaine and clonidine on both stimuli were tested by isobolographic analysis. General behavior and motor function were examined as side effects. The 50% effective doses of bupivacaine and clonidine were significantly smaller when combined compared with each single drug in both the tail flick test (2.82 and 0.11 microg versus 7.1 and 0.29 microg, respectively) and phase 1 (0.24 and 0.009 microg versus 5.7 and 0.15 microg) and phase 2 (0.31 and 0.012 microg versus 3.2 and 0.16 microg) of the formalin test. Side effects were decreased by the combination. These results suggest a favorable combination of intrathecal bupivacaine and clonidine in the management of acute and inflammatory pain. The analgesic interaction between intrathecally administered bupivacaine and clonidine was examined during acute thermal and inflammatory-induced pain in rats. The analgesia produced by the combination of these two drugs was synergistic in both acute thermal and inflammatory induced pain, with a decrease in behavioral side effects.

Optogenetic Silencing of Nav1.8-Positive Afferents Alleviates Inflammatory and Neuropathic Pain123

PubMed Central

Daou, Ihab; Beaudry, Hélène; Ase, Ariel R.; Wieskopf, Jeffrey S.; Ribeiro-da-Silva, Alfredo; Mogil, Jeffrey S.

2016-01-01

Abstract We report a novel transgenic mouse model in which the terminals of peripheral nociceptors can be silenced optogenetically with high spatiotemporal precision, leading to the alleviation of inflammatory and neuropathic pain. Inhibitory archaerhodopsin-3 (Arch) proton pumps were delivered to Nav1.8+ primary afferents using the Nav1.8-Cre driver line. Arch expression covered both peptidergic and nonpeptidergic nociceptors and yellow light stimulation reliably blocked electrically induced action potentials in DRG neurons. Acute transdermal illumination of the hindpaws of Nav1.8-Arch+ mice significantly reduced mechanical allodynia under inflammatory conditions, while basal mechanical sensitivity was not affected by the optical stimulation. Arch-driven hyperpolarization of nociceptive terminals was sufficient to prevent channelrhodopsin-2 (ChR2)-mediated mechanical and thermal hypersensitivity in double-transgenic Nav1.8-ChR2+-Arch+mice. Furthermore, prolonged optical silencing of peripheral afferents in anesthetized Nav1.8-Arch+ mice led to poststimulation analgesia with a significant decrease in mechanical and thermal hypersensitivity under inflammatory and neuropathic conditions. These findings highlight the role of peripheral neuronal inputs in the onset and maintenance of pain hypersensitivity, demonstrate the plasticity of pain pathways even after sensitization has occurred, and support the involvement of Nav1.8+ afferents in both inflammatory and neuropathic pain. Together, we present a selective analgesic approach in which genetically identified subsets of peripheral sensory fibers can be remotely and optically inhibited with high temporal resolution, overcoming the compensatory limitations of genetic ablations. PMID:27022626

Pseudomembranous Colitis

PubMed Central

Farooq, Priya D.; Urrunaga, Nathalie H.; Tang, Derek M.; von Rosenvinge, Erik C.

2015-01-01

Pseudomembranous colitis is an inflammatory condition of the colon characterized by elevated yellow-white plaques that coalesce to form pseudomembranes on the mucosa. Patients with the condition commonly present with abdominal pain, diarrhea, fever, and leukocytosis. Because pseudomembranous colitis is often associated with C. difficile infection, stool testing and empiric antibiotic treatment should be initiated when suspected. When results of C. difficile testing are negative and symptoms persist despite escalating empiric treatment, early gastroenterology consultation and lower endoscopy would be the next step in the appropriate clinical setting. If pseudomembranous colitis is confirmed endoscopically, colonic biopsies should be obtained, as histology can offer helpful clues to the underlying diagnosis. The less common non-C. difficile causes of pseudomembranous colitis should be entertained, as a number of etiologies can result in this condition. Examples include Behcet’s disease, collagenous colitis, inflammatory bowel disease, ischemic colitis, other infections organisms (e.g. bacteria, parasites, viruses), and a handful of drugs and toxins. Pinpointing the correct underlying etiology would better direct patient care and disease management. Surgical specialists would be most helpful in colonic perforation, gangrenous colon, or severe disease. PMID:25769243

[Evaluation of anti-inflammatory activity of extracts from Siberian plants].

PubMed

Nesterova, Iu V; Povet'eva, T N; Aksinenko, S G; Suslov, N I; Gaĭdamovich, N N; Nagorniak, Iu G; Popova, E V; Kravtsova, S S; Andreeva, T I

2009-01-01

Experimental investigations have shown that water-alcohol extracts from plants containing alkaloids (Aconitum baikalense, Aconitum septentrionale, Delphinium elatum L., Conium maculatum) and salicylic acid (Filipendula ulmaria, Salix viminalis, Fragaria vesca, Rubus idaeus) inhibited the development of main symptoms of inflammation, viz. exudation, pain, fever, to the same extent as non-steroidal anti-inflammatory agents. The substances studied in this work may be used to develop new efficient pharmacological preparations for the treatment of different inflammatory conditions associated with severe pain syndrome.

Multilevel lumbar fusion and postoperative physiotherapy rehabilitation in a patient with persistent pain.

PubMed

Pons, Tracey; Shipton, Edward A

2011-04-01

There are no comparative randomised controlled trials of physiotherapy modalities for chronic low back and radicular pain associated with multilevel fusion. Physiotherapy-based rehabilitation to control pain and improve activation levels for persistent pain following multilevel fusion can be challenging. This is a case report of a 68-year-old man who was referred for physiotherapy intervention 10 months after a multilevel spinal fusion for spinal stenosis. He reported high levels of persistent postoperative pain with minimal activity as a consequence of his pain following the surgery. The physiotherapy interventions consisted of three phases of rehabilitation starting with pool exercise that progressed to land-based walking. These were all combined with transcutaneous electrical nerve stimulation (TENS) that was used consistently for up to 8 hours per day. As outcome measures, daily pain levels and walking distances were charted once the pool programme was completed (in the third phase). Phase progression was determined by shuttle test results. The pain level was correlated with the distance walked using linear regression over a 5-day average. Over a 5-day moving average, the pain level reduced and walking distance increased. The chart of recorded pain level and walking distance showed a trend toward decreased pain with the increased distance walked. In a patient undergoing multilevel lumbar fusion, the combined use of TENS and a progressive walking programme (from pool to land) reduced pain and increased walking distance. This improvement was despite poor medication compliance and a reported high level of postsurgical pain.

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

Self-System Therapy for Distress Associated with Persistent Low Back Pain: A Randomized Clinical Trial

PubMed Central

Waters, Sandra J.; McKee, Daphne C.; Campbell, Lisa C.; Shelby, Rebecca A.; Dixon, Kim E.; Fras, Anne Marie; Keefe, Francis J.

2015-01-01

Objective Persistent low back pain (PLBP) is associated with vulnerability to depression. PLBP frequently requires major changes in occupation and lifestyle, which can lead to a sense of failing to attain one’s personal goals (self-discrepancy). Method We conducted a clinical trial to examine the efficacy of self-system therapy (SST), a brief structured therapy for depression based on self-discrepancy theory. A total of 101 patients with PLBP and clinically significant depressive symptoms were randomized either to SST, pain education, or standard care. Results Patients receiving SST showed significantly greater improvement in depressive symptoms. Reduction in self-discrepancy predicted reduction in depressive symptoms only within the SST condition. Conclusions Findings support the utility of SST for individuals facing persistent pain and associated depression. PMID:26079438

Foreign body reaction to acellular dermal matrix allograft in biologic glenoid resurfacing.

PubMed

Namdari, Surena; Melnic, Christopher; Huffman, G Russell

2013-08-01

Biologic glenoid resurfacing is a treatment option for young patients with glenohumeral arthritis. An optimal synthetic graft for glenoid resurfacing should allow repopulation with host cells, be durable enough to tolerate suture fixation and forces across the joint, and present no host inflammatory response. We report two cases of giant cell reaction to GraftJacket(®) after biologic glenoid resurfacing. Two patients who underwent hemiarthroplasty and biologic glenoid resurfacing using GraftJacket(®) had a foreign body giant cell reaction that required revision surgery. Intraoperatively, both patients were observed to have a well-fixed humeral component and a dense, erythematous, synovitic membrane overlying the glenoid. Pathology specimens showed a benign reactive synovium, chronic inflammation, and foreign body giant cell reaction. After débridement and conversion to total shoulder arthroplasty, both patients continued to be pain-free at greater than 1-year followup. Multinucleated giant cell and mononuclear cell responses have been observed in an animal model after use of GraftJacket(®). Although the use of acellular matrix-based scaffold for biologic glenoid resurfacing is not new, the possibility of foreign body reaction as a source of persistent symptoms has not been described. Given the lack of data to indicate an advantage to biologic resurfacing of the glenoid over hemiarthroplasty alone, resurfacing should not introduce significant additional surgical complications. We suggest foreign body reaction be considered in the differential diagnosis for a persistently painful shoulder after biologic glenoid resurfacing using an acellular allograft patch.

A Leptin-Mediated Central Mechanism in Analgesia-Enhanced Opioid Reward in Rats

PubMed Central

Lim, Grewo; Kim, Hyangin; McCabe, Michael F.; Chou, Chiu-Wen; Wang, Shuxing; Chen, Lucy L.; Marota, John J.A.; Blood, Anne; Breiter, Hans C.

2014-01-01

Opioid analgesics are commonly used in chronic pain management despite a potential risk of rewarding. However, it remains unclear whether opioid analgesia would enhance the opioid rewarding effect thereby contributing to opioid rewarding. Utilizing a rat paradigm of conditioned place preference (CPP) combined with ankle monoarthritis as a condition of persistent nociception, we showed that analgesia induced by either morphine or the nonsteroid anti-inflammatory drug ibuprofen increased CPP scores in arthritic rats, suggesting that analgesia itself had a rewarding effect. However, arthritic rats exhibited a significantly higher CPP score in response to morphine than ibuprofen. Thus, the rewarding effect of morphine was enhanced in the presence of persistent nociception, producing a phenomenon of analgesia-enhanced opioid reward. At the cellular level, administration of morphine activated a cascade of leptin expression, glial activation, and dopamine receptor upregulation in the nucleus accumbens (NAc), while administration of ibuprofen decreased glial activation with no effect on leptin expression in the NAc. Furthermore, the morphine rewarding effect was blocked in leptin deficient ob/ob mice or by neutralizing leptin or interleukin-1β in the NAc without diminishing morphine analgesia. The data indicate that systemic opioid can activate a leptin-mediated central mechanism in the NAc that led to the enhanced opioid rewarding effect. These findings provide evidence for an interaction between opioid analgesia and opioid rewarding, which may have implications in clinical opioid dose escalation in chronic pain management. PMID:25031415

Therapeutic effect of melittin on a rat model of chronic prostatitis induced by Complete Freund's Adjuvant.

PubMed

Lin, Li; Zhu, Bao-Ping; Cai, Liang

2017-06-01

The present study was aimed to establish a model of chronic prostatitis in rat with the use of intraprostatic injection of Complete Freund's Adjuvant, and to examine the anti-inflammatory and analgesic effects of melittin on the newly-developed chronic prostatic pain model. Adult male Sprague-Dawley rats were injected with Complete Freund's Adjuvant (CFA) into the prostate. Twelve days after model rats of the treatment group were injected melittin into the prostate, while those of the control group received sterile saline injection. The nociceptive effects of CFA were evaluated by using a behavior approach (i.e. mechanical pain threshold measurement) on the day of CFA injection and 6, 12, and 18days after CFA injection. After the in-live study was done, the prostate was collected for histological examination of inflammatory cell infiltration. Levels of cyclooxygenase (COX)-2 in prostate and glial fibrillary acidic protein (GFAP) in spinal cord were determined using immunohistochemistry. Rats of the sham control group received intraprostatic injection of sterile saline and were studied using the same methods RESULTS: Intraprostatic CFA injection induced local allodynia that lasted over at least 2 weeks. The pain behavior of rat was associated with increases in inflammatory cell infiltration into the prostate. Levels of COX-2 in prostate and GFAP in spinal cord were also elevated. Treatment with melittin significantly raised pain threshold, decreased inflammatory infiltrates, and suppressed COX-2 and GFAP expression. Intraprostatic injection of CFA induced neurogenic prostatitis and prostatic pain. The established model will be useful to the study of CP/CPPS pathogenesis. Melittin demonstrated profound anti-inflammatory and analgesic effects on the chronic prostatic pain model, suggesting melittin may hold promise as a novel therapeutic for treatment of CP/CPPS. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The effect of FAAH, MAGL, and Dual FAAH/MAGL inhibition on inflammatory and colorectal distension-induced visceral pain models in Rodents.

PubMed

Sakin, Y S; Dogrul, A; Ilkaya, F; Seyrek, M; Ulas, U H; Gulsen, M; Bagci, S

2015-07-01

Recent studies showed that the pharmacological inhibition of endocannabinoid degrading enzymes such as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) elicit promising analgesic effects in a variety of nociceptive models without serious side effects. However, the full spectrum of activities is not observed upon inhibition of either FAAH or MAGL enzymes alone and thus dual FAAH and MAGL inhibitors have been described. Visceral pain is strongly associated with inflammation and distension of the gut. Thus, we explored the comparable effects of FAAH, MAGL, and dual FAAH/MAGL inhibitors on inflammatory and mechanically evoked visceral pain models. Visceral inflammatory and distension-induced pain were assessed with the 0.6% acetic acid writhing test in mice and colorectal distension (CRD) test in rats, respectively. The selective FAAH inhibitor PF 3845, MAGL inhibitor JZL 184, dual inhibitor JZL 195, and the cannabis analog CP 55,940 were given systemically 30 min prior to nociceptive testing. PF 3845 (5, 10, and 20 mg/kg), JZL 184 (5, 10, and 20 mg/kg), and JZL 195 (5, 10, and 20 mg/kg) elicit dose-dependent antinociceptive in the acetic acid writhing test. In the CRD model, while JZL 195 (5, 10, or 20 mg/kg) and PF3845 (10, 20, and 40 mg/kg) produced dose-dependent antinociceptive effects comparable to those of CP 55,940 (0.1, 0.3, or 1 mg/kg), JZL 184 (10, 20, and 40 mg/kg) alone did not alter the visceromotor response (VMR). The selective FAAH inhibitor and dual FAAH/MAGL inhibitors were effective in both inflammatory and mechanically evoked visceral pain, while the MAGL inhibitor elicited an analgesic effect in inflammatory, but not in distension-induced, visceral pain. © 2015 John Wiley & Sons Ltd.

Targeting the minor pocket of C5aR for the rational design of an oral allosteric inhibitor for inflammatory and neuropathic pain relief.

PubMed

Moriconi, Alessio; Cunha, Thiago M; Souza, Guilherme R; Lopes, Alexandre H; Cunha, Fernando Q; Carneiro, Victor L; Pinto, Larissa G; Brandolini, Laura; Aramini, Andrea; Bizzarri, Cinzia; Bianchini, Gianluca; Beccari, Andrea R; Fanton, Marco; Bruno, Agostino; Costantino, Gabriele; Bertini, Riccardo; Galliera, Emanuela; Locati, Massimo; Ferreira, Sérgio H; Teixeira, Mauro M; Allegretti, Marcello

2014-11-25

Chronic pain resulting from inflammatory and neuropathic disorders causes considerable economic and social burden. Pharmacological therapies currently available for certain types of pain are only partially effective and may cause severe adverse side effects. The C5a anaphylatoxin acting on its cognate G protein-coupled receptor (GPCR), C5aR, is a potent pronociceptive mediator in several models of inflammatory and neuropathic pain. Although there has long been interest in the identification of C5aR inhibitors, their development has been complicated, as for many peptidomimetic drugs, mostly by poor drug-like properties. Herein, we report the de novo design of a potent and selective C5aR noncompetitive allosteric inhibitor, DF2593A, guided by the hypothesis that an allosteric site, the "minor pocket," previously characterized in CXC chemokine receptors-1 and -2, is functionally conserved in the GPCR class. In vitro, DF2593A potently inhibited C5a-induced migration of human and rodent neutrophils. In vivo, oral administration of DF2593A effectively reduced mechanical hyperalgesia in several models of acute and chronic inflammatory and neuropathic pain, without any apparent side effects. Mechanical hyperalgesia after spared nerve injury was also reduced in C5aR(-/-) mice compared with WT mice. Furthermore, treatment of C5aR(-/-) mice with DF2593A did not produce any further antinociceptive effect compared with C5aR(-/-) mice treated with vehicle. The successful medicinal chemistry strategy confirms that a conserved minor pocket is amenable for the rational design of selective inhibitors and the pharmacological results support that the allosteric blockade of the C5aR represents a highly promising therapeutic approach to control chronic inflammatory and neuropathic pain.

Synergism between fentanyl and tramadol in tonic inflammatory pain: the orofacial formalin test.

PubMed

Miranda, Hugo F; Noriega, Viviana; Zepeda, Ramiro J; Sierralta, Fernando; Prieto, Juan C

2012-06-01

Opioids have been used for long time to management of pain, the coadministration of two opioids may induce synergism. The present study was conducted to determine the antinociceptive interaction between the dual mechanism of action of tramadol compared to the main of fentanyl antinociception in the orofacial formalin which represents a model of persistent cutaneous nociception in the region innervated by the trigeminal nerve. The i.p. administration of tramadol and fentanyl induced a dose-dependent antinociception with an ED(50) of 2.97 ± 0.32 mg/kg for phase I and 1.79 ± 0.30 mg/kg for phase II and 0.062 ± 0.0040 mg/kg in phase I and 0.041 ± 0.0039 mg/kg in phase II, respectively. The coadministration of fentanyl with tramadol induced synergism in both phases of the test with an interaction index of 0.343 and 0.163 for phase I and phase II, respectively. This finding could be explained by the more complex pharmacology of tramadol compared to fentanyl.

Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain

PubMed Central

Wang, Xiao-Min; Wu, Tian-Xia; Hamza, May; Ramsay, Edward S.; Wahl, Sharon M.; Dionne, Raymond A.

2007-01-01

New insights into the biological properties of cyclooxygenase-2 (COX-2) and its response pathway challenge the hypothesis that COX-2 is simply pro-inflammatory and inhibition of COX-2 solely prevents the development of inflammation and ameliorates inflammatory pain. The present study performed a comprehensive analysis of gene/protein expression induced by a selective inhibitor of COX-2, rofecoxib, compared with a non-selective COX inhibitor, ibuprofen, and placebo in a clinical model of acute inflammatory pain (the surgical extraction of impacted third molars) using microarray analysis followed by quantitative RT-PCR verification and Western blotting. Inhibition of COX-2 modulated gene expression related to inflammation and pain, the arachidonic acid pathway, apoptosis/angiogenesis, cell adhesion and signal transduction. Compared to placebo, rofecoxib treatment increased the gene expression of ANXA3 (annexin 3), SOD2 (superoxide dismutase 2), SOCS3 (suppressor of cytokine signaling 3) and IL1RN (IL1 receptor antagonist) which are associated with inhibition of phospholipase A2 and suppression of cytokine signaling cascades, respectively. Both rofecoxib and ibuprofen treatment increased the gene expression of the pro-inflammatory mediators, IL6 and CCL2 (chemokine C-C motif ligand 2), following tissue injury compared to the placebo treatment. These results indicate a complex role for COX-2 in the inflammatory cascade in addition to the well-characterized COX-dependent pathway, as multiple pathways are also involved in rofecoxib-induced anti-inflammatory and analgesic effects at the gene expression level. These findings may also suggest an alternative hypothesis for the adverse effects attributed to selective inhibition of COX-2. PMID:17070997

Influence of communal and private folklore on bringing meaning to the experience of persistent pain.

PubMed

Hendricks, Joyce Marie

2015-11-01

To provide an overview of the relevance and strengths of using the literary folkloristic methodology to explore the ways in which people with persistent pain relate to and make sense of their experiences through narrative accounts. Storytelling is a conversation with a purpose. The reciprocal bond between researcher and storyteller enables the examination of the meaning of experiences. Life narratives, in the context of wider traditional and communal folklore, can be analysed to discover how people make sense of their circumstances. This paper draws from the experience of the author, who has previously used this narrative approach. It is a reflection of how the approach may be used to understand those experiencing persistent pain without a consensual diagnosis. Using an integrative method, peer-reviewed research and discussion papers published between January 1990 and December 2014 and listed in the CINAHL, Science Direct, PsycINFO and Google Scholar databases were reviewed. In addition, texts that addressed research methodologies such as literary folkloristic methodology and Marxist literary theory were used. The unique role that nurses play in managing pain is couched in the historical and cultural context of nursing. Literary folkloristic methodology offers an opportunity to gain a better understanding and appreciation of how the experience of pain is constructed and to connect with sufferers. Literary folkloristic methodology reveals that those with persistent pain are often rendered powerless to live their lives. Increasing awareness of how this experience is constructed and maintained also allows an understanding of societal influences on nursing practice. Nurse researchers try to understand experiences in light of specific situations. Literary folkloristic methodology can enable them to understand the inter-relationship between people in persistent pain and how they construct their experiences.

Controlling joint pain in older people.

PubMed

Paisley, Peter; Serpell, Mick

2016-01-01

Jont pain in oldder people The prevalence of chronic pain in older people in the community ranges from 25 to 76% and for those in residential care, it is even higher at 83 to 93%. The most common sites affected are the back, hip, or knee, and other joints. There is increased reporting of pain in women (79%) compared with men (53%). Common conditions include osteoarthritis and, to a lesser extent, the inflammatory arthropathies such as rheumatoid arthritis. The differential diagnosis includes non-articular pain such as vascular limb pain and nocturnal cramp, some neuropathic pain conditions (such as compressive neuropathies and postherpetic neuralgia), soft tissue disorders such as fibromyalgia and myofascial pain syndromes. In addition to an assessment of pain intensity, a biopsychosocial model should be adopted to ascertain the effect of the pain on the patient's degree of background pain at rest. The disease is often localised to the large load-bearing joints, predominantly the hips and knees. In contrast to osteoarthritis, the inflammatory arthritides typically present with symmetrical swollen, stiff, and painful small joints of the hands and feet, usually worse in the morning.

Pharmacological action of choline and aspirin coadministration on acute inflammatory pain.

PubMed

Yong-Ping, Shi; Jin-Da, Wang; Ru-Huan, Wang; Xiang-Di, Zhao; Hai-Tao, Yu; Hai, Wang

2011-09-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain but undesirable side effects limit their clinical usefulness. Choline is a α7 nicotinic receptor agonist that has antinociceptive effects in a variety of pain models. Drug combination is a strategy in the management of pain to reduce side effects. The aim of the study was to evaluate the nature of the interaction between choline and aspirin in two distinct inflammatory pain models. The analgesic mechanism of choline was also investigated. In the writhing test, intravenous administration of choline or aspirin showed dose-dependent antinociceptive activity, and isobolographic analysis revealed a synergistic nature of the interaction between choline and aspirin. More importantly, coadministration choline with aspirin could significantly shorten the antinociceptive latency of aspirin and prolong the antinociceptive duration of aspirin in the writhing test. In the carrageenan test, single administration of choline or aspirin significantly attenuated carrageenan-induced thermal hyperalgesia in a dose-dependent relationship. Coadministration of non-analgesic doses of aspirin with choline significantly suppressed the thermal hyperalgesia, with a longer duration efficacy. Furthermore, we found that α7 nicotinic, muscarinic, and opioid-receptors are involved in the antinociceptive effect of choline in the writhing test and the antinociceptive effect produced by systemically administered choline may be via a peripheral mechanism. In conclusion, coadministration of choline and aspirin holds promise for development as a safe analgesic drug combination for inflammatory pain, with a higher potency and longer duration than either aspirin or choline alone. Copyright © 2011 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

5. Diagnosis and Treatment of Lyme Arthritis

PubMed Central

Arvikar, Sheila L.; Steere, Allen C.

2015-01-01

SYNOPSIS In the United States, Lyme arthritis is the most common feature of late stage infection with the tick-borne spirochete, Borrelia burgdorferi, usually beginning months after the initial tick bite. However, in some patients, including most of those seen today, the earlier phases of the infection are asymptomatic and arthritis is the presenting manifestation of the disease. Patients with Lyme arthritis have intermittent or persistent attacks of joint swelling and pain in one or a few large joints, especially the knee, usually over a period of several years, without prominent systemic manifestations. Serologic testing is the mainstay of diagnosis. Synovial fluid PCR testing for B. burgdorferi DNA is often positive prior to treatment, but it is not a reliable marker of spirochetal eradication after antibiotic therapy. Responses to oral or intravenous antibiotic treatment are generally excellent, although a small percentage of patients have persistent synovitis after 2-3 months of oral and IV antibiotics, which usually then responds to anti-inflammatory therapies, disease modifying anti-rheumatic drugs (DMARDs), or synovectomy. This chapter reviews the clinical manifestations, diagnosis, and management of Lyme arthritis. PMID:25999223

Effects of Pilates-based exercises on pain and disability in individuals with persistent nonspecific low back pain: a systematic review with meta-analysis.

PubMed

Lim, Edwin Choon Wyn; Poh, Ruby Li Choo; Low, Ai Ying; Wong, Wai Pong

2011-02-01

A systematic review with meta-analysis. To compare pain and disability in individuals with persistent nonspecific low back pain who were treated with Pilates exercises compared to minimal or other interventions. Searches of Medline, CINAHL, Embase, Cochrane library, PEDro, and ProQuest Dissertations and Thesis databases were conducted. Randomized controlled trials (RCTs) were selected and reviewed if they compared pain and disability in individuals with persistent nonspecific low back pain who were treated with Pilates exercises compared to other treatment approaches. Quality of the trials was evaluated. Data for pain and disability scores were extracted. Narrative synthesis plus meta-analyses were performed, with either a fixed-effects or random-effects model, standardized mean differences (SMDs), and tests for heterogeneity. Seven RCTs were identified and included in the meta-analyses. Data pooling was performed using RevMan 5. When compared to minimal intervention, Pilates-based exercise provided superior pain relief (pooled SMD, -2.72; 95% CI: -5.33, -0.11; P = .04) but the pooled disability scores were not significantly different (pooled SMD, -0.74; 95% CI: -1.81, 0.33;P = .17). No significant differences were found when comparing Pilates-based exercise to other forms of exercise for pain (pooled SMD, 0.03; 95% CI: -0.52, 0.58; P = .92) or disability scores (pooled SMD, -0.41; 95% CI: -0.96, 0.14; P = .14). Pilates-based exercises are superior to minimal intervention for pain relief. Existing evidence does not establish superiority of Pilates-based exercise to other forms of exercise to reduce pain and disability for patients with persistent nonspecific low back pain. However, the relatively low quality of existing studies and the heterogeneity of pooled studies in this systematic review combine to suggest that these results should be interpreted with caution. Therapy, level 1a.

Condition-specific role of colonic inflammatory molecules in persistent functional colorectal hypersensitivity in the mouse

PubMed Central

La, Jun-Ho; Gebhart, G. F.

2014-01-01

Background A low-level inflammation has been hypothesized to mediate visceral hypersensitivity in functional bowel disorders that persist after or even in the absence of gut inflammation. We aimed to test the efficacy of a steroidal anti-inflammatory treatment, and identify local inflammatory molecules mediating post- and non-inflammatory colorectal hypersensitivity using two mouse models. Methods Visceromotor responses to colorectal distension were quantified as a measure of colorectal sensitivity. On day 1, mice received intracolonic saline (control), trinitrobenzenesulfonic acid (post-inflammatory on day 15), or acidified hypertonic saline (non-inflammatory). Colorectal sensitivity before (day 10) and after (day 15) four-day dexamethasone treatment was compared, and colonic gene expression of inflammatory molecules was quantified. Results Dexamethasone effectively inhibited gene expression of inflammatory molecules such as interleukin (IL)-1β and mast cell protease-1 in the colon, but did not attenuate colorectal hypersensitivity in either model. Gene expression of inflammatory molecules in the colon did not differ between control and the non-inflammatory model, but the post-inflammatory model showed increased IL-10 and tight junction protein 2, and decreased IL-6, transforming growth factor (TGF)-β, a precursor of β-endorphin, occludin, and mucin 2. While no common molecule explained colorectal hypersensitivity in these models, hypersensitivity was positively correlated with TGF-β2 mRNA in control, and with IL-1β, inhibin βA and prostaglandin E2 synthase in the dexamethasone-treated post-inflammatory model. In the non-inflammatory model, cyclooxygenase-2 mRNA was negatively correlated with colorectal sensitivity. Conclusion These results suggest that persistent functional colorectal hypersensitivity is mediated by condition-specific mediators whose gene expression in the colon is not inevitably sensitive to steroidal anti-inflammatory treatment. PMID:25307695

Regulatory components for treating persistent pain in long-term care.

PubMed

Planton, Jonathan; Edlund, Barbara J

2010-04-01

Persistent or chronic pain is frequently reported by older adults and has the potential to dramatically influence quality of life. Estimates indicate that 25% to 50% of community-dwelling older adults experience this kind of pain. This rate is even higher in long-term care facilities, where 50% to 75% of residents have chronic pain syndromes that are untreated or undertreated. To promote optimal pain management and enumerate the responsibilities of skilled nursing facilities to effectively treat and prevent pain, the Centers for Medicare & Medicaid Services released a new pain management surveyor guidance, F-Tag 309, which endorses the presence of an interdisciplinary team approach to pain management that involves the resident. The guidance delineates pain management principles, the need for ongoing professional education in all components of pain management, and emphasizes the important role of appropriate pharmacological treatment in conjunction with nonpharmacological interventions to aggressively manage pain. This directive will help skilled nursing facilities achieve optimal pain management for their residents. Copyright 2010, SLACK Incorporated.

Therapy recommendation "act as usual" in patients with whiplash injuries QTF I°.

PubMed

Dehner, Christoph; Kraus, Michael; Schöll, Hendrik; Schneider, Florian; Richter, Peter; Kramer, Michael

2012-08-20

Up to now no therapy study has used the classification system of the Quebec Task Force (QTF) to differentiate between patients with (QTF II°) and without functional disorders (QTF I°). This differentiation seems meaningful, as this difference may be relevant for the correct treatment planning. In this context the effect of the therapy recommendation "act as usual" has been evaluated in a homogeneous patient collective with whiplash injuries QTF I°. 470 patients with acute whiplash injuries had been catched in this study and classified according to the QTF. 359 patients (76.4%) with QTF I° injuries could be identified. Out of that 162 patients were enrolled to the study and received the therapy recommendation "act as usual" and the adapted pain treatment with non-steroidal anti-inflammatory drugs (NSAID). After six months the outcome was evaluated by phone. After injury the median pain score assessed by a visual analogue scale (VAS) was 5.4 (min = 3.3; max = 8.5). After six months 5 of the 162 patients complained intermittent pain symptoms (VAS values < 2). This is consistent with a chronification rate of 3.1%. After injury, the median pain disability index (PDI) was 3.9 (min = 1.9; max = 7.7). After six months 3 of the 162 patients stated persisting disability during sporting and physical activities (VAS values < 1). The therapy recommendation "act as usual" in combination with an adapted pain treatment is sufficient. Usually patients with whiplash injuries QTF I° do not need physical therapy. An escalation of therapy measures should be reserved to patients with complicated healing processes.

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.

A 9-year follow-up of a self-management group intervention for persistent neck pain in primary health care: a randomized controlled trial

PubMed Central

Gustavsson, Catharina; von Koch, Lena

2017-01-01

Background and objective In previous short-term and 2-year follow-ups, a pain and stress self-management group intervention (PASS) had better effect on pain-related disability, self-efficacy, catastrophizing, and perceived pain control than individually administered physiotherapy (IAPT) for patients with persistent tension-type neck pain. Studies that have evaluated long-term effects of self-management approaches toward persistent neck pain are sparse. The objective of this study was to compare pain-related disability, self-efficacy for activities of daily living (ADL), catastrophizing, pain, pain control, use of analgesics, and health care utilization in people with persistent tension-type neck pain 9 years after they received the PASS or IAPT. Materials and methods Of 156 people (PASS, n = 77; IAPT, n = 79) originally included in a randomized controlled trial, 129 people (PASS, n = 63; IAPT, n = 66) were eligible and were approached for the 9-year follow-up. They were sent a self-assessment questionnaire, comprising the Neck Disability Index, the Self-Efficacy Scale, the Coping Strategies Questionnaire, and questions regarding pain, analgesics, and health care utilization. Mixed linear models for repeated measures analysis or generalized estimating equations were used to evaluate the differences between groups and within groups over time (baseline, previous follow-ups, and 9-year follow-up) and the interaction effect of “time by group”. Results Ninety-four participants (73%) responded (PASS, n = 48; IAPT, n = 46). At 9 years, PASS participants reported less pain-related disability, pain at worst, and analgesics usage, and a trend toward better self-efficacy compared to IAPT participants. There was a difference between groups in terms of change over time for disability, self-efficacy for ADL, catastrophizing, perceived pain control, and health care visits in favor of PASS. Analyses of simple main effects at 9 years showed that the PASS group had less disability (p = 0.006) and a trend toward better self-efficacy (p = 0.059) than the IAPT group. Conclusion The favorable effects on pain-related disability of PASS were sustained 9 years after the intervention. PMID:28115865

Antihyperalgesic/antinociceptive effects of ceftriaxone and its synergistic interactions with different analgesics in inflammatory pain in rodents.

PubMed

Stepanovic-Petrovic, Radica M; Micov, Ana M; Tomic, Maja A; Kovacevic, Jovana M; Boškovic, Bogdan D

2014-03-01

The β-lactam antibiotic ceftriaxone stimulates glutamate transporter GLT-1 expression and is effective in neuropathic and visceral pain models. This study examined the effects of ceftriaxone and its interactions with different analgesics (ibuprofen, celecoxib, paracetamol, and levetiracetam) in somatic and visceral pain models in rodents. The effects of ceftriaxone (intraperitoneally/intraplantarly), analgesics (orally), and their combinations were examined in the carrageenan-induced paw inflammatory hyperalgesia model in rats (n = 6-12) and in the acetic acid-induced writhing test in mice (n = 6-10). The type of interaction between ceftriaxone and analgesics was determined by isobolographic analysis. Pretreatment with intraperitoneally administered ceftriaxone (10-200 mg/kg per day) for 7 days produced a significant dose-dependent antihyperalgesia in the somatic inflammatory model. Acute administration of ceftriaxone, via either intraperitoneal (10-200 mg/kg) or intraplantar (0.05-0.2 mg per paw) routes, produced a significant and dose-dependent but less efficacious antihyperalgesia. In the visceral pain model, significant dose-dependent antinociception of ceftriaxone (25-200 mg/kg per day) was observed only after the 7-day pretreatment. Isobolographic analysis in the inflammatory hyperalgesia model revealed approximately 10-fold reduction of doses of both drugs in all examined combinations. In the visceral nociception model, more than 7- and 17-fold reduction of doses of both drugs was observed in combinations of ceftriaxone with ibuprofen/paracetamol and celecoxib/levetiracetam, respectively. Ceftriaxone exerts antihyperalgesia/antinociception in both somatic and visceral inflammatory pain. Its efficacy is higher after a 7-day pretreatment than after acute administration. The two-drug combinations of ceftriaxone and the nonsteroidal analgesics/levetiracetam have synergistic interactions in both pain models. These results suggest that ceftriaxone, particularly in combinations with ibuprofen, celecoxib, paracetamol, or levetiracetam, may provide useful approach to the clinical treatment of inflammation-related pain.

Corticolimbic anatomical characteristics predetermine risk for chronic pain

PubMed Central

Vachon-Presseau, Etienne; Tétreault, Pascal; Petre, Bogdan; Huang, Lejian; Berger, Sara E.; Torbey, Souraya; Baria, Alexis T.; Mansour, Ali R.; Hashmi, Javeria A.; Griffith, James W.; Comasco, Erika; Schnitzer, Thomas J.

2016-01-01

See Tracey (doi:10.1093/brain/aww147) for a scientific commentary on this article. Mechanisms of chronic pain remain poorly understood. We tracked brain properties in subacute back pain patients longitudinally for 3 years as they either recovered from or transitioned to chronic pain. Whole-brain comparisons indicated corticolimbic, but not pain-related circuitry, white matter connections predisposed patients to chronic pain. Intra-corticolimbic white matter connectivity analysis identified three segregated communities: dorsal medial prefrontal cortex–amygdala–accumbens, ventral medial prefrontal cortex–amygdala, and orbitofrontal cortex–amygdala–hippocampus. Higher incidence of white matter and functional connections within the dorsal medial prefrontal cortex–amygdala–accumbens circuit, as well as smaller amygdala volume, represented independent risk factors, together accounting for 60% of the variance for pain persistence. Opioid gene polymorphisms and negative mood contributed indirectly through corticolimbic anatomical factors, to risk for chronic pain. Our results imply that persistence of chronic pain is predetermined by corticolimbic neuroanatomical factors. PMID:27190016

Beneficial Effects of Trillium govanianum Rhizomes in Pain and Inflammation.

PubMed

Ur Rahman, Shafiq; Adhikari, Achyut; Ismail, Muhammad; Raza Shah, Muhammad; Khurram, Muhammad; Shahid, Muhammad; Ali, Farman; Haseeb, Abdul; Akbar, Fazal; Iriti, Marcello

2016-08-20

Trillium govanianum rhizome is used as an analgesic and anti-inflammatory remedy in traditional medicine in northern Pakistan. In an attempt to establish its medicinal value, the present research evaluated the analgesic and anti-inflammatory potential of T. govanianum. The in vivo anti-inflammatory activity of extract and fractions was investigated in the carrageenan induced paw edema assay. The in vitro suppression of oxidative burst of extract, fractions and isolated compounds was assessed through luminol-enhanced chemiluminescence assay. The in vivo analgesic activity was assayed in chemical and thermal induced nociceptive pain models. The crude methanol extract and its solvent fractions showed anti-inflammatory and analgesic responses, exhibited by significant amelioration of paw edema and relieve of the tonic visceral chemical and acute phasic thermal nociception. In the oxidative burst assay, based on IC50, the crude methanol extract and n-butanol soluble fraction produced a significant inhibition, followed by chloroform and hexane soluble fractions as compared to ibuprofen. Similarly, the isolated compounds pennogenin and borassoside E exhibited significant level of oxidative burst suppressive activity. The in vivo anti-inflammatory and analgesic activities as well as the in vitro inhibition of oxidative burst validated the traditional use of T. govanianum rhizomes as a phytotherapeutic remedy for both inflammatory conditions and pain. The observed activities might be attributed to the presence of steroids and steroid-based compounds. Therefore, the rhizomes of this plant species could serve as potential novel source of compounds effective for alleviating pain and inflammation.

Reminders of cancer risk and pain catastrophizing: relationships with cancer worry and perceived risk in women with a first-degree relative with breast cancer.

PubMed

Whitney, Colette A; Dorfman, Caroline S; Shelby, Rebecca A; Keefe, Francis J; Gandhi, Vicky; Somers, Tamara J

2018-04-20

First-degree relatives of women with breast cancer may experience increased worry or perceived risk when faced with reminders of their own cancer risk. Worry and risk reminders may include physical symptoms (e.g., persistent breast pain) and caregiving experiences. Women who engage in pain catastrophizing may be particularly likely to experience increased distress when risk reminders are present. We examined the degree to which persistent breast pain and experience as a cancer caregiver were related to cancer worry and perceived risk in first-degree relatives of women with breast cancer (N = 85) and how catastrophic thoughts about breast pain could impact these relationships. There was a significant interaction between persistent breast pain and pain catastrophizing in predicting cancer worry (p = .03); among women who engaged in pain catastrophizing, cancer worry remained high even in the absence of breast pain. Pain catastrophizing also moderated the relationships between caregiving involvement and cancer worry (p = .003) and perceived risk (p = .03). As the degree of caregiving responsibility increased, cancer worry and perceived risk increased for women who engaged in pain catastrophizing; levels of cancer worry and perceived risk remained low and stable for women who did not engage in pain catastrophizing regardless of caregiving experience. The results suggest that first-degree relatives of breast cancer survivors who engage in pain catastrophizing may experience greater cancer worry and perceived risk and may benefit from interventions aimed at reducing catastrophic thoughts about pain.

The long-term impact of early life pain on adult responses to anxiety and stress: Historical perspectives and empirical evidence.

PubMed

Victoria, Nicole C; Murphy, Anne Z

2016-01-01

Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10-18 painful and inflammatory procedures each day. Remarkably, pre-emptive analgesics and/or anesthesia are administered less than 25% of the time. Unalleviated pain during the perinatal period is associated with permanent decreases in pain sensitivity, blunted cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and pain behavior occur, and whether such alterations can be prevented by appropriate analgesia at the time of insult, remains unclear. Work in our lab using a rodent model of early life pain suggests that inflammatory pain experienced on the day of birth blunts adult responses to stress- and pain-provoking stimuli, and dysregulates the hypothalamic pituitary adrenal (HPA) axis in part through a permanent upregulation in central endogenous opioid tone. This review focuses on the long-term impact of neonatal inflammatory pain on adult anxiety- and stress-related responses, and underlying neuroanatomical changes in the context of endogenous pain control and the HPA axis. These two systems are in a state of exaggerated developmental plasticity early in postnatal life, and work in concert to respond to noxious or aversive stimuli. We present empirical evidence from animal and clinical studies, and discuss historical perspectives underlying the lack of analgesia/anesthetic use for early life pain in the modern NICU. Copyright © 2015 Elsevier Inc. All rights reserved.

The Long-term Impact of Early Life Pain On Adult Responses to Anxiety and Stress: Historical Perspectives and Empirical Evidence

PubMed Central

Victoria, Nicole C.; Murphy, Anne Z.

2016-01-01

Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10–18 painful and inflammatory procedures each day. Remarkably, pre-emptive analgesics and/or anesthesia are administered less than 25% of the time. Unalleviated pain during the perinatal period is associated with permanent decreases in pain sensitivity, blunted cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and pain behavior occur, and whether such alterations can be prevented by appropriate analgesia at the time of insult, remains unclear. Work in our lab using a rodent model of early life pain suggests that inflammatory pain experienced on the day of birth blunts adult responses to stress- and pain-provoking stimuli, and dysregulates the hypothalamic pituitary adrenal (HPA) axis in part through a permanent upregulation in central endogenous opioid tone. This review focuses on the long-term impact of neonatal inflammatory pain on adult anxiety- and stress-related responses, and underlying neuroanatomical changes in the context of endogenous pain control and the HPA axis. These two systems are in a state of exaggerated developmental plasticity early in postnatal life, and work in concert to respond to noxious or aversive stimuli. We present empirical evidence from animal and clinical studies, and discuss historical perspectives underlying the lack of analgesia/anesthetic use for early life pain in the modern NICU. PMID:26210872

The association of mast cells and serotonin in children with chronic abdominal pain of unknown etiology

PubMed Central

2010-01-01

Background Abdominal pain of unknown origin affects up to 20% of school-aged children. Evaluation of children is symptom-based without clear guidelines to investigate molecular mechanisms of abdominal pain. Aberrant molecular mechanisms may increase intestinal permeability leading to interactions between the immune and nervous systems, subclinical inflammation, and visceral pain. This study evaluated the association between interleukin-6 (IL-6), mast cell infiltrates, and serotonin (5-HT) levels in gastrointestinal (GI) biopsies, with perceived abdominal pain in a pediatric cohort. Methods Clinical data and biopsy samples from pediatric patients (n = 48) with chronic abdominal pain, with and without inflammation were included. Formalin-fixed paraffin-embedded GI biopsies were sectioned and immunohistochemistry performed for IL-6 and 5-HT; mast cells were identified with toluidine blue stain. Histological findings were compared to self-reported abdominal pain between groups. Results There was significantly greater IL-6 immunoreactivity in biopsies with confirmed histologic inflammation (p = 0.004). There was a greater number of mast cells per HPF in non-inflammatory biopsies (3.5 ± 2.9) compared to the inflammatory biopsies (2.6 ± 1.8) p = 0.049. The non-inflammatory biopsy group was significantly less likely to respond to standard treatment as evidenced by higher pain reports (p = .018). Mast cells (p = .022) and 5-HT (p = .02) were significantly related to abdominal pain scores. Conclusions A potential association between self-reported abdominal pain, number of mast cells, and 5-HT levels, which may contribute to perceived GI pain in pediatric patients may exist. PMID:20964845

The Anti-Inflammatory Actions of Auricular Point Acupressure for Chronic Low Back Pain

PubMed Central

Lin, Wei-Chun; Morone, Natalia E.; Albers, Kathryn M.

2015-01-01

Background. Auricular point acupressure (APA) is a promising treatment for pain management. Few studies have investigated the physiological mechanisms of APA analgesics. Method. In this pilot randomized clinical trial (RCT), a 4-week APA treatment was used to manage chronic low back pain (CLBP). Sixty-one participants were randomized into a real APA group (n = 32) or a sham APA group (n = 29). Blood samples, pain intensity, and physical function were collected at baseline and after 4 weeks of treatment. Results. Subjects in the real APA group reported a 56% reduction of pain intensity and a 26% improvement in physical function. Serum blood samples showed (1) a decrease in IL-1β, IL-2, IL-6, and calcitonin gene-related peptide [CGRP] and (2) an increase in IL-4. In contrast, subjects in the sham APA group (1) reported a 9% reduction in pain and a 2% improvement in physical function and (2) exhibited minimal changes of inflammatory cytokines and neuropeptides. Statistically significant differences in IL-4 and CGRP expression between the real and sham APA groups were verified. Conclusion. These findings suggest that APA treatment affects pain intensity through modulation of the immune system, as reflected by APA-induced changes in serum inflammatory cytokine and neuropeptide levels. PMID:26170869

[Penile Tuberculosis : A Case Report].

PubMed

Imanaka, Takahiro; Nomura, Hironori; Tsujimura, Go; Ko, Yoko; Kinjyo, Takanori; Yoshioka, Iwao; Takada, Shingo; Yahata, Yoko; Mizutani, Tetsu

2017-04-01

A 66-year-old man presented with a chief complaint of glans penis pain, induration, and discharge of pus. He was prescribed a course of antibiotics, but the condition persisted despite treatment. Thus, we differrentially diagnosed the patient with penile tuberculosis and pyoderma gangrenosum, and performed a biopsy of the penis. The biopsy result was thickening of the horny layer epidermis with only a foreign body granuloma composed of inflammatory cells, and did not lead to a definitive diagnosis. Thoraca-abdominal computed tomography revealed axillary lymphadenopathy with necrosis. Suspecting tuberculosis lymphadenitis, we performed T-spot and QuantiFERONtests. The result was T-spot negative and QuantiFERONpositive, so we diagnosed the patient with penile tuberculosis, and started antituberculosis medication. In about half a year after the start of treatment the symptoms subsided, and lymphadenopathy showed reduction.

Consumption of and satisfaction with health care among opioid users with chronic non-malignant pain.

PubMed

Hansen, A B; Skurtveit, S; Borchgrevink, P C; Dale, O; Romundstad, P R; Mahic, M; Fredheim, O M

2015-11-01

Although persons with chronic pain are frequent users of the health care system, they report poor satisfaction with health care services. Participants with persistent opioid use in Nord-Trøndelag Health Study (HUNT)3 report severe pain in spite of treatment. The aim of the study was to test the hypothesis that subjects with persistent opioid use have both a higher consumption of health care services and a poorer satisfaction than the remaining subjects reporting chronic pain. This cross-sectional study was based on linkage of self-reported data from the substudy (10,238 were invited, 6927 met the inclusion criteria) of health care use in HUNT3; a population-based health survey during the years 2006-2008 and the complete national registers of the Norwegian Prescription Database and the Cancer Registry of Norway. Patients with chronic pain are stratified according to the level of opioid use as persistent users of opioids, intermittent users, and persons not using opioids. Persons with chronic non-malignant pain reported a higher consumption of all health care services compared to the control group. Consumption of health care services increased with increasing level of opioid use. Persons with persistent opioid use were highly satisfied with all health care services, although less satisfied than persons without chronic pain. Combined with previous findings of high levels of pain in spite of opioid treatment, the present findings indicate that symptomatic relief is not a prerequisite for patient satisfaction. The study shows higher patient satisfaction compared to previous studies. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Open-Label Milnacipran for Patients With Persistent Knee Pain 1 Year or Longer After Total Knee Arthroplasty: A Pilot Study

PubMed Central

Bolognesi, Michael P.

2013-01-01

Objective: The current study investigates whether milnacipran is effective in reducing pain and improving function in patients with persistent pain ≥ 1 year after total knee arthroplasty. Method: This was a 12-week open-label study of flexibly dosed milnacipran in patients (N = 5) experiencing chronic persistent knee pain ≥ 1 year following total knee arthroplasty in the absence of new injury, infection, or implant failure. Subjects were identified from October 2010 to August 2011 through the Duke University Medical Center orthopedic clinic (Durham, North Carolina), typically during 1-year postoperative follow-up visits, and were referred by their orthopedic surgeon. Results: Milnacipran treatment was associated with reduction in pain according to the primary outcome measure of the visual analog scale (VAS) score for pain (effect size of 1.15) and secondary outcome measures of Knee Society Score (KSS) evaluation subscale score (effect size of 1.37) and Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) bodily pain subscale (effect size of 1.16) at week 12. Secondary outcome measures of functional change were mixed in such that, at week 12, the SF-36 physical functioning subscale showed improvement (effect size of 1.16), but the KSS function subscale score was just below the threshold for meaningful effect size (0.98). Conclusions: Open-label milnacipran demonstrated reduced pain and some evidence of functional improvement in this small sample of patients with chronic persistent pain 1 year or more after total knee arthroplasty such that well-powered studies are warranted. Trial Registration: ClinicalTrials.gov identifier: NCT01780389 PMID:24392250

[CLINICAL ENTITIES AND CHARACTERISTICS OF PAIN IN PATIENTS WITH RHEUMATIC DISEASES].

PubMed

Prus, Višnja; Kardum, Željka

Musculoskeletal pain is the most common symptom present in almost all rheumatic diseases. Rheumatic diseases include more than 150 clinical entities. There is no uniform classification of rheumatic diseases. In general, we distinguish inflammatory rheumatic diseases, non-inflammatory degenerative articular diseases, systemic connective tissue diseases, metabolic disorders with articular manifestations, and regional and extended pain syndromes. According to the International Association for the Study of Pain (IASP), pain is defined as an unpleasant sensation associated with tissue damage or reported simultaneously with such damage. Pain has a physical, mental, and social component. In rheumatic diseases the pain is mostly chronic and may severely impair the patient’s general condition. The defining criteria involve a period of more than 3 or 6 months, and according to some definitions more than 6 weeks. In most cases the pain is nociceptive rather than neuropathic. Musculoskeletal pain, especially chronic pain, is a global public health problem because of its prevalence, as well as the frequently associated muslculoskeletal function impairment and development of chronic pain syndrome, which can be considered as a separate clinical entity and requires a biopsychosocial treatment approach.

Inflammation and fertility in the mare.

PubMed

Christoffersen, M; Troedsson, Mht

2017-08-01

A transient uterine inflammation post-breeding is a normal physiological reaction in the mare, and it is believed that the inflammatory response is necessary to eliminate bacteria and excess spermatozoa introduced into the uterine lumen. A tight balance between multiple pro- and anti-inflammatory factors is required for resolving the breeding-induced inflammation within 24-36 hr in the reproductively healthy mare, whereas a subpopulation of mares is susceptible to development of a persistent infection that can interfere with fertility. The aetiology of persistent endometritis can be either bacterial or semen-induced and both scenarios can threaten the establishment of pregnancy. Several factors associated with susceptibility to persistent endometritis have been identified including altered innate immune response in the early inflammatory process, reduced myometrial contractions and impaired opsonization; however, the pathogenesis to susceptibility has not been fully elucidated. Current research focuses on the initial hours of uterine inflammatory responses to semen and bacteria, and potential treatments to modify this altered innate immune response. An increased understanding of the mechanisms involved in the disease progression is necessary to improve the treatment and management of these mares. This review attempts to summarize the current knowledge of the uterine inflammatory and immunological responses to breeding-induced endometritis, persistent breeding-induced endometritis (PBIE) and bacterial endometritis in the mare. © 2017 Blackwell Verlag GmbH.

Predictors of task-persistent and fear-avoiding behaviors in women with sexual pain disorders.

PubMed

Brauer, Marieke; Lakeman, Mariëlle; van Lunsen, Rik; Laan, Ellen

2014-12-01

Dyspareunia and vaginismus are the most common sexual pain disorders (SPDs). Literature suggests that many women with dyspareunia continue with intercourse despite pain (task persistence), whereas many women with vaginismus avoid penetrative activities that may cause pain (fear avoidance). Both forms of sexual pain behavior may maintain or aggravate complaints. This study examined (i) whether women with SPD differ from pain-free controls in motives for sexual intercourse, sexual autonomy, maladaptive beliefs regarding vaginal penetration, and partner responses to pain; and (ii) which of these factors best predict whether women with SPD stop or continue painful intercourse (attempts). Women with superficial dyspareunia (n = 50), women with lifelong vaginismus (n = 20), and pain-free controls (n = 45) completed questionnaires. For Aim 1, the main outcome measures were (i) motives for intercourse; (ii) sexual autonomy; (iii) maladaptive beliefs regarding vaginal penetration; and (iv) partner responses to pain. For Aim 2, sexual pain behavior (to continue or discontinue with painful intercourse) was the outcome measure. (i) Women with dyspareunia exhibited more mate guarding and duty/pressure motives for intercourse and were less sexually autonomous than controls. (ii) Symptomatic women had more maladaptive penetration-related beliefs than controls, with women with vaginismus reporting the strongest maladaptive beliefs. (iii) Partners of women with dyspareunia self-reported more negative responses to pain than those of women with vaginismus. (iv) The factors that best predicted sexual pain behavior were the partner responses to pain and the woman's maladaptive beliefs regarding vaginal penetration. Our findings reveal support for task persistence in women with dyspareunia and fear avoidance in women with lifelong vaginismus. As such, it is important to consider these distinct types of responding to sexual pain when treating SPD. © 2014 International Society for Sexual Medicine.

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.

Persistent orofacial muscle pain: Its synonymous terminology and presentation.

PubMed

Spierings, Egilius L H; Mulder, Maxim J H L

2017-09-01

The purpose of the present paper is to describe the presentation of persistent orofacial muscle pain, also commonly referred to as myofascial temporomandibular disorder. In this practice survey, the authors reviewed the demographic and clinical features of 34 patients who were evaluated and diagnosed personally. The majority of the 34 patients were women (82.4%), and their age at consultation averaged 44.6 ± 12.6 (SD) years. The median pain duration was 4.0 years (range: 0.2-34 years). In 97.1% of patients, the pain occurred daily and continuously, and in 51.9% it was unilateral. Chewing or eating made the pain worse in 50% of the patients, and talking in 29.4%. On examination, tightness of the masseter muscle(s) was present in 58.8%, and tenderness in 58.8%. Persistent orofacial muscle pain mostly affects women, generally occurs daily and continuously, and is equally often unilateral and bilateral. Chewing, eating, and talking are the most common aggravating factors, and tightness or tenderness of the masseter muscle(s) is often found on examination.

Antinociceptive and anti-inflammatory effects of the methanolic stem bark extract of Antrocaryon klaineanum Pierre (Anacardiaceae) in mice and rat.

PubMed

Fongang, Annie Laure Magne; Laure Nguemfo, Edwige; Djouatsa Nangue, Yolande; Bogning Zangueu, Calvin; Fouokeng, Yannick; Azebaze, Anatole Guy Blaise; José Llorent-Martínez, Eulogio; Córdova, Maria Luisa Fernández-de; Bertrand Dongmo, Alain; Vierling, Wolfgang

2017-05-05

Antrocaryon klaineanum is used by traditional healers to treat many disorders including pain and inflammatory diseases. This study aimed to evaluate the analgesic and antiinflammatory activities of methanol extract of A. klaineanum in mice and rats. Reverse phase high-performance liquid chromatography (RP-HPLC) was performed to establish the chromatographic fingerprint and to identify various chemical components of the plant extract. The anti-nociceptive activity of methanol extract of A. klaineanum was assessed using the acetic acid-induced abdominal constriction model, formalin test, capsaicin and cinnamaldehyde induced-neurogenic pain and hot plate test. Anti-inflammatory activity was assessed on carrageenan-induced inflammation. Extract was administrated orally at 200, 400 and 600mg/kg. Phytochemical analysis indicated the presence of proanthocyanidins, phenolic acids and flavonoids. The results of anti-nociceptive and anti-inflammatory activities showed that methanol extract significantly (p<0.01) reduced the pain induced by acetic acid with an inhibition percentage of 45.49% (600mg/kg). In the formalin test, the extract also significantly (p<0.01) reduced linking time in both phase (neurogenic and inflammatory) of the test with inhibition percentage of 56.28% and 60.73% respectively at the dose of 600mg/kg. The methanol extract of A. klaineanum significantly (P<0.001) reduced neurogenic pain linking time induced by capsaicin and cinnamaldehyde by 82.54% and 75.94% at the highest dose (600mg/kg) respectively. More over the extract significantly increase the reaction time in hot plate test. In the inflammatory test, the plant extract significantly reduced the carrageen induced rat paw oedema from 30min to 6h with a maximum percentage inhibition of 89.88% (6h) at the dose of 600mg/kg. These results demonstrate that the methanol extract of A. klaineanum may possess analgesic and anti-inflammatory effects and provide support of the traditional use of this plant in the treatment of different pain and inflammatory conditions. Further investigation could reveal metabolites of the extract responsible for the observed effects. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Immunological Mechanisms Underlying Chronic Pelvic Pain and Prostate Inflammation in Chronic Pelvic Pain Syndrome

PubMed Central

Breser, María L.; Salazar, Florencia C.; Rivero, Viginia E.; Motrich, Rubén D.

2017-01-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most common urologic morbidity in men younger than 50 years and is characterized by a diverse range of pain and inflammatory symptoms, both in type and severity, that involve the region of the pelvis, perineum, scrotum, rectum, testes, penis, and lower back. In most patients, pain is accompanied by inflammation in the absence of an invading infectious agent. Since CP/CPPS etiology is still not well established, available therapeutic options for patients are far from satisfactory for either physicians or patients. During the past two decades, chronic inflammation has been deeply explored as the cause of CP/CPPS. In this review article, we summarize the current knowledge regarding immunological mechanisms underlying chronic pelvic pain and prostate inflammation in CP/CPPS. Cumulative evidence obtained from both human disease and animal models indicate that several factors may trigger chronic inflammation in the form of autoimmunity against prostate, fostering chronic prostate recruitment of Th1 cells, and different other leukocytes, including mast cells, which might be the main actors in the consequent development of chronic pelvic pain. Thus, the local inflammatory milieu and the secretion of inflammatory mediators may induce neural sensitization leading to chronic pelvic pain development. Although scientific advances are encouraging, additional studies are urgently needed to establish the relationship between prostatitis development, mast cell recruitment to the prostate, and the precise mechanisms by which they would induce pelvic pain. PMID:28824626

Derivatives of furanditerpenes from Pterodon genus: Pharmacological studies disclose their potential as chronic pain relief in mice.

PubMed

Spindola, Humberto M; Grando, Rogério; Figueiredo, Mariana C; Basting, Rosana; Queiroz, N C A; de Fátima, Ângelo; de Carvalho, João E; Wang, Zaijie J; Foglio, M A

2017-06-05

Pterodon genus fruits are commercially available at the Brazilian medicinal market used in folk medicine due to their anti-inflammatory, analgesic, and anti-rheumatic effects. Previous studies demonstrated that furanditerpenes possessing vouacapan skeleton, isolated from Pterodon genus, possess expressive antinociceptive activities, with promising moiety for the development of new analgesic products. The antinociceptive properties of compounds 6α,7β-6α-hidroxivouacapan-7β-17β-lactone (HVL) and 6α-oxovouacapan-7β-17β-lactone (OVL), semi-synthetic analogues of furanditerpenes previously reported as analgesic agents were evaluated on animal experimental models (Spindola et al., 2010, 2011). The chemical-induced pain methods used in the present work, demonstrated for the first time that both compounds HVL and OVL have potential as important templates for the development of chronic pain control drugs. The main findings of this work were that both compounds were: effective in the writhing test; reduced paw edema in the carrageenan test; effective in the inflammatory phase of the formalin test corroborating their activity against inflammatory pain conditions; effective on reducing pain through the stimulation of vanilloid receptors sensible to capsaicin (an important pathway for chronic pain maintenance); reduced the pain stimulus caused by PGE 2 injection (a pathway involved in chronic pain hypersensitivity); effective on decreasing mechanical allodynia in the CFA-model, demonstrating their potential use against chronic pain disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Peripheral inflammatory pain sensitisation is independent of mast cell activation in male mice.

PubMed

Lopes, Douglas M; Denk, Franziska; Chisholm, Kim I; Suddason, Tesha; Durrieux, Camille; Thakur, Matthew; Gentry, Clive; McMahon, Stephen B

2017-07-01

The immune and sensory systems are known for their close proximity and interaction. Indeed, in a variety of pain states, a myriad of different immune cells are activated and recruited, playing a key role in neuronal sensitisation. During inflammatory pain it is thought that mast cells (MC) are one of the immune cell types involved in this process, but so far the evidence outlining their direct effect on neuronal cells remains unclear. To clarify whether MC are involved in inflammatory pain states, we used a transgenic mouse line (Mctp5Cre-iDTR) in which MC could be depleted in an inducible manner by administration of diphtheria toxin. Our results show that ablation of MC in male mice did not result in any change in mechanical and thermal hypersensitivity in the CFA model of inflammatory pain. Similarly, edema and temperature triggered by CFA inflammation at the injection site remained identical in MC depleted mice compared with their littermate controls. In addition, we show that Mctp5Cre-iDTR mice display normal levels of mechanical hypersensitivity after local injection of nerve growth factor (NGF), a factor well characterised to produce peripheral sensitisation and for being upregulated upon injury and inflammation. We also demonstrate that NGF treatment in vitro does not lead to an increased level of tumor necrosis factor-α in bone marrow-derived MC. Furthermore, our qRT-PCR data reveal that MC express negligible levels of NGF receptors, thereby explaining the lack of response to NGF. Together, our data suggest that MC do not play a direct role in peripheral sensitisation during inflammatory conditions.

Laparoscopic surgery for chronic groin pain in athletes is more effective than nonoperative treatment: a randomized clinical trial with magnetic resonance imaging of 60 patients with sportsman's hernia (athletic pubalgia).

PubMed

Paajanen, Hannu; Brinck, Tuomas; Hermunen, Heikki; Airo, Ilari

2011-07-01

Chronic groin pain in athletes presents often a diagnostic and therapeutic challenge. Sportsman's hernia (also called "athletic pubalgia") is a deficiency of the posterior wall of the inguinal canal, which is often repaired by laparoscopic mesh placement. Endoscopic mesh repair may offer a faster recovery for athletes with sportsman's hernia than nonoperative therapy. A randomized, prospective study was conducted on 60 patients with a diagnosis of chronic groin pain and suspected sportsman's hernia. Clinical data and MRI were collected on all patients. After 3 to 6 months of groin symptoms, the patients were randomized into an operative or a physiotherapy group (n = 30 patients in each group). Operation was performed using a totally extraperitoneal repair in which mesh was placed behind the symphysis and painful groin area. Conservative treatment included at least 2 months of active physiotherapy, including corticosteroid injections and oral anti-inflammatory analgesics. The outcome measures were pre- and postoperative pain using a visual analogue scale and partial or full recovery to sports activity at 1, 3, 6, and 12 months after randomization. The athletes in both treatment groups had similar characteristics and pain scores. Operative repair was more effective than nonoperative treatment to decrease chronic groin pain after 1 month and up to 12 months of follow-up (P < .001). Of the 30 athletes who underwent operation, 27 (90%) returned to sports activities after 3 months of convalescence compared to 8 (27%) of the 30 athletes in the nonoperative group (P < .0001). Of the 30 athletes in the conservatively treated group, 7 (23 %) underwent operation later because of persistent groin pain. This randomized controlled study indicated that the endoscopic placement of retropubic mesh was more efficient than conservative therapy for the treatment of sportsman's hernia (athletic pubalgia). Copyright © 2011 Mosby, Inc. All rights reserved.

Specific muscle stabilizing as home exercises for persistent pelvic girdle pain after pregnancy: a randomized, controlled clinical trial.

PubMed

Gutke, Annelie; Sjödahl, Jenny; Oberg, Birgitta

2010-11-01

To investigate the efficacy of home-based specific stabilizing exercises focusing on the local stabilizing muscles as the only intervention in the treatment of persistent postpartum pelvic girdle pain. A prospective, randomized, single-blinded, clinically controlled study. Eighty-eight women with pelvic girdle pain were recruited 3 months after delivery. The treatment consisted of specific stabilizing exercises targeting the local trunk muscles. The reference group had a single telephone contact with a physiotherapist. Primary outcome was disability measured with Oswestry Disability Index. Secondary outcomes were pain, health-related quality of life (EQ-5D), symptom satisfaction, and muscle function. No significant differences between groups could be found at 3- or 6-month follow-up regarding primary outcome in disability. Within-group comparisons showed some improvement in both groups in terms of disability, pain, symptom satisfaction and muscle function compared with baseline, although the majority still experienced pelvic girdle pain. Treatment with this home-training concept of specific stabilizing exercises targeting the local muscles was no more effective in improving consequences of persistent postpartum pelvic girdle pain than the clinically natural course. Regardless of whether treatment with specific stabilizing exercises was carried out, the majority of women still experienced some back pain almost one year after pregnancy.

Stress-related psychological symptoms contribute to axial pain persistence after motor vehicle collision: path analysis results from a prospective longitudinal study.

PubMed

Feinberg, Rose K; Hu, JunMei; Weaver, Mark A; Fillingim, Roger B; Swor, Robert A; Peak, David A; Jones, Jeffrey S; Rathlev, Niels K; Lee, David C; Domeier, Robert M; Hendry, Phyllis L; Liberzon, Israel; McLean, Samuel A

2017-04-01

Posttraumatic stress disorder (PTSD) symptoms and pain after traumatic events such as motor vehicle collision (MVC) have been proposed to be mutually promoting. We performed a prospective multicenter study that enrolled 948 individuals who presented to the emergency department within 24 hours of MVC and were discharged home after evaluation. Follow-up evaluations were completed 6 weeks, 6 months, and 1 year after MVC. Path analysis results supported the hypothesis that axial pain after MVC consistently promotes the maintenance of hyperarousal and intrusive symptoms, from the early weeks after injury through 1 year. In addition, path analysis results supported the hypothesis that one or more PTSD symptom clusters had an influence on axial pain outcomes throughout the year after MVC, with hyperarousal symptoms most influencing axial pain persistence in the initial months after MVC. The influence of hyperarousal symptoms on pain persistence was only present among individuals with genetic vulnerability to stress-induced pain, suggesting specific mechanisms by which hyperarousal symptoms may lead to hyperalgesia and allodynia. Further studies are needed to better understand the specific mechanisms by which pain and PTSD symptoms enhance one another after trauma, and how such mechanisms vary among specific patient subgroups, to better inform the development of secondary preventive interventions.

Length Is Associated with Pain: Jellyfish with Painful Sting Have Longer Nematocyst Tubules than Harmless Jellyfish.

PubMed

Kitatani, Ryuju; Yamada, Mayu; Kamio, Michiya; Nagai, Hiroshi

2015-01-01

A large number of humans are stung by jellyfish all over the world. The stings cause acute pain followed by persistent pain and local inflammation. Harmful jellyfish species typically cause strong pain, whereas harmless jellyfish cause subtle or no pain. Jellyfish sting humans by injecting a tubule, contained in the nematocyst, the stinging organ of jellyfish. The tubule penetrates into the skin leading to venom injection. The detailed morphology of the nematocyst tubule and molecular structure of the venom in the nematocyst has been reported; however, the mechanism responsible for the difference in pain that is caused by harmful and harmless jellyfish sting has not yet been explored or explained. Therefore, we hypothesized that differences in the length of the nematocyst tubule leads to different degrees of epithelial damage. The initial acute pain might be generated by penetration of the tubule, which stimulates pain receptor neurons, whilst persistent pain might be caused by injection of venom into the epithelium. To test this hypothesis we compared the lengths of discharged nematocyst tubules from harmful and harmless jellyfish species and evaluated their ability to penetrate human skin. The results showed that the harmful jellyfish species, Chrysaora pacifica, Carybdea brevipedalia, and Chironex yamaguchii, causing moderate to severe pain, have nematocyst tubules longer than 200 μm, compared with a jellyfish species that cause little or no pain, Aurelia aurita. The majority of the tubules of harmful jellyfishes, C. yamaguchii and C. brevipedalia, were sufficiently long to penetrate the human epidermis and physically stimulate the free nerve endings of Aδ pain receptor fibers around plexuses to cause acute pain and inject the venom into the human skin epithelium to cause persistent pain and inflammation.

Incidence and Location of Pain in Young, Active Patients Following Hip Arthroplasty.

PubMed

Nam, Denis; Nunley, Ryan M; Sauber, Timothy J; Johnson, Staci R; Brooks, Peter J; Barrack, Robert L

2015-11-01

Persistent pain following hip arthroplasty remains a concern, especially in young, active patients. Four hundred twenty patients less than 60 years of age with a pre-symptomatic UCLA score ≥ 6 (196 total hip arthroplasty [THA]; 224 surface replacement arthroplasty [SRA]) completed a pain-drawing questionnaire investigating the location, severity, and frequency of pain around the hip. At a mean of 2.9 years of follow-up, 40% reported pain in at least one location around the hip. There was no difference in the incidence of groin pain between SRA and THA patients (32% vs. 29%, P=0.6), but THA patients had a greater incidence of anterior (25% vs. 8%, P<0.001) and lateral (20% vs. 10%, P=0.01) thigh pain. A high percentage of young, active patients experience persistent pain following hip arthroplasty. Copyright © 2015 Elsevier Inc. All rights reserved.

Antioxidant Supplementation Reduces Endometriosis Related Pelvic Pain in Humans

PubMed Central

Santanam, Nalini; Kavtaradze, Nino; Murphy, Ana; Dominguez, Celia; Parthasarathy, Sampath

2012-01-01

We had previously suggested that women with endometriosis have increased oxidative stress in the peritoneal cavity. In order to assess whether antioxidant supplementation would ameliorate endometriosis associated symptoms, we performed a randomized, placebo controlled trial of antioxidant vitamins (Vitamin E and C) in women with pelvic pain and endometriosis. Fifty nine women, ages 19–41 years, with pelvic pain and history of endometriosis and/or infertility were recruited for this study. Patients were randomly assigned to two groups: vitamin E (1200 IU) and vitamin C (1000 mg) combination or placebo, daily for eight weeks before surgery. Pain scales were administered at baseline and bi-weekly. Inflammatory markers were measured in the peritoneal fluid obtained from both groups of patients at the end of therapy. Our results indicated that, after treatment with antioxidants, chronic pain (“everyday pain”) improved in 43% of patients in antioxidant treatment group (p=0.0055) as compared to the placebo group. In the same group, dysmenorrhea (“pain associated with menstruation”) and dyspareunia (“pain with sex”) decreased in 37% and 24% patients, respectively. In the placebo group, dysmenorrhea associated pain decreased in 4 patients and no change was seen in chronic pain or dyspareunia. There was significant decrease in peritoneal fluid inflammatory markers, RANTES (p≤0.002), interleukin-6 (p≤0.056) and monocyte chemotactic protein-1 (p≤0.016) after antioxidant therapy compared to patients not on antioxidants. In conclusion, results of this clinical trial show that administration of antioxidants reduces chronic pelvic pain in women with endometriosis and inflammatory markers in the peritoneal fluid. PMID:22728166

Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia.

PubMed

Huang, Chun-Ping; Chen, Hsiang-Ni; Su, Hong-Lin; Hsieh, Ching-Liang; Chen, Wei-Hsin; Lai, Zhen-Rung; Lin, Yi-Wen

2013-01-01

Several voltage-gated sodium channels (Navs) from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA) analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG). We injected carrageenan and complete Freund's adjuvant (CFA) into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST36) acupoint at 2 Hz low frequency. Mechanical hyperalgesia was evaluated by using electronic von Frey filaments, and thermal hyperalgesia was assessed using Hargreaves' test. Furthermore, we observed the expression and quality of Navs in DRG neurons. Our results showed that EA reduced mechanical and thermal pain in inflammatory animal model. The expression of Nav1.7 and Nav1.8 was increased after 4 days of carrageenan- and CFA-elicited inflammatory pain and further attenuated by 2 Hz EA stimulation. The attenuation cannot be observed in Nav1.9 sodium channels. We demonstrated that EA at Zusanli (ST36) acupoint at 2 Hz low-frequency stimulation attenuated inflammatory pain accompanied by decreasing the expression of Nav1.7 and 1.8, rather than Nav1.9, sodium channels in peripheral DRG neurons.

Impaired insula functional connectivity associated with persistent pain perception in patients with complex regional pain syndrome

PubMed Central

Jang, Joon Hwan; Lee, Do-Hyeong; Lee, Kyung-Jun; Lee, Won Joon; Moon, Jee Youn; Kim, Yong Chul

2017-01-01

Given that the insula plays a contributory role in the perception of chronic pain, we examined the resting-state functional connectivity between the insular cortex and other brain regions to investigate neural underpinnings of persisting perception of background pain in patients with complex regional pain syndrome (CRPS). A total of 25 patients with CRPS and 25 matched healthy controls underwent functional magnetic resonance imaging at rest. With the anterior and posterior insular cortices as seed regions, we compared the strength of the resting-state functional connectivity between the two groups. Functional connectivity between the anterior and posterior insular cortices and the postcentral and inferior frontal gyri, cingulate cortices was reduced in patients with CRPS compared with controls. Additionally, greater reductions in functional connectivity between the anterior insula and right postcentral gyrus were associated with more severe sensory pain in patients with CRPS (short-form McGill Pain Questionnaire sensory subscores, r = -.517, P = .023). The present results imply a possible role of the insula in aberrant processing of pain information in patients with CRPS. The findings suggest that a functional derangement of the connection between one of the somatosensory cortical functions of perception and one of the insular functions of awareness can play a significant role in the persistent experience of regional pain that is not confined to a specific nerve territory. PMID:28692702

Analgesic and Sensory Effects of the Pecs Local Anesthetic Block in Patients with Persistent Pain after Breast Cancer Surgery: A Pilot Study.

PubMed

Wijayasinghe, Nelun; Andersen, Kenneth G; Kehlet, Henrik

2017-02-01

Persistent pain after breast cancer surgery (PPBCS) develops in 15% to 25% of patients, sometimes years after surgery. Approximately 50% of PPBCS patients have neuropathic pain in the breast, which may be due to dysfunction of the pectoral nerves. The Pecs local anesthetic block proposes to block these nerves and has provided pain relief for patients undergoing breast cancer surgery, but has yet to be evaluated in patients with PPBCS. The aim of this pilot study was to examine the effects of the Pecs block on summed pain intensity (SPI) and sensory function (through quantitative sensory testing [QST]) in eight patients with PPBCS. SPI and QST measurements were recorded before and 30 minutes after administration of the Pecs block (20 mL 0.25% bupivacaine). Pain intensity and sleep interference were measured daily before and after the block for 7 days. Patients experienced analgesia (P = 0.008) and reduced hypoesthesia areas to cold (P = 0.004) and warmth (P = 0.01) after 30 minutes. The reported pain relief (P = 0.02) and reduced sleep interference (P = 0.01) persisted for 7 days after the block. This pilot study suggests that the pectoral nerves play a role in the maintenance of pain in the breast area in PPBCS and begs for further research. © 2016 World Institute of Pain.

Referred Pain Patterns Provoked on Intra-Pelvic Structures among Women with and without Chronic Pelvic Pain: A Descriptive Study

PubMed Central

Butler, Stephen; Peterson, Magnus; Eriksson, Margaretha

2015-01-01

Objectives To describe referred pain patterns provoked from intra-pelvic structures in women with chronic pelvic pain (CPP) persisting after childbirth with the purpose to improve diagnostics and give implications for treatment. Materials and Methods In this descriptive and comparative study 36 parous women with CPP were recruited from a physiotherapy department waiting list and by advertisements in newspapers. A control group of 29 parous women without CPP was consecutively assessed for eligibility from a midwifery surgery. Inclusion criterion for CPP was: moderate pain in the sacral region persisting at least six months after childbirth confirmed by pelvic pain provocation tests. Exclusion criteria in groups with and without CPP were: persistent back or pelvic pain with onset prior to pregnancy, previous back surgery and positive neurological signs. Pain was provoked by palpation of 13 predetermined intra-pelvic anatomical landmarks. The referred pain distribution was expressed in pain drawings and described in pain maps and calculated referred pain areas. Results Pain provoked by palpation of the posterior intra-pelvic landmarks was mostly referred to the sacral region and pain provoked by palpation of the ischial and pubic bones was mostly referred to the groin and pubic regions, with or without pain referred down the ipsilateral leg. The average pain distribution area provoked by palpation of all 13 anatomical landmarks was 30.3 mm² (19.2 to 53.7) in women with CPP as compared to 3.2 mm² (1.0 to 5.1) in women without CPP, p< 0.0001. Conclusions Referred pain patterns provoked from intra-pelvic landmarks in women with CPP are consistent with sclerotomal sensory innervation. Magnification of referred pain patterns indicates allodynia and central sensitization. The results suggest that pain mapping can be used to evaluate and confirm the pain experience among women with CPP and contribute to diagnosis. PMID:25793999

Prevalence and pattern of co-occurring musculoskeletal pain and its association with back-related disability among people with persistent low back pain: protocol for a systematic review and meta-analysis.

PubMed

Overaas, Cecilie K; Johansson, Melker S; de Campos, Tarcisio F; Ferreira, Manuela L; Natvig, Bard; Mork, Paul J; Hartvigsen, Jan

2017-12-16

Individuals with persistent low back pain commonly have a broad range of other health concerns including co-occurring musculoskeletal pain, which significantly affect their quality of life, symptom severity, and treatment outcomes. The purpose of this review is to get a better understanding of prevalence and patterns of co-occurring musculoskeletal pain complaints in those with persistent low back pain and its potential association with age, sex, and back-related disability as it might affect prognosis and management. This systematic review protocol has been designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. We will perform a comprehensive search, with no date limit, in the following bibliographic databases: MEDLINE and Embase (via Ovid), CINAHL, and Scopus for citation tracking, based on the following domains: back pain, co-occurring musculoskeletal pain, combined with a focus group that emphasizes study design. Appropriate papers will be screened against the eligibility criteria by three reviewers independently, data extracted by two independent author pairs and disagreement resolved by consensus meetings or other reviewers if required. Assessment of methodological quality and risk of bias will be conducted using a modified version of the Risk of Bias Tool for Prevalence Studies developed by Hoy and colleagues. The overall risk of bias will be determined for each included study based on the raters' consensus of the responses to the items in this tool. In case of sufficiently homogenous studies, meta-analysis will be performed. Given the lack of standard terms used to define co-occurring musculoskeletal pain, the search strategy will include the broader term "back pain," different terms for the "other co-occurring pain," and specific study designs combined with several exclusion terms. The results of this proposed review will identify the prevalence and patterns of co-occurring musculoskeletal pain among those with persistent low back pain, which is likely to inform clinical management, research, and policy in management of musculoskeletal disorders. PROSPERO CRD42017068807.

Effects of Adding an Internet-Based Pain Coping Skills Training Protocol to a Standardized Education and Exercise Program for People With Persistent Hip Pain (HOPE Trial): Randomized Controlled Trial Protocol

PubMed Central

Rini, Christine; Keefe, Francis; French, Simon; Nelligan, Rachel; Kasza, Jessica; Forbes, Andrew; Dobson, Fiona; Haxby Abbott, J.; Dalwood, Andrew; Vicenzino, Bill; Harris, Anthony; Hinman, Rana S.

2015-01-01

Background Persistent hip pain in older people is usually due to hip osteoarthritis (OA), a major cause of pain, disability, and psychological dysfunction. Objective The purpose of this study is to evaluate whether adding an Internet-based pain coping skills training (PCST) protocol to a standardized intervention of education followed by physical therapist–instructed home exercise leads to greater reductions in pain and improvements in function. Design An assessor-, therapist-, and participant-blinded randomized controlled trial will be conducted. Setting The study will be conducted in a community setting. Participants The participants will be 142 people over 50 years of age with self-reported hip pain consistent with hip OA. Intervention Participants will be randomly allocated to: (1) a control group receiving a 24-week standardized intervention comprising an 8-week Internet-based education package followed by 5 individual physical therapy exercise sessions plus home exercises (3 times weekly) or (2) a PCST group receiving an 8-week Internet-based PCST protocol in addition to the control intervention. Measurements Outcomes will be measured at baseline and 8, 24, and 52 weeks, with the primary time point at 24 weeks. Primary outcomes are hip pain on walking and self-reported physical function. Secondary outcomes include health-related quality-of-life, participant-perceived treatment response, self-efficacy for pain management and function, pain coping attempts, pain catastrophizing, and physical activity. Measurements of adherence, adverse events, use of health services, and process measures will be collected at 24 and 52 weeks. Cost-effectiveness will be assessed at 52 weeks. Limitations A self-reported diagnosis of persistent hip pain will be used. Conclusions The findings will help determine whether adding an Internet-based PCST protocol to standardized education and physical therapist–instructed home exercise is more effective than education and exercise alone for persistent hip pain. This study has the potential to guide clinical practice toward innovative modes of psychosocial health care provision. PMID:26023213

Effects of Adding an Internet-Based Pain Coping Skills Training Protocol to a Standardized Education and Exercise Program for People With Persistent Hip Pain (HOPE Trial): Randomized Controlled Trial Protocol.

PubMed

Bennell, Kim L; Rini, Christine; Keefe, Francis; French, Simon; Nelligan, Rachel; Kasza, Jessica; Forbes, Andrew; Dobson, Fiona; Abbott, J Haxby; Dalwood, Andrew; Vicenzino, Bill; Harris, Anthony; Hinman, Rana S

2015-10-01

Persistent hip pain in older people is usually due to hip osteoarthritis (OA), a major cause of pain, disability, and psychological dysfunction. The purpose of this study is to evaluate whether adding an Internet-based pain coping skills training (PCST) protocol to a standardized intervention of education followed by physical therapist-instructed home exercise leads to greater reductions in pain and improvements in function. An assessor-, therapist-, and participant-blinded randomized controlled trial will be conducted. The study will be conducted in a community setting. The participants will be 142 people over 50 years of age with self-reported hip pain consistent with hip OA. Participants will be randomly allocated to: (1) a control group receiving a 24-week standardized intervention comprising an 8-week Internet-based education package followed by 5 individual physical therapy exercise sessions plus home exercises (3 times weekly) or (2) a PCST group receiving an 8-week Internet-based PCST protocol in addition to the control intervention. Outcomes will be measured at baseline and 8, 24, and 52 weeks, with the primary time point at 24 weeks. Primary outcomes are hip pain on walking and self-reported physical function. Secondary outcomes include health-related quality-of-life, participant-perceived treatment response, self-efficacy for pain management and function, pain coping attempts, pain catastrophizing, and physical activity. Measurements of adherence, adverse events, use of health services, and process measures will be collected at 24 and 52 weeks. Cost-effectiveness will be assessed at 52 weeks. A self-reported diagnosis of persistent hip pain will be used. The findings will help determine whether adding an Internet-based PCST protocol to standardized education and physical therapist-instructed home exercise is more effective than education and exercise alone for persistent hip pain. This study has the potential to guide clinical practice toward innovative modes of psychosocial health care provision. © 2015 American Physical Therapy Association.

Cognitive-behavioral therapy for persistent pain: does adherence after treatment affect outcome?

PubMed

Curran, Charlotte; Williams, Amanda C de C; Potts, Henry W W

2009-02-01

It is a tenet of cognitive behavioral treatment of persistent pain problems that ex-patients should adhere to treatment methods over the longer term, in order to maintain and to extend treatment gains. However, no research has quantified the causal influence of adherence on short-term outcome in this field. The aims of this study are to assess determinants of adherence to treatment recommendations in several domains, and to examine the extent to which cognitive and behavioral adherence predicts better outcome of cognitive behavioral treatment for persistent pain. Longitudinal data from a sample of 2345 persistent pain patients who attended a multicomponent treatment programme were subjected to structural equation modeling. Adherence emerged as a mediating factor linking post-treatment and follow-up treatment outcome, but contributed only 3% unique variance to follow-up outcomes. Combined end-of-treatment outcomes and adherence factors accounted for 72% of the variance in outcome at one-month follow-up. Notwithstanding shortcomings in the measurement of adherence, these findings question the emphasis normally given to adherence in the maintenance of behavioral and cognitive change, and clinical implications are discussed.

Correlates of Neuropsychological Impairment in Older Adult Pain Clinic Patients

PubMed Central

Karp, Jordan F.; Reynolds, Charles F.; Butters, Meryl; Dew, Mary Amanda; Mazumdar, Sati; Begley, Amy E.; Lenze, Eric; Weiner, Debra K.

2010-01-01

Objective Persistent pain and cognitive impairment are common in older adults. Memory and mental flexibility are cognitive domains which may be vulnerable in the aging brain. We were interested in examining the effects of persistent pain and opioid use on cognition in community dwelling, non-demented older adults. Setting Older Adult Pain Management Program. Design 57 new patients (mean age 76.1) were recruited to describe 1) rates of persistent pain conditions and pain intensity, 2) cognition (memory and mental flexibility), 3) rates and severity of depression, and 4) sleep quality. All patients had non-malignant pain for at least 3 months. Pain intensity was measured with the McGill Pain Questionnaire. Diagnosis of depression was via the Patient Health Questionnaire and depression severity assessed with the Hamilton Rating Scale for Depression. Cognition was assessed with: 1) Mini Mental State Examination, 2) number-letter-switching and motor speed trail-making subtests, 3) Digit Symbol Subtest of the WAIS-R, and 4) free and paired recall of the WAIS-R. To determine which variables predicted poorer outcomes on mental flexibility tests, these variables were entered into a multiple regression. Results Pain severity was associated with impaired number-letter switching (r = −0.42, p = 0.002). Multiple regression showed pain severity was associated with impaired mental flexibility (parameter estimate = −0.29 (t = −2.00), p = 0.05). Patients taking opioids had worse memory (t = 2.17, df = 39, p = 0.04). Conclusions In community-dwelling older adults, pain severity is associated with impaired mental flexibility. In addition, opioids may increase memory problems. PMID:17014605

Extinction of Fear Generalization: A Comparison Between Fibromyalgia Patients and Healthy Control Participants.

PubMed

Meulders, Ann; Meulders, Michel; Stouten, Iris; De Bie, Jozef; Vlaeyen, Johan W S

2017-01-01

Fear learning deficiencies might contribute to the development and maintenance of chronic pain disability. Fear is often not restricted to movements (conditioned stimulus [CS+]) originally associated with pain (unconditioned stimulus), but expands to similar movements (generalization stimuli [GSs]). This spreading of fear becomes dysfunctional when overgeneralization to safe stimuli occurs. More importantly, persistence of pain-related fear to GSs despite corrective feedback might even be more debilitating and maintain long-term chronic pain disability. Yet, research on this topic is lacking. Using a voluntary joystick movement paradigm, we examined (extinction of) pain-related fear generalization in fibromyalgia patients (FM) and healthy control participants (HC). During acquisition, one movement (CS+) predicted pain; another did not (CS-). We tested (extinction of) fear generalization to 5 GSs varying in similarity with the CS+ and CS-. Results revealed flatter pain expectancy generalization gradients in FM than in HC due to elevated responses to GSs more similar to the CS-; the fear generalization gradients did not differ. Although pain-related fear and expectancy to the GSs decreased during extinction, responses to the GSs remained higher for FM than HC, suggesting that extinction of generalization is impaired in chronic pain patients. Persistence of excessive protective responses may contribute to maintaining long-term chronic pain disability. Pain-related fear and expectancy to movements-varying in similarity with the original painful and nonpainful movement-decrease during extinction in HC and FM. Yet, conditioned responses remain elevated in patients despite corrective feedback, indicating impaired extinction of generalization. Persistent excessive protective responses may contribute to preserving pain disability. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Diagnosis of neglected tropical diseases among patients with persistent digestive disorders (diarrhoea and/or abdominal pain ≥14 days): Pierrea multi-country, prospective, non-experimental case-control study.

PubMed

Polman, Katja; Becker, Sören L; Alirol, Emilie; Bhatta, Nisha K; Bhattarai, Narayan R; Bottieau, Emmanuel; Bratschi, Martin W; Burza, Sakib; Coulibaly, Jean T; Doumbia, Mama N; Horié, Ninon S; Jacobs, Jan; Khanal, Basudha; Landouré, Aly; Mahendradhata, Yodi; Meheus, Filip; Mertens, Pascal; Meyanti, Fransiska; Murhandarwati, Elsa H; N'Goran, Eliézer K; Peeling, Rosanna W; Ravinetto, Raffaella; Rijal, Suman; Sacko, Moussa; Saye, Rénion; Schneeberger, Pierre H H; Schurmans, Céline; Silué, Kigbafori D; Thobari, Jarir A; Traoré, Mamadou S; van Lieshout, Lisette; van Loen, Harry; Verdonck, Kristien; von Müller, Lutz; Yansouni, Cédric P; Yao, Joel A; Yao, Patrick K; Yap, Peiling; Boelaert, Marleen; Chappuis, François; Utzinger, Jürg

2015-08-18

Diarrhoea still accounts for considerable mortality and morbidity worldwide. The highest burden is concentrated in tropical areas where populations lack access to clean water, adequate sanitation and hygiene. In contrast to acute diarrhoea (<14 days), the spectrum of pathogens that may give rise to persistent diarrhoea (≥14 days) and persistent abdominal pain is poorly understood. It is conceivable that pathogens causing neglected tropical diseases play a major role, but few studies investigated this issue. Clinical management and diagnostic work-up of persistent digestive disorders in the tropics therefore remain inadequate. Hence, important aspects regarding the pathogenesis, epidemiology, clinical symptomatology and treatment options for patients presenting with persistent diarrhoea and persistent abdominal pain should be investigated in multi-centric clinical studies. This multi-country, prospective, non-experimental case-control study will assess persistent diarrhoea (≥14 days; in individuals aged ≥1 year) and persistent abdominal pain (≥14 days; in children/adolescents aged 1-18 years) in up to 2000 symptomatic patients and 2000 matched controls. Subjects from Côte d'Ivoire, Indonesia, Mali and Nepal will be clinically examined and interviewed using a detailed case report form. Additionally, each participant will provide a stool sample that will be examined using a suite of diagnostic methods (i.e., microscopic techniques, rapid diagnostic tests, stool culture and polymerase chain reaction) for the presence of bacterial and parasitic pathogens. Treatment will be offered to all infected participants and the clinical treatment response will be recorded. Data obtained will be utilised to develop patient-centred clinical algorithms that will be validated in primary health care centres in the four study countries in subsequent studies. Our research will deepen the understanding of the importance of persistent diarrhoea and related digestive disorders in the tropics. A diversity of intestinal pathogens will be assessed for potential associations with persistent diarrhoea and persistent abdominal pain. Different diagnostic methods will be compared, clinical symptoms investigated and diagnosis-treatment algorithms developed for validation in selected primary health care centres. The findings from this study will improve differential diagnosis and evidence-based clinical management of digestive syndromes in the tropics. ClinicalTrials.gov; identifier: NCT02105714 .

Pain management in patients with inflammatory bowel disease: insights for the clinician

PubMed Central

Srinath, Arvind Iyengar; Walter, Chelsea; Newara, Melissa C.

2012-01-01

Abdominal pain is a common symptom in patients with inflammatory bowel disease (IBD) and has a profound negative impact on patients’ lives. There are growing data suggesting that pain is variably related to the degree of active inflammation. Given the multifactorial etiologies underlying the pain, the treatment of abdominal pain in the IBD population is best accomplished by individualized plans. This review covers four clinically relevant categories of abdominal pain in patients with IBD, namely, inflammation, surgical complications, bacterial overgrowth, and neurobiological processes and how pain management can be addressed in each of these cases. The role of genetic factors, psychological factors, and psychosocial stress in pain perception and treatment will also be addressed. Lastly, psychosocial, pharmacological, and procedural pain management techniques will be discussed. An extensive review of the existing literature reveals a paucity of data regarding pain management specific to IBD. In addition, there is growing consensus suggesting a spectrum between IBD and irritable bowel syndrome (IBS) symptoms. Thus, this review for adult and pediatric clinicians also incorporates the literature for the treatment of functional abdominal pain and the clinical consensus from IBD and IBS experts on pharmacological, behavioral, and procedural methods to treat abdominal pain in this population. PMID:22973418

Abdominal pain and the neurotrophic system in ulcerative colitis.

PubMed

Deberry, Jennifer J; Bielefeldt, Klaus; Davis, Brian M; Szigethy, Eva M; Hartman, Douglas J; Coates, Matthew D

2014-12-01

We undertook a study to test the hypothesis that inflammation alters peripheral sensory mechanisms, thereby contributing to chronic abdominal pain in ulcerative colitis (UC). Patients with UC and healthy individuals rated abdominal pain using a visual analog scale and completed surveys describing anxiety or depression (Hospital Anxiety and Depression Score) and gastrointestinal symptoms (Rome III questionnaire). Patient age, sex, and severity of inflammation were determined. Rectal biopsies were processed using immunohistochemical techniques to assess nerve fiber density and real-time PCR to determine transcript expression of neurotrophins (nerve growth factor, glial cell-derived neurotrophic factor, artemin, neurturin), ion channels (transient receptor potential vanilloid type 1, transient receptor potential ankyrin 1) and inflammatory mediators (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, IL-10, IL-17). A total of 77 patients with UC (27 female, 50 male) and 21 controls (10 female, 11 male) were enrolled. Patients with UC with pain had significantly higher depression scores than controls and patients with UC without pain (P < 0.05). There was no correlation between any of the inflammatory markers and pain scores. Visual analog scale pain scores significantly correlated with younger age, higher depression scores, increased expression of neurturin and decreased expression of transient receptor potential ankyrin 1 in the mucosa. Mucosal nerve fiber density did not correlate with any measures of inflammation or pain. Only higher depression scores independently predicted pain in UC (r > 0.5). We did not observe changes in mucosal innervation and did not see a significant relationship between nerve fiber density, inflammatory mediators, neurotrophic factors, or mucosal ion channel expression and pain. In contrast, the importance of depression as the only independent predictor of pain ratings mirrors functional disorders, where central processes significantly contribute to symptom development and/or perpetuation.

Pain: Systematic Review of Pharmacy Compounding of Pain Medication.

PubMed

Shawaqfeh, Mohammad S; Harrington, Catherine

2018-01-01

There are limited resources available for pharmacists and doctors to reference proper compounded formulas for pain medications. The systematic review discussed within this article provides the foundation for a searchable database, allowing users to find various compounded formulations. It also provides data about the safety and efficacy of the preparations. Compounding information about several drug classes was reviewed. Those drug classes included, but were not limited to, opioids, non-steroidal anti-inflammatory drugs, central nervous system agents, and anesthetics, with evidence that of the various drugs that could be compounded for pain, anesthetics, non-steroidal anti-inflammatory drugs, and opioids ranked highest within the articles researched. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Motivational Implications of Pain: Chronicity, Psychological Distress, and Work Goal Construal in a National Sample of Adults

PubMed Central

Karoly, Paul; Ruehlman, Linda S.

2005-01-01

A heterogeneous national sample of adults (mean age = 40 years) employed in management positions was contacted by random digit dialing procedures and interviewed about current pain experience, work-goal cognitions, and psychological status (depression and anxiety). In accord with predictions, persistent pain experience was differentially related to the construal of work-related goals. Specifically, individuals with both persistent and episodic pain (relative to those with no pain) reported lower levels of goal-centered value, self-efficacy, and positive arousal and heightened perceptions of goal-based self-criticism, negative arousal, and conflict between work and nonwork goals. Furthermore, regression analyses revealed that goal cognition accounted for unique variance in depression and anxiety over and above the contribution of pain chronicity. PMID:8891717

Chronic Pain: The Impact on Academic, Social, and Emotional Functioning

ERIC Educational Resources Information Center

Parkins, Jason M.; Gfroerer, Susan D.

2009-01-01

Chronic pain is persistent and recurrent pain that tends to fluctuate in severity, quality, regularity, and predictability. It can occur in a single or multiple body regions or organ systems. Some of the most frequently reported types of chronic pain include headaches, recurrent abdominal pain (RAP), and musculoskeletal pain. In contrast to acute…

Unexpected Complication after Caudal Epidural Steroid Injection: Hiccup

PubMed Central

Kaydu, Ayhan; Kılıç, Ebru Tarıkçı; Gökçek, Erhan; Akdemir, Mehmet Salim

2017-01-01

Persistent hiccup is uncommon, and the mechanism is poorly understood. We present the case of a 43-year-old male patient referred to the Algology department due to chronic back pain who developed what we believe a rare case of persistent hiccup secondary to caudal epidural steroid injection (CESI). The causes of hiccup are many and include electrolyte derangement, nutritional deficiencies, gastrointestinal disorders and instrumentation, cardiovascular disorders, renal impairment, central nervous system disorders, and drugs; however, the cause may be unknown. CESI is one of the treatments of back pain, in addition to various other modalities including surgical interventions. CESI has gained rapid and widespread acceptance for the treatment of lumbar and lower extremity pain. However, there are only a few well-designed, randomized, controlled studies on the effectiveness of steroid injections. Consequently, side effects should be considered. We aimed to present a persistent hiccup after CESI for chronic low back pain. PMID:28928587

Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain.

PubMed

Liu, Cui-Cui; Zhang, Xin-Sheng; Ruan, Yu-Ting; Huang, Zhu-Xi; Zhang, Su-Bo; Liu, Meng; Luo, Hai-Jie; Wu, Shao-Ling; Ma, Chao

2017-08-01

Lumbar disk herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood, and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels. In rats, implantation of autologous nucleus pulposus (NP) to the left lumbar 5 spinal nerve root, which mimicked LDH, induced mechanical allodynia, increased MG level in plasma and dorsal root ganglion (DRG), and enhanced the excitability of small DRG neurons (<30 μm in diameter). Intrathecal injection of MG also induced mechanical allodynia, and its application to DRG neurons ex vivo increased the number of action potentials evoked by depolarizing current pulses. Furthermore, inhibition of MG accumulation by aminoguanidine attenuated the enhanced excitability of small DRG neurons and the mechanical allodynia induced by NP implantation. In addition, NP implantation increased levels of advanced glycation end products (AGEs) in DRG, and intrathecal injection of MG-derived AGEs induced the mechanical allodynia and DRG neuronal hyperactivity. Intrathecal injection of MG also significantly increased the expression of AGEs in DRG. Importantly, scavenging of MG by aminoguanidine also attenuated the increase in AGEs induced by NP implantation. These results suggested that LDH-induced MG accumulation contributed to persistent pain by increasing AGE levels. Thus generation of AGEs from MG may represent a target for treatment of LDH-induced pain. NEW & NOTEWORTHY Our study demonstrates that methylglyoxal accumulation via increasing advanced glycation end-product levels in dorsal root ganglion contributes to the persistent pain induced by lumbar disk herniation, which proposed potential targets for the treatment of lumbar disk herniation-induced persistent pain. Copyright © 2017 the American Physiological Society.

Nonspecific abdominal pain in pediatric primary care: evaluation and outcomes.

PubMed

Wallis, Elizabeth M; Fiks, Alexander G

2015-01-01

To describe the characteristics of children with nonspecific abdominal pain (AP) in primary care, their evaluation, and their outcomes. Between 2007 and 2009, a retrospective cohort of children from 5 primary care practices was followed from an index visit with AP until a well-child visit 6 to 24 months later (outcome visit). Using International Classification of Disease, 9th Revision (ICD-9), codes and chart review, we identified afebrile children between 4 and 12 years old with AP. Use of diagnostic testing was assessed. Multivariable logistic regression was used to model the association of index visit clinical and demographic variables with persistent pain at the outcome visit, and receipt of a specific diagnosis. Three hundred seventy-five children presented with AP, representing 1% of the total population of 4- to 12-year-olds during the study period. Eighteen percent of children had persistent pain, and 70% of the study cohort never received a specific diagnosis for their pain. Seventeen percent and 14% of children had laboratory and radiology testing at the index visit, respectively. Only 3% of laboratory evaluations helped to yield a diagnosis. Among variables considered, only preceding pain of more than 7 days at the index visit was associated with persistent pain (odds ratio 2.15, 95% confidence interval 1.19-3.89). None of the variables considered was associated with receiving a specific diagnosis. Most children with AP do not receive a diagnosis, many have persistent pain, and very few receive a functional AP diagnosis. Results support limited use of diagnostic testing and conservative management consistent with national policy statements. Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

[Pain management in chronic pancreatitis and chronic inflammatory bowel diseases].

PubMed

Preiß, J C; Hoffmann, J C

2014-06-01

Apart from local inflammation and defects in secretion, central mechanisms are important for pain etiology in chronic pancreatitis. Therefore, centrally acting co-analgetic agents can be used in addition to classical pain medications. Endoscopic interventions are preferred in patients with obvious dilation of the pancreatic duct. Surgical interventions are generally more effective although they are usually reserved for patients with prior failure of conservative treatment. Diverse surgical options with different efficacies and morbidities are used in individual patients.One of the main problems in chronic inflammatory bowel diseases is abdominal pain. Primarily the underlying disease needs to be adequately treated. Symptomatic pain management will most likely include treatment with acetaminophen and tramadol as well as occasionally principles of a multimodal pain regimen. For the treatment of arthralgia as well as enteropathy-associated arthritis the same treatment options are available as for other spondyloarthritic disorders.

[Musculoskeletal-related chest pain].

PubMed

Sturm, C; Witte, T

2017-01-01

Approximately 10-50% of chest pains are caused by musculoskeletal disorders. The association is twice as frequent in primary care as in emergency admissions. This article provides an overview of the most important musculoskeletal causes of chest pain and on the diagnostics and therapy. A selective search and analysis of the literature related to the topic of musculoskeletal causes of chest pain were carried out. Non-inflammatory diseases, such as costochondritis and fibromyalgia are frequent causes of chest pain. Inflammatory diseases, such as rheumatoid arthritis, spondyloarthritis and systemic lupus erythematosus are much less common but are more severe conditions and therefore have to be diagnosed and treated. The diagnostics and treatment often necessitate interdisciplinary approaches. Chest pain caused by musculoskeletal diseases always represents a diagnosis by exclusion of other severe diseases of the heart, lungs and stomach. Physiotherapeutic and physical treatment measures are particularly important, including manual therapy, transcutaneous electrical stimulation and stabilization exercises, especially for functional myofascial disorders.

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.

Evidence of Nervous System Sensitization in Commonly Presenting and Persistent Painful Tendinopathies: A Systematic Review.

PubMed

Plinsinga, Melanie L; Brink, Michel S; Vicenzino, Bill; van Wilgen, C Paul

2015-11-01

Study Design Systematic review. Objectives To elucidate if there is sensitization of the nervous system in those with persistent rotator cuff (shoulder), lateral elbow, patellar, and Achilles tendinopathies. Background Tendinopathy can be difficult to treat, and persistent intractable pain and dysfunction are frequent. It is hypothesized that induction or maintenance of persistent pain in tendinopathy may be, at least in part, based on changes in the nervous system. Methods The PRISMA guidelines were followed. Relevant articles were identified through a computerized search in Embase, PubMed, and Web of Science, followed by a manual search of reference lists of retained articles. To be eligible, studies had to include quantitative sensory testing and evaluate individuals diagnosed with a persistent tendinopathy of the rotator cuff (shoulder), lateral elbow, patella, or Achilles tendon. Methodological quality assessment was evaluated with the Newcastle-Ottawa Scale. Results In total, 16 full-text articles met the criteria for inclusion, of which the majority were case-control studies with heterogeneous methodological quality. No studies on Achilles tendinopathy were found. Mechanical algometry was the predominant quantitative sensory testing used. Lowered pressure pain threshold was observed across different tendinopathies at the site of tendinopathy, as well as at other sites, the latter being suggestive of central sensitization. Conclusion Although more research on sensory abnormalities is warranted, it appears likely that there is an association between persistent tendon pain and sensitization of the nervous system. This evidence is primarily from studies of upper-limb tendinopathy, and caution should be exercised with inference to lower-limb tendinopathy. J Orthop Sports Phys Ther 2015;45(11):864-875. Epub 21 Sep 2015. doi:10.2519/jospt.2015.5895.

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

What low back pain is and why we need to pay attention.

PubMed

Hartvigsen, Jan; Hancock, Mark J; Kongsted, Alice; Louw, Quinette; Ferreira, Manuela L; Genevay, Stéphane; Hoy, Damian; Karppinen, Jaro; Pransky, Glenn; Sieper, Joachim; Smeets, Rob J; Underwood, Martin

2018-03-20

Low back pain is a very common symptom. It occurs in high-income, middle-income, and low-income countries and all age groups from children to the elderly population. Globally, years lived with disability caused by low back pain increased by 54% between 1990 and 2015, mainly because of population increase and ageing, with the biggest increase seen in low-income and middle-income countries. Low back pain is now the leading cause of disability worldwide. For nearly all people with low back pain, it is not possible to identify a specific nociceptive cause. Only a small proportion of people have a well understood pathological cause-eg, a vertebral fracture, malignancy, or infection. People with physically demanding jobs, physical and mental comorbidities, smokers, and obese individuals are at greatest risk of reporting low back pain. Disabling low back pain is over-represented among people with low socioeconomic status. Most people with new episodes of low back pain recover quickly; however, recurrence is common and in a small proportion of people, low back pain becomes persistent and disabling. Initial high pain intensity, psychological distress, and accompanying pain at multiple body sites increases the risk of persistent disabling low back pain. Increasing evidence shows that central pain-modulating mechanisms and pain cognitions have important roles in the development of persistent disabling low back pain. Cost, health-care use, and disability from low back pain vary substantially between countries and are influenced by local culture and social systems, as well as by beliefs about cause and effect. Disability and costs attributed to low back pain are projected to increase in coming decades, in particular in low-income and middle-income countries, where health and other systems are often fragile and not equipped to cope with this growing burden. Intensified research efforts and global initiatives are clearly needed to address the burden of low back pain as a public health problem. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

The effects of pre-emptive low-dose X-ray irradiation on MIA induced inflammatory pain in rats

NASA Astrophysics Data System (ADS)

Hahm, Suk-Chan; Lee, Go-Eun; Kim, Eun-Hye; Kim, Junesun; Lee, Taewoong; Lee, Wonho

2013-07-01

This study was performed to determine the effect of pre-emptive low-dose irradiation on the development of inflammatory pain and to characterize the potential mechanisms underlying this effect in osteoarthritis (OA) animal model. Whole-body X-irradiations with 0.1, 0.5, 1 Gy or sham irradiations were performed for 3 days before the induction of ostearthritis with monosodium iodoacetate (MIA) (40 µl, in saline) into the right knee joint in male Sprague Dawley rats. Behavioral tests for arthritic pain including evoked and non-evoked pain were conducted before and after MIA injection and inducible nitric-oxide synthase (iNOS) expression level was measured by western blot. Low-dose radiation significantly prevented the development of mechanical allodynia and thermal hyperalgesia and reduction in weight bearing that is regarded as a behavioral signs of non-evoked pain following MIA injection. Low-dose radiation significantly inhibited the increase in iNOS expression after MIA injection in spinal L3-5 segments in rat. These data suggest that low-dose X-irradiation is able to prevent the development of arthritic pain through modulation of iNOS expression in the spinal cord dorsal horn. Thus, low-dose radiotherapy could be substituted in part for treatment with drugs for patients with chronic inflammatory disease in clinical setting.

Longitudinal profiles of back pain across adulthood and their relationship with childhood factors: evidence from the 1946 British birth cohort

PubMed Central

Muthuri, Stella G.; Kuh, Diana; Cooper, Rachel

2018-01-01

Abstract This study aimed to (1) characterise long-term profiles of back pain across adulthood and (2) examine whether childhood risk factors were associated with these profiles, using data from 3271 participants in the Medical Research Council National Survey of Health and Development. A longitudinal latent class analysis was conducted on binary outcomes of back pain at ages 31, 36, 43, 53, 60 to 64, and 68 years. Multinomial logistic regression models were used to examine associations between selected childhood risk factors and class membership; adjusted for sex, adult body size, health status and behaviours, socioeconomic position, and family history of back pain. Four profiles of back pain were identified: no or occasional pain (57.7%), early-adulthood only (16.1%), mid-adulthood onset (16.9%), and persistent (9.4%). The “no or occasional” profile was treated as the referent category in subsequent analyses. After adjustment, taller height at age 7 years was associated with a higher likelihood of early-adulthood only (relative risk ratio per 1 SD increase in height = 1.31 [95% confidence interval: 1.05-1.65]) and persistent pain (relative risk ratio = 1.33 [95% confidence interval: 1.01-1.74]) in women (P for sex interaction = 0.01). Factors associated with an increased risk of persistent pain in both sexes were abdominal pain, poorest care in childhood, and poorer maternal health. Abdominal pain and poorest housing quality were also associated with an increased likelihood of mid-adulthood onset pain. These findings suggest that there are different long-term profiles of back pain, each of which is associated with different early life risk factors. This highlights the potential importance of early life interventions for the prevention and management of back pain. PMID:29408834

Pain-related avoidance versus endurance in primary care patients with subacute back pain: psychological characteristics and outcome at a 6-month follow-up.

PubMed

Hasenbring, Monika I; Hallner, Dirk; Klasen, Bernhard; Streitlein-Böhme, Irmgard; Willburger, Roland; Rusche, Herbert

2012-01-01

Recent research has found individual differences in back pain patients due to behavioral avoidance vs persistence. However, there is a lack of prospective studies of nonspecific low back pain patients. The avoidance-endurance model (AEM) suggests at least 3 pathways leading to chronic pain: fear-avoidance response, distress-endurance response, and eustress-endurance response. We sought to compare these 3 maladaptive subgroups with an adaptive group using a classification tool that included the following scales: the thought suppression and behavioral endurance subscale of the Avoidance-Endurance Questionnaire and the Beck Depression Inventory. The psychological characteristics, and pain and disability of the AEM subgroups were investigated. We report results from 177 patients with subacute nonspecific low back pain at the start of outpatient treatment and at follow-up after 6 months. At baseline, a multivariate analysis of variance found that the fear-avoidance patients scored higher in pain catastrophizing than the other groups. The distress-endurance patients displayed elevated anxiety/depression and helplessness/hopelessness accompanied with the highest scores in the classification variables thought suppression and persistence behavior. The eustress-endurance patients had the highest humor/distraction scores, pain persistence, and positive mood despite pain. All 3 maladaptive groups revealed a higher pain intensity than the adaptive patients at follow-up after 6 months; however, disability at follow-up was elevated only in the fear-avoidance and distress-endurance patients. The study provides preliminary evidence for the construct and prospective validity of AEM-based subgroups of subacute, nonspecific back pain patients. The results suggest the need for individually targeted cognitive behavioral treatments in the maladaptive groups. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Psychiatric comorbidity in new daily persistent headache: A cross-sectional study.

PubMed

Uniyal, R; Paliwal, V K; Tripathi, A

2017-07-01

New daily persistent headache (NDPH) is a type of chronic daily headache. NDPH can have migrainous (NDPH-CM) or tension-type character (NDPH-CTTH). Recently, NDPH patients have shown to have associated anxiety and depression. We compared anxiety, depressive symptoms, somatization and pain catastrophization among NDPH, healthy controls and patients with chronic low-back pain and between NDPH-CM and NDPH-CTTH. We assessed the study population for depressive symptoms by Patient Health Questionnaire-9, anxiety by Generalized Anxiety Disorder Scale - 7, somatoform disorder using DSM IV (TR) criteria and pain catastrophizing by using Pain Catastrophizing Scale. Fifty-five patients each with NDPH (mean age 28.24 ± 12.05 years, 45.5% females) and age/sex matched healthy individuals and patients with chronic low-back pain were enrolled. Among NDPH patients, somatoform disorder was seen in 32.7%, severe anxiety in 65.5%, severe depressive symptoms in 40%, significant pain catastrophization in 85.5%. NDPH patients had significantly higher frequency of all psychiatric co-morbidities as compared to healthy controls and patients with chronic low-back pain. NDPH-CM patients had significantly higher frequency of depression and pain catastrophizing behaviour as compared to NDPH-CTTH. Anxiety, depressive symptoms, somatization and pain catastrophizing were significantly more prevalent in NDPH when compared to healthy individuals and patients with chronic low back pain. Such effects should be sought for, as they might contribute to refractoriness to treatment. Anxiety, depressive symptoms, somatization and pain catastrophizing were significantly more prevalent in new daily persistent headache when compared to healthy individuals and patients with chronic low back pain. Such effects should be sought for, as they might contribute to refractoriness to treatment. © 2017 European Pain Federation - EFIC®.

Monocytes/Macrophages Control Resolution of Transient Inflammatory Pain

PubMed Central

Willemen, Hanneke L. D. M.; Eijkelkamp, Niels; Carbajal, Anibal Garza; Wang, Huijing; Mack, Matthias; Zijlstra, Jitske; Heijnen, Cobi J.; Kavelaars, Annemieke

2014-01-01

Insights into mechanisms governing resolution of inflammatory pain are of great importance for many chronic pain–associated diseases. Here we investigate the role of macrophages/monocytes and the anti-inflammatory cytokine interleukin-10 (IL-10) in the resolution of transient inflammatory pain. Depletion of mice from peripheral monocytes/macrophages delayed resolution of intraplantar IL-1β- and carrageenan-induced inflammatory hyperalgesia from 1 to 3 days to >1 week. Intrathecal administration of a neutralizing IL-10 antibody also markedly delayed resolution of IL-1β- and carrageenan-induced inflammatory hyperalgesia. Recently, we showed that IL-1β- and carrageenan-induced hyperalgesia is significantly prolonged in LysM-GRK2+/− mice, which have reduced levels of G-protein-coupled receptor kinase 2 (GRK2) in LysM+ myeloid cells. Here we show that adoptive transfer of wild-type, but not of GRK2+/−, bone marrow-derived monocytes normalizes the resolution of IL-1β-induced hyperalgesia in LysM-GRK2+/− mice. Adoptive transfer of IL-10−/− bone marrow-derived monocytes failed to normalize the duration of IL-1β-induced hyperalgesia in LysM-GRK2+/− mice. Mechanistically, we show that GRK2+/− macrophages produce less IL-10 in vitro. In addition, intrathecal IL-10 administration attenuated IL-1β-induced hyperalgesia in LysM-GRK2+/− mice, whereas it had no effect in wild-type mice. Our data uncover a key role for monocytes/macrophages in promoting resolution of inflammatory hyperalgesia via a mechanism dependent on IL-10 signaling in dorsal root ganglia. Perspective We show that IL-10-producing monocytes/macrophages promote resolution of transient inflammatory hyperalgesia. Additionally, we show that reduced monocyte/macrophage GRK2 impairs resolution of hyperalgesia and reduces IL-10 production. We propose that low GRK2 expression and/or impaired IL-10 production by monocytes/macrophages represent peripheral biomarkers for the risk of developing chronic pain after inflammation. PMID:24793056

Specific Management of Post-Chikungunya Rheumatic Disorders: A Retrospective Study of 159 Cases in Reunion Island from 2006-2012

PubMed Central

Javelle, Emilie; Ribera, Anne; Degasne, Isabelle; Gaüzère, Bernard-Alex; Marimoutou, Catherine; Simon, Fabrice

2015-01-01

Background Since 2003, the tropical arthritogenic chikungunya (CHIK) virus has become an increasingly medical and economic burden in affected areas as it can often result in long-term disabilities. The clinical spectrum of post-CHIK (pCHIK) rheumatic disorders is wide. Evidence-based recommendations are needed to help physicians manage the treatment of afflicted patients. Patients and methods We conducted a 6-year case series retrospective study in Reunion Island of patients referred to a rheumatologist due to continuous rheumatic or musculoskeletal pains that persisted following CHIK infection. These various disorders were documented in terms of their clinical and therapeutic courses. Post-CHIK de novo chronic inflammatory rheumatisms (CIRs) were identified according to validated criteria. Results We reviewed 159 patient medical files. Ninety-four patients (59%) who were free of any articular disorder prior to CHIK met the CIR criteria: rheumatoid arthritis (n=40), spondyloarthritis (n=33), undifferentiated polyarthritis (n=21). Bone lesions detectable by radiography occurred in half of the patients (median time: 3.5 years pCHIK). A positive therapeutic response was achieved in 54 out of the 72 patients (75%) who were treated with methotrexate (MTX). Twelve out of the 92 patients (13%) received immunomodulatory biologic agents due to failure of contra-indication of MTX treatment. Other patients mainly presented with mechanical shoulder or knee disorders, bilateral distal polyarthralgia that was frequently associated with oedema at the extremities and tunnel syndromes. These pCHIK musculoskeletal disorders (MSDs) were managed with pain-killers, local and/or general anti-inflammatory drugs, and physiotherapy. Conclusion Rheumatologists in Reunion Island managed CHIK rheumatic disorders in a pragmatic manner following the outbreak in 2006. This retrospective study describes the common mechanical and inflammatory pCHIK disorders. We provide a diagnostic and therapeutic algorithm to help physicians deal with chronic patients, and to limit both functional and economic impacts. The therapeutic indication of MTX in pCHIK CIR could be approved in future efficacy trials. PMID:25760632

A computational model unifies apparently contradictory findings concerning phantom pain

PubMed Central

Boström, Kim J.; de Lussanet, Marc H. E.; Weiss, Thomas; Puta, Christian; Wagner, Heiko

2014-01-01

Amputation often leads to painful phantom sensations, whose pathogenesis is still unclear. Supported by experimental findings, an explanatory model has been proposed that identifies maladaptive reorganization of the primary somatosensory cortex (S1) as a cause of phantom pain. However, it was recently found that BOLD activity during voluntary movements of the phantom positively correlates with phantom pain rating, giving rise to a model of persistent representation. In the present study, we develop a physiologically realistic, computational model to resolve the conflicting findings. Simulations yielded that both the amount of reorganization and the level of cortical activity during phantom movements were enhanced in a scenario with strong phantom pain as compared to a scenario with weak phantom pain. These results suggest that phantom pain, maladaptive reorganization, and persistent representation may all be caused by the same underlying mechanism, which is driven by an abnormally enhanced spontaneous activity of deafferented nociceptive channels. PMID:24931344

The Role of Inflammation in the Pain, Fatigue, and Sleep Disturbance Symptom Cluster in Advanced Cancer.

PubMed

Kwekkeboom, Kristine L; Tostrud, Lauren; Costanzo, Erin; Coe, Christopher L; Serlin, Ronald C; Ward, Sandra E; Zhang, Yingzi

2018-05-01

Symptom researchers have proposed a model of inflammatory cytokine activity and dysregulation in cancer to explain co-occurring symptoms including pain, fatigue, and sleep disturbance. We tested the hypothesis that psychological stress accentuates inflammation and that stress and inflammation contribute to one's experience of the pain, fatigue, and sleep disturbance symptom cluster (symptom cluster severity, symptom cluster distress) and its impact (symptom cluster interference with daily life, quality of life). We used baseline data from a symptom cluster management trial. Adult participants (N = 158) receiving chemotherapy for advanced cancer reported pain, fatigue, and sleep disturbance on enrollment. Before intervention, participants completed measures of demographics, perceived stress, symptom cluster severity, symptom cluster distress, symptom cluster interference with daily life, and quality of life and provided a blood sample for four inflammatory biomarkers (interleukin-1β, interleukin-6, tumor necrosis factor-α, and C-reactive protein). Stress was not directly related to any inflammatory biomarker. Stress and tumor necrosis factor-α were positively related to symptom cluster distress, although not symptom cluster severity. Tumor necrosis factor-α was indirectly related to symptom cluster interference with daily life, through its effect on symptom cluster distress. Stress was positively associated with symptom cluster interference with daily life and inversely with quality of life. Stress also had indirect effects on symptom cluster interference with daily life, through its effect on symptom cluster distress. The proposed inflammatory model of symptoms was partially supported. Investigators should test interventions that target stress as a contributing factor in co-occurring pain, fatigue, and sleep disturbance and explore other factors that may influence inflammatory biomarker levels within the context of an advanced cancer diagnosis and treatment. Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

A novel antagonist of the prostaglandin E(2) EP(4) receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models.

PubMed

Chen, Q; Muramoto, K; Masaaki, N; Ding, Y; Yang, H; Mackey, M; Li, W; Inoue, Y; Ackermann, K; Shirota, H; Matsumoto, I; Spyvee, M; Schiller, S; Sumida, T; Gusovsky, F; Lamphier, M

2010-05-01

Rheumatoid arthritis (RA) is an autoimmune disorder involving subsets of activated T cells, in particular T helper (Th) 1 and Th17 cells, which infiltrate and damage tissues and induce inflammation. Prostaglandin E(2) (PGE(2)) enhances the Th17 response, exacerbates collagen-induced arthritis (CIA) and promotes inflammatory pain. The current study investigated whether selective antagonism of the PGE(2) EP(4) receptor would suppress Th1/Th17 cell development and inflammatory arthritis in animal models of RA. Effects of PGE(2) and a novel EP(4) receptor antagonist ER-819762 on Th1 differentiation, interleukin-23 (IL-23) production by dendritic cells (DCs), and Th17 development were assessed in vitro. The effect of ER-819762 was evaluated in CIA and glucose-6-phosphate isomerase (GPI)-induced arthritis models. In addition, the effects of ER-819762 on pain were evaluated in a model of chronic inflammatory pain induced by complete Freund's adjuvant (CFA) in the rat. Stimulation of the EP(4) receptor enhanced Th1 differentiation via phosphatidylinositol 3 kinase signalling, selectively promoted Th17 cell expansion, and induced IL-23 secretion by activated DCs, effects suppressed by ER-819762 or anti-PGE(2) antibody. Oral administration of ER-19762 suppressed Th1 and Th17 cytokine production, suppressed disease in collagen- and GPI-induced arthritis in mice, and suppressed CFA-induced inflammatory pain in rats. PGE(2) stimulates EP(4) receptors to promote Th1 differentiation and Th17 expansion and is critically involved in development of arthritis in two animal models. Selective suppression of EP(4) receptor signalling may have therapeutic value in RA both by modifying inflammatory arthritis and by relieving pain.

Cannabinoid receptor 2 agonist attenuates pain related behavior in rats with chronic alcohol/high fat diet induced pancreatitis.

PubMed

Zhang, Liping; Kline, Robert H; McNearney, Terry A; Johnson, Michael P; Westlund, Karin N

2014-11-17

Chronic Pancreatitis (CP) is a complex and multifactorial syndrome. Many contributing factors result in development of dysfunctional pain in a significant number of patients. Drugs developed to treat a variety of pain states fall short of providing effective analgesia for patients with chronic pancreatitis, often providing minimal to partial pain relief over time with significant side effects. Recently, availability of selective pharmacological tools has enabled great advances in our knowledge of the role of the cannabinoid receptors in pathophysiology. In particular, cannabinoid receptor 2 (CB2) has emerged as an attractive target for management of chronic pain, as demonstrated in several studies with inflammatory and neuropathic preclinical pain models. In this study, the analgesic efficacy of a novel, highly selective CB2 receptor agonist, LY3038404 HCl, is investigated in a chronic pancreatitis pain model, induced with an alcohol/high fat (AHF) diet. Rats fed the AHF diet developed visceral pain-like behaviors detectable by week 3 and reached a maximum at week 5 that persists as long as the diet is maintained. Rats with AHF induced chronic pancreatitis were treated with LY3038404 HCl (10 mg/kg, orally, twice a day for 9 days). The treated animals demonstrated significantly alleviated pain related behaviors after 3 days of dosing, including increased paw withdrawal thresholds (PWT), prolonged abdominal withdrawal latencies (ABWL), and decreased nocifensive responses to noxious 44°C hotplate stimuli. Terminal histological analysis of pancreatic tissue sections from the AHF chronic pancreatitis animals demonstrated extensive injury, including a global pancreatic gland degeneration (cellular atrophy), vacuolization (fat deposition), and fibrosis. After the LY3038404 HCl treatment, pancreatic tissue was significantly protected from severe damage and fibrosis. LY3038404 HCl affected neither open field exploratory behaviors nor dark/light box preferences as measures of higher brain and motor functions. LY3038404 HCl, a potent CB2 receptor agonist, possesses tissue protective and analgesic properties without effects on higher brain function. Thus, activation of CB2 receptors is suggested as a potential therapeutic target for visceral inflammation and pain management.

VIPER: Chronic Pain after Amputation: Inflammatory Mechanisms, Novel Analgesic Pathways, and Improved Patient Safety

DTIC Science & Technology

2017-10-01

Through analysis of data obtained in the Molecular Signatures of Chronic Pain Subtypes study termed Veterans Integrated Pain Evaluation Research...immune cells (macrophages) to chronic pain while also evaluating novel analgesics in relevant animal models. The current proposal also attempts to...analysis of data obtained in the Molecular Signatures of Chronic Pain Subtypes study termed Veterans Integrated Pain Evaluation Research (VIPER

Gene transfer of a naked plasmid (pUDK-HGF) encoding human hepatocyte growth factor attenuates skin/muscle incision and retraction-induced chronic post-surgical pain in rats.

PubMed

Hu, C; Lu, Y; Chen, X; Wu, Z; Zhang, Q

2018-05-01

Chronic post-surgical pain (CPSP) remains a major clinical problem and is often refractory to current treatments. New analgesic medications and strategies for pain relief are needed. Hepatocyte growth factor (HGF) is known to be a multi-functional growth factor and regulates various biological activities. We investigated the analgesic effect and underlying mechanism of plasmid pUDK-HGF encoding human HGF gene on CPSP induced by skin/muscle incision and retraction (SMIR) in rats. The possible changes of inflammatory factors, glial cell activation and pain sensitivity after pUDK-HGF administration were investigated by ELISA, western blot and Von Frey tests, respectively. In behavioural assays, we found that a single intramuscular or intrathecal injection of pUDK-HGF significantly attenuated mechanical hypersensitivity to von Frey stimulation of plantar ipsilateral hind paw after SMIR. Intramuscular injection of pUDK-HGF promoted blood flow and proliferation of satellite cells and inhibited inflammatory cells recruitment, collagen accumulation and expression of pronociceptive factors. Intrathecal injection of pUDK-HGF inhibited activation of spinal glial cells and production of inflammatory mediators induced by SMIR. pUDK-HGF has a strong analgesic potency and efficacy in CPSP induced by SMIR in rats. This study highlights a new strategy for the treatment of CPSP. The CPSP occurs following various surgical procedures and remains a major clinical problem due to the lack of study on the mechanisms of CPSP. Our findings provide the first evidence that pUDK-HGF attenuates SMIR-induced pain behaviuors through peripheral or central mechanisms. The peripheral analgesic effect of pUDK-HGF is associated with promoting tissue repair and inhibiting inflammatory response; furthermore, pUDK-HGF inhibits activation of spinal glial cells and overexpression of inflammatory mediators in spinal cord. Therefore, naked pUDK-HGF may be a potential therapeutic strategy for treatment of CPSP in clinic. © 2018 European Pain Federation - EFIC®.

Targeting human Mas-related G protein-coupled receptor X1 to inhibit persistent pain

PubMed Central

Li, Zhe; Tseng, Pang-Yen; Tiwari, Vinod; Xu, Qian; He, Shao-Qiu; Wang, Yan; Zheng, Qin; Han, Liang; Wu, Zhiping; Blobaum, Anna L.; Cui, Yiyuan; Tiwari, Vineeta; Sun, Shuohao; Cheng, Yingying; Huang-Lionnet, Julie H. Y.; Geng, Yixun; Xiao, Bo; Peng, Junmin; Hopkins, Corey; Raja, Srinivasa N.; Guan, Yun; Dong, Xinzhong

2017-01-01

Human Mas-related G protein-coupled receptor X1 (MRGPRX1) is a promising target for pain inhibition, mainly because of its restricted expression in nociceptors within the peripheral nervous system. However, constrained by species differences across Mrgprs, drug candidates that activate MRGPRX1 do not activate rodent receptors, leaving no responsive animal model to test the effect on pain in vivo. Here, we generated a transgenic mouse line in which we replaced mouse Mrgprs with human MrgprX1. This humanized mouse allowed us to characterize an agonist [bovine adrenal medulla 8–22 (BAM8–22)] and a positive allosteric modulator (PAM), ML382, of MRGPRX1. Cellular studies suggested that ML382 enhances the ability of BAM8–22 to inhibit high-voltage-activated Ca2+ channels and attenuate spinal nociceptive transmission. Importantly, both BAM8–22 and ML382 effectively attenuated evoked, persistent, and spontaneous pain without causing obvious side effects. Notably, ML382 by itself attenuated both evoked pain hypersensitivity and spontaneous pain in MrgprX1 mice after nerve injury without acquiring coadministration of an exogenous agonist. Our findings suggest that humanized MrgprX1 mice provide a promising preclinical model and that activating MRGPRX1 is an effective way to treat persistent pain. PMID:28223516

Churg-Strauss Syndrome

MedlinePlus

... Sinus pain and inflammation (sinusitis). You may experience facial pain and develop nasal polyps, which are soft, noncancerous ( ... go away, especially if it's accompanied by persistent facial pain. Also see your doctor if you have asthma ...

An Endocannabinoid Uptake Inhibitor from Black Pepper Exerts Pronounced Anti-Inflammatory Effects in Mice.

PubMed

Reynoso-Moreno, Inés; Najar-Guerrero, Israel; Escareño, Noé; Flores-Soto, Mario Eduardo; Gertsch, Jürg; Viveros-Paredes, Juan Manuel

2017-11-01

Guineensine is a dietary N-isobutylamide widely present in black and long pepper (Piper nigrum and Piper longum) previously shown to inhibit cellular endocannabinoid uptake. Given the role of endocannabinoids in inflammation and pain reduction, here we evaluated guineensine in mouse models of acute and inflammatory pain and endotoxemia. Significant dose-dependent anti-inflammatory effects (95.6 ± 3.1% inhibition of inflammatory pain at 2.5 mg/kg ip and 50.0 ± 15.9% inhibition of edema formation at 5 mg/kg ip) and acute analgesia (66.1 ± 28.1% inhibition at 5.0 mg/kg ip) were observed. Moreover, guineensine inhibited proinflammatory cytokine production in endotoxemia. Intriguingly, guineensine and LPS independently induced catalepsy, but in combination this effect was abolished. Both hypothermia and analgesia were blocked by the CB1 receptor inverse agonist rimonabant, but the pronounced hypolocomotion was CB1 receptor-independent. A subsequent screen of 45 CNS-related receptors, ion channels, and transporters revealed apparent interactions of guineensine with the dopamine transporter DAT, 5HT2A, and sigma receptors, uncovering its prospective polypharmacology. The described potent pharmacological effects of guineensine might relate to the reported anti-inflammatory effects of pepper.

[Peroral and transdermal application of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of regional musculoskeletal pain syndromes].

PubMed

Hodinka, László; Bálint, Géza; Budai, Erika; Géher, Pál; Papp, Renáta; Somogyi, Péter; Szántó, Sándor; Vereckei, Edit

2017-12-01

In this review the available evidences regarding the most frequently applied medication (peroral and transdermal non-steroidal anti-inflammatory agents) for the most frequent musculoskeletal complaints (regional pain syndromes) have been collected for the appropriate medical professionals who are most frequently faced with these conditions (general practitioners, rheumatologists, orthopedics, occupational and sports medicine experts). The special population at risk (with repeated and high energy overuse because of occupational or sport activities) and the pathology of their syndromes are identified. Mode of action, pharmacological properties of the non-steroidal anti-inflammatory drugs and the unwanted effects of their application especially in infants and elderly are highlighted. Recommendations of the general and specific pain management guidelines have been selected and listed in the review. Orv Hetil. 2017; 158(Suppl. 3): 3-30.

Experimental tooth pain elevates substance P and matrix metalloproteinase-8 levels in human gingival crevice fluid.

PubMed

Avellán, Nina-Li; Sorsa, Timo; Tervahartiala, Taina; Forster, Clemens; Kemppainen, Pentti

2008-02-01

Tooth pain can induce a neurogenic inflammatory reaction in gingiva in association with local elevations of matrix metalloproteinase (MMP)-8, which is considered the major tissue destructive protease in gingival crevice fluid (GCF). The pro-inflammatory neuropeptides released by sensory nerves coordinate the activities of the immuno-effector cells and may influence the secretion of MMP-8. With this background, we studied whether experimental tooth pain can trigger changes in GCF levels of the neuropeptide substance P (SP) and MMP-8. The GCF SP levels of stimulated and non-stimulated teeth were analyzed for SP using a competitive enzyme immunoassay (EIA). The GCF MMP-8 levels were determined by quantitative immunofluorometric assay (IFMA). Painful stimulation of the upper central incisor caused significant elevations in GCF SP and MMP-8 levels of the stimulated tooth. At the same time, the GCF SP and MMP-8 levels of non-stimulated control teeth were unchanged. These data indicate that experimental tooth pain can induce local elevations of SP and MMP-8 levels in GCF simultaneously. This supports the possibility of a local neurogenic spread of inflammatory reactions from intrapulpal to surrounding periodontal tissues.

The Ablation or Reduction of Intraoperative Tourniquet Pain with Preoperative Administration of IV Ketorolac Tromethamine

DTIC Science & Technology

1994-08-01

non - steroidal anti - inflammatory drug . Anticipated conclusions of...tromethamine is a nonsteroidal, anti - inflammatory drug (NSAID) that does not have CNS activity. It is a potent analgesic with less anti - inflammatory ...nonsteroidal, anti - inflammatory drug that inhibits prostaglandin production. Administration of ketorolac tromethamine prior to tourniquet inflation

Comparison of the Levels of Pro-Inflammatory Cytokines Released in the Vastus Lateralis Muscle of Patients with Fibromyalgia and Healthy Controls during Contractions of the Quadriceps Muscle – A Microdialysis Study

PubMed Central

Christidis, Nikolaos; Ghafouri, Bijar; Larsson, Anette; Palstam, Annie; Mannerkorpi, Kaisa; Bileviciute-Ljungar, Indre; Löfgren, Monika; Bjersing, Jan; Kosek, Eva; Gerdle, Björn; Ernberg, Malin

2015-01-01

Objective Fibromyalgia is associated with central hyperexcitability, but it is suggested that peripheral input is important to maintain central hyperexcitability. The primary aim was to investigate the levels of pro-inflammatory cytokines released in the vastus lateralis muscle during repetitive dynamic contractions of the quadriceps muscle in patients with fibromyalgia and healthy controls. Secondarily, to investigate if the levels of pro-inflammatory cytokines were correlated with pain or fatigue during these repetitive dynamic contractions. Material and Methods 32 women with fibromyalgia and 32 healthy women (controls) participated in a 4 hour microdialysis session, to sample IL-1β, IL-6, IL-8, and TNF from the most painful point of the vastus lateralis muscle before, during and after 20 minutes of repeated dynamic contractions. Pain (visual analogue scale; 0–100) and fatigue Borg’s Rating of Perceived Exertion Scale; 6–20) were assessed before and during the entire microdialysis session. Results The repetitive dynamic contractions increased pain in the patients with fibromyalgia (P < .001) and induced fatigue in both groups (P < .001). Perceived fatigue was significantly higher among patients with fibromyalgia than controls (P < .001). The levels of IL-1β did not change during contractions in either group. The levels of TNF did not change during contractions in patients with fibromyalgia, but increased in controls (P < .001) and were significantly higher compared to patients with fibromyalgia (P = .033). The levels of IL-6 and IL-8 increased in both groups alike during and after contractions (P’s < .001). There were no correlations between pain or fatigue and cytokine levels after contractions. Conclusion There were no differences between patients with fibromyalgia and controls in release of pro-inflammatory cytokines, and no correlations between levels of pro-inflammatory cytokines and pain or fatigue. Thus, this study indicates that IL-1β, IL-6, IL-8, and TNF do not seem to play an important role in maintenance of muscle pain in fibromyalgia. PMID:26624891

Peripheral analgesic sites of action of anti-inflammatory drugs.

PubMed

Ferreira, S H

2002-07-01

Inflammatory signs and symptoms of redness, swelling, heat and pain are due to the effects of inflammatory mediators released during the inflammatory response. Depending on the type of injurious stimuli and the tissue involved, the array of mediators may differ but eicosanoids are involved in the genesis of inflammatory pain. They are responsible for the hypersensitisation of the nociceptors (allodynialhyperalgesia). The basic mechanism of analgesic action of nonsteroidal anti-inflammatory drugs results from the inhibition of prostaglandin synthesis (prostacyclin or PGE2), thus preventing nociceptor threshold lowering. Because there is a temporal hierarchy in the release of inflammatory mediators, there are several targets for the action of peripheral acting analgesics before and after the inhibition of prostaglandin synthesis. Blockade of the release and inhibition of inducible cyclooxygenase explain the analgesic action of glucocorticoids. Nimesulide also has an inhibitory action on the cascade of hypersensitising cytokines. Some analgesics, such as dipyrone, flurbiprofen or diclofenac, act directly upon ongoing inflammatory hypersensitisation. Those analgesics restore the nociceptor by stimulating the arginine/NO/cGMP/K(ATP) channel pathway.

Epidurals in Pancreatic Resection Outcomes (E-PRO) study: protocol for a randomised controlled trial

PubMed Central

Pak, Linda Ma; Haroutounian, Simon; Hawkins, William G; Worley, Lori; Kurtz, Monika; Frey, Karen; Karanikolas, Menelaos; Swarm, Robert A; Bottros, Michael M

2018-01-01

Introduction Epidural analgesia provides an important synergistic method of pain control. In addition to reducing perioperative opioid consumption, the deliverance of analgesia into the epidural space, effectively creating a sympathetic blockade, has a multitude of additional potential benefits, from decreasing the incidence of postoperative delirium to reducing the development of persistent postsurgical pain (PPSP). Prior studies have also identified a correlation between the use of epidural analgesia and improved oncological outcomes and survival. The aim of this study is to evaluate the effect of epidural analgesia in pancreatic operations on immediate postoperative outcomes, the development of PPSP and oncological outcomes in a prospective, single-blind, randomised controlled trial. Methods The Epidurals in Pancreatic Resection Outcomes (E-PRO) study is a prospective, single-centre, randomised controlled trial. 150 patients undergoing either pancreaticoduodenectomy or distal pancreatectomy will be randomised to receive an epidural bupivacaine infusion following anaesthetic induction followed by continued epidural bupivacaine infusion postoperatively in addition to the institutional standardised pain regimen of hydromorphone patient-controlled analgesia (PCA), acetaminophen and ketorolac (intervention group) or no epidural infusion and only the standardised postoperative pain regimen (control group). The primary outcome was the postoperative opioid consumption, measured in morphine or morphine-equivalents. Secondary outcomes include patient-reported postoperative pain numerical rating scores, trend and relative ratios of serum inflammatory markers (interleukin (IL)-1β, IL-6, tumour necrosis factor-α, IL-10), occurrence of postoperative delirium, development of PPSP as determined by quantitative sensory testing, and disease-free and overall survival. Ethics and dissemination The E-PRO trial has been approved by the institutional review board. Recruitment began in May 2016 and will continue until the end of May 2018. Dissemination plans include presentations at scientific conferences and scientific publications. Trial registration number NCT02681796. PMID:29374667

Therapy Recommendation “Act as Usual” in Patients with Whiplash Injuries QTF I°

PubMed Central

Dehner, Christoph; Kraus, Michael; Schöll, Hendrik; Schneider, Florian; Richter, Peter; Kramer, Michael

2012-01-01

Up to now no therapy study has used the classification system of the Quebec Task Force (QTF) to differentiate between patients with (QTF II°) and without functional disorders (QTF I°). This differentiation seems meaningful, as this difference may be relevant for the correct treatment planning. In this context the effect of the therapy recommendation “act as usual” has been evaluated in a homogeneous patient collective with whiplash injuries QTF I°. 470 patients with acute whiplash injuries had been catched in this study and classified according to the QTF. 359 patients (76.4%) with QTF I° injuries could be identified. Out of that 162 patients were enrolled to the study and received the therapy recommendation “act as usual” and the adapted pain treatment with non-steroidal anti-inflammatory drugs (NSAID). After six months the outcome was evaluated by phone. After injury the median pain score assessed by a visual analogue scale (VAS) was 5.4 (min = 3.3; max = 8.5). After six months 5 of the 162 patients complained intermittent pain symptoms (VAS values < 2). This is consistent with a chronification rate of 3.1%. After injury, the median pain disability index (PDI) was 3.9 (min = 1.9; max = 7.7). After six months 3 of the 162 patients stated persisting disability during sporting and physical activities (VAS values < 1). The therapy recommendation “act as usual” in combination with an adapted pain treatment is sufficient. Usually patients with whiplash injuries QTF I° do not need physical therapy. An escalation of therapy measures should be reserved to patients with complicated healing processes. PMID:23121740

Temporal dynamics of anxiety phenotypes in a dental pulp injury model.

PubMed

Shang, Lin; Xu, Tian-Le; Li, Fei; Su, Jiansheng; Li, Wei-Guang

2015-06-30

Accumulating clinical and preclinical evidence indicates that chronic pain is often comorbid with persistent low mood and anxiety. However, the mechanisms underlying pain-induced anxiety, such as its causality, temporal progression, and relevant neural networks are poorly understood, impeding the development of efficacious therapeutic approaches. Here, we have identified the sequential emergence of anxiety phenotypes in mice subjected to dental pulp injury (DPI), a prototypical model of orofacial pain that correlates with human toothache. Compared with sham controls, mice subjected to DPI by mechanically exposing the pulp to the oral environment exhibited significant signs of anxiogenic effects, specifically, altered behaviors on the elevated plus maze (EPM), novelty-suppressed feeding (NSF) tests at 1 but not 3 days after the surgery. Notably, at 7 and 14 days, the DPI mice again avoided the open arm, center area, and novelty environment in the EPM, open field, and NSF tests, respectively. In particular, DPI-induced social phobia and increased repetitive grooming did not occur until 14 days after surgery, suggesting that DPI-induced social anxiety requires a long time. Moreover, oral administration of an anti-inflammatory drug, ibuprofen, or an analgesic agent, ProTx-II, which is a selective inhibitor of NaV1.7 sodium channels, both significantly alleviated DPI-induced avoidance in mice. Finally, to investigate the underlying central mechanisms, we pharmacologically blocked a popular form of synaptic plasticity with a GluA2-derived peptide, long-term depression, as that treatment significantly prevented the development of anxiety phenotype upon DPI. Together, these results suggest a temporally progressive causal relationship between orofacial pain and anxiety, calling for more in-depth mechanistic studies on concomitant pain and anxiety disorders.

[Expression of hemokinin-1 in rat spinal cord after peripheral inflammation].

PubMed

Ando, Yuko

2009-06-01

Hemokinin-1 (HK-1) is a novel peptide described as a member of the tachykinin family. Substance P (SP), a representative member of the tachykinin family, has been well characterized and is thought to play a part in inflammation and pain. While several studies indicate that HK-1 is involved in inflammation and pain, the biological functions of HK-1 are not fully understood. In the present study we investigated the expression of HK-1 mRNA (TAC4) and SP mRNA (TAC1) in the dorsal spinal cord of rat after inducing peripheral inflammation by administering complete Freund's adjuvant (CFA) into the hind paw, using real-time RT-PCR. In the behavioral studies, the thresholds of withdrawal response of the hind paw to thermal stimulation significantly decreased on the ipsilateral side, but not on the contralateral side, 6 hours after CFA injection and thermal hyperalgesia persisted until 4 days after CFA injection. The level of HK-1 mRNA expression significantly increased on the bilateral sides of the dorsal spinal cord 6 hours after CFA injection and returned to the base level 1 day after injection. On the other hand, the level of SP mRNA expression did not change in the spinal cord 6 hours and 1 day after CFA injection. These results indicate that HK-1 may contribute to inflammatory pain, in the early phase, in a different manner from SP.

Increasing Optimism Protects Against Pain-Induced Impairment in Task-Shifting Performance.

PubMed

Boselie, Jantine J L M; Vancleef, Linda M G; Peters, Madelon L

2017-04-01

Persistent pain can lead to difficulties in executive task performance. Three core executive functions that are often postulated are inhibition, updating, and shifting. Optimism, the tendency to expect that good things happen in the future, has been shown to protect against pain-induced performance deterioration in executive function updating. This study tested whether this protective effect of a temporary optimistic state by means of a writing and visualization exercise extended to executive function shifting. A 2 (optimism: optimism vs no optimism) × 2 (pain: pain vs no pain) mixed factorial design was conducted. Participants (N = 61) completed a shifting task once with and once without concurrent painful heat stimulation after an optimism or neutral manipulation. Results showed that shifting performance was impaired when experimental heat pain was applied during task execution, and that optimism counteracted pain-induced deterioration in task-shifting performance. Experimentally-induced heat pain impairs shifting task performance and manipulated optimism or induced optimism counteracted this pain-induced performance deterioration. Identifying psychological factors that may diminish the negative effect of persistent pain on the ability to function in daily life is imperative. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Medic - Abdominal Pain: A Decision Support Program for the Management of Acute Abdominal Pain. (User’s Manual)

DTIC Science & Technology

1989-10-11

presence of diverticular disease does not preclude development of acute appendicitis concxitantly. The initial medical treatment is the same as for...appendicitis see APPENDICITIS. c. Pelvic inflammatory disease see PID. d. Diverticulitis most commonly involves the descending (left) colon . Symptoms...Five additional categories are included for female patients. These are: pelvic inflammatory disease (PID), urinary tract infection (UTI), ovarian cyst

Role overload, pain and physical dysfunction in early rheumatoid or undifferentiated inflammatory arthritis in Canada.

PubMed

Mustafa, Sally Sabry; Looper, Karl Julian; Zelkowitz, Phyllis; Purden, Margaret; Baron, Murray

2012-05-03

Inflammatory arthritis impairs participation in societal roles. Role overload arises when the demands by a given role set exceed the resources; time and energy, to carry out the required tasks. The present study examines the association between role overload and disease outcomes in early inflammatory arthritis (EIA). Patients (n = 104) of 7.61 months mean duration of inflammatory arthritis completed self-report questionnaires on sociodemographics, disease characteristics and role overload. Pain was assessed using the Short Form McGill Pain Questionnaire (MPQ) and physical functioning was measured with the Medical Outcomes Study Short Form 36 (SF-36) physical functioning score. Role overload was measured by the Role Overload Scale. Patients indicated the number of social roles they occupied from a total of the three typical roles; marital, parental and paid work. Participants' mean age was 56 years and 70.2% were female. Role overload was not correlated to the number of social roles, however, it was positively associated with pain (p = 0.004) and negatively associated with physical functioning (p = 0.001). On multivariate analysis, role overload was negatively associated with physical functioning after controlling for the relevant sociodemographic variables. This study identifies a possible reciprocal relationship between role overload and physical functioning in patients with EIA.

[Juvenile idiopathic arthritis with dry synovitis: clinical case and review of literature].

PubMed

Dias, Bruno Leonardo Scofano; Imamura, Erica Ueno; Izumi, Ana Paula; Pinheiro, Lúcia Virgínia de Melo; Borigato, Eliana Valverde Magro

2009-01-01

Juvenile idiopathic arthritis is a term that encompasses all forms of arthritis that begin before the age of 16 years, persist for more than 6 weeks and are of unknown cause. Dry synovitis is still not completely understood nor commonly described. It is associated with juvenile idiopathic arthritis and must be considered in patients with minimal swelling but pain and stiffness along with flexion contractures as well as other evidence of an inflammatory process (lab changes and/or other symptoms, such as uveitis or rash), and often follow a destructive course. The authors present a case of a brazilian child with a rheumatoid factor- negative polyarthritis compatible with the subtype dry synovitis, who had great clinical and functional improvement after participation in rehabilitation activities and beginning of pharmacological treatment usually used in Juvenile idiopathic arthritis, including immunossuppressive therapy.

Mechanisms of Corneal Pain and Implications for Postoperative Pain After Laser Correction of Refractive Errors.

PubMed

Garcia, Renato; de Andrade, Daniel C; Teixeira, Manoel J; Nozaki, Siro S; Bechara, Samir J

2016-05-01

The cornea is the target of most surgeries for refractive disorders, as myopia. It is estimated that almost 1 million patients undergo corneal refractive surgery each year in the United States. Refractive surgery includes photorefractive keratectomy (PRK) that produces intense postoperative pain. This review presents the main pain mechanisms behind PRK-related pain and the available therapeutic options for its management. Data sources included literature of cornea anatomy, treatment of PRK postoperative pain, mechanisms of corneal pain, in 3 electronic databases: Pubmed, Scopus, and Web of Science. Only double-blinded controlled trials on pain control after PRK were selected to show the endpoints, treatment, and control strategies. A total of 18 double-blind, controlled trials were identified. These studies have shown the use of topical nonsteroidal anti-inflammatory drugs, topical steroidal anti-inflammatory drugs, systemic analgesics, cold balanced saline solution, topical anesthetic, gabapentin, and morphine to treat postoperative pain in PRK. The percentage of responders has seldom been reported, and few studies allow for the formal calculation of the number necessary to treat. Postoperative intense pain after PRK laser surgery remains the main challenge to its widespread use for the correction of refractive errors.

Clinical and psychological moderators of the effect of mindfulness-based cognitive therapy on persistent pain in women treated for primary breast cancer - explorative analyses from a randomized controlled trial.

PubMed

Johannsen, M; O'Toole, M S; O'Connor, M; Jensen, A B; Zachariae, R

2017-02-01

Mindfulness-based intervention has been found efficacious in reducing persistent pain in women treated for breast cancer. Little, however, is known about possible moderators of the effect. We explored clinical and psychological moderators of the effect on pain intensity previously found in a randomized controlled trial of mindfulness-based cognitive therapy (MBCT) with women treated for breast cancer with persistent pain. A total of 129 women treated for breast cancer reporting persistent pain were randomized to MBCT or a wait-list control. The primary outcome of pain intensity (11-point numeric rating scale) was measured at baseline, post-intervention, three, and six months follow-up. Proposed clinical moderators included age, axillary lymph node dissection (ALND), radiotherapy, and endocrine treatment. Psychological moderators included psychological distress [the Hospital Anxiety and Depression Scale (HADS)], the adult attachment dimensions anxiety and avoidance [the Experiences in Close Relationships Short Form (the ECR-SF)], and alexithymia [the Toronto Alexithymia Scale (TAS-20)]. Multi-level models were used to test moderation effects over time, i.e. time × group × moderator. Only attachment avoidance (p = 0.03, d = 0.36) emerged as a statistically significant moderator. Higher levels of attachment avoidance predicted a larger effect of MBCT in reducing pain intensity compared with lower levels attachment avoidance. None of the remaining psychological or clinical moderators reached statistical significance. However, based on the effect size, radiotherapy (p = 0.075, d = 0.49) was indicated as a possible clinical moderator of the effect, with radiotherapy being associated with a smaller effect of MBCT on pain intensity over time compared with no radiotherapy. Attachment avoidance, and potentially radiotherapy, may be clinically relevant factors for identifying the patients who may benefit most from MBCT as a pain intervention. Due to the exploratory nature of the analyses, the results should be considered preliminary.

Pharmacogenetics in obstetric anesthesia.

PubMed

Landau, Ruth; Kraft, John C

2010-06-01

Genomic research in pain, anesthesia and analgesia generated some hope that pharmacogenetics may guide anesthesiologists to provide effective medicine in a 'tailored' manner. Within the field of obstetric anesthesia, relatively few studies have evaluated the effect of polymorphisms on the perception of labor or postcesarean pain or the response to analgesics for childbirth. Because of the multifactorial nature of labor and delivery pain and particularly challenging clinical context, many consider that 'titration of drugs to the desired effect works just fine'. With recent evidence highlighting an association between severe postdelivery pain and persistent pain, early recognition of an increased susceptibility for acute pain has become particularly relevant. Neuraxial labor analgesia is influenced by a common polymorphism of the mu-opioid receptor gene. This polymorphism also affects the analgesic response to systemic opioids for postcesarean pain and other types of surgeries. Finally, the risk for persistent pain after cesarean deliveries may be associated with a certain genetic profile. Although still premature to anticipate clinical implications and a change in practice based on these recent discoveries, genetic variability clearly appears to affect pain perception, response to analgesics and predisposition for the development of chronic pain.

Post-traumatic arthritis: overview on pathogenic mechanisms and role of inflammation

PubMed Central

Punzi, Leonardo; Galozzi, Paola; Luisetto, Roberto; Favero, Marta; Ramonda, Roberta; Oliviero, Francesca; Scanu, Anna

2016-01-01

Post-traumatic arthritis (PTA) develops after an acute direct trauma to the joints. PTA causes about 12% of all osteoarthritis cases, and a history of physical trauma may also be found in patients with chronic inflammatory arthritis. Symptoms include swelling, synovial effusion, pain and sometimes intra-articular bleeding. Usually, PTA recoveries spontaneously, but the persistence of symptoms after 6 months may be considered pathological and so-called chronic PTA. A variety of molecular, mechanobiological and cellular events involved in the pathogenesis and the progression of PTA have been identified. The activation of inflammatory mechanisms during the PTA acute phase appears to play a critical role in the chronic disease onset. Human studies and experimental models have revealed that a series of inflammatory mediators are released in synovial fluid immediately after the joint trauma. These molecules have been proposed as markers of disease and as a potential target for the development of specific and preventative interventions. Currently, chronic PTA cannot be prevented, although a large number of agents have been tested in preclinical studies. Given the relevance of inflammatory reaction, anticytokines therapy, in particular the inhibition of interleukin 1 (IL-1), seems to be the most promising strategy. At the present time, intra-articular injection of IL-1 receptor antagonist is the only anticytokine approach that has been used in a human study of PTA. Despite the fact that knowledge in this area has increased in the past years, the identification of more specific disease markers and new therapeutic opportunities are needed. PMID:27651925

Comparative efficacy of oral meloxicam and phenylbutazone in 2 experimental pain models in the horse

PubMed Central

Banse, Heidi; Cribb, Alastair E.

2017-01-01

The efficacy of oral phenylbutazone [PBZ; 4.4 mg/kg body weight (BW), q12h], a non-selective non-steroidal anti-inflammatory drug (NSAID), and oral meloxicam (MXM; 0.6 mg/kg BW, q24h), a COX-2 selective NSAID, were evaluated in 2 experimental pain models in horses: the adjustable heart bar shoe (HBS) model, primarily representative of mechanical pain, and the lipopolysaccharide-induced synovitis (SYN) model, primarily representative of inflammatory pain. In the HBS model, PBZ reduced multiple indicators of pain compared with the placebo and MXM. Meloxicam did not reduce indicators of pain relative to the placebo. In the SYN model, MXM and PBZ reduced increases in carpal skin temperature compared to the placebo. Meloxicam reduced lameness scores and lameness-induced changes in head movement compared to the placebo and PBZ. Phenylbutazone reduced lameness-induced change in head movement compared to the placebo. Overall, PBZ was more effective than MXM at reducing pain in the HBS model, while MXM was more effective at reducing pain in the SYN model at the oral doses used. PMID:28216685

Does thalidomide have an analgesic effect? Current status and future directions.

PubMed

Goli, Veeraindar

2007-04-01

Dramatic relief of pain and life-altering changes in quality of life in some patients treated with immunomodulators such as thalidomide compel us to look more closely at unconventional mechanisms that may be involved in propagation of persistent pain. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 are the cytokines with the most evidence in pain modulation. TNF-alpha and IL-1beta seem to initiate neuropathic pain, IL-6 maintains such pain, and IL-10 inhibits this persistent pain. Thalidomide was found to be effective in animal models by inhibiting TNF-alpha production. Several case reports and case series in humans have demonstrated mixed results, with some patients having dramatic responses, especially in chronic intractable conditions such as complex regional pain syndrome. Thalidomide may be an alternative for some patients with intractable pain. However, use of thalidomide is limited by its neurotoxic and teratogenic effects. Newer analogues may significantly improve the risk/benefit of using such immunomodulators.

The effects of lumbar extensor strength on disability and mobility in patients with persistent low back pain.

PubMed

Helmhout, Pieter H; Witjes, Marloes; Nijhuis-VAN DER Sanden, Ria W; Bron, Carel; van Aalst, Michiel; Staal, J Bart

2017-04-01

It is assumed that low back pain patients who use pain-avoiding immobilizing strategies may benefit from specific back flexion and extension exercises aimed at reducing sagittal lumbar hypomobility. The aim of this study was to test this potential working mechanism in chronic low back pain patients undergoing lumbar extensor strengthening training. A single-group prospective cohort design was used in this study. Patients with persistent low back complaints for at least 2 years were recruited at a specialized physical therapy clinics center. They participated in a progressive 11-week lumbar extensor strength training program, once a week. At baseline, sagittal lumbar mobility in flexion and extension was measured with a computer-assisted inclinometer. Self-rated pain intensity was measured using a visual analogue scale, back-specific functional status was assessed with the Quebec Back Pain Disability Scale and the Patient Specific Complains questionnaire. Statistically significant improvements were found in pain (28% decrease) and functional disability (23% to 36% decrease). Most progress was seen in the first 5 treatment weeks. Lumbar mobility in flexion showed non-significant increases over time (+12%). Pre-post treatment changes in flexion and extension mobility did not contribute significantly to the models. The retained factors together explained 15% to 48% of the variation in outcome. Specific lumbar strengthening showed clinically relevant improvements in pain and disability in patients with persistent chronic low back pain. These improvements did not necessarily relate to improvements in lumbar mobility. Parameters representing other domains of adaptations to exercise may be needed to evaluate the effects of back pain management.

Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits.

PubMed

Hashmi, Javeria A; Baliki, Marwan N; Huang, Lejian; Baria, Alex T; Torbey, Souraya; Hermann, Kristina M; Schnitzer, Thomas J; Apkarian, A Vania

2013-09-01

Chronic pain conditions are associated with abnormalities in brain structure and function. Moreover, some studies indicate that brain activity related to the subjective perception of chronic pain may be distinct from activity for acute pain. However, the latter are based on observations from cross-sectional studies. How brain activity reorganizes with transition from acute to chronic pain has remained unexplored. Here we study this transition by examining brain activity for rating fluctuations of back pain magnitude. First we compared back pain-related brain activity between subjects who have had the condition for ∼2 months with no prior history of back pain for 1 year (early, acute/subacute back pain group, n = 94), to subjects who have lived with back pain for >10 years (chronic back pain group, n = 59). In a subset of subacute back pain patients, we followed brain activity for back pain longitudinally over a 1-year period, and compared brain activity between those who recover (recovered acute/sub-acute back pain group, n = 19) and those in which the back pain persists (persistent acute/sub-acute back pain group, n = 20; based on a 20% decrease in intensity of back pain in 1 year). We report results in relation to meta-analytic probabilistic maps related to the terms pain, emotion, and reward (each map is based on >200 brain imaging studies, derived from neurosynth.org). We observed that brain activity for back pain in the early, acute/subacute back pain group is limited to regions involved in acute pain, whereas in the chronic back pain group, activity is confined to emotion-related circuitry. Reward circuitry was equally represented in both groups. In the recovered acute/subacute back pain group, brain activity diminished in time, whereas in the persistent acute/subacute back pain group, activity diminished in acute pain regions, increased in emotion-related circuitry, and remained unchanged in reward circuitry. The results demonstrate that brain representation for a constant percept, back pain, can undergo large-scale shifts in brain activity with the transition to chronic pain. These observations challenge long-standing theoretical concepts regarding brain and mind relationships, as well as provide important novel insights regarding definitions and mechanisms of chronic pain.

Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits

PubMed Central

Hashmi, Javeria A.; Baliki, Marwan N.; Huang, Lejian; Baria, Alex T.; Torbey, Souraya; Hermann, Kristina M.; Schnitzer, Thomas J.; Apkarian, A. Vania

2013-01-01

Chronic pain conditions are associated with abnormalities in brain structure and function. Moreover, some studies indicate that brain activity related to the subjective perception of chronic pain may be distinct from activity for acute pain. However, the latter are based on observations from cross-sectional studies. How brain activity reorganizes with transition from acute to chronic pain has remained unexplored. Here we study this transition by examining brain activity for rating fluctuations of back pain magnitude. First we compared back pain-related brain activity between subjects who have had the condition for ∼2 months with no prior history of back pain for 1 year (early, acute/subacute back pain group, n = 94), to subjects who have lived with back pain for >10 years (chronic back pain group, n = 59). In a subset of subacute back pain patients, we followed brain activity for back pain longitudinally over a 1-year period, and compared brain activity between those who recover (recovered acute/sub-acute back pain group, n = 19) and those in which the back pain persists (persistent acute/sub-acute back pain group, n = 20; based on a 20% decrease in intensity of back pain in 1 year). We report results in relation to meta-analytic probabilistic maps related to the terms pain, emotion, and reward (each map is based on >200 brain imaging studies, derived from neurosynth.org). We observed that brain activity for back pain in the early, acute/subacute back pain group is limited to regions involved in acute pain, whereas in the chronic back pain group, activity is confined to emotion-related circuitry. Reward circuitry was equally represented in both groups. In the recovered acute/subacute back pain group, brain activity diminished in time, whereas in the persistent acute/subacute back pain group, activity diminished in acute pain regions, increased in emotion-related circuitry, and remained unchanged in reward circuitry. The results demonstrate that brain representation for a constant percept, back pain, can undergo large-scale shifts in brain activity with the transition to chronic pain. These observations challenge long-standing theoretical concepts regarding brain and mind relationships, as well as provide important novel insights regarding definitions and mechanisms of chronic pain. PMID:23983029

Still's Disease in a Pediatric Patient after Liver Transplantation.

PubMed

Meza, Juan-Carlos; Muñoz-Buitrón, Evelyn; Bonilla-Abadía, Fabio; Cañas, Carlos Alberto; Tobón, Gabriel J

2013-01-01

Still's disease (SD) is a multisystemic inflammatory disease characterized by persistent arthritis and in many cases with fever of unknown origin. Diagnosis of SD is challenging because of nonspecific characteristics and especially in the case of a patient with solid organ transplantation and immunosuppressive therapy where multiple causes of fever are possible. There is no diagnostic test for SD, even though some useful diagnostic criteria or laboratory findings, such as serum ferritin levels, have been proposed, and useful imaging studies for the diagnosis or followup of SD have not been developed. We report the case of a 9-year-old child who presented with high grade fever associated with joint pain after a history of liver transplantation and immunosuppressive therapy. Laboratory tests showed increased acute phase reactants, elevated ferritin, and leukocytosis. An 18 F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) was performed identifying abnormal hypermetabolic areas localized in spleen, transplanted liver, and bone marrow secondary to inflammatory process. All infectious, autoimmune, and malignant causes were ruled out. A diagnosis of SD was performed and a steroid-based regimen was initiated with adequate response and no evidence of recurrence. To our knowledge this is the first case of SD following a solid organ transplant.

Decreased microRNA-125a-3p contributes to upregulation of p38 MAPK in rat trigeminal ganglions with orofacial inflammatory pain.

PubMed

Dong, Yingchun; Li, Pengfei; Ni, Yanhong; Zhao, Junjie; Liu, Zhiqiang

2014-01-01

Orofacial inflammatory pain is a difficult clinical problem, and the specific molecular mechanisms for this pain remain largely unexplained. The present study aimed to determine the differential expression of microRNAs (miRNAs) and disclose the underlying role of miR-125a-3p in orofacial inflammatory pain induced by complete Freund's adjuvant (CFA). Thirty-two differentially expressed miRNAs were first screened using a microarray chip in ipsilateral trigeminal ganglions (TGs) following CFA injection into the orofacial skin innervated by trigeminal nerve, and a portion of them, including miR-23a*, -24-2*, -26a, -92a, -125a-3p, -183 and -299 were subsequently selected and validated by qPCR. The target genes were predicted based on the miRWalk website and were further analyzed by gene ontology (GO). Further studies revealed miR-125a-3p expression was down-regulated, whereas both the expression of p38 MAPK (mitogen-activated protein kinase) alpha and CGRP (calcitonin gene-related peptide) were up-regulated in ipsilateral TGs at different time points after CFA injection compared with control. Furthermore, mechanistic study revealed that miR-125a-3p negatively regulates p38 alpha gene expression and is positively correlated with the head withdrawal threshold reflecting pain. Luciferase assay showed that binding of miR-125a-3p to the 3'UTR of p38 alpha gene suppressed the transcriptional activity, and overexpression of miR-125a-3p significantly inhibited the p38 alpha mRNA level in ND8/34 cells. Taken together, our results show that miR-125a-3p is negatively correlated with the development and maintenance of orofacial inflammatory pain via regulating p38 MAPK.

Lipopolysaccharide-mediated inflammatory priming potentiates painful post-traumatic trigeminal neuropathy.

PubMed

Boucher, Yves; Moreau, Nathan; Mauborgne, Annie; Dieb, Wisam

2018-06-18

We explored the molecular and behavioral effects of a perineural Lipopolysaccharide (LPS)-mediated inflammatory priming on the development and maintenance of painful post-traumatic trigeminal neuropathy (PPTTN) following infra-orbital nerve chronic constriction injury (CCI-IoN) in rats. Rats were pretreated with repetitive perineural injections in the vicinity of the IoN of either LPS or vehicle (Vhcl) before being submitted to CCI-IoN. Orofacial pain-like behaviors (response to Von Frey Filament testing and spontaneous isolated face grooming) were measured during the period of LPS injections (three weeks) and following CCI-IoN surgery (two weeks). Local LPS administration induced an early pain-like behavior (i.e. an increase in spontaneous pain [SP] or mechanical static allodynia [MSA]) in both conditions, and following CCI-IoN, MSA and SP developed earlier and more severely in LPS-pretreated rats than in the control group. Ipsilateral increases of key neuropathic pain mRNA markers in the IoN parenchyma, trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) were observed in CCI-IoN injured animals as compared to controls. Although no significant molecular differences could be observed within the IoN parenchyma between LPS and Vhcl-pretreated animals, a significant increase of key inflammatory cytokine Interleukin 1 beta (IL - 1β) could be found in the TG of LPS-pretreated CCI-injured animals versus controls. Finally, a higher increase of inducible nitric oxide synthase (iNOS) in ipsilateral Sp5C of LPS-pretreated animals was observed as compared to Sp5C of Vhcl-pretreated animals. These results suggest a key role of inflammatory priming in the development and maintenance of PPTTN implicating IL-1β/iNOS-dependent central sensitization mechanisms. Copyright © 2018. Published by Elsevier Inc.

TRPM8 is the Principal Mediator of Menthol-induced Analgesia of Acute and Inflammatory Pain

PubMed Central

Liu, Boyi; Fan, Lu; Balakrishna, Shrilatha; Sui, Aiwei; Morris, John B.; Jordt, Sven-Eric

2013-01-01

Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat and inflammation (complete Freund's adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, while other analgesics (acetaminophen) remained effective. Loss of L-menthol-induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol and WS-12 induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively with diminished side effects. PMID:23820004

Chrysophyllum cainito leaves are effective against pre-clinical chronic pain models: Analysis of crude extract, fraction and isolated compounds in mice.

PubMed

Meira, Nicole Anzanelo; Rocha, Lilian W; da Silva, Gislaine F; Quintal, Zhelmy Martin; Delle Monache, Franco; Cechinel Filho, Valdir; Quintão, Nara Lins Meira

2016-05-26

Chrysophyllum cainito L. (Sapotaceae), commonly known as caimito or star apple, is a neotropical tree valued for its ornamental quality and edible fruits. Besides its culinary use, the leaves are also popularly used to treat diabetes mellitus and several inflammatory diseases. This study aimed to complement previous data obtained about the anti-hypersensitivity effects of the crude methanol extract (CME), CHCl3 fraction and isolated compounds obtained from C. cainito. The CME, CHCl3 fraction and two isolated triterpenes identified as 3β-Lup-20(29)-en-3-yl acetate (1) and Lup-20(29)-en-3β-O-hexanoate (2) were evaluated regarding their effects using clinical pain models, such as post-operative, inflammatory and neuropathic pain. Acute inflammatory pain models induced by PGE2, epinephrine, LPS and CFA were also used to improve the knowledge about the mechanism of action. The animals treated with the CME and submitted to PGE2, epinephrine, LPS or CFA had the mechanical hypersensitivity significantly reduced. When repeatedly administered, the CME enhanced the mechanical withdrawal threshold of mice submitted to post-operative pain model, CFA-induced chronic inflammatory pain and two different models of neuropathic pain. In turn, the CHCl3 fraction presented anti-hypersensitivity effect against epinephrine- or LPS-induced hypersensitivity, with a more prominent activity in both the neuropathic pain models. The compound 1 seems to present the same profile of the CHCl3, whereas compound 2 exhibited activity similar to the CME. This data suggests that the CME effect involves interference in the production, release or action of some chemical mediators, such as PGE2, sympathetic amines, cytokines, etc. Part of these effects was observed with the CHCl3 fraction, emphasizing the prominent inhibition of neuropathic pain. The results also demonstrated that part of the CME effects are due to the presence of the triterpenes 1 and 2, but it is important to mention that we cannot discard the effects of countless other compounds presented in the crude extract, acting in a synergic way. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

American football and other sports injuries may cause migraine/persistent pain decades later and can be treated successfully with electrical twitch-obtaining intramuscular stimulation (ETOIMS).

PubMed

Chu, J; McNally, S; Bruyninckx, F; Neuhauser, D

2017-04-01

Autonomous twitch elicitation at myofascial trigger points from spondylotic radiculopathies-induced denervation supersensitivity can provide favourable pain relief using electrical twitch-obtaining intramuscular stimulation (ETOIMS). To provide objective evidence that ETOIMS is safe and efficacious in migraine and persistent pain management due to decades-old injuries to head and spine from paediatric American football. An 83-year-old mildly hypertensive patient with 25-year history of refractory migraine and persistent pain self-selected to regularly receive fee-for-service ETOIMS 2/week over 20 months. He had 180 sessions of ETOIMS. Pain levels, blood pressure (BP) and heart rate/pulse were recorded before and immediately after each treatment alongside highest level of clinically elicitable twitch forces/session, session duration and intervals between treatments. Twitch force grades recorded were from 1 to 5, grade 5 twitch force being strongest. Initially, there was hypersensitivity to electrical stimulation with low stimulus parameters (500 µs pulse-width, 30 mA stimulus intensity, frequency 1.3 Hz). This resolved with gradual stimulus increments as tolerated during successive treatments. By treatment 27, autonomous twitches were noted. Spearman's correlation coefficients showed that pain levels are negatively related to twitch force, number of treatments, treatment session duration and directly related to BP and heart rate/pulse. Treatment numbers and session durations directly influence twitch force. At end of study, headaches and quality of life improved, hypertension resolved and antihypertensive medication had been discontinued. Using statistical process control methodology in an individual patient, we showed long-term safety and effectiveness of ETOIMS in simultaneous diagnosis, treatment, prognosis and prevention of migraine and persistent pain in real time obviating necessity for randomised controlled studies.

The health-seeking behaviours of first-time mothers with persistent pelvic girdle pain after childbirth in Ireland: A descriptive qualitative study.

PubMed

Wuytack, Francesca; Curtis, Elizabeth; Begley, Cecily

2015-11-01

to explore the health-seeking behaviours of primiparous women with pelvic girdle pain persisting for more than three months post partum. a descriptive qualitative design involving face-to-face semi-structured interviews following institutional ethical approval. Transcripts were analysed using thematic analysis. an urban hospital in Ireland. a purposive sample of 23 consenting first-time mothers with pelvic girdle pain persisting for at least three months post partum. 'they didn't ask, I didn't tell' was a key theme, which included emerging categories of a perceived lack of follow-up post partum, and feeling ignored by healthcare professionals. The theme 'Seeking advice and support' describes women's role of talking to others, and triggers and barriers to getting help. 'Coping strategies' was the third theme emerging from the interviews, whereby participants described different strategies they used to deal with their symptoms, although many expressed uncertainty about what to do or who to see. our findings show the importance of appropriate information and follow-up care for women with pelvic girdle pain and highlight barriers they encounter in seeking help. They also question the duration of postnatal care as participants felt that postnatal care was stopped too early. The findings may assist maternity care providers in addressing mothers' expectations and needs related to persistent pelvic girdle pain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nociceptor Sensitization Depends on Age and Pain Chronicity123

PubMed Central

Dodge, Amanda K.

2016-01-01

Abstract Peripheral inflammation causes mechanical pain behavior and increased action potential firing. However, most studies examine inflammatory pain at acute, rather than chronic time points, despite the greater burden of chronic pain on patient populations, especially aged individuals. Furthermore, there is disagreement in the field about whether primary afferents contribute to chronic pain. Therefore, we sought to evaluate the contribution of nociceptor activity to the generation of pain behaviors during the acute and chronic phases of inflammation in both young and aged mice. We found that both young (2 months old) and aged (>18 months old) mice exhibited prominent pain behaviors during both acute (2 day) and chronic (8 week) inflammation. However, young mice exhibited greater behavioral sensitization to mechanical stimuli than their aged counterparts. Teased fiber recordings in young animals revealed a twofold mechanical sensitization in C fibers during acute inflammation, but an unexpected twofold reduction in firing during chronic inflammation. Responsiveness to capsaicin and mechanical responsiveness of A-mechanonociceptor (AM) fibers were also reduced chronically. Importantly, this lack of sensitization in afferent firing during chronic inflammation occurred even as these inflamed mice exhibited continued behavioral sensitization. Interestingly, C fibers from inflamed aged animals showed no change in mechanical firing compared with controls during either the acute or chronic inflammatory phases, despite strong behavioral sensitization to mechanical stimuli at these time points. These results reveal the following two important findings: (1) nociceptor sensitization to mechanical stimulation depends on age and the chronicity of injury; and (2) maintenance of chronic inflammatory pain does not rely on enhanced peripheral drive. PMID:26866058

The aetiopathogenesis of fatigue: unpredictable, complex and persistent

PubMed Central

Clark, James E.; Fai Ng, W.; Watson, Stuart; Newton, Julia L.

2016-01-01

Background Chronic fatigue syndrome is a common condition characterized by severe fatigue with post-exertional malaise, impaired cognitive ability, poor sleep quality, muscle pain, multi-joint pain, tender lymph nodes, sore throat or headache. Its defining symptom, fatigue is common to several diseases. Areas of agreement Research has established a broad picture of impairment across autonomic, endocrine and inflammatory systems though progress seems to have reached an impasse. Areas of controversy The absence of a clear consensus view of the pathophysiology of fatigue suggests the need to switch from a focus on abnormalities in one system to an experimental and clinical approach which integrates findings across multiple systems and their constituent parts and to consider multiple environmental factors. Growing points We discuss this with reference to three key factors, non-determinism, non-reductionism and self-organization and suggest that an approach based on these principles may afford a coherent explanatory framework for much of the observed phenomena in fatigue and offers promising avenues for future research. Areas timely for developing research By adopting this approach, the field can examine issues regarding aetiopathogenesis and treatment, with relevance for future research and clinical practice. PMID:26872857

Burning Mouth Syndrome: A Review of the Etiopathologic Factors and Management.

PubMed

Vellappally, Sajith

2016-02-01

Burning mouth syndrome (BMS) is characterized by pain in the mouth with or with no inflammatory signs and no specific lesions. Synonyms found in literature include glossodynia, oral dysesthesia, glossopyrosis, glossalgia, stomatopyrosis, and stomatodynia. Burning mouth syndrome generally presents as a triad: Mouth pain, alteration in taste, and altered salivation, in the absence of visible mucosal lesions in the mouth. The syndrome generally manifests spontaneously, and the discomfort is typically of a continuous nature but increases in intensity during evening and at night. The etiopathogenesis seems to be complex and in a large number of patients probably involves interactions among local, systemic, and/or psychogenic factors. The differential diagnosis requires the exclusion of oral mucosal lesions or blood test alterations that can produce burning mouth sensation. Management is always based on the etiological agents involved. If burning persists after local or systemic conditions are treated, then treatment is aimed at controlling neuropathic symptoms. Treatment of BMS is still unsatisfactory, and there is no definitive cure. As a result, a multidisciplinary approach is required to bring the condition under better control. The aim of this review was to discuss several aspects of BMS, update current knowledge, and provide guidelines for patient management.

Inflammatory Mediators and Pain in the First Year After Acute Episode of Low-Back Pain in Elderly Women: Longitudinal Data from Back Complaints in the Elders-Brazil.

PubMed

Queiroz, Bárbara Zille; Pereira, Daniele Sirineu; Rosa, Nayza Maciel de Britto; Lopes, Renata Antunes; Andrade, André Gustavo Pereira; Felício, Diogo Carvalho; Jardim, Renata Muniz Freire Vinhal Siqueira; Leopoldino, Amanda Aparecida Oliveira; Silva, Juscélio Pereira; Pereira, Leani Souza Máximo

2017-08-01

The aims of this study were to determine the course of plasma levels of inflammatory mediators (interleukin 6 [IL-6], tumor necrosis factor α [TNF-α], soluble TNF receptor 1 [sTNF-R1]) and the severity of low-back pain (LBP) over 6 to 12 months after an acute episode of LBP in elderly women and to establish an association between inflammatory mediators and LBP recovery. This was a longitudinal study of a subsample (155 elderly women with acute LBP, aged ≥65 years) of the international Back Complaints in the Elders cohort study. Plasma levels of IL-6, TNF-α, and sTNF-R1 were measured using enzyme-linked immunosorbent assays and pain severity using the numerical pain scale. There was a decrease in the severity of LBP (P = 0.033) and in the levels of IL-6 and TNF-α (P < 0.001) and an increase in sTNF-R1 (P < 0.001) in the first year after an acute episode of LBP. The probability of occurrence of pain relief at the 12-month follow-up was 2.22 times higher in elderly women who had low levels of IL-6 (<1.58 pg/mL) at baseline. Our findings showed a relationship between inflammation and LBP by establishing that low IL-6 plasma levels preceded outcome (LBP recovery), supporting the concept that proinflammatory cytokines promote pain.

Experiences of First-Time Mothers With Persistent Pelvic Girdle Pain After Childbirth: Descriptive Qualitative Study.

PubMed

Wuytack, Francesca; Curtis, Elizabeth; Begley, Cecily

2015-10-01

Pelvic girdle pain (PGP) is common during pregnancy and negatively affects women's lives. When PGP persists after the birth, the way it affects women's lives may change, particularly for first-time mothers as they adjust to motherhood, yet the experiences of women with persistent PGP remain largely unexplored. The objective of this study was to explore primiparous women's experiences of persistent PGP and its impact on their lives postpartum, including caring for their infant and their parental role. This was a descriptive qualitative study. Following institution ethical approval, 23 consenting primiparous women with PGP that had started during pregnancy and persisted for at least 3 months postpartum participated in individual interviews. These interviews were recorded, transcribed, and analyzed using thematic analysis. Four themes emerged: (1) "Putting up with the pain: coping with everyday life," in which women put up with the pain but had to balance activities and were grateful for support from family and friends to face everyday challenges; (2) "I don't feel back to normal," in which women's feelings of physical limitations, frustration, and a negative impact on their mood were described; (3) "Unexpected," in which persistent symptoms were unexpected for women due to a lack of information given about PGP; and (4) "What next?," in which the future of women's symptoms was met with great uncertainty, and they expressed worry about having another baby. For first-time mothers, having persistent PGP postpartum affects their daily lives in many ways. These findings provide important information for health care providers, which will improve their understanding of these women's experiences, will enhance rapport, and can be used to provide information and address concerns to optimize maternity care during pregnancy and beyond. © 2015 American Physical Therapy Association.

Impacts of persistent general and site-specific pain on activities of daily living and physical performance: A prospective analysis of the English Longitudinal Study of Ageing.

PubMed

Yiengprugsawan, Vasoontara; Steptoe, Andrew

2018-03-23

Pain is an increasingly common phenomenon as people age; pain over a long period can result in limited functioning. The present study investigated the impacts of general and multisite-specific pain on activities of daily living and physical performance among older adults. Data were analyzed from the English Longitudinal Study of Ageing, a representative sample of the population aged ≥50 years. Face-to-face interview and nurse records were used from waves 2-6 (2004-2012) for analyses. General and site-specific pain (back, hip and knee) were measured biennially between 2004 and 2008 (n = 5010). Impaired activity of daily living and physical performance measures (chair rise and grip strength) between 2008 and 2012 were aggregated across assessments as outcomes. Multinomial logistic regressions were used for the former and linear regression for the latter, adjusting for potential covariates. General pain (moderate-to-severe) was prevalent, with close to one-quarter of participants reporting pain at least twice during the follow-up period. Multisite pain reports were strong predictors of subsequent limited activities of daily living (adjusted odds ratio range 1.86-3.97 for back and hip, 2.04-4.19 for back and knee, and 2.08-5.16 for hip and knee). Persistent pain was also strongly associated with worse physical performance outcomes. Our data confirm the longitudinal impacts of persistent pain among older adults. The findings highlight the value of monitoring and management of both general and site-specific pain in order to promote sustained independence at older ages. Geriatr Gerontol Int 2018; ••: ••-••. © 2018 Japan Geriatrics Society.

Identification of oxalic acid and tartaric acid as major persistent pain-inducing toxins in the stinging hairs of the nettle, Urtica thunbergiana.

PubMed

Fu, Han Yi; Chen, Shiang Jiuun; Chen, Ruei Feng; Ding, Wang Hsien; Kuo-Huang, Ling Long; Huang, Rong Nan

2006-07-01

Once human skin contacts stinging hairs of Urtica spp. (stinging nettles), the irritant is released and produces pain, wheals or a stinging sensation which may last for >12 h. However, the existence of pain-inducing toxins in the stinging hairs of Urtica thunbergiana has never been systematically demonstrated. Experiments were therefore conducted to identify the persistent pain-inducing agents in the stinging hairs of U. thunbergiana. The stinging hairs of U. thunbergiana were removed and immersed in deionized water. After centrifugation, the clear supernatants were then subjected to high-performance liquid chromatography (HPLC), enzymatic analysis and/or behavioural bioassays. The HPLC results showed that the major constituents in the stinging hairs of U. thunbergiana were histamine, oxalic acid and tartaric acid. However, the well-recognized pain-inducing agents, serotonin and formic acid, existed at a low concentration as estimated by HPLC and/or enzymatic analyses. The behavioural tests showed that 2% oxalic acid and 10% tartaric acid dramatically elicited persistent pain sensations in rats. In contrast, 10% formic acid and 2% serotonin only elicited moderate pain sensation in the first 10 min. Moreover, no significant pain-related behavioural response was observed after injecting 10% acetylcholine and histamine in rats. Oxalic acid and tartaric acid were identified, for the first time, as major long-lasting pain-inducing toxins in the stinging hairs of U. thunbergiana. The general view that formic acid, histamine and serotonin are the pain-inducing agents in the stinging hairs of U. dioica may require updating, since their concentrations in U. thunbergiana were too low to induce significant pain sensation in behavioural bioassays.

The severity and duration of postoperative pain and analgesia requirements in children after tonsillectomy, orchidopexy, or inguinal hernia repair.

PubMed

Stewart, David W; Ragg, Philip G; Sheppard, Suzette; Chalkiadis, George A

2012-02-01

To provide parents of children with accurate information regarding postoperative pain, its management, and functioning following common surgical procedures. The increasing prevalence of pediatric day-case procedures demands a more thorough understanding of the recovery profiles associated with these operations. To document postdischarge pain profiles, analgesia requirements, and functional limitation in children following tonsillectomy, orchidopexy, or inguinal hernia repair (IHR). Following hospital discharge, parents were asked to record their children's pain levels, analgesia consumption, and degree of functional limitation each day until complete recovery. Pain and functional limitation were measured using the Parents' Postoperative Pain Measurement (PPPM) scale and Functional Activity Score, respectively. Significant pain was defined as PPPM ≥ 6. One hundred and five patients (50, tonsillectomy; 24, orchidopexy; and 31, IHR) were recruited. Median PPPM was always <6 after IHR, ≥6 only on day 1 after orchidopexy and persisted through to day 8 after tonsillectomy. Mild or severe functional limitation was observed after all surgeries and persisted for 4, 5, and 4 days after median PPPM < 6 after IHR, orchidopexy, and tonsillectomy, respectively. Combination analgesia was commonly administered after orchidopexy and tonsillectomy but less so after IHR. The general practitioner consultation rate following tonsillectomy was 54%. After tonsillectomy, children experience significant pain and severe functional limitation for 7 days after surgery. For many children, pain and functional limitation persists throughout the second postoperative week. In children undergoing orchidopexy, paracetamol and ibuprofen provide adequate analgesia. Pain begins to subside after the first postoperative day, and normal activity resumes after 7 days. After IHR, children experience mild pain that can be treated with paracetamol and return to normal functioning after 4 days. © 2011 Blackwell Publishing Ltd.

Back pain and scoliosis in children: When to image, what to consider.

PubMed

Calloni, Sonia F; Huisman, Thierry Agm; Poretti, Andrea; Soares, Bruno P

2017-10-01

Back pain and scoliosis in children most commonly present as benign and self-limited entities. However, persistent back pain and/or progressive scoliosis should always be taken seriously in children. Dedicated diagnostic work-up should exclude etiologies that may result in significant morbidity. Clinical evaluation and management require a comprehensive history and physical and neurological examination. A correct imaging approach is important to define a clear diagnosis and should be reserved for children with persistent symptoms or concerning clinical and laboratory findings. This article reviews the role of different imaging techniques in the diagnostic approach to back pain and scoliosis, and offers a comprehensive review of the main imaging findings associated with common and uncommon causes of back pain and scoliosis in the pediatric population.

Back to School Foot Pain (Flip-Flops)

MedlinePlus

... ankle surgeons can usually reduce or eliminate students' foot pain with simple treatment methods, including stretching exercises, ice massage, anti-inflammatory medications and custom or over-the- ...

Antinociceptive and anti-inflammatory activities of a pomegranate (Punica granatum L.) extract rich in ellagitannins.

PubMed

González-Trujano, María Eva; Pellicer, Francisco; Mena, Pedro; Moreno, Diego A; García-Viguera, Cristina

2015-01-01

Pomegranate (Punica granatum L.) has been used for centuries for the treatment of inflammatory diseases. However, there is a lack of comprehensive information focused on the properties of a certain pomegranate (poly)phenolic profile to cure pain and gastric injury induced by anti-inflammatory drugs. This study investigated the systemic effects of different doses of a HPLC-characterized pomegranate extract on the formalin-induced nociceptive behavior in mice. The effect of the extract against gastric injury caused by non-steroidal anti-inflammatory drugs and ethanol was also assessed. Pomegranate reduced nociception in both phases of the formalin test, suggesting central and peripheral activities to inhibit nociception. Indomethacin-induced gastric injury was not produced in the presence of pomegranate, which also protected against ethanol-induced gastric lesions. The present results reinforce the benefits of pomegranate (poly)phenolics in the treatment of pain as well as their anti-inflammatory properties.

Lysergic acid diethylamide and psilocybin for the management of patients with persistent pain: a potential role?

PubMed

Whelan, Andy; Johnson, Mark I

2018-05-01

Recently, there has been interest in lysergic acid diethylamide (LSD) and psilocybin for depression, anxiety and fear of death in terminal illness. The aim of this review is to discuss the potential use of LSD and psilocybin for patients with persistent pain. LSD and psilocybin are 5-hydroxytryptamine receptor agonists and may interact with nociceptive and antinociceptive processing. Tentative evidence from a systematic review suggests that LSD (7 studies, 323 participants) and psilocybin (3 studies, 92 participants) may be beneficial for depression and anxiety associated with distress in life-threatening diseases. LSD and psilocybin are generally safe if administered by a healthcare professional, although further investigations are needed to assess their utility for patients with persistent pain, especially associated with terminal illness.

Antinociceptive effects of JWH015 in female and male rats.

PubMed

Craft, Rebecca M; Greene, Nicholas Z; Wakley, Alexa A

2018-04-01

Despite greater chronic pain prevalence in females compared with males, and the analgesic potential of cannabinoid receptor type 2 (CB2) agonists, CB2 agonists have rarely been tested in females. The aim of the present study was to compare the antinociceptive effects of a CB2-preferring agonist, (2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone (JWH015), in female and male rats against acute pain and persistent inflammatory pain. JWH015 (5-20 mg/kg, intraperitoneally) produced dose-dependent and time-dependent increases in latency to respond on the tail withdrawal and paw pressure tests that did not differ statistically between the sexes. JWH015 dose-dependently decreased locomotor activity in both sexes, but was more potent in females than males. JWH015 produced little catalepsy in either sex. In females, the antinociceptive effects of JWH015 against acute pain were blocked by rimonabant and SR144528, whereas locomotor suppression was antagonized by rimonabant. When administered 3 days after intraplantar injection of complete Freund's adjuvant, JWH015 produced a significantly greater antiallodynic effect in females at the highest dose tested (10 mg/kg, intraperitoneally). Antiallodynic effects of JWH015 were antagonized by rimonabant and SR144528 in both sexes. These studies indicate that systemically administered JWH015 produced antinociception that was both CB1 and CB2 receptor-mediated in both sexes. Unlike [INCREMENT]-9-tetrahydrocannabinol and other nonselective cannabinoid agonists, the CB2-preferring agonist JWH015 may produce more equivalent antinociception in females and males.

Ketamine for chronic pain: risks and benefits

PubMed Central

Niesters, Marieke; Martini, Christian; Dahan, Albert

2014-01-01

The anaesthetic ketamine is used to treat various chronic pain syndromes, especially those that have a neuropathic component. Low dose ketamine produces strong analgesia in neuropathic pain states, presumably by inhibition of the N-methyl-D-aspartate receptor although other mechanisms are possibly involved, including enhancement of descending inhibition and anti-inflammatory effects at central sites. Current data on short term infusions indicate that ketamine produces potent analgesia during administration only, while three studies on the effect of prolonged infusion (4–14 days) show long-term analgesic effects up to 3 months following infusion. The side effects of ketamine noted in clinical studies include psychedelic symptoms (hallucinations, memory defects, panic attacks), nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity. The recreational use of ketamine is increasing and comes with a variety of additional risks ranging from bladder and renal complications to persistent psychotypical behaviour and memory defects. Blind extrapolation of these risks to clinical patients is difficult because of the variable, high and recurrent exposure to the drug in ketamine abusers and the high frequency of abuse of other illicit substances in this population. In clinical settings, ketamine is well tolerated, especially when benzodiazepines are used to tame the psychotropic side effects. Irrespective, close monitoring of patients receiving ketamine is mandatory, particularly aimed at CNS, haemodynamic, renal and hepatic symptoms as well as abuse. Further research is required to assess whether the benefits outweigh the risks and costs. Until definite proof is obtained ketamine administration should be restricted to patients with therapy-resistant severe neuropathic pain. PMID:23432384

Treatment of folliculitis decalvans using intensity-modulated radiation via tomotherapy.

PubMed

Elsayad, Khaled; Kriz, Jan; Haverkamp, Uwe; Plachouri, Kerasia-Maria; Jeskowiak, Antonia; Sunderkötter, Cord; Eich, Hans Theodor

2015-11-01

Folliculitis decalvans (FD) is a form of primary neutrophilic scarring alopecia that is characterized clinically by chronic suppurative folliculitis and often associated with pruritus or even pain. Treatment of FD is often difficult. Herein, we report a case of recalcitrant and painful folliculitis decalvans refractory to antibiotic and anti-inflammatory therapies, which was successfully treated by intensity-modulated radiotherapy (IMRT) in order to irreversibly eliminate hair follicles that prove to be one etiological trigger. A 45-year-old male patient with a refractory FD presented with a crusting suppurative folliculitis and atrophic scarring patches on the scalp associated with pain and pruritus. We attempted relief of symptoms by reducing scalp inflammation and eliminating hair follicles through radiation. We delivered 11.0 Gy in two radiation series using tomotherapy, 5.0 Gy in 5 equivalent fractions as a first radiation course. The symptoms markedly decreased but did not totally disappear. Therefore, we delivered a second radiation series 4 months later with an additional 6 Gy. This led to almost complete epilation on the scalp and abolished pain and pruritus on the capillitium. The patient was regularly followed up until 26 months after radiotherapy. Draining lesions or exudation did not recur. He only experienced discrete hair regrowth in the occipital region with folliculitis 12 months after radiotherapy. These residual lesions are currently treated with laser epilation therapy. A radical approach to eliminating hair follicles by repeated radiation therapy may induce lasting relief of symptoms in chronic suppurative FD associated with persistent trichodynia.

Brain natriuretic peptide suppresses pain induced by BmK I, a sodium channel-specific modulator, in rats.

PubMed

Li, Zheng-Wei; Wu, Bin; Ye, Pin; Tan, Zhi-Yong; Ji, Yong-Hua

2016-12-01

A previous study found that brain natriuretic peptide (BNP) inhibited inflammatory pain via activating its receptor natriuretic peptide receptor A (NPRA) in nociceptive sensory neurons. A recent study found that functional NPRA is expressed in almost all the trigeminal ganglion (TG) neurons at membrane level suggesting a potentially important role for BNP in migraine pathophysiology. An inflammatory pain model was produced by subcutaneous injection of BmK I, a sodium channel-specific modulator from venom of Chinese scorpion Buthus martensi Karsch. Quantitative PCR, Western Blot, and immunohistochemistry were used to detect mRNA and protein expression of BNP and NPRA in dorsal root ganglion (DRG) and dorsal horn of spinal cord. Whole-cell patch clamping experiments were conducted to record large-conductance Ca 2+ -activated K + (BK Ca ) currents of membrane excitability of DRG neurons. Spontaneous and evoked pain behaviors were examined. The mRNA and protein expression of BNP and NPRA was up-regulated in DRG and dorsal horn of spinal cord after BmK I injection. The BNP and NPRA was preferentially expressed in small-sized DRG neurons among which BNP was expressed in both CGRP-positive and IB4-positive neurons while NPRA was preferentially expressed in CGRP-positive neurons. BNP increased the open probability of BK Ca channels and suppressed the membrane excitability of small-sized DRG neurons. Intrathecal injection of BNP significantly inhibited BmK-induced pain behaviors including both spontaneous and evoked pain behaviors. These results suggested that BNP might play an important role as an endogenous pain reliever in BmK I-induced inflammatory pain condition. It is also suggested that BNP might play a similar role in other pathophysiological pain conditions including migraine.

Plasma IL-8 signature correlates with pain and depressive symptomatology in patients with burning mouth syndrome: Results from a pilot study.

PubMed

Barry, Alison; O'Halloran, Ken D; McKenna, Joseph P; McCreary, Christine; Downer, Eric J

2018-02-01

Burning mouth syndrome (BMS) is a neuropathic orofacial pain condition of unknown aetiology that encompasses intra-oral burning pain without abnormal clinical findings. Psychological, neural and inflammatory processes are associated with BMS pathogenesis. Currently, studies characterising plasma cytokine/chemokine profiles with pain and depression in patients with BMS are lacking. Considering that inflammation is associated with the pathophysiology of BMS, and that inflammation is closely associated with pain and depression, we aimed to correlate depressive symptomatology and oral cavity pain with plasma cytokine/chemokine signatures in a cohort of patients with BMS. In this study, plasma protein levels of Th1 cytokines (IFN-γ, IL-2, IL-12p70, TNF-α), Th2 cytokines (IL-4, IL-10, IL-6, IL-13) and the chemokine IL-8 were assessed in patients with BMS (n = 10) and healthy volunteers (n = 10), using pro-inflammatory-10-plex assays. Clinical histories, alongside self-rated oral cavity pain intensities and depressive symptomatology were assessed using a visual analogue scale and the 16-item Quick Inventory of Depressive Symptomatology questionnaires, respectively. We present evidence that BMS is associated with increased depressive symptomatology and enhanced oral cavity pain. Plasma isolated from BMS patients display enhanced expression of the pro-inflammatory chemokine IL-8, when compared to plasma from healthy individuals. Plasma IL-8 signature correlates with pain and depressive symptomatology in the study cohort. Overall, these findings indicate that plasma IL-8 profiles are dysregulated in BMS and that modulation of IL-8 production in the disorder may be a tool in the management of BMS symptomatology. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Innovative Opioid Peptides and Biased Agonism: Novel Avenues for More Effective and Safer Analgesics to Treat Chronic Pain.

PubMed

Bedini, Andrea; Spampinato, Santi Mario

2017-02-15

Chronic pain is a clinically relevant and yet unsolved conditions that is poorly treated with the currently available drugs, thus highlighting the urgent need of innovative analgesics. Although opiates are not very effective in the treatment of inflammatory and neuropathic pain, developing novel opioid receptor peptide agonists, as well as modulating the opioid receptor-mediated responses in a ligand-specific fashion, may represent an innovative and promising strategy to identify more efficacious and safer antalgic drugs. In this review, novel analogues of endomorphin 1 (a mu opioid receptor selective agonist able to induce analgesia in different animal models of pain - including neuropathic pain) and dermorphin (one of the most potent opioid peptide existing in nature) will be discussed as they are emerging as a promising starting point to develop novel opioid agonists: endomorphin 1 analogues, in fact, may determine antinociception in different models of neuropathic pain with reduced side effects as compared to classic opiates as morphine; dermorphin analogues may elicit analgesia in animal models of both inflammatory and neuropathic pain and with less severe adverse effects. Furthermore, such opioid peptides may allow to explore unprecedented modalities of ligand-receptor interactions, helping to characterize biased agonism at opioid receptors: exploiting functional selectivity at opioid receptor may lead to identify innovative analgesic with improved pharmacological responses and optimized side effects. Thus, innovative opioid peptides, as those outlined in this review, are promising candidates to develop more effective opioid analgesics to be employed as medications for chronic pain states, as inflammatory or neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pregnancy-related low back pain and pelvic girdle pain approximately 14 months after pregnancy – pain status, self-rated health and family situation

PubMed Central

2014-01-01

Background Pelvic girdle pain (PGP) in pregnancy is distinct from pregnancy-related low back pain (PLBP). However, women with combined PLBP and PGP report more serious consequences in terms of health and function. PGP has been estimated to affect about half of pregnant women, where 25% experience serious pain and 8% experience severe disability. To date there are relatively few studies regarding persistent PLBP/PGP postpartum of more than 3 months, thus the main objective was to identify the prevalence of persistent PLBP and PGP as well as the differences over time in regard to pain status, self-rated health (SRH) and family situation at 12 months postpartum. Methods The study is a 12 month follow-up of a cohort of pregnant women developing PLBP and PGP during pregnancy, and who experienced persistent pain at 6 month follow-up after pregnancy. Women reporting PLBP/PGP (n = 639) during pregnancy were followed up with a second questionnaire at approximately six month after delivery. Women reporting recurrent or persistent LBP/PGP at the second questionnaire (n = 200) were sent a third questionnaire at 12 month postpartum. Results A total of 176 women responded to the questionnaire. Thirty-four women (19.3%) reported remission of LBP/PGP, whereas 65.3% (n = 115) and 15.3% (n = 27), reported recurrent LBP/PGP or continuous LBP/PGP, respectively. The time between base line and the 12 months follow-up was in actuality 14 months. Women with previous LBP before pregnancy had an increased odds ratio (OR) of reporting ‘recurrent pain’ (OR = 2.47) or ‘continuous pain’ (OR = 3.35) postpartum compared to women who reported ‘no pain’ at the follow-up. Women with ‘continuous pain’ reported statistically significant higher level of pain at all measure points (0, 6 and 12 months postpartum). Non-responders were found to report a statistically significant less positive scoring regarding relationship satisfaction compared to responders. Conclusions The results from this study demonstrate that persistent PLBP/PGP is a major individual and public health issue among women 14 months postpartum, negatively affecting their self-reported health. However, the perceived relationship satisfaction seems to be stable between the groups. PMID:24460727

Celastrol attenuates inflammatory and neuropathic pain mediated by cannabinoid receptor type 2.

PubMed

Yang, Longhe; Li, Yanting; Ren, Jie; Zhu, Chenggang; Fu, Jin; Lin, Donghai; Qiu, Yan

2014-08-06

Celastrol, a major active ingredient of Chinese herb Tripterygium wilfordii Hook. f. (thunder god vine), has exhibited a broad spectrum of pharmacological activities, including anti-inflammation, anti-cancer and immunosuppression. In the present study, we used animal models of inflammatory pain and neuropathic pain, generated by carrageenan injection and spared nerve injury (SNI), respectively, to evaluate the effect of celastrol and to address the mechanisms underlying pain processing. Intraperitoneal (i.p.) injection of celastrol produced a dose-dependent inhibition of carrageenan-induced edema and allodynia. Real-time PCR analysis showed that celastrol (0.3 mg/kg, i.p.) significantly reduced mRNA expressions of inflammatory cytokines, TNF-α, IL-6, IL-1β, in carrageenan-injected mice. In SNI mice, pain behavior studies showed that celastrol (1 mg/kg, i.p.) effectively prevented the hypersensitivity of mechanical nociceptive response on the third day post-surgery and the seventh day post-surgery. Furthermore, the anti-hyperalgesic effects of celastrol in carrageenan-injected mice and SNI mice were reversed by SR144528 (1 mg/kg, i.p.), a specific cannabinoid receptor-2 (CB2) receptor antagonist, but not by SR141716 (1 mg/kg, i.p.), a specific cannabinoid receptor-1 (CB1) receptor antagonist. Taken together, our results demonstrate the analgesia effects of celastrol through CB2 signaling and propose the potential of exploiting celastrol as a novel candidate for pain relief.

Carbonic Anhydrase-8 Regulates Inflammatory Pain by Inhibiting the ITPR1-Cytosolic Free Calcium Pathway

PubMed Central

Zhuang, Gerald Z.; Keeler, Benjamin; Grant, Jeff; Bianchi, Laura; Fu, Eugene S.; Zhang, Yan Ping; Erasso, Diana M.; Cui, Jian-Guo; Wiltshire, Tim; Li, Qiongzhen; Hao, Shuanglin; Sarantopoulos, Konstantinos D.; Candiotti, Keith; Wishnek, Sarah M.; Smith, Shad B.; Maixner, William; Diatchenko, Luda; Martin, Eden R.; Levitt, Roy C.

2015-01-01

Calcium dysregulation is causally linked with various forms of neuropathology including seizure disorders, multiple sclerosis, Huntington’s disease, Alzheimer’s, spinal cerebellar ataxia (SCA) and chronic pain. Carbonic anhydrase-8 (Car8) is an allosteric inhibitor of inositol trisphosphate receptor-1 (ITPR1), which regulates intracellular calcium release fundamental to critical cellular functions including neuronal excitability, neurite outgrowth, neurotransmitter release, mitochondrial energy production and cell fate. In this report we test the hypothesis that Car8 regulation of ITPR1 and cytoplasmic free calcium release is critical to nociception and pain behaviors. We show Car8 null mutant mice (MT) exhibit mechanical allodynia and thermal hyperalgesia. Dorsal root ganglia (DRG) from MT also demonstrate increased steady-state ITPR1 phosphorylation (pITPR1) and cytoplasmic free calcium release. Overexpression of Car8 wildtype protein in MT nociceptors complements Car8 deficiency, down regulates pITPR1 and abolishes thermal and mechanical hypersensitivity. We also show that Car8 nociceptor overexpression alleviates chronic inflammatory pain. Finally, inflammation results in downregulation of DRG Car8 that is associated with increased pITPR1 expression relative to ITPR1, suggesting a possible mechanism of acute hypersensitivity. Our findings indicate Car8 regulates the ITPR1-cytosolic free calcium pathway that is critical to nociception, inflammatory pain and possibly other neuropathological states. Car8 and ITPR1 represent new therapeutic targets for chronic pain. PMID:25734498

REMIFENTANIL VS FENTANYL DURING DAY CASE DENTAL SURGERY IN PEOPLE WITH SPECIAL NEEDS: A COMPARATIVE, PILOT STUDY OF THEIR EFFECT ON STRESS RESPONSE AND POSTOPERATIVE PAIN.

PubMed

Sklika, Eirini; Kalimeris, Konstantinos; Perrea, Despina; Stavropoulos, Nikolaos; Kostopanagiotou, Georgia; Matsota, Paraskevi

2016-06-01

People with special needs undergoing dental surgery frequently require general anesthesia. We investigated the effect of remifentanil vs fentanyl on stress response and postoperative pain in people with special needs undergoing day-case dental surgery. Forty-six adult patients with cognitive impairment undergoing day-case dental surgery under general anesthesia were allocated to receive intraoperatively either fentanyl 50 μg iv bolus (group F, n = 23) or continuous infusion of remifentanil 0.5-1 μg/kg/min (group R, n = 23). Iintraoperative hemodynamic parameters were recorded and serum inflammatory mediators [tumor necrosis factor-α, substance-P], stress hormons (melatonin, cortisol) and β-endorphin were measured. Postoperative pain was assessed during the first postoperative 12 hours with the Wong-Baker faces pain-rating scale. Demographics were similar in two groups. The two groups did not differ regarding their effects on inflammatory mediators, stress hormons and postoperative pain scores. However, the use of remifentanil prevented intraoperative increases of arterial blood pressure and heart rate. Remifentanil and fentanyl did not affect differently stress and inflammatory hormones during day-case dental surgery, although remifentanil may render intraoperative management of hemodynamic responses easier. Both opioids are equally efficient for postoperative pain management following dental surgery in people with special needs.

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.

Neural tissue engineering scaffold with sustained RAPA release relieves neuropathic pain in rats.

PubMed

Ding, Tan; Zhu, Chao; Kou, Zhen-Zhen; Yin, Jun-Bin; Zhang, Ting; Lu, Ya-Cheng; Wang, Li-Ying; Luo, Zhuo-Jing; Li, Yun-Qing

2014-09-01

To investigate the effect of locally slow-released rapamycin (RAPA) from bionic peripheral nerve stent to reduce the incidence of neuropathic pain or mitigate the degree of pain after nerve injury. We constructed a neural tissue engineering scaffold with sustained release of RAPA to repair 20mm defects in rat sciatic nerves. Four presurgical and postsurgical time windows were selected to monitor the changes in the expression of pain-related dorsal root ganglion (DRG) voltage-gated sodium channels 1.3 (Nav1.3), 1.7 (Nav1.7), and 1.8 (Nav1.8) through immunohistochemistry (IHC) and Western Blot, along with the observation of postsurgical pathological pain in rats by pain-related behavior approaches. Relatively small upregulation of DRG sodium channels was observed in the experimental group (RAPA+poly(lactic-co-glycolic acid) (PLGA)+stent) after surgery, along with low degrees of neuropathic pain and anxiety, which were similar to those in the Autologous nerve graft group. Autoimmune inflammatory response plays a leading role in the occurrence of post-traumatic neuropathic pain, and that RAPA significantly inhibits the abnormal upregulation of sodium channels to reduce pain by alleviating inflammatory response. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional up-regulation of Nav1.8 sodium channel in Aβ afferent fibers subjected to chronic peripheral inflammation

PubMed Central

2014-01-01

Background Functional alterations in the properties of Aβ afferent fibers may account for the increased pain sensitivity observed under peripheral chronic inflammation. Among the voltage-gated sodium channels involved in the pathophysiology of pain, Nav1.8 has been shown to participate in the peripheral sensitization of nociceptors. However, to date, there is no evidence for a role of Nav1.8 in controlling Aβ-fiber excitability following persistent inflammation. Methods Distribution and expression of Nav1.8 in dorsal root ganglia and sciatic nerves were qualitatively or quantitatively assessed by immunohistochemical staining and by real time-polymerase chain reaction at different time points following complete Freund’s adjuvant (CFA) administration. Using a whole-cell patch-clamp configuration, we further determined both total INa and TTX-R Nav1.8 currents in large-soma dorsal root ganglia (DRG) neurons isolated from sham or CFA-treated rats. Finally, we analyzed the effects of ambroxol, a Nav1.8-preferring blocker on the electrophysiological properties of Nav1.8 currents and on the mechanical sensitivity and inflammation of the hind paw in CFA-treated rats. Results Our findings revealed that Nav1.8 is up-regulated in NF200-positive large sensory neurons and is subsequently anterogradely transported from the DRG cell bodies along the axons toward the periphery after CFA-induced inflammation. We also demonstrated that both total INa and Nav1.8 peak current densities are enhanced in inflamed large myelinated Aβ-fiber neurons. Persistent inflammation leading to nociception also induced time-dependent changes in Aβ-fiber neuron excitability by shifting the voltage-dependent activation of Nav1.8 in the hyperpolarizing direction, thus decreasing the current threshold for triggering action potentials. Finally, we found that ambroxol significantly reduces the potentiation of Nav1.8 currents in Aβ-fiber neurons observed following intraplantar CFA injection and concomitantly blocks CFA-induced mechanical allodynia, suggesting that Nav1.8 regulation in Aβ-fibers contributes to inflammatory pain. Conclusions Collectively, these findings support a key role for Nav1.8 in controlling the excitability of Aβ-fibers and its potential contribution to the development of mechanical allodynia under persistent inflammation. PMID:24606981

Chronic Pain Patients: Implications for Rehabilitation Counseling.

ERIC Educational Resources Information Center

Scott, Lori T.

Chronic pain syndrome appears to have certain dimensions which make it unique as a disabling condition. When pain persists, the resulting anxiety and depression, others' reactions to the patient's sick role behaviors, and situational variables such as disability benefits may all contribute to the pain syndrome and complicate the rehabilitation…

Stromal cells in chronic inflammation and tertiary lymphoid organ formation.

PubMed

Buckley, Christopher D; Barone, Francesca; Nayar, Saba; Bénézech, Cecile; Caamaño, Jorge

2015-01-01

Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflammatory cells within inflamed tissues. Furthermore, at many sites of chronic inflammation, structures that mimic secondary lymphoid tissues are observed, suggesting that chronic inflammation and lymphoid tissue formation share common activation programs. Similarly, blood and lymphatic endothelial cells contribute to tissue homeostasis and disease persistence in chronic inflammation. This review highlights our increasing understanding of the role of stromal cells in inflammation and summarizes the novel immunological role that stromal cells exert in the persistence of inflammatory diseases.

A potent and selective calcitonin gene-related peptide (CGRP) receptor antagonist, MK-8825, inhibits responses to nociceptive trigeminal activation: Role of CGRP in orofacial pain.

PubMed

Romero-Reyes, Marcela; Pardi, Vanessa; Akerman, Simon

2015-09-01

Temporomandibular disorders (TMDs) are orofacial pains within the trigeminal distribution, which involve the masticatory musculature, the temporomandibular joint or both. Their pathophysiology remains unclear, as inflammatory mediators are thought to be involved, and clinically TMD presents pain and sometimes limitation of function, but often appears without gross indications of local inflammation, such as visible edema, redness and increase in temperature. Calcitonin gene-related peptide (CGRP) has been implicated in other pain disorders with trigeminal distribution, such as migraine, of which TMD shares a significant co-morbidity. CGRP causes activation and sensitization of trigeminal primary afferent neurons, independent of any inflammatory mechanisms, and thus may also be involved in TMD. Here we used a small molecule, selective CGRP receptor antagonist, MK-8825, to dissect the role of CGRP in inducing spontaneous nociceptive facial grooming behaviors, neuronal activation in the trigeminal nucleus, and systemic release of pro-inflammatory cytokines, in a mouse model of acute orofacial masseteric muscle pain that we have developed, as a surrogate of acute TMD. We show that CFA masseteric injection causes significant spontaneous orofacial pain behaviors, neuronal activation in the trigeminal nucleus, and release of interleukin-6 (IL-6). In mice pre-treated with MK-8825 there is a significant reduction in these spontaneous orofacial pain behaviors. Also, at 2 and 24h after CFA injection the level of Fos immunoreactivity in the trigeminal nucleus, used as a marker of neuronal activation, was much lower on both ipsilateral and contralateral sides after pre-treatment with MK-8825. There was no effect of MK-8825 on the release of IL-6. These data suggest that CGRP may be involved in TMD pathophysiology, but not via inflammatory mechanisms, at least in the acute stage. Furthermore, CGRP receptor antagonists may have therapeutic efficacy in the treatment of TMD, as they do with migraine. Copyright © 2015 Elsevier Inc. All rights reserved.

The prevalence of sacroiliitis in patients with acne vulgaris using isotretinoin.

PubMed

Baykal Selçuk, Leyla; Aksu Arıca, Deniz; Baykal Şahin, Hanife; Yaylı, Savas; Bahadır, Sevgi

2017-06-01

Acne vulgaris is a chronic inflammatory disease affecting the pilosebaceous unit in the skin. Isotretinoin is a synthetic vitamin A derivative regarded as the most effective agent in the treatment of acne. There have recently been increasing reports of adverse effects of isotretinoin on the skeletal system. Our aim in this study was to evaluate the rheumatic side-effects triggered by this drug, and particularly the prevalence of sacroiliitis. A total of 73 patients receiving isotretinoin due to moderate or severe acne vulgaris were included. All patients were questioned about inflammatory low back pain and musculoskeletal pains during the treatment process. Inflammatory low back pain was evaluated using Assessment of Spondyloarthritis International Society (ASAS) criteria. Patients meeting ASAS criteria were evaluated with radiography and when necessary with sacroiliac magnetic resonance. The dose range for isotretinoin was between 0.4 and 0.8 mg/kg/day (mean 0.53 mg/kg/day). Treatment lasted for 6-8 months (mean 6.8 months). Lethargy was determined in 37 (50.7%) patients, myalgia in 31 (42.5%) and low back pain in 36 (49.3%). Mechanical low back pain symptoms were present in 20 of the patients describing low back pain and inflammatory low back pain in 16. Acute sacroiliitis was determined in six patients (8.2%) following a sacroiliac magnetic resonance imaging (MRI). Five (83.3%) of the patients with sacroiliitis were female and one (16.7%) was male. No statistically significant difference was determined between male and female patients in terms of prevalence of sacroiliitis (p = 0.392). The incidence of sacroiliitis in patients using isotretinoin is quite high. Patients using isotretinoin must be questioned about sacroiliitis findings and must be subjected to advanced assessment when necessary. Further studies regarding the development of sacroiliitis under isotretinoin therapy are now needed.

The economic impact of chronic pain in adolescence: methodological considerations and a preliminary costs-of-illness study.

PubMed

Sleed, Michelle; Eccleston, Christopher; Beecham, Jennifer; Knapp, Martin; Jordan, Abbie

2005-12-15

Chronic pain in adulthood is one of the most costly conditions in modern western society. However, very little is known about the costs of chronic pain in adolescence. This preliminary study explored methods for collecting economic-related data for this population and estimated the cost-of-illness of adolescent chronic pain in the United Kingdom. The client service receipt inventory was specifically adapted for use with parents of adolescent chronic pain patients to collect economic-related data (CSRI-Pain). This method was compared and discussed in relation to other widely used methods. The CSRI-Pain was sent to 52 families of adolescents with chronic pain to complete as a self-report retrospective questionnaire. These data were linked with unit costs to estimate the total care cost package for each family. The economic impact of adolescent chronic pain was found to be high. The mean cost per adolescent experiencing chronic pain was approximately 8,000 pounds per year, including direct and indirect costs. The adolescents attending a specialised pain management unit, who had predominantly non-inflammatory pain, accrued significantly higher costs, than those attending rheumatology outpatient clinics, who had mostly inflammatory diagnoses. Extrapolating the mean total cost to estimated UK prevalence data of adolescent chronic pain demonstrates a cost-of-illness to UK society of approximately 3,840 million pounds in one year. The implications of the study are discussed.

The benefit of therapeutic medial branch blocks after cervical operations.

PubMed

Klessinger, Stephan

2010-01-01

Persistent neck pain is a common problem after surgery of the cervical spine. No therapy recommendation exists for these patients. The objective of this study was to determine if a therapeutic medial branch block is a rational treatment for patients with postoperative neck pain after cervical spine operations. Retrospective practice audit. Review of charts of all patients who underwent cervical spine operations for degenerative reasons during a time period of 3 years. Patients with persistent postsurgical pain were treated with therapeutic medial branch blocks (local anesthetic and steroid). A positive treatment response was defined if at least 80% reduction of pain could be achieved or if the patient was sufficiently satisfied with the relief. All patients with a minimum follow up time of 6 months were included. Of the 312 operations performed, 128 were artificial disc operations, 125 were stand alone cages, and 59 were fusions with cage and plate. Persistent neck pain occurred in 33.3% of the patients. There was no difference between the patients with neck pain and the whole group of patients. More than half of the patients with neck pain--52.9%--were treated successfully with therapeutic medial branch blocks. Since no further treatment was necessary, the initial treatment was considered successful. Nearly a third--32.2%--of the patients were initially treated successfully, but their pain recurred and further diagnostics and treatments were necessary. In this group of patients, significantly more with double level operations were found (P = 0.003). Patients not responding to the medial branch block were 14.9%. This audit is retrospective and observational, and therefore does not represent a high level of evidence. However, to our knowledge, since this information has not been previously reported and no recommendation for the treatment of post-operative zygapophysial joint pain exists, it appears to be the best available research upon which to recommend treatment and to plan higher quality studies. For persistent postsurgical neck pain only limited therapy recommendations exist. This study suggests treating these patients in a first instance with therapeutic medial branch blocks. The success rate is 52.9 %.

Influencing Nursing Knowledge and Attitudes to Positively Affect Care of Patients with Persistent Pain in the Hospital Setting.

PubMed

Keen, Alyson; McCrate, Brian; McLennon, Susan; Ellis, Alexis; Wall, Donna; Jones, Sarah

2017-06-01

Hospitalized patients with persistent pain are among the most challenging populations to effectively manage because of coexistence with acute pain. Nurses play a vital role in pain management; however, gaps in knowledge and detrimental attitudes exist. The purpose of this study was to evaluate the effectiveness of a targeted evidence-based pain education program to increase nurses' knowledge and attitudes about pain management. One group, paired, pretest/posttest educational intervention. A convenience sample of nurses from three medical and surgical inpatient units were recruited. Participants completed a pretest, the Knowledge and Attitudes Survey Regarding Pain Scale, to assess education needs. Identified gaps were targeted during program design. The program consisted of two 30-minute interactive educational sessions approximately 1 month apart. The first session, delivered by a pharmacist, covered pharmacology and pathophysiology content. The second session, delivered by trained registered nurses, used case studies paired with video scenarios. A total of 51 nurses completed the pretest. The final sample consisted of 24 nurses who completed both the pretest and posttest. The mean age was 30 years; 88% were female, and 92% were baccalaureate prepared. Paired t tests indicated higher posttest total scores (p < .001) after the education program compared with pretest scores. Overall program satisfaction was positive. This study found improvement in persistent pain management knowledge and attitudes among direct care nurses caring for hospitalized patients. A targeted educational program may be an effective and efficient delivery method. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Pain and fracture-related limitations persist 6 months after a fragility fracture.

PubMed

Sale, Joanna E M; Frankel, Lucy; Thielke, Stephen; Funnell, Larry

2017-08-01

Our objective was to examine the experience of pain after a fracture beyond the conventional healing duration of 6 months. We conducted a phenomenological study in participants who were deemed high risk for future fracture and recruited through an urban fracture clinic in Toronto, Canada. In-depth interviews were conducted with questions addressing the experience of pain, the status of recovery from the fracture, ways in which the fracture affected one's daily activities, and interactions with health care providers. Two researchers coded the transcripts within the phenomenological perspective to develop a structure of the pain experience, promoting rigour through the use of multiple analysts, searching for negative cases, and supporting claims with direct quotations from participants. We interviewed 21 participants who had sustained fractures of the wrist (n = 4), hip (n = 6), vertebrae (n = 2), and multiple or other locations (n = 9). All patients were ambulatory, had a range of socioeconomic status, and lived in the community. Eleven of the 21 participants reported persistent pain at the site of the fracture. Of the 10 participants who reported no pain, four indicated they had ongoing difficulties with range of motion and specific activities and two others described persistent pain from a previous fracture or reliance on a scooter for mobility. Our study demonstrated that over two-thirds of older adults reported fracture-related pain and/or limitations at, or beyond, 6 months post-fracture. We suggest that health care providers ask questions about post-fracture pain and/or limitations when assessing fracture status beyond 6 months.

Surgical treatment of rib fracture nonunion: A single center experience.

PubMed

de Jong, M B; Houwert, R M; van Heerde, S; de Steenwinkel, M; Hietbrink, F; Leenen, L P H

2018-03-01

In contrast to the emerging evidence on the operative treatment of flail chest, there is a paucity of literature on the surgical treatment of rib fracture nonunion. The purpose of this study was to describe our standardized approach and report the outcome (e.g. patient satisfaction, pain and complications) after surgical treatment of a rib fracture nonunion. A single centre retrospective cohort study was performed at a level 1 trauma centre. Symptomatic rib nonunion was defined as a severe persistent localized pain associated with the nonunion of one or more rib fractures on a chest CT scan at least 3 months after the initial trauma. Patients after initial operative treatment of rib fractures were excluded. Nineteen patients (11 men, 8 women), with symptomatic nonunions were included. Fourteen patients were referred from other hospitals and 8 patients received treatment from a pain medicine specialist. The mean follow-up was 36 months. No in-hospital complications were observed. In 2 patients, new fractures adjacent to the implant, without new trauma were observed. Furthermore 3 patients requested implant removal with a persistent nonunion in one patient. There was a mean follow-up of 36 months, the majority of patients (n = 13) were satisfied with the results of their surgical treatment and all patients experienced a reduction in the number of complaints. Persisting pain was a common complaint. Three patients reporting severe pain used opioid analgesics on a daily or weekly basis. Only 1 patient needed ongoing treatment by a pain medicine specialist. Surgical fixation of symptomatic rib nonunion is a safe and feasible procedure, with a low perioperative complication rate, and might be beneficial in selected symptomatic patients in the future. In our study, although the majority of patients were satisfied and the pain level subjectively decreases, complaints of persistent pain were common. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

Recent development in antihyperalgesic effect of phytochemicals: anti-inflammatory and neuro-modulatory actions.

PubMed

Singh, Ajeet Kumar; Kumar, Sanjay; Vinayak, Manjula

2018-05-16

Pain is an unpleasant sensation triggered by noxious stimulation. It is one of the most prevalent conditions, limiting productivity and diminishing quality of life. Non steroidal anti inflammatory drugs (NSAIDs) are widely used as pain relievers in present day practice as pain is mostly initiated due to inflammation. However, due to potentially serious side effects, long term use of these antihyperalgesic drugs raises concern. Therefore there is a demand to search novel medicines with least side effects. Herbal products have been used for centuries to reduce pain and inflammation, and phytochemicals are known to cause fewer side effects. However, identification of active phytochemicals of herbal medicines and clear understanding of the molecular mechanism of their action is needed for clinical acceptance. In this review, we have briefly discussed the cellular and molecular changes during hyperalgesia via inflammatory mediators and neuro-modulatory action involved therein. The review includes 54 recently reported phytochemicals with antihyperalgesic action, as per the literature available with PubMed, Google Scholar and Scopus. Compounds of high interest as potential antihyperalgesic agents are: curcumin, resveratrol, capsaicin, quercetin, eugenol, naringenin and epigallocatechin gallate (EGCG). Current knowledge about molecular targets of pain and their regulation by these phytochemicals is elaborated and the scope of further research is discussed.

Predicting Persistent Back Symptoms by Psychosocial Risk Factors: Validity Criteria for the ÖMPSQ and the HKF-R 10 in Germany.

PubMed

Riewe, E; Neubauer, E; Pfeifer, A C; Schiltenwolf, M

2016-01-01

10% of all individuals in Germany develop persistent symptoms due to nonspecific back pain (NSBP) causing up to 90% of direct and indirect expenses for health care systems. Evidence indicates a strong relationship between chronic nonspecific back pain and psychosocial risk factors. The Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ) and the German Heidelberger Kurzfragebogen Rückenschmerz (HKF-R 10) are deemed valid in prediction of persistent pain, functional loss or amount of sick leave. This study provides and discusses validity criteria for these questionnaires using ROC-curve analyses. Quality measurements included sensitivity and specificity, likelihood-ratio related test-efficiencies and clinical utility in regard to predictive values. 265 patients recruited from primary and secondary care units completed both questionnaires during the same timeframe. From the total, 133 patients returned a 6-month follow-up questionnaire to assess the validity criteria for outcomes of pain, function and sick leave. Based on heterogeneous cut-offs for the ÖMPSQ, sensitivity and specificity were moderate for outcome of pain (72%/75%). Very high sensitivity was observed for function (97%/57%) and high specificity for sick leave (63%/85%). The latter also applied to the HKF-R 10 (pain 50%/84%). Proportions between sensitivity and specificity were unbalanced except for the ÖMPSQ outcome of pain. Likelihood-ratios and positive predictive values ranged from low to moderate. Although the ÖMPSQ may be considered useful in identification of long-term functional loss or pain, over- and underestimation of patients at risk of chronic noncspecific back pain led to limited test-efficiencies and clinical utility for both questionnaires. Further studies are required to quantify the predictive validity of both questionnaires in Germany.

A metabolomics and mouse models approach to study inflammatory and immune responses to radiation

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

Fornace, Albert J.; Li, Henghong

2013-12-02

The three-year project entitled "A Metabolomics and Mouse Models Approach to Study Inflammatory and Immune Responses to Radiation" was initiated in September 2009. The overall objectives of this project were to investigate the acute and persistent effects of low dose radiation on T cell lymphocyte function and physiology, as well the contributions of these cells to radiation-induced inflammatory responses. Inflammation after ionizing radiation (IR), even at low doses, may impact a variety of disease processes, including infectious disease, cardiovascular disease, cancer, and other potentially inflammatory disorders. There were three overall specific aims: 1. To investigate acute and persistent effects ofmore » low dose radiation on T cell subsets and function; 2. A genetic approach with mouse models to investigate p38 MAPK pathways that are involved in radiation-induced inflammatory signaling; 3. To investigate the effect of radiation quality on the inflammatory response. We have completed the work proposed in these aims.« less

Influence of route of administration/drug formulation and other factors on adherence to treatment in rheumatoid arthritis (pain related) and dyslipidemia (non-pain related).

PubMed

Fautrel, Bruno; Balsa, Alejandro; Van Riel, Piet; Casillas, Marta; Capron, Jean-Philippe; Cueille, Carine; de la Torre, Inmaculada

2017-07-01

A comprehensive review was performed to investigate the effect of route of administration on medication adherence and persistence in rheumatoid arthritis (RA) and to compare adherence/persistence with oral medications between RA and a non-painful disease (dyslipidemia). Comprehensive database searches were performed to identify studies investigating medication adherence and/or persistence in adults with RA receiving conventional synthetic or biologic agents. Similar searches were performed for studies of patients with dyslipidemia receiving statins. Studies had to be published after 1998 in English and involve ≥6 months' follow up. Adherence and persistence were compared between the different routes of drug administration in RA, and between the two diseases for oral medications. A total of 35 and 28 papers underwent data extraction for RA and dyslipidemia, respectively. Within the constraints of the analysis, adherence and persistence rates appeared broadly similar for the different routes of drug administration in RA. Adherence to oral medications was also broadly similar across the two diseases, but persistence was lower in dyslipidemia. Poor adherence has clinical consequences in both diseases: greater disease activity and risk of flare in RA, and increased serum cholesterol levels and risk of heart and cerebrovascular disease in dyslipidemia. Over 1-3 years, poor adherence to biologic RA medications led to increased resource use and medical costs but lower total direct costs due to reduced biologic drug costs. Conversely, poor adherence to dyslipidemia medications resulted in increased total direct costs. In both diseases, adherence improved with patient education/support. The route of drug administration and the symptomatic (pain) nature of the disease do not appear to be dominant factors for drug adherence or persistence in RA. The wide range of adherence and persistence values and definitions across studies made comparisons between drug formulations and diseases difficult.

Synthesis and Study of Analgesic and Anti-inflammatory Activities of Amide Derivatives of Ibuprofen.

PubMed

Ahmadi, Abbas; Khalili, Mohsen; Olama, Zahra; Karami, Shirin; Nahri-Niknafs, Babak

2017-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs worldwide and represent a mainstay in the therapy of acute and chronic pain and inflammation. The traditional NSAIDs like ibuprofen (I) contain free carboxylic acid group which can produce gastrointestinal (GI) damage for long-term use. In order to obtain the novel NSAIDs with less side effects; carboxylic acid moiety has been modified into various amide groups which is the most active area of research in this family. In this research, synthesis of various pharmacological heterocyclic amides of ibuprofen is described. All the new compounds were tested for their analgesic and anti-inflammatory activities in mice and compared with standard (Ibuprofen) and control (saline) groups. The results revealed that all the synthesized compounds (III-VI) exhibited more analgesic and anti-inflammatory activities in tail immersion (as a model of acute thermal pain), formalin (as a model of acute chemical and chronic pain) and paw edema (as a model of acute inflammation) tests when compared with standard and control animals. These pharmacological activities were significant for VI compared to other new compounds (III-V) which may be concern to more effective role of morpholin for the reduction of pain and inflammation compared to other used heterocyclic amines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Cholinergic anti-inflammatory pathway of some non-pharmacological therapies of complementary medicine: possible implications for treatment of rheumatic and autoimmune diseases].

PubMed

Gamus, Dorit

2011-08-01

Rheumatologic and autoimmune diseases are among foremost diseases for which patients seek complementary and integrative medicine options. Therefore, physicians should be informed on the advances in research of these therapies, in order to be able to discuss possible indications and contraindications for these treatment modalities with their patients. This review summarizes several therapeutic modalities of complementary medicine that may be involved in the cholinergic anti-inflammatory pathway. The analysis of systematic reviews of acupuncture for rheumatic conditions has concluded that the evidence is sufficiently sound to warrant positive recommendations of this therapy for osteoarthritis, low back pain and lateral elbow pain. There is relatively strong evidence to support the use of hypnosis in pain treatment, such as in cases of fibromyalgia. A recent controlled study that evaLuated tai-chi in fibromyalgia has reported reductions in pain, improvements in mood, quality of Life, self efficacy and exercise capacity. There is also cumulative evidence that acupuncture, hypnosis and tai-chi may decrease the high frequency of heart rate variability, suggesting enhancement of vagus nerve activity. Hence, it has been hypothesized that these modalities might impact the cholinergic anti-inflammatory pathway to modulate inflammation. Further clinical and basic research to confirm this hypothesis should be performed in order to validate integration of these therapies in comprehensive treatment for some inflammatory and autoimmune diseases.

Role overload, pain and physical dysfunction in early rheumatoid or undifferentiated inflammatory arthritis in Canada

PubMed Central

2012-01-01

Background Inflammatory arthritis impairs participation in societal roles. Role overload arises when the demands by a given role set exceed the resources; time and energy, to carry out the required tasks. The present study examines the association between role overload and disease outcomes in early inflammatory arthritis (EIA). Methods Patients (n = 104) of 7.61 months mean duration of inflammatory arthritis completed self-report questionnaires on sociodemographics, disease characteristics and role overload. Pain was assessed using the Short Form McGill Pain Questionnaire (MPQ) and physical functioning was measured with the Medical Outcomes Study Short Form 36 (SF-36) physical functioning score. Role overload was measured by the Role Overload Scale. Patients indicated the number of social roles they occupied from a total of the three typical roles; marital, parental and paid work. Results Participants’ mean age was 56 years and 70.2% were female. Role overload was not correlated to the number of social roles, however, it was positively associated with pain (p = 0.004) and negatively associated with physical functioning (p = 0.001). On multivariate analysis, role overload was negatively associated with physical functioning after controlling for the relevant sociodemographic variables. Conclusion This study identifies a possible reciprocal relationship between role overload and physical functioning in patients with EIA. PMID:22554167

Mycolactone displays anti-inflammatory effects on the nervous system

PubMed Central

Isaac, Caroline; Mauborgne, Annie; Grimaldi, Alfonso; Ade, Kemy; Pohl, Michel; Limatola, Cristina; Boucher, Yves; Demangel, Caroline

2017-01-01

Background Mycolactone is a macrolide produced by the skin pathogen Mycobacterium ulcerans, with cytotoxic, analgesic and immunomodulatory properties. The latter were recently shown to result from mycolactone blocking the Sec61-dependent production of pro-inflammatory mediators by immune cells. Here we investigated whether mycolactone similarly affects the inflammatory responses of the nervous cell subsets involved in pain perception, transmission and maintenance. We also investigated the effects of mycolactone on the neuroinflammation that is associated with chronic pain in vivo. Methodology/ Principle findings Sensory neurons, Schwann cells and microglia were isolated from mice for ex vivo assessment of mycolactone cytotoxicity and immunomodulatory activity by measuring the production of proalgesic cytokines and chemokines. In all cell types studied, prolonged (>48h) exposure to mycolactone induced significant cell death at concentrations >10 ng/ml. Within the first 24h treatment, nanomolar concentrations of mycolactone efficiently suppressed the cell production of pro-inflammatory mediators, without affecting their viability. Notably, mycolactone also prevented the pro-inflammatory polarization of cortical microglia. Since these cells critically contribute to neuroinflammation, we next tested if mycolactone impacts this pathogenic process in vivo. We used a rat model of neuropathic pain induced by chronic constriction of the sciatic nerve. Here, mycolactone was injected daily for 3 days in the spinal canal, to ensure its proper delivery to spinal cord. While this treatment failed to prevent injury-induced neuroinflammation, it decreased significantly the local production of inflammatory cytokines without inducing detectable cytotoxicity. Conclusion/ Significance The present study provides in vitro and in vivo evidence that mycolactone suppresses the inflammatory responses of sensory neurons, Schwann cells and microglia, without affecting the cell viability. Together with previous studies using peripheral blood leukocytes, our work implies that mycolactone-mediated analgesia may, at least partially, be explained by its anti-inflammatory properties. PMID:29149212

Cuboid-Navicular Tarsal Coalition in an Adolescent Female Athlete: A Case Report.

PubMed

Kamiya, Tomoaki; Watanabe, Kota; Teramoto, Atsushi; Yamashita, Toshihiko

2015-01-01

A fourteen-year-old female shot-putter developed midfoot pain with activity that initially responded to nonoperative care. However, the symptoms subsequently returned and became persistent. Advanced imaging demonstrated a fibrous cuboid-navicular tarsal coalition. Surgical resection of the tarsal coalition was performed when the patient was seventeen years old, and she returned to sports activities postoperatively with no pain. Although fibrous cuboid-navicular tarsal coalition is a very rare condition, it should be considered as one cause of persistent midfoot pain in an adolescent athlete. Surgical resection of the tarsal coalition can lead to a resolution of symptoms.

Persistent scrotal pain and suspected orchido-epididymitis of a young boy during pinworm (Enterobius vermicularis) infection in the bowel.

PubMed

Sinikumpu, J-J; Serlo, W

2011-08-01

Pinworm (Enterobius vermicularis) is the most common parasite among mankind. Ectopic pinworm infections in number of organs are broadly reported. The aim of this report is to review the pinworm infection in the scrotum on the basis of our case. Our patient is a young boy with persistent pain in the scrotums together with abdominal symptoms. He underwent several urgent operations. Pinworm was finally found in appendix vermiformis. We hypothesize that concurrent unresponsive orchido-epididymitis was caused by pinworm as well. Eradication happened finally with pyvrinembonate. Pinworm is a parasite that lives usually in the bowel. Many ectopic locations, like scrotum, are known. Orchido-epididymitis by pinworm has to be kept in mind when treating boys with persistent scrotal pain. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

Prevalence of foot problems in people with inflammatory arthritis in Singapore.

PubMed

Carter, K; Lahiri, M; Cheung, P P; Santosa, A; Rome, K

2016-01-01

Foot problems are highly prevalent in people with inflammatory arthritis reported from studies in the UK, Europe and New Zealand, but there is limited evidence from Southeast Asia. The study aim was to evaluate the prevalence of foot problems in people with inflammatory arthritis in Singapore. People with inflammatory arthritis were recruited from the rheumatology outpatient clinic of a tertiary hospital in Singapore. Disease and clinical characteristics included age, sex, disease duration, current blood tests and medications. The Leeds Foot Impact Scale was used to evaluate foot impairment/disability and the Modified Health Assessment Questionnaire was used to assess global function. We recruited 101 people with inflammatory arthritis, of which 50 % were female. The majority of participants were Chinese (70 %). The mean (SD) age was 52 (15) years, and the mean (SD) disease duration was 9.3 (0.3) years. The most commonly reported inflammatory arthritic conditions were rheumatoid arthritis (46), gout (31) and spondyloarthritis (15 %). The mean (SD) of the total Leeds Foot Impact Scale was 17 (13) indicating moderate to severe levels of foot impairment and activity limitation. Over 80 of participants reported foot pain during the course of their condition, and 48 % reported current foot pain. Despite the high prevalence of foot pain, only 21 participants (21 %) had been referred to a podiatrist. This is the first study to investigate the prevalence of foot problems in people with inflammatory arthritis from Singapore. The majority of the participants reported foot problems, but had not been referred to a podiatry service.

Analgesic and anti-inflammatory effects of honey: the involvement of autonomic receptors.

PubMed

Owoyele, Bamidele Victor; Oladejo, Rasheed Olajiire; Ajomale, Kayode; Ahmed, Rasheedat Omotayo; Mustapha, Abdulrasheed

2014-03-01

The use of honey for therapeutic purposes is on the increase and many studies have shown that honey has the ability to influence biological systems including pain transmission. Therefore, this study was designed to investigate the analgesic and anti-inflammatory effects of honey and the effects of concurrent administration of autonomic nervous system blocking drugs. Studies on analgesic activities was carried out using hotplate and formalin-induced paw licking models while the anti-inflammatory activity was by the carrageenan paw oedema method. Animals were distributed into six groups consisting of five animals each. They were administered saline, honey (600 mg/kg), indomethacin (5 mg/kg), autonomic blockers (3 μg/kg of tamsulosin, 20 mg/kg (intraperitoneally) of propranolol, 2 ml/kg of atropine or 10 mg/kg (intra muscularly) of hexamethonium) or honey (200 and 600 mg/kg) with one of the blockers. The results showed that honey reduced pain perception especially inflammatory pain and the administration of tamsulosin and propranolol spared the effect of honey. Hexamethonium also spared the effects of honey at the early and late phases of the test while atropine only inhibited the early phase of the test. However, atropine and hexamethonium spared the anti-inflammatory effects of honey but tamsulosin abolished the effects while propranolol only abolished the anti-inflammatory effects at the peak of the inflammation. The results suggest the involvement of autonomic receptors in the anti-nociceptive and anti-inflammatory effects of honey although the level of involvement depends on the different types of the receptors.

The non-peptide GLP-1 receptor agonist WB4-24 blocks inflammatory nociception by stimulating β-endorphin release from spinal microglia

PubMed Central

Fan, Hui; Gong, Nian; Li, Teng-Fei; Ma, Ai-Niu; Wu, Xiao-Yan; Wang, Ming-Wei; Wang, Yong-Xiang

2015-01-01

BACKGROUND AND PURPOSE Two peptide agonists of the glucagon-like peptide-1 (GLP-1) receptor, exenatide and GLP-1 itself, exert anti-hypersensitive effects in neuropathic, cancer and diabetic pain. In this study, we have assessed the anti-allodynic and anti-hyperalgesic effects of the non-peptide agonist WB4-24 in inflammatory nociception and the possible involvement of microglial β-endorphin and pro-inflammatory cytokines. EXPERIMENTAL APPROACH We used rat models of inflammatory nociception induced by formalin, carrageenan or complete Freund's adjuvant (CFA), to test mechanical allodynia and thermal hyperalgesia. Expression of β-endorphin and pro-inflammatory cytokines was measured using real-time quantitative PCR and fluorescent immunoassays. KEY RESULTS WB4-24 displaced the specific binding of exendin (9–39) in microglia. Single intrathecal injection of WB4-24 (0.3, 1, 3, 10, 30 and 100 μg) exerted dose-dependent, specific, anti-hypersensitive effects in acute and chronic inflammatory nociception induced by formalin, carrageenan and CFA, with a maximal inhibition of 60–80%. Spinal WB4-24 was not effective in altering nociceptive pain. Subcutaneous injection of WB4-24 was also antinociceptive in CFA-treated rats. WB4-24 evoked β-endorphin release but did not inhibit expression of pro-inflammatory cytokines in either the spinal cord of CFA-treated rats or cultured microglia stimulated by LPS. WB4-24 anti-allodynia was prevented by a microglial inhibitor, β-endorphin antiserum and a μ-opioid receptor antagonist. CONCLUSIONS AND IMPLICATIONS Our results suggest that WB4-24 inhibits inflammatory nociception by releasing analgesic β-endorphin rather than inhibiting the expression of proalgesic pro-inflammatory cytokines in spinal microglia, and that the spinal GLP-1 receptor is a potential target molecule for the treatment of pain hypersensitivity including inflammatory nociception. PMID:25176008

Potential for Developing Purinergic Drugs for Gastrointestinal Diseases

PubMed Central

Ochoa-Cortes, Fernando; Liñán-Rico, Andromeda; Jacobson, Kenneth A.; Christofi, Fievos L.

2014-01-01

Treatments for IBD, IBS, FD or motility disorders are not adequate, and purinergic drugs offer exciting new possibilities. GI symptoms that could be targeted for therapy include visceral pain, inflammatory pain, dysmotility, constipation and diarrhea. The focus of this review is on potential for developing purinergic drugs for clinical trials to treat GI symptoms. Purinergic receptors are divided into adenosine P1 (A1,A2A,A2B,A3), ionotropic ATP-gated P2X ion channel (P2X1–7) or metabotropic P2Y1,2,4,6,11–14 receptors. There is good experimental evidence for targeting A2A, A2B, A3, P2X7, P2X3 receptors or increasing endogenous adenosine levels to treat IBD, inflammatory pain, IBS/visceral pain, inflammatory-diarrhea and motility disorders. Purine genes are also potential biomarkers of disease. Advances in medicinal-chemistry have an accelerated pace toward clinical trials: Methotrexate and sulfasalazine, used to treat IBD, act by stimulating CD73-dependent adenosine production. ATP protects against NSAID-induced enteropathy and has pain-relieving properties in humans. A P2X7R antagonist AZD9056 is in clinical trials for CD. A3 AR drugs target inflammatory diseases (e.g. CF101; CF102). Dipyridamole, a nucleoside uptake-inhibitor, is in trials for endotoxemia. Drugs for pain in clinical-trials include P2X3/P2X2/3(AF-219) and P2X7(GSK1482160) antagonists and A1(GW493838) or A2A(BVT.115959) agonists. IberogastR is a phytopharmacon targeting purine-mechanisms with efficacy in IBS and FD. Purinergic drugs have excellent safety/efficacy profile for prospective clinical trials in IBD, IBS, FD and inflammatory-diarrhea. Genetic polymorphisms and caffeine consumption may affect susceptibility to treatment. Further studies in animals can clarify mechanisms and test new-generation drugs. Finally, there is still a huge gap in our knowledge of human pathophysiology of purinergic signaling. PMID:24859298