Background: Commissural myelotomy can be valuable for patients with intractable pain associated with malignancy in the abdominal or pelvic region. Methods: Between December 1992 and June 2009, 11 patients underwent commissural myelotomy at the University of Texas MD Anderson Cancer Center for the treatment of intractable lower extremity, thoracic, pelvic or sacral pain associated with unresectable tumors. The various surgical
Ashwin Viswanathan; Allen W. Burton; Andy Rekito; Ian E. McCutcheon
Cryoanalgesia, the local application of extreme cold to nerves to produce analgesia, has been used to treat patients with intractable perineal pain. The cryoprobe was inserted percutaneously through the sacral hiatus into the sacral canal to produce anaesthesia of the lower sacral nerve roots. Forty patients received a total of 70 treatments: 31 patients (78%) were helped by the procedure and the median duration of improvement was 30 days. The treatment was more successful in relieving symptoms in patients suffering from pelvic cancer and coccydynia. The best results were obtained in those patients who received numerous freeze applications or prolonged freezing. Images Figure 1.
Evans, P J; Lloyd, J W; Jack, T M
The mechanism of visceral pain is still less understood compared with that of somatic pain. This is primarily due to the diverse nature of visceral pain compounded by multiple factors such as sexual dimorphism, psychological stress, genetic trait, and the nature of predisposed disease. Due to multiple contributing factors there is an enormous challenge to develop animal models that ideally mimic the exact disease condition. In spite of that, it is well recognized that visceral hypersensitivity can occur due to (1) sensitization of primary sensory afferents innervating the viscera, (2) hyperexcitability of spinal ascending neurons (central sensitization) receiving synaptic input from the viscera, and (3) dysregulation of descending pathways that modulate spinal nociceptive transmission. Depending on the type of stimulus condition, different neural pathways are involved in chronic pain. In early-life psychological stress such as maternal separation, chronic pain occurs later in life due to dysregulation of the hypothalamic–pituitary–adrenal axis and significant increase in corticotrophin releasing factor (CRF) secretion. In contrast, in early-life inflammatory conditions such as colitis and cystitis, there is dysregulation of the descending opioidergic system that results excessive pain perception (i.e., visceral hyperalgesia). Functional bowel disorders and chronic pelvic pain represent unexplained pain that is not associated with identifiable organic diseases. Often pain overlaps between two organs and approximately 35% of patients with chronic pelvic pain showed significant improvement when treated for functional bowel disorders. Animal studies have documented that two main components such as (1) dichotomy of primary afferent fibers innervating two pelvic organs and (2) common convergence of two afferent fibers onto a spinal dorsal horn are contributing factors for organ-to-organ pain overlap. With reports emerging about the varieties of peptide molecules involved in the pathological conditions of visceral pain, it is expected that better therapy will be achieved relatively soon to manage chronic visceral pain.
Sengupta, Jyoti N.
The broad changes that have occurred in the treatment of intractable pain are considered. There is a new understanding of the anatomy and physiology of pain pathways and pain appreciation. Thus gate control theory, the spinal laminae, and the descending inhibitory pain pathway through the raphe nuclei are discussed in relation to the recent discovery of the opioid (enkephalin) systems. Out of this arises the stimulation methods of pain relief--transcutaneous neural stimulation, periaqueductal stimulation, and acupuncture. These are valuable in patients with a normal expectation of life. For patients with a shortened expectation of life other methods, especially destructive ones, are valuable (though in all types of chronic pain drug therapy is still the most used method). Basic changes in techniques and the equipment used to bring this about are detailed broadly. In particular, the use of the image intensifier X-ray machine and the stimulation and destruction available from the modern lesion generator when used in combination provide accuracy and safety. Techniques and methods are constantly altering and examples of this are given. All this costs money in time, personnel, and equipment; the costings of the Liverpool Centre for Pain Relief are given. Finally, the Pain Relief Foundation is in being in Liverpool in the grounds of Walton Hospital. This has been made possible by a large 'seed' donation by the Wolfson Foundation. Images Fig. 1 Fig. 2
\\u000a Visceral pain is the most frequent form of clinically relevant pain. The study of its mechanisms is therefore immediately\\u000a relevant to human pain conditions but it also offers a unique insight into the generation of hyperalgesic states. All forms\\u000a of visceral pain generate enhancements of pain sensitivity in locations remote from the originating injury, a process known\\u000a as “referred hyperalgesia”
Fernando Cervero; Jennifer M. A. Laird
Although the vast majority of patients with cancer pain receive effective analgesia from standard therapy, a few patients, particularly those with neuropathic pain, continue to experience severe pain despite large doses of systemic or intraspinal opioids. Animal studies suggest intraspinal ?2-adrenergic agonists may be effective in such cases. Eighty-five patients with severe cancer pain despite large doses of opioids or
James C. Eisenach; Stuart DuPen; Michel Dubois; Rafael Miguel; Douglas Allin
Summary ?Nauta et al. reported on a successful punctate midline myelotomy (PMM) for the treatment of intractable pelvic pain. The authors describe\\u000a an other case history of a patient with multiple anaplastic carcinomas of the small intestine, peritoneal carcinosis and retroperitoneal\\u000a lymphomas, suffering from severe visceral pain in the hypo-, meso-, and epigastrium. Nauta's PMM was successfully performed\\u000a at the Th4
R. Becker; U. Sure; H. Bertalanffy
Visceral pain is studied at the level of the primary afferent fiber, spinal cord, subcortical, and cortical levels electrophysiologically and using brain imaging, which provides an objective measure of excitation at each level. However, correlation of these with actual perception of pain in conscious animal models has been problematic, and we rely on indirect measures in most preclinical research. The main method is electromyographic recording of abdominal muscle contractions in response to colorectal distension (CRD), which may reflect reflexes set up at several levels of the above pathway. Several experimental treatments for visceral pain have failed in clinical trials, possibly because of failure to translate from preclinical observations on CRD responses in animals to perception of spontaneous events in patients. Therefore, we need more objective outcomes. In this NGM issue, Hultin et al. show feasibility of routine recordings of cortical evoked electrical potentials (CEP) using implanted cranial electrodes in response to graded CRD in rats. CEP comprised three temporal components with latencies of approximately 20-50 ms, 90-180 ms, and 300 ms, which were reproducible and graded in intensity and latency with distension pressure. From this basic study it is clear that colorectal evoked potentials can be recorded reliably in awake rats and may serve as an objective marker for centrally projecting visceral sensory signals in rodents. It remains to be seen how these responses are affected by drugs under development for clinical management of visceral pain, and if there is improved translation. PMID:22967008
Blackshaw, L A
Visceral pain is experienced by 40% of the population, and 28% of cancer patients suffer from pain arising from intra- abdominal metastasis or from treatment. Neuroanatomy of visceral nociception and neurotransmitters, receptors, and ion channels that modulate visceral pain are qualitatively or quantitatively different from those that modulate somatic and neuropathic pain. Visceral pain should be recognized as distinct pain phenotype. TRPV1, Na 1.8, and ASIC3 ion channels and peripheral kappa opioid receptors are important mediators of visceral pain. Mu agonists, gabapentinoids, and GABAB agonists reduce pain by binding to central receptors and channels. Combinations of analgesics and adjuvants in animal models have supra-additive antinociception and should be considered in clinical trials. This paper will discuss the neuroanatomy, receptors, ion channels, and neurotransmitters important to visceral pain and provide a basic science rationale for analgesic trials and management.
Davis, Mellar P.
Loin pain hematuria syndrome (LPHS) is a rare pain syndrome, which is somewhat poorly characterized and challenging to treat. The condition of LPHS is still controversial and there is no consensus of validated diagnostic criteria or optimal treatment strategies. The epidemiology of LPHS is unknown and the mechanisms/etiologies contributing to LPHS remain uncertain. There exists some debate whether LPHS represents neuropathic pain or visceral pain. Curiously, for such a controversial pain syndrome there is substantially more written in the literature regarding surgical-type treatments than conservative treatments. A brief review of LPHS potential pathophysiology and potential treatment approaches is presented. PMID:22699133
Smith, Howard S; Bajwa, Zahid H
Objective: Our purpose was to evaluate visceral sensitivity and psychologic profiles in children with functional gastrointestinal disorders. Study design: We measured visceral perception in the stomach and in the rectum by using an electronic barostat. Psychologic questionnaires were completed. Ten children with recurrent abdominal pain (RAP)(8 female, mean age 11.3 ± 0.8 years), 10 children with irritable bowel syndrome (IBS)
Carlo Di Lorenzo; Nader N. Youssef; Luther Sigurdsson; Lisa Scharff; Janet Griffiths; Arnold Wald
Sacral nerve stimulation (SNS) is an effective treatment for bladder and bowel dysfunction, and also has a role in the treatment of chronic pelvic pain. We report two cases of intractable pain associated with cauda equina syndrome (CES) that were treated successfully by SNS. The first patient suffered from intractable pelvic pain with urinary incontinence and fecal incontinence after surgery for a herniated lumbar disc. The second patient underwent surgery for treatment of a burst fracture and developed intractable pelvic area pain, right leg pain, excessive urinary frequency, urinary incontinence, voiding difficulty and constipation one year after surgery. A SNS trial was performed on both patients. Both patients' pain was significantly improved and urinary symptoms were much relieved. Neuromodulation of the sacral nerves is an effective treatment for idiopathic urinary frequency, urgency, and urge incontinence. Sacral neuromodulation has also been used to control various forms of pelvic pain. Although the mechanism of action of neuromodulation remains unexplained, numerous clinical success reports suggest that it is a therapy with efficacy and durability. From the results of our research, we believe that SNS can be a safe and effective option for the treatment of intractable pelvic pain with incomplete CES.
Kim, Jong-Hoon; Hong, Joo-Chul; Kim, Min-Su
Epidemiological studies have implicated stress (psychosocial and physical) as a trigger of first onset or exacerbation of irritable bowel syndrome (IBS) symptoms of which visceral pain is an integrant landmark. A number of experimental acute or chronic exteroceptive or interoceptive stressors induce visceral hyperalgesia in rodents although recent evidence also points to stress-related visceral analgesia as established in the somatic pain field. Underlying mechanisms of stress-related visceral hypersensitivity may involve a combination of sensitization of primary afferents, central sensitization in response to input from the viscera and dysregulation of descending pathways that modulate spinal nociceptive transmission or analgesic response. Biochemical coding of stress involves the recruitment of corticotropin releasing factor (CRF) signaling pathways. Experimental studies established that activation of brain and peripheral CRF receptor subtype 1 plays a primary role in the development of stress-related delayed visceral hyperalgesia while subtype 2 activation induces analgesic response. In line with stress pathways playing a role in IBS, non-pharmacologic and pharmacologic treatment modalities aimed at reducing stress perception using a broad range of evidence-based mind-body interventions and centrally-targeted medications to reduce anxiety impact on brain patterns activated by visceral stimuli and dampen visceral pain.
Larauche, Muriel; Mulak, Agata; Tache, Yvette
Ever since the application in 1980 of morphine for spinal analgesia in patients with refractory cancer pain, spinal infusion\\u000a therapy has become one of the cornerstones for the management of chronic, medically intractable pain. Initially, spinal infusion\\u000a therapy was indicated only for patients with cancer pain that could not be adequately controlled with systemic narcotics.\\u000a However, over the past decade,
Richard K. Osenbach; Susan Harvey
Objective To contrast differences in pain and treatment outcomes between neuromyelitis optica (NMO) and multiple sclerosis (MS). Design Retrospective, cross-sectional cohort study. Setting Academic MS center. Patients Complete ascertainment of an academic MS center cohort of NMO and an MS comparison sample cohort. Main Outcome Measures Current pain was quantified by a 10-point scale and the McGill Pain Questionnaire. Expanded Disability Status Scale score and number of involved spinal cord levels were collected in addition to testing for cognition, fatigue, depression, and quality of life. Number and types of pain medications were tabulated. Results Current pain was more common in subjects with NMO (n=29) vs MS (n=66) (86.2% vs 40.9%; P<.001) and more severe on a 10-point scale (5.38 vs 1.85; P <.001). Pain remained more common after controlling for disability and number of spinal cord segments (P=.03). Prescription pain medication was used more frequently in subjects with NMO compared with subjects with MS (75.9% vs 37.8%; P<.001), often requiring more than 1 medication (65.5% vs 15.2%; P<.001). No subject with NMO taking pain medication (22 of 29) rated their current pain as 0 of 10, whereas almost half of those taking pain medication with MS were currently free of pain (0% vs 48%; P=.006). Conclusions Neuromyelitis optica is frequently associated with severe pain that appears insufficiently controlled by pharmacologic interventions. Future studies should evaluate the efficacy of a multidisciplinary and multimodal approach to pain management.
Qian, Peiqing; Lancia, Samantha; Alvarez, Enrique; Klawiter, Eric C.; Cross, Anne H.; Naismith, Robert T.
At Howard University Hospital, nine terminally ill cancer patients with chronic pain have been treated with continuous intrathecal infusion of morphine delivered by the implantable Infusaid pump. The case of a patient treated at Howard University Hospital with this method of pain management is presented. Following Infusaid pump insertion, the patient lived for 22 months and obtained substantial relief of his cancer pain with no adverse side effects.
Bryant, D'Orsay D.; DeWitty, Robert L.; Dennis, Gary C.
Despite significant progress in our understanding of the cellular and molecular mechanisms underlying sensory transduction and nociception, clinical pain management remains a considerable challenge in health care and basic research. The identification of the superfamily of transient receptor potential (TRP) cation channels, particularly TRPV1 and TRPA1, has shed light on the molecular basis of pain signaling during inflammatory conditions. TRPV1 and TRPA1 are considered as potential targets in the treatment of inflammatory pain because of their ability to be activated by nociceptive signals and sensitized by pro-inflammatory mediators. Notably, TRPA1 is expressed in visceral afferent neurons and is known to participate in inflammatory responses and the establishment of hypersensitivity. This review summarizes the current knowledge of the role of TRPA1 in sensory transduction, particularly in the context of visceral inflammation and pain in the gastrointestinal and urinary tracts. PMID:21993194
Lapointe, Tamia K; Altier, Christophe
Hitchcock's original method of hypothermic subarachnoid irrigation employed both temperature and osmolarity. Spinal cooling was then abandoned in favour of intrathecal injection of normothermic hypertonic salilne. Modifications of the procedure that followed have continued to accept hyperosmolarity as the factor causing pain relief. Fifty patients were treated by a technique evolved to enhance the effect of hypothermia while avoiding the complications associated with hyperosmolar solutions. For the cases of terminal carcinoma and others considered to be poor surgical risks, the results have been quite satisfactory. For non-neoplastic painful syndromes, rapid perfusion cooling of the subarachnoid space offers an alternative therapeutic approach.
Savitz, Martin H.; Malis, Leonard I.
The durable effectiveness of intrathecal morphine administration is well established for the management of intractable cancer pain, after failure of systemic opioids, secondary to the persistence of non-reversible undesirable side effects. Many patients are referred to late in the disease course. This conservative method to control pain of malignant origin must not be reserved for last resort treatment for terminal patients. Intra-cerebro-ventricular morphine administration is a very effective and generally safe method for controlling intractable cancer pain. Because of the chronic implantation of an intra-ventricular catheter this method is somewhat invasive. Its indications remain a simple and effective alternative when the topography of nociceptive pain is diffuse or cephalic. In clinical practice, intrathecal and/or intra-cerebro-ventricular administration of opioids is limited by cost, the need for specialized maintenance and mechanical malfunctions if implantable drug delivery systems, or by the risk of bacterial contamination and ambulatory constraints when repeated daily injections via an intrathecal access port are used. To answer these limitations, cell therapy using intrathecal chromaffin cell allograft is a promising approach for the management of cancer pain refractory to traditional drug therapy and pain lesion surgery. The basic rationale and preclinical studies on experimental pain models have enabled starting prospective clinical trials. Prior to transplantation, handling and preparation of the chromaffin tissue is critical for allograft viability. The initial results of clinical trials with human chromaffin cell grafts from intractable cancer pain have reported long-lasting pain relief, in correlation with met-enkephalin release into the CSF. Convincing evidence will require controlled studies. The limitations of this innovative cell therapy and especially the lack of human adrenal gland availability point to the need for new sources of cells. Perspectives include xenogenic or engineered cell lines. PMID:11084478
Lazorthes, Y; Sallerin, B; Verdie, J C; Sol, J C; Duplan, H; Tkaczuk, J; Tafani, M; Bastide, R; Bes, J C
Visceral noxious stimulation induces central neuronal plasticity changes and suggests that the c-AMP-dependent protein kinase (PKA) signal transduction cascade contributes to long-term changes in nociceptive processing at the spinal cord level. Our previous studies reported the clinical neurosurgical interruption of post synaptic dorsal column neuron (PSDC) pathway by performing midline myelotomy effectively alleviating the intractable visceral pain in patients with severe pain. However, the intracellular cascade in PSDC neurons mediated by PKA nociceptive neurotransmission was not known. In this study, by using multiple experimental approaches, we investigated the role of PKA in nociceptive signaling in the spinal cord and PSDC neurons in a visceral pain model in rats with the intracolonic injection of mustard oil. We found that mustard oil injection elicited visceral pain that significantly changed exploratory behavior activity in rats in terms of decreased numbers of entries, traveled distance, active and rearing time, rearing activity, and increased resting time when compared to that of rats receiving mineral oil injection. However, the intrathecal infusion of PKA inhibitor, H 89 partially reversed the visceral pain-induced effects. Results from Western blot studies showed that mustard oil injection significantly induced the expression of PKA protein in the lumbosacral spinal cord. Immunofluorescent staining in pre-labeled PSDC neurons showed that mustard oil injection greatly induces the neuronal profile numbers. We also found that the intrathecal infusion of a PKA inhibitor, H89 significantly blocked the visceral pain-induced phosphorylation of c-AMP –responsive element binding (CREB) protein in spinal cord in rats. The results of our study suggest that the PKA signal transduction cascade may contribute to visceral nociceptive changes in spinal PSDC pathways.
Wu, Jing; Su, Guangxiao; Ma, Long; Zhang, Xuan; Lei, Yongzhong; Lin, Qing; Nauta, Haring J.W.; Li, Junfa; Fang, Li
A multimodal stepped care approach has been successfully applied to a patient with complex regional pain syndrome type 1 and severe intractable pain, not responding to regular neuropathic pain medication. The choice to administer drugs in creams was made because of the intolerable adverse effects to oral medication. With this method, peak-dose adverse effects did not occur. The multimodal stepped care approach resulted in considerable and clinically relevant decrease in pain after every step, using topical amitriptyline, ketamine, and dimethylsulphoxide.
Kopsky, David J.; Keppel Hesselink, Jan M.
Objective The aim of this study was to evaluate effect of pulsed radiofrequency (PRF) neuromodulation of suprascpaular nerve (SSN) in patients with chronic shoulder pain due to adhesive capsulitis and/or rotator cuff tear. Methods The study included 11 patients suffering from chronic shoulder pain for at least 6 months who were diagnosed with adhesive capsulitis (n=4), rotator cuff tear (n=5), or adhesive capsulitis+rotator cuff tear (n=2) using shoulder magnetic resonance imaging or extremity ultrasonography. After a favorable response to a diagnostic suprascapular nerve block twice a week (pain improvement >50%), PRF neuromodulation was performed. Shoulder pain and quality of life were assessed using a Visual Analogue Scale (VAS) and the Oxford Shoulder Score (OSS) before the diagnostic block and every month after PRF neuromodulation over a 9-month period. Results The mean VAS score of 11 patients before PRF was 6.4±1.49, and the scores at 6-month and 9 month follow-up were 1.0±0.73 and 1.5±1.23, respectively. A significant pain reduction (p<0.001) was observed. The mean OSS score of 11 patients before PRF was 22.7±8.1, and the scores at 6-month and 9 month follow-up were 41.5±6.65 and 41.0±6.67, respectively. A significant OSS improvement (p<0.001) was observed. Conclusion PRF neuromodulation of the suprascapular nerve is an effective treatment for chronic shoulder pain, and the effect was sustained over a relatively long period in patients with medically intractable shoulder pain.
Jang, Ji Su; Kang, Suk Hyung; Yang, Jin Seo; Lee, Jae Jun; Hwang, Sung Mi
Several studies have shown that N-methyl-D-aspartate (NMDA)-receptor activation in anterior cingulate cortex (ACC) neurons plays critical roles in modulating visceral pain responses in visceral hypersensitivity (VH) rats. However, there are few reports about the expressions of NMDA and ?-amino-3-hydroxy-5-methyl-4-isox-azolepropionic-acid (AMPA) receptor subtypes in ACC of VH model rats at different time points. The current study was undertaken to investigate NR2A, NR2B and GluR2 expressions in ACC of VH rats that were induced by administration with 5% mustard oil. Our results indicated that NR2B, but not NR2A, was highly expressed in VH model group on day 15, 22, and 36 compared with normal group (p < 0.05). GluR2 expression was also higher in VH model group on day 15, 22, and 36 than that of normal group (p < 0.05). These findings suggested increased expression of NR2B and GluR2 might be key mechanisms for long-term synaptic plastic changes in VH rats. PMID:24487031
Zhou, Lin; Huang, Junjing; Gao, Jun; Zhang, Guanpo; Jiang, Jinjin
Stereotactic cingulotomy constitutes a psychosurgical procedure nowadays advocated in the treatment of medically intractable obsessive-compulsive disorder, chronic pain and drug addiction. From its theoretical conception to the first cingulectomies performed and modern stereotactic-guided cingulotomies, various target localization methods, different surgical techniques, and numerous lesioning devices have been utilized. In the current article, the authors performed a literature review related to
Alexandros G. Brotis; Eftychia Z. Kapsalaki; Konstantinos Paterakis; Joseph R. Smith; Kostas N. Fountas
Phenytoin is an anti-convulsant and anti-arrhythmic medication. Manufactured by various pharmaceutical companies with various brand names, phenytoin (PHT) is also known as Dilantain, Hydantoin or Phenytek in the United States; Dilantain or Remytoine in Canada; Epamin, Hidantoina in Mexico; and Fenidatoin or Fenitron or other names elsewhere in the world. Phenytoin (PHT) is especially useful for patients suffering from intractable oral and facial pain especially those who exhibit anger, stress, depression and irrational emotions commonly seen in the patients with oral and facial pain. When used properly, Phenytoin is also an effective anxiolysis drug in addition to its theraputic effects on pain and can be used alone or, even better, if combined with other compatible sedatives. Phenytoin is particularly valuable when combined with acupuncture for patients with trigeminal neuralgia, glossopharyneal neuralgia, Bell's palsy, and some other facial paralysis and pain. It also has an advantage of keeping the patient relatively lucid after treatment. Either PHT or acupuncture alone can benefit patients but the success of treatment outcome may be limited. We found by combining both acupuncture and PHT with Selective Drug Uptake Enhancement by stimulating middle finger at the first segment of ventral (palmar) and lateral surfaces, as well as prescribing PHT with the dosage predetermined for each patient by Bi-Digital O-Ring Test (BDORT), the treatment outcome was much better resulted with less recurrence and intensity of pain during episodes of attack. Patients with Bell's palsy were most benefited by acupuncture therapy that could completely get rid of the illness. PMID:21830351
Lu, Dominic P; Lu, Winston I; Lu, Gabriel P
This report describes the long term safety and efficacy of intrathecal therapy using Sufentanil for the management of chronic intractable neuropathic pain in 12 chronic pain patients. Standardized psychological screening was used to determine treatment suitability. Evaluation data included the Visual Analog Scale (VAS), Wong-Baker Faces Scale, Brief Pain Inventory (BPI), Disability of Arm, Shoulder, and Hand (DASH), McGill Quality of Life Questionnaire, and complications (granulomas, toxicity, withdrawal, or deaths). SPSS version 18 was used for data analysis. Pre- and post- treatment BPI measures and pain scale scores showed a statistically significant difference. There were no complications directly related to drug toxicity, nor drug withdrawals, granulomas, or deaths. Intrathecal therapy with Sufentanil therapy offers a good treatment alternative for those cases that have failed both surgery and standard pain treatment. Strict patient selection based on psychological screening, control of co-morbidities, a proper pain management may contribute to successful outcome.
Monsivais, Diane Burn
This report describes the long term safety and efficacy of intrathecal therapy using Sufentanil for the management of chronic intractable neuropathic pain in 12 chronic pain patients. Standardized psychological screening was used to determine treatment suitability. Evaluation data included the Visual Analog Scale (VAS), Wong-Baker Faces Scale, Brief Pain Inventory (BPI), Disability of Arm, Shoulder, and Hand (DASH), McGill Quality of Life Questionnaire, and complications (granulomas, toxicity, withdrawal, or deaths). SPSS version 18 was used for data analysis. Pre- and post- treatment BPI measures and pain scale scores showed a statistically significant difference. There were no complications directly related to drug toxicity, nor drug withdrawals, granulomas, or deaths. Intrathecal therapy with Sufentanil therapy offers a good treatment alternative for those cases that have failed both surgery and standard pain treatment. Strict patient selection based on psychological screening, control of co-morbidities, a proper pain management may contribute to successful outcome. PMID:25031819
Monsivais, Jose Jesus; Monsivais, Diane Burn
Background Pain contains both sensory and affective dimensions. Using a rodent visceral pain assay that combines the colorectal distension (CRD) model with the conditioned place avoidance (CPA) paradigms, we measured a learned behavior that directly reflects the affective component of visceral pain, and showed that perigenual anterior cingulate cortex (pACC) activation is critical for memory processing involved in long-term visceral affective state and prediction of aversive stimuli by contextual cue. Progress has been made and suggested that activation of vagal afferents plays a role in the behavioral control nociception and memory storage processes. In human patients, electrical vagus nerve stimulation enhanced retention of verbal learning performance. Cholecystokinin-octapeptide (CCK), which is a gastrointestinal hormone released during feeding, has been shown to enhance memory retention. Mice access to food immediately after training session enhanced memory retention. It has been well demonstrated that CCK acting on vagal afferent fibers mediates various physiological functions. We hypothesize that CCK activation of vagal afferent enhances visceral pain-related affective memory. Results In the presented study, infusion of CCK-8 at physiological concentration combining with conditional training significantly increased the CRD-induced CPA scores, and enhanced the pain affective memory retention. In contrast, CCK had no effect on CPA induced by non-nociceptive aversive stimulus (U69,593). The physiological implications were further strengthened by the similar effects observed in the rats with duodenal infusion of 5% peptone, which has been shown to induce increases in plasma CCK levels. CCK-8 receptor antagonist CR-1409 or perivagal application of capsaicin abolished the effect of CCK on aversive visceral pain memory, which was consistent with the notion that vagal afferent modulates affective aspects of visceral pain. CCK does not change the nociceptive response (visceral pain sensitivity) and anterior cingulate cortex neuronal responses to CRD. Conclusion CCK activating vagal afferent C fibers enhances memory consolidation and retention involved in long-term visceral negative affective state. Thus, in a number of gastrointestinal disorders, such as irritable bowel syndrome, nutrient content may contribute to painful visceral perception by enhancing visceral aversive memory via acts on vagal afferent pathway.
We present the first patient in New Zealand to undergo Spinal Cord Stimulation (SCS) for intractable upper abdominal pain. The patient was a 53-year-old man with a 20-year history of debilitating upper abdominal pain associated with chronic pancreatitis secondary to pancreatic divisum. Prior to the SCS, he was prescribed 680 mg of morphine sulphate equi-analgesia a day. Despite the intense analgesia, he still suffered monthly attacks of upper abdominal pain requiring hospitalisation. Nine months after implanting a Spinal Cord Stimulator, the monthly attacks ceased, his background pain was effectively controlled and the need for opioids decreased to 510 mg of morphine sulphate equi-analgesia a day. PMID:23321890
Al-Mahrouqi, Haitham; Munro, Zea; Acland, Richard H; MacFarlane, Martin R
Background & Aims Chronic visceral pain is frequent, extremely debilitating, and generally resistant to pharmacological treatment. It has been shown that chronic visceral inflammation, through altered afferent visceral sensory input, leads to plastic changes in the central nervous system that ultimately sustain pain. Therefore approaches aiming at modulation of brain activity are attractive candidates to control visceral pain. Methods Here we report findings of a phase II, sham-controlled clinical trial assessing the clinical and neurophysiological effects of a 10-day course of daily sessions of slow frequency, repetitive transcranial magnetic stimulation (rTMS) targeting the right secondary somatosensory cortex (SII) in patients with chronic pancreatitis and severe visceral pain. Results Our results show a significant reduction in pain after real rTMS that lasted for at least 3 weeks following treatment. These clinical changes were correlated with increases in glutamate and N-acetyl aspartate (NAA) levels - neurometabolites associated with cortical activity and brain damage - as measured by in vivo single-voxel proton magnetic resonance spectroscopy (1H-MRS). Adverse effects in the real rTMS group were mild and short-lasting. Conclusions Our results support preliminary findings showing that modulation of right SII with rTMS is associated with a significant analgesic effect and that this effect is correlated with an increase in excitatory neurotransmitter levels such as glutamate and NAA.
Fregni, Felipe; Potvin, Kimberly; DaSilva, Deborah; Wang, Xiaoen; Lenkinski, Robert; Freedman, Steven D.; Pascual-Leone, Alvaro
We report three cases of successful treatment of intractable delirium associated with cancer pain with continuous dexmedetomidine (DEX) infusion. Case 1 : An 83-year-old man receiving oral oxycodone for lung cancer pain developed delirium. He was resistant to haloperidol infusion, oral quetiapine, and opioid rotation. DEX infusion was administered at 0.4 microg kg-1 hr-1, and his delirium resolved. Case 2: A 50-year-old woman with cervical cancer of the uterus suffered from sepsis but could not take oral oxycodone. After continuous morphine infusion, she developed delirium. She was resistant to haloperidol infusion or injections of oxycodone for opioid rotation, but DEX infusion at 0.4 microg kg-1hr-1 led to disappearance of delirium symptoms. Case 3: A 71-year-old woman with advanced renal cancer was treated with epidural analgesia to alleviate cancer pain. She subsequently developed delirium but was resistant to haloperidol or chlorpromazine infusion. DEX infusion at 0.3 microg kg-1 hr-1 led to disappearance of delirium symptoms and orientation recovery. DEX infusion may be effective for the treatment of intractable delirium associated with cancer pain. PMID:24498781
Komasawa, Nobuyasu; Kimura, Yoshie; Hato, Akio; Ikegaki, Junichi
Background and Aims Sumatriptan is used specifically to relieve headache pain. The possible efficacy of sumatriptan was investigated in two models of visceral pain. Methods Pancreatic inflammation was induced by intravenous injection of dibutyltin dichloride. Non-inflammatory irritable bowel syndrome was induced by intracolonic instillation of sodium butyrate. The effects of systemic sumatriptan on referred hypersensitivity were tested in both models. Effects of sumatriptan within the rostral ventromedial medulla (RVM), a site of descending modulation of visceral pain, was determined by (a) testing the effects of RVM administration of 5HT1B/D antagonists on systemic sumatriptan action and (b) determining whether RVM application of sumatriptan reproduced the actions of systemic drug administration. Results Systemic sumatriptan elicited a dose- and time-related blockade of referred hypersensitivity in both models that was blocked by systemic administration of either 5HT1B or 5HT1D antagonists. Sumatriptan administered into the RVM similarly produced dose- and time-related blockade of referred hypersensitivity in both visceral pain models. This was blocked by local microinjection of the 5HT1B antagonist, but not the 5HT1D antagonist. Microinjection of 5HT1B or 5HT1D antagonists into the RVM did not block the effects of systemic sumatriptan. Conclusions Our findings suggest that sumatriptan suppresses either inflammatory or non-inflammatory visceral pain, most likely through peripheral 5HT1B/1D receptors. Actions at 5HT1B receptors within the RVM offer an additional potential site of action for the modulation of visceral pain by triptans. These studies offer new insights into the development of strategies which may improve therapy of visceral pain conditions using already available medications.
Vera-Portocarrero, Louis P.; Ossipov, Michael H.; King, Tamara; Porreca, Frank
Studies of both humans and animals suggest that anterior cingulate cortex (ACC) is important for processing pain perception. We identified that perigenul ACC (pACC) sensitization and enhanced visceral pain in a visceral hypersensitive rat in previous studies. Pain contains both sensory and affective dimensions. Teasing apart the mechanisms that control the neural pathways mediating pain affect and sensation in nociceptive behavioral response is a challenge. In this study, using a rodent visceral pain assay that combines the colorectal distension (CRD)-induced visceromotor response (VMR) with the conditioning place avoidance (CPA), we measured a learned behavior that directly reflects the affective component of visceral pain. When CRD was paired with a distinct environment context, the rats spent significantly less time in this compartment on the post-conditioning test days as compared with the pre-conditioning day. Effects were lasted for 14 days. Bilateral pACC lesion significantly reduced CPA scores without reducing acute visceral pain behaviors (CRD-induced VMR). Bilateral administration of non-NMDA receptor antagonist CNQX or NMDA receptor antagonist AP5 into the pACC decreased the CPA scores. AP5 or CNQX at dose of 400 mM produced about 70% inhibition of CRD-CPA in the day 1, 4 and 7, and completely abolished the CPA in the day 14 after conditioning. We concluded that neurons in the pACC are necessary for the "aversiveness" of visceral nociceptor stimulation. pACC activation is critical for the memory processing involved in long-term negative affective state and prediction of aversive stimuli by contextual cue. PMID:22107830
Yan, Ni; Cao, Bing; Xu, Jiahe; Hao, Chun; Zhang, Xu; Li, Ying
The autonomic nervous system (ANS) integrates afferent and motor activity for homeostatic processes including pain. The aim of the study was to compare hitherto poorly characterised relations between brainstem autonomic control and personality in response to visceral and somatic pain. Eighteen healthy subjects (16 females, mean age 34) had recordings during rest and pain of heart rate (HR), cardiac vagal tone (CVT), cardiac sensitivity to baroreflex (CSB), skin conductance level (SC), cardiac sympathetic index (CSI) and mean blood pressure (MBP). Visceral pain was induced by balloon distension in proximal (PB) and distal (DB) oesophagus and somatic pain by nail-bed pressure (NBP). Eight painful stimuli were delivered at each site and unpleasantness and intensity measured. Personality was profiled with the Big Five inventory. (1) Oesophageal intubation evoked "fight-flight" responses: HR and sympathetic (CSI, SC, MBP) elevation with parasympathetic (CVT) withdrawal (p<0.05). (2) Pain at all sites evoked novel parasympathetic/sympathetic co-activation with elevated HR but vasodepression (all p<0.05). (3) Personality traits correlated with slope of distal oesophageal pain-related CVT changes wherein more neurotic-introvert subjects had greater positive pain-related CVT slope change (neuroticism r 0.8, p<0.05; extroversion r -0.5, p<0.05). Pain-evoked heart rate increases were mediated by parasympathetic and sympathetic co-activation - a novel finding in humans but recently described in mammals too. Visceral pain-related parasympathetic change correlated with personality. ANS defence responses are nuanced and may relate to personality type for visceral pain. Clinical relevance of these findings warrants further exploration. PMID:19398272
Paine, Peter; Kishor, Jessin; Worthen, Sian F; Gregory, Lloyd J; Aziz, Qasim
Women demonstrate higher pain sensitivity and prevalence of chronic visceral pain conditions such as functional gastrointestinal disorders than men. The role of sex differences in the brain processing of visceral pain is still unclear. In 16 male and 16 female healthy subjects we compared personality, anxiety levels, skin conductance response (SCR), and brain processing using functional MRI during anticipation and pain induced by esophageal distension at pain toleration level. There was no significant difference in personality scores, anxiety levels, SCR, and subjective ratings of pain between sexes. In group analysis, both men and women demonstrated a similar pattern of brain activation and deactivation during anticipation and pain consistent with previous reports. However, during anticipation women showed significantly greater activation in the cuneus, precuneus, and supplementary motor area (SMA) and stronger deactivation in the right amygdala and left parahippocampal gyrus, whereas men demonstrated greater activation in the cerebellum. During pain, women demonstrated greater activation in the midcingulate cortex, anterior insula, premotor cortex, and cerebellum and stronger deactivation in the caudate, whereas men showed increased activity in the SMA. The pattern of brain activity suggests that, during anticipation, women may demonstrate stronger limbic inhibition, which is considered to be a cognitive modulation strategy for impending painful stimulation. During pain, women significantly activate brain areas associated with the affective and motivation components of pain. These responses may underlie the sex differences that exist in pain conditions, whereby women may attribute more emotional importance to painful stimuli compared with men.
Kano, Michiko; Farmer, Adam D.; Aziz, Qasim; Giampietro, Vincent P.; Brammer, Michael J.; Williams, Steven C. R.; Fukudo, Shin
Irritable bowel syndrome (IBS) is often seen in women, and symptom severity is known to vary over the menstrual cycle. In addition, activation of the hypothalamic-pituitary-adrenal (HPA) axis enhances symptomology and patients with IBS have increased activation of the amygdala, a brain region known to facilitate HPA output. However, little is known about the effects of amygdala activation during different stages of the menstrual cycle. We therefore investigated the effects of amygdala activation on somatic and visceral pain perception over the rat estrous cycle. Female Wistar rats were implanted with either corticosterone (Cort) or cholesterol as a control onto the dorsal margin of the central amygdala. Visceral sensitivity was quantified by recording the visceromotor response (VMR) to colorectal distension (CRD) and somatic sensitivity was assessed via the Von Frey test. In cholesterol controls, both visceral and somatic sensitivity varied over the estrous cycle. Rats in proestrus/estrus responded to CRD with an increased VMR compared with rats in metestrus/diestrus. Somatic sensitivity followed a similar pattern with enhanced sensitivity during proestrus/estrus compared with metestrus/diestrus. Elevated amygdala Cort induced visceral hypersensitivity during metestrus/diestrus but had no effect during proestrus/estrus. In contrast, elevated amygdala Cort increased somatic sensitivity during both metestrus/diestrus and proestrus/estrous. These results suggests that amygdala activation by Cort eliminates spontaneously occurring differences in visceral and somatic pain perception, which could explain the lowered pain thresholds and higher incidence of somatic pain observed in women with IBS. PMID:21454447
Gustafsson, Jenny K; Greenwood-Van Meerveld, Beverley
We introduce an intradural approach to spinal cord stimulation for the relief of intractable pain, and describe the biophysical rationale that underlies its design and performance requirements. The proposed device relies on wireless, inductive coupling between a pial surface implant and its epidural controller, and we present the results of benchtop experiments that demonstrate the ability to transmit and receive a frequency-modulated 1.6 MHz carrier signal between micro-coil antennae scaled to the ~ 1 cm dimensions of the implant, at power levels of about 5 mW. Plans for materials selection, microfabrication, and other aspects of future development are presented and discussed.
Howard, M. A.; Utz, M.; Brennan, T. J.; Dalm, B. D.; Viljoen, S.; Jeffery, N. D.; Gillies, G. T.
The discovery of the tetrodotoxin-resistant (TTX-R) Na+ channel in nociceptive neurons has provided a special target for analgesic intervention. In a previous study we found that both morphine tolerance and persistent visceral inflammation resulted in visceral hyperalgesia. It has also been suggested that hyperexcitability of sensory neurons due to altered TTX-R Na+ channel properties and expression contributes to hyperalgesia; however, we do not know if some TTX-R Na+ channel property changes can be triggered by visceral hyperalgesia and morphine tolerance, or whether there are similar molecular or channel mechanisms in both situations. To evaluate the effects of morphine tolerance and visceral inflammation on the channel, we investigated the dorsal root ganglia (DRG) neuronal change following these chronic treatments. Using whole-cell patch clamp recording, we recorded TTX-R Na+ currents in isolated adult rat lumbar and sacral (L6?S2) DRG neurons from normal and pathologic rats with colon inflammatory pain or chronic morphine treatment. We found that the amplitudes of TTX-R Na+ currents were significantly increased in small-diameter DRG neurons with either morphine tolerance or visceral inflammatory pain. Meanwhile, the result also showed that those treatments altered the kinetics properties of the electrical current (ie, the activating and inactivating speed of the channel was accelerated). Our current results suggested that in both models, visceral chronic inflammatory pain and morphine tolerance causes electrophysiological changes in voltage-gated Na channels due to the chronic administration of these medications. For the first time, the present investigation explored the adaptations of this channel, which may contribute to the hyperexcitability of primary afferent nerves and hyperalgesia during these pathologic conditions. The results also suggest that neurophysiologic mechanisms of morphine tolerance and visceral hyperalgesia are related at the TTX-R Na+ channel.
Chen, Jinghong; Gong, Ze-hui; Yan, Hao; Qiao, Zhijun; Qin, Bo-yi
The ?2-adrenoceptor agonist, clonidine, modulates colorectal sensorimotor functions in humans and, given intrathecally, has analgesic effects in the colorectal distension (CRD) model in rats. We tested the effects of systemic clonidine on the visceral pain-related viscerosomatic and autonomic cardiovascular responses to CRD and colonic compliance in rats using clinically relevant CRD protocols. The activity of the abdominal musculature (viscerosomatic response),
Mikael Brusberg; Anna Ravnefjord; Magnus Lindgreen; Håkan Larsson; Erik Lindström; Vicente Martinez
The mechanism underlying estrogen modulation of visceral pain remains unclear. Our previous studies indicate activation of estrogen receptor ? (ER?) enhances visceral pain. The purpose of the present study was to investigate the role of estrogen receptor ? (ER?) activation in spinal processing of visceral stimuli. The effects of selective ER? agonists on the visceromotor response (VMR) and dorsal horn neuronal responses to colorectal distention (CRD) were tested in ovariectomized and intact female rats. The magnitude of the VMR to CRD was significantly attenuated by ER? agonists diarylpropionitrile (DPN) and WAY200070 four hours after subcutaneous injection. Pretreatment with the estrogen receptor antagonist ICI 182,780 obscured the DPN-evoked attenuation. There was no effect of DPN on the VMR at earlier time points. Subcutaneous and spinal administration of DPN attenuated the response of visceroceptive dorsal horn neurons with a comparable time course. DPN attenuated the VMR in intact rats regardless of estrous cycle stage. The timecourse of effect of ER? activation on the visceromotor response and neuronal activity is consistent with transcriptional or translational modulation of neuronal activity. Perspective Activation of ER? is antinociceptive in the colorectal distention model of visceral pain, which may provide a therapeutic target to manage IBS in the clinic.
Cao, Dong-Yuan; Ji, Yaping; Tang, Bin; Traub, Richard J.
Epigenetic molecular mechanisms, which include DNA methylation and histone deacetylation, are implicated in the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Previously, we demonstrated that repeated water avoidance stress (WAS), a validated model of chronic psychological stress, induces heightened visceral pain behaviors in rodents that resemble irritable bowel syndrome (IBS) sequelae. However, the involvement of epigenetic molecular mechanisms in the pathophysiology of stress-induced visceral pain has not been explored. Our hypothesis is that epigenetic mechanisms within the central nervous system (CNS) are important to chronic stress-induced visceral hypersensitivity. Adult male F-344 rats with intracerebroventricular (i.c.v.) cannulae were exposed to 7 days of repeated WAS. Controls received a SHAM stress. Following the daily 1h stressor, trichostatin A (TSA; 100 ng/ml), a potent histone deacetylase inhibitor, or vehicle (VEH; 0.1% DMSO/saline,) as control was administered via the i.c.v. cannula. Visceral sensitivity was assessed 24h after the final WAS and quantified the visceromotor response (VMR) by recording the number of abdominal contractions in response to graded pressures (20-60 mmHg) of colorectal distensions (CRD). From a separate group of rats that were exposed to repeated WAS or SHAM stress, the amygdala was isolated to assess the methylation status of glucocorticoid receptor (GR) and corticotropin releasing-factor (CRF) genes via bisulfite sequencing and verified by pyrosequencing. GR and CRF gene expression was quantified via qRT-PCR. Stressed rats exhibited visceral hypersensitivity that was significantly attenuated by TSA. Compared to SHAM controls, methylation of the GR gene was increased following WAS while expression of the GR gene was decreased. Methylation of the CRF promoter was decreased with WAS with a concomitant increase in CRF expression. This study demonstrates the involvement of central epigenetic mechanisms in regulating stress-induced visceral hypersensitivity and provides a foundation for exploring the epigenetic mechanisms that may contribute to IBS-like symptomatology. PMID:23084728
Tran, L; Chaloner, A; Sawalha, A H; Greenwood Van-Meerveld, B
OBJECTIVE:We sought to identify central loci that activate in response to visceral stimuli (stool and pain). We had a particular interest in observing the anterior cingulate gyrus and frontal cortex in normals and in patients with intestinal disease, including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS).METHODS:Subjects underwent rectal balloon distention to a sensation of stool and to a
Charles N Bernstein; Uta N Frankenstein; Patricia Rawsthorne; Marshall Pitz; Randy Summers; Michael C McIntyre
In addition to its possible role as a replacement source in CNS degenerative diseases, neural transplantation may be used to augment the normal production of neuroactive substances. Our laboratory at the University of Illinois at Chicago has shown, in both acute and chronic pain models, that transplantation of adrenal medullary tissue or isolated chromaffin cells into CNS pain modulatory regions can reduce pain sensitivity in rodents. Chromaffin cells were chosen as the donor source since they produce high levels of both opioid peptides and catecholamines, substances which reduce pain sensitivity when injected locally into the spinal subarachnoid space. The analgesia produced by these transplants probably results from the release of both opioid peptides and catecholamines since it can be blocked or attenuated by both opiate and adrenergic antagonists. Studies indicate that even over long periods there is no apparent development of tolerance. Promising results have been obtained in preliminary clinical studies using allografts of adrenal medulla to relieve cancer pain. This clinical review encompasses results at two Medical Centers-University of Illinois at Chicago and University Paul Sabatier, Toulouse, France-in assessing efficacy of subarachnoid adrenal medullary transplantation for alleviating cancer pain. Our clinical and autopsy data strongly support our previous laboratory studies, i.e., that chromaffin cell transplants into the subarachnoid space represent a promising new approach to the alleviation of chronic pain. It is suggested that further clinical studies are now warranted. PMID:9090640
Pappas, G D; Lazorthes, Y; Bès, J C; Tafani, M; Winnie, A P
Background and Aims Irritable bowel syndrome (IBS) is linked to post-inflammatory and stress-correlated factors that cause changes in the perception of visceral events. Probiotic bacteria may be effective in treating IBS symptoms. Here, we have investigated whether early life administration of VSL#3, a mixture of 8 probiotic bacteria strains, protects against development of visceral hypersensitivity driven by neonatal maternal separation (NMS), a rat model of IBS. Methods Male NMS pups were treated orally with placebo or VSL#3 from days 3 to 60, while normal, not separated rats were used as controls. After 60 days from birth, perception of painful sensation induced by colorectal distension (CRD) was measured by assessing the abdominal withdrawal reflex (score 0–4). The colonic gene expression was assessed by using the Agilent Whole Rat Genome Oligo Microarrays platform and confirmed by real time PCR. Results NMS rats exhibited both hyperalgesia and allodynia when compared to control rats. VSL#3 had a potent analgesic effect on CRD-induced pain without changing the colorectal compliance. The microarray analysis demonstrated that NMS induces a robust change in the expression of subsets of genes (CCL2, NOS3, THP1, NTRK1, CCR2, BDRKRB1, IL-10, TNFRSF1B, TRPV4, CNR1 and OPRL1) involved in pain transmission and inflammation. TPH1, tryptophan hydroxylase 1, a validated target gene in IBS treatment, was markedly upregulated by NMS and this effect was reversed by VSL#3 intervention. Conclusions Early life administration of VSL#3 reduces visceral pain perception in a model of IBS and resets colonic expression of subsets of genes mediating pain and inflammation. Transcript profiling Accession number of repository for expression microarray data is GSE38942 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38942).
Distrutti, Eleonora; Cipriani, Sabrina; Mencarelli, Andrea; Renga, Barbara; Fiorucci, Stefano
Recognition and management of equine pain have been studied extensively in recent decades and this has led to significant advances. However, there is still room for improvement in the ability to identify and treat pain in horses that have undergone emergency gastrointestinal surgery. This study assessed the validity and clinical application of the composite pain scale (CPS) in horses after emergency gastrointestinal surgery. Composite pain scores were determined every 4h over 3days following emergency gastrointestinal surgery in 48 horses. Inter-observer reliability was determined and another composite visceral pain score (numerical rating scale, NRS) was determined simultaneously with CPS scores. CPS scores had higher inter-observer reliability (r=0.87, K=0.84, P<0.001), compared to NRS scores (r=0.68, K=0.72, P<0.001). Horses that survived without complications had significantly lower CPS and NRS scores compared to horses that were euthanased or had to undergo re-laparotomy (P<0.001). Breed and the location in the intestinal tract (small or large intestine) did not influence pain scores. In conclusion, the use of the CPS improved objectivity of pain scoring in horses following emergency gastrointestinal surgery. High inter-observer reliability allows for comparisons between different observers. This will be of great benefit in larger veterinary hospitals where several attending clinicians are often involved in the care of each case. PMID:24491373
van Loon, Johannes P A M; Jonckheer-Sheehy, Valerie S M; Back, Willem; René van Weeren, P; Hellebrekers, Ludo J
Activation of guanylate cyclase-C (GC-C) expressed predominantly on intestinal epithelial cells by guanylin, uroguanylin or the closely related GC-C agonist peptide, linaclotide, stimulates generation, and release of cyclic guanosine-3?,5?-monophosphate (cGMP). Evidence that the visceral analgesic effects of linaclotide are mediated by a novel, GC-C-dependent peripheral sensory mechanism was first demonstrated in animal models of visceral pain. Subsequent studies with uroguanylin or linaclotide have confirmed the activation of a GC-C/cGMP pathway leading to increased submucosal cGMP mediated by cGMP efflux pumps, which modulates intestinal nociceptor function resulting in peripheral analgesia. These effects can be reproduced by the addition of exogenous cGMP and support a role for GC-C/cGMP signaling in the regulation of visceral sensation, a physiological function that has not previously been linked to the GC-C/cGMP pathway. Notably, targeting the GC-C/cGMP pathway for treatment of gastrointestinal pain and abdominal sensory symptoms has now been validated in the clinic. In 2012, linaclotide was approved in the United States and European Union for the treatment of adult patients with irritable bowel syndrome with constipation.
Hannig, Gerhard; Tchernychev, Boris; Kurtz, Caroline B.; Bryant, Alexander P.; Currie, Mark G.; Silos-Santiago, Inmaculada
Few studies have verified the validity of behavioral and physiological methods of pain assessment in cattle. This prospective, blinded, randomized controlled experimental study aimed to validate different methods of pain assessment during acute and chronic (up to 21 d postintervention) conditions in dairy cattle, in response to 3 analgesic treatments for traumatic reticuloperitonitis. Cerebrospinal fluid (CSF) biomarkers and mechanical sensitization were measured as indicators of centralized pain. Proteomics in the CSF were examined to detect specific (to pain intensity) and sensitive (responsive to analgesia) markers. Recordings of spontaneous behavior with video analysis, telemetered motor activity, pain scales, electrodermal activity, and plasma cortisol concentration were quantified at regular intervals. Cows were assigned to group 1 (n=4, standard control receiving aspirin), group 2 (n=5, test group receiving preemptive tolfenamic acid), or group 3 (n=3, positive control receiving preemptive multimodal analgesia composed of epidural morphine, plus tolfenamic acid and butorphanol). Rescue analgesia was administered as needed. Generalized estimating equations tested group differences and the influence of rescue analgesia on the measurements. All 3 groups demonstrated a long-term decrease in a CSF protein identified as transthyretin. The decrease in transthyretin expression inversely correlated with the expected level of analgesia (group 1<2<3). Moreover, in group 1, CSF noradrenaline decreased long term, cows were hypersensitive to mechanical stimulation, and they demonstrated signs of discomfort with higher motor activity and "agitation while lying" recorded from video analysis. Decreased "feeding behavior," observer-reported pain scales, electrodermal activity, and plasma cortisol concentration were inconsistent to differentiate pain intensity between groups. In summary, changes in CSF biomarkers and mechanical sensitization reflected modulation of central pain in dairy cows. The spontaneous behavior "agitation while lying" was the only behavioral outcome validated for assessing acute and chronic pain in this visceral pain model. PMID:24534501
Rialland, P; Otis, C; de Courval, M-L; Mulon, P-Y; Harvey, D; Bichot, S; Gauvin, D; Livingston, A; Beaudry, F; Hélie, P; Frank, D; Del Castillo, J R E; Troncy, E
Optimal symptoms control in advanced cancer disease, with refractory to conventional pain treatment, needs an interventional procedure. This paper presents coadministration of local anesthetic (LA) via paravertebral blockade (PVB) as the alternative to an unsuccessful subcutaneous fentanyl pain control in a 71-year old cancer patient with pathological fracture of femoral neck, bone metastases, and contraindications to morphine. Bupivacaine in continuous infusion (0.25%, 5 mL · hour?1) or in boluses (10 mL of 0.125%–0.5% solution), used for lumbar PVB, resulted in pain relief, decreased demand for opioids, and led to better social interactions. The factors contributing to an increased risk of systemic toxicity from LA in the patient were: renal impairment; heart failure; hypoalbuminemia; hypocalcemia; and a complex therapy with possible drug-drug interactions. These factors were taken into consideration during treatment. Bupivacaine’s side effects were absent. Coadministered drugs could mask LA’s toxicity. Elevated plasma ?1-acid glycoprotein levels were a protective factor. To evaluate the benefit-risk ratio of the PVB treatment in boluses and in constant infusion, bupivacaine serum levels were determined and the drug plasma half-lives were calculated. Bupivacaine’s elimination was slower when administered in constant infusion than in boluses (t½ = 7.80 hours versus 2.64 hours). Total drug serum concentrations remained within the safe ranges during the whole treatment course (22.9–927.4 ng mL?1). In the case presented, lumbar PVB with bupivacaine in boluses (? 137.5 mg · 24 hours?1) was an easy to perform, safe, effective method for pain control. Bupivacaine in continuous infusion (?150 mg · 12 hours?1) had an acceptable risk-benefits ratio, but was ineffective.
Zaporowska-Stachowiak, Iwona; Kotlinska-Lemieszek, Aleksandra; Kowalski, Grzegorz; Kosicka, Katarzyna; Hoffmann, Karolina; Glowka, Franciszek; Luczak, Jacek
Optimal symptoms control in advanced cancer disease, with refractory to conventional pain treatment, needs an interventional procedure. This paper presents coadministration of local anesthetic (LA) via paravertebral blockade (PVB) as the alternative to an unsuccessful subcutaneous fentanyl pain control in a 71-year old cancer patient with pathological fracture of femoral neck, bone metastases, and contraindications to morphine. Bupivacaine in continuous infusion (0.25%, 5 mL · hour(-1)) or in boluses (10 mL of 0.125%-0.5% solution), used for lumbar PVB, resulted in pain relief, decreased demand for opioids, and led to better social interactions. The factors contributing to an increased risk of systemic toxicity from LA in the patient were: renal impairment; heart failure; hypoalbuminemia; hypocalcemia; and a complex therapy with possible drug-drug interactions. These factors were taken into consideration during treatment. Bupivacaine's side effects were absent. Coadministered drugs could mask LA's toxicity. Elevated plasma ?1-acid glycoprotein levels were a protective factor. To evaluate the benefit-risk ratio of the PVB treatment in boluses and in constant infusion, bupivacaine serum levels were determined and the drug plasma half-lives were calculated. Bupivacaine's elimination was slower when administered in constant infusion than in boluses (t½ = 7.80 hours versus 2.64 hours). Total drug serum concentrations remained within the safe ranges during the whole treatment course (22.9-927.4 ng mL(-1)). In the case presented, lumbar PVB with bupivacaine in boluses (? 137.5 mg · 24 hours(-1)) was an easy to perform, safe, effective method for pain control. Bupivacaine in continuous infusion (?150 mg · 12 hours(-1)) had an acceptable risk-benefits ratio, but was ineffective. PMID:24043944
Zaporowska-Stachowiak, Iwona; Kotlinska-Lemieszek, Aleksandra; Kowalski, Grzegorz; Kosicka, Katarzyna; Hoffmann, Karolina; G?ówka, Franciszek; Luczak, Jacek
Background: The surgical treatment of patients with chronic abdominal pain resulting from intraabdominal adhesions is controversial.\\u000a We report our experience with treatment of this challenging patient population using laparoscopic lysis of adhesions (LOA)\\u000a and placement of Seprafilm (Genzyme, Cambridge, MA, USA). Methods: The participants in this study were 19 consecutive patients\\u000a (2 men and 17 women) who underwent laparoscopic LOA
L. Khaitan; S. Scholz; H. L. Houston; W. O. Richards
The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5min of administration, systemic injection of the drug produced a delayed effect (60min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia. PMID:24485889
Kannampalli, Pradeep; Pochiraju, Soumya; Bruckert, Mitchell; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N
A 51 year-old man presented with acute abdominal pain in our emergency room. The first examination revealed no pathological findings except coprostasis and after an enteroclysis the patient was sent home without any complaints. During a recent episode of abdominal pain a computer tomography was performed, showing dissection of the superior mesenteric and the celiac artery. Without any signs of mesenteric ischemia additional examinations like laboratory studies, x-rays, and abdominal ultrasound might be normal and therefore not helpful for diagnosis. In patients presenting with persistent abdominal pain and unspecific clinical and laboratory findings rare causes of abdominal symptoms should be considered. Despite the rarity of visceral artery dissection, awareness of this pathology is crucial because of its possible lifethreatening complications. Appropriate diagnostic imaging tests may avoid postmortem diagnosis by the pathologist. PMID:15032139
Ruggieri, F; Amann-Vesti, B R; Nigg, C
In the modern age of advanced surgical techniques and pharmacologic management, bacterial spinal infections (SIs) can be managed (either eradicated or suppressed) in many hosts. However, the optimal management of SIs may be limited by patient comorbidities, which do not allow for surgical management, or limited by antimicrobial options due to side effects, toxicities, or emerging drug resistance. In these settings, frank and honest discussion regarding risks and benefits of treatment should be pursued, including that the SI may be a terminal illness. In this case series, we present 3 patients who had bacterial SIs whose treatments were limited by the above-mentioned factors. Furthermore, each case presented challenges regarding optimal medical management of somatic and neuropathic pain associated with the SI.
Olsen, Molly L.; Havyer, Rachel D. A.; Smith, Thomas J.; Swetz, Keith M.
Painful bladder syndrome is a debilitating condition that affects 3–6% of women in the United States. Multiple lines of evidence suggest that changes in central nervous system processing are key to the development of chronic bladder pain conditions, but little is known regarding the underlying cellular, molecular, and neuronal mechanisms. Using a mouse model of distension-induced bladder pain, we found that the central nucleus of the amygdala (CeA) is a critical site of neuromodulation for processing of bladder nociception. Furthermore, we demonstrate that metabotropic glutamate receptor 5 (mGluR5) activation in the CeA induces bladder pain sensitization by increasing CeA output. Thus, pharmacological activation of mGluR5 in the CeA is sufficient to increase the response to bladder distension. Additionally, pharmacological blockade or virally-mediated conditional deletion of mGluR5 in the CeA reduced responses to bladder distention suggesting that mGluR5 in the CeA is also necessary for these responses. Finally, we used optogenetic activation of the CeA and demonstrated that this caused a robust increase in the visceral pain response. The CeA localized effects on responses to bladder distention are associated with changes in extracellular signal regulated kinases 1/2 phosphorylation in the spinal cord. Overall, these data demonstrate that mGluR5 activation leads to increased CeA output that drives bladder pain sensitization.
Crock, Lara W.; Kolber, Benedict J.; Morgan, Clinton D; Sadler, Katelyn E.; Vogt, Sherri K.; Bruchas, Michael R.; Gereau, Robert W.
We have previously shown that subcutaneous bee venom (BV) injection reduces visceral pain behavior in mice, but it is not clear which constituent of BV is responsible for its antinociceptive effect. In the present study, we now demonstrate that a water-soluble subfraction of BV (BVA) reproduces the antinociceptive effect of BV in acetic acid-induced visceral pain model. We further evaluated
Young Bae Kwon; Tae Won Ham; Hyun Woo Kim; Dae Hyun Roh; Seo Yeon Yoon; Ho Jae Han; Il Suk Yang; Kee Won Kim; Alvin J. Beitz; Jang Hern Lee
In patients with irritable bowel syndrome, visceral pain is evoked more readily following distension of the colorectum. However, the identity of extrinsic afferent nerve pathway that detects and transmits visceral pain from the colorectum to the spinal cord is unclear. In this study, we identified which extrinsic nerve pathway(s) underlies nociception from the colorectum to the spinal cord of rodents. Electromyogram recordings were made from the transverse oblique abdominal muscles in anesthetized wild type (C57BL/6) mice and acute noxious intraluminal distension stimuli (100-120?mmHg) were applied to the terminal 15?mm of colorectum to activate visceromotor responses (VMRs). Lesioning the lumbar colonic nerves in vivo had no detectable effect on the VMRs evoked by colorectal distension. Also, lesions applied to the right or left hypogastric nerves failed to reduce VMRs. However, lesions applied to both left and right branches of the rectal nerves abolished VMRs, regardless of whether the lumbar colonic or hypogastric nerves were severed. Electrical stimulation applied to either the lumbar colonic or hypogastric nerves in vivo, failed to elicit a VMR. In contrast, electrical stimulation (2-5?Hz, 0.4?ms, 60?V) applied to the rectum reliably elicited VMRs, which were abolished by selective lesioning of the rectal nerves. DiI retrograde labeling from the colorectum (injection sites 9-15?mm from the anus, measured in unstretched preparations) labeled sensory neurons primarily in dorsal root ganglia (DRG) of the lumbosacral region of the spinal cord (L6-S1). In contrast, injection of DiI into the mid to proximal colon (injection sites 30-75?mm from the anus, measured in unstretched preparations) labeled sensory neurons in DRG primarily of the lower thoracic level (T6-L2) of the spinal cord. The visceral pain pathway activated by acute noxious distension of the terminal 15?mm of mouse colorectum is transmitted predominantly, if not solely, through rectal/pelvic afferent nerve fibers to the spinal cord. The sensory neurons of this spinal afferent pathway lie primarily in the lumbosacral region of the spinal cord, between L6 and S1. PMID:21390285
Kyloh, Melinda; Nicholas, Sarah; Zagorodnyuk, Vladimir P; Brookes, Simon J; Spencer, Nick J
Pain and learning memory have striking similarities in synaptic plasticity. Activation of the N-methyl-d-aspartic acid receptors 2B subunits (NR2B-NMDAs) is responsible for the hippocampal LTP in memory formation. In our previous studies, we found the significant enhancement of CA1 hippocampal long-term potentiation (LTP) induced by high-frequency stimulation (HFS) in rats with chronic visceral pain. However, it is unclear whether the NR2B-NMDAs are required for the LTP in chronic visceral pain. In this study, a rat model with irritable bowel syndrome (IBS) was established by colorectal distention (CRD). The sensitivity of visceral pain and HFS-induced LTP at SC-CA1 synapses were significantly enhanced in IBS-like rats (p<0.05). In addition, hippocampal NR2B protein levels significantly increased in IBS-like rats (p<0.05). To test whether NR2B-NMDAs are responsible for the LTP, effects of Ro 25-6981, a selective antagonist of NR2B-NMDAs, on field potential in CA1 region were investigated in vitro. Our results demonstrated that Ro 25-6981 dose-dependently inhibited the facilitation of CA1 LTP in IBS-like rats. The plausible activation mechanism of hippocampal NR2B-NMDAs in the LTP enhancement was further explored. Western blot data indicated that expression of tyrosine phosphorylated NR2B protein in hippocampus significantly enhanced in IBS-like rats. Accordingly, genistein, a specific inhibitor of tyrosine kinases, dose-dependently blocked the facilitation of hippocampal LTP in IBS-like rats. Furthermore, EMG data revealed that intra-hippocampal injection of Ro 25-6981 dose-dependently attenuated the visceral hypersensitivity. In conclusion, hippocampal NR2B-NMDAs are responsible for the facilitation of CA1 LTP via tyrosine phosphorylation, which leads to visceral hypersensitivity. PMID:24824341
Chen, Yu; Chen, Ai-Qin; Luo, Xiao-Qing; Guo, Li-Xia; Tang, Ying; Bao, Cheng-Jia; Lin, Ling; Lin, Chun
This study assessed the effects of two N-acylethanolamides in established rat models of visceral and somatic inflammatory pain. (1) The therapeutic effects of the cannabinoid anandamide and the putative CB2 agonist palmitoylethanolamide were tested in a model of persistent visceral pain (turpentine inflammation of the urinary bladder). Both anandamide (at a dose of 25 mg\\/kg) and palmitoylethanolamide (at doses of
Sian I. Jaggar; Fauzia S. Hasnie; Senthy Sellaturay; Andrew S. C. Rice
A history of early life adversity (ELA) has health-related consequences that persist beyond the initial maltreatment and into adulthood. Childhood adversity is associated with abnormal glucocorticoid signaling within the hypothalamic-pituitary-adrenal (HPA) axis and the development of functional pain disorders such as the irritable bowel syndrome (IBS). IBS and many adult psychopathologies are more frequently diagnosed in women, and ovarian hormones have been shown to modulate pain sensitivity. Therefore, the sexually dimorphic effects of ELA and the role of ovarian hormones in visceral pain perception represent critical research concepts to enhance our understanding of the etiology of IBS. In this review, we discuss current animal models of ELA and the potential mechanisms through which ovarian hormones modulate the HPA axis to alter nociceptive signaling pathways and induce functionally relevant changes in pain behaviors following ELA.
Chaloner, Aaron; Greenwood-Van Meerveld, Beverley
A history of early life adversity (ELA) has health-related consequences that persist beyond the initial maltreatment and into adulthood. Childhood adversity is associated with abnormal glucocorticoid signaling within the hypothalamic-pituitary-adrenal (HPA) axis and the development of functional pain disorders such as the irritable bowel syndrome (IBS). IBS and many adult psychopathologies are more frequently diagnosed in women, and ovarian hormones have been shown to modulate pain sensitivity. Therefore, the sexually dimorphic effects of ELA and the role of ovarian hormones in visceral pain perception represent critical research concepts to enhance our understanding of the etiology of IBS. In this review, we discuss current animal models of ELA and the potential mechanisms through which ovarian hormones modulate the HPA axis to alter nociceptive signaling pathways and induce functionally relevant changes in pain behaviors following ELA. PMID:23407595
Chaloner, Aaron; Greenwood-Van Meerveld, Beverley
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal illnesses and is characterized by altered visceral perception. Previous studies in IBS have failed to demonstrate altered somatic or cutaneous perception. The aims of the study were to determine whether IBS patients have visceral hypersensitivity and cutaneous heat-induced hyperalgesia restricted to lumbosacral dermatomes, consistent with a localized segmental mechanism.
G. Nicholas Verne; Michael E Robinson; Donald D Price
Background & Aims Electrophysiological and behavioral studies have demonstrated that increased N-methyl-D-aspartate (NMDA) receptor activation of anterior cingulate cortex (ACC) neurons has a critical role in modulating visceral pain responses in viscerally hypersensitive (VH) rats. This study aimed to identify the NMDA receptor subtypes in perigenual ACC (pACC) neurons involved in the facilitation of visceral nociception. Methods We performed in vivo electrophysiological recordings of pACC neurons and examined the visceromotor response (VMR) to colorectal distention (CRD) in normal and VH rats induced by colonic anaphylaxis. The NR2A subtype receptor antagonist NVP-AAM077 and the NR2B receptor antagonist Ro25-6981 were microinjected into the pACC. To downregulate NR2B receptor gene expression, an NR2B-specific small interfering RNA (siRNA) and a plasmid (pEGFP-N1) that expressed the green fluorescent protein were administered into ACC neurons by electroporation. Results Reverse microdialysis of NVP-AAM077 had no effect on basal and CRD-induced ACC neuronal firing in VH and control groups. In VH rats, Ro25-6981 (500 ?M) inhibited ACC neuronal firing, evoked by 30 and 50 mmHg CRD, by 98%, and 52%, respectively. NVP-AAM077 did not affect the VMR in either group. Ro25-6981 significantly suppressed the VMR in VH but not normal rats. Immunoblot analysis showed increased NR2B receptor expression in the pACC of VH rats. NR2B siRNA-treated VH rats showed a significant reduction in the VMR, compared to controls. Conclusions The NR2B subunit of the NMDA receptor has a critical role in the modulation of ACC sensitization and visceral pain responses in VH rats.
Fan, Jing; Wu, Xiaoyin; Cao, Zhijun; Chen, Shengliang; Owyang, Chung; Li, Ying
Intrinsic neurons containing serotonin (5-HT) are involved in the regulation of gastrointestinal motor function and are also thought to be important in the modulation of visceral sensory function. We have evaluated the effect of a specific 5-HT3 antagonist (ondansetron, O) on visceral sensation and rectal compliance in a randomized, double-blind, cross-over, placebo (P) controlled study of·16 mg 3 times\\/day, in
Paul A. Goldberg; Michael A. Kamm; Paulo Setti-Carraro; Christian Roth
A 15-year-old girl with combined immune deficiency syndrome, diagnosed with metastatic squamous cell cancer of the anus, had significant pain secondary to vulvar-perianal condyloma. Conventional treatment with oral and intravenous analgesics was limited by significant side effects of mental status changes and urinary retention leading to clinical deterioration that precluded attempts at chemotherapy. An intrathecal pump was implanted in the challenging setting of neutropenia. There was a drastic improvement in her quality of life and the ability to tolerate further chemotherapy. The option of an intrathecal pump for pain control extended our patient's ability to enjoy important quality time with family by several months. PMID:23652866
Bengali, Raheel; Huang, Mary S; Gulur, Padma
This study describes the antinociceptive effects of ?-opioid agonists, d-Ala(2),N-Me-Phe(4),Gly(5)-ol-enkephalin (DAMGO) and morphine in a model of rat visceral pain in which nociceptive responses were triggered by 2% acetic acid intraperitoneal (i.p.) injections. DAMGO and morphine were administered i.p., to the same site where acetic acid was delivered or intracerebroventricularly (i.c.v.). The antinociceptive actions of i.p. versus i.c.v. administered DAMGO or morphine were evaluated in the late phase of permanent visceral nociceptive responses. Both compounds inhibited the nociceptive responses in a dose-dependent manner and exhibited more potent agonist activity after i.c.v. than i.p. administration. DAMGO and morphine showed comparable ED(50) values after i.p. injections. However, DAMGO was much stronger than morphine after central administration. Co-administration of the peripherally restricted opioid antagonist, naloxone methiodide (NAL-M), significantly attenuated the antinociceptive effects of i.p. DAMGO or morphine. On the other hand, i.c.v. injections of NAL-M partially antagonized the antinociceptive effect of i.p. morphine and failed to affect the antinociceptive action of i.p. DAMGO indicating the partial and pure peripheral antinociceptive effects of morphine and DAMGO, respectively. These results suggest the role of either central or peripheral ?-opioid receptors (MOR) in mediating antinociceptive effects of i.p. ?-opioid agonists in the rat late permanent visceral pain model which closely resembles the clinical situation. PMID:22079588
Al-Khrasani, Mahmoud; Lackó, Erzsébet; Riba, Pál; Király, Kornél; Sobor, Melinda; Timár, Júlia; Mousa, Shaaban; Schäfer, Michael; Fürst, Susanna
OBJECTIVES:Mechanisms of chest pain in gastroesophageal reflux disease (GERD) are poorly understood. The recent demonstration in healthy subjects that lower esophageal acid exposure induces pain hypersensitivity within the nonacid-exposed upper esophagus (secondary allodynia) raises the possibility that an increase in spinal neuronal excitability (i.e., central sensitization) contributes to chest pain in GERD. The aim of this study was to determine
Sanchoy Sarkar; David G. Thompson; Clifford J. Woolf; Anthony R. Hobson; Teri Millane; Qasim Aziz
OBJECTIVE:Abdominal pain is thought to be a hallmark of the irritable bowel syndrome (IBS), although currently used symptom criteria do not differentiate between abdominal pain and discomfort. By focusing on viscerosensory symptoms, we sought to determine: 1) which type of symptoms are most commonly reported by IBS patients, and 2) whether patients who report pain as their most bothersome symptom
Tony Lembo; Bruce Naliboff; Julie Munakata; Steve Fullerton; Lynn Saba; Scott Tung; Max Schmulson; Emeran A Mayer
Abnormal responses of the brain to delivered and expected aversive gut stimuli have been implicated in the pathophysiology of irritable bowel syndrome (IBS), a visceral pain syndrome occurring more commonly in women. Task-free resting-state functional magnetic resonance imaging (fMRI) can provide information about the dynamics of brain activity that may be involved in altered processing and/or modulation of visceral afferent signals. Fractional amplitude of low-frequency fluctuation is a measure of the power spectrum intensity of spontaneous brain oscillations. This approach was used here to identify differences in the resting-state activity of the human brain in IBS subjects compared with healthy controls (HCs) and to identify the role of sex-related differences. We found that both the female HCs and female IBS subjects had a frequency power distribution skewed toward high frequency to a greater extent in the amygdala and hippocampus compared with male subjects. In addition, female IBS subjects had a frequency power distribution skewed toward high frequency in the insula and toward low frequency in the sensorimotor cortex to a greater extent than male IBS subjects. Correlations were observed between resting-state blood oxygen level-dependent signal dynamics and some clinical symptom measures (e.g., abdominal discomfort). These findings provide the first insight into sex-related differences in IBS subjects compared with HCs using resting-state fMRI. PMID:23864686
Hong, Jui-Yang; Kilpatrick, Lisa A; Labus, Jennifer; Gupta, Arpana; Jiang, Zhiguo; Ashe-McNalley, Cody; Stains, Jean; Heendeniya, Nuwanthi; Ebrat, Bahar; Smith, Suzanne; Tillisch, Kirsten; Naliboff, Bruce; Mayer, Emeran A
This resource is part of the AAA Education and Teaching Session. In particular this resource is a summary of the presentation from the AAA Annual Meeting/EB 2010 Master Class: The Problem with Pain. MASTER CLASS: THE PROBLEM WITH PAIN
Dr. Jennifer M McBride (Cleveland Clinic, Lerner College of Medicine of Case Western Reserve University, Surgery)
We report a 54-year-old man who developed visceral varicella-zoster virus (VZV) infection after autologous peripheral blood stem cell transplantation (auto-PBSCT) without using immunosuppressive agents for multiple myeloma. He suffered from severe abdominal pain 2 months after auto-PBSCT, and morphine chloride was needed to control it. Since the characteristic skin rash of VZV infection appeared over his entire body on the seventh hospital day, aciclovir was immediately started with favorable results. It is extremely difficult to diagnose VZV infection when severe abdominal pain proceeds and the eruptions characteristic of VZV infections are absent. This may also result in devastating delays in effective antiviral treatment. The increase in fat density around the celiac trunk and the root of the superior mesenteric artery on computed tomography shown in this case may has contributed to the correct diagnosis of visceral VZV infection. PMID:21139364
Yamada, Satoshi; Iwasaki, Tomohiro; Satoh, Akito; Tsuboi, Yasunori; Yanagi, Masahiko; Takahashi, Toru; Usuda, Hiroyuki; Emura, Iwao
Intraperitoneal injection of propofol inhibits subsequent acetic acid-induced writhing response in mice. Propofol increases the sensitivity of dorsal root ganglion neurons to capsaicin through transient receptor potential ankyrin subtype-1 (TRPA1) and protein kinase C? (PKC?)-mediated phosphorylation of transient receptor potential vanilloid subtype-1 (TRPV1). Intraperitoneal co-injection of propofol may increase visceral nociception induced by TRPV1 agonists via sensitization of TRPV1. Therefore, we investigated the effects of intraperitoneal co-injection of propofol on nociception induced by acetic acid and capsaicin. The number of writhing movements induced by acetic acid or nociception time by capsaicin with or without propofol were counted. Neonatal capsaicin-treated mice were also used to demonstrate the role of TRPV1 in the effects of propofol on nociception, induced by TRPV1 agonists. Co-injection of propofol resulted in a pronociceptive effect on the writhing response induced by acetic acid, while the same dose of propofol ameliorated the response to capsaicin. The writhing response to intraperitoneal acetic acid was sharply inhibited following neonatal treatment with capsaicin. Co-injection with propofol reduced the number of writhing movements induced by acetic acid in neonatal capsaicin-treated mice. These results suggest that propofol binds to TRPV1 at the capsaicin-binding pocket.
JI, WENJIN; CUI, CAN; ZHANG, ZHIWEI; LIANG, JIEXIAN
Afferent fibers innervating the gastrointestinal tract have major roles in consciously evoked sensations including pain. We reported previously that the activation of ERK1/2, a member of the mitogen-activated protein kinase (MAPK) family, in primary sensory neurons was involved in acute visceral pain. Moreover, we also revealed that this activation of ERK1/2 occurred through transient receptor potential (TRP) A1, a member of the TRP family of ion channels. In contrast, it is known that the activation of p38 MAPK (p38) contributes to the development and maintenance of inflammatory and neuropathic pain. On the basis of these results, the aim of this study was to investigate the involvement of p38 and TRPA1 in acute visceral pain. Male Sprague-Dawley rats were used. Electromyographic responses to gastric distension (GD) were recorded from the acromiotrapezius muscle. We then examined the phosphorylated-p38 (p-p38) labeling in the dorsal root ganglion (DRG) after GD using immunohistochemistry. Noxious GD induced p-p38 in DRG neurons with a peak at 2 min after GD. We also found a stimulus intensity-dependent increase in the number of p-p38-immunoreactive neurons in the DRG. Intrathecal administration of the p38 inhibitor, SB203580, attenuated the electromyographic response to noxious GD. Furthermore, intrathecal administration of TRPA1 antisense oligodeoxynucleotide decreased the p38 activation in DRG neurons. The activation of p38 pathways in DRG neurons by noxious GD may be correlated with the activation state of the primary afferent neurons through TRPA1, and further, involved in the development of visceral pain. PMID:23222658
Kondo, Takashi; Sakurai, Jun; Miwa, Hiroto; Noguchi, Koichi
It has been shown that imipramine, a tricyclic antidepressant (TCA), is a potent analgesic agent. However, the effect of imipramine on visceral pain has not been extensively investigated. In the current study, our aim was to characterise the putative analgesic effect of intravenous imipramine on visceral pain in rats. Our second aim was to assess the involvement of serotonergic (5-HT2, 3, 4) and noradrenergic (?2A, 2B, 2C) receptor subtypes in this putative antinociceptive effect of imipramine. Male Sprague Dawley rats (250-300g) were implanted with venous catheters for drug administration and implanted with enamelled nichrome electrodes for electromyography of the external oblique muscles. Noxious visceral stimulation was applied via by colorectal distension (CRD). The visceromotor responses (VMRs) to CRD were quantified electromyographically before and after imipramine administration at 5, 15, 30, 60, 90 and 120min. In the antagonist groups, the agents were administered 10min before imipramine. The administration of imipramine (5-40mg/kg) produced a dose-dependent reduction in VMR. The administration of yohimbine (a nonselective ?2-adrenoceptor antagonist, 1mg/kg), BRL-44408 (an ?2A-adrenoceptor antagonist, 1mg/kg) or MK-912 (an ?2C-adrenoceptor antagonist, 300?g/kg) but not imiloxan (an ?2B-adrenoceptor antagonist, 1mg/kg) inhibited the antinociceptive effect of imipramine (20mg/kg). Additionally, ketanserin (a 5-HT2 receptor antagonist, 0.5, 1, and 2mg/kg) and GR113808 (a 5-HT4 receptor antagonist, 1mg/kg) enhanced, and ondansetron (a 5-HT3 receptor antagonist, 0.5, 1, and 2mg/kg) failed to alter the imipramine-induced antinociceptive effect. Our data demonstrated that, in the CDR-induced rat visceral pain model, intravenous imipramine appeared to have antinociceptive potential and that ?2A-/?2C-adrenoceptors and 5-HT2/5-HT4 receptors may be responsible for the antinociceptive effect of imipramine on visceral pain in rats. PMID:24582849
Ilkaya, Fatih; Bilge, S S?rr?; Bozkurt, Ayhan; Ba?, Duygu B; Erdal, Arzu; Ciftçio?lu, Engin; Kesim, Yüksel
Treatment of pain of urogenital origin, chronic pelvic pain syndrome, can be frustrating for patients and physicians. The\\u000a usual approaches do not always produce the desired results. Visceral pain from pelvic organs and myofascial pain from muscle\\u000a trigger points share common characteristics. Referred pain from myofascial trigger points can mimic visceral pain syndromes\\u000a and visceral pain syndromes can induce trigger
Eight patients with intractable diplopia are presented. A classification of intractable diplopia is proposed, as well as a possible unifying view of its pathogenesis. Currently available treatment modalities are reviewed.
William D. Gruzensky; Earl A. Palmer
Laser acupuncture is defined as the stimulation of traditional acupuncture points with low-intensity, non-thermal laser irradiation. We explored the clinical efficacy of a very low level diode laser wavelength 670nm (Biolite LP020, RGM, Genoa, Italy), used to stimulate acupoints ST36 Zu San Li and TH5 Waiguan, on well-established experimental models of acute and persistent pain in the rat, e.g. acute
L. Lorenzini; A. Giuliani; L. Giardino; L. Calzà
An intractable case of Post-herpetic Neuralgia (PHN) in which all other treat- ment options were exhausted was suc- cessfully treated with intrathecal baclofen infusion with a complex continuous deliv- ery mode. A 72-year old man presented to the pain clinic with a 4-year history of left lower extremity PHN. He had seen multiple experts in the field, failed numerous pharmacological
Amr Hosny; Thomas Simopoulos; Beth Collins
Background Stress worsens abdominal pain experienced by patients with irritable bowel syndrome (IBS), a chronic disorder of unknown origin with comorbid anxiety. We have previously demonstrated colonic hypersensitivity in Wistar-Kyoto rats (WKYs), a high-anxiety strain, that models abdominal pain in IBS. In low-anxiety rats, we have demonstrated that the central nucleus of the amygdala (CeA) regulates colonic hypersensitivity and anxiety induced by selective activation of either glucocorticoid receptors (GR) or mineralocorticoid receptors (MR), which is also mediated by the corticotropin releasing factor (CRF) type-1 receptor. The goal of the present study was to test the hypothesis that the CeA through GR, MR and/or CRF-1R regulates colonic hypersensitivity in WKYs. Methods One series of WKYs had micropellets of a GR antagonist, an MR antagonist or cholesterol (control) stereotaxically implanted onto the CeA. Another series were infused in the CeA with CRF-1R antagonist or vehicle. Colonic sensitivity was measured as a visceromotor response (VMR) to graded colorectal distension (CRD). Key Results The exaggerated VMR to graded CRD in WKYs was unaffected by GR or MR antagonism in the CeA. In contrast, direct CeA infusion of CRF-1R antagonist significantly inhibited the VMR to CRD at noxious distension pressures. Conclusions & Inferences Stress-hormones in the CeA regulate colonic hypersensitivity in the rat through strain-dependent parallel pathways. The colonic hypersensitivity in WKYs is mediated by a CRF-1R mechanism in the CeA, independent of GR and MR. These complementary pathways suggest multiple etiologies whereby stress hormones in the CeA may regulate abdominal pain in IBS patients.
Johnson, Anthony C.; Tran, Lee; Schulkin, Jay; Greenwood-Van Meerveld, Beverley
A case of high-voltage electrical injury with massive retroperitoneal muscle necrosis, focal hepatic coagulation necrosis, acute pancreatitis, and an acute coagulopathy with factor V, factor X, and platelet deficits occurred. Visceral involvement by elect...
K. Eurenius P. W. Curreri T. W. Newsome
Brainstem and spinal mechanisms mediating visceral nociception are investigated here using electrophysiology and immunohistochemistry techniques in a model of acute visceral pain. Colorectal distension (CRD) produced graded visceromotor responses (VMR) in normal rats, and these were facilitated by intracolonic mustard oil (MO) that generated acute visceral hyperalgesia. The neuropathic pain drug pregabalin (PGB) is thought to have state-dependent effects in attenuating neuropathic, but not acute somatic pain, likely by impairing calcium-channel trafficking. We found that systemic PGB produced antinociceptive effects on CRD-evoked VMRs in naïve rats lacking pathophysiology and in MO-pretreated rats. Systemic PGB also significantly reduced Fos labelling in lumbosacral spinal cords of rats given noxious repetitive CRD; however, PGB did not alter this measure of neural activity in the brainstem. Differential brainstem processing of noxious somatic and visceral stimuli may underlie the unique lack of state-dependent actions of PGB in this visceral pain model. Single-unit recordings in the rostral ventromedial medulla (RVM) verify that brainstem processing of somatic and visceral stimuli differs. The effects of CRD on RVM cells classed as ON, OFF, or NEUTRAL were independent of their somatic responses, with surprising changes in RVM cell activity to innocuous visceral stimulation. PGB also markedly reduced the visceral responses of RVM ON-cells to noxious CRD. These results illustrate clear differences in the central processing of visceral and somatic stimuli, yet a common role for descending modulation by brainstem activity in mediating evoked pain measures.
Sikandar, Shafaq; Dickenson, Anthony H.
Brainstem and spinal mechanisms mediating visceral nociception are investigated here using electrophysiology and immunohistochemistry techniques in a model of acute visceral pain. Colorectal distension (CRD) produced graded visceromotor responses (VMR) in normal rats, and these were facilitated by intracolonic mustard oil (MO) that generated acute visceral hyperalgesia. The neuropathic pain drug pregabalin (PGB) is thought to have state-dependent effects in attenuating neuropathic, but not acute somatic pain, likely by impairing calcium-channel trafficking. We found that systemic PGB produced antinociceptive effects on CRD-evoked VMRs in naïve rats lacking pathophysiology and in MO-pretreated rats. Systemic PGB also significantly reduced Fos labelling in lumbosacral spinal cords of rats given noxious repetitive CRD; however, PGB did not alter this measure of neural activity in the brainstem. Differential brainstem processing of noxious somatic and visceral stimuli may underlie the unique lack of state-dependent actions of PGB in this visceral pain model. Single-unit recordings in the rostral ventromedial medulla (RVM) verify that brainstem processing of somatic and visceral stimuli differs. The effects of CRD on RVM cells classed as ON, OFF, or NEUTRAL were independent of their somatic responses, with surprising changes in RVM cell activity to innocuous visceral stimulation. PGB also markedly reduced the visceral responses of RVM ON-cells to noxious CRD. These results illustrate clear differences in the central processing of visceral and somatic stimuli, yet a common role for descending modulation by brainstem activity in mediating evoked pain measures. PMID:21778018
Sikandar, Shafaq; Dickenson, Anthony H
Background: Epistaxis is a common otolaryngology emergency and is often controlled with first-line interventions such as cautery, hemostatic agents, or anterior nasal packing. A subset of patients will continue to bleed and require more aggressive therapy. Methods: Intractable spontaneous epistaxis was traditionally managed with posterior nasal packing and prolonged hospital admission. In an effort to reduce patient morbidity and shorten hospital stay, surgical and endovascular techniques have gained popularity. A literature review was conducted. Results: Transnasal endoscopic sphenopalatine artery ligation and arterial embolization provide excellent control rates but the decision to choose one over the other can be challenging. The role of transnasal endoscopic anterior ethmoid artery ligation is unclear but may be considered in certain cases when bleeding localizes to the ethmoid region. Conclusion: This article will focus on the management of intractable spontaneous epistaxis and discuss the role of endoscopic arterial ligation and embolization as it pertains to this challenging clinical scenario.
Visceral leishmaniasis (VL) is a vector-borne parasitic disease targeting tissue macrophages. It is among the most neglected infectious diseases. Classical manifestations of VL include chronic fever, hepatosplenomegaly, and pancytopenia. Most cases can be detected through serologic and molecular testing. Although therapy has historically relied on antimonials, newer therapeutic options include conventional or liposomal amphotericin B, paromomycin and miltefosine. Coinfection with human immunodeficiency virus (HIV) is increasingly reported and comes with additional diagnostic and therapeutic challenges. This article provides an up-to-date clinical review of VL focusing on clinical presentation, diagnosis, management, and issues related to HIV coinfection. PMID:22632641
van Griensven, Johan; Diro, Ermias
Visceral hypersensitivity is currently considered a key pathophysiological mechanism involved in pain perception in large\\u000a subgroups of patients with functional gastrointestinal disorders, including irritable bowel syndrome (IBS). In IBS, visceral\\u000a hypersensitivity has been described in 20%–90% of patients. The contribution of the central nervous system and psychological\\u000a factors to visceral hypersensitivity in patients with IBS may be significant, although still
Giovanni Barbara; Cesare Cremon; Roberto De Giorgio; Giovanni Dothel; Lisa Zecchi; Lara Bellacosa; Giovanni Carini; Vincenzo Stanghellini; Roberto Corinaldesi
Common factors contributing to intractable pain and medical problems with insufficient drug uptake in areas to be treated, and their pathogenesis and treatment: Part I. Combined use of medication with acupuncture, (+) Qi gong energy-stored material, soft laser or electrical stimulation.
Most frequently encountered causes of intractable pain and intractable medical problems, including headache, post-herpetic neuralgia, tinnitus with hearing difficulty, brachial essential hypertension, cephalic hypertension and hypotension, arrhythmia, stroke, osteo-arthritis, Minamata disease, Alzheimer's disease and neuromuscular problems, such as Amyotrophic Lateral Sclerosis, and cancer are often found to be due to co-existence of 1) viral or bacterial infection, 2) localized microcirculatory disturbances, 3) localized deposits of heavy metals, such as lead or mercury, in affected areas of the body, 4) with or without additional harmful environmental electro-magnetic or electric fields from household electrical devices in close vicinity, which create microcirculatory disturbances and reduced acetylcholine. The main reason why medications known to be effective prove ineffective with intractable medical problems, the authors found, is that even effective medications often cannot reach these affected areas in sufficient therapeutic doses, even though the medications can reach the normal parts of the body and result in side effects when doses are excessive. These conditions are often difficult to treat or may be considered incurable in both Western and Oriental medicine. As solutions to these problems, the authors found some of the following methods can improve circulation and selectively enhance drug uptake: 1) Acupuncture, 2) Low pulse repetition rate electrical stimulation (1-2 pulses/second), 3) (+) Qi Gong energy, 4) Soft lasers using Ga-As diode laser or He-Ne gas laser, 5) Certain electro-magnetic fields or rapidly changing or moving electric or magnetic fields, 6) Heat or moxibustion, 7) Individually selected Calcium Channel Blockers, 8) Individually selected Oriental herb medicines known to reduce or eliminate circulatory disturbances. Each method has advantages and limitations and therefore the individually optimal method has to be selected. Applications of (+) Qi Gong energy stored paper or cloth every 4 hours, along with effective medications, were often found to be effective, as Qigongnized materials can often be used repeatedly, as long as they are not exposed to rapidly changing electric, magnetic or electro-magnetic fields. Application of (+) Qi Gong energy-stored paper or cloth, soft laser or changing electric field for 30-60 seconds on the area above the medulla oblongata, vertebral arteries or endocrine representation area at the tail of pancreas reduced or eliminated microcirculatory disturbances and enhanced drug uptake.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1353650
Omura, Y; Losco, B M; Omura, A K; Takeshige, C; Hisamitsu, T; Shimotsuura, Y; Yamamoto, S; Ishikawa, H; Muteki, T; Nakajima, H
Establishing an appropriate treatment strategy for patients presenting with low-back pain, in the absence of stenosis or spondylolisthesis, remains a controversial subject. Inherent to this situation is often an inability to adequately identify the source of low-back pain to justify various treatment recommendations, such as lumbar fusion. The current evidence does not identify a single best treatment alternative for these patients. Based on a number of prospective, randomized trials, comparable outcomes, for patients presenting with 1- or 2-level degenerative disc disease, have been demonstrated following either lumbar fusion or a comprehensive rehabilitation program with a cognitive element. Limited access to such comprehensive rehabilitative programs may prove problematic when pursuing this alternative. For patients whose pain is refractory to conservative care, lumbar fusion is recommended. Limitations of these studies preclude the ability to present the most robust recommendation in support of lumbar fusion. A number of lesser-quality studies, primarily case series, also support the use of lumbar fusion in this patient population. PMID:24980584
Eck, Jason C; Sharan, Alok; Ghogawala, Zoher; Resnick, Daniel K; Watters, William C; Mummaneni, Praveen V; Dailey, Andrew T; Choudhri, Tanvir F; Groff, Michael W; Wang, Jeffrey C; Dhall, Sanjay S; Kaiser, Michael G
Epilepsy surgery can be divided into two categories, resective and disconnective procedures. The former includes lesionectomy, corticectomy, and lobectomy. The latter comprises MST (multiple subpial transection), corpus callosotomy, and hemispherotomy. In this presentation, the preoperative diagnosis and surgical outcomes of temporal lobectomy and MST will be illustrated. Temporal lobe epilepsy is one of the most common seizures in adult intractable epilepsy. Noninvasive preoperative evaluation, including analysis of seizure semiology, repetitive scalp EEG, and MR imaging, can definitely localize the seizure focus, without depending on invasive monitoring, in 70% of the cases. Seizure outcome after temporal lobectomy is generally satisfactory, with 70% seizure-free and > 90% significantly improved. However, verbal amnesia is an unavoidable sequela when the focus is on the speech-dominant side and preoperative MRI reveals little or no hippocampal atrophy. MST is an epoch-making surgical technique by which surgical treatment of eloquent cortex has become possible. In cases with neocortical epilepsy treated by MST alone or combined with corticectomy, 80% showed significant improvement, that is compatible with reported outcomes of corticectomy. MST can be also applied to treatments of extensive epileptic foci, Rasmussen's encephalitis, or Landau-Kleffner syndrome. PMID:12235806
Disruption of the kappa-opioid receptor gene in mice enhances sensitivity to chemical visceral pain, impairs pharmacological actions of the selective kappa-agonist U-50,488H and attenuates morphine withdrawal.
***micro***-, delta- and kappa-opioid receptors are widely expressed in the central nervous system where they mediate the strong analgesic and mood-altering actions of opioids, and modulate numerous endogenous functions. To investigate the contribution of the kappa-opioid receptor (KOR) to opioid function in vivo, we have generated KOR-deficient mice by gene targeting. We show that absence of KOR does not modify expression of the other components of the opioid system, and behavioural tests indicate that spontaneous activity is not altered in mutant mice. The analysis of responses to various nociceptive stimuli suggests that the KOR gene product is implicated in the perception of visceral chemical pain. We further demonstrate that KOR is critical to mediate the hypolocomotor, analgesic and aversive actions of the prototypic kappa-agonist U-50, 488H. Finally, our results indicate that this receptor does not contribute to morphine analgesia and reward, but participates in the expression of morphine abstinence. Together, our data demonstrate that the KOR-encoded receptor plays a modulatory role in specific aspects of opioid function.
Simonin, F; Valverde, O; Smadja, C; Slowe, S; Kitchen, I; Dierich, A; Le Meur, M; Roques, B P; Maldonado, R; Kieffer, B L
The nociceptive transmission under pathological chronic pain conditions involves transcriptional and/or translational alteration in spinal neurotransmitters and receptors expression, and modification of neuronal function. Studies indicate the involvement of MicroRNA (miRNA)-mediated transcriptional deregulation in pathophysiology of acute and chronic pain. In the present study, we tested the hypothesis that long-term cross-organ colonic hypersensitivity in neonatally zymosan-induced cystitis is due to miRNA-mediated posttranscriptional suppression of the developing spinal GABAergic system. Cystitis was produced by intravesicular injection of zymosan (1% in saline) into the bladder during postnatal (P) days P14 through P16 and spinal dorsal horns (L6-S1) were collected either on P60 (unchallenge groups) or on P30 following a zymosan re-challenge on P29 (re-challenge groups). miRNA arrays and Real-time reverse transcription polymerase chain reaction revealed significant, but differential, upregulation of mature miR-181a in the L6-S1 spinal dorsal horns from zymosan-treated rats compared with saline controls in both unchallenge and re-challenge groups. The target gene analysis demonstrated multiple complementary binding sites in miR-181a for GABAA receptor subunit GABAA??1 gene with a miRSVR score of ?1.83. Increase in miR-181a concomitantly resulted in significant downregulation of GABAA??1 receptor subunit gene and protein expression in adult spinal cords from neonatal cystitis rats. Intrathecal administration of GABAA receptor agonist muscimol failed to attenuate viscero-motor response (VMR) to colon distension in neonatal cystitis rats, whereas, in adult zymosan-treated rats the drug produced significant decrease in VMR. These results support an integral role for miRNA-mediated transcriptional deregulation of GABAergic system in neonatal cystitis-induced chronic pelvic pain.
Sengupta, JN; Pochiraju, S; Kannampalli, P; Bruckert, M; Addya, S; Yadav, P; Miranda, A; Shaker, R; Banerjee, B
A 38-year-old male with a past history of intravenous drug use, AIDS and Visceral Leishmaniasis in 2000, was hospitalized after presenting with fever, myalgias and arthralgias, fatigue, hepatosplenomegaly and oedema of the inferior limbs. On the tenth day of admission, the patient developed painful subcutaneous nodules of the thighs and a Dermatology consultation was requested. A clinical and histological diagnosis of Leishmania Panniculitis was made, in the setting of Visceral Leishmaniasis recurrence. Leishmania Panniculitis is rarely found simultaneously with Visceral Leishmaniasis, and it is more frequently seen in HIV co-infected patients. In this case, the skin involvement allowed for an early diagnosis and histological confirmation of Leishmaniasis recrudescence to be made. PMID:22521027
Lencastre, André; João, Alexandre; Lopes, Maria João
The nociceptive transmission under pathological chronic pain conditions involves transcriptional and/or translational alteration in spinal neurotransmitters, receptor expressions, and modification of neuronal functions. Studies indicate the involvement of microRNA (miRNA) - mediated transcriptional deregulation in the pathophysiology of acute and chronic pain. In the present study, we tested the hypothesis that long-term cross-organ colonic hypersensitivity in neonatal zymosan-induced cystitis is due to miRNA-mediated posttranscriptional suppression of the developing spinal GABAergic system. Cystitis was produced by intravesicular injection of zymosan (1% in saline) into the bladder during postnatal (P) days P14 through P16 and spinal dorsal horns (L6-S1) were collected either on P60 (unchallenged groups) or on P30 after a zymosan re-challenge on P29 (re-challenged groups). miRNA arrays and real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed significant, but differential, up-regulation of mature miR-181a in the L6-S1 spinal dorsal horns from zymosan-treated rats compared with saline-treated controls in both the unchallenged and re-challenged groups. The target gene analysis demonstrated multiple complementary binding sites in miR-181a for GABA(A) receptor subunit GABA(A?-1) gene with a miRSVR score of -1.83. An increase in miR-181a concomitantly resulted in significant down-regulation of GABA(A?-1) receptor subunit gene and protein expression in adult spinal cords from rats with neonatal cystitis. Intrathecal administration of the GABA(A) receptor agonist muscimol failed to attenuate the viscero-motor response (VMR) to colon distension in rats with neonatal cystitis, whereas in adult zymosan-treated rats the drug produced significant decrease in VMR. These results support an integral role for miRNA-mediated transcriptional deregulation of the GABAergic system in neonatal cystitis-induced chronic pelvic pain. PMID:23273104
Sengupta, Jyoti N; Pochiraju, Soumya; Pochiraju, Soumiya; Kannampalli, Pradeep; Bruckert, Mitchell; Addya, Sankar; Yadav, Priyanka; Miranda, Adrian; Shaker, Reza; Banerjee, Banani
Background When lung cancer fears emerged in the 1950s, cigarette companies initiated a shift in cigarette design from unfiltered to filtered cigarettes. Both the ineffectiveness of cigarette filters and the tobacco industry's misleading marketing of the benefits of filtered cigarettes have been well documented. However, during the 1950s and 1960s, American cigarette companies spent millions of dollars to solve what the industry identified as the ‘filter problem’. These extensive filter research and development efforts suggest a phase of genuine optimism among cigarette designers that cigarette filters could be engineered to mitigate the health hazards of smoking. Objective This paper explores the early history of cigarette filter research and development in order to elucidate why and when seemingly sincere filter engineering efforts devolved into manipulations in cigarette design to sustain cigarette marketing and mitigate consumers' concerns about the health consequences of smoking. Methods Relevant word and phrase searches were conducted in the Legacy Tobacco Documents Library online database, Google Patents, and media and medical databases including ProQuest, JSTOR, Medline and PubMed. Results 13 tobacco industry documents were identified that track prominent developments involved in what the industry referred to as the ‘filter problem’. These reveal a period of intense focus on the ‘filter problem’ that persisted from the mid-1950s to the mid-1960s, featuring collaborations between cigarette producers and large American chemical and textile companies to develop effective filters. In addition, the documents reveal how cigarette filter researchers' growing scientific knowledge of smoke chemistry led to increasing recognition that filters were unlikely to offer significant health protection. One of the primary concerns of cigarette producers was to design cigarette filters that could be economically incorporated into the massive scale of cigarette production. The synthetic plastic cellulose acetate became the fundamental cigarette filter material. By the mid-1960s, the meaning of the phrase ‘filter problem’ changed, such that the effort to develop effective filters became a campaign to market cigarette designs that would sustain the myth of cigarette filter efficacy. Conclusions This study indicates that cigarette designers at Philip Morris, British-American Tobacco, Lorillard and other companies believed for a time that they might be able to reduce some of the most dangerous substances in mainstream smoke through advanced engineering of filter tips. In their attempts to accomplish this, they developed the now ubiquitous cellulose acetate cigarette filter. By the mid-1960s cigarette designers realised that the intractability of the ‘filter problem’ derived from a simple fact: that which is harmful in mainstream smoke and that which provides the smoker with ‘satisfaction’ are essentially one and the same. Only in the wake of this realisation did the agenda of cigarette designers appear to transition away from mitigating the health hazards of smoking and towards the perpetuation of the notion that cigarette filters are effective in reducing these hazards. Filters became a marketing tool, designed to keep and recruit smokers as consumers of these hazardous products.
Advancement in high throughput DNA sequencing technologies has supported a rapid proliferation of microbial genome sequencing projects, providing the genetic blueprint for for in-depth studies. Oftentimes, difficult to sequence regions in microbial genomes are ruled intractable resulting in a growing number of genomes with sequence gaps deposited in databases. A procedure was developed to sequence such difficult regions in the non-contiguous finished Desulfovibrio desulfuricans ND132 genome (6 intractable gaps) and the Desulfovibrio africanus genome (1 intractable gap). The polynucleotides surrounding each gap formed GC rich secondary structures making the regions refractory to amplification and sequencing. Strand-displacing DNA polymerases used in concert with a novel ramped PCR extension cycle supported amplification and closure of all gap regions in both genomes. These developed procedures support accurate gene annotation, and provide a step-wise method that reduces the effort required for genome finishing.
Hurt, Jr., Richard Ashley [ORNL; Brown, Steven D [ORNL; Podar, Mircea [ORNL; Palumbo, Anthony Vito [ORNL; Elias, Dwayne A [ORNL
In 16 infants with intractable diarrhoea, latent otomastoiditis was found in 9 (3 at necropsy and 6 at myringotomy-antrotomy). In 5 of the 6 operated group, surgery was followed by a striking cessation of the diarrhoea and with weight gain. It is concluded that (1) latent otomastoiditis may be a perpetuating factor in intractable diarrhoea; (2) myringotomy-antrotomy should be considered if other forms of treatment have failed, and especially if there is leucocytosis; (3) mastoiditis with diffuse osteitis seems to be associated with a poor prognosis.
Salazar de Sousa, J; da Silva, A; da Costa Ribeiro, V
Persistent and intractable hiccups (with respective durations of more than 48 hours and 1 month) can result in depression, fatigue, impaired sleep, dehydration, weight loss, malnutrition, and aspiration syndromes. The conventional treatments for hiccups are either non-pharmacological, pharmacological or a nerve block treatment. Pulsed radiofrequency lesioning (PRFL) has been proposed for the modulation of the excited nervous system pathway of pain as a safe and nondestructive treatment method. As placement of the electrode in close proximity to the targeted nerve is very important for the success of PRFL, ultrasound appears to be well suited for this technique. A 74-year-old man suffering from intractable hiccups that had developed after a coronary artery bypass graft and had continued for 7 years was referred to our pain clinic. He had not been treated with conventional methods or medications. We performed PRFL of the phrenic nerve guided by ultrasound and the hiccups disappeared.
Kang, Keum Nae; Park, In Kyung; Suh, Jeong Hun; Leem, Jeong Gill
The effectiveness of systemic lidocaine in relieving acute and chronic pain has been recognized for over 35 years. In particular, systemic lidocaine has been utilized both as a diagnostic and therapeutic tool for intractable neuropathic pain during the last decade. The introduction of oral lidocaine congeners such as mexiletine has significantly extended the usage of lidocaine therapy in chronic pain
Jianren Mao; Lucy L. Chen
Results: Medical records of 424 adult patients under- going strabismus surgery were studied. Of these pa- tients, 143 (34%) experienced diplopia when tested pre- operatively with prisms to simulate the desired surgical outcome. Only 40 patients (9%) had temporary diplo- pia after surgery, which resolved in all cases by 6 weeks postoperatively. Three patients (0.8%) developed per- sistent intractable diplopia.
Burton J. Kushner
Interstitial cystitis represents a diagnostic and therapeutic challenge. Most patients can be managed conservatively, but a small number of patients do not respond to conservative therapy and for them surgical treatment is indicated. This article reviews the historical and currently used surgical modalities. Enterocystoplasty is the surgical treatment of choice for intractable interstitial cystitis. The results of enterocystoplasty are satisfactory
G. Zhang; D. Kappor; A. Sidi
Over the past 11 years, I have experienced a few patients with intractable ascites after extended radical surgery for gastric carcinomas, which accounted for 1.0% (4 of 394) of all gastric carcinomas resected in our institute. These 4 patients underwent total or subtotal gastrectomy with extended lymphadenectomy, including the lymph nodes of the hepatoduodenal ligament. Histopathologic examination of an intraoperative
Background & Aims: Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity, possibly related to abnormal brain-gut communication. Positron emission tomography imaging has suggested specific central nervous system (CNS) abnormalities in visceral pain processing in IBS. This study aimed to determine (1) if functional magnetic resonance imaging (fMRI) detects CNS activity during painful and nonpainful visceral stimulation; and (2) if
Howard Mertz; Victoria Morgan; Gordon Tanner; David Pickens; Ronald Price; Yu Shyr; Robert Kessler
In this paper the Authors report their experience on diagnostic and surgical procedures with respect to aneurysms of the visceral district. The clinical review during the last ten years of surgical activity in the Istituto di Clinica Chirurgica (Università di Ferrara) regards 13 patients with different visceral aneurysms. The study reports the different percentage of localization, the diagnostic approach, the surgical procedure performed and discussion of results obtained. Patients at risk for this disease are pointed out. PMID:1808538
Vettorello, G F; Mascoli, F; Taddia, M C; Gasbarro, V; Zamboni, P; Occhionorelli, S; Vasquez, G; Mari, F; Donini, A; Bresadola, V
\\u000a Gene therapy shows great potential to assist numerous patients with inadequate relief of inflammatory or neuropathic pain,\\u000a or intractable pain associated with advanced cancer. A brief overview is provided of the methods of gene therapy and of preclinical\\u000a findings in animal models of prolonged inflammatory, neuropathic and cancer pain. Preclinical findings demonstrate no efficacy\\u000a of gene therapy on basal thermal
William R. Lariviere; Doris K. Cope
ObjectiveTraditional surgical procedures for intractable idiopathic constipation are associated with a variable outcome and substantial morbidity. The symptomatic response, physiological effect and effect on quality of life of sacral nerve stimulation (SNS) were evaluated in patients with constipation (slow transit and normal transit with impaired evacuation).MethodsIn a prospective study at five European sites patients who failed conservative treatment underwent 21
Michael A Kamm; Thomas C Dudding; Jarno Melenhorst; Michael Jarrett; Zengri Wang; Steen Buntzen; Claes Johansson; Søren Laurberg; Harald Rosen; Carolynne J Vaizey; Klaus Matzel; Cor Baeten
Chronic orchalgia is a frustrating clinical problem for both the patient and the physician. We present a 17-year-old boy with a bilateral idiopathic chronic intractable orchalgia with failed conservative treatment. For 2 years, he suffered from severe attacks of scrotal pain that affected his daily activities and caused frequent absence from school. Ultrasound-guided pulsed radiofrequency ablation (PRF) of the genital branches of the genitofemoral nerve performed after local anesthetic nerve block confirmed the diagnosis and yielded 6 weeks of symptom relief. Seven-month follow-up revealed complete satisfactory analgesia. The use of PRF is an effective and non-invasive approach to treat intractable chronic orchalgia.
Terkawi, Abdullah Sulieman; Romdhane, Kamel
We present the cases of two men with isolated spontaneous dissection of visceral arteries diagnosed by multidetector CT. In the first patient, dissection of the celiac trunk was associated with periarterial changes. In the second patient, dissection of the superior mesenteric artery was associated with stenosis at the root of the celiac trunk. Both patients presented with acute pain, which was more intense and longer lasting in the first patient. Aortic dissection was suspected clinically in both patients. Both dissections were short and had patent saccular false lumens and reduced caliber of the true lumens. This morphological type is one of the most uncommon within this rare entity. However, in recent years, the number of cases published is rising. This suggests that this entity may have been underdiagnosed before the widespread use of multidetector CT. We discuss the two morphological classifications of dissection of the visceral arteries and the need to adapt therapeutic management to the particular circumstances of each case. PMID:21724211
Corral, M A; Encinas, J; Fernández-Pérez, G C
According to Amnesty International government-sanctioned torture is verified in one third of the countries in the world. The physical and psychological sequelae are numerous. This study focuses on pain diagnosis, characterising pain types as nociceptive, visceral or neuropathic. Torture victims from the Middle East, treated at the Rehabilitation and Research Centre for Torture Victims (RCT) in Copenhagen, participated in the
Annemarie B Thomsen; Jørgen Eriksen; Knud Smidt-Nielsen
Summary Eighteen patients who underwent percutaneous trigeminal tractotomy for relief of intractable facial pain are reported. The author uses a new method of radiographic delineation of the obex with emulsified Pantopaque. RF current passed through the correctly placed electrode results in analgesia and pain relief with preservation of touch sensation in cancer patients.
J. L. Fox
SUMMARY Purpose In a population-based retrospective cohort of children with newly-diagnosed epilepsy, to determine (1) what proportion meet criteria for early medical intractability, and (2) predictors of enduring intractability. Methods Children with newly-diagnosed epilepsy between 1980–2009 while resident in Olmsted County, MN, and followed >36 months were stratified into groups, based on both early medical intractability (“apparent” medical intractability in the first 2 years) and enduring intractability (persisting intractability at final follow-up or having undergone surgery for intractable epilepsy), and variables predicting these outcomes were evaluated. Key Findings Three hundred and eighty one children were included, representing 81% of our cohort with newly diagnosed epilepsy. Seventy five (19.7%) had early medical intractability, and predictors of this outcome on multivariable analysis were neuroimaging abnormality (p=0.0004), abnormal neurological examination at diagnosis (p=0.015) and mode of onset [association was significant for focal vs generalized onset (p<0.0001) but not unknown vs generalized onset (p=0.065)]. After a median follow-up of 11.7 years, 49% remained intractable, 8% had rare seizures (?q6 months), and the remainder were seizure-free. The only factor predicting for enduring intractability on multivariable analysis was neuroimaging abnormality (p=0.0006). Significance While a significant minority of children with early medical intractability ultimately achieved seizure control without surgery, those with an abnormal imaging study did poorly. For this subgroup, early surgical intervention is strongly advised to limit co-morbidities of ongoing, intractable seizures. Conversely, a cautious approach is suggested for those with normal imaging, as most will remit with time.
Wirrell, Elaine C.; Wong-Kisiel, Lily C.-L.; Mandrekar, Jay; Nickels, Katherine C.
Irritable bowel syndrome remains an incompletely understood, common syndrome with significant unmet medical needs. In IBS patients, abdominal pain is a primary factor related to quality of life impairment, symptom severity and health care utilization, and chronic visceral hyperalgesia has been identified as an important aspect of IBS pathophysiology. However, the development of therapies aimed at reducing this hyperalgesia (visceral analgesics) has been only partially successful despite preclinical evidence supporting the potential usefulness of several preclinical compounds aimed at peripheral as well as central targets.
Bradesi, Sylvie; Herman, Jeremy; Mayer, Emeran A
The study examined the antiinflammatory and antinociceptive effects of the sesquiterpene (-)-?-bisabolol (BISA). The antiinflammatory effect was evaluated on acute models of dermatitis induced by Croton oil, arachidonic acid, phenol and capsaicin, respectively, in mouse ear. BISA inhibited the dermatitis induced by all noxious agents, except capsaicin. BISA was assessed in two established mouse models of visceral nociception. Mice were pretreated orally with BISA, and the pain-related behavioral responses to intraperitoneal cyclophosphamide or to intracolonic mustard oil were analyzed. BISA showed a dose-unrelated significant antinociception. Collectively, the results suggest that BISA may be an topical antiinflammatory and visceral antinociceptive agent. PMID:20875845
Leite, Gerlânia de O; Leite, Laura H I; Sampaio, Renata de S; Araruna, Mariana Késsia A; de Menezes, Irwin Rose A; da Costa, José Galberto M; Campos, Adriana R
Intractable conflicts are demoralizing. Beyond destabilizing the families, communities, or international regions in which they occur, they tend to perpetuate the very conditions of misery and hate that contributed to them in the first place. Although the common factors and processes associated with intractable conflicts have been identified…
Vallacher, Robin R.; Coleman, Peter T.; Nowak, Andrzej; Bui-Wrzosinska, Lan
Rosacea is a common chronic cutaneous disorder that primarily occurs on the convex surfaces of the central face and is often characterized by exacerbations and remissions. A case of a 52-yr-old woman visited our clinic in February 2008 complaining typical features of rosacea including multiple pinhead to rice-sized erythematous papules. We applied various conventional treatments including topical benzoyl peroxide and metronidazole as well as oral metronidazole, isotretinoin, and doxycycline. The lesions were not controlled but were rather aggravated by complications from these treatments. Therefore, we prescribed oral azithromycin, which has anti-inflammatory effects and reduces reactive oxygen species. Ten weeks after the administration of oral azithromycin, 500 mg per day for 2 weeks, the lesions had mostly disappeared and no specific side effects related to the azithromycin were noted. Oral azithromycin dosing 500 mg/day for 2 weeks is effective for treatment of intractable rosacea.
Kim, Jae-Hong; Oh, Yoon Seok
Visceral leishmaniasis (VL), commonly known as kala-azar, is caused by Leishmania donovani and Leishmania infantum (Leishmania chagasi in the Americas). These Leishmania species infect macrophages throughout the viscera, and parasites are typically found in the spleen, liver, and bone marrow. Patients with active disease typically exhibit marked immunosuppression, lack reactivity to the Leishmania skin test (LST), a delayed type hypersensitivity test, and their peripheral blood mononuclear cells (PBMC) fail to respond when stimulated with leishmanial antigens in vitro. However, most people infected with visceralizing species of Leishmania never develop disease. Understanding immune failure and the underlying immune mechanism that lead to disease as well as control of infection are key questions for research in this field. In this review, we discuss immunological events described in human and experimental VL and how these can affect the outcome of infection.
Kumar, Rajiv; Nylen, Susanne
Purpose: To assess the efficacy and safety of microcatheter embolization in the treatment of intractable idiopathic epistaxis. Methods: Thirty-seven patients underwent microcatheter embolization in 1991-1998. We evaluated retrospectively the technical and clinical outcome, the number of complications, the duration of embolization in each case, and the number of blood transfusions needed. All embolizations were done with biplane digital subtraction angiography (DSA) equipment. The procedure was carried out under local anesthesia using transfemoral catheterization, except in one case where the translumbar route was used. Tracker 18 or 10 microcatheters were advanced as far as possible to the distal branches of the sphenopalatine artery. Polyvinyl alcohol (PVA) particles were used for embolization in most cases, while platinum coils or a combination of these two materials were occasionally used. The primary outcome was always assessed immediately by angiography. Follow-up data were obtained from patient records, by interviewing patients on the telephone or by postal questionnaires when necessary. The mean follow-up time was 21 months. Results: The embolization was technically successful in all 37 cases. A curative outcome was achieved in 33 cases (89%). The mean duration of the procedure was 110 min. Four patients (8%) had mild transient complications, but no severe or persistent complications were encountered. Twenty-three patients needed a blood transfusion. Slight rebleeding occurred in three patients during the follow-up; all responded to conservative treatment. One patient suffered two episodes of rebleeding within 2 months after primary embolization. Re-embolizations successfully stopped the bleeding. Conclusion: Embolization is the primary invasive modality for treating intractable idiopathic epistaxis. It proved both safe and effective over a relatively long follow-up.
Leppaenen, Martti; Seppaenen, Seppo [Department of Radiology, Tampere University Hospital, P.O. Box 2000, FIN-33521 Tampere (Finland); Laranne, Jussi [Department of Otolaryngology, Tampere University Hospital, P.O. Box 2000, FIN-33521 Tampere (Finland); Kuoppala, Katriina [Department of Neurology, Seinaejoki Central Hospital, Hanneksenrinne 7, FIN-60220 Seinaejoki (Finland)
Objective Bismuth has antidiarrheal, antibacterial, and anti-inflammatory properties. We report our single-center experience with oral colloidal bismuth subcitrate (CBS) treatment for patients with chronic intractable diarrhea. Method We interrogated our web-based Inflammatory Bowel Disease Clinical and Research database to ascertain clinical details on all patients in our tertiary hospital gastroenterology service treated with CBS between 2000 and 2010. Treatment responses were based on prospective scoring of daily number of liquid stools. Responses were recorded prior to commencement of CBS and at follow-up visits over 12 months. Results Thirty-one patients, mean age 47 years (range 17–79 years) and a mean duration of diarrhea of 22 weeks (range 6–104 weeks), were prescribed CBS at doses ranging from 120 mg to 480 mg/day for ?1 month. Of these, 23 patients (74%) had an initial clinical response and 12 (39%) who continued with this treatment had a sustained clinical response at 1 year. Twelve patients with pouchitis and four patients with indeterminate colitis had initial responses of 92% and 75%, respectively, and sustained responses of 50% and 75%, respectively. Ulcerative colitis patients (n = 5) responded poorly with respect to both initial and sustained responses. Three patients with microscopic colitis showed encouraging initial response of 100% but did not have any sustained benefit. Three of four patients with diarrhea-predominant irritable bowel syndrome (dIBS) had an initial response and two (50%) had good sustained responses. There were no serious adverse events. One patient stopped therapy because of nausea. Conclusion This is the largest report of oral bismuth treatment in chronic intractable diarrhea. CBS is cheap and appears to have the potential to be effective for ameliorating diarrheal symptoms in indeterminate colitis, pouchitis, and dIBS. An appropriately powered, blinded, randomized, controlled study appears warranted to establish the position of oral bismuth in routine practice.
Thazhath, Sony S; Haque, Mazhar; Florin, Timothy H
Control and treatment of chronic pain remain major clinical challenges. Progress may be facilitated by a greater understanding of the mechanisms underlying pain processing. Here we show that the calcium-sensing protein DREAM is a transcriptional repressor involved in modulating pain. dream?\\/? mice displayed markedly reduced responses in models of acute thermal, mechanical, and visceral pain. dream?\\/? mice also exhibited reduced
Hai-Ying M. Cheng; Graham M. Pitcher; Steven R. Laviolette; Ian Q. Whishaw; Kit I. Tong; Lisa K. Kockeritz; Teiji Wada; Nicholas A. Joza; Michael Crackower; Jason Goncalves; Ildiko Sarosi; James R. Woodgett; Antonio J. Oliveira-dos-Santos; Mitsuhiko Ikura; Derek van der Kooy; Michael W. Salter; Josef M. Penninger
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal illnesses and is characterized by altered visceral perception. The aim of the study was to determine if local anesthetic blockade of peripheral visceral nociceptive input reduces both visceral and cutaneous secondary hyperalgesia in IBS patients. Ten women with IBS (mean age 30+/-10 years) and ten control subjects (all women) (mean age 29+/-7 years) rated pain intensity and unpleasantness to distension of the rectum (35 mmHg) and thermal stimulation (47 degrees C) of the foot before and after rectal administration of either lidocaine jelly or saline jelly in a double blind crossover design. Intrarectal lidocaine (300 mg) reduced reported rectal and cutaneous pain in all of the IBS patients. The effects were statistically much greater than those of placebo and most of the effects were present within 5-15 min after the onset of the treatment. In the control subjects, rectal lidocaine did not decrease pain report from visceral and cutaneous stimuli. The results of this study support the hypothesis that local anesthetic blockade of peripheral impulse input from the rectum/colon reduces both visceral and cutaneous secondary hyperalgesia in IBS patients. The results provide further evidence that visceral hyperalgesia and secondary cutaneous hyperalgesia in IBS reflects central sensitization mechanisms that are dynamically maintained by tonic impulse input from the rectum/colon. Rectal administration of lidocaine jelly may also be a safe and effective means of reducing pain symptoms in IBS patients. PMID:14499439
Verne, G Nicholas; Robinson, Michael E; Vase, Lene; Price, Donald D
Purpose: Response to infliximab treatment diminishes as body mass index (BMI) increases in patients with ankylosing spondylitis (AS). The purpose of the study was to determine if diminished response to infliximab treatment in patients with AS could be associated with increased visceral adipose tissue rather than increased BMI. Methods: Twenty six AS patients (21 males and five females) who fulfilled the modified New York criteria and who were currently receiving infliximab treatment were enrolled in the study. Pain was measured by the visual analogue scale (VAS). The disease activity and functional status were assessed by the Bath AS Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI). The Bath AS Metrology Index (BASMI) was used to evaluate mobility restrictions. Weight and visceral body composition were measured without shoes in light indoor clothes using a bio-impedance meter. Results: There was a significant correlation between visceral adipose tissue amount and disease activity under infliximab treatment. In correlation analysis, visceral fat showed significant correlations between BASDAI (r=0.545, p=0.004) and VAS (r=0.458, p=0.019). Total body fat also showed a significant correlation with BASDAI (r=0.463, p=0.017). Conclusion: A significant correlation was found between visceral adipose tissue amount and disease activity in patients with AS. PMID:24895992
Aydin, Mesut; Aydin, Fatma; Yuksel, Murat; Yildiz, Abdulkadir; Polat, Nihat; Akil, Mehmet A; Bilik, Mehmet Z; Akyuz, Abdurrahman; Batmaz, Ibrahim; Alan, Sait
We describe a young woman with complete cervical spinal cord transsection, who developed significant abdominal pain, triggered by gastric distension and deep abdominal palpation. On the basis of the nature of her spinal cord injury, her brain-gut axis was limited to vagal pathways. Studies in mammalian models of human visceral sensation consistently showed that the subdiaphragmatic vagus contains a homogeneous population of afferents that are activated by low-intensity stimuli, which are generally believed to be important in regulating autonomic function and perhaps contributing to visceral sensory experiences triggered by such low-intensity stimuli (e.g. fullness, nausea), but not pain, although many fibers encode stimuli well into the noxious range. In contrast, spinal afferent pathways include fibers with high-activation thresholds that are thought to represent specialized nociceptors. This illustrative case argues against an exclusive role of specialized nociceptive pathways in visceral pain, but supports a concept of intensity coding with the composite of vagal and spinal input contributing to conscious perception and pain. PMID:22266836
Levinthal, David J; Bielefeldt, Klaus
Ketamine has been shown to have analgesic effect by blocking N-methyl-D-aspartate receptor, thus preventing and reducing central sensitization caused by peripheral nociceptive stimulation. However, due to lack of knowledge about its safety and toxicity in the central nervous system, either epidural or intrathecal injection of ketamine still remains controversial. Here, we describe a case report of satisfactory pain relief after the addition of ketamine in epidural injection in a patient with severe herpes zoster pain that was refractory to conventional medication, intravenous opioids and continuous epidural block. This case indicates the viability of epidural ketamine injection in patients with intractable herpetic neuralgia.
Lee, Jin Young; Kim, Kyung Mi; Oh, Min Seok; Lee, Ji Eun
Asymptomatic human visceral leishmaniasis was identified in Israel by using an enzyme-linked immunosorbent assay. Positive serum samples were more prevalent in visceral leishmaniasis–endemic (2.97%) compared to nonendemic (1.01%) regions (p=0.021). Parasite exposure was higher than expected, despite the small number of clinical cases, suggesting factors other than infection per se influence clinical outcome.
Adini, Irit; Ephros, Moshe; Chen, Jacopo
Objective: Visceral leishmaniasis (VL) in children is endemic in southern Europe but has not been previously reported from Albania. This prospective study reports the clinical and laboratory findings in 50 children with visceral leishmaniasis, the value of a direct agglutination test (DAT), and the result of treatment with meglumine antimonate.Materials and Methods: Sera obtained from 50 children with VL confirmed
Gjeorgjina Lito; Farzin Davachi; Genc Sulcebe; Hamaide Bregu; Mira Basha
Visceral larva migrans (VLM) is a systemic manifestation of migration of second stage larvae of nematodes through the tissue of human viscera. It is not uncommon but is underdiagnosed in developing countries. The liver is the most common organ to be involved due to its portal venous blood supply. The imaging findings are subtle and differentiation from hepatocellular carcinoma (HCC), metastases, cystic mesenchymal hamartoma and granulomatous diseases is difficult. This case report highlights the imaging features of hepatic lesions of VLM along with clinical and laboratory data which help in clinching the diagnosis. PMID:23853189
Rohilla, Seema; Jain, Nitin; Yadav, Rohtas; Dhaulakhandi, Dhara Ballabh
Visceral pain is the most common reason for physician visits in US. Glutamate is the major excitatory neurotransmitter and mediates visceral nociceptive neuro-transmission and hypersensitivity. Removal of extracellular glutamate is predominantly mediated by glial glutamate transporter-1 (GLT-1). The pharmacological approach to up-regulate GLT-1 by 1 week administration of ceftriaxone (CTX) has been successful to mitigate visceral nociception. The present study shows that intrathecal delivery of selective GLT-1 antagonist dihydrokainate reversed CTX-blunted visceral nociceptive response, suggesting a spinal site of action. The role of GLT-1 up-regulation in animal models of colitis was studied. CTX treatment reversed TNBS-induced visceral hypersensitivity. In addition, CTX treatment initiated one week after the onset of DSS-induced visceral inflammation also attenuated visceral hypersensitivity, revealing a potential therapeutic effect. Cephalothin, a cephalosporin antibiotic lacking GLT-1 induction activity, failed to attenuate visceral nociception. CTX-induced changes in fecal microbiota do not support a role of probiotic effects in mitigating visceral nociception/hypersensitivity. Finally, adeno-associated virus serotype 9-mediated GLT-1 over-expression was effective to mitigate visceromotor response to 60?mmHg colo-rectal distension. These studies indicate that GLT-1 over-expression is a novel and effective method to attenuate visceral nociception, and is deserving of further study as a translationally relevant approach to treat visceral pain.
Lin, Y.; Roman, K.; Foust, K. D.; Kaspar, B. K.; Bailey, M. T.; Stephens, R. L.
Dragon's blood, the red sap from Croton urucurana Baill. (Euphorbiaceae) has a profound history of traditional use in conditions such as inflammation, diarrhoea and gastrointestinal distress. Previous studies established its anti-inflammatory, antidiarrhoeal and analgesic properties and in this study we verified its potential to suppress visceral pain, using capsaicin- and cyclophosphamide-induced models of visceral nociception. Mice that received intra-colonic capsaicin
Vietla S. Rao; Luilma A. Gurgel; Roberto C. P. Lima-Júnior; Domingos T. O. Martins; Valdir Cechinel-Filho; Flávia A. Santos
ObjectivesThe aim of the study described here was to characterize the efficacy and safety of vagus nerve stimulation in a population of patients with tuberous sclerosis complex (TSC) and intractable epilepsy.
Philippe Major; Elizabeth A. Thiele
The prevalence and classification of pain were investigated in 46 patients admitted consecutively with traumatic spinal cord injury to a rehabilitation hospital. All were studied within 2 years of trauma. Forty-six percent experienced pain of moderate-to-severe intensity. The patients with pain were classified into five categories: diffuse pain, segmental pain, root pain, visceral pain and non-neurogenic pain. Most patients experienced
A G Wagner Anke; A E Stenehjem; J Kvalvik Stanghelle; AGW Anke
Clinical and experimental evidence on referred pain and spinal-afferent convergence demonstrates a close relationship between\\u000a visceral and somatosensory perception, which is important for current models of symptom perception and central body representation.\\u000a The study uses a psychophysical approach to quantify these interactions at the perceptual level, taking into account problems\\u000a of comparable intermodal scaling and the role of awareness. An
Rupert Hölzl; Andreas Möltner; Claus W. Neidig
A 58 year old man had been suffering from intractable left ophthalmic post herpetic neuralgia (PHN) for 7 years. He has also been treated for polyarteritis nodosa for 10 years. For pain relief, he was treated initially with frequent (4 times a day) stellate ganglion block (SGB) and peripheral ophthalmic nerve block for a month without relief. Then supraorbital nerve block with neurolytics, TENS and acupuncture were done with a slight relief of his pain. Recently his pain became worse even with imipramine 75 mg and carbamazepine 100 mg a day which relieved effectively the patient from the pain for the last 3 years. The pain was so severe to disturb his usual daily activity. Gasserian ganglion block with methyl prednisolone acetate 10 mg was done. After the block, his ADL improved markedly. Three months after the block, he had no spontaneous pain and slight pain with light touch on the injured skin did not annoy him. Several days before the block, electric stimulation to control his pain was tested. Stimulation with the electricity (4.5 mA, 10 cycle and 400 microseconds) brought him complete relief from the pain during the stimulation. Trigeminal SEP showed no response to the stimulation of injured skin. PMID:2246814
Yamashiro, H; Hara, K; Gotoh, Y
Chronic orchalgia is a frustrating clinical problem for both the patient and the physician. We present a 17-year-old boy with a bilateral idiopathic chronic intractable orchalgia with failed conservative treatment. For 2 years, he suffered from severe attacks of scrotal pain that affected his daily activities and caused frequent absence from school. Ultrasound-guided pulsed radiofrequency ablation (PRF) of the genital branches of the genitofemoral nerve performed after local anesthetic nerve block confirmed the diagnosis and yielded 6 weeks of symptom relief. Seven-month follow-up revealed complete satisfactory analgesia. The use of PRF is an effective and non-invasive approach to treat intractable chronic orchalgia. PMID:24843352
Terkawi, Abdullah Sulieman; Romdhane, Kamel
OBJECTIVE—To examine the clinical characteristics of intractable diarrhoea associated with secondary amyloidosis in rheumatoid arthritis (RA).?METHODS—Of 179 RA patients with biopsy confirmed secondary amyloidosis, 24 cases (23 women and one man) with intractable diarrhoea lasting for more than one month were retrospectively evaluated.?RESULTS—The mean (SD) duration of diarrhoea was 87 (64) days. Prodromal symptoms of gastrointestinal dysfunction (n = 21) and impaired peristalsis (n = 16) were observed. Laboratory data showed hypoproteinaemia (4.7 (0.85) g/dl) caused by malabsorption or protein loss and high values of C reactive protein (17.0 (9.3) mg/dl). Recurrence of intractable diarrhoea (n = 4) and transition from intractable diarrhoea to other gastrointestinal problems of amyloidosis (ischaemic colitis (n = 2) and intestinal pseudo-obstruction (n = 4)) were observed. In 19 patients (25 episodes) the duration of intravenous hyperalimentation at remission (18 episodes) was 68 (52) days. Corticosteroid pulse therapy was administered to 10 patients (11 times) and the time elapsed from the end of corticosteroid pulse therapy to the end of diarrhoea was 18 (14) days. One and five year survival rates after the onset of intractable diarrhoea were 73.4% and 38.9% . Seven of 13 patients (54%) had died as a result of infectious diseases.?CONCLUSION—Intractable diarrhoea associated with secondary amyloidosis in RA is a serious clinical entity and the prognosis is poor. Although it is assumed that intravenous hyperalimentation treatment and corticosteroid pulse therapy are favourable regimens for intractable diarrhoea, the patients should be monitored for possible infectious complications.??
Okuda, Y.; Takasugi, K.; Oyama, T.; Oyama, H.; Nanba, S.; Miyamoto, T.
Objectives Vidian neurectomy could be considered the treatment of choice for intractable rhinitis, because it is the only method that can permanently block the pathophysiological mechanism of rhinitis. The goal of this study was to evaluate the effect of vidian neurectomy on nasal symptoms and tear production, and to assess for possible complications. Methods Six patients with intractable rhinitis who underwent endoscopic transnasal vidian neurectomy were enrolled. The degree of symptom improvement and complications were assessed through retrospective review of medical records prior to, and 1 year following surgery, and telephone survey after 6.9±2.1 years. Schirmer's test was performed before surgery, and these values were compared to postoperative results at 1 day, 1 month, and 2 months. Results Changes in the visual analogue scale were significant in nasal obstruction (8.5±2.5 to 3.0±2.0, P<0.05) and rhinorrhea (9.0±2.2 to 2.0±1.6, P<0.05). Improvements persisted for up to 7 years after the primary surgery. Patients complained of mild dry eyes for 1 month after vidian neurectomy. However, five out of six reported marked improvement of xerophthalmia after 2 months. Aside from mild crusting of the nasal cavity and mild postoperative pain, there were no major complications. During the entire follow-up period, no patient needed additional treatment, such as antihistamines or corticosteroids. Conclusion Vidian neurectomy is effective in alleviating nasal symptoms in patients with intractable rhinitis refractory to other treatments. This effect is sustained for at least 7 years with minimal postoperative complications.
Kim, Young Hyo; Shin, Seung-Ho
Irritable bowel syndrome (IBS) is a very frequent functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort and alteration of bowel habits. The IBS physiopathology is extremely complex. Visceral hypersensitivity plays an important role in the pathogenesis of abdominal pain in both in vitro and in vivo models of this functional disorder. In order to obtain a general view of the participation of the main ion channels and receptors regarding the visceral hypersensitivity in the IBS and to describe their chemical structure, a literature review was carried out. A bibliographical research in the following electronic databases: Pubmed and Virtual Library in Health (BVS) was fulfilled by using the search terms “ion channels” “or” “receptors” “and” “visceral hypersensitivity” “or” “visceral nociception” “and” “irritable bowel syndrome”. Original and review articles were considered for data acquisition. The activation of the ATP ion-gated channels, voltage-gated sodium (Nav) and calcium (Cav) channels, as well as the activation of protease-activated receptors (PAR2), transient receptor potential vanilloide-1, serotonin, cannabinoids and cholecystokinin are involved in the genesis of visceral hypersensitivity in IBS. The involvement of ion channels and receptors concerning visceral hypersensitivity is noteworthy in IBS models.
de Carvalho Rocha, Heraldo Arcela; Dantas, Bruna Priscilla Vasconcelos; Rolim, Thaisa Leite; Costa, Bagnolia Araujo; de Medeiros, Arnaldo Correia
Background—Visceral hyperalgesia is a hallmark of functional gastrointestinal disorders. Antidepressants improve symptoms in these patients, although their mode of action is unclear. Antidepressant, anticholinergic, and analgesic mechanisms have been proposed. ?Aims—To investigate whether imipramine, which has a visceral analgesic effect, increases pain thresholds to experimental visceral pain. ?Methods—Visceral perception for first sensation and pain was measured with intraoesophageal balloon distension in 15 male volunteers. The effect of imipramine was studied in a double blind, placebo controlled, crossover study. Imipramine was given in ascending doses for 12 days (25 mg days 1-3, 50 mg days 4-6, 75 mg days 7-12), with oesophageal perception studied on day 13. ?Results—Inflation volumes and intraballoon pressures at first sensation were not different between placebo and imipramine. Balloon inflation volume at pain threshold was higher on imipramine (p=0.015). Median intraballoon pressures were not different at pain threshold for placebo and imipramine. Oesophageal wall compliance was not affected by imipramine. ?Conclusion—Increased pain thresholds on imipramine in this group of normal male volunteers in the absence of changes in oesophageal tone imply the presence of a visceral analgesic effect. ?? Keywords: antidepressants; imipramine; visceral hyperalgesia; oesophageal balloon; distension; functional bowel syndromes
Peghini, P; Katz, P; Castell, D
Although there are various treatments for postherpetic neuralgia (PHN), none produces definitive effects. We report a case of 72-year-old woman who developed intractable PHN of the chest in which treatment with endoscopic transthoracic sympathicotomy (ETS) produced long-term effective results. When hyperesthesia of the sympathetic nerve participates in PHN, the blocking of sympathetic excitation seems to be effective for PHN suppression. The method using a single resectoscope is safe, accurate, yields excellent results cosmetically, and generates minimal invasion and very little postoperative pain. Although ETS is not always effective for all cases of PHN, it could be a useful method of treating patients with PHN that is resistant to conventional therapies. PMID:12171855
Matsumoto, Isao; Oda, Makoto; Shintani, Hiromoto
Patient: Male, 63 Final Diagnosis: Cytomegalo virus (CMV) infection Symptoms: Diarrhea Medication:— Clinical Procedure:— Specialty: Infectious Diseases Objective: Unusual clinical course Background: Coinfection with cytomegalovirus in a patient with Clostridium difficile persistent diarrhea and colitis can lead to a delay in diagnosis and treatment. Case Report: A 63-year-old man with squamous cell carcinoma of the lower lip, status post surgical resection and currently on chemoradiation presented with intractable diarrhea and abdominal pain. Initial workup showed Clostridium difficile diarrhea with pancolitis. Diarrhea persisted despite being on antibiotics and bacteriological cure for C. difficile. Further noninvasive work up revealed associated cytomegalovirus infection, and patient had a dramatic response to ganciclovir without any relapse. Conclusions: Physicians should be cognizant about other causes of diarrhea and colitis in immunocompromised patient when treatment for primary diagnosis fails to resolve their symptoms.
John, Santhosh Gheevarghese; Dominguez, Cristian; Chandiramani, Vijay; Vemulappalli, Tejo
Occipital neuralgia is a form of headache that involves the posterior occiput in the greater or lesser occipital nerve distribution. Pain can be severe and persistent with conservative treatment. We present a case of intractable occipital neuralgia that conventional therapeutic modalities failed to ameliorate. We speculate that, in this case, the cause of headache could be the greater occipital nerve entrapment by the obliquus capitis inferior muscle. After steroid and local anesthetic injection into obliquus capitis inferior muscles under fluoroscopic and sonographic guidance, the visual analogue scale was decreased from 9-10/10 to 1-2/10 for 2-3 weeks. The patient eventually got both greater occipital neurectomy and partial resection of obliquus capitis inferior muscles due to the short term effect of the injection. The successful steroid and local anesthetic injection for this occipital neuralgia shows that the refractory headache was caused by entrapment of greater occipital nerves by obliquus capitis inferior muscles.
Kim, Ok Sun; Jeong, Seung Min; Ro, Ji Young; Kim, Duck Kyoung; Koh, Young Cho; Ko, Young Sin; Lim, So Dug; Kim, Hae Kyoung
BACKGROUND: Despite recent recognition that visceral pain differs from somatic pain in its neurophysiologic basis and treatment modalities, most laboratory studies of postoperative pain use a model of superficial somatic injury, and there is no model of postoperative pain after gynecologic surgery. We describe spontaneous behavior in rats after laparotomy with or without noxious stimulation of the uterus and cervix
Chuanyao Tong; Dawn Conklin; James C. Eisenach
BACKGROUND: Functional abdominal pain syndrome (FAPS) has chronic unexplained abdominal pain and is similar to the psychiatric diagnosis of somatoform pain disorder. A patient with irritable bowel syndrome (IBS) also has chronic unexplained abdominal pain, and rectal hypersensitivity is observed in a majority of the patients. However, no reports have evaluated the visceral sensory function of FAPS precisely. We aimed
Tsukasa Nozu; Miwako Kudaira
We herein report that naratriptan remarkably improved intractable migraine-like headaches in a patient with Sturge-Weber syndrome (SWS) despite his past history of cerebral infarction. In addition, lamotrigine had a prophylactic effect on his visual aura and headaches. An 18-year-old male patient with SWS had intractable migraine-like headaches every several months from the age of 3years. His migraine-like headaches were characterized by pulsating attacks preceded by left homonymous hemianopsia, which persisted after headache disappearance. In addition, after 14years of age, the pulsating headaches were preceded by photophobia without homonymous hemianopsia and occurred almost daily. Headache pains were not improved by acetaminophen or loxoprofen sodium hydrate. Furthermore, various prophylactic drugs were ineffective. After obtaining informed consent, naratriptan was administered. The pain severity was reduced and the duration of headache with homonymous hemianopsia was shortened from several days to several hours. Interestingly, naratriptan also shortened the duration of homonymous hemianopsia to several hours. We confirmed that his headache attacks were not epileptic seizures by ictal electroencephalography. However, 25mg/day of lamotrigine had a prophylactic effect on the frequency of headache. Moreover, lamotrigine led to complete remission of his headache without homonymous hemianopsia. Lamotrigine may have an advantage in terms of reducing the risk of cerebrovascular disease caused by migraine-like headaches and the use of triptans. The most effective management for migraine-like headaches in patients with SWS has not been established. Lamotrigine is a potentially effective option for patients with SWS with migraine-like headaches. PMID:23877022
Nomura, Shohei; Shimakawa, Shuichi; Fukui, Miho; Tanabe, Takuya; Tamai, Hiroshi
Leishmania species are the causative agents of leishmaniasis, a neglected tropical disease. These parasitic protozoans are usually transmitted between vertebrate hosts by the bite of blood sucking female phlebotomine sand flies. This review focuses on the two parasites causing most human visceral leishmaniasis (VL), which leads to substantial health problems or death for up to 400,000 people per year. Except for travel cases, Leishmania donovani infections are restricted to the (sub-)tropics of Asia and Africa, where transmission is mostly anthroponotic, while Leishmania infantum occurs in the drier parts of Latin America as well as in the Mediterranean climate regions of the Old World, with the domestic dog serving as the main reservoir host. The prevalence of VL caused by L. infantum has been declining where living standards have improved. In contrast, infections of L. donovani continue to cause VL epidemics in rural areas on the Indian subcontinent and in East Africa. The current review compares and contrasts these continental differences and suggests priorities for basic and applied research that might improve VL control. Transmission cycles, pathogenesis, diagnosis, treatment and prognosis, prevention (including vector control), surveillance, transmission modeling, and international control efforts are all reviewed. Most case detection is passive, and so routine surveillance does not usually permit accurate assessments of any changes in the incidence of VL. Also, it is not usually possible to estimate the human inoculation rate of parasites by the sand fly vectors because of the limitations of survey methods. Consequently, transmission modeling rarely passes beyond the proof of principle stage, and yet it is required to help develop risk factor analysis for control programs. Anthroponotic VL should be susceptible to elimination by rapid case detection and treatment combined with local vector control, and one of the most important interventions may well be socioeconomic development.
Ready, Paul D
Leishmania species are the causative agents of leishmaniasis, a neglected tropical disease. These parasitic protozoans are usually transmitted between vertebrate hosts by the bite of blood sucking female phlebotomine sand flies. This review focuses on the two parasites causing most human visceral leishmaniasis (VL), which leads to substantial health problems or death for up to 400,000 people per year. Except for travel cases, Leishmania donovani infections are restricted to the (sub-)tropics of Asia and Africa, where transmission is mostly anthroponotic, while Leishmania infantum occurs in the drier parts of Latin America as well as in the Mediterranean climate regions of the Old World, with the domestic dog serving as the main reservoir host. The prevalence of VL caused by L. infantum has been declining where living standards have improved. In contrast, infections of L. donovani continue to cause VL epidemics in rural areas on the Indian subcontinent and in East Africa. The current review compares and contrasts these continental differences and suggests priorities for basic and applied research that might improve VL control. Transmission cycles, pathogenesis, diagnosis, treatment and prognosis, prevention (including vector control), surveillance, transmission modeling, and international control efforts are all reviewed. Most case detection is passive, and so routine surveillance does not usually permit accurate assessments of any changes in the incidence of VL. Also, it is not usually possible to estimate the human inoculation rate of parasites by the sand fly vectors because of the limitations of survey methods. Consequently, transmission modeling rarely passes beyond the proof of principle stage, and yet it is required to help develop risk factor analysis for control programs. Anthroponotic VL should be susceptible to elimination by rapid case detection and treatment combined with local vector control, and one of the most important interventions may well be socioeconomic development. PMID:24833919
Ready, Paul D
Executive Summary Objective The objective of this health technology policy assessment was to determine the effectiveness of spinal cord stimulation (SCS) to manage chronic intractable neuropathic pain and to evaluate the adverse events and Ontario-specific economic profile of this technology. Clinical Need SCS is a reversible pain therapy that uses low-voltage electrical pulses to manage chronic, intractable neuropathic pain of the trunk or limbs. Neuropathic pain begins or is caused by damage or dysfunction to the nervous system and can be difficult to manage. The prevalence of neuropathic pain has been estimated at about 1.5% of the population in the United States and 1% of the population in the United Kingdom. These prevalence rates are generalizable to Canada. Neuropathic pain is extremely difficult to manage. People with symptoms that persist for at least 6 months or who have symptoms that last longer than expected for tissue healing or resolution of an underlying disease are considered to have chronic pain. Chronic pain is an emotional, social, and economic burden for those living with it. Depression, reduced quality of life (QOL), absenteeism from work, and a lower household income are positively correlated with chronic pain. Although the actual number is unknown, a proportion of people with chronic neuropathic pain fail to obtain pain relief from pharmacological therapies despite adequate and reasonable efforts to use them. These people are said to have intractable neuropathic pain, and they are the target population for SCS. The most common indication for SCS in North America is chronic intractable neuropathic pain due to failed back surgery syndrome (FBSS), a term that describes persistent leg or back and leg pain in patients who have had back or spine surgery. Neuropathic pain due to complex regional pain syndrome (CRPS), which can develop in the distal aspect of a limb a minor injury, is another common indication. To a lesser extent, chronic intractable pain of postherpetic neuralgia, which is a persistent burning pain and hyperesthesia along the distribution of a cutaneous nerve after an attack of herpes zoster, is also managed with SCS. For each condition, SCS is considered as a pain management therapy only after conventional pain therapies, including pharmacological, nonpharmacological, and surgical treatments, if applicable, have been attempted and have failed. The Technology The SCS technology consists of 3 implantable components: a pulse generator, an extension cable, and a lead (a small wire). The pulse generator is the power source for the spinal cord stimulator. It generates low-voltage electrical pulses. The extension cable connects the pulse generator to the lead. The lead is a small, insulated wire that has a set of electrodes at one end. The lead is placed into the epidural space on the posterior aspect of the spinal cord, and the electrodes are positioned at the level of the nerve roots innervating the painful area. An electrical current from the electrodes induces a paresthesia, or a tingling sensation that masks the pain. Before SCS is initiated, candidates must have psychological testing to rule out major psychological illness, drug habituation, and issues of secondary gain that can negatively influence the success of the therapy. Successful candidates will have a SCS test stimulation period (trial period) to assess their responsiveness to SCS. The test stimulation takes about 1 week to complete, and candidates who obtain at least 50% pain relief during this period are deemed suitable to receive a permanent implantation of a spinal cord stimulator Review Strategy The Medical Advisory Secretariat (MAS) reviewed all published health technology assessments of spinal cord stimulation. Following this, a literature search was conducted from 2000 to January, 2005 and a systematic review of the literature was completed. The primary outcome for the systematic review was pain relief. Secondary outcomes included functional status and quality of life. After applying the predetermined inclusion and exclus
Summary Over the past 5 years 9 patients underwent partial or complete corpus callosotomy for treatment of medically intractable epileptic seizures. A beneficial effect of the procedure was observed in 8 patients. Criteria for performance of the procedure included CT evidence of unilateral cerebral damage and non-localized epileptic foci in that hemisphere with secondary spread to the uninvolved side. The
Z. H. Rappaport; P. Lerman
Vagus nerve stimulation (VNS) is gaining increasing popularity and credibility as a treatment option for children with intractable epilepsy. VNS offers several advantages over extant treatments. Its efficacy is maintained during prolonged stimulation, and seizure control actually improves with time. There is no associated cognitive impairment and no adverse drug interactions. Unlike cerebral surgery, VNS is a potentially reversible form
Arun Paul Amar; Michael L. Levy; J. Gordon McComb; Michael L. J. Apuzzo
Intractable hiccup and nausea (IHN) was found in eight of 47 cases of relapsing neuromyelitis optica (NMO) (17%) but in none of 130 cases of multiple sclerosis (MS). IHN resolved with methylprednisolone. In six cases, MRI detected linear medullary lesions involving the pericanal region, the area postrema, and the nucleus tractus solitarius. Like long and centrally located myelitis, a linear
T. Misu; K. Fujihara; I. Nakashima; S. Sato; Y. Itoyama
Intractable glaucoma results from hindrances in the eyeball aqueous humor pathways that increase the intraocular pressure above normal physiological levels (over 20 mmHg). In this study porous PTFE membranes were made hydrophilic with a photochemical method that use ethyl alcohol and water for the chemical solution.
Murahara, Masataka M.; Sato, Yuji; Fernandez, Viviana; Fantes, Francisco; Nose, Izuru; Lee, William E.; Milne, Peter J.; Parel, Jean-Marie A.
Essential palatal tremor (EPT) is a rare disorder which shows rhythmic involuntary movement of the muscles of soft palate, especially tensor veli palatini muscle. EPT is classified by two subtypes, which is primary and secondary EPT. Secondary EPT includes psychogenic type. We describe a case of intractable psychogenic EPT.
Chung, Eun Joo; Jung, Hyun; Kim, Sang Jin
This case report describes the remarkable recovery of a patient with very long-standing, medically intractable and disabling, lower-limb, complex regional pain syndrome type II following the resection, crushing, and relocation of sensory nerves. PMID:24502845
Watson, C Peter N; Mackinnon, Susan E; Dostrovsky, Jonathan O; Bennett, Gary J; Farran, R Peter; Carlson, Torie
The group of diseases known as the leishmaniases are caused by obligate intracellular protozoa of the genus Leish- mania (39). Natural transmission of leishmania is carried out by a certain species of sandfly of the genus Phlebotomus (Old World) or Lutzomyia (New World). These are present in three different forms: (i) visceral leishmaniasis (VL), (ii) cutaneous leishmaniasis, and (iii) mucocutaneous
Shyam Sundar; M. Rai
Regional cerebral blood flow changes were evaluated in different subcortical brain targets following deep brain stimulation (DBS) for chronic pain. Three patients with intractable neuropathic pain were assessed; one had stimulating electrodes in the ventroposterolateral thalamic nucleus (VPL), one in the periventricular grey (PVG) area, and one had electrodes in both targets. Pain relief was achieved in all patients. Cerebral
Erlick A. C. Pereira; Alexander L. Green; Kevin M. Bradley; Nigel Soper; Liz Moir; John F. Stein; Tipu Z. Aziz
Comparison of the visceral analgesic effects of xylazine, morphine, butorphanol, pentazocine, meperidine, dipyrone, and flunixin in a cecal distention model of colic pain indicated that xylazine produces the most relief from abdominal discomfort. Repeated administration of xylazine may reduce visceral pain so effectively that the seriousness of abdominal disease is obscured. Xylazine decreased propulsive motility in the jejunum and pelvic flexure of healthy ponies. Morphine and butorphanol also gave relief from visceral pain in the cecal distention model. Morphine may inhibit colonic, and butophanol jejunal, motility. Whether xylazine or opiate mediated decreases in gut motility cause clinically important slowing of ingesta transit is controversial and requires further investigation. The development of behavioral changes (i.e., apprehension and pawing) in horses given opiate therapy may limit the use of these drugs. Combinations of xylazine and morphine or butorphanol produce excellent, safe, visceral analgesia and sedation without untoward behavioral effects. Although flunixin fails to demonstrate good visceral analgesic effects in the cecal distention model, this drug produces analgesia in some cases of colic by blocking prostaglandin mediated induction of pain. Improvement of propulsive gut motility in patients with ileus may follow administration of neostigmine (which is particularly effective when the large bowel is hypomotile), naloxone (which experimentally stimulates propulsive colonic motility), and metoclopramide (which stimulates stomach and proximal small intestinal motility). PMID:3065495
Kohn, C W; Muir, W W
Eosinophilic necrotizing granulomas in the liver, known as visceral larva migrans (VLM), are a rare cause of liver abscesses. The term VLM refers to infections in human tissues caused by the larval stages of ascarid worms of dogs and cats. We report two cases of VLM which presented with high grade fever and abdominal pain for 3-4 months. Marked peripheral eosinophilia, multiple confluent perivenous lesions in the right lobe of liver with characteristic migratory tracts on imaging and biopsy evidence of necrotizing eosinophilic granulomas led to the diagnosis. Complete recovery was achieved with repeated courses of a combination of anthelmintics. PMID:24100348
Ramachandran, Jeyamani; Chandramohan, Anuradha; Gangadharan, Sajith Kattiparambil; Unnikrishnan, L S; Priyambada, Leena; Simon, Anna
Visceral leishmaniasis (VL) is usually characterized by splenomegaly, pallor and fever. Pleural effusion is an uncommon feature of this disease, which is encountered in immunocompromised patients. Here, we report a case of VL with pleural effusion in an immunocompetent patient. Pulmonary symptoms in VL are usually related to bacterial lung infection, vagal nerve compression by splenomegaly, and hypoalbuminaemia with mild pulmonary edema. Our patient presented with cough and chest pain. The clinical features of this case were baffling since they mimicked that of pulmonary tuberculosis. This case report emphasizes the need to recognize the diverse nature of presentation of this curable yet fatal infectious disease. PMID:24669085
Dasgupta, Senjuti; Saha, Moutushi; Chakrabarti, Sudipta; Chakraborty, Jayati
Chronic visceral pain in patients with irritable bowel syndrome (IBS) has been difficult to treat effectively partially because its pathophysiology is not fully understood. Recent studies show that norepinephrine (NE) plays an important role in the development of visceral hypersensitivity. In this study, we designed to investigate the role of adrenergic signaling in visceral hypersensitivity induced by heterotypical intermittent stress (HIS). Abdominal withdrawal reflex scores (AWRs) used as visceral sensitivity were determined by measuring the visceromoter responses to colorectal distension. Colon-specific dorsal root ganglia neurons (DRGs) were labeled by injection of DiI into the colon wall and were acutely dissociated for whole-cell patch-clamp recordings. Blood plasma level of NE was measured using radioimmunoassay kits. The expression of ?2-adrenoceptors was measured by western blotting. We showed that HIS-induced visceral hypersensitivity was attenuated by systemic administration of a ?-adrenoceptor antagonist propranolol, in a dose-dependent manner, but not by a ?-adrenoceptor antagonist phentolamine. Using specific ?–adrenoceptor antagonists, HIS-induced visceral hypersensitivity was alleviated by ?2 adrenoceptor antagonist but not by ?1- or ?3-adrenoceptor antagonist. Administration of a selective ?2-adrenoceptor antagonist also normalized hyperexcitability of colon-innervating DRG neurons of HIS rats. Furthermore, administration of ?-adrenoceptor antagonist suppressed sustained potassium current density (IK) without any alteration of fast-inactivating potassium current density (IA). Conversely, administration of NE enhanced the neuronal excitability and produced visceral hypersensitivity in healthy control rats, and blocked by ?2-adrenoceptor antagonists. In addition, HIS significantly enhanced the NE concentration in the blood plasma but did not change the expression of ?2-adrenoceptor in DRGs and the muscularis externa of the colon. The present study might provide a potential molecular target for therapy of visceral hypersensitivity in patents with IBS.
Zhou, Yuan-Yuan; Ju, Zhong; Zhang, Hong-Hong; Hu, Chuang-Ying; Xiao, Ying; Xu, Guang-Yin
The effects of topiramate (TPM) were evaluated in 51 patients with intractable epilepsy. Callosotomy and hemispherotomy were performed in 16 patients and one patient before the administration of TPM, respectively. The 50% responder rate (50%RR) was recorded in 39% of the total patient population and in 58% of patients with symptomatic location-related epilepsy (SLE). TPM was most effective for frontal lobe epilepsy (FLE), and the 50%RR was recorded in 88% of those patients. TPM (50%RR) was more effective in secondary generalized seizures (in 75%) and complex partial seizures (in 67%) in comparison to that of tonic-clonic seizures (in 44%) and drop attacks (in 29%). Seventy-one percent of the patients with atypical absence seizures increased seizure frequency. The 50%RR was recorded in 22% of the patients who underwent epilepsy surgery, and 29% of those patients also showed seizure aggravation due to TPM. These results suggest the efficacy of TPM for intractable epilepsy. PMID:22844761
Matsuo, Mitsuhiro; Matsuzaka, Tetsuo
Video-EEG monitoring was done in 26 patients with paroxysmal intractable attacks of uncertain etiology to determine the nature and cause. Two broad categories were identified: Those with prominent motor activity and those with attacks of collapse/limpness. Events were recorded in 16 patients of which 11 showed no abnormality on the simultaneously recorded EEG, thus helping to confirm their diagnosis of pseudoseizures. PMID:9282559
Bhatia, M; Jain, S; Maheshwari, M C
Transcatheter embolization for intractable hemorrhage from pelvic organs was performed in 46 patients. Advantages are discussed regarding different embolic materials, particle size, and embolization directed at branch vessels versus divisional arteries. An optimal approach for managing hemorrhage of different etiologies is developed, taking advantage of (a) selective embolization techniques, (b) pharmacologic manipulation of blood flow, and (c) the ability of embolic material to allow restitution of flow and/or continued collateral perfusion via the precapillary plexus.
Objectives: The management of intractable leg ulcers requires a team approach which includes vascular surgeons and plastic surgeons. We retrospectively reviewed the results of the management of intractable leg ulcers by plastic surgeons. Patients and Methods: A total of 73 patients with intractable leg ulcers, (79 limbs) were treated at the Department of Plastic Surgery at our institution. Skin perfusion pressure (SPP) around the ulcer on the limb was measured before and after arterial reconstructive procedures. Local ulcer management involved intra-wound continuous negative pressure and irrigation therapy or negative pressure wound therapy. We examined the rates of wound healing and associated prognostic factors. Results: There were 21 limbs without ischemia (non-peripheral arterial disease [Non-PAD] group) and 58 limbs with ischemia (PAD group). The healing rates were 66% in the PAD group and 81% in the Non-PAD group, but the difference between the groups was not significant. A total of 41 limbs in the PAD group underwent revascularization, which involved bypass surgery in 18 limbs and endovascular therapy in 23 limbs. The salvage rate of the revascularized limbs was 83% at 1 year. The primary patency rates at 1 year were 87% for bypass surgery and 58% for endovascular therapy. The healing rate of the revascularized limbs was 66%, and the presence of concomitant hemodialysis, infected ulcers, and limbs without improved SPP were shown to be poor prognostic factors. Limbs treated with bypass surgery had a better healing rate than limbs treated with endovascular therapy, but the difference was not significant. Conclusion: Good ulcer-healing rates were achieved by effective revascularization and aggressive local management. These results suggest that a team approach is useful for the management of intractable leg ulcers. (English translation of Jpn J Vasc Surg 2011; 20: 913-920)
Kiyokawa, Kensuke; Akaiwa, Keiichi; Ishida, Masaru; Furuyama, Tadashi; Onohara, Toshihiro
At a tertial referral epilepsy centre 39 children were consecutively enrolled in an open add-on study with topiramate (TPM). All children had intractable epilepsy; the mean seizure frequency was 36 per month, and 31 children were treated with polypharmacy. All but five children were mentally retarded. The initial dose of TPM was 1–5 mg\\/kg daily, slowly titrated with 1–3 mg\\/kg
Peter Uldall; Jette M Ruchholt
There is evidence to support that the cerebellum contributes to the neural processing of both emotions and painful stimuli. This could be particularly relevant in conditions associated with chronic abdominal pain, such as the irritable bowel syndrome (IBS), which are often also characterized by affective disturbances. We aimed to test the hypothesis that in IBS, symptoms of anxiety and depression modulate brain activation during visceral stimulation within the cerebellum. We reanalyzed a previous data set from N = 15 female IBS patients and N = 12 healthy women with a specific focus on the cerebellum using advanced normalization methods. Rectal distension-induced brain activation was measured with functional magnetic resonance imaging using non-painful and painful rectal distensions. Symptoms of anxiety and depression, assessed with the Hospital Anxiety and Depression scale, were correlated with cerebellar activation within IBS patients. Within IBS, depression scores were associated with non-painful distension-induced activation in the right cerebellum primarily in Crus II and lobule VIIIb, and additionally in Crus I. Depression scores were also associated with painful distension-induced activation predominantly in vermal lobule V with some extension to the intermediate cerebellum. Anxiety scores correlated significantly with non-painful induced activation in Crus II. Symptoms of anxiety and depression, which are frequently found in chronic pain conditions like IBS, modulate activation during visceral sensory signals not only in cortical and subcortical brain areas but also in the cerebellum. PMID:22910984
Rosenberger, Christina; Thürling, Markus; Forsting, Michael; Elsenbruch, Sigrid; Timmann, Dagmar; Gizewski, Elke R
Background Dysfunction of brain-gut interaction is thought to underlie visceral hypersensitivity which causes unexplained abdominal pain syndromes. However, the mechanism by which alteration of brain function in the brain-gut axis influences the perception of visceral pain remains largely elusive. In this study we investigated whether altered brain activity can generate visceral hyperalgesia. Results Using a forebrain specific ?CaMKII promoter, we established a line of transgenic (Tg) mice expressing a dominant-negative pore mutant of the Kv7.2/KCNQ2 channel which suppresses native KCNQ/M-current and enhances forebrain neuronal excitability. Brain slice recording of hippocampal pyramidal neurons from these Tg mice confirmed the presence of hyperexcitable properties with increased firing. Behavioral evaluation of Tg mice exhibited increased sensitivity to visceral pain induced by intraperitoneal (i.p.) injection of either acetic acid or magnesium sulfate, and intracolon capsaicin stimulation, but not cutaneous sensation for thermal or inflammatory pain. Immunohistological staining showed increased c-Fos expression in the somatosensory SII cortex and insular cortex of Tg mice that were injected intraperitoneally with acetic acid. To mimic the effect of cortical hyperexcitability on visceral hyperalgesia, we injected KCNQ/M channel blocker XE991 into the lateral ventricle of wild type (WT) mice. Intracerebroventricular injection of XE991 resulted in increased writhes of WT mice induced by acetic acid, and this effect was reversed by co-injection of the channel opener retigabine. Conclusions Our findings provide evidence that forebrain hyperexcitability confers visceral hyperalgesia, and suppression of central hyperexcitability by activation of KCNQ/M-channel function may provide a therapeutic potential for treatment of abdominal pain syndromes.
The extensive literature on this subject is in direct contrast to the limited range of clinical uses for ligands of the transient receptor potential cation channels (TRPs) in diseases of the viscera. TRPV1 is the most spectacular example of this imbalance, as it is in other systems, but it is nonetheless the only TRP target that is currently targeted clinically in bladder sensory dysfunction. It is not clear why this discrepancy exists, but a likely answer is in the promiscuity of TRPs as sensors and transducers for environmental mechanical and chemical stimuli. This review first describes the different sensory pathways from the viscera, and on which nociceptive and non-nociceptive neurones within these pathways TRPs are expressed. They not only fulfil roles as both mechano- and chemo-sensors on visceral afferents, but also form an effector mechanism for cell activation after activation of GPCR and cytokine receptors. Their role may be markedly changed in diseased states, including chronic pain and inflammation. Pain presents the most obvious potential for further development of therapeutic interventions targeted at TRPs, but forms of inflammation are emerging as likely to benefit also. However, despite much basic research, we are still at the beginning of exploring such potential in visceral sensory pathways. PMID:24641218
Blackshaw, L Ashley
Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical challenge. Basic studies of pancreatic nerves and experimental human pain research have provided evidence that pain processing is abnormal in these patients and in many cases resembles that seen in neuropathic and chronic pain disorders. An important ultimate outcome of such aberrant pain processing is that once the disease has advanced and the pathophysiological processes are firmly established, the generation of pain can become self-perpetuating and independent of the initial peripheral nociceptive drive. Consequently, the management of pain by traditional methods based on nociceptive deafferentation (e.g., surgery and visceral nerve blockade) becomes difficult and often ineffective. This novel and improved understanding of pain aetiology requires a paradigm shift in pain management of chronic pancreatitis. Modern mechanism based pain treatments taking into account altered pain processing are likely to increasingly replace invasive therapies targeting the nociceptive source, which should be reserved for special and carefully selected cases. In this review, we offer an overview of the current available pharmacological options for pain management in chronic pancreatitis. In addition, future options for pain management are discussed with special emphasis on personalized pain medicine and multidisciplinarity.
Olesen, S?ren S; Juel, Jacob; Graversen, Carina; Kolesnikov, Yuri; Wilder-Smith, Oliver HG; Drewes, Asbj?rn M
The brainstem is classically divided into functional columns including special and general subdivisions for somatic and visceral components. The term 'special visceral motor' is applied to branchiomotor nuclei, while 'special visceral sensory' refers to nuclei devoted to incoming gustatory and olfactory senses. The use of the term 'special visceral motor' is questioned in that the branchiomotor neurons function more like general somatic than general visceral motoneurons. The designation of taste and smell as 'special visceral sensory' systems seems inconsistent on several bases. First, taste and smell are not homologous systems: (1) the receptors are grossly dissimilar in morphology and relationship to other elements of the nervous system; (2) the two systems mediate very different behaviors and respond to different types of chemical stimuli, and (3) chemosensory systems are not 'special' (i.e. limited to cranial nerves) in that solitary chemoreceptor cells, which are distributed across the body surface, can be innervated by spinal or cranial nerves. Finally, taste is considered 'special' because it involves specialized chemosensory end organs; the visceral nerves also provide innervation to other specialized chemoreceptors (e.g. carotid body) which are considered part of the general visceral sensory system. Thus the term 'special visceral sensory' appears without solid foundation when applied to gustatory systems in contradistinction to nongustatory branchial and thoracic interoceptive systems. A reformulation of the functional columns of the brainstem is suggested in which six columns can be identified: (1) somatic motor; (2) branchial motor; (3) visceral motor; (4) visceral sensory; (5) somatic sensory, and (6) hair cell (dorsolateral placode) sensory. PMID:8109195
Finger, T E
We describe a 30-year-old female with intractable symptomatic epilepsy caused by an insular calcified mass, which was histologically proved as psammomatous meningioma. Seizures were described as consciousness impairment, motionless stare and automatism. After total removal of the tumor with a neuronavigation system and motor evoked potential (MEP) monitoring, seizures completely disappeared without neurological deficit. We emphasize that insular meningioma presents complex partial seizures which mimic medial temporal lobe epilepsy and seizures are controlled by total resection of the tumor. PMID:22915702
Imoto, Hirochika; Fujii, Masami; Maruta, Yuichi; Sadahiro, Hirokazu; Ideguchi, Makoto; Ishihara, Hideyuki; Nomura, Sadahiro; Suzuki, Michiyasu
Intractable chronic pelvic pain (CPP) despite a multidisciplinary approach is challenging to treat. Every structure in the\\u000a abdomen and\\/or pelvis could have a role in the etiology of CPP. Management of chronic pelvic pain may require a combination\\u000a of interventions, including pharmacological, physical and psychological therapy. Interventions suggested to date include nerve\\u000a blocks (ilioinguinal, iliohypogastric, genitofemoral, hypogastric, presacral) and trigger
Patients with irritable bowel syndrome (IBS) show decreased discomfort and pain thresholds to visceral stimuli, as well hypervigilance to gastrointestinal sensations, symptoms, and the context in which these visceral sensations and symptoms occur. Previous research demonstrated normalization of visceral hypersensitivity following repeated exposure to experimental rectal stimuli over a 12 month period that was associated with reduction in cortical regions functionally associated with attention and arousal. Building upon these functional analyses, multivariate functional and effective connectivity analyses were applied to [15O] water positron emission tomography (PET) data from 12 IBS patients (male=4) participating in a PET study before and after 4 visceral sensory testing sessions involving rectal balloon distensions over a 1 year period. First, behavioral partial least squares was applied to test for networks related to reduced subjective ratings observed following repeated application of an aversive rectal stimulus. Next, path analysis within a structural equation modeling framework tested the hypothesis that perceptual habituation to the repeated visceral stimuli resulted in part from the reduced connectivity within a selective attention to threat network over time. Two independent, perception-related networks comprised of interoceptive, attentional and arousal regions were engaged differentially during expectation and distension. In addition, changes in the effective connectivity of an attentional network as well as modulatory amygdala influence suggested that perceptual habituation associated with repeated stimulus delivery results both in an increase in top down modulation of attentional circuits, as well as in a reduction of amygdala-related interference with attentional mechanisms.
Labus, Jennifer S; Naliboff, Bruce D; Berman, Steve M; Suyenobu, Brandall; Vianna, Eduardo P; Tillisch, Kirsten; Mayer, Emeran A
More than 80% of cancer patients experience cancer pain. Among them, more than 50% experience moderate to severe pain. To control cancer pain, a variety of methods have been used, including medications and nerve blocks. In some patients, however, it is impossible to perform nerve blocks due to caner metastasis into the epidural space, while in other patients, opioid dose escalation is impossible due to opioid side effects; thus, cancer pain management is difficult. Scrambler therapy is a novel approach for pain control that uses EKG-like pads, which are applied above and below the site of pain. Scrambler therapy synthesizes 16 different types of nerve action potentials that provide "non-pain" information via cutaneous nerves. The advantages of this treatment are that it is non-invasive and safe and has no significant side effects. In this case series, we report the treatment results of using scrambler therapy in three cancer patients with intractable pain.
Park, Hong Sik; Sin, Woo Kyung; Kim, Hye Young; Park, Soo Young; Kim, Yong Chul; Lee, Sang Chul
Background: Many children with constipation fail to respond with conventional medical therapy. Surgery can produce a good result in dysfunction of the colon secondary to aganglionosis. However, its role in treating idiopathic constipation is more controversial. Patients and Methods: A consecutive series of 44 patients with chronic idiopathic intractable constipation were included in this study. All children were investigated by barium enema and anorectal manometry. Due to inadequate response to medical therapy, all of these patients were selected for internal sphincter myomectomy. Patients were followed-up from 3 to 12 months. Results: Short-term (3 months) and long-term (6 months) follow-up was available for all patients. The histology examinations showed normal ganglion cells in 32, hypoganglionosis in eight and aganglionosis in four patients. In short-term, regular bowel habits, without the need for laxatives or low dose drugs were recorded in 35 patients (79.5%). Overall there was an improvement in 68.2% of the children after 6 months follow-up. There was not any correlation between histopathological findings, duration of symptoms, age and sex of operation and response to myectomy. Conclusion: anorectal myectomy is an effective procedure in patients with intractable idiopathic constipation. It relieves symptoms in 68.2% of patients with chronic refractory constipation. PMID:24841016
Mousavi, Seyed Abdollah; Karami, Hasan; Rajabpoor, Ahmad Ali
A 66-year-old man visited our hospital with a chief complaint of a sore throat. On examination, the pharyngeal and laryngeal mucosa was reddish and localized mucosal erosion was present on the left side. Based on an initial diagnosis of acute pharyngitis caused by bacteriological infection or mycotic infection, treatment with antibacterial and antimycotic agents was initiated. However, the patient's sore throat gradually worsened and he developed intractable hiccups. Intravenous steroids were given for the treatment of the severe sore throat, and this symptom was gradually alleviated. However, the intractable hiccups persisted. In addition, the patient began to have convulsive syncope episodes and was subsequently admitted to our hospital. Further examination revealed that the syncope episodes were linked to the hiccups. To treat the hiccups, baclofen and Chinese medicine were prescribed, and the convulsive syncope episodes disappeared immediately. The patient's hiccups also improved and disappeared six days thereafter. Based on this clinical evidence, we concluded that the hiccups were caused by pharyngitis, resulting in the stimulation of the glossopharyngeal nerve, while the convulsive syncope episodes were a type of situational syncope related to hiccups. PMID:24313063
Sueyoshi, Shintaro; Shin, Buichiro; Nakashima, Tadashi
Fat distribution, especially increased visceral fat, may be as important as overall obesity in increasing risk of heart disease, type 2 diabetes and certain cancers. Risk of disease, as well as visceral fat, increases dramatically with age. Cross-sectional data suggests that increased risk of disease may be largely prevented if the age related increase in visceral fat does not occur. The objective of this short review is to present data that shows visceral fat increasing over 200% in men and 400% in women between the 3rd and 7th decades, show that a combination of weight gain, loss of muscle, and a shift from peripheral to central fat patterning contributes to this increase, and identify hormones that may be responsible for the shift. Finally, the review will show how participation in exercise can slow the age related shift in visceral fat.
Hunter, Gary R.; Gower, Barbara A.; Kane, Brandon L.
Spinal epidural lipomatosis (SEL) is an overgrowth of the normally encapsulated adipose tissue in the epidural space around the spinal cord in the thoracic and lumbar spine causing compression of the neural components. Idiopathic SEL in non-obese patients is exceptional. Idiopathic SEL can result in thoracic myelopathy and lumbar radiculopathy. A thoracic radiculopathy due to idiopathic SEL has not been reported yet. We report a case of idiopathic SEL with intractable chest pain and paresthesia. We suggest that idiopathic SEL should be considered as a cause of chest pain.
Lee, Sang-Beom; Chang, Jae-Chil; Jin, So-Young
SUMMARY Background Irritable bowel syndrome is characterised by chronic abdominal pain and frequent comorbid anxiety. The substance P/neurokinin-1 receptor system is implicated in the regulation of both pain and anxiety, suggesting a potential therapeutic target in IBS. Aim To determine whether inhibition of the neurokinin-1 receptor (NK1R) will change pain ratings and brain responses to experimental visceral pain and anxiety symptoms in women with IBS or not. Methods Rome II positive IBS women were recruited for a double-blind, placebo-controlled, cross-over study of NK1R antagonist AV608. Treatment periods were 3 weeks with a 2-week washout period. Functional MRI during a visceral distension paradigm was performed before first treatment and after treatment blocks. SPM8 was used to compare brain activity during painful and nonpainful visceral stimuli in regions associated with emotional arousal and interoception. Negative affect, anxiety symptoms and pain ratings were assessed. Results Eleven subjects completed the study and eight subjects provided fMRI data. AV608, compared with placebo, was associated with reduced anxiety, negative affect, and pain ratings. During AV608 treatment, the amygdala, hippocampus and anterior cingulate gyrus showed decreased activity during visceral distension. AV608 was also associated with decreases in activity in brain regions associated with interoception (posterior insula, anterior mid-cingulate gyrus). Conclusions Chronic treatment with AV608 in IBS is associated with improved mood and pain ratings and activity of emotional arousal related brain regions. This suggests that further exploration of NK1R antagonists is warranted in visceral pain disorders, particularly in patients with comorbid anxiety symptoms.
Tillisch, K.; Labus, J.; Nam, B.; Bueller, J.; Smith, S.; Suyenobu, B.; Siffert, J.; McKelvy, J.; Naliboff, B.; Mayer, E.
Studies in healthy human subjects and patients with irritable bowel syndrome suggest sex differences in cerebral nociceptive processing. Here we examine sex differences in functional brain activation in the rat during colorectal distention (CRD), a preclinical model of acute visceral pain. [14C]-iodoantipyrine was injected intravenously in awake, nonrestrained female rats during 60-mmHg or 0-mmHg CRD while electromyographic abdominal activity (EMG) and pain behavior were recorded. Regional cerebral blood flow related tissue radioactivity was analyzed by statistical parametric mapping from autoradiographic images of 3-dimensionally reconstructed brains. Sex differences were addressed by comparing current data with our previously published data collected from male rats. While sex differences in EMG and pain scores were modest, significant differences were noted in functional brain activation. Females showed widespread changes in limbic (amygdala, hypothalamus) and paralimbic structures (ventral striatum, nucleus accumbens, raphe), while males demonstrated broad cortical changes. Sex differences were apparent in the homeostatic afferent network (parabrachial nucleus, thalamus, insular and dorsal anterior cingulate cortices), in an emotional-arousal network (amygdala, locus coeruleus complex), and in cortical areas modulating these networks (prefrontal cortex). Greater activation of the ventromedial prefrontal cortex and broader limbic/paralimbic changes in females suggest greater engagement of affective mechanisms during visceral pain. Greater cortical activation in males is consistent with the concept of greater cortical inhibitory effects on limbic structures in males, which may relate to differences in attentional and cognitive attribution to visceral stimuli. These findings show remarkable similarities to reported sex differences in brain responses to visceral stimuli in humans.
Bradesi, Sylvie; Labus, Jennifer S.; Maarek, Jean-Michel I.; Lee, Kevin; Winchester, Wendy J.; Mayer, Emeran A.; Holschneider, Daniel P.
Chronic pain affects billions of lives globally and is a major public health problem in the United States. However, pain management is still a challenging task due to a lack of understanding of the fundamental mechanisms of pain. In the past decades transient receptor potential (TRP) channels have been identified as molecular sensors of tissue damage and inflammation. Activation/sensitization of TRP channels in peripheral nociceptors produces neurogenic inflammation and contributes to both somatic and visceral pain. Pharmacological and genetic studies have affirmed the role of TRP channels in multiple forms of inflammatory and neuropathic pain. Thus pain-evoking TRP channels emerge as promising therapeutic targets for a wide variety of pain and inflammatory conditions. PMID:24396340
Luo, Jialie; Walters, Edgar T; Carlton, Susan M; Hu, Hongzhen
Chronic pain affects billions of lives globally and is a major public health problem in the United States. However, pain management is still a challenging task due to a lack of understanding of the fundamental mechanisms of pain. In the past decades transient receptor potential (TRP) channels have been identified as molecular sensors of tissue damage and inflammation. Activation/sensitization of TRP channels in peripheral nociceptors produces neurogenic inflammation and contributes to both somatic and visceral pain. Pharmacological and genetic studies have affirmed the role of TRP channels in multiple forms of inflammatory and neuropathic pain. Thus pain-evoking TRP channels emerge as promising therapeutic targets for a wide variety of pain and inflammatory conditions
Luo, Jialie; Walters, Edgar T.; Carlton, Susan M.; Hu, Hongzhen
Objective: To investigate the clinical value, technique, indications and contraindications of laryngotracheal closure (LTC) and cricopharyngeal myotomy (CPM) for intractable aspiration and dysphagia secondary to a cerebrovascular accident (CVA). Materials and Methods: Patients (n = 45) with intractable aspiration and dysphagia secondary to a CVA were treated with LTC and CPM. The LTC was performed by suturing the double cords,
Shen-Hong Qu; Min Li; Jian-Ping Liang; Zheng-Zhong Su; Shi-Qiang Chen; Xiao-Guang He
In this article, the authors use the Israeli–Palestinian conflict as an example of ostensibly intractable ethnonational conflict and examine the psychological dynamics that contribute to its intractability. They review the unique characteristics of this conflict and the clash of narratives. They argue that some ethnonational conflicts have characteristics that increase their resistance to change and that societies in such conflicts
Nadim N. Rouhana; Daniel Bar-Tal
Pruritus due to cholestatic liver disease can be particularly difficult to manage and frequently is intractable to a variety of medical therapies. The aim of our study is to evaluate the efficacy of ?-9-tetrahydrocannabinol (?-9-THC) for intractable cholestatic related pruritus (ICRP) that has failed conventional (and unconventional) remedies. Three patients were evaluated for plasmapheresis because of ICRP. All 3 patients
Guy W Neff; Christopher B O’Brien; K. Rajender Reddy; Nora V Bergasa; Arie Regev; Enrique Molina; Rafael Amaro; Miguel J Rodriguez; VeEtta Chase; Lennox Jeffers; Eugene Schiff
Objectives: To contrast and compare self-reported qual- ity of life in patients with intractable epilepsy and pseu- doseizures and to examine the relationship between self- reports and objective measures of cognitive functioning in both of these groups. Design: Case series using profile analysis and analysis of covariance. Setting: University epilepsy surgery program. Participants: Forty-three patients with intractable com- plex partial
Joshua I. Breier; Hiroshi Yamauchi; Bonnie L. Brookshire; Yasuhiro Nagahama; Yukinori Katsumi; Jules Constantinou; L. James Willmore; Junji Konishi; Jun Kimura; Kathleen L. Fuchs; James Wheless; Azreena B. Thomas; Hans A. Carpay; Willem F. M. Arts; Ada T. Geerts; Hans Stroink; Oebele F. Brouwer; A. C. Boudewyn Peters; Cees A. van Donselaar; William P. Goldman; Jack D. Baty; Virginia D. Buckles; Shirley Sahrmann; John C. Morris
Abdominal pain is frequently related to visceral hypersensitivity. This is associated with increased neuronal excitability in the central nervous system (CNS), which can be manifested as discrete electroencephalographic (EEG) alterations. In the current placebo-controlled study, visceral hypersensitivity was evoked by chemical irritation of the esophagus with acid and capsaicin perfusion. The resulting hyperexcitability of the CNS was evaluated by evoked brain potentials following painful electrical stimulations of a remote organ—the rectosigmoid colon. Alterations in individual EEG power distributions between baseline and after perfusion were quantified by extracting features from the evoked brain potentials using an optimized discrete wavelet transform. Visceral hypersensitivity was identified as increased EEG power in the delta, theta and alpha frequency bands. By applying a support vector machine in regression mode, the individual baseline corrected alterations after sensitization were discriminated from alterations caused by placebo perfusions. An accuracy of 91.7% was obtained (P < 0.01). The regression value representing the overall alteration of the EEG correlated with the degree of hyperalgesia (P = 0.03). In conclusion, this study showed that classification of EEG can be used to detect biomarkers reflecting central neuronal changes. In the future, this may be used in studies of pain physiology and pharmacological interventions.
Graversen, Carina; Brock, Christina; Mohr Drewes, Asbjørn; Farina, Dario
This book contains 13 chapters. Some of the chapter titles are: Importance of the Problem; Neurophysiology and Biochemistry of Pain; Assessment of Pain in Patients with Cancer; Drug Therapy; Chemotherapy and Radiotherapy for Cancer Pain; Sympton Control as it Relates to Pain Control; and Palliative Surgery in Cancer Pain Treatment.
M. Swerdlow; V. Ventafridda
Chronic pancreatitis affects many individuals around the world, and the study of the underlying mechanisms leading to better treatment possibilities are important tasks. Therefore, animal models are needed to illustrate the basic study of pancreatitis. Recently, animal models of acute and chronic pancreatitis have been thoroughly reviewed, but few reviews address the important aspect on the translation of animal studies to human studies. It is well known that pancreatitis is associated with epigastric pain, but the understanding regarding to mechanisms and appropriate treatment of this pain is still unclear. Using animal models to study pancreatitis associated visceral pain is difficult, however, these types of models are a unique way to reveal the mechanisms behind pancreatitis associated visceral pain. In this review, the animal models of acute, chronic and un-common pancreatitis are briefly outlined and animal models related to pancreatitis associated visceral pain are also addressed.
Zhao, Jing-Bo; Liao, Dong-Hua; Nissen, Thomas Dahl
This report describes a rare case of postoperative hyperventilation attack after an endoscopic third ventriculostomy in a 46-year-old woman. About 60 min after the termination of the operation, an intractable hyperventilation started with respiratory rate of 65 breaths/min and EtCO2, 16.3 mm Hg. Sedation with benzodiazepine, thiopental sodium, fentanyl, and propofol/remifentanil infusion was tried under a rebreathing mask at a 4 L/min of oxygen. With aggressive sedative challenges, ventilation pattern was gradually returned to normal during the 22 hrs of time after the surgery. A central neurogenic hyperventilation was suspected due to the stimulating central respiratory center by cold acidic irrigation solution during the neuroendoscopic procedure.
Lee, Hae Mi; Shin, Kyung Bae; Kim, Seong Ho
Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous disorder and both clinical course and response to treatment vary widely. Because of the propensity for relapse, CIDP requires maintenance therapy after the initial response to treatment. There is no consensus regarding this in the published literature. Present report: A patient with CIDP was treated with oral prednisolone and cyclophosphamide pulse therapy but required repeated plasma exchange and intravenous immunoglobulin (IVIg). Treatment with ciclosporin freed the patient from repeated IVIg administration. Therapeutic responses in 14 subsequent cases including three patients who showed improvement with ciclosporin are also presented along with an algorithm of the authors' suggested protocol for treatment. Conclusion: Ciclosporin should be considered for patients with intractable CIDP who require repeated IVIg.
Odaka, M; Tatsumoto, M; Susuki, K; Hirata, K; Yuki, N
We describe a female insulinoma patient who presented with recurrent attacks of abnormal behavior, confusion, and seizure. Her interictal EEG showed epileptiform discharges on the left temporal area, therefore she was initially misdiagnosed as temporal lobe epilepsy. In the video-EEG monitoring, hypoglycemic state was detected during the seizure attack, so the right diagnosis was made after the endocrinologic investigations. After surgical removal of the tumor, the patient became seizure-free, and no abnormality was found in the follow-up EEG after six months. Since insulinoma shares some common clinical and EEG features with complex partial seizure of temporal lobe origin, insulioma should be included in the differential diagnosis for medically intractable temporal lobe epilepsy.
Park, So-Hee; Kim, Dong Wook
There has been a long-standing controversy as to whether or not internal organs are innervated by a special category of 'visceral nociceptor'. Recent experimental studies on the afferent supply of some viscera have thrown new light on this issue by demonstrating the presence of several categories of visceral sensory receptor, including high-threshold receptors, 'silent' nociceptors and intensity-encoding receptors. Advances in the understanding of how the CNS processes nociceptive signals have also helped to clarify the issue. The authors of this report, originally having different points of view, present here a common and closer approach to the visceral nociceptor controversy. PMID:1279857
Cervero, F; Jänig, W
Visceral artery aneurysms, although uncommon, can present with life-threatening hemorrhage. The increasing use of imaging studies has allowed for earlier identification and intervention of these aneurysms, thus avoiding the high morbidity and mortality associated with rupture. The treatment options for visceral artery aneurysms range from conventional open surgical repair to minimally invasive techniques using covered stents or embolization materials. Anatomic features and patient selection determine which treatment option would result in the most durable treatment and outcome. This article reviews our experience with the endovascular treatment of visceral artery aneurysms. PMID:17942851
Carroccio, Alfio; Jacobs, Tikva S; Faries, Peter; Carroccio, Alfio; Jacobs, Tikva S; Faries, Peter; Ellozy, Sharif H; Teodorescu, Victoria J; Ting, Windsor; Marin, Michael L
Pancreatic cancer and chronic pancreatitis are clinical syndromes associated with severe pain that is difficult to manage. Thus, seeking additional pain reduction therapies is warranted. Excessive alcohol consumption over an extended period of time is the primary causal agent in pancreatitis. The efficacy of a replication defective Herpes (HSV-1, DPE) viral vector construct encoding the human preproenkephalin gene (HSV-Enk), used as a molecular therapy for alleviation of pancreatitis pain, is reviewed here. The characteristics of the gene therapy treatment for inflammation and pain-related behavior in two alcoholic pancreatitis animal models is described. Significant analgesia and protection of pancreatic tissue was provided for the duration of the transgene expression (approximately 4-6 weeks). These studies establish a basis for use of HSV-based gene therapy for chronic visceral pain. Targeted enkephalin gene therapy approaches are providing clear promise for pain control. As innovative means of significantly reducing pancreatic inflammation and preserving tissue architecture, they may extend their clinical usefulness for pancreatitis and pancreatic cancer pain patients. PMID:19262610
Westlund, K N
We wished to determine if visceral perception in the rectum and stomach is altered in patients with irritable bowel syndrome and to evaluate the effects on visceral sensation of 5-HT3 receptor blockade. Twelve community patients with diarrhea-predominant irritable bowel syndrome and 10 healthy controls were studied in a double-blind, randomized, placebo-controlled study. Using two barostats, the stomach and rectum were
Jaime Zighelboim; Nicholas J. Talley; Sidney F. Phillips; William S. Harmsen; Alan R. Zinsmeister
This article reviews the available published knowledge about the diagnosis, pathophysiology and treatment of myofascial pain syndromes from trigger points. Furthermore, epidemiologic data and clinical characteristics of these syndromes are described, including a detailed account of sensory changes that occur at both painful and nonpainful sites and their utility for diagnosis and differential diagnosis; the identification/diagnostic criteria available so far are critically reviewed. The key role played by myofascial trigger points as activating factors of pain symptoms in other algogenic conditions--headache, fibromyalgia and visceral disease--is also addressed. Current hypotheses on the pathophysiology of myofascial pain syndromes are presented, including mechanisms of formation and persistence of primary and secondary trigger points as well as mechanisms beyond referred pain and hyperalgesia from trigger points. Conventional and most recent therapeutic options for these syndromes are described, and their validity is discussed on the basis of results from clinical controlled studies. PMID:22094195
Giamberardino, Maria Adele; Affaitati, Giannapia; Fabrizio, Alessandra; Costantini, Raffaele
Spontaneous dissection of a visceral artery without associated aortic dissection is rare, although more cases have recently been reported because of the advancement of diagnostic techniques. The risk factors, causes, and natural history of spontaneous isolated visceral artery dissection are unclear. Treatment with open surgery, endovascular stenting, or anticoagulation therapy has been proposed; however, there is no consensus on the optimal management. We present three cases of spontaneous and isolated dissection of visceral arteries. Dissection involved the superior mesenteric artery in one and the celiac artery in two. All three patients presented with acute abdominal pain but lacked any peritoneal irritation. The patients were treated nonoperatively with anticoagulants or antiplatelets. No surgical or endovascular intervention was performed. Follow-up imaging studies demonstrated improvement of the dissection in two patients and no change in one patient. All patients were symptom-free over a mean follow-up of 17 months. Nonoperative treatment with close observation is an acceptable strategy in the management of spontaneous isolated dissection of visceral arteries. Emergent intervention is not mandatory in symptomatic patients without evidence of acute bowel ischemia or hemorrhage. PMID:18774686
Zhang, Wayne W; Killeen, J David; Chiriano, Jason; Bianchi, Christian; Teruya, Theodore H; Abou-Zamzam, Ahmed M
Background Facial pain may be divided into several distinct categories, each requiring a specific treatment approach. In some cases, however, such categorization is difficult and treatment is ineffective. We reviewed our extensive clinical experience and designed an algorithmic approach to the treatment of medically intractable facial pain that can be treated through surgical intervention. Methods Our treatment algorithm is based on taking into account underlying pathological processes, the anatomical distribution of pain, pain characteristics, the patient's age and medical condition, associated medical problems, the history of previous surgical interventions, and, in some cases, the results of psychological evaluation. The treatment modalities involved in this algorithm include diagnostic blocks, peripheral denervation procedures, craniotomy for microvascular decompression of cranial nerves, percutaneous rhizotomies using radiofrequency ablation, glycerol injection, balloon compression, peripheral nerve stimulation procedures, stereotactic radiosurgery, percutaneous trigeminal tractotomy, and motor cortex stimulation. We recommend that some patients not receive surgery at all, but rather be referred for other medical or psychological treatment. Results Our algorithmic approach was used in more than 100 consecutive patients with medically intractable facial pain. Clinical evaluations and diagnostic workups were followed in each case by the systematic choice of the appropriate intervention. The algorithm has proved easy to follow, and the recommendations include the identification of the optimal surgery for each patient with other options reserved for failures or recurrences. Our overall success rate in eliminating facial pain presently reaches 96%, which is higher than that observed in most clinical series reported to date Conclusion This treatment algorithm for the intractable facial pain appears to be effective for patients with a wide variety of painful conditions and may be recommended for use in other institutions.
Slavin, Konstantin V; Nersesyan, Hrachya; Colpan, Mustafa E; Munawar, Naureen
Our data demonstrate that approximately 23-29% of standard dorsal root entry zone (DREZ) microcoagulation procedures fail to relieve pain due to inadequate thermal lesions and that approximately 39% fail due to insufficient superior extent of lesions. The remaining failures are related to inadequate lesion placement, improper selection of patients, and, rarely, posttraumatic spinal deafferentation pain resulting from other non-DREZ mechanisms. Computer-assisted DREZ microcoagulation is a satisfactory procedure to treat intractable posttraumatic spinal deafferentation pain, brachial plexus avulsion pain, and lumbosacral nerve root avulsion pain. In all these conditions we have identified areas of abnormal focal hyperactivity in the DREZ area. Perhaps this procedure can be applied to other central pain conditions if, using this technique, abnormal focal hyperactivity is demonstrated to be present. PMID:8439716
Edgar, R E; Best, L G; Quail, P A; Obert, A D
Objective To investigate the clinical efficacy of individual endovascular management for the treatment of different traumatic pseudoaneurysms presenting as intractable epistaxis. Materials and Methods For 14 consecutive patients with traumatic pseudoaneurysm presenting as refractory epistaxes, 15 endovascular procedures were performed. Digital subtraction angiography revealed that the pseudoaneurysms originated from the internal maxillary artery in eight patients; and all were treated with occlusion of the feeding artery. In six cases, they originated from the internal carotid artery (ICA); out of which, two were managed with detachable balloons, two with covered stents, one by means of cavity embolization, and the remaining one with parent artery occlusion. All of these cases were followed up clinically from six to 18 months, with a mean follow up time of ten months; moreover, three cases were also followed with angiography. Results Complete cessation of bleeding was achieved in all the 15 instances (100%) immediately after the endovascular therapies. Of the six patients who suffered from ICA pseudoaneurysms, one presented with a permanent stroke and one had an episode of rebleeding requiring intervention. Conclusion In patients presenting with a history of craniocerebral trauma, traumatic pseudoaneurysm must be considered as a differential diagnosis. Individual endovascular treatment is a relatively safe, plausible, and reliable means of managing traumatic pseudoaneurysms.
Zhang, Chang wei; You, Chao; Mao, Bo yong; Wang, Chao hua; He, Min; Sun, Hong
With an annual incidence of 50/100,000 people, nearly 1% of the population suffers from epilepsy. Treatment with antiepileptic medication fails to achieve seizure remission in 20-30% of patients. One treatment option for refractory epilepsy patients who would not otherwise be surgical candidates is electrical stimulation of the brain, which is a rapidly evolving and reversible adjunctive therapy. Therapeutic stimulation can involve direct stimulation of the brain nuclei or indirect stimulation of peripheral nerves. There are three stimulation modalities that have class I evidence supporting their uses: vagus nerve stimulation (VNS), stimulation of the anterior nuclei of the thalamus (ANT), and, the most recently developed, responsive neurostimulation (RNS). While the other treatment modalities outlined deliver stimulation regardless of neuronal activity, the RNS administers stimulation only if triggered by seizure activity. The lower doses of stimulation provided by such responsive devices can not only reduce power consumption, but also prevent adverse reactions caused by continuous stimulation, which include the possibility of habituation to long-term stimulation. RNS, as an investigational treatment for medically refractory epilepsy, is currently under review by the FDA. Eventually systems may be developed to enable activation by neurochemical triggers or to wirelessly transmit any information gathered. We review the mechanisms, the current status, the target options, and the prospects of RNS for the treatment of medically intractable epilepsy. PMID:23735806
Liu, Chong; Wen, Xiong-Wei; Ge, Yan; Chen, Ning; Hu, Wen-Han; Zhang, Tan; Zhang, Jian-Guo; Meng, Fan-Gang
Autonomic dysfunction and mood disorders are frequently described in Crohn's disease (CD) and are known to influence visceral sensitivity. We addressed the link between vagal tone, negative affect, and visceral sensitivity in CD patients without concomitant features of irritable bowel syndrome (IBS). Rectal distensions to a discomfort threshold of 70% and onset of pain were performed in nine CD patients in remission and eight healthy controls. Autonomic parameters were evaluated with heart rate variability and electrodermal reactivity. We showed that CD patients had (i) higher scores of depressive symptomatology (12 ± 3 in patients vs 4 ± 1 in controls on the Center for Epidemiologic Studies-Depression Scale; p = 0.038), (ii) reduced vagal tone (HF 257 ± 84 ms(2) vs 1607 ± 1032 ms(2) , p = 0.043; LF 455 ± 153 ms(2) vs 1629 ± 585 ms(2) , p = 0.047), (iii) decreased sympathetic reactivity during an aversive stimulus, and (iv) higher tolerance to rectal distension pressures (43 ± 3 mmHg vs 30 ± 2 mmHg, p = 0.002) and low sensitivity index scores. In conclusion, our results provide preliminary evidence that patients with quiescent CD, in the absence of IBS, are hyposensate to experimental rectal distension. These data provide further evidence that anxiety and depressive symptomatology in addition to autonomic dysfunction modulate visceral pain perception in quiescent CD patients in the absence of IBS. PMID:24861415
Rubio, A; Pellissier, S; Picot, A; Dantzer, C; Bonaz, B
Evaluated was the use of an oral elemental diet consisting of crystalline amino acids, glucose, electrolytes, and vitamins to control severe intractable diarrhea in 27 infants (1-day to 9-months of age). (DB)
Sherman, Joseph O.; And Others
Background Gossypiboma is a term used to describe a mass that forms around a cotton sponge or abdominal compress accidentally left in a patient during surgery. Transmural migration of an intra-abdominal gossypiboma has been reported to occur in the digestive tract, bladder, vagina and diaphragm. Open surgery is the most common approach in the treatment of gossypiboma. However, gossypibomas can be extracted by endoscopy while migrating into the digestive tract. We report a case of intractable duodenal ulcer caused by transmural migration of gossypiboma successfully treated by duodenorrhaphy. A systemic literature review is provided and a scheme of the therapeutic approach is proposed. Case presentation A 61-year-old Han Chinese man presented with intermittent epigastric pain for the last 10 months. He had undergone laparoscopic cholecystectomy conversion to open cholecystectomy for acute gangrenous cholecystitis 10 months ago at another hospital. Transmural migration of gossypiboma into the duodenum was found. Endoscopic intervention failed to remove the entire gauze, and duodenal ulcer caused by the gauze persisted. Surgical intervention was performed and the gauze was removed successfully. The penetrated ulcer was repaired with duodenorrhaphy. The postoperative period was uneventful. We systematically reviewed the literature on transmural migration of gossypiboma into duodenum and present an overview of published cases. Our PubMed search yielded seven reports of transmural migration of retained surgical sponge into the duodenum. Surgical interventions were necessary in two patients. Conclusion Transmural migration of gossypiboma into the duodenum is a rare surgical complication. The treatment strategies include endoscopic extraction and surgical intervention. Prompt surgical intervention should be considered for emergent conditions such as active bleeding, gastrointestinal obstruction, or intra-abdominal sepsis. For non-emergent conditions, surgical intervention could be considered for intractable cases in which endoscopic extraction failed.
Pain is a ubiquitous yet highly variable experience. The psychophysiological and genetic factors responsible for this variability remain unresolved. We hypothesised the existence of distinct human pain clusters (PCs) composed of distinct psychophysiological and genetic profiles coupled with differences in the perception and the brain processing of pain. We studied 120 healthy subjects in whom the baseline personality and anxiety traits and the serotonin transporter-linked polymorphic region (5-HTTLPR) genotype were measured. Real-time autonomic nervous system parameters and serum cortisol were measured at baseline and after standardised visceral and somatic pain stimuli. Brain processing reactions to visceral pain were studied in 29 subjects using functional magnetic resonance imaging (fMRI). The reproducibility of the psychophysiological responses to pain was assessed at year. In group analysis, visceral and somatic pain caused an expected increase in sympathetic and cortisol responses and activated the pain matrix according to fMRI studies. However, using cluster analysis, we found 2 reproducible PCs: at baseline, PC1 had higher neuroticism/anxiety scores (P ? 0.01); greater sympathetic tone (P<0.05); and higher cortisol levels (P ? 0.001). During pain, less stimulus was tolerated (P ? 0.01), and there was an increase in parasympathetic tone (P ? 0.05). The 5-HTTLPR short allele was over-represented (P ? 0.005). PC2 had the converse profile at baseline and during pain. Brain activity differed (P ? 0.001); greater activity occurred in the left frontal cortex in PC1, whereas PC2 showed greater activity in the right medial/frontal cortex and right anterior insula. In health, 2 distinct reproducible PCs exist in humans. In the future, PC characterization may help to identify subjects at risk for developing chronic pain and may reduce variability in brain imaging studies. PMID:23714265
Farmer, Adam D; Coen, Steven J; Kano, Michiko; Paine, Peter A; Shwahdi, Mustafa; Jafari, Jafar; Kishor, Jessin; Worthen, Sian F; Rossiter, Holly E; Kumari, Veena; Williams, Steven C R; Brammer, Michael; Giampietro, Vincent P; Droney, Joanne; Riley, Julia; Furlong, Paul L; Knowles, Charles H; Lightman, Stafford L; Aziz, Qasim
We report a case in which motor cortex stimulation (MCS) improved neuropathic facial pain due to peripheral nerve injury and\\u000a restored tactile and thermal sensory loss. A 66-year-old man developed intractable trigeminal neuropathic pain after trauma\\u000a of the supraorbital branch of the Vth nerve, associated with tactile and thermal sensory loss in the painful area. MCS was\\u000a performed using neuronavigation
Denys Fontaine; Jean Louis Bruneto; Hasna El Fakir; Philippe Paquis; Michel Lanteri-Minet
Genetically modified (GM) crops may contain newly expressed proteins that are described as "intractable". Safety assessment of these proteins may require some adaptations to the current assessment procedures. Intractable proteins are defined here as those proteins with properties that make it extremely difficult or impossible with current methods to express in heterologous systems; isolate, purify, or concentrate; quantify (due to low levels); demonstrate biological activity; or prove equivalency with plant proteins. Five classes of intractable proteins are discussed here: (1) membrane proteins, (2) signaling proteins, (3) transcription factors, (4) N-glycosylated proteins, and (5) resistance proteins (R-proteins, plant pathogen recognition proteins that activate innate immune responses). While the basic tiered weight-of-evidence approach for assessing the safety of GM crops proposed by the International Life Sciences Institute (ILSI) in 2008 is applicable to intractable proteins, new or modified methods may be required. For example, the first two steps in Tier I (hazard identification) analysis, gathering of applicable history of safe use (HOSU) information and bioinformatics analysis, do not require protein isolation. The extremely low level of expression of most intractable proteins should be taken into account while assessing safety of the intractable protein in GM crops. If Tier II (hazard characterization) analyses requiring animal feeding are judged to be necessary, alternatives to feeding high doses of pure protein may be needed. These alternatives are discussed here. PMID:24662477
Bushey, Dean F; Bannon, Gary A; Delaney, Bryan F; Graser, Gerson; Hefford, Mary; Jiang, Xiaoxu; Lee, Thomas C; Madduri, Krishna M; Pariza, Michael; Privalle, Laura S; Ranjan, Rakesh; Saab-Rincon, Gloria; Schafer, Barry W; Thelen, Jay J; Zhang, John X Q; Harper, Marc S
Sexual pain is an underrecognized and poorly treated constellation of disorders that significantly impact affected women and their partners. Recognized as a form of chronic pain, sexual pain disorders are heterogeneous and include dyspareunia (superficial and deep), vaginismus, vulvodynia, vestibulitis, and noncoital sexual pain disorder. Women too often tolerate pain in the belief that this will meet their partners' needs. This article provides a review of the terminology and definition of the condition, theories on the pathophysiology, diagnostic considerations, and recommendations on the management of female sexual pain. PMID:20393420
Boardman, Lori A; Stockdale, Colleen K
Starting from the observation of the relationships of the biological system with its environments and of the genetically determined neuronal properties of plasticity and rhythmicity, it is possible to propose a new hypothesis about the functional role and organization of the visceral nervous system based on the physical model of the Dissipative Structure by I. Prigogine. The similarily between the visceral nervous system function and this model is supported by the following observations: (1) The visceral nervous system is a complex system, composed of many interacting units, which works away from thermodynamic equilibrium; (2) the functional organization of the nervous system is strongly dependent on internal and external environmental stimuli; (3) it is characterized by the presence of rhythms and periodic behaviors and (4) the internal order of the system is maintained in the continuous interplay between function, structure and fluctuations. On the basis of the present hypothesis, a few general principles can be formulated: (1) the higher brain centers, the fluid matrix and the external world, are the visceral nervous system natural environments; (2) with which it is plastically interfaced as a thermodynamic dissipative structure; (3) its main functional role is to regulate, distribute and maintain ordered exchanges of matter, energy and information between these environments. The present is a general interpretation of the operations of the visceral nervous system as a whole. In the frame of this interpretation the hypotheses so far formulated, including the homeostatic theory, can be viewed as the description of discrete and complementary aspects of the visceral nervous system functions. PMID:11812179
Focal epilepsy with ictal abdominal pain is an unusual partial epilepsy characterized by paroxysmal episodes of abdominal or visceral pain, disturbance of awareness and electroencephalographic abnormalities. We describe a new case of ictal abdominal pain in which gastrointestinal complaints were the only manifestation of seizures and review the previously described pediatric patients. In our patient clinical findings, ictal EEG abnormalities, and a good response to antiepileptic drugs allowed us to make a diagnosis of focal epilepsy with ictal abdominal pain. This is a rare epileptic phenomenon that should be suspected in patients with unexplained paroxysmal abdominal pain and migraine-like symptoms. We suggest that, after the exclusion of more common etiologies, focal epilepsy with ictal abdominal pain should be considered in patients with paroxysmal abdominal pain and ictal EEG abnormalities. PMID:24321431
Cerminara, Caterina; El Malhany, Nadia; Roberto, Denis; Curatolo, Paolo
This article explicates a theory that oxytocin, a sexually dimorphic neurotransmitter and paracrine hormone, is a plausible mechanism linking early relational trauma with posttraumatic self disorders (e.g., dissociation, somatization, and interpersonal sensitivity), posttraumatic stress disorder, and pelvic visceral dysregulation disorders (e.g., irritable bowel syndrome, chronic pelvic pain, interstitial cystitis, and hyperemesis gravidarum). This posttraumatic oxytocin dysregulation disorders theory is consistent
Julia S. Seng
\\u000a \\u000a \\u000a \\u000a \\u000a \\u000a \\u000a Patients suffering with chronic diffuse pain who lack objective clinical and laboratory findings (e.g., fibromyalgia) frequently\\u000a are dismissed as not having real pain, which only perpetuates their illness.\\u000a \\u000a \\u000a \\u000a \\u000a \\u000a \\u000a There are four principal categories of pain: nociceptive pain, neuropathic pain, chronic pain of complex etiology, and psychogenic\\u000a pain.\\u000a \\u000a \\u000a \\u000a \\u000a \\u000a \\u000a Pain assessment should include attention to possible psychological and sociocultural
John B. Winfield
Paroxysmal orofacial pains can cause diagnostic problems, especially when different clinical pictures occur simultaneously. Pain due to pulpitis, for example, may show the same characteristics as pain due to trigeminal neuralgia would. Moreover, the trigger point of trigeminal neuralgia can either be located in a healthy tooth or in the temporomandibular joint. Neuralgic pain is distinguished into trigeminal neuralgia, glossopharyngeal neuralgia, Horton's neuralgia, cluster headache and paroxysmal hemicrania. In 2 cases trigeminal neuralgia is successfully managed with a neurosurgical microvascular decompression procedure according to Jannetta. Characteristic pain attacks resembling neuralgic pain result from well understood pathophysiological mechanisms. Consequently, adequate therapy, such as a Janetta procedure and specific pharmacological therapy, is available. PMID:17147031
de Bont, L G M
Joint pain may result from traumas or repeated microtraumas, as in sports injuries. Pain in osteoarthritis starts before any\\u000a objective finding. It has been demonstrated that in the first stages of this disease, pain is due to intraosseous venous engorgement\\u000a for the earlier thickening of the cortical bone under the articular cartilage. The mechanisms of inflammatory pain are more\\u000a complex
Massimo Zoppi; Elisabetta Beneforti
: Vertebral fracture is the most common complication of osteoporosis. It results in significant mortality and morbidity, including\\u000a prolonged and intractable pain in a minority of patients. Vertebroplasty and kyphoplasty, procedures that involve percutaneous\\u000a injection of bone cement into a collapsed vertebra, have recently been introduced for treatment of osteoporotic patients who\\u000a have prolonged pain (several weeks or longer) following
N. B. Watts; S. T. Harris; H. K. Genant
The action of botulinum neurotoxins (BoNTs) at the neuromuscular junction has been extensively investigated and knowledge gained in this field laid the foundation for the use of BoNTs in human pathologies characterized by excessive muscle contractions. Although much more is known about the action of BoNTs on the peripheral system, growing evidence has demonstrated several effects also at the central level. Pain conditions, with special regard to neuropathic and intractable pain, are some of the pathological states that have been recently treated with BoNTs with beneficial effects. The knowledge of the action and potentiality of BoNTs utilization against pain, with emphasis for its possible use in modulation and alleviation of chronic pain, still represents an outstanding challenge for experimental research. This review highlights recent findings on the effects of BoNTs in animal pain models.
Pavone, Flaminia; Luvisetto, Siro
Models of stress-induced hyperalgesia state that exposure to stress can exaggerate subsequent pain experiences. Studies using both animal and human subjects have shown evidence for hyperalgesia as a function of stress [e.g., Jorum E. Analgesia or hyperalgesia following stress correlates with emotional behavior in rats. Pain 1988;32:341-48; Peckerman A, Hurwitz BE, Saab PG, Llabre MM, McCabe PM, Schneiderman N. Stimulus dimensions of the cold pressor test and the associated patterns of cardiovascular response. Psychophysiology 1994;31:282-90; Gameiro et al. Nociception and anxiety-like behavior in rats submitted to different periods of restraint stress. Physiol. Behav. 2006;87:643-49; Lucas et al. Visceral pain and public speaking stress: neuroendocrine and immune cell responses in healthy subjects. Brain Behav. Immun. 2006;20:49-56]. However, the role of stress in pediatric pain is not well understood. This study examined stress reactivity and pain tolerance and sensitivity in a population of children with Recurrent abdominal pain (RAP). Forty-nine children meeting criteria for RAP (28 female; mean age 13years; range 9-17years) were randomly assigned to either a condition in which they completed an experimental stressor paradigm (stress interview, serial subtraction task) followed by a pain task (cold pressor) or a condition in which they received the pain task prior to the stress tasks. Children who underwent the stress tasks before the pain task exhibited lower levels of pain tolerance than those who received the pain task first (p<.01); no differences were found between the two groups in pain threshold or pain intensity ratings. Further, pain tolerance was not related to individual differences in physiological reactivity (heart rate change) to the stressor. The present research demonstrates the first evidence of the occurrence of stress-induced hyperalgesia in a pediatric pain population. PMID:17716818
Dufton, Lynette M; Konik, Brian; Colletti, Richard; Stanger, Catherine; Boyer, Margaret; Morrow, Sara; Compas, Bruce E
The pain response to urinary tract infection is largely uncharacterized, but the symptomatic response to urinary tract infection contrasts with the lack of pain response among individuals with asymptomatic bacteriuria. Quantifying pelvic pain in a murine urinary tract infection model, uropathogenic Escerichia?coli induces transient pelvic pain, whereas an asymptomatic bacteriuria E.?coli isolate causes no pain, thus recapitulating the spectrum of clinical responses to intravesical E.?coli. These differential pain responses are not correlated with bladder colonization or inflammation, but instead are intrinsic to E.?coli lipopolysaccharide and dependent on the lipopolysaccharide receptor, TLR4. Epidemiological data suggest a link between interstitial cystitis and a history of urinary tract infection, so it was evaluated whether repetitive uropathogenic E.?coli instillation would result in chronic pain through central sensitization. Although repeated infection with wild type uropathogenic E.?coli results in only transient episodes of acute pain, a uropathogenic E.?coli mutant lacking O-antigen causes chronic, post-urinary tract infection pelvic pain. Similarly, a K-12 E.?coli strain lacking O-antigen induces chronic pain that persisted long after bacterial clearance, and expressing O-antigen nullified the pain phenotype. Spinal cords isolated from mice with post-urinary tract infection chronic pain showed deficits in short-term depression consistent with central sensitization. Deleting O-antigen gene complex from a uropathogenic E.?coli strain and subsequent heterologous expression of O-antigen gene clusters shows that a single bacterial isolate can exhibit pain phenotypes ranging from a null phenotype, an acute pain phenotype, to a chronic pain phenotype. Post-urinary tract infection chronic pain is also associated with voiding dysfunction and anxious/depressive behavior. These effects are also mediated by TRPV1 at the level of pain establishment and CCR2 at the level of pain maintenance. Together, these findings show that transient infection with E.?coli might result in chronic visceral pain with the hallmarks of neuropathic pain. This pattern of behaviors mimics the spectrum of interstitial cystitis symptoms, thus supporting the possibility of an infectious etiology of interstitial cystitis. PMID:24807489
Rosen, John M; Klumpp, David J
Background Pain can significantly influence an individual's health status and can have serious negative consequences: poor nutrition, decreased appetite, abnormal sleep patterns, fatigue, and impairment of daily living activities. Pain can cause psychological impairment and decrease healing and recovery from injuries and illness. A hallmark of many chronic conditions, pain affects more patients' lives than diabetes mellitus, heart disease, and cancer combined. However, many chronic sufferers do not have access to effective pain management for a variety of reasons, including limited access, restrictions, and personal and cultural biases. Methods This review summarizes issues of access, distribution, and cultural bias with regard to opioid agents and seeks to clarify the challenges related to opioid delivery. The considerable negative physical and mental consequences of chronic pain are discussed for the general and palliative care population. Results Opioids are an effective treatment for various intractable painful conditions, but problems in global opioid access for safe and rational use in pain management contribute to unnecessary suffering. These problems persist despite increased understanding in recent years of the pathophysiology of pain. Conclusions Comprehensive guidelines for goal-directed and patient-friendly chronic opiate therapy will potentially enhance the outlook for future chronic pain management. The improvement of pain education in undergraduate and postgraduate training will benefit patients and clinicians. The promise of new medications, along with the utilization of multimodal approaches, has the potential to provide effective pain relief to future generations of sufferers.
Manjiani, Deepak; Paul, D. Baby; Kunnumpurath, Sreekumar; Kaye, Alan David; Vadivelu, Nalini
We performed a four year study to investigate the Visceral Leishmaniasis (VL) cases in, Turkey. Fifty- nine patients with suspected VL from Istanbul were included in this work. Bone marrow and blood samples of these patients were tested for possible VL infection using several methods including serological tests, microscopy, PCR. Nineteen (32.2%) patients had positive results for VL after one
Huseyin Cakan; Suat Saribas; Vecdet Oz; Erdal Polat; Mustafa Aslan
OBJECTIVE: The aim of the present review was to close the gap in the approach to pregnant women with visceral leishmaniasis (kala-azar) by providing up-to-date information to obstetricians about physiopathology, epidemiology, vertical transmission, drugs and treatment during pregnancy. BACKGROUND: Infection with Leishmania chagasi during pregnancy is rare and deserves special attention since little information is available regarding the occurrence of visceral leishmaniasis during gestational period and the real possibility of vertical transmission of this disease. Because specific areas in the world are endemic for the disease and considering the continuous growth of the population, cases of pregnant women with visceral leishmaniasis are becoming more frequent. Unfortunately, textbooks on infectious diseases do not include this specific group of patients, and studies in the literature on aspects related to pregnancy and visceral leishmaniasis are scarce. CONCLUSIONS: Vertical transmission of leishmaniasis is possible and the institution of treatment is imperative in cases of pregnant women with kala-azar. Amphotericin B is strongly recommended as the first choice drug due to its fewer maternal-fetal adverse effects.
Figueiro-Filho, Ernesto Antonio; Duarte, Geraldo; El-Beitune, Patricia; Quintana, Silvana Maria; Maia, Tamara Lemos
Visceral leishmaniasis (VL) is an important zoonosis caused by Leishmania infantum, which has in the domestic dog its principal vertebrate host. VL is usually transmitted by phlebotomine sand flies, however atypical routes of transmission have been described. In this review we discuss the the role of sexual and vertical transmissions, and their role in the maintenance of VL in canine populations. PMID:24727504
Turchetti, Andreia P; Souza, Tayse D; Paixão, Tatiane A; Santos, Renato L
This research was carried out at the University Hospital of the University of São Paulo and deals with the experiment of papain utilization for visceral irrigation in patients with severe infection. It was observed that seventy two hours after treatment, there was a considerable reduction of purulent secretion, and that the medium time of cicatrization of all lesions was thirty days. PMID:8715729
Rogenski, N M; Guedes, M L; Baptista, C M; Costa, L D
Leishmaniasis is a vector-borne neglected tropical disease associated with a spectrum of clinical manifestations, ranging from self-healing cutaneous lesions to fatal visceral infections. Among the most important questions in Leishmania research is why some species like L. donovani infect visceral organs, whereas other species like L. major remain in the skin. The determinants of visceral leishmaniasis are still poorly understood, although genomic, immunologic, and animal models are beginning to provide important insight into this disease. In this review, we discuss the vector, host, and pathogen factors that mediate the development of visceral leishmaniasis. We examine the progression of the parasite from the initial site of sand fly bite to the visceral organs and its ability to survive there. The identification of visceral disease determinants is required to understand disease evolution, to understand visceral organ survival mechanisms, and potentially to develop better interventions for this largely neglected disease.
McCall, Laura-Isobel; Zhang, Wen-Wei; Matlashewski, Greg
Objective Preclinical evidence indicates that gene transfer to the dorsal root ganglion (DRG) using replication defective herpes simplex virus (HSV)-based vectors can reduce pain-related behavior in animal models of pain. This clinical trial was carried out to assess the safety and explore the potential efficacy of this approach in humans. Methods We conducted a multicenter, dose-escalation, Phase I clinical trial of NP2, a replication defective HSV-based vector expressing human preproenkephalin (PENK) in subjects with intractable focal pain caused by cancer. NP2 was injected intradermally into the dermatome(s) corresponding to the radicular distribution of pain. The primary outcome was safety. As secondary measures, efficacy of pain relief was assessed using a numeric rating scale (NRS), the Short Form McGill Pain Questionnaire (SF-MPQ) and concurrent opiate usage. Results Ten subjects with moderate to severe intractable pain despite treatment with more than 200 mg/day of morphine (or equivalent) were enrolled into the study. Treatment was well tolerated with no study agent-related serious adverse events (SAE) observed at any point in the study. Subjects receiving the low dose of NP2 reported no substantive change in pain. Subjects in the middle and high dose cohorts reported pain relief as assessed by NRS and SF-MPQ. Interpretation Treatment of intractable pain with NP2 was well tolerated. There were no placebo controls in this relatively small study, but the dose-responsive analgesic effects suggest that NP2 may be effective in reducing pain and warrants further clinical investigation.
Fink, David J.; Wechuck, James; Mata, Marina; Glorioso, Joseph C.; Goss, James; Krisky, David; Wolfe, Darren
From the early 1900s, visceral leishmaniasis (VL; kala-azar) has been among the most important health problems in Sudan, particularly in the main endemic area in the eastern and central regions. Several major epidemics have occurred, the most recent--in Western Upper Nile province in southern Sudan, detected in 1988--claiming over 100,000 lives. The disease spread to other areas that were previously not known to be endemic for VL. A major upsurge in the number of cases was noted in the endemic area. These events triggered renewed interest in the disease. Epidemiological and entomological studies confirmed Phlebotomus orientalis as the vector in several parts of the country, typically associated with Acacia seyal and Balanites aegyptiaca vegetation. Infection rates with Leishmania were high, but subject to seasonal variation, as were the numbers of sand flies. Parasites isolated from humans and sand flies belonged to three zymodemes (MON-18, MON-30 and MON-82), which all belong to the L. donovani sensu lato cluster. Transmission dynamics have not been elucidated fully; heavy transmission in relatively scarcely populated areas such as Dinder national park suggested zoonotic transmission whereas the large numbers of patients with post kala-azar dermal leishmaniasis (PKDL) in heavily affected villages may indicate a human reservoir and anthroponotic transmission. Clinical presentation in adults and in children did not differ significantly, except that children were more anaemic. Fever, weight loss, hepato-splenomegaly and lymphadenopathy were the most common findings. PKDL was much more common than expected (56% of patients with VL developed PKDL), but other post-VL manifestations were also found affecting the eyes (uveitis, conjunctivitis, blepharitis), nasal and/or oral mucosa. Evaluation of diagnostic methods showed that parasitological diagnosis should still be the mainstay in diagnosis, with sensitivities for lymph node, bone marrow and spleen aspirates of 58%, 70% and 96%, respectively. Simple, cheap serological tests are needed. The direct agglutination test (DAT) had a sensitivity of 72%, specificity of 94%, positive predictive value of 78% and negative predictive value of 92%. As with other serological tests, the DAT cannot distinguish between active disease, subclinical infection or past infection. The introduction of freeze-dried antigen and control sera greatly improved the practicality and accuracy of the DAT in the field. An enzyme-linked immunosorbent assay using recombinant K39 antigen had higher sensitivity than DAT (93%). The polymerase chain reaction using peripheral blood gave a sensitivity of 70-93% and was more sensitive than microscopy of lymph node or bone marrow aspirates in patients with suspected VL. The leishmanin skin test (LST) was typically negative during active VL and converted to positive in c. 80% of patients 6 months after treatment. Immunological studies showed that both Th1 and Th2 cell responses could be demonstrated in lymph nodes from VL patients as evidenced by the presence of messenger ribonucleic acid for interleukin (IL)-10, interferon gamma and IL-2. Treatment of peripheral blood mononuclear cells from VL patients with IL-12 was found to drive the immune response toward a Th1 type response with the production of interferon gamma, indicating a potential therapeutic role for IL-12. VL responded well to treatment with sodium stibogluconate, which is still the first line drug at a dose of 20 mg/kg intravenously or intramuscularly per day for 15-30 d. Side effects and resistance were rare. Liposomal amphotericin B was effective, with few side effects. Control measures have not been implemented. Based on observations that VL does not occur in individuals who have a positive LST, probably because of previous cutaneous leishmaniasis, a vaccine containing heat-killed L. major promastigotes is currently undergoing a phase III trial. PMID:11370250
Zijlstra, E E; el-Hassan, A M
Growth retardation is common among children with epilepsy, and poor dietary intake may be one of the causes. The goal of this cross-sectional study was to compare the nutrient intake of children 1 to 8 years of age with intractable epilepsy to healthy children of the same age from the National Health and Nutrition Examination Survey 2001 to 2002 (N=1,718) and with the Dietary Reference Intakes. Children with intractable epilepsy were divided into two age groups: 1.0 to 3.9 and 4.0 to 8.9 years, to correspond with the Dietary Reference Intakes. Forty-three children with intractable epilepsy, mean age=4.7+/-2.2 years, had significantly lower intakes (P<0.05) of total energy; protein; carbohydrate; fat; dietary fiber; vitamins A, E, B-6, and B-12; riboflavin; niacin; folate; calcium; phosphorus; magnesium; zinc; copper; and selenium compared with healthy children. Thirty percent or more of the children with intractable epilepsy in both age groups had intakes below the Recommended Dietary Allowance or Adequate Intake for vitamins D, E, and K; folate; calcium; linoleic acid; and alpha-linolenic acid. Health care professionals caring for children with intractable epilepsy should be aware of this pattern of decreased nutrient intake and educate families to provide an adequate diet and/or consider vitamin/mineral supplementation. PMID:17524723
Volpe, Stella L; Schall, Joan I; Gallagher, Paul R; Stallings, Virginia A; Bergqvist, A G Christina
Prurigo nodularis (PN) is an eruption of lichenified or excoriated nodules related to intractable pruritus. A few reports have shown that a 308-nm excimer lamp/laser (EL) is effective for intractable PN. Herein, we report on two cases of intractable prurigo nodularis successfully treated with a new EL equipped with a filter to cut wavelengths shorter than 297 nm. Because this newly developed EL yields a therapeutic effect with low cumulative dosages of UV and a lower risk of DNA damage, it can be a new treatment option for intractable PN. PMID:24945654
Nakashima, Chisa; Tanizaki, Hideaki; Otsuka, Atsushi; Miyachi, Yoshiki; Kabashima, Kenji
Neuropathic pain remains intractable and the development of new therapeutic strategies are urgently required. Accumulating evidence indicates that overproduction of oxidative stress is a key event in the pathogenesis of neuropathic pain. However, repeated intra-peritoneal or intrathecal injections of antioxidants are unsuitable for continuous use in therapy. Here we show a novel therapeutic method against neuropathic pain: drinking water containing molecular hydrogen (H2) as antioxidant. The effect of hydrogen on neuropathic pain was investigated using a partial sciatic nerve ligation model in mice. As indicators of neuropathic pain, temporal aspects of mechanical allodynia and thermal hyperalgesia were analysed for 3 weeks after ligation. Mechanical allodynia and thermal hyperalgesia were measured using the von Frey test and the plantar test, respectively. When mice were allowed to drink water containing hydrogen at a saturated level ad libitum after ligation, both allodynia and hyperalgesia were alleviated. These symptoms were also alleviated when hydrogen was administered only for the induction phase (from day 0 to 4 after ligation). When hydrogen was administered only for the maintenance phase (from day 4 to 21 after ligation), hyperalgesia but not allodynia was alleviated. Immunohistochemical staining for the oxidative stress marker, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine, showed that hydrogen administration suppressed oxidative stress induced by ligation in the spinal cord and the dorsal root ganglion. In conclusion, oral administration of hydrogen water may be useful for alleviating neuropathic pain in a clinical setting.
Kawaguchi, Masanori; Satoh, Yasushi; Otsubo, Yukiko; Kazama, Tomiei
The objective of this study was to assess the impact of parent attention and distraction on symptom complaints by children with and without chronic functional abdominal pain. The water load symptom provocation task was used to induce visceral discomfort in pediatric patients with abdominal pain (N=104) and well children (N=119), ages 8–16 years. Parents were randomly assigned and trained to
Lynn S. Walker; Sara E. Williams; Craig A. Smith; Judy Garber; Deborah A. Van Slyke; Tricia A. Lipani
Neuropathic pain is triggered by lesions to the somatosensory nervous system that alter its structure and function so that pain occurs spontaneously and responses to noxious and innocuous stimuli are pathologically amplified. The pain is an expression of maladaptive plasticity within the nociceptive system, a series of changes that constitute a neural disease state. Multiple alterations distributed widely across the nervous system contribute to complex pain phenotypes. These alterations include ectopic generation of action potentials, facilitation and disinhibition of synaptic transmission, loss of synaptic connectivity and formation of new synaptic circuits, and neuroimmune interactions. Although neural lesions are necessary, they are not sufficient to generate neuropathic pain; genetic polymorphisms, gender, and age all influence the risk of developing persistent pain. Treatment needs to move from merely suppressing symptoms to a disease-modifying strategy aimed at both preventing maladaptive plasticity and reducing intrinsic risk.
Costigan, Michael; Scholz, Joachim; Woolf, Clifford J.
Chronic pelvic pain presents difficulties for women suffering its complex presentation. It also presents difficulties for clinicians involved in diagnosing and managing the problem. We review here clinically relevant information related to visceral pathology and its association with peripheral and central aspects of pain hypersensitivity. We address why surgery appears to be successful in some cases but less than successful in others, and what cautionary indicators should be taken into account. A categorization of chronic pelvic pain based on our understanding of pain physiology and mechanisms involved is proposed. The benefits of multidimensional sensory and pain testing in gynaecological care are reviewed. PMID:23870777
Jarrell, John; Arendt-Nielsen, Lars
The Deg/ENaC family of ion channels, including ASIC1, 2 and 3, are candidate mechanotransducers in visceral and somatic sensory neurons, although each channel may play a different role in different sensory pathways. Here we determined which distinct populations of visceral sensory neurons are sensitive to the non-selective Deg/ENaC blocker benzamil, and which ASIC channels are targets for benzamil by studying its actions in knockout mice. Single afferent fiber recordings were made in vitro from mouse high threshold colonic thoracolumbar splanchnic afferents and low threshold gastroesophageal vagal afferents. mRNA expression of ASIC subtypes was compared between colonic and gastroesophageal afferents by quantitative RT-PCR of transcripts following laser capture microdissection of retrogradely labeled cell bodies. Mechanosensitivity of colonic afferents was potently reduced by benzamil (10(-6)-3 x 10(-4)M), whereas gastroesophageal afferents were marginally inhibited. Inhibition of colonic afferent mechanosensitivity by benzamil was markedly diminished in ASIC2-/- and ASIC3-/- mice, but unchanged in ASIC1a-/-. Therefore ASIC2 and 3 are targets for benzamil to inhibit colonic afferent mechanosensitivity. Conversely, gastroesophageal afferents are less sensitive to benzamil, and its action depends less on ASIC expression. mRNA for ASIC3 showed higher and ASIC1a showed lower relative expression in colonic afferents from thoracolumbar dorsal root ganglia than in gastric afferents from nodose (vagal) ganglia. These data indicate that ASICs on colonic afferents present distinct pharmacological targets for visceral pain. PMID:17467171
Page, Amanda J; Brierley, Stuart M; Martin, Christopher M; Hughes, Patrick A; Blackshaw, L Ashley
Background We previously described the visceral antinociceptive property of ?-bisabolol (BISA) in mouse models of visceral nociception induced by cyclophosphamide and mustard oil (MO). This study examined the effect of BISA in mouse models of visceral nociception induced by acetic acid, capsaicin, formalin, and the contribution of the nitric oxide system, ?2, KATP, 5-HT3 and TRPV1 receptors to the effect of BISA on MO-evoked nociceptive behaviors. Mice were pretreated orally with BISA (50, 100 and 200 mg/kg) or vehicle, and the pain-related behavioral responses to intraperitoneal administration of acetic acid or intracolonic injection of MO were analyzed. Results BISA significantly suppressed the nociceptive behaviors in a dose-unrelated manner. The antinociceptive effect of BISA (50 mg/kg) was show to be glibenclamide resistant, but it was not blocked by pretreatment with the other antagonists tested. In the open-field test that detects sedative or motor abnormality, mice received 50 mg/kg BISA did not show any per se influence in ambulation frequency. Conclusions However, their precise antinociceptive mechanisms of action have not been determined.
Co-infection of visceral leishmaniasis and pulmonary tuberculosis are increasing public health problem in eastern region of country. A large number of clinical cases of leishmaniasis and tuberculosis have been reported in Sudan. Such type of co-infections lead to decreased host's immune system. This is a case report of 48 years old male with visceral leishmaniasis and pulmonary tuberculosis. He arrived at hospital with complaints of fever with rigor, abdominal pain, weakness, loss of appetite, yellowish discoloration of urine and sclerosis at lower back. Bone marrow aspiration cytology revealed the presence of Leishmania donovani bodies (2+). His treatment was initiated with amphotericin B deoxycholate (inj. Fungizone) 15 infusions on alternate days with 5% dextrose. He had 20 years past history of pulmonary tuberculosis. His chest X-ray showed increased bronchovascular marking encysted pleural effusion on lower segment of right lung. Ultrasonography guided fine needle aspiration cytology of pleural fluid for protein, sugar, lactate dehydrogenase, adenosine deaminase, cell type and cell count. Cytological reports confirmed pulmonary tuberculosis. Antitubercular therapy (four drug regimen: rifampicin, isoniazid, ethambutal, and pyrazinamide) was started. Co-infection of visceral leishmaniasis and pulmonary tuberculosis is a real threat in developing countries. There is a need of cost effective diagnostic and therapeutic facilities for these co-infections.
Shweta; Bhatnagar, Surabhi; Gupta, Ashok Kumar; Murti, Krishna; Pandey, Krishna
Palliative sedation (sedation to unconsciousness) as an option of last resort for intractable end-of-life distress has been the subject of ongoing discussion and debate as well as policy formulation. A particularly contentious issue has been whether some dying patients experience a form of intractable suffering not marked by physical symptoms that can reasonably be characterized as "existential" in nature and therefore not an acceptable indication for palliative sedation. Such is the position recently taken by the American Medical Association. In this essay we argue that such a stance reflects a fundamental misunderstanding of the nature of human suffering, particularly at the end of life, and may deprive some dying patients of an effective means of relieving their intractable terminal distress. PMID:20088855
Cassell, Eric J; Rich, Ben A
Hiccups are an involuntarily powerful spasm of the diaphragm, followed by a sudden inspiration with a closure of the glottis. Hiccups that are caused by gastric distention, spicy foods and neural dysfunction can resolve themselves without any treatment. Some hiccups are associated with certain diseases or they occur postsurgically, and life-restricting intractable hiccups should be treated. The cause of hiccups should be quickly determined so as to administer the proper treatment. Hiccups often remit spontaneously within a short period of time, but they may also occur without remission for a prolonged period in some cases. We report here on a 36-year-old man who suffered with intractable hiccups for 5 years. We administered a single oral dose of baclofen, and then the hiccups disappeared. We conclude that a single dose of baclofen is a good treatment for intractable hiccups.
Lee, Ju Hwan; Kim, Tai Yo; Lee, Hyun Wook; Choi, Yu Sun; Moon, Seo Young
Gamma knife radiosurgery is a minimally invasive procedure which can be used for patients with intractable epilepsies as an alternative for surgical corpus callosotomy. We report a 13-year-old boy with intractable epilepsy who underwent radiosurgical callosotomy. The patient demonstrated significant clinical improvement after gamma knife radiosurgery and was free of seizures 10 months after the procedure. However, He developed four short focal seizures with clonic movements during the 20 months post radiosurgery. Corpus callosotomy decreased epileptiform discharges in both hemispheres, indicating a role for the callosal neurons to facilitate an asymmetric epileptogenic susceptible state within the two hemispheres such that bisynchronous and bisymmetrical epileptiform discharges develop. Our result demonstrates that this novel therapeutic approach is a safe and effective option for the treatment of intractable generalised epilepsies. PMID:21628134
Bodaghabadi, Mohammad; Bitaraf, Mohammad Ali; Aran, Shima; Alikhani, Mazdak; Ashrafian, Hossein; Zahiri, Alireza; Alahverdi, Mahmud
Wolman disease (WD) is a rare, inherited, rapidly fatal condition presenting in early infancy. The disease manifests in the first month of life with failure to thrive, vomiting, diarrhea, abdominal distension, hepatosplenomegaly and bilateral adrenal calcification and is nearly always fatal before the age of 1 year. Barring a case report of isolated fetal ascites, there is no report of intractable ascites as the presentation of WD till date. We report two siblings with WD who both had intractable ascites and required therapeutic paracentesis, albumin infusion, and diuretics to control tense ascites. Although rare, WD should be considered in the differential diagnosis of infantile ascites. PMID:23007684
Kathuria, Rachana; Poddar, Ujjal; Ghosh, Jayanta; Yachha, Surender Kumar; Gnanapriya, V; Pandey, Rakesh; Kaur, Anupriya; Phadke, Subha; Srivastava, Anshu
Symptomatic cytomegalovirus (CMV) infection mainly affects preterm and immunocompromised infants and usually manifest as rash, pneumonia, hepatospleenomegaly or encephalitis. To our knowledge intractable diarrhoea at two weeks of age caused by postnatally acquired CMV in immunocompetent term neonate is not reported. An unusual case of postnatally acquired CMV enterocolitis manifesting as protracted diarrhoea in an immunocompetent baby in neonatal period is reported. We conclude that CMV should be considered in the differential diagnosis of intractable diarrhoea in neonatal period and treatment with intravenous ganciclovir for CMV enterocolitis is not only indicated but is therapeutic. PMID:23780993
Gupta, Amit Kumar; Maria, Arti; Goyal, Deepak; Verma, Arushi
Visceral leishmaniasis was first reported in Bhutan in 2006. We conducted studies of the parasite, possible vectors and reservoirs, and leishmanin skin test and risk factor surveys in three villages. Nineteen cases were reported from seven districts. Parasite typing yielded two novel microsatellite sequences, both related to Indian L. donovani. In one case village, 40 (18.5%) of 216 participants had positive leishmanin skin test results, compared with 3 (4.2%) of 72 in the other case village and 0 of 108 in the control village. Positive results were strongly associated with the village and increasing age. None of the tested dogs were infected. Eighteen sand flies were collected, 13 Phlebotomus species and 5 Sergentomyia species; polymerase chain reaction for leishmanial DNA was negative. This assessment suggests that endemic visceral leishmaniasis transmission has occurred in diverse locations in Bhutan. Surveillance, case investigations, and further parasite, vector, and reservoir studies are needed. The potential protective impact of bed nets should be evaluated.
Yangzom, Thinley; Cruz, Israel; Bern, Caryn; Argaw, Daniel; den Boer, Margriet; Velez, Ivan Dario; Bhattacharya, Sujit K.; Molina, Ricardo; Alvar, Jorge
Leishmaniasis is a neglected disease resulting in a global morbidity of 2,090 thousand Disability-Adjusted Life Years and a mortality rate of approximately 60,000 per year. Among the three clinical forms of leishmaniasis (cutaneous, mucosal, and visceral), visceral leishmaniasis (VL) accounts for the majority of mortality, as if left untreated VL is almost always fatal. Caused by infection with Leishmania donovani or L. infantum, VL represents a serious public health problem in endemic regions and is rapidly emerging as an opportunistic infection in HIV patients. To date, no vaccine exists for VL or any other form of leishmaniasis. In endemic areas, the majority of those infected do not develop clinical symptoms and past infection leads to robust immunity against reinfection. Thus the development of vaccine for Leishmania is a realistic public health goal, and this paper summarizes advances in vaccination strategies against VL.
Evans, Krystal J.; Kedzierski, Lukasz
A b s t r ac t P<0.001); and in patients receiving amphotericin B, as compared with those receiving paromomycin, nephrotoxicity (4% vs. 0, P<0.001), fevers (57% vs. 3%), rigors (24% vs. 0, P<0.001), and vomiting (10% vs. <1%, P<0.001). Conclusions Paromomycin was shown to be noninferior to amphotericin B for the treatment of visceral leishmaniasis in India. (ClinicalTrials.gov number,
Shyam Sundar; T. K. Jha; Chandreshwar P. Thakur; Prabhat K. Sinha; Sujit K. Bhattacharya
Visceral leishmaniasis, which is also known as kala-azar, reappeared in Bangladesh during the 1980s, approximately 7-8 years after large-scale use of DDT had been abandoned by the malaria eradication programme in the country. Pabna, Mymensingh and Rajshahi were the regions most affected with kala-azar. The article presents a historical review and information about the present status of leishmaniasis in Bangladesh together with control strategies and a proposed plan of operation. PMID:2650901
Elias, M; Rahman, A J; Khan, N I
In 1994-1995, a child and five dogs from villages located between Jerusalem and Tel-Aviv, Israel were diagnosed with visceral leishmaniasis (VL). Based on these findings, the distribution of VL in domestic and wild canids in central Israel was examined. In the two villages where canine index cases were identified, a substantial proportion (11.5%, 14 of 122) of the dogs examined
GAD BANETH; GILLIAN DANK; EPHRAIM KEREN-KORNBLATT; ELIEZER SEKELES; IRIT ADINI; CAROL L. EISENBERGER; LIONEL F. SCHNUR; RONI KING; CHARLES L. JAFFE
Pain, which afflicts up to 20% of the population at any time, provides both a massive therapeutic challenge and a route to understanding mechanisms in the nervous system. Specialised sensory neurons (nociceptors) signal the existence of tissue damage to the central nervous system (CNS), where pain is represented in a complex matrix involving many CNS structures. Genetic approaches to investigating
Tom Foulkes; John N. Wood
Background Chronic psychological stress-induced alterations in visceral sensitivity have been predominantly assessed in male rodents. We investigated the effect of acute and repeated water avoidance stress (WAS) on the visceromotor response (VMR) to colorectal distension (CRD) and the role of opioids in male and cycling female Wistar rats using a novel non-invasive manometric technique. Methods After a baseline VMR (1st CRD, day 0), rats were exposed to WAS (1h/day) either once or for 4 consecutive days, without injection or with naloxone (1 mg/kg) or saline injected subcutaneously before each WAS session. Key Results The VMR to CRD recorded on day 1 or 4 immediately after the last WAS was reduced in both females and males. The visceral analgesia was mainly naloxone-dependent in females but naloxone-independent in males. In non-injected animals, on days 2 and 5, VMR was not significantly different from baseline in males while females exhibited a significant VMR increase at 60 mmHg on day 5. Basal CRD and CRD on days 1, 2 and 5 in both sexes without WAS induced similar VMR. Conclusions and Inferences When monitored non-invasively, psychological stress induces an immediate post-stress visceral analgesia mediated by an opiate signaling system in females while naloxone-independent in males, and hyperalgesia at 24 h after repeated stress only in females. These data highlights the importance of sex-specific interventions to modulate visceral pain response to stress.
LARAUCHE, Muriel; MULAK, Agata; KIM, Yong Sung; LABUS, Jennifer; MILLION, Mulugeta; TACHE, Yvette
Subcutaneous application of Herpes Simplex Virus type 1 (HSV-1) vectors mediating enkephalin transfer to the sensory neurons of the dorsal root ganglia, were shown to induce analgesia and reduce hyperalgesic reactions. These results prompted to use these vectors in the treatment of chronic intractable pain and human clinical trials based on these approaches are expected in the near future. Since
Isabel Martins; Marta Pinto; Steven Wilson; Deolinda Lima; Isaura Tavares
Background Clinical studies indicate that patients with post-traumatic stress disorder (PTSD) frequently share comorbidity with numerous chronic pain conditions. However, the sustained effects of PTSD-like stress over time on visceral nociception and hyperalgesia have been rarely studied, and the underlying mechanisms of stress-induced modulation of visceral hyperalgesia remain elusive. The purpose of this study was to investigate the characterization of visceral nociception and hyperalgesia over time in rats exposed to PTSD-like stress, and to explore the potential role of protein kinase C gamma (PKC?) in mediating visceral hyperalgesia following exposure to PTSD-like stress. Results On day 1, the rats exposed to single-prolonged stress (SPS, an established animal model for PTSD) exhibited an analgesic response and its visceromotor response (VMR) to graded colorectal distention (CRD) at 40 and 60 mmHg was reduced compared with the control group (all P?0.05). On day 6, the VMR returned to the baseline value. However, as early as 7 days after SPS, VMR dramatically increased compared with its baseline value and that in the controls (all P?0.001) and this increase persisted for 28 days, with the peak on day 9. Abdominal withdrawal reflex (AWR) scores were higher in SPS rats than in controls on days 7, 9, 14, 21 and 28 (all P?0.001). Intrathecal administration of GF109203X (an inhibitor of PKC gamma), attenuated the SPS-induced increase in both VMR and AWR scores on days 7, 14, 21 and 28 (all P?0.05). PKC? protein expression determined by immunofluorescence was reduced in the spinal cord within 3 days after the exposure to SPS (P?0.01), which returned to normal levels between days 4 and 6, and significantly increased from day 7, and this increase was maintained on days 14, 21, and 28 (all P?0.001), with the peak on day 9. In addition, Western blotting showed a consistent trend in the changes of PKC? protein expression. Conclusions The modified SPS alters visceral sensitivity to CRD, and contributes to the maintenance of visceral hyperalgesia, which is associated with enhanced PKC? expression in the spinal cord. Functional blockade of the PKC? receptors attenuates SPS-induced visceral hyperalgesia. Thus, the present study identifies a specific molecular mechanism for visceral hyperalgesia which may pave the way for novel therapeutic strategies for PTSD-like conditions.
Pain is one of the most common experiences of humans. Neuroimaging techniques can visualize the main brain areas involved in pain modulation, the pain matrix. It is noteworthy that many of the brain areas forming the pain matrix are also involved in modulating autonomic nervous system (ANS) activity that in turn plays a major role in determining the best adaptive response to the pain experience. The tight connection between the pain system and ANS is also evident from neuroanatomical studies indicating that the lamina 1 neurons receive both painful and visceral stimuli from all visceral organs giving rise to the spinothalamocortical pathway concerned with conveying interoceptive information to central structures. The resulting interoceptive stream projects to the viscerosensory cortex in the mid-insula and onto the right anterior insula and orbitofrontal cortices. Right anterior insula activation is involved in the sympathetic arousal associated with mental tasks. This brain region receives numerous other inputs including pain and painful stimuli are conveyed somatotopically to both insulae. A similar somatotopic organization of painful stimuli has also been shown in the basal ganglia involved in cognitive, affective, motor and autonomic states. This highly specialized organization of nociceptive information in these brain areas may subserve a number of functions, particularly of coupling pain with the most appropriate autonomic states and affective/emotional states. The anterior cingulated cortex, another brain area playing a crucial role in nociception, is also directly involved in the control of autonomic functions such as arousal during volitional behaviour, including effortful cognitive processing. It is evident that the nociceptive system and ANS closely interact in many processes involved in maintaining internal homeostatis and in order to give the most appropriate biological substrate for cognitive, affective and emotional states. PMID:16688617
Leone, M; Proietti Cecchini, A; Mea, E; Tullo, V; Curone, M; Bussone, G
Metabotropic glutamate receptors (mGluR) have a diverse range of structures and molecular coupling mechanisms. There are eight mGluR subtypes divided into three major groups. Group I (mGluR1 and 5) is excitatory; groups II (mGluR2 and 3) and III (mGluR 4, 6, and 7) are inhibitory. All mGluR are found in the mammalian nervous system but some are absent from sensory neurons. The focus here is on mGluR in sensory pathways from the viscera, where they have been explored as therapeutic targets. Group I mGluR are activated by endogenous glutamate or constitutively active without agonist. Constitutive activity can be exploited by inverse agonists to reduce neuronal excitability without synaptic input. This is promising for reducing activation of nociceptive afferents and pain using mGluR5 negative allosteric modulators. Many inhibitory mGluR are also expressed in visceral afferents, many of which markedly reduce excitability. Their role in visceral pain remains to be determined, but they have shown promise in inhibition of the triggering of gastro-esophageal reflux, via an action on mechanosensory gastric afferents. The extent of reflux inhibition is limited, however, and may not reach a clinically useful level. On the other hand, negative modulation of mGluR5 has very potent actions on reflux inhibition, which has produced the most likely candidates so far as therapeutic drugs. These act probably outside the central nervous system, and may therefore provide a generous therapeutic window. There are many unanswered questions about mGluR along visceral afferent pathways, the answers to which may reveal many more therapeutic candidates. PMID:21472028
Blackshaw, L Ashley; Page, Amanda J; Young, Richard L
The present study investigated whether inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for anandamide catabolism, produces antinociception in the acetic acid-induced abdominal stretching model of visceral nociception. Genetic deletion or pharmacological inhibition of FAAH reduced acetic acid-induced abdominal stretching. Transgenic mice that express FAAH exclusively in the nervous system displayed the antinociceptive phenotype, indicating the involvement of peripheral fatty acid amides. The cannabinoid receptor 1 (CB1) receptor antagonist, rimonabant, but not the cannabinoid receptor 2 (CB2) receptor antagonist, SR144528, blocked the antinociceptive phenotype of FAAH(-/-) mice and the analgesic effects of URB597 (3?-carbamoyl-biphenyl-3-yl-cyclohexylcarbamate) or OL-135 (1-oxo-1[5-(2-pyridyl)-2-yl]-7-phenyl heptane), respective irreversible and reversible FAAH inhibitors, administered to C57BL/6 mice. The opioid receptor antagonist, naltrexone, did not block the analgesic effects of either FAAH inhibitor. URB597, ED50 [95% confidence interval (CI) = 2.1 (1.5-2.9) mg/kg], and the nonselective cyclooxygenase inhibitor, diclofenac sodium [ED50 (95% CI) = 9.8 (8.2-11.7) mg/kg], dose-dependently inhibited acetic acid-induced abdominal stretching. Combinations of URB597 and diclofenac yielded synergistic analgesic interactions according to isobolographic analysis. It is important that FAAH(-/-) mice and URB597-treated mice displayed significant reductions in the severity of gastric irritation caused by diclofenac. URB597 lost its gastroprotective effects in CB1(-/-) mice, whereas it maintained its efficacy in CB2(-/-) mice, indicating a CB1 mechanism of action. Taken together, the results of the present study suggest that FAAH represents a promising target for the treatment of visceral pain, and a combination of FAAH inhibitors and NSAIDs may have great utility to treat visceral pain, with reduced gastric toxicity.
Naidu, Pattipati S.; Booker, Lamont; Cravatt, Benjamin F.; Lichtman, Aron H.
The present study investigated whether inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for anandamide catabolism, produces antinociception in the acetic acid-induced abdominal stretching model of visceral nociception. Genetic deletion or pharmacological inhibition of FAAH reduced acetic acid-induced abdominal stretching. Transgenic mice that express FAAH exclusively in the nervous system displayed the antinociceptive phenotype, indicating the involvement of peripheral fatty acid amides. The cannabinoid receptor 1 (CB(1)) receptor antagonist, rimonabant, but not the cannabinoid receptor 2 (CB(2)) receptor antagonist, SR144528, blocked the antinociceptive phenotype of FAAH(-/-) mice and the analgesic effects of URB597 (3'-carbamoyl-biphenyl-3-yl-cyclohexylcarbamate) or OL-135 (1-oxo-1[5-(2-pyridyl)-2-yl]-7-phenyl heptane), respective irreversible and reversible FAAH inhibitors, administered to C57BL/6 mice. The opioid receptor antagonist, naltrexone, did not block the analgesic effects of either FAAH inhibitor. URB597, ED(50) [95% confidence interval (CI) = 2.1 (1.5-2.9) mg/kg], and the nonselective cyclooxygenase inhibitor, diclofenac sodium [ED(50) (95% CI) = 9.8 (8.2-11.7) mg/kg], dose-dependently inhibited acetic acid-induced abdominal stretching. Combinations of URB597 and diclofenac yielded synergistic analgesic interactions according to isobolographic analysis. It is important that FAAH(-/-) mice and URB597-treated mice displayed significant reductions in the severity of gastric irritation caused by diclofenac. URB597 lost its gastroprotective effects in CB(1)(-/-) mice, whereas it maintained its efficacy in CB(2)(-/-) mice, indicating a CB(1) mechanism of action. Taken together, the results of the present study suggest that FAAH represents a promising target for the treatment of visceral pain, and a combination of FAAH inhibitors and NSAIDs may have great utility to treat visceral pain, with reduced gastric toxicity. PMID:19118134
Naidu, Pattipati S; Booker, Lamont; Cravatt, Benjamin F; Lichtman, Aron H
To assess the effects of neurofeedback on brain electrophysiology and to determine how biofeedback works, power spectral density (PSD) and approximate entropy (ApEn) analyses are applied to the EEGs of six patients with intractable epilepsy who received neurofeedback training. After sessions of treatment, the EEG sensorimotor rhythm to theta PSD ratio calculated from the C4 electrode site becomes larger than
Longlian Zhao; Wenqing Wu; Zuoqing Liang; Guangshu Hu
We present a patient with intractable postpartum hemorrhage resulting from uterine artery pseudoaneurysm despite bilateral hypogastric artery ligation who was successfully treated by an endovascular approach via the collateral route. Although there is a good argument for postponing surgery until transcatheter embolization has been attempted, this case shows that embolization can still be successful even if the iliac vessels have been ligated.
Doenmez, Halil, E-mail: firstname.lastname@example.org; Oztuerk, M. Halil; Guergen, Fatma; Soylu, Serra O.; Hekimoglu, Baki [S.B. Diskapi Yildirim Beyazit Egitim ve Arastirma Hastanesi, Department of Radiology (Turkey)
The explosive growth of civil aviation is among the most difficult issues in transportation policy, and nowhere are the fundamental economic and environmental challenges it poses more apparent than in airport expansion. Conventional policy analyses have ineffectively handled these problems, characterized by uncertainty, complexity, and polarization. Increasingly, policy analysts and public managers depend on stakeholder involvement to recast intractable issues
Michel J. G. van Eeten
Five hemiplegic patients with intractable epilepsy were studied with transcranial magnetic stimulation (TMS) before and after various surgical treatments. These patients had unilateral widespread cerebral lesions acquired at various times, including congenital, infantile and childhood injury. Motor evoked potentials (MEPs) of the abductor pollicis brevis (APB) muscles were simultaneously recorded on both sides following TMS of the motor cortex in
TOHRU KAMIDA; HIROSHI BABA; KENJI ONO; MASATO YONEKURA; MINORU FUJIKI; HIDENORI KOBAYASHI
Objective: Epilepsy can be considered as a result of the imbalance of the excitatory and inhibitory processes. Therefore, the artificial enhancement of the activity of brain inhibitory mechanisms might lead to a beneficial therapeutic effect for intractable epilepsy patients. Material and methods: Studies of the inhibitory effects of electrical stimulation of the head of the caudate nucleus (HCN), cerebellar dentate
Sozari A Chkhenkeli; Miron Šramka; George S Lortkipanidze; Tamaz N Rakviashvili; Eteri Sh Bregvadze; George E Magalashvili; Tamar Sh Gagoshidze; Irina S Chkhenkeli
Purpose – The paper seeks to investigate the characteristics of irresolvable interpersonal conflicts by comparing irresolvable conflicts to resolvable and resolved conflicts on each of Coleman's common social psychological factors associated with intractable conflicts. Design\\/methodology\\/approach – Undergraduate students were randomly assigned to complete questionnaires about an irresolvable conflict, a resolvable conflict, or a resolved conflict. Participants reported on conflicts in
Courtney Waite Miller; Michael E. Roloff
Vagus nerve stimulation (VNS) constitutes an adjunctive, modern management of medically intractable seizures, especially when surgery is inadvisable. Objective: To evaluate the long-term results as regards efficacy, safety and tolerability of VNS in epileptic subjects, with focal and\\/or generalised seizures, refractory to old and new AEDs, without indication for resective surgery. Patients: 51 epileptic subjects (30 males, 21 females), aged
Paolo Tanganelli; Sergio Ferrero; Patrizio Colotto; Giovanni Regesta
This paper discusses a case study of therapeutic intervention with a 2-year-old boy. The child's major presenting symptom is intractable insomnia caused by nightmares, but his problems are linked to general patterns resulting from early paternal loss. The report analyzes the first 30 sessions of treatment. Discussion focuses on the unusual…
A peritoneovenous shunt has become one of the most efficient procedures for intractable ascites due to liver cirrhosis. A case of intractable ascites due to hepatic lymphorrhea after hepatectomy for hepatocellular carcinoma that was successfully treated by the placement of a peritoneovenous shunt is presented. A 72-year-old Japanese man underwent partial resection of the liver for hepatocellular carcinoma associated with hepatitis C viral infection. After hepatectomy, a considerable amount of ascites ranging from 800-4600 mL per day persisted despite conservative therapy, including numerous infusions of albumin and plasma protein fraction and administration of diuretics. Since the patient's general condition deteriorated, based on the diagnosis of intractable hepatic lymphorrhea, a subcutaneous peritoneovenous shunt was inserted. The patient's postoperative course was uneventful and the ascites decreased rapidly, with serum total protein and albumin levels and hepatic function improving accordingly. For intractable ascites due to hepatic lymphorrhea after hepatectomy, we recommend the placement of a peritoneovenous shunt as a procedure that can provide immediate effectiveness without increased surgical risk. PMID:21286221
Inoue, Yoshihiro; Hayashi, Michihiro; Hirokawa, Fumitoshi; Takeshita, Atsushi; Tanigawa, Nobuhiko
This paper discusses the presence of "peacebuilding islands" within civil society as potential agents of transformation in the midst of intractable conflict. Focusing on the particular case of the Israeli-Palestinian conflict, the argument stems from a deconstruction of the legacy of national myopia perpetuated through social and political…
Summary We provide a detailed case history of the first patient to receive bilateral hypothalamic stimulation to control severe bilateral chronic intractable cluster headaches initially occurring mostly on the left. These attacks were accompanied by life-threatening hypertensive crises and a grave deterioration in the patient's psychological state. Destructive surgery to the left trigeminal was absolutely contraindicated. Electrode implantation and continuous
M. Leone; A. Franzini; G. Broggi; A. May; G. Bussone
To report clinical manifestations, bleeding point localization, and outcomes of management in 16 patients with 16 instances of intractable epistaxis after radiation therapy for nasopharyngeal carcinoma. Retrospective chart review of 16 patients with nasopharyngeal carcinoma (mean age 52.06 ± 14.37 years) with 16 instances of intractable epistaxis during the past 5 years, whose diagnosis was confirmed by angiography (n = 10) or MRI/CT imaging studies and clinical manifestations (n = 6). The mean radiation dose to the affected carotid artery was 101.37 ± 34.85 Gy. Bleeding points were detected in the internal carotid artery (n = 8) or external carotid artery (n = 8). Detachable balloons were used in one affected artery for vascular occlusion; six were treated using an absorbable gelatin sponge (n = 4) or microcoils (diameter 1 mm) (n = 2). Endovascular embolization was successful in seven radiation carotid blowout syndromes with cessation of hemorrhage. One patient underwent external carotid artery ligation and one patient recovered without treatment. The clinical follow-up was 3 months. Therapeutic endovascular embolization of intractable epistaxis is both efficient and safe. It should be considered as the primary treatment modality in intractable epistaxis of nasopharyngeal carcinoma. PMID:23846664
He, Cheng-Cheng; Si, Yong-Feng; Xie, Yu-An; Yu, Lei
This paper describes an explanation-based ap proach lo learning plans despite a computationall y intractable domain theory. In this approach, the system learns an initial plan using limited infer ence. In order to detect plans in which the limited inference causes a faulty plan the system monitors goal achievement in plan execution. When a plan unexpectedly fails to achieve a
Steve A. Chien
Background The quantification of pain intensity in vivo is essential for identifying the mechanisms of various types of pain or for evaluating the effects of different analgesics. A variety of behavioral tests for pain measurement have been devised, but many are limited because animals are physically restricted, which affects pain sensation. In this study, pain assessment was attempted with minimal physical restriction, and voluntary movements of unrestrained animals were used to evaluate the intensities of various types of pain. Results The number of times animals reared or total distances traveled was measured using a motion-tracking device and found to be markedly reduced in carrageenan-induced inflammatory, acetic acid-induced visceral, and streptozotocin-induced neuropathic pain tests. These two voluntary movement parameters were found to be highly correlated with paw withdrawal latency from irradiating heat. In addition, these parameters were markedly reversed by morphine and by non-steroidal anti-inflammatory drugs in inflammatory pain models. These parameters were also useful to detect hypoalgesia in TRPV1-/- mice. Conclusions These results suggest that parameters of voluntary movement, such as, number of rearing and total distance moved, are effective indicators of pain intensity for many types of pain and that they can be used to evaluate degree of pain perception.
About 10% of paraplegics suffer from intractable pain. The onset of pain may be immediate or delayed for months to several years after the injury. The delayed onset of pain is highly suggestive of the development of a spinal cyst. This is a report of 18 paraplegics who developed a delayed onset of intractable pain who were found at the time of surgery to have associated spinal cord cysts. Treatment consisted of the dorsal root entry zone (DREZ) operation in addition to evacuation of the cyst. Burning pain was the most common complaint occurring years after the trauma. In this study we compared the relationship between the onset and character of the pain, the time of the spinal injury, the operative findings, and the results of the DREZ procedure and evacuation of the traumatic spinal cyst. We believe that the combination of paraplegia, pain and spinal cyst has not been emphasized in the neurosurgical literature although it is well known that cystic formation can follow spinal trauma. Two patients developed spinal cysts with nontraumatic lesions of the spinal cord. A single cyst was found in 14 patients while four had two separate cysts. The diagnosis was made on the basis of history and clinical examination with radiographic confirmation using delayed CT scan and myelography and more recently magnetic resonance imaging. Intraoperative ultrasound was employed in the study of some patients. All patients were treated with combined DREZ lesions and evacuation of the cysts with good pain relief in 77.7%. PMID:2222879
Nashold, B S; Vieira, J; el-Naggar, A O
Background Neurocysticercosis is a major cause of epilepsy in developing countries and is endemic in Brazil. To test the hypothesis that the aetiological profile of patients with intractable epilepsy in Brazil includes neurocysticercosis, we conducted a cross sectional study investigating the aetiology of intractable epilepsy. Methods A total of 512 patients evaluated at the outpatient clinic for intractable epilepsy at the Ribeirão Preto School of Medicine were included in the survey. Medical intractability was determined on the basis of seizure incidence and severity, and response to appropriate epilepsy management. Neuroimaging included brain CT with non?contrasted and contrasted phases and high resolution MRI. Patients were divided into neurocysticercosis and non?neurocysticercosis groups according to previous diagnostic criteria. Results The most common epileptogenic lesions were mesial temporal sclerosis (MTS; 56.0%), malformations of cortical development (12.1%), and brain tumours (9.9%). Neuroimaging was normal in 8.7% of patients. Calcifications were found in 27% of patients and were significantly more common in patients with MTS than in those without MTS (p<0.001). Isolated neurocysticercosis was found in only eight patients (1.56%). Conclusions These data suggest that neurocysticercosis is an uncommon cause of intractable epilepsy, even in an endemic region such as Brazil, and that it may only represent a coexistent pathology. However, an analysis of our findings reveals that neurocysticercosis was more common in patients with MTS. This finding could suggest either that there is a cause?effect relationship between MTS and neurocysticercosis, or that MTS and neurocysticercosis co?vary with a missing variable, such as socio?economic status.
Velasco, T R; Zanello, P A; Dalmagro, C L; Araujo, D; Santos, A C; Bianchin, M M; Alexandre, V; Walz, R; Assirati, J A; Carlotti, C G; Takayanagui, O M; Sakamoto, A C; Leite, J P
OBJECTIVE--To investigate the possibility that spinal cord stimulation (SCS) used for pain relief can conceal acute myocardial infarction (AMI). DESIGN--Prospective evaluation of patients treated with SCS. SETTING--University hospital. PATIENTS--50 patients with coronary artery disease and severe, otherwise intractable angina treated with SCS for 1-57 months. MAIN OUTCOME MEASURES--Necropsy findings, symptoms, serum enzyme concentrations, electrocardiographic changes. RESULTS--Ten patients were considered to have had AMI. In nine of these SCS did not conceal precordial pain and in one patient no information about precordial pain could be obtained. CONCLUSION--There was no evidence that SCS concealed acute myocardial infarction.
Andersen, C.; Hole, P.; Oxh?j, H.
Summary objective To facilitate the choice of the best visceral leishmaniasis (VL) treatment strategy for first-line health services in (VL)-endemic areas, we compared in a formal decision analysis the cost and the cost- effectiveness of the different available options. methods We selected four drug regimens for VL on the basis of frequency of use, feasibility and reported efficacy studies. The
V. Vanlerberghe; G. Diap; P. J. Guerin; F. Meheus; S. Gerstl; P. Van der Stuyft; M. Boelaert
Background A key to understanding the evolution of the nervous system on a large phylogenetic scale is the identification of homologous neuronal types. Here, we focus this search on the sensory and motor neurons of bilaterians, exploiting their well-defined molecular signatures in vertebrates. Sensorimotor circuits in vertebrates are of two types: somatic (that sense the environment and respond by shaping bodily motions) and visceral (that sense the interior milieu and respond by regulating vital functions). These circuits differ by a small set of largely dedicated transcriptional determinants: Brn3 is expressed in many somatic sensory neurons, first and second order (among which mechanoreceptors are uniquely marked by the Brn3+/Islet1+/Drgx+ signature), somatic motoneurons uniquely co-express Lhx3/4 and Mnx1, while the vast majority of neurons, sensory and motor, involved in respiration, blood circulation or digestion are molecularly defined by their expression and dependence on the pan-visceral determinant Phox2b. Results We explore the status of the sensorimotor transcriptional code of vertebrates in mollusks, a lophotrochozoa clade that provides a rich repertoire of physiologically identified neurons. In the gastropods Lymnaea stagnalis and Aplysia californica, we show that homologues of Brn3, Drgx, Islet1, Mnx1, Lhx3/4 and Phox2b differentially mark neurons with mechanoreceptive, locomotory and cardiorespiratory functions. Moreover, in the cephalopod Sepia officinalis, we show that Phox2 marks the stellate ganglion (in line with the respiratory — that is, visceral— ancestral role of the mantle, its target organ), while the anterior pedal ganglion, which controls the prehensile and locomotory arms, expresses Mnx. Conclusions Despite considerable divergence in overall neural architecture, a molecular underpinning for the functional allocation of neurons to interactions with the environment or to homeostasis was inherited from the urbilaterian ancestor by contemporary protostomes and deuterostomes.
The general regularities of habituation in visceral systems according to the Thompson-Spencer criteria were investigated in acute experiments on chloralose-narcotized cats. Changes in systemic reactions (blood pressure and heart rate) and dynamics of neuronal activity in the medulla oblongata and cerebral cortex to repeated long stimulation of visceral (splanchnic and mesenteric) nerves were used as indicators of habituation. It was
S. S. Musyashchikova; M. S. Sinyaya; A. A. Mokrushin; I. V. Ryzhova
We used liposomal amphotericin B as first-choice treatment of visceral leishmaniasis in 106 immunocompetent children who acquired the infection in a temperate region of southern Europe (Italy) where Leishmania infantum visceral leishmaniasis is endemic. The aim of the study was to identify the minimum total dose of liposomal amphotericin B needed to cure the infection in children and reduce the
Lucio di Martino; Robert N. Davidson; Raffella Giacchino; Silvestro Scotti; Francesco Raimondi; Elio Castagnola; Loredana Tasso; Antonio Cascio; Luigi Gradoni; Marina Gramiccia; Massimo Pettoello-Mantovani; Anthony D. M. Bryceson
Summary Data on the efficacy and safety of pentavalent antimony in the treatment of visceral leishmaniasis during pregnancy are scanty. A case of visceral leishmaniasis in a 39-year-old woman in the second trimester of pregnancy is reported here. The patient was hospitalized in poor condition with high fever and pancytopenia which had lasted for 6 weeks. A bone marrow aspirate
R. Utili; A. Rambaldi; Marie Françoise Tripodi; A. Andreana
Visceral leishmaniasis is a chronic parasitic disease associated with severe immune dysfunction. Treatment options are limited to relatively toxic drugs, and there is no vaccine for humans available. Hence, there is an urgent need to better understand immune responses following infection with Leishmania species by studying animal models of disease and clinical samples from patients. Here, we review recent discoveries in these areas and highlight shortcomings in our knowledge that need to be addressed if better treatment options are to be developed and effective vaccines designed.
Faleiro, Rebecca J.; Kumar, Rajiv; Hafner, Louise M.; Engwerda, Christian R.
Interoceptive feedback signals from the body are transmitted to hypothalamic neurons that control pituitary hormone release. This review article describes the organization of central neural pathways that convey ascending visceral sensory signals to endocrine neurons in the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus in rats. A special emphasis is placed on viscerosensory inputs to corticotropin releasing factor (CRF)-containing PVN neurons that drive the hypothalamic-pituitary-adrenal axis, and on inputs to magnocellular PVN and SON neurons that release vasopressin (AVP) or oxytocin (OT) from the posterior pituitary. The postnatal development of these ascending pathways also is considered.
The present paper reports a case of 6-year-old male child, suffering from pallor, fever and hepatosplenomegaly. A clinical diagnosis of enteric fever with a second possibility of malaria was considered. Laboratory findings included bicytopenia, hyperbilirubinemia and raised liver enzymes. Bone marrow examination revealed active hemophagocytosis. On extensive search few amastigote forms of Leishmania donovani were seen. Patient was negative for other viral, bacterial and malaria infections. The final diagnosis of hemophagocytic syndrome associated with visceral leishmaniasis was made. There was response of anti-Leishmanial treatment with improvement in clinical condition. PMID:16741336
Agarwal, Shilpi; Narayan, Shashi; Sharma, Sunita; Kahkashan, Eram; Patwari, A K
Background Pain tolerance is subject to considerable inter-individual variation, which may be influenced by a number of genetic and non-genetic factors. The mu, delta and kappa opioid receptors play a role in pain perception and are thought to mediate different pain modalities. The aim of this study was to explore associations between pain thresholds and gender and genetic variants in the three opioid receptor genes (OPRM, OPRD and OPRK). Experimental multi-modal pain data from previously published studies carried out in healthy Caucasian volunteers were used in order to limit the number of confounders to the study outcome. Data on thermal skin pain (n=36), muscle pressure pain (n=31) and mechanical visceral pain (n=50)) tolerance thresholds were included. Results Nineteen genetic polymorphisms were included in linear regression modeling. Males were found to tolerate higher thermal and muscle pressure pain than females (p=0.003 and 0.02). Thirty four percent of variability in thermal skin pain was accounted for by a model consisting of OPRK rs6473799 and gender. This finding was just outside significance when correction for multiple testing was applied. Variability in muscle pressure pain tolerance was associated with OPRK rs7016778 and rs7824175. These SNPs accounted for 43% of variability in muscle pressure pain sensitivity and these findings remained significant after adjustment for multiple testing. No association was found with mechanical visceral pain. Conclusion This is a preliminary and hypothesis generating study due to the relatively small study size. However, significant association between the opioid receptor genes and experimental pain sensitivity supports the influence of genetic variability in pain perception. These findings may be used to generate hypotheses for testing in larger clinical trials of patients with painful conditions.
This article reviews recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms, as well as randomized clinical trials employing cannabinoids in pain treatment. Tetrahydrocannabinol (THC, Marinol®) and nabilone (Cesamet®) are currently approved in the United States and other countries, but not for pain indications. Other synthetic cannabinoids, such as ajulemic acid, are in development. Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation. Sativex®, a cannabis derived oromucosal spray containing equal proportions of THC (partial CB1 receptor agonist ) and cannabidiol (CBD, a non-euphoriant, anti-inflammatory analgesic with CB1 receptor antagonist and endocannabinoid modulating effects) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis, and in 2007 for intractable cancer pain. Numerous randomized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain, rheumatoid arthritis and cancer pain. An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006. Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles. Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise.
Russo, Ethan B
Postamputation pain (PAP) is highly prevalent after limb amputation but remains an extremely challenging pain condition to treat. A large part of its intractability stems from the myriad pathophysiological mechanisms. A state-of-art understanding of the pathophysiologic basis underlying postamputation phenomena can be broadly categorized in terms of supraspinal, spinal, and peripheral mechanisms. Supraspinal mechanisms involve somatosensory cortical reorganization of the area representing the deafferentated limb and are predominant in phantom limb pain and phantom sensations. Spinal reorganization in the dorsal horn occurs after deafferentataion from a peripheral nerve injury. Peripherally, axonal nerve damage initiates inflammation, regenerative sprouting, and increased “ectopic” afferent input which is thought by many to be the predominant mechanism involved in residual limb pain or neuroma pain, but may also contribute to phantom phenomena. To optimize treatment outcomes, therapy should be individually tailored and mechanism based. Treatment modalities include injection therapy, pharmacotherapy, complementary and alternative therapy, surgical therapy, and interventions aimed at prevention. Unfortunately, there is a lack of high quality clinical trials to support most of these treatments. Most of the randomized controlled trials in PAP have evaluated medications, with a trend for short-term Efficacy noted for ketamine and opioids. Evidence for peripheral injection therapy with botulinum toxin and pulsed radiofrequency for residual limb pain is limited to very small trials and case series. Mirror therapy is a safe and cost-effective alternative treatment modality for PAP. Neuromodulation using implanted motor cortex stimulation has shown a trend toward effectiveness for refractory phantom limb pain, though the evidence is largely anecdotal. Studies that aim to prevent PA P using epidural and perineural catheters have yielded inconsistent results, though there may be some benefit for epidural prevention when the infusions are started more than 24 hours preoperatively and compared with nonoptimized alternatives. Further investigation into the mechanisms responsible for and the factors associated with the development of PAP is needed to provide an evidence-based foundation to guide current and future treatment approaches.
Hsu, Eugene; Cohen, Steven P
Introduction.?Loin pain-hematuria syndrome (LPHS) is a rare clinical entity causing unilateral or bilateral intractable flank and loin pain with hematuria. The etiology is poorly understood, and the diagnosis is made by exclusion of urological and nephrological conditions. The management is mainly symptomatic aiming for pain relief with nonopioid and opioids analgesics, and interventions such as capsaicin infusion into the renal pelvis, percutaneous regional nerve blocks, and laparoscopic or open surgical procedures, none of them providing lasting pain relief. Methods.?We describe four cases of LPHS in which long-term pain relief was achieved successfully by neuromodulation of lumbar sympathetic plexus with implanted electrodes. All patients underwent an initial successful trial of neuromodulation with Stimulong monoelectrode (Pajunk, GmbH, Geisingen, Germany) inserted percutaneously to lie adjacent to L3-L4 vertebral bodies followed by permanent implantation of the stimulation system using four contact electrodes (Medtronic Inc, Minneapolis, Minnesota, USA) in two patients with excellent long-term pain relief. Results.?All our patients had significant reductions in visual analog scale scores and analgesic consumption for the duration of the monoelectrode trial and in one patient beyond six months. Of the two patients who had full implants, pain relief is excellent with minimal analgesic consumption and one has resumed employment. There were no complications. Discussion.?LPHS is very difficult to treat with some experts maintaining it is mainly psychological. Conservative treatments are often unsatisfactory and radical measures not reliable. Peripheral stimulation of nerves and plexuses has been successful as shown from case reports. All our patients preferred low-frequency stimulation although its precise mode of action is uncertain. Conclusion.?Our experience shows that lumbar sympathetic chain neuromodulation in intractable LPHS not amenable to conservative therapy is a reasonable alternative before radical interventions. More experience is needed in multiple centers before its recommendation for refractory LPHS. PMID:22151418
Goroszeniuk, Teodor; Khan, Riaz; Kothari, Sandesha
Although systemic or visceral candidosis can be diagnosed during life, it is usually discovered at autopsy. Early diagnosis is important since treatment with specific antifungal drugs is effective. The diagnosis should rest on all available clinical and laboratory evidence. Mucocutaneous lesions and chorioretinitis are important clinical findings in the presence of predisposing illness and iatrogenic factors. Repeatedly positive blood cultures for Candida in the absence of an indwelling intravenous line and Candida colony counts of 10 000/ml or greater in urine freshly obtained by catheter in the absence of an indwelling Foley catheter are very significant. Similarly significant is recovery of Candida from closed spaces (pleural, peritoneal, joint or subarachnoid). The agar gel diffusion test for Candida antibodies has a sensitivity and specificity of 85% or greater and can confirm the diagnosis in otherwise doubtful cases. The various antibody tests for Candida are not suitable for random screening because of the low prevalence of visceral or systemic candidosis in the general population. PMID:7044510
Kozinn, P J; Taschdjian, C L; Kodsi, B E; Wise, G J; Seelig, M S; Goldberg, P K
Vaccination is the most effective method of preventing infectious diseases. Since the eradication of small pox in 1976, many other potentially life compromising if not threatening diseases have been dealt with subsequently. This event was a major leap not only in the scientific world already burdened with many diseases but also in the mindset of the common man who became more receptive to novel treatment options. Among the many protozoan diseases, the leishmaniases have emerged as one of the largest parasite killers of the world, second only to malaria. There are three types of leishmaniasis namely cutaneous (CL), mucocutaneous (ML), and visceral (VL), caused by a group of more than 20 species of Leishmania parasites. Visceral leishmaniasis, also known as kala-azar is the most severe form and almost fatal if untreated. Since the first attempts at leishmanization, we have killed parasite vaccines, subunit protein, or DNA vaccines, and now we have live recombinant carrier vaccines and live attenuated parasite vaccines under various stages of development. Although some research has shown promising results, many more potential genes need to be evaluated as live attenuated vaccine candidates. This mini-review attempts to summarize the success and failures of genetically modified organisms used in vaccination against some of major parasitic diseases for their application in leishmaniasis. PMID:24860575
Chhajer, Rudra; Ali, Nahid
Familial visceral myopathy is the most common cause of chronic primary (idiopathic) intestinal pseudo-obstruction. We studied four family groups with this disease and found that it has a characteristic morphologic appearance. Grossly, there is segmental dilatation of the alimentary tract, often involving multiple sites and most commonly producing a megaduodenum. Microscopically, the involved areas show a characteristic change consisting of degenerating muscle cells and fibrosis, which may involve the full thickness of the muscularis propria but is often more prominent in or limited to the external layer. Degenerating muscle cells appear pale, poorly defined, and fragmented. As residual thread-like remnants become surrounded by collagen or as muscle cells are destroyed, leaving apparent spaces surrounded by collagen, the longitudinal and circular muscles take on a vacuolated appearance easily recognized at low magnifications. Recognition of this change is greatly facilitated by use of a trichrome stain, and mild lesions may be recognized only with such stains. The nondilated segments of intestine show similar changes but of a less severe degree. Neural and vascular structures are apparently normal. Although the lesion most closely resembles progressive systemic sclerosis, the degenerating muscle cells and vacuolated appearance of the muscle serve to distinguish familial visceral myopathy from the latter entity. PMID:6896696
Mitros, F A; Schuffler, M D; Teja, K; Anuras, S
Although systemic or visceral candidosis can be diagnosed during life, it is usually discovered at autopsy. Early diagnosis is important since treatment with specific antifungal drugs is effective. The diagnosis should rest on all available clinical and laboratory evidence. Mucocutaneous lesions and chorioretinitis are important clinical findings in the presence of predisposing illness and iatrogenic factors. Repeatedly positive blood cultures for Candida in the absence of an indwelling intravenous line and Candida colony counts of 10 000/ml or greater in urine freshly obtained by catheter in the absence of an indwelling Foley catheter are very significant. Similarly significant is recovery of Candida from closed spaces (pleural, peritoneal, joint or subarachnoid). The agar gel diffusion test for Candida antibodies has a sensitivity and specificity of 85% or greater and can confirm the diagnosis in otherwise doubtful cases. The various antibody tests for Candida are not suitable for random screening because of the low prevalence of visceral or systemic candidosis in the general population. Images FIG. 1
Kozinn, P. J.; Taschdjian, C. L.; Kodsi, B. E.; Wise, G. J.; Seelig, M. S.; Goldberg, P. K.
Vaccination is the most effective method of preventing infectious diseases. Since the eradication of small pox in 1976, many other potentially life compromising if not threatening diseases have been dealt with subsequently. This event was a major leap not only in the scientific world already burdened with many diseases but also in the mindset of the common man who became more receptive to novel treatment options. Among the many protozoan diseases, the leishmaniases have emerged as one of the largest parasite killers of the world, second only to malaria. There are three types of leishmaniasis namely cutaneous (CL), mucocutaneous (ML), and visceral (VL), caused by a group of more than 20 species of Leishmania parasites. Visceral leishmaniasis, also known as kala-azar is the most severe form and almost fatal if untreated. Since the first attempts at leishmanization, we have killed parasite vaccines, subunit protein, or DNA vaccines, and now we have live recombinant carrier vaccines and live attenuated parasite vaccines under various stages of development. Although some research has shown promising results, many more potential genes need to be evaluated as live attenuated vaccine candidates. This mini-review attempts to summarize the success and failures of genetically modified organisms used in vaccination against some of major parasitic diseases for their application in leishmaniasis.
Chhajer, Rudra; Ali, Nahid
Visceral leishmaniasis (VL) is a disease that has both zoonotic and anthroponotic etiologies. In India, VL is endemic, considered to be anthroponotic, and caused by Leishmania donovani . Anthroponotic diseases are maintained by transmission from human to human and to a lesser extent from human to animals. Serum samples from 1,220 animals from 7 human VL endemic districts of Bihar, India, were tested for antibodies to a recombinant kinetoplast antigen (rK39 antigen) present in amastigotes of visceralizing Leishmania species, i.e., L. donovani complex. Additionally, PCR was used to examine samples positive by rK39 antigen serology. Antibodies to rK39 indicative of VL were detected in 33 of 1,220 animals. Thirty-one of 867 goats (Capra hircus), 1 of 161 cattle (Bos indicus), and 1 of 54 wild rats (Rattus sp.) were positive by rK39 serology. None of 106 chickens (Gallus domesticus), 26 sheep (Ovis aries), 3 water buffaloes (Bubalus bubalus), or 3 dogs (Canis familiaris) was positive by rK39 serology. Leishmania donovani DNA was detected by PCR in 20 rK39 positive blood samples from goats and 1 sample from a cow. The present study indicates that goats are potential animal reservoirs of human VL in India. PMID:22765517
Singh, Niti; Mishra, Jyotsna; Singh, Ram; Singh, Sarman
This study evaluated the performance of the EIE-leishmaniose-visceral-canina-Bio-Manguinhos (EIE-LVC) kit and to compare it with that of the IFI-leishmaniose-visceral-canina-Bio-Manguinhos (IFI-LVC) kit. Four groups of dogs were studied: group 1 (G1), dogs with clinical signs indicative of CVL and testing positive for the parasite (n=25); group 2 (G2), dogs with only a presumed diagnosis of CVL (n=62); group 3 (G3), dogs
R. A. Lira; M. Paiva Cavalcanti; M. Nakazawa; A. G. P. Ferreira; E. D. Silva; F. G. C. Abath; L. C. Alves; W. V. Souza; Y. M. Gomes
We conducted a study to determine whether intractable postoperative stiffness or deltoid damage results from primary arthroscopic anterior acromioplasty and mini-open repair of full-thickness tears of the superior rotator cuff. Eighty-three repairs (80 patients) were available for follow-up at a mean (range) of 57.2 (12-98) months. Range of motion at presentation and motion in contralateral shoulder at final follow-up were used for comparison. Significant improvements were seen in active forward elevation, passive forward elevation, and active external rotation at 90° abduction. Final motion in the operative and contralateral shoulders was similar. American Shoulder and Elbow Surgeons shoulder index improved significantly (P<.0001) from 50.0 before surgery to 88.3 after surgery. Although 1 patient had a symptomatic retear that required revision surgery, there were no cases of intractable stiffness, and there were no cases of deltoid damage. PMID:22268017
Doppelt, Jason D; Neviaser, Robert J
Intractable post-operative chylous ascites had been managed successfully using a peritoneovenous shunt (PVshunt). A 4-year-old girl with neuroblastoma originated from the right adrenal gland was admitted to our hospital. Following the preoperative chemotherapy, tumor resection, and lymph node dissection of the abdominal paraaortic region were carried out. Post-operative radiation therapy 9.6 gray to the tumor bed and to the paraaortic
Hiroshi Matsufuji; Takeki Nishio; Ryota Hosoya
The management of high-operative-risk patients with a pneumothorax is complicated. The case of a 79-year old man with an intractable secondary pneumothorax, who had taken oral steroids to control asthma, is presented. Since the patient could not tolerate general anaesthesia because of poor cardiac function, thoracoscopic surgery was performed under local anaesthesia. A successful lung fistula closure was achieved and the continuous air leakage disappeared immediately after the surgery.
Yutaka, Yojiro; Katakura, Hiromichi; Kaneda, Shohei; Yamanaka, Akira
Black occlusive intraocular devices have been used successfully for intractable binocular diplopia. We describe a novel technique of implanting both a black occlusive device and a clear poly(methyl methacrylate) intraocular lens (IOL) in the capsular bag during phacoemulsification surgery. If the need should arise at a later date, this approach will allow safer and easier explantation of the black occlusive device, avoiding the need for IOL exchange. PMID:22088851
Byard, Stephen D; Lee, Richard M H; Lam, Fook Chang; Simpson, Andrew R H; Liu, Christopher S C
We report a case of a 43-year-old man who developed intractable hematuria after percutaneous nephrolithotomy. Angiography detected a pseudoaneurysm arising from the lower polar artery; however, embolization could not be performed because of unfavorable vascular anatomy. A percutaneous thrombin injection under ultrasound guidance initially controlled the bleeding, but hematuria subsequently recurred as a result of recanalization of the aneurysm. The case was successfully managed with ultrasound- and fluoroscopic-guided direct injection of cyanoacrylate glue into the pseudoaneurysm.
Lal, Anupam, E-mail: email@example.com; Kumar, Ajay; Prakash, Mahesh; Singhal, Manphool [Post Graduate Institute of Medical Education and Research (PGIMER), Department of Radiodiagnosis and Imaging (India); Agarwal, Mayank Mohan; Sarkar, Debansu [Post Graduate Institute of Medical Education and Research (PGIMER), Department of Urology (India); Khandelwal, Niranjan [Post Graduate Institute of Medical Education and Research (PGIMER), Department of Radiodiagnosis and Imaging (India)
Shoulder pain is a frequent complaint encountered in the emergency setting. A brief review of shoulder anatomy and physical examination sets the foundation for evaluation of shoulder pain. Considerations of patient's age are helpful to predict injuries. Fractured clavicles are often seen in traumatic injuries in children and young adults, whereas fractures of the humeral head are more often seen in the elderly from traumatic injuries. Shoulder dislocations are more common in teens to fourth decade. This article reviews specific acute injuries, chronic conditions, and radiologic considerations of patients with shoulder complaints encountered in emergency settings. PMID:21543907
Ramponi, Denise R
Chronic regional pain syndrome (CRPS) can be intractable to treat and patients sometimes suffer for many years. Therefore, new treatment strategies are needed to alleviate symptoms in CRPS patients. This case report describes a patient suffering from intractable CRPS type 1 for 13 years. Due to her swollen painful feet and left knee she is wheelchair-bound. The combination of palmitoylethanolamide and ketamine 10% cream reduced her pain by more than 50% after 1 month of treatment, and a marked reduction in swelling and skin discoloration was noticed. Furthermore, she could walk independently again and she experienced no side effects. Thus, palmitoylethanolamide and topical ketamine could be a combination therapy option for treating CRPS patients. PMID:23658493
Keppel Hesselink, Jan M; Kopsky, David J
Chronic regional pain syndrome (CRPS) can be intractable to treat and patients sometimes suffer for many years. Therefore, new treatment strategies are needed to alleviate symptoms in CRPS patients. This case report describes a patient suffering from intractable CRPS type 1 for 13 years. Due to her swollen painful feet and left knee she is wheelchair-bound. The combination of palmitoylethanolamide and ketamine 10% cream reduced her pain by more than 50% after 1 month of treatment, and a marked reduction in swelling and skin discoloration was noticed. Furthermore, she could walk independently again and she experienced no side effects. Thus, palmitoylethanolamide and topical ketamine could be a combination therapy option for treating CRPS patients.
Keppel Hesselink, Jan M; Kopsky, David J
Chronic post-thoracotomy pain syndrome (PTPS) can cause significant patient distress and is frequently difficult to manage. Percutaneous intercostal nerve (ICN) cryoablation by palpation of surface landmarks can be risky, as inaccurate probe placement can lead to hemo- or pneumothorax. Experience with image-guided ICN cryoablation with treatment planning and device navigation is limited. A patient with intractable PTPS was treated with ICN cryoablation under cone-beam computed tomography guidance with software-assisted needle trajectory planning and ablation zone simulation. This procedure provided the patient ~8 weeks of relief. This case demonstrated that ICN cryoablation is feasible under image guidance with device navigation and ablation simulation and may result in a few months of pain relief in cases of intractable PTPS. PMID:23954965
Koethe, Yilun; Mannes, Andrew J; Wood, Bradford J
A prospective study was done to evaluate the role of short-term Video EEG (VEEG) recording in assessing the nature of clinical behaviour and in classification of seizures in children with frequent intractable seizure episodes. Forty five children upto 12 years of age with frequent intractable seizure episodes (> or =3/week) were included in the study. VEEG was done on an outpatient basis until an event was recorded or for a minimum period of 6 hours. The events were detected in 78% of cases. The seizures were classified in all children with recorded events and seizure classification was changed in 22%. Anti-epileptic drugs could be stopped or reduced in 11%. Short term VEEG monitoring was useful in characterising events and in classification of seizures in children with frequent, intractable seizure episodes. Use of this investigation as a screening procedure for diagnosis in children with frequent episodes is stressed, thereby reducing the cost associated with prolonged VEEG recordings and disability associated with misdiagnosis of epilepsy. PMID:10751810
Srikumar, G; Bhatia, M; Jain, S; Maheshwari, M C
Background Progressive familial intrahepatic cholestasis type 1 (PFIC1), an inherited liver disease caused by mutations in ATP8B1, progresses to severe cholestasis with a sustained intractable itch. Currently, no effective therapy has been established for PFIC1. Decreased function of the bile salt export pump (BSEP) in hepatocytes is suggested to be responsible for the severe cholestasis observed in PFIC1. We found a previously unidentified pharmacological effect of 4-phenylbutyrate (4PB) that increases the expression and function of BSEP. Here, we tested 4PB therapy in three patients with PFIC1. Methods The therapeutic potency of 4PB in these patients was tested by oral administration of this drug with gradually increasing dosage (200, 350, and 500 mg/kg/day) for 6 months. Biochemical, histological, and clinical data were collected. Results 4PB therapy had no beneficial effect on the patients’ liver functions, as assessed by biochemical and histological analyses, despite an increase in hepatic BSEP expression. However, therapy with 4PB at a dosage of 350 or 500 mg/kg/day significantly relieved the intractable itch. Serum levels of potential pruritogens in cholestasis were much higher than the reference ranges during the 4PB therapy. Conclusions 4PB therapy may be a new medication for patients with intractable cholestatic pruritus and may improve quality of life for patients and their families.
We performed a retrospective study of 51 consecutive patients who underwent operation for intractable partial epilepsy related to low-grade intracerebral neoplasms between 1984 and 1990. All patients had medically refractory partial seizures and a mass lesion identified on neuroimaging studies. Lesionectomy was performed on 17 patients, and 34 had lesion resection and corticectomy. Mean postoperative follow-up was 4.4 years (range 2-8 years). Sixty-six percent of patients were seizure-free, and 88% experienced a significant reduction in seizure frequency. In 16 patients (31%), antiepileptic drugs (AEDs) were successfully discontinued. Twenty-five of 31 (81%) eligible patients obtained a driver's license after successful operation. Patients with complete tumor resection and no interictal epileptiform activity on postoperative EEG studies had the best operative outcome. Epilepsy surgery can result in long-term improvement in seizure control and quality of life (QOL) in selected patients with intractable tumor-related epilepsy. Our results should be useful to clinicians considering treatment options for patients with intractable seizures related to low-grade intracerebral neoplasms. PMID:7988500
Britton, J W; Cascino, G D; Sharbrough, F W; Kelly, P J
The long-term evolution to intractable epilepsy in children treated with cyclosporine administered for graft-versus-host-disease after hematopoietic stem cell transplantation was evaluated. In a group of 185 children treated with cyclosporine after bone marrow transplantation, 15 (8%) presented with acute seizures that were generalized in 7 and focal in 7 and had absence status in 1. Electroencephalography (EEG) and neuroimaging showed predominant abnormalities in the occipital regions. One patient died shortly after the seizure; in seven cases, seizures remitted, whereas relapses were observed in seven others. After the first year, seizures persisted chronically in four cases and evolved to intractable epilepsy. Focal temporal epilepsy was diagnosed in three cases, whereas in the fourth case, a multifocal epilepsy was observed. Magnetic resonance imaging (MRI) detected mesial temporal sclerosis in all of these cases. The risk factors associated with evolution to epilepsy included lower age at transplantation (3-5 years), more than one relapsing seizure in the first year after transplantation, and longer treatment with cyclosporine. Not only can cyclosporine cause acute central nervous system toxicity, it can also determine intractable epilepsy associated with mesial temporal sclerosis. PMID:17005102
Gaggero, Roberto; Haupt, Riccardo; Paola Fondelli, Maria; De Vescovi, Raffaella; Marino, Alessia; Lanino, Edoardo; Dallorso, Sandro; Faraci, Maura
Background: Functional magnetic resonance imaging (fMRI), a non-invasive technique with high spatial resolution and blood oxygen level dependent (BOLD) contrast, has been applied to localize and map cognitive functions in the clinical condition of chronic intractable epilepsy. Purpose: fMRI was used to map the language and memory network in patients of chronic intractable epilepsy pre- and post-surgery. Materials and Methods: After obtaining approval from the institutional ethics committee, six patients with intractable epilepsy with an equal number of age-matched controls were recruited in the study. A 1.5 T MR scanner with 12-channel head coil, integrated with audio-visual fMRI accessories was used. Echo planar imaging sequence was used for BOLD studies. There were two sessions in TLE (pre- and post-surgery). Results: In TLE patients, BOLD activation increased post-surgery in comparison of pre-surgery in inferior frontal gyrus (IFG), middle frontal gyrus (MFG), and superior temporal gyrus (STG), during semantic lexical, judgment, comprehension, and semantic memory tasks. Conclusion: Functional MRI is useful to study the basic concepts related to language and memory lateralization in TLE and guide surgeons for preservation of important brain areas during ATLR. This will help in understanding future directions for the diagnosis and treatment of such disease.
Chaudhary, Kapil; Kumaran, S Senthil; Chandra, Sarat P; Wadhawan, Ashima Nehra; Tripathi, Manjari
We studied cases of visceral leishmaniasis (VL) over a 2-year period among immunocompetent patients who presented to a rural medical college in West Bengal, India to determine a clinical and hematological profile among these patients. We studied a total of 36 cases of VL; the male to female ratio of the cases was 1.6:1 and the mean age was 20.1+/-11.1 years. A detailed history, physical examination, hemogram, bone marrow or splenic aspiration and chest x-ray were conducted on all cases. A CT-scan of the thorax and fiberoptic bronchoscopy were performed in selected cases. Fever and splenomegaly were present in all cases. Weakness, abdominal pain, bleeding, and hepatomegaly were seen in 63.9, 27.8, 8.3 and 58.3% of cases, respectively. Pancytopenia, bicytopenia, leukopenia and thrombocytopenia were seen in 58.3, 41.7, 61.1 and 83.3% of cases, respectively. Five patients (13.9%) had cough, 2 (5.6%) had hemoptysis, 6 (16.7%) had an abnormal chest x-ray and 3 (8.3%) had localized reticulo-nodular opacities on a CT-scan of the thorax. Bronchoalveolar lavage showed gram-positive cocci in 2 cases (5.6%). One patient died of acute respiratory distress syndrome. Cytopenia was common among the series of VL patients. Pulmonary complications, usually secondary infection, were less frequent (found in 13.9% cases) but was fatal in one patient. PMID:23691621
Chakrabarti, Sudipta; Sarkar, Supriya; Goswami, Bidyut Krishna; Sarkar, Niladri; Das, Shikha
AIM: To evaluate the therapeutic effect of Shugan-decoction (SGD) on visceral hyperalgesia and colon gene expressions using a rat model. METHODS: Ninety-six adult male Wistar rats were randomized into six equal groups for assessment of SGD effects on psychological stress-induced changes using the classic water avoidance stress (WAS) test. Untreated model rats were exposed to chronic (1 h/d for 10 d consecutive) WAS conditions; experimental treatment model rats were administered with intragastric SGD at 1 h before WAS on consecutive days 4-10 (low-dose: 0.1 g/mL; mid-dose: 0.2 g/mL; high-dose: 0.4 g/mL); control treatment model rats were similarly administered with the irritable bowel syndrome drug, dicetel (0.0042 g/mL); untreated normal control rats received no drug and were not subjected to the WAS test. At the end of the 10-d WAS testing period, a semi-quantitative measurement of visceral sensitivity was made by assessing the abdominal withdrawal reflex (AWR) to colorectal balloon-induced distension (at 5 mmHg increments) to determine the pain pressure threshold (PPT, evidenced by pain behavior). Subsequently, the animals were sacrificed and colonic tissues collected for assessment of changes in expressions of proteins related to visceral hypersensitivity (transient receptor potential vanilloid 1, TRPV1) and sustained visceral hyperalgesia (substance P, SP) by immunohistochemistry and real-time polymerase chain reaction. Inter-group differences were assessed by paired t test or repeated measures analysis of variance. RESULTS: The WAS test successfully induced visceral hypersensitivity, as evidenced by a significantly reduced AWR pressure in the untreated model group as compared to the untreated normal control group (190.4 ± 3.48 mmHg vs 224.0 ± 4.99 mmHg, P < 0.001). SGD treatments at mid-dose and high-dose and the dicetel treatment significantly increased the WAS-reduced PPT (212.5 ± 2.54, 216.5 ± 3.50 and 217.7 ± 2.83 mmHg respectively, all P < 0.001); however, the low-dose SGD treatment produced no significant effect on the WAS-reduced PPT (198.3 ± 1.78 mmHg, P > 0.05). These trends corresponded to the differential expressions observed for both TRPV1 protein (mid-dose: 1.64 ± 0.08 and high-dose: 1.69 ± 0.12 vs untreated model: 3.65 ± 0.32, P < 0.001) and mRNA (0.44 ± 0.16 and 0.15 ± 0.03 vs 1.39 ± 0.15, P < 0.001) and SP protein (0.99 ± 0.20 and 1.03 ± 0.23 vs 2.03 ± 0.12, P < 0.01) and mRNA (1.64 ± 0.19 and 1.32 ± 0.14 vs 2.60 ± 0.33, P < 0.05). These differential expressions of TRPV1 and SP related to mid- and high-dose SGD treatments were statistically similar to the changes induced by dicetel treatment. No signs of overt damage to the rat system were observed for any of the SGD dosages. CONCLUSION: Shugan-decoction can reduce chronic stress-induced visceral hypersensitivity in rats, and the regulatory mechanism may involve mediating the expressions of TRPV1 and SP in colon tissues.
Shang, Jing-Juan; Yuan, Jian-Ye; Xu, Hui; Tang, Rong-Zhu; Dong, Yue-Bin; Xie, Jian-Qun
We assessed the impact of vagus nerve stimulation on a cohort of patients with intractable epilepsy. A 1-year prospective trial of vagus nerve stimulation for intractable epilepsy was done in 26 patients. Seizure frequency, anti-epileptic drugs, and quality of life were assessed using QOLIE-89, ELDQOL, and a Likert scale of impact of treatment. Seizures were reduced by more than 50%
Richard S. McLachlan; Mark Sadler; Neelan Pillay; Alan Guberman; Michael Jones; Samuel Wiebe; Jack Schneiderman
Metastatic involvement of the viscera in men with advanced castration-resistant prostate cancer (CRPC) has been poorly characterised to date. In 359 CRPC patients treated between June 2003 and December 2011, the frequency of radiologically detected visceral metastases before death was 32%. Of the 92 patients with computed tomography performed within 3 mo of death, 49% had visceral metastases. Visceral metastases most commonly involved the liver (20%) and lung (13%). Median survival from diagnosis of visceral disease was 7.1 mo (95% confidence interval, 5.9-8.3). Survival was affected by the degree of bone involvement at detection of visceral disease, varying from 6.1 mo in men with more than six bone metastases to 18.2 mo in men with no bone metastases (p=0.001). Heterogeneity was noted in clinical phenotypes and prostate-specific antigen trends at development of visceral metastases. Visceral metastases are now more commonly detected in men with CRPC, likely due to the introduction of novel survival-prolonging treatments. PMID:24295792
Pezaro, Carmel J; Omlin, Aurelius; Lorente, David; Nava Rodrigues, Daniel; Ferraldeschi, Roberta; Bianchini, Diletta; Mukherji, Deborah; Riisnaes, Ruth; Altavilla, Amelia; Crespo, Mateus; Tunariu, Nina; de Bono, Johann S; Attard, Gerhardt
Five ailments which can cause pain in the achilles tendon area are: (1) muscular strain, involving the stretching or tearing of muscle or tendon fibers; (2) a contusion, inflammation or infection called tenosynovitis; (3) tendonitis, the inflammation of the tendon; (4) calcaneal bursitis, the inflammation of the bursa between the achilles tendon…
Connors, G. Patrick
... itching to the hospice nurse. Often such side effects can be treated and may stop after taking the medication for a few days. • Other things that might make the pain better are: - Relaxing activities - Distracting activities such as watching TV, listening to music or playing a game - Heat (such as a ...
This chapter focuses on what social pain is and how it should be managed. In order to understand social pain in a cancer patient, it is necessary to recognize the change in the patient's daily life after the diagnosis of cancer. Because the degree of suffering and the relationships with family members and the people he or she worked with differ from patient to patient, it is important to note that the context of social pain is different in each patient. Five points shown below are essential in managing social pain. 1. Economical suffering may be alleviated by utilization of the social security system while taking into account each patient's standard of living. 2. Burdens on family members should be lessened, such as by not having them stay at the patient's bedside every day and letting them go home occasionally. 3. The normal patterns of communication, support, and conflict in the family should be identified, and the extent to which they have been disrupted by the illness should be assessed. 4. It is important to understand the ethnic, cultural, and religious background of the patient and the potential impact of their influence on the individual and the illness. 5. Practical or emotional unfinished business that the patient has needs to be identified, and efforts should be made to support fulfillment. PMID:21950034
Shimoyama, Naohito; Shimoyama, Megumi
Background This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF) modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity. In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) and cholinergic nerves (ChAT) was studied one week after one or two intravesical instillations of the growth factor. To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG) neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. Results In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment) reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation) caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na+ channels (VGSC) in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. Conclusions For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a key modulator of neural plasticity in the pelvis and enhanced VEGF content may be associated with visceral hyperalgesia, abdominal discomfort, and/or pelvic pain.
Spinal cord stimulation (SCS) uses electrical stimulation of the dorsal columns of the spinal cord to prevent the perception\\u000a of intractable neuropathic pain signals, but its mechanisms and consequences of use are poorly understood. Two overweight\\u000a female patients who were implanted with SCS systems (Precision™; Advanced Bionics\\/Boston Scientific, Valencia, CA) reported\\u000a better than 50% relief of their chronic back and
Eugene Pereira; Allison Foster
Disseminated visceral coccidiosis (DVC) caused by Eimeria spp was first recognized as a disease entity in captive sandhill cranes (Grus canadensis) and whooping cranes (G americana) at the Patuxent Wildlife Research Center. Because cranes produced at the Center are reintroduced to the wild to augment wild populations, studies involving both experimentally induced and natural infections were initiated to determine the potential or actual occurrence of DVC in wild Gruidae. Nine sandhill cranes dosed orally with eimerian oocysts of wild origin developed lesions characteristic of DVC. Extraintestinal granulomas associated with developing schizonts were found in 6 birds. Similar lesions were observed in wild sandhill cranes throughout parts of midwestern United States, Alaska, and Saskatchewan. These studies revealed the wide geographic distribution and the high frequency of occurrence of DVC in wild cranes.
Carpenter, J.W.; Novilla, M.N.; Fayer, R.; Iverson, G.C.
A 64-year-old man was admitted with fever, weight loss, fatigue and night sweats. He was known to have rheumatoid arthritis and had been taking methotrexate for 1 year. He had worked in Saudi Arabia until 1994 and had been living in Spain for 6 months every year. Clinical examination showed an enlarged spleen. Routine investigations showed pancytopaenia. Serial blood cultures were negative. CT scan confirmed splenomegaly and was otherwise unremarkable. Bone marrow biopsy revealed Leishmania amastigote consistent with a diagnosis of visceral leishmaniasis. After discussing with the hospital for tropical diseases (HTD), he was started on liposomal amphotericin B. Following two infusions of amphotericin B, he started improving as his fever, night sweats and weakness had settled. He was then discharged and followed up in HTD clinic 4 weeks later where he was found to be consistently improving.
TOQEER, Muhammad; Rahman, Nadeem; Whitehead, Mark W; Lockwood, Diana
Visceral leishmaniasis (VL) is a vector-borne protozoal infection caused by replication of Leishmania species in macrophages. VL is characterized by fever, hepatosplenomegaly and cytopenia. Apart from those classic clinical characteristics, VL has been associated with autoimmune clinical and laboratory features. Reported herein are 16 consecutive patients with VL who were checked for laboratory autoimmune manifestations. A variety of autoimmune antibodies including elevated titers of antinuclear antibodies and rheumatoid factor were detected in all patients. Of note, no laboratory autoimmune manifestations were detected in the seven patients who were re-evaluated 3 months after therapy. It is concluded that autoimmune laboratory manifestations during VL infection are common. These may mistakenly lead to diagnosis of an autoimmune disorder. PMID:22516744
Liberopoulos, Evangelos; Kei, Anastazia; Apostolou, Fotini; Elisaf, Moses
Background Visceral pain is common symptom involved in many gastrointestinal disorders such as inflammatory bowel disease. The underlying molecular mechanisms remain elusive. We investigated the molecular mechanisms and the role for voltage gated calcium channel (VGCC) in the pathogenesis in a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced visceral inflammatory hypersensitivity. Results Using Agilent cDNA arrays, we found 172 genes changed significantly in dorsal root ganglia (DRG) of TNBS treated rats. Among these changed genes, Cav1.2 and Cav2.3 were significantly up-regulated. Then the RT-PCR and Western blot further confirmed the up-regulation of Cav1.2 and Cav2.3. The whole cell patch clamp recording of acutely dissociated colonic specific DRG neurons showed that the peak IBa density was significantly increased in colonic neurons of TNBS treated rats compared with control rats (?127.82?±?20.82 pA/pF Vs ?91.67?±?19.02 pA/pF, n?=?9, *P?0.05). To distinguish the different type of calcium currents with the corresponding selective channel blockers, we found that L-type (?38.56?±?3.97 pA/pF Vs ?25.75?±?3.35 pA/pF, n?=?9, * P?0.05) and R-type (?13.31?±?1.36 pA/pF Vs ?8.60?±?1.25 pA/pF, n?=?9, * P?0.05) calcium current density were significantly increased in colonic DRG neurons of TNBS treated rats compared with control rats. In addition, pharmacological blockade with L-type antagonist (nimodipine) and R-type antagonist (SNX-482) with intrathecal injection attenuates visceral pain in TNBS induced inflammatory visceral hypersensitivity. Conclusion Cav1.2 and Cav2.3 in colonic primary sensory neurons play an important role in visceral inflammatory hyperalgesia, which maybe the potential therapeutic targets.
Background/Aims DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Co-rydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. Methods Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. Results In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. Conclusions The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity.
Kim, Eun Ran; Min, Byung-Hoon; Lee, Tae Ho; Son, Miwon; Rhee, Poong-Lyul
What people feel shapes their perceptions of others. In the studies reported here, we examined the assimilative influence of visceral states on social judgment. Replicating prior research, we found that participants who were outside during winter overestimated the extent to which other people were bothered by cold (Study 1), and participants who ate salty snacks without water thought other people were overly bothered by thirst (Study 2). However, in both studies, this effect evaporated when participants believed that the other people under consideration held political views opposing their own. Participants who judged these dissimilar others were unaffected by their own strong visceral-drive states, a finding that highlights the power of dissimilarity in social judgment. Dissimilarity may thus represent a boundary condition for embodied cognition and inhibit an empathic understanding of shared out-group pain. Our findings reveal the need for a better understanding of how people's internal experiences influence their perceptions of the feelings and experiences of those who may hold values different from their own. PMID:22402799
O'Brien, Ed; Ellsworth, Phoebe C
Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and postsurgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk both of developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.
Woolf, Clifford J
Communication between neurons and glia in the dorsal root ganglia (DRG) and the central nervous system is critical for nociception. Both glial activation and proinflammatory cytokine induction underlie this communication. We investigated whether satellite glial cell (SGC) and tumor necrosis factor-? (TNF-?) activation in DRG participates in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rat model of visceral hyperalgesia. In TNBS-treated rats, TNF-? expression increased in DRG and was colocalized to SGCs enveloping a given neuron. These SGCs were activated as visualized under electron microscopy: they had more elongated processes projecting into the connective tissue space and more gap junctions. When nerves attached to DRG (L6-S1) were stimulated with a series of electrical stimulations, TNF-? were released from DRG in TNBS-treated animals compared with controls. Using a current clamp, we noted that exogenous TNF-? (2.5 ng/ml) increased DRG neuron activity, and visceral pain behavioral responses were reversed by intrathecal administration of anti-TNF-? (10 ?g·kg(-1)·day(-1)). Based on our findings, TNF-? and SGC activation in neuron-glial communication are critical in inflammatory visceral hyperalgesia. PMID:24627565
Song, Dan-dan; Li, Yong; Tang, Dong; Huang, Li-ya; Yuan, Yao-zong
Irritable bowel syndrome is characterized by colorectal hypersensitivity and contributed to by sensitized mechanosensitive primary afferents and recruitment of mechanoinsensitive (silent) afferents. Neurotrophic factors are well known to orchestrate dynamic changes in the properties of sensory neurons. Although pain modulation by proteins in the glial cell line-derived neurotrophic factor (GDNF) family has been documented in various pathophysiological states, their role in colorectal hypersensitivity remains unexplored. Therefore, we investigated the involvement of the GDNF family receptor ?-3 (GFR?3) signaling in visceral hypersensitivity by quantifying visceromotor responses (VMR) to colorectal distension before and after intracolonic treatment with 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baseline responses to colorectal distension did not differ between C57BL/6 and GFR?3 knockout (KO) mice. Relative to intracolonic saline treatment, TNBS significantly enhanced the VMR to colorectal distension in C57BL/6 mice 2, 7, 10, and 14 days posttreatment, whereas TNBS-induced visceral hypersensitivity was significantly suppressed in GFR?3 KO mice. The proportion of GFR?3 immunopositive thoracolumbar and lumbosacral colorectal dorsal root ganglion neurons was significantly elevated 2 days after TNBS treatment. In single fiber recordings, responses to circumferential stretch of colorectal afferent endings in C57BL/6 mice were significantly increased (sensitized) after exposure to an inflammatory soup, whereas responses to stretch did not sensitize in GFR?3 KO mice. These findings suggest that enhanced GFR?3 signaling in visceral afferents may contribute to development of colorectal hypersensitivity. PMID:21193524
Tanaka, T; Shinoda, M; Feng, B; Albers, K M; Gebhart, G F
Irritable bowel syndrome is characterized by colorectal hypersensitivity and contributed to by sensitized mechanosensitive primary afferents and recruitment of mechanoinsensitive (silent) afferents. Neurotrophic factors are well known to orchestrate dynamic changes in the properties of sensory neurons. Although pain modulation by proteins in the glial cell line-derived neurotrophic factor (GDNF) family has been documented in various pathophysiological states, their role in colorectal hypersensitivity remains unexplored. Therefore, we investigated the involvement of the GDNF family receptor ?-3 (GFR?3) signaling in visceral hypersensitivity by quantifying visceromotor responses (VMR) to colorectal distension before and after intracolonic treatment with 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baseline responses to colorectal distension did not differ between C57BL/6 and GFR?3 knockout (KO) mice. Relative to intracolonic saline treatment, TNBS significantly enhanced the VMR to colorectal distension in C57BL/6 mice 2, 7, 10, and 14 days posttreatment, whereas TNBS-induced visceral hypersensitivity was significantly suppressed in GFR?3 KO mice. The proportion of GFR?3 immunopositive thoracolumbar and lumbosacral colorectal dorsal root ganglion neurons was significantly elevated 2 days after TNBS treatment. In single fiber recordings, responses to circumferential stretch of colorectal afferent endings in C57BL/6 mice were significantly increased (sensitized) after exposure to an inflammatory soup, whereas responses to stretch did not sensitize in GFR?3 KO mice. These findings suggest that enhanced GFR?3 signaling in visceral afferents may contribute to development of colorectal hypersensitivity.
Shinoda, M.; Feng, B.; Albers, K. M.; Gebhart, G. F.
Culinary use of the pungent spices has potential health benefits including a reduction in food intake. Pungent spices often contain ingredients that activate members of the transient receptor potential (TRP) family A1 and evoke pain from capsaicin-sensitive somatosensory neurons. TRPA1 channel have also been identified on cranial visceral afferent neurons but their distribution and functional contributions are poorly understood. Visceral vagal neurons transduce mechanical and chemical signals from peripheral organs to the nucleus tractus solitarii. Many capsaicin-sensitive vagal afferents participate in peripheral satiety signaling that includes cholecystokinin (CCK) sensitive neurons. To assess signaling, the TRPA1 selective agonist allyl isothiocyanate (AITC) was tested together with CCK and capsaicin (200nM), a TRPV1 specific agonist. In isolated nodose neurons, AITC (0.05-0.2mM) evoked concentration-dependent inward currents in 38% of the tested neurons. The TRPA1 specific antagonist HC-030031 (10?M) blocked AITC responses. TRPA1 responses were mixed across neurons that were capsaicin-sensitive and -insensitive. However CCK evoked inward currents only on capsaicin-sensitive neurons and 28% of the CCK-sensitive neurons expressed TRPA1. Our results indicate that TRPA1 is co-expressed with TRPV1 in CCK-sensitive nodose neurons. The findings indicate a potential mechanism by which spices can act within cranial visceral afferent pathways mediating satiety and contribute to the reduction of the food intake associated with spiced diets. PMID:21316356
Choi, Myung-Jin; Jin, Zhenhua; Park, Yong Seek; Rhee, Young Kyoung; Jin, Young-Ho
Visceral Leishmaniasis or Kala Azar is endemic in certain regions of India. In endemic areas, the constellation of fever, progressive weight loss, weakness, pronounced splenomegaly, anemia, leukopenia, and hypergammaglobulinemia is highly suggestive of visceral leishmaniasis. Demonstration of the parasite in liver, splenic or bone marrow aspirates is confirmatory. We present a case in which Leishmania donovani (LD) bodies were demonstrated on splenic aspirate. We were unable to demonstrate LD bodies on bone marrow aspiration.
Jetley, S; Rana, S; Khan, S; Zeeba, JS; Hassan, MJ; Kapoor, P
Visceral leishmaniaisis (kala-azar) is a disseminated proto- zoal infection, transmitted by sandfly bite, in which macro- phages of the liver, spleen, and bone marrow are preferentially parasitized and support intracellular replication. Most human infections caused by visceralizing strains of Leishmania are probably subclinical (13, 101, 139), attesting to innate resis- tance or, more likely, to T (Th1)-cell-dependent immune re- sponses
HENRY W. MURRAY
The adverse metabolic consequences of obesity are best predicted by the quantity of visceral fat. Excess glucocorticoids produce visceral obesity and diabetes, but circulating glucocorticoid levels are normal in typical obesity. Glucocorticoids can be produced locally from inactive 11-keto forms through the enzyme 11beta hydroxysteroid dehydrogenase type 1 (11beta HSD-1). We created transgenic mice overexpressing 11beta HSD-1 selectively in adipose
Hiroaki Masuzaki; Janice Paterson; Hiroshi Shinyama; Nicholas M. Morton; John J. Mullins; Jonathan R. Seckl; Jeffrey S. Flier
A 27 year old man with intestinal pseudo-obstruction who developed parenteral nutrition induced hyperlipidaemia and who also had ophthalmoplegia and an undifferentiated myopathy is described. Histological examination of biopsy specimens and molecular analysis show that this patient had both familial visceral myopathy and a mitochondrial myopathy, suggesting that a mitochondrial DNA mutation is the molecular lesion in familial visceral myopathy. Images Figure 2 Figure 3 Figure 4 Figure 5
Lowsky, R; Davidson, G; Wolman, S; Jeejeebhoy, K N; Hegele, R A
The 5-HT(4) receptor agonist tegaserod (TEG) has been reported to modulate visceral pain. However, the underlying mechanism remains unknown. The objective of the present study was to examine the analgesic mechanism and site of action of TEG. In male rats, visceral pain was assessed by measuring visceromotor response (VMR) to colorectal distension (CRD). Inflammation was induced by intracolonic injection of tri-nitrobenzene sulfonic acid (TNBS). The effect of TEG on the VMR was tested by injecting intraperitoneal (i.p.), intrathecal (i.t.), intracerebroventricular (i.c.v) or in the rostroventral medulla (RVM). The effect of the drug was also tested on responses of CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons. Systemic injection of TEG attenuated VMR in naive and TNBS-treated rats. Similarly, supraspinal, but not spinal, injection of TEG attenuated the VMR. While GR113808, (selective 5-HT(4) antagonist) blocked the effect, naloxone (NLX) an opioid receptor antagonist reversed the effect of TEG. Although i.t. NLX did not block the inhibitory effect of TEG in VMR study, i.t. injection of ?2-adrenergic receptor antagonist yohimbine blocked the effect of TEG when given systemically. While TEG had no effect on the responses of CRD-sensitive PNA, it inhibited the responses of CRD-sensitive LS neurons in spinal intact condition. This inhibition was blocked by GR113808, NLX and ?-funaltrexamine (?-FNA) when injected into the RVM. Results indicate that TEG produces analgesia via activation of supraspinal 5-HT(4) receptors which triggers the release of opioids at supraspinal site, which activates descending noradrenergic pathways to the spinal cord to produce analgesia. PMID:24334068
Sengupta, Jyoti N; Mickle, Aaron; Kannampalli, Pradeep; Spruell, Russell; McRorie, John; Shaker, Reza; Miranda, Adrian
There is a link between visceral white adipose tissue (WAT) and the metabolic syndrome in humans, with health improvements produced with small visceral WAT reduction. By contrast, subcutaneous WAT provides a site for lipid storage that is rather innocuous relative to ectopic lipid storage in muscle or liver. The sympathetic nervous system (SNS) is the principal initiator for lipolysis in WAT by mammals. Nothing is known, however, about the central origins of the SNS circuitry innervating the only true visceral WAT in rodents, mesenteric WAT (MWAT), which drains into the hepatic portal vein. We tested whether the central sympathetic circuits to subcutaneous [inguinal WAT (IWAT)] and visceral WAT (MWAT) are separate or shared and whether they possess differential sympathetic drives with food deprivation in Siberian hamsters. Using two isogenic strains of pseudorabies virus, a retrograde transneuronal viral tract tracer within the same hamsters, we found some overlap (?20-55% doubly infected neurons) between the two circuitries across the neural axis with lesser overlap proximal to the depots (spinal cord and sympathetic chain) and with more neurons involved in the innervation of IWAT than MWAT in some brain regions. Food deprivation triggered a greater sympathetic drive to subcutaneous (IWAT) than visceral (MWAT) depots. Collectively, we demonstrated both shared and separate populations of brain, spinal cord, and sympathetic chain neurons ultimately project to a subcutaneous WAT depot (IWAT) and the only visceral WAT depot in rodents (MWAT). In addition, the lipolytic stimulus of food deprivation only increased SNS drive to subcutaneous fat (IWAT). PMID:24452544
Nguyen, Ngoc Ly T; Randall, Jessica; Banfield, Bruce W; Bartness, Timothy J
To identify the upstream signals of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy (TLE), we evaluated by immunohistochemistry and confocal microscopy brain tissues of 13 TLE patients and 5 control patients regarding expression of chemokines and cell-cycle proteins. The chemokine RANTES (CCR5) and other CC-chemokines and apoptotic markers (caspase-3, -8, -9) were expressed in lateral temporal cortical and hippocampal neurons of TLE patients, but not in neurons of control cases. The chemokine RANTES is usually found in cytoplasmic and extracellular locations. However, in TLE neurons, RANTES was displayed in an unusual location, the neuronal nuclei. In addition, the cell-cycle regulatory transcription factor E2F1 was found in an abnormal location in neuronal cytoplasm. The pro-inflammatory enzyme cyclooxygenase-2 and cytokine interleukin-1? were expressed both in neurons of patients suffering from temporal lobe epilepsy and from cerebral trauma. The vessels showed fibrin leakage, perivascular macrophages and expression of IL-6 on endothelial cells. In conclusion, the cytoplasmic effects of E2F1 and nuclear effects of RANTES might have novel roles in neuronal apoptosis of TLE neurons and indicate a need to develop new medical and/or surgical neuroprotective strategies against apoptotic signaling by these molecules. Both RANTES and E2F1 signaling are upstream from caspase activation, thus the antagonists of RANTES and/or E2F1 blockade might be neuroprotective for patients with medically intractable temporal lobe epilepsy. The results have implications for the development of new medical and surgical therapies based on inhibition of chemotactic and mitogenic stimuli of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy.
Fiala, Milan; Avagyan, Hripsime; Merino, Jose Joaquin; Bernas, Michael; Valdivia, Juan; Espinosa-Jeffrey, Araceli; Witte, Marlys; Weinand, Martin
Loin pain haematuria syndrome (LPHS) is a severe renal pain condition of uncertain origin and often resistant to treatment. Nephrectomy and renal autotrasplantation have occasionally been performed in very severe cases. Its pathogenesis is controversial. A 40-year-old hypertensive lady was diagnosed with LPHS after repeated diagnostic imaging procedures had ruled out any renal, abdominal or spinal conditions to justify pain. Notwithstanding treatment with three drugs, she had frequent hypertensive crises during which the loin pain was dramatically exacerbated. Vascular causes of the pain and hypertension were investigated and excluded. Her renal function was normal. The patient was referred to a multidisciplinary pain clinic, but had no significant improvement in her pain symptoms despite the use of non-steroidal anti-inflammatory drugs, adjuvant antidepressants and opioid-like agents. The pain and the discomfort were so severe that her quality of life was very poor, and her social and professional activities were compromised. Nephrectomy and renal autotransplantation have occasionally been performed in these cases. Since visceral pain signals flow through afferent sympathetic fibres, we felt that percutaneous catheter-based radiofrequency ablation of the renal sympathetic nerve fibres (recently introduced for the treatment of drug-resistant hypertension) could be valuable for pain relief. We treated the patient with radiofrequency ablation (Medtronic Symplicity Catheter) applied only to the right renal artery. After a 6-month follow-up, the patient is pain free and normotensive with all drugs withdrawn. She has experienced no hypertensive crises in the meantime. This observation suggests that percutaneous sympathetic denervation could prove to be an effective mini-invasive strategy for the treatment of chronic renal pain, and LPHS in particular. PMID:23658250
Gambaro, Giovanni; Fulignati, Pierluigi; Spinelli, Alessio; Rovella, Valentina; Di Daniele, Nicola
Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of MARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus. PMID:19030215
Lemoine, Maud; Revaux, Aurelie; Francoz, Claire; Ducarme, Guillaume; Brechignac, Sabine; Jacquemin, Emmanuel; Uzan, Michele; Ganne-Carrie, Nathalie
This article describes and evaluates an integrative pain therapy model as a beneficial form of pain-management for chronic\\u000a pain. The author based his model on cognitive-behavioral modalities, progressive relaxation combined with art therapy, sensory\\u000a awareness combined with indirect clinical hypnosis, formal clinical hypnosis and self-hypnosis. Those techniques were applied\\u000a in small group settings to systematically alter pain perception, pain interpretations
AIM: To prove the hypothesis that patients with chronic pancreatitis would show increased theta activity during painful visceral stimulation. METHODS: Eight patients and 12 healthy controls underwent an experiment where the esophagus was electrically stimulated at the pain threshold using a nasal endoscope. The electroencephalogram (EEG) was recorded from 64 surface electrodes and “topographic matching pursuit” was used to extract the EEG information in the early brain activation after stimulation. RESULTS: A major difference between controls and patients were seen in delta and theta bands, whereas there were only minor differences in other frequency bands. In the theta band, the patients showed higher activity than controls persisting throughout the 450 ms of analysis with synchronous brain activation between the channels. The main theta components oscillated with 4.4 Hz in the patients and 5.5 Hz in the controls. The energy in the delta (0.5-3.5 Hz) band was higher in the controls, whereas the patients only showed scattered activity in this band. CONCLUSION: The differences in the theta band indicate that neuropathic pain mechanisms are involved in chronic pancreatitis. This has important implications for the understanding and treatment of pain in these patients, which should be directed against drugs with effects on neuropathic pain disorders.
Drewes, Asbj?rn M; Gratkowski, Maciej; Sami, Saber AK; Dimcevski, Georg; Funch-Jensen, Peter; Arendt-Nielsen, Lars
A 61-year-old man presented with diffuse myalgia and arthralgia. The physical examination showed diffuse musculoskeletal tenderness and joint stiffness without the presence of synovitis or arthritis. Nerve conduction study showed combined mild axonal degenerative and demyelinating change. Muscle biopsy analysis showed unspecific mild muscle atrophy with myopathic changes found on electromyography. A diagnosis of isolated adrenocorticotropic hormone deficiency was made on the basis of endocrinological evaluation. The widespread musculoskeletal pain resolved as a result of administration of physiological dose of hydrocortisone replacement. In a patient with unexplained rheumatic symptoms, adrenocortical insufficiency should be considered in the possible aetiology.
Hoshino, Chisho; Satoh, Noriyuki; Narita, Masashi; Kikuchi, Akio; Inoue, Minoru
Background & Aims: Visceral hypersensitivity was detected in patients with functional gastrointestinal disorders and has been proposed as a biological marker of irritable bowel syndrome (IBS). The purpose of this study was to assess the sensitivity, specificity, and the predictive values of pain thresholds evaluated by rectal distention using an electronic barostat in patients with or without IBS and in
Mickael Bouin; Victor Plourde; Michel Boivin; Monique Riberdy; France Lupien; Marie Laganière; Pierre Verrier; Pierre Poitras
The effects of tramadol versus placebo administration on behavioral indicators of ureteral pain, pelvic pain and referred lumbar muscle hyperalgesia were investigated in a rat model of viscero-visceral hyperalgesia from endometriosis plus ureteral calculosis (endo + stone). Fifty female Sprague-Dawley rats underwent surgical induction of endometriosis and, 2 weeks later, were randomly assigned to five groups (10 each), to be treated i.p., twice a day, with tramadol (0.625, 1.25, 2.5, or 5 mg/kg) or saline for 5 days (14-18th day postendometriosis; prestone treatment). On the 21st day, they underwent laparotomy for stone formation in the upper left ureter (dental cement injection). All were video-taped 24 h nonstop for 7 days before and 4 days after stone formation (14-25th day postendometriosis) to record ureteral and pelvic pain behaviors. Lumbar sensitivity (L1) was tested bilaterally, daily over the same period, by verifying presence/absence of vocalization upon muscle pinching at a predefined pressure (calibrated forceps). Additional fifty endo + stone rats underwent the same protocol, except that treatment was performed on 21st-25th day (poststone treatment). Tramadol vs. saline significantly reduced number and duration of ureteral crises, duration of pelvic behavior, and incidence of muscle hyperalgesia (P < 0.0001), with a dose-dependent effect. Prestone treatment was significantly more effective than poststone treatment for the 1.25 dose for all parameters and 2.5 dose for pelvic and muscle parameters (0.003 > P < 0.02). Tramadol, even at low doses, is thus highly protective against pain from 'viscero-visceral hyperalgesia' in endometriosis plus ureteral calculosis; it can represent a valid therapeutic approach in women with these comorbidities. PMID:23786290
Lopopolo, Mariangela; Affaitati, Giannapia; Fabrizio, Alessandra; Massimini, Francesca; Lapenna, Domenico; Giamberardino, Maria Adele; Costantini, Raffaele
The interface between psychiatry and stress-related gastrointestinal disorders (GI), such as irritable bowel syndrome (IBS), is well established, with anxiety and depression the most frequently occurring comorbid conditions. Moreover, stress-sensitive Wistar Kyoto (WKY) rats, which display anxiety- and depressive-like behaviors, exhibit GI disturbances akin to those observed in stress-related GI disorders. Additionally, there is mounting preclinical and clinical evidence implicating mast cells as significant contributors to the development of abdominal visceral pain in IBS. In this study we examined the effects of the rat connective tissue mast cell (CTMC) stabiliser, disodium cromoglycate (DSCG) on visceral hypersensitivity and colonic ion transport, and examined both colonic and peritoneal mast cells from stress-sensitive WKY rats. DSCG significantly decreased abdominal pain behaviors induced by colorectal distension in WKY animals independent of a reduction in colonic rat mast cell mediator release. We further demonstrated that mast cell-stimulated colonic ion transport was sensitive to inhibition by the mast cell stabiliser DSCG, an effect only observed in stress-sensitive rats. Moreover, CTMC-like mast cells were significantly increased in the colonic submucosa of WKY animals, and we observed a significant increase in the proportion of intermediate, or immature, peritoneal mast cells relative to control animals. Collectively our data further support a role for mast cells in the pathogenesis of stress-related GI disorders.
Carroll, Siobhan Yvonne; O'Mahony, Siobhain Mary; Grenham, Susan; Cryan, John Francis; Hyland, Niall Patrick
A series of experiments in monkeys utilizing the fluorescent tracer substances, FB and NY, injected into the ciliary ganglion have demonstrated labeling in three distinct regions in the mesencephalon: (1) the AM, (2) the NP, and (3) the EWN. Further, it was shown that the caudal extensions of the EWN reached to the level of the CCN of the somatic complex and that the LVC divided into a major and accessory column at the junction of the middle and posterior one-third of the somatic complex. The latter finding, ie, projections from the LVC to the ciliary ganglion in concert with the known connections of the retinorecipient areas in the pretectum with the visceral nuclei, allowed the formation of postulates about the reflex pupillary light pathways. Images FIGURE 1 A FIGURE 1 B FIGURE 1 C FIGURE 1 D FIGURE 2 FIGURE 3 A FIGURE 3 B FIGURE 4 A FIGURE 4 B FIGURE 5 A FIGURE 5 B FIGURE 6 A FIGURE 6 B FIGURE 6 C FIGURE 6 D
Burde, R M
Visceral leishmaniasis (VL) or kala-azar is a chronic protozoan infection in humans associated with significant global morbidity and mortality. The causative agent is a haemoflagellate protozoan Leishmania donovani, an obligate intracellular parasite that resides and multiplies within macrophages of the reticulo-endothelial system. Most of the existing anti-leishmanial drugs have serious side effects that limit their clinical application. As an alternate strategy, vaccination is also under experimental and clinical trials. The in vitro evaluation designed to facilitate rapid testing of a large number of drugs has been focussed on the promastigotes milt little attention on the clinically relevant parasite stage, amastigotes. Screening designed to closely reflect the situation in vivo is currently time consuming, laborious, and expensive, since it requires intracellular amastigotes and animal model. The ability to select transgenic Leishmania expressing reporter proteins, such as the green fluorescent proteins (GFP) or the luciferase opened up new possibilities for the development of drug screening models. Many experimental animal models like rodents, dogs and monkeys have been developed, each with specific features, but none accurately reproduces what happens in humans. Available in vitro and in vivo methodologies for antileishmanial drug screening and their respective advantages and disadvantages are reviewed. PMID:21321417
The aim of our study was to describe the distribution of Visceral Leishmaniasis (VL) in Italy, focusing on HIV-infected patients, to estimate the burden of the disease and the public health actions that should be undertaken. A review of official notifications and hospitalization data has been performed. From 2006 to 2008, a total of 289 cases of VL were notified; the overall notification rate was 1.63/1,000,000 (95% CI 1.45-1.83). In total, 1192 VL-associated hospitalizations were detected, with a hospitalization rate of 6.71/1,000,000 (95% CI 6.34-7.10). For the age group "? 24 years", a statistically significant increase was detected (p<0.05). A total of 68.9% (n = 821) of hospitalizations were detected in HIV-positive patients. The geographic distribution of rates revealed a significant increase in the north-eastern area of the country. Our study confirms that the epidemiological pattern of VL is changing and that, in Italy, control measures and preventive strategies should be based on not only the official notification system but also hospital data. This would lead to the identification of areas of parasite spread and to the creation of awareness campaigns geared toward general practitioners in the affected areas. Easy case detection would allow for timely public health actions and strategies for the implementation of more effective interventions for reservoir control. PMID:23999330
Abdalmaula, Giuma Harun; Barbadoro, Pamela; Marigliano, Anna; Illuminati, Diego; Di Stanislao, Francesco; D'Errico, Marcello Mario; Prospero, Emilia
At present sporadic foci of visceral leishmaniasis (VL) are encountered mainly in the natural foci. The natural foci of VL are situated mainly in valleys and foothills. In southern areas of the Turkmen SSR the majority of cases were registered in small settlements situated near wells in interbarkhan lowerings. The reservoir of pathogen here may be Vulpes vulpes and dogs and the most likely vector is Phlebotomus turanicus. In Kazakhstan cases of VL are encountered in the thickets of the Syr-Darya floodlands in Kzyl-Orda Province, where the natural reservoir of the pathogen are Canis aureus L. and Vulpes corsac, and the vector is P. smirnovi. Synanthropic foci in Dzhambul and Chimkent, where dogs were most likely the source of the infection and P. longiductus was the vector, are at present inactive. The maps have been plotted where landscape dissemination of mosquitoes (VL vectors) is compared to places of habitation of Canis aureus L. and VL incidence in humans at peaks of the disease endemia. Medical personnel should be on the look-out for VL on the whole territory with VL natural foci. PMID:2146471
Dergacheva, T I; Darchenkova, N N
The aim of this study was to examine whether severity of epilepsy, motor functioning, and epilepsy-related restrictions change in children with medically intractable epilepsy who are ineligible for epilepsy surgery. The study was a prospective, longitudinal, 2-year follow-up of 28 children (14 females, 14 males). Their median age was 6 years 1 month (range 7mo-15y 4mo). Seizure types were: complex partial seizures (n=16), secondary generalized seizures (n=7), simple partial seizures (n=2), and mixed seizures (n=3). Severity of seizures, motor impairments, motor development, activities of daily life, and epilepsy-related restrictions were rated at baseline and 6, 12, and 24 months thereafter. Seizure severity did not change significantly, nor did muscle strength, range of motion, or muscle tone. Motor retardation was ubiquitous but did not increase in 20 children without spasticity. Motor function of eight children with spasticity improved (Gross Motor Function Measure: baseline 70.5 [SD 35.5]; 24 months later 81.6 [SD 29.6], p < 0.05) but remained below reference values in four children. In the entire group, functional skills increased and caregiver assistance lessened. Restrictions did not change significantly. We conclude that during a 2-year follow-up period, in children with medically intractable epilepsy who do not have surgical intervention, seizure severity does not deteriorate, motor impairments do not increase, motor development does not deflect negatively, and activities of daily living and restrictions do not worsen. PMID:17355479
van Empelen, Ron; Helders, Paul J M; van Rijen, Peter C; Jennekens-Schinkel, Aag; van Nieuwenhuizen, Onno
Summary Background and purpose Serotonin is a major regulator of structural brain plasticity, which may occur following cortical resection in humans. In this study we used positron emission tomography (PET) with alpha[11C]methyl-L-tryptophan (AMT) to evaluate serotonergic alterations in subcortical structures following cortical resection in children with intractable epilepsy. Methods AMT uptake in the thalamus and lentiform nucleus was evaluated postoperatively (1–89 months following resection) in 19 children (mean age: 8.7 years) with a previous cortical resection due to intractable epilepsy. Ten children with partial epilepsy but without resection and seven normal children served as controls. Results There was an increased AMT uptake in the lentiform nucleus ipsilateral to the resection as compared to the contralateral side (mean asymmetry: 4.2 ± 3.0%), and the asymmetries were significantly higher than those measured in the control groups (p ? 0.001). Post-resection asymmetry indices in the lentiform nucleus correlated inversely with postoperative time (r = ?0.67; p = 0.002), but not with age (p = 0.29) or the extent of resection (p = 0.77). In contrast, thalamic AMT uptake asymmetries were not different among the three groups (p = 0.63). Conclusions Cortical resection results in a sustained increase of AMT uptake in the lentiform nucleus, suggesting increased serotonin synthesis. Serotonergic activation in the deafferented striatum may play a role in the functional reorganization of cortico-striatal projections in humans.
Chugani, Harry T.; Juhasz, Csaba; Chugani, Diane C.; Lawrenson, Lesley; Muzik, Otto; Chakraborty, Pulak K.; Sood, Sandeep
The aim of the present study was to shed light on the executive functioning deficits that might differentiate children with frontal lobe epilepsy (FLE) from children with temporal lobe epilepsy (TLE). Participants included 19 youth with intractable FLE and 47 youth with intractable TLE. Participants completed the Wisconsin Card Sorting Test (WCST), verbal fluency, Trail Making Test (Trails A and B), Digit Span Forward (DSF), and Digit Span Backward (DSB). When compared to the normative sample, the FLE group performed significantly worse on DSF, DSB, Trails B, and the WCST. Similarly, the TLE group performed significantly worse on DSF and DSB compared to the normative sample. Youth with FLE had significantly greater difficulty on the WCST compared to the TLE group. Overall, the results indicated that youth with FLE had significantly greater difficulty with concept formation compared to children with TLE. No differences between groups emerged on tasks assessing attention, working memory, mental flexibility, or rapid word retrieval. Both groups performed significantly below the normative sample levels on attention and working memory tasks. As a whole, it appears that some, although not all, executive dysfunction is specific to FLE. PMID:23246148
Longo, Carmelinda A; Kerr, Elizabeth N; Smith, Mary Lou
Most patients with herpes simplex virus Type I encephalitis experience an acute, monophasic illness. Chronic encephalitis is much less common, and few late relapses are associated with intractable seizure disorders. A 10-year-old boy was admitted to our institution for intractable epilepsy as part of an evaluation for epilepsy surgery. His history was significant for herpes meningitis at age 4 months. At that time, he presented to an outside hospital with fever for three days, with acyclovir treatment beginning on day 4 of his 40-day hospital course. He later developed infantile spasms and ultimately a mixed seizure disorder. Video electroencephalogram showed a Lennox-Gastaut-type pattern with frequent right frontotemporal spikes. Imaging studies showed an abnormality in the right frontal operculum. Based on these findings, he underwent a right frontal lobectomy. Neuropathology demonstrated chronic granulomatous inflammation with focal necrosis and mineralizations. Scattered lymphocytes, microglial nodules and nonnecrotizing granulomas were present with multinucleated giant cells. Immunohistochemistry for herpes simplex virus showed focal immunoreactivity. After undergoing acyclovir therapy, he returned to baseline with decreased seizure frequency. This rare form of herpes encephalitis has only been reported in children, but the initial presentation of meningitis and the approximate 10-year-time interval in this case are unusual.
Hackney, James R.; Harrison, D. Keith; Rozzelle, Curtis; Kankirawatana, Suthida; Kankirawatana, Pongkiat; Palmer, Cheryl Ann
Mutations of the gene encoding the ?1 subunit of neuronal sodium channel, SCN1A, are reported to cause Dravet syndrome (DS). The prevalence of mutations reported in such studies (mainly in clinically confirmed DS) seems high enough to make genetic diagnosis feasible. In fact, commercially operating genetic diagnostic laboratories offering genetic analyses of SCN1A are available. Still, the exact prevalence of mutations of SCN1A remains elusive. Fukuoka University has been serving as a genetic diagnostic laboratory for DS for the last 10 years. In this study, we determined the prevalence of SCN1A mutations (SCN1A, SCN2A, SCN1B and SCN2B) in 448 patients with suspected DS and intractable childhood epilepsy. A total of 192 SCN1A mutations were identified in 188 of 448 patients (42.0%). The frequencies of SCN1A mutations in suspected severe myoclonic epilepsy of infancy (SMEI), its borderline phenotype (SMEB) and intractable epilepsy were 56.2%, 41.9% and 28.9% respectively. In addition, four SCN2A mutations were identified in 4 of 325 patients. No mutations of SCN1B and SCN2B were identified. These results are potentially helpful for the diagnosis of DS at early stage. PMID:23195492
Wang, Ji-wen; Shi, Xiu-yu; Kurahashi, Hirokazu; Hwang, Su-Kyeong; Ishii, Atsushi; Higurashi, Norimichi; Kaneko, Sunao; Hirose, Shinichi
role of gabapentin in pain treatment will be discussed with an attempt to identify pain symptoms that are likely to be responsive to gabapentin; 2) animal stud- ies of gabapentin on neuropathic pain and other pain behaviors will be evaluated; and 3) possible mecha- nisms of gabapentin actions will be considered in re- lation to mechanisms of neuropathic pain in
Jianren Mao; Lucy L. Chen
Neuropathic cranial pain, i.e. pain due to central or peripheral nervous system damage localized in cranial area, is a clinical challenge for the neurologist. Despite major advances in knowledge of physiology and biochemistry of pain, relief for many patients suffering from neuropathic pain remains incomplete. Adjuvant analgesics play a key role in the management of neuropathic pain. The introduction in
B. Colombo; P. O. L. Annovazzi; G. Comi
Background: Urolithiasis refers to renal or ureteral calculi referred to in lay terminology as a kidney stone. Utolithiasis is a potential emergency often resulting in acute abdominal, low back, flank or groin pain. Chiropractors may encounter patients when they are in acute pain or after they have recovered from the acute phase and should be knowledgeable about the signs, symptoms, potential complications and appropriate recommendations for management. Case presentation: A 52 year old male with acute right flank pain presented to the emergency department. A ureteric calculus with associated hydronephrosis was identified and he was prescribed pain medications and discharged to pass the stone naturally. One day later, he returned to the emergency department with severe pain and was referred to urology. He was managed with a temporary ureteric stent and antibiotics. Conclusion: This case describes a patient with acute right flank and lower quadrant pain which was diagnosed as an obstructing ureteric calculus. Acute management and preventive strategies in patients with visceral pathology such as renal calculi must be considered in patients with severe back and flank pain as it can progress to hydronephrosis and kidney failure.
Chung, Chadwick; Stern, Paula J.; Dufton, John
The Canine Visceral Leishmaniasis is a worldwide distributed zoonosis caused by protozoa of the genus Leishmania and Leishmania chagasi is the causal agent of the disease in Brazil. The transmission between vertebrate hosts occurs through the bite of a phlebotomine, whose main representative in the country is the Lutzomyia longipalpis. The disease has been described in some cities, presenting important
Object Vagus nerve stimulation (VNS) is a viable option for patients with medically intractable epilepsy. However, there are no studies examining its effect on individuals with brain tumor associated intractable epilepsy. This study aims to evaluate the efficacy of VNS in patients with brain tumor associated medically intractable epilepsy. Methods Epilepsy surgery databases at two separate epilepsy centers were reviewed to identify patients in whom a VNS was placed for tumor-related intractable epilepsy between January 1999 and December 2011. Pre-operative and post-operative seizure frequency and type as well as antiepileptic drug (AED) regimens and degree of tumor progression were evaluated. Statistical analysis was performed using odds ratio and T tests to examine efficacy. Results Sixteen patients were included in the study. Eight patients (50%) had an improved outcome (Engel I, II, or III) with an average follow-up of 39.6 months. The mean reduction in seizure frequency was 41.7% (p = .002). There was no significant change in AED regimens. Seizure frequency decreased by 10.9% in patients with progressing tumors and 65.6% in patients with stable tumors (p = .008). Conclusion VNS therapy in individuals with brain tumor associated medically intractable epilepsy was shown to be comparably effective in regards to seizure reduction and response rates to the general population of VNS therapy patients. Outcomes were better in patients with stable as opposed to progressing tumors. Our findings support the recommendation of VNS therapy in patients with brain tumor associated intractable epilepsy, especially in cases where imminent tumor progression is not expected. VNS may not be indicated in more malignant tumors.
Patel, Kunal S.; Moussazadeh, Nelson; Doyle, Werner K.; Labar, Douglas R.; Schwartz, Theodore H.
SUMMARY Asimadoline is a potent ?-opioid receptor agonist with a diaryl acetamide structure. It has high affinity for the ? receptor, with IC50 of 5.6 nM (guinea pig) and 1.2 nM (human recombinant), and high selectively with ?: ?: ? binding ratios of 1:501:498 in human recombinant receptors. It acts as a complete agonist in in vitro assay. Asimadoline reduced sensation in response to colonic distension at subnoxious pressures in healthy volunteers and in IBS patients without alteration of colonic compliance. Asimadoline reduced satiation and enhanced the postprandial gastric volume (in female volunteers). However, there were no significant effects on gastrointestinal transit, colonic compliance, fasting or postprandial colonic tone. In a clinical trial in 40 patients with functional dyspepsia (Rome II), asimadoline did not significantly alter satiation or symptoms over 8 weeks. However, asimadoline, 0.5 mg, significantly decreased satiation in patients with higher postprandial fullness scores, and daily postprandial fullness severity (over 8 weeks); the asimadoline 1.0 mg group was borderline significant. In a clinical trial in patients with IBS, average pain 2 hours post-on-demand treatment with asimadoline was not significantly reduced. Post-hoc analyses suggest asimadoline was effective in mixed IBS. In a 12-week study in 596 patients, chronic treatment with asimadoline, 0.5 mg and 1.0 mg, was associated with adequate relief of pain and discomfort, improvement in pain score and number of pain free days in patients with IBS-D. The 1.0 mg dose was also efficacious in IBS-alternating. There were also weeks with significant reduction in bowel frequency and urgency. Asimadoline has been well tolerated in human trials to date.
Background Pain drawings are a diagnostic adjunct to history taking, clinical examinations, and biomedical tests in evaluating pain. We hypothesized that somatoform-functional pain, is mirrored in distinctive graphic patterns of pain drawings. Our aim was to identify the most sensitive and specific graphic criteria as a tool to help identifying somatoform-functional pain. Methods We compared 62 patients with somatoform-functional pain with a control group of 49 patients with somatic-nociceptive pain type. All patients were asked to mark their pain on a pre-printed body diagram. An investigator, blinded with regard to the patients’ diagnoses, analyzed the drawings according to a set of numeric or binary criteria. Results We identified 13 drawing criteria pointing with significance to a somatoform-functional pain disorder (all p-values???0.001). The most specific and most sensitive criteria combination for detecting somatoform-functional pain included the total number of marks, the length of the longest mark, and the presence of symmetric patterns. The area under the ROC-curve was 96.3% for this criteria combination. Conclusion Pain drawings are an easy-to-administer supplementary technique which helps to identify somatoform-functional pain in comparison to somatic-nociceptive pain.
We have investigated nine patients with cemented Furlong (JRI, London, UK) titanium hip replacements who presented with early pain despite a well-fixed, aseptic prosthesis. All were followed up clinically and radiologically at regular intervals. Pain was located in the thigh and was worse at night. Radiographs showed cortical hypertrophy of the femur around the tip of the stem. Eight of the nine patients subsequently required single-stage revision using an uncemented prosthesis, which relieved the pain. At revision, the pH of the tip of the stem was found to be highly acidic with macroscopic evidence of corrosion consisting of multiple layers of titanium oxides when studied by X-ray dispersive analysis. Cemented titanium implants have a potential for crevice corrosion leading to cortical hypertrophy and intractable pain. PMID:14765860
Hallam, P; Haddad, F; Cobb, J
BACKGROUND: The use of opioids for chronic noncancer pain (CNCP) remains very controversial. There are several randomized controlled trials, mostly in neuropathic pain, reporting efficacy and safety in the short term, but more long-term data are needed. Randomized controlled trials may be limited in providing data about the patients who benefit from often high-dose opioids over the long term. The present article provides details of these patients and adds to a previous case series. METHODS: The present article contains 17 case reports of 11 CNCP conditions (followed to 2011) selected to illustrate specific issues from a survey of 84 patients with intractable CNCP treated with opioids and followed every three months for a median of 11 years. The previous published survey of this group reported outcomes of pain severity, adverse effects, pain relief, satisfaction, mood, problematic opioid use, tolerance, physical dependency, functional status, health-related quality of life (HRQL), immune status and sexual function. The outcome measures for that study included a numerical rating scale for pain, the Hospital Anxiety and Depression Scale, the Brief Pain Inventory Interference Scale, the Pain Disability Index and, for HRQL, the Short-Form Health Survey 12 version 2. Most patients in the total sample reported 50% or greater relief and a moderate improvement in disability. Scores for functional status and HRQL were not severely affected. Problematic use, tolerance and serious adverse effects, including constipation, were not major issues. These selected patient reports were chosen, not to illustrate optimal results, but rather important aspects of the diagnoses, opioids and doses, the paucity of intolerable adverse effects, particular issues (concurrent addiction history, bipolar disorder and combination therapy), disease-specific and other outcomes and duration of follow-up with complex pain problems. RESULTS: Opioids were found to be safe and useful in the long term for these particular patients, as well as in the larger group from which they originated. INTERPRETATION: These 17 reports of patients with intractable CNCP treated with opioids with some success over many years puts a face on more of the participants in the larger survey of 84 subjects, suggesting that this approach is effective and safe for some patients over many years.
Watson, C Peter N
Trace elements represent a group of essential metals or metaloids necessary for life, present in minute amounts. Analgesic adjuvants can enhance the effect of other pain drugs or be used for pain control themselves. Previous studies on the effects of trace elements on nociception and their potential use as analgesic adjuvants have yielded conflicting results. In this study, we tested the hypothesis that three vital trace elements (Zn²?, Mg²?, Cu²?) have direct antinociceptive effects. Groups of eight Swiss mice were intraperitoneally (i.p) injected with incremental concentrations of Zn²? sulfate (0.5, 2.0 mg/kg), Zn²? citrate (0.125, 0.5 mg/kg), Mg²? chloride (37.5, 75, 150 mg/kg), Cu²? chloride (0.5, 1.0, 2.0 mg/kg), and Cu²? sulfate (0.5, 1.0 mg/kg) or saline (control). Evaluations were made by hot plate (HP) and tail flick (TF) tests for central antinociceptive effect, writhing test (WT) for visceral antinociceptive effect, and activity cage (AC) test for spontaneous behavior. Zn²? induced pain inhibition in HP/TF tests (up to 17%) and WT (up to 25%), with no significant differences among the salts used. Mg²? salts induced pain inhibition for all performed tests (up to 85% in WT). Cu²? salts showed antinociceptive effects for HP/TF (up to 28.6%) and WT (57.28%). Only Mg²? and Cu²? salts have displayed significant effects in AC (Mg²? anxiolytic/depressant effect; Cu²? anxiolytic effect). We interpret these data to mean that all tested trace elements induced antinociceptive effects in central and visceral pain tests. Our data indicate the potential use of these cheap adjuvants in pain therapy. PMID:23362003
Tamba, Bogdan I; Leon, Maria-Magdalena; Petreus, Tudor
Five patients with multiple sebaceous neoplasms of the skin in association with multiple visceral cancers are reported. The visceral cancers involved particularly the gastrointestinal tract, and multiple adenocarcinomas of the colon were common. This repo...
D. B. Rulon E. B. Helwig
Background In the context of increasing obesity prevalence, the relationship between large visceral adipose tissue (VAT) volumes and type 2 diabetes mellitus (T2DM) is unclear. In a clinical sample of severely obese women (mean body mass index [BMI], 46 kg/m2) with fasting normoglycemia (n=40) or dysglycemia (impaired fasting glucose+diabetes; n=20), we sought to determine the usefulness of anthropometric correlates of VAT and associations with dysglycemia. Methods VAT volume was estimated using multi-slice computer tomography; anthropometric surrogates included sagittal abdominal diameter (SAD), waist circumference (WC) and BMI. Insulin sensitivity (Si), and beta-cell dysfunction, measured by insulin secretion (AIRg) and the disposition index (DI), were determined by frequently sampled intravenous glucose tolerance test. Results Compared to fasting normoglycemic women, individuals with dysglycemia had greater VAT (P<0.001) and SAD (P=0.04), but BMI, total adiposity and Si were similar. VAT was inversely associated with AIRg and DI after controlling for ancestry, Si, and total adiposity (standardized beta, ?0.32 and ?0.34, both P<0.05). In addition, SAD (beta=0.41, P=0.02) was found to be a better estimate of VAT volume than WC (beta=0.32, P=0.08) after controlling for covariates. Receiver operating characteristic analysis showed that VAT volume, followed by SAD, outperformed WC and BMI in identifying dysglycemic participants. Conclusions Increasing VAT is associated with beta-cell dysfunction and dysglycemia in very obese women. In the presence of severe obesity, SAD is a simple surrogate of VAT, and an indicator of glucose dysregulation.
Kahn, Henry S.; Gasevic, Danijela; Liang, Zhe; Frediani, Jennifer K.; Torres, William E.; Ziegler, Thomas R.; Phillips, Lawrence S.; Lin, Edward
Arylimidamides (AIAs) represent a new class of molecules that exhibit potent antileishmanial activity (50% inhibitory concentration [IC50], <1 ?M) against both Leishmania donovani axenic amastigotes and intracellular Leishmania, the causative agent for human visceral leishmaniasis (VL). A systematic lead discovery program was employed to characterize in vitro and in vivo antileishmanial activities, pharmacokinetics, mutagenicities, and toxicities of two novel AIAs, DB745 and DB766. They were exceptionally active (IC50 ? 0.12 ?M) against intracellular L. donovani, Leishmania amazonensis, and Leishmania major and did not exhibit mutagenicity in an Ames screen. DB745 and DB766, given orally, produced a dose-dependent inhibition of liver parasitemia in two efficacy models, L. donovani-infected mice and hamsters. Most notably, DB766 (100 mg/kg of body weight/day for 5 days) reduced liver parasitemia in mice and hamsters by 71% and 89%, respectively. Marked reduction of parasitemia in the spleen (79%) and bone marrow (92%) of hamsters was also observed. Furthermore, these compounds distributed to target tissues (liver and spleen) and had a moderate oral bioavailability (up to 25%), a large volume of distribution, and an elimination half-life ranging from 1 to 2 days in mice. In a repeat-dose toxicity study of mice, there was no indication of liver or kidney toxicity for DB766 from serum chemistries, although mild hepatic cell eosinophilia, hypertrophy, and fatty changes were noted. These results demonstrated that arylimidamides are a promising class of molecules that possess good antileishmanial activity and desirable pharmacokinetics and should be considered for further preclinical development as an oral treatment for VL.
Wang, Michael Zhuo; Zhu, Xiaohua; Srivastava, Anuradha; Liu, Qiang; Sweat, J. Mark; Pandharkar, Trupti; Stephens, Chad E.; Riccio, Ed; Parman, Toufan; Munde, Manoj; Mandal, Swati; Madhubala, Rentala; Tidwell, Richard R.; Wilson, W. David; Boykin, David W.; Hall, James Edwin; Kyle, Dennis E.; Werbovetz, Karl A.
Pre-clinical bone cancer pain models mimicking the human condition are required to respond to clinical realities. Breast or prostate cancer patients coping with bone metastases experience intractable pain, which affects their quality of life. Advanced monitoring is thus required to clarify bone cancer pain mechanisms and refine treatments. In our model of rat femoral mammary carcinoma MRMT-1 cell implantation, pain onset and tumor growth were monitored for 21 days. The surgical procedure performed without arthrotomy allowed recording of incidental pain in free-moving rats. Along with the gradual development of mechanical allodynia and hyperalgesia, behavioral signs of ambulatory pain were detected at day 14 by using a dynamic weight-bearing apparatus. Osteopenia was revealed from day 14 concomitantly with disorganization of the trabecular architecture (µCT). Bone metastases were visualized as early as day 8 by MRI (T1-Gd-DTPA) before pain detection. PET (Na18F) co-registration revealed intra-osseous activity, as determined by anatomical superimposition over MRI in accordance with osteoclastic hyperactivity (TRAP staining). Pain and bone destruction were aggravated with time. Bone remodeling was accompanied by c-Fos (spinal) and ATF3 (DRG) neuronal activation, sustained by astrocyte (GFAP) and microglia (Iba1) reactivity in lumbar spinal cord. Our animal model demonstrates the importance of simultaneously recording pain and tumor progression and will allow us to better characterize therapeutic strategies in the future.
Dore-Savard, Louis; Otis, Valerie; Belleville, Karine; Lemire, Myriam; Archambault, Melanie; Tremblay, Luc; Beaudoin, Jean-Francois; Beaudet, Nicolas; Lecomte, Roger; Lepage, Martin; Gendron, Louis; Sarret, Philippe
This article examines the use of lobotomy as a treatment for chronic intractable pain and reconstructs then-common perceptions of pain and of the patients who suffered from it. It delineates the social expectations and judgments implicit in physicians' descriptions of the patients, analyzing what was expected from such patients and how the medical establishment responded to non-normative expressions of suffering. I argue that the medicalized response to an expectation for normativity demonstrates the convergence between psychiatric and palliative interventions. Based on a historically informed perspective of psychiatric interventions in the field of pain medicine, I examine the use of psychiatric medications for pain syndromes today and evaluate the interface between depression, chronic pain, and terminal illness. While not detracting from the medical imperative to alleviate pain, I question the usage of social criteria and normative judgments in the clinical decision of how to treat pain. What normalizing social function does the use of psychiatric interventions in pain treatment fulfill? This approach leads to a reexamination of perceptions of dualism in pain medicine. PMID:19855124
Background Chronic, intractable pain is a problem of pandemic proportions. Pain caused by nerve injuries (neuropathic pain) is extremely difficult to treat. For centuries, opiates such as morphine have been the first-line treatment for severe chronic pain. However, opiates are often ineffective against neuropathic pain, leaving few options for suffering patients. We previously demonstrated that platelet-derived growth factor- ? (PDGFR-?) inhibition completely eliminated morphine tolerance. In these studies, we determined whether PDGFR-? inhibition could improve the effectiveness of morphine for neuropathic pain treatment. Results and Findings Spinal nerve ligation was performed in male Sprague-Dawley rats. The clinically used PDGFR antagonist imatinib did not relieve mechanical pain in a nerve injury model as determined by Von Frey assay. Surprisingly, combining imatinib with a previously ineffective dose of morphine led to complete pain relief. Scavenging released PDGF-B also markedly augmented the analgesic effect of morphine. Conclusions These findings suggest the novel hypothesis that PDGF-B released by injured nerves renders animals resistant to morphine, implying that PDGFR-? inhibition could potentially eliminate the tremendous suffering caused by neuropathic pain.
Donica, Courtney L.; Cui, Yan; Shi, Shanping; Gutstein, Howard B.
Pediatric focal epilepsies often involve more extratemporal regions than adult epilepsies. This study aims to investigate the population of oligodendroglia-like cells (OLCs) in the pediatric focal epilepsy patients requiring surgery. We hypothesize that OLCs are one of the factors that extend the pediatric epileptic network in intractable epilepsy. Thirty (18 female) patients (1.8-16.9 years old with a mean of 9.7 years), who underwent resective surgery for the intractable epilepsy from 2010 to 2012 were retrospectively studied. Seizure types consisted of epileptic spasms in nine patients, partial seizures in 17 patients and partial seizure with secondary generalization in four patients. Eight autopsy cases without neurological disease served as controls. The neuropathology examination utilized the H&E/LFB stain and immunohistochemical staining for NeuN, GFAP and Olig2 as a marker of OLCs. OLCs were counted in three sites: (a) gray matter, (b) junction of gray/white matter, and (c) white matter. We also examined the correlation between the density of OLC among the three sites and the clinical features. Fifteen (50%) patients underwent multiple lobe resections, consisting of both temporal and extratemporal lobe resections in 12 patients and extratemporal lobe resections in 3 patients. The other 15 (50%) patients underwent single lobe resection including 3 (10%) patients with temporal lobectomy sparing hippocampus. Pathological diagnosis of epilepsy patients was as follows: 14 (47%) patients=focal cortical dysplasia (type I, 4; II, 9; III, 1); 6 (20%)=oligodendrogliosis; 6 (20%)=astrocytic gliosis; 2 (7%)=hyaline protoplasmic astrocytopathy and 2 (7%)=tuberous sclerosis complex. The numbers of OLCs at all three sites in epilepsy group were significantly higher than those of control group (p<0.001). In the epilepsy group, there was a significant difference among the number of OLCs at gray matter, junction of gray and white matter, and white matter (p<0.001). The number of OLCs significantly increased from gray matter and junction of gray/white matter to white matter. In the control group, there was no difference among the number of OLCs at three sites. There was no significant difference in the numbers of OLCs between focal cortical dysplasia types I and II. The significantly increased OLCs, especially in the white matter may contribute to the extensive epileptic network in children with intractable focal epilepsy. PMID:24631559
Sakuma, Satoru; Halliday, William C; Nomura, Ruka; Ochi, Ayako; Otsubo, Hiroshi
Background Psychological stress plays an important role in the onset and course of Meniere's disease. Surgical therapy and intratympanic gentamicin treatment are options for cases that are intractable to conventional medical therapy. Psychotherapy, however, including autogenic training (AT), which can be used for general relaxation, is not widely accepted. This paper describes the successful administration of AT in a subject suffering from intractable Meniere's disease. Case presentation A 51-year-old male patient has suffered from fluctuating right sensorineural hearing loss with vertigo since 1994. In May 2002, he was first admitted to our hospital due to a severe vertigo attack accompanied by right sensorineural hearing loss. Spontaneous nystagmus toward the right side was observed. Since April 2004, he has experienced vertigo spells with right-sided tinnitus a few times per month that are intractable to conventional medical therapy. After four months, tympanic tube insertion was preformed in the right tympanic membrane. Intratympanic injection of dexamethasone was ineffective. He refused Meniett therapy and intratympanic gentamicin injection. In addition to his vertigo spells, he suffered from insomnia, tinnitus, and anxiety. Tranquilizers such as benzodiazepines and antidepressants such as serotonin selective re-uptake inhibitors (SSRIs) failed to stop the vertigo and only slightly improved his insomnia. In December 2006, the patient began psychological counseling with a psychotherapist. After brief psychological counseling along with cognitive behavior therapy (CBT), he began AT. He diligently and regularly continued his AT training in his home according to a written timetable. His insomnia, tinnitus, and vertigo spells disappeared within a few weeks after only four psychotherapy sessions. In order to master the six standard formulas of AT, he underwent two more sessions. Thereafter, he underwent follow-up for 9 months with no additional treatment. He is now free from drugs, including tranquilizers, and has continued AT. No additional treatment was performed. When we examined him six and nine months later for follow-up, he was free of vertigo and insomnia. Conclusion AT together with CBT can be a viable and palatable treatment option for Meniere's disease patients who are not responsive to other therapies.
Goto, Fumiyuki; Nakai, Kimiko; Kunihiro, Takanobu; Ogawa, Kaoru
The radiological manifestations of asbestos-related visceral pleural changes are described. Generally, visceral pleural reactions follow the mesothelial cells response to various injurious substances, including asbestos, and even saline. The changes are nonspecific. They may occur subsequent to pleural reactions associated with many conditions, which include tuberculosis, viral pleurisy, malignancy and lymphoma, lupus, or rheumatoid-induced effusions, cardiac failure, and pulmonary embolism, among other etiologies. The failure to absorb the fibrinous exudate on the visceral pleural surface can lead to the development of diffuse fibrosis of the serosal surface, interlobar pleural thickening, localized pleural filaments (strands), subpleural wedge, and lenticular-shaped masses, and could be the forerunner of lobular atelectasis (pseudotumor) formation. Some of the features are recognized on posteroanterior chest radiographs and the counterparts corroborated with the use of routine and high-resolution computed tomography studies. PMID:2008921
Toxocariasis is a cosmopolitan infection of dogs and cats with a roundworm resembling Ascaris. Man becomes infected by ingesting eggs from the environment. The infection occurs mainly in children. There are two distinct syndromes: visceral larva migrans and ocular toxocariasis. The author describes the case of a 70 year old Norwegian female with visceral larva migrans. One month after a visit to Spain she developed fever, hepatomegaly and marked eosinophilia. Liver biopsy revealed subacute hepatitis with eosinophilic leucocyte infiltration. Toxocara ELISA was strongly positive. Treatment with albendazol 400 mg b.i.d. and prednisone 10 mg daily for three weeks was successful. A clinical relapse after three months was treated in the same way for one month. Prolonged treatment is recommended. To our knowledge, this is the first reported case of visceral larva migrans in an adult Norwegian. Epidemiology, diagnosis and treatment are discussed. PMID:8928142
Viscero-somatic referral and sensitization has been well documented clinically and widely investigated, whereas viscero-visceral referral and sensitization (termed cross-organ sensitization) has only recently received attention as important to visceral disease states. Because second order neurons in the CNS have been extensively shown to receive convergent input from different visceral organs, it has been assumed that cross-organ sensitization arises by the same convergence-projection mechanism as advanced for viscero-somatic referral and sensitization. However, increasing evidence also suggests participation of peripheral mechanisms to explain referral and sensitization. We briefly summarize behavioral, morphological and physiological support of and focus on potential mechanisms underlying cross-organ sensitization.
Brumovsky, P.R.; Gebhart, G.F.
We report a case in which motor cortex stimulation (MCS) improved neuropathic facial pain due to peripheral nerve injury and restored tactile and thermal sensory loss. A 66-year-old man developed intractable trigeminal neuropathic pain after trauma of the supraorbital branch of the Vth nerve, associated with tactile and thermal sensory loss in the painful area. MCS was performed using neuronavigation and transdural electric stimulation to localize the upper facial area on the motor cortex. One month after surgery, pain was decreased from 80/100 to 20/100 on visual analogic scale, and sensory discrimination improved in the painful area. Two months after surgery, quantitative sensory testing confirmed the normalization of thermal detection thresholds. This case showed that MCS could restore tactile and thermal sensory loss, resulting from peripheral nerve injury. Although the mechanisms leading to this effect remain unclear, this observation enhanced the hypothesis that MCS acts through modulation of the sensory processing. PMID:19350361
Fontaine, Denys; Bruneto, Jean Louis; El Fakir, Hasna; Paquis, Philippe; Lanteri-Minet, Michel
Endovascular intervention can provide an alternative method of treatment for visceral artery aneurysms. We conducted a retrospective review of all patients with visceral artery aneurysms at a single university medical center from 1990 to 2003, focusing on the outcome of endovascular therapy. Sixty-five patients with visceral artery aneurysms were identified: 39 splenic (SAA), 13 renal, seven celiac, three superior mesenteric
Stephanie S. Saltzberg; Thomas S. Maldonado; Patrick J. Lamparello; Neal S. Cayne; Matthew M. Nalbandian; Robert J. Rosen; Glenn R. Jacobowitz; Mark A. Adelman; Paul J. Gagne; Thomas S. Riles; Caron B. Rockman
Clinical symptoms of chronic widespread pain (CWP) conditions including fibromyalgia (FM), include pain, stiffness, subjective weakness, and muscle fatigue. Muscle pain in CWP is usually described as fluctuating and often associated with local or generalized tenderness (hyperalgesia and/or allodynia). This tenderness related to muscle pain depends on increased peripheral and/or central nervous system responsiveness to peripheral stimuli which can be either noxious (hyperalgesia) or non-noxious (allodynia). For example, patients with muscle hyperalgesia will rate painful muscle stimuli higher than normal controls, whereas patients with allodynia may perceive light touch as painful, something that a “normal” individual will never describe as painful. The pathogenesis of such peripheral and/or central nervous system changes in CWP is unclear, but peripheral soft tissue changes have been implicated. Indirect evidence from interventions that attenuate tonic peripheral nociceptive impulses in patients with CWP syndromes like FM suggest that overall FM pain is dependent on peripheral input. More importantly, allodynia and hyperalgesia can be improved or abolished by removal of peripheral impulse input. Another potential mechanism for CWP pain is central disinhibition. However, this pain mechanism also depends on tonic impulse input, even if only inadequately inhibited. Thus a promising approach to understanding CWP is to determine whether abnormal activity of receptors in deep tissues is fundamental to the development and maintenance of this chronic pain disorder. Conclusions Most CWP patients present with focal tissue abnormalities including myofascial trigger points, ligamentous trigger points, or osteoarthritis of the joints and spine. While not predictive for the development of CWP these changes nevertheless represent important pain generators that may initiate or perpetuate chronic pain. Local chemical mediators, including lactic acid, ATP, and cytokines seem to play an important role in sensitizing deep tissue nociceptors of CWP patients. Thus the combination of peripheral impulse input and increased central pain sensitivity may be responsible for wide-spread chronic pain disorders including FM.
We report this case of a 74-year-old man with altered anatomy secondary to Billroth-II surgery who underwent endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis and subsequently developed severe diffuse abdominal pain with drop in hemoglobin. Patient was found to have hemorrhagic shock requiring aggressive resuscitative measures. Patient was found to have large peripancreatic hematoma secondary to bleeding from gastroduodenal and superior pancreaticoduodenal artery pseudoaneurysms. Gastroduodenal artery aneurysm is the rarest of all the splanchnic artery aneurysms, and to our knowledge this is the only reported case of a gastroduodenal artery pseudoaneurysm complicating ERCP.
Pseudohypoparathyroidism is a rare disorder of calcium metabolism that involves target organ resistance to the action of the parathyroid hormone. As a result, calcium levels may become dangerously low, sometimes leading to seizures and other symptoms. We present a case of a 23-year-old Somalian female on antiepileptic therapy presenting with intractable epilepsy. She was subsequently found to have pseudohypoparathyroidism type Ia. She had multiple reasons accounting for loss of seizure control, including worsening hypocalcemia from resistance to the parathyroid hormone; vitamin D deficiency, which could have resulted from lack of exposure to direct sunlight and her antiepileptic medication; and extensive calcium deposition in the brain due to pseudohypoparathyroidism. The patient was stabilized with intravenous therapy and oral calcium, vitamin D, and calcitriol. Her antiepileptic therapy was changed to a medication that did not interfere with vitamin D metabolism or contribute to worsening hypocalcemia.
Raghavan, Pooja; Katz, Charles M
Multidrug resistance mechanisms underlying the intractability of malignant melanomas remain largely unknown. In this study, we demonstrate that the development of multidrug resistance in melanomas involves subcellular sequestration of intracellular cytotoxic drugs such as cis-diaminedichloroplatinum II (cisplatin; CDDP). CDDP is initially sequestered in subcellular organelles such as melanosomes, which significantly reduces its nuclear localization when compared with nonmelanoma/KB-3-1 epidermoid carcinoma cells. The melanosomal accumulation of CDDP remarkably modulates melanogenesis through a pronounced increase in tyrosinase activity. The altered melanogenesis manifested an 8-fold increase in both intracellular pigmentation and extracellular transport of melanosomes containing CDDP. Thus, our experiments provide evidence that melanosomes contribute to the refractory properties of melanoma cells by sequestering cytotoxic drugs and increasing melanosome-mediated drug export. Preventing melanosomal sequestration of cytotoxic drugs by inhibiting the functions of melanosomes may have great potential as an approach to improving the chemosensitivity of melanoma cells. cancer | melanosomes | skin | tumor therapy | multidrug resistance
Chen, Kevin G.; Valencia, Julio C.; Lai, Barry; Zhang, Guofeng; Paterson, Jill K.; Rouzaud, François; Berens, Werner; Wincovitch, Stephen M.; Garfield, Susan H.; Leapman, Richard D.; Hearing, Vincent J.; Gottesman, Michael M.
Identification of the epileptic focus is the most important requirement for a successful surgical outcome in intractable epilepsy. Patients with normal MRI on high-resolution imaging pose a significant challenge in this regard. We tried to identify the epileptic focus using interictal / ictal SPECT and ictal EEG patterns in 14 patients with normal MRI. Rhythmic ictal onset activity helped to identify a single focus in 10 patients (71.43%). Inter ictal SPECT detected a focus corresponding to ictal EEG in 6 out of 10 patients (60%) in whom the test was performed. Ictal SPECT done in 5 patients correctly identified the focus in all patients (100%). Our data indicate that it is possible to obtain localization in patients with normal MRI using a combination of ictal EEG patterns and an ictal SPECT study. PMID:12577092
Thomas, R; Bhatia, M; Bal, C S; Gaikwad, S; Singh, V P; Jain, S
We report a case of a 5-year-old boy with intractable epilepsy who underwent therapeutic corticectomy. Histopathologic findings within the resection specimen included severe cortical dysplasia associated with abundant subpial and intraparenchymal Rosenthal fibers in a large right frontal lesion that merged into the basal ganglia. Rosenthal fiber proliferation may represent a reactive process, are frequent in pilocytic astrocytomas, and are a defining feature of Alexander disease. There was no evidence of neoplasm or leukodystrophy in this case. Genetic analysis of the specimen showed a few previously reported polymorphisms but no mutation in the GFAP gene. This case is unique among several hundred cortical resection specimens that we have studied, including numerous cases of severe cortical dysplasia. PMID:19427021
Khanlou, Négar; Mathern, Gary W; Mitchell, Wendy G; Salamon, Noriko; Pope, Whitney B; Yong, William H; Vinters, Harry V
Summary Recent studies have provided much needed data on the probability of seizure remission among adults with chronic intractable epilepsy treated medically. Here we provide an extended follow-up to our earlier study in order to provide a more comprehensive picture of long-term prognosis in this patient population during medical treatment. The prevalence cohort was followed for two outcomes—complete seizure remission for ?12 months and subsequent seizure relapse among those attaining a seizure remission. The study outcomes were estimated using Kaplan–Meier analysis. We found that the probability of attaining a ?12 months of complete seizure freedom to be approximately 3–4% per year through 8 years of follow-up. By year 5 since the start of seizure remission, the cumulative probability of seizure relapse was 81%, although only half of the patients with seizure relapse went on to experience their previous seizure frequency
Choi, Hyunmi; Heiman, Gary A.; Munger Clary, Heidi; Etienne, Mill; Resor, Stanley R.; Hauser, W. Allen
Coeliac disease (CD) is an autoimmune disorder which leads to chronic inflammation of the gut. Untreated CD is associated with upper gastrointestinal malignancies, Small-bowel lymphoma and adenocarcinoma are recognized complications of untreated coeliac disease (CD). We report the case of a 43-year-old male suffering from CD who was treated with a gluten-free diet one year, presenting with complaints of intractable nausea and vomiting. After several studies, He underwent push enteroscopy, which identified one large mass lesion in the third part of duodenum. However, histopathological examination showed adenocarcinoma. Subsequently, a duodenal segment resection was performed. After surgery, the patient recovered well and left our hospital in good condition. Clinicians should take into small bowel adenocarcinoma is rare but associated with CD particularly in CD patients with worrying symptoms such as nausea and vomiting unresponsiveness to treatment and these patients should be screened for long term complications like malignancy.
Rajabalinia, Hassan; Dabiri, Reza; Shahbazi, Shahin; Ghobakhlou, Mehdi; Bahreiny, Rasoul; Molaei, Mahsa; Nejad, Mohammad Rostami
Anti-disaster measures along with disaster medicine aims at reducing loss of property and life and facilitating grief work of the suffered people. In contrast the care system for patients with intractable disease has the same aim. According to the experiences of two large earthquakes including Chuetsu (2004) and Chuetsu-oki earthquake (2007), earthquake-resistant buildings are necessary for maintaining hospital function as well as reviving community after occurrence of large earthquake. A list of patients living with ventilator and their individual care plan designed for disaster need to be prepared to transport each patient to the hospital at appropriate timing, when electricity and visiting nurse care system are damaged. Satellite telephone is very useful for communicating with such patients and medical teams because telephone connection is limited to only the specific calling number just after occurrence of earthquake. PMID:20030235
A male patient in his thirties presented to the emergency room of our hospital after a traffic injury. He was in hemorrhagic shock and was diagnosed with a pelvic bone fracture by computed tomography. Despite a massive transfusion of red cells, platelets, and fresh frozen plasma, the bleeding was determined to be continuous because his blood pressure remained unstable and his platelet count and coagulation parameters did not improve. Because ordinary replacement therapy was ineffective, the patient was infused with fibrinogen concentrates and recombinant activated factor VII (rFVIIa), although these are off-label indications in Japan. He recovered from the hemorrhagic shock immediately after the infusion. Although there have been several reports on the management of intractable hemorrhage secondary to severe trauma using rFVIIa, we have experienced few such cases. This patient was rescued by hemostatic treatment with fibrinogen concentrates and rFVIIa. PMID:24598191
Fujii, Teruhisa; Saito, Seiji
Limbic associated pelvic pain is a proposed pathophysiology designed to explain features commonly encountered in patients with chronic pelvic pain, including the presence of multiple pain diagnoses, the frequency of previous abuse, the minimal or discordant pathologic changes of the involved organs, the paradoxical effectiveness of many treatments, and the recurrent nature of the condition. These conditions include endometriosis, interstitial cystitis, irritable bowel syndrome, levator ani syndrome, pelvic floor tension myalgia, vulvar vestibulitis, and vulvodynia. The hypothesis is based on recent improvements in the understanding of pain processing pathways in the central nervous system, and in particular the role of limbic structures, especially the anterior cingulate cortex, hippocampus and amygdala, in chronic and affective pain perception. Limbic associated pelvic pain is hypothesized to occur in patients with chronic pelvic pain out of proportion to any demonstrable pathology (hyperalgesia), and with more than one demonstrable pain generator (allodynia), and who are susceptible to development of the syndrome. This most likely occurs as a result of childhood sexual abuse but may include other painful pelvic events or stressors, which lead to limbic dysfunction. This limbic dysfunction is manifest both as an increased sensitivity to pain afferents from pelvic organs, and as an abnormal efferent innervation of pelvic musculature, both visceral and somatic. The pelvic musculature undergoes tonic contraction as a result of limbic efferent stimulation, which produces the minimal changes found on pathological examination, and generates a further sensation of pain. The pain afferents from these pelvic organs then follow the medial pain pathway back to the sensitized, hypervigilant limbic system. Chronic stimulation of the limbic system by pelvic pain afferents again produces an efferent contraction of the pelvic muscles, thus perpetuating the cycle. This cycle is susceptible to disruption through blocking afferent signals from pelvic organs, either through anesthesia or muscle manipulation. Disruption of limbic perception with psychiatric medication similarly produces relief. Without a full disruption of both the central hypervigilance and pelvic organ dysfunction, pain recurs. To prevent recurrence, clinicians will need to include some form of therapy, either medical or cognitive, targeted at the underlying limbic hypervigilance. Further research into novel, limbic targeted therapies can hopefully be stimulated by explicitly stating the role of the limbic system in chronic pain. This hypothesis provides a framework for clinicians to rationally approach some of the most challenging patients in medicine, and can potentially improve outcomes by including management of limbic dysfunction in their treatment. PMID:17292560
Fenton, Bradford W
Innovative treatments of epileptic seizures are needed to improve the outcome of epilepsy. We studied the effect of pranlukast on seizure outcome in patients with intractable partial epilepsy. An open study was conducted to evaluate the clinical efficacy of 24-week pranlukast add-on therapy in 50 patients with intractable partial seizures. Serum concentrations of matrix metalloproteinase (MMP)-9 were determined using Biotrak Activity Assay System. Cytokines in cerebrospinal fluid (CSF) were measured by the BioPlex (BioRad) system and soluble TNF receptor1 (sTNFR1) in CSF was measured by the ELISA. Surface markers of lymphocytes in CSF were examined by cell-sorter. Seizure-free rate (SFR) was 13.6%, responder rate (RR) was 47.7%, and aggravation rate (AR) was 18.2% at the 13-24 week period after starting pranlukast. In patients with increased serum MMP-9 before pranlukast therapy (baseline), comparison of paired serum levels showed a significant decrease after pranlukast therapy. Baseline CSF levels of IL-1? and IL-6 were elevated in patients compared with disease controls. Of four patients with paired data, three (including a responder to pranlukast) showed decreased pro-inflammatory cytokines (IL-1?, IL-6, and TNF?), and four showed decreased sTNFR1, after pranlukast treatment, and only a responder had markedly decreased frequency of CD8+ T cells in CSF. Pranlukast reduces seizure frequencies probably by pleiotropic effects including normalization of MMP-9 in sera, reduced leakage of pro-inflammatory cytokines into CNS, and inhibition of extravasation of leucocytes from brain capillaries. Further investigations by double-blind control study and animal models are warranted. PMID:22571867
Takahashi, Yukitoshi; Imai, Katsumi; Ikeda, Hitoshi; Kubota, Yuko; Yamazaki, Etsuko; Susa, Fuminobu
Ulcerative colitis (UC) is a chronic inflammatory bowel disease that may become intractable when treated with conventional medications such as aminosalicylates, corticosteroids, and azathioprine. The herbal medicine Qing Dai has traditionally been used in Chinese medicine to treat UC patients, but there is a lack of published data on the efficacy of Qing Dai in UC treatment. We report several cases of patients with intractable UC who take Qing Dai in a retrospective observational study. Furthermore, we explore the mechanisms of action of Qing Dai. Nine patients with active UC who received conventional medications but wished to receive Qing Dai as an alternative medication were included in our analysis. The UC severity level was determined based on the clinical activity index (CAI). Additionally, 5 of the 9 patients were endoscopically evaluated according to the Matts grading system. Each patient received 2 g/d of Qing Dai orally and continued taking other medications for UC as prescribed. Electron spin resonance was applied to explore the mechanisms of action of Qing Dai. After 4 mo of treatment with Qing Dai, the CAI score decreased from 8.3 ± 2.4 to 2.4 ± 3.4 (mean ± SD; P < 0.001). Similarly, the endoscopic Matts grade decreased from 3.4 ± 0.5 to 2.2 ± 0.8 (P = 0.02). Six of 7 patients who were on prednisolone upon enrollment in the study were able to discontinue this corticosteroid. Electron spin resonance revealed that Qing Dai possesses strong hydroxyl radical scavenging activity. Qing Dai showed significant clinical and endoscopic efficacy in patients who failed to respond to conventional medications. Scavenging of hydroxyl radicals appears to be a potential mechanism through which Qing Dai acts, but the significance of the scavenging ability of Qing Dai with respect to the anti-inflammatory effect in UC patients warrants further investigation.
Suzuki, Hideo; Kaneko, Tsuyoshi; Mizokami, Yuji; Narasaka, Toshiaki; Endo, Shinji; Matsui, Hirofumi; Yanaka, Akinori; Hirayama, Aki; Hyodo, Ichinosuke
Terminal sedation is a phrase that has appeared in the palliative care literature in the last few years. There has not been a clear definition proposed for this term, nor has there been any agreement on the frequency with which the technique is used. A postal survey of 61 selected palliative care experts (59 physicians, two nurses) was carried out to examine their response to a proposed definition for 'terminal sedation', to estimate the frequency of this practice and the reasons for its use, to identify the drugs and dosages used, to determine the outcome, and to explore the decision-making process. Opinions on physician-assisted suicide and voluntary euthanasia were also sought. Eighty-seven per cent of the experts responded from eight countries, although predominantly from Canada and the United Kingdom. Forty per cent agreed unequivocally with the proposed definition, while 4% disagreed completely. Eighty-nine per cent agreed that 'terminal sedation' is sometimes necessary and 77% reported using it in the last 12 months--over half of these for up to four patients. Reasons for using this method included various physical and psychological symptoms. The most common drugs used were midazolam and methotrimeprazine. Decision making usually involved the patient or family, and varied with respect to the ease with which the decision was made. The use of sedation was perceived to be successful in 90 out of 100 patients recalled. Ninety per cent of respondents did not support legalization of euthanasia. In conclusion, sedating agents are used by palliative care experts as tools for the management of symptoms. The term 'terminal sedation' should be abandoned and replaced with the phrase 'sedation for intractable distress in the dying'. Further research into the management of intractable symptoms and suffering is warranted. PMID:9743824
Chater, S; Viola, R; Paterson, J; Jarvis, V
Background and Purpose Hemispherectomy reportedly produces remarkable results in terms of seizure outcome and quality of life for medically intractable hemispheric epilepsy in children. We reviewed the neuroradiologic findings, pathologic findings, epilepsy characteristics, and clinical long-term outcomes in pediatric patients following a hemispheric disconnection. Methods We retrospectively studied 12 children (8 males) who underwent a hemispherectomy at Asan Medical Center between 1997 and 2005. Clinical, EEG, neuroradiological, and surgical data were collected. Long-term outcomes for seizure, motor functions, and cognitive functions were evaluated at a mean follow-up of 1