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Sample records for chronic central neuropathic

  1. Mechanisms of chronic central neuropathic pain after spinal cord injury.

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    Hulsebosch, Claire E; Hains, Bryan C; Crown, Eric D; Carlton, Susan M

    2009-04-01

    Not all spinal contusions result in mechanical allodynia, in which non-noxious stimuli become noxious. The studies presented use the NYU impactor at 12.5 mm drop or the Infinite Horizons Impactor (150 kdyn, 1 s dwell) devices to model spinal cord injury (SCI). Both of these devices and injury parameters, if done correctly, will result in animals with above level (forelimb), at level (trunk) and below level (hindlimb) mechanical allodynia that model the changes in evoked somatosensation experienced by the majority of people with SCI. The sections are as follows: 1) Mechanisms of remote microglial activation and pain signaling in "below-level" central pain 2) Intracellular signaling mechanisms in central sensitization in "at-level" pain 3) Peripheral sensitization contributes to "above level" injury pain following spinal cord injury and 4) Role of reactive oxygen species in central sensitization in regional neuropathic pain following SCI. To summarize, differential regional mechanisms contribute to the regional chronic pain states. We propose the importance of understanding the mechanisms in the differential regional pain syndromes after SCI in the chronic condition. Targeting regional mechanisms will be of enormous benefit to the SCI population that suffer chronic pain, and will contribute to better treatment strategies for other chronic pain syndromes.

  2. AAPT Diagnostic Criteria for Central Neuropathic Pain

    DEFF Research Database (Denmark)

    Widerstrom-Noga, Eva; Loeser, John D.; Jensen, Troels Staehelin

    2017-01-01

    ) initiative, invited a working group to develop diagnostic criteria for central neuropathic pain. The criteria for central neuropathic pain that were developed expand upon existing criteria for neuropathic pain and the International Classification of Diseases 11th Revision draft criteria to ensure consistency......: The AAPT chronic central neuropathic pain taxonomy provides a classification for central pain associated with spinal cord injury, stroke, and multiple sclerosis. The diagnostic criteria are organized according to the AAPT multidimensional framework, specifically: 1) core diagnostic criteria, 2) common......Central neuropathic pain, which is pain caused by a lesion or disease of the central somatosensory nervous system, is a serious consequence of spinal cord injury, stroke, multiple sclerosis, and other conditions affecting the central nervous system. A collaborative effort between the Analgesic...

  3. Non-invasive brain stimulation interventions for management of chronic central neuropathic pain: a scoping review protocol.

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    Chen, Mei Lin; Yao, Lin; Boger, Jennifer; Mercer, Kathryn; Thompson, Benjamin; Jiang, Ning

    2017-10-16

    Pain can affect people regardless of age, gender or ethnicity. Chronic central neuropathic pain (CCNP) is a debilitating condition that affects populations such as stroke survivors, amputees, spinal cord injury patients and patients with multiple sclerosis, with prevalence rates between 30% and 80%. This condition can be caused by a lesion or disease affecting the somatosensory system. CCNP is notoriously drug resistant, and few effective CCNP treatment or management strategies exist. The emergence of non-invasive brain stimulation and neuromodulation techniques provide novel avenues for managing chronic central neuropathic pain. This scoping review aims to systematically identify the methods and effectiveness of non-invasive brain stimulation techniques for treating and managing chronic central neuropathic pain. The following databases will be searched systematically: PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Institute of Electric and Electronic Engineers (IEEE), Association of Computing Machinary (ACM) and Scopus. Additional literature will be identified by searching the reference lists of identified studies. Studies will include reviews and original research in both published and grey literatures. Two reviewers will independently screen identified studies for final inclusion. A quantitative analysis on the intervention type, application and efficacy will be synthesised along with a qualitative analysis to describe the effectiveness of each intervention. No primary data will be collected and hence formal ethics review is not required. The results of the scoping review will be presented at relevant national and international conferences, published in a peer-reviewed journal and provided to the stakeholders with plain language to be posted on their websites. This scoping review will provide a foundation to guide the development of future primary research on non-invasive brain stimulation and CCNP. © Article author(s) (or

  4. Tetrahydrocannabinol (Delta 9-THC Treatment in Chronic Central Neuropathic Pain and Fibromyalgia Patients: Results of a Multicenter Survey

    Directory of Open Access Journals (Sweden)

    Janet Weber

    2009-01-01

    Full Text Available Central neuropathic pain is difficult to treat, but delta 9-Tetrahydrocannabinol (delta 9-THC may be a promising therapeutic agent. We administered in 172 patients on average 7.5 mg delta 9-THC over 7 months. Of these, 48 patients prematurely withdrew due to side effects, insufficient analgesia, or expense of therapy. Thus, 124 patients were assessed retrospectively in a multicenter telephone survey. Reported changes in pain intensity, recorded on a numeric rating scale (NRS, Pain Disability Index (PDI, Medical Outcomes Short-Form (SF-12, Quality of Life Impairment by Pain (QLIP, Hospital Anxiety Depression Scale (HADS, and amount of concomitant pain medication were recorded. Psychometric parameters (PDI, SF-12, QLIP, HADS and pain intensity improved significantly during delta 9-THC treatment. Opioid doses were reduced and patients perceived THC therapy as effective with tolerable side effects. About 25% of the patients, however, did not tolerate the treatment. Therapy success and tolerance can be assessed by a transient delta 9-THC titration and its maintained administration for several weeks. The present survey demonstrates its ameliorating potential for the treatment of chronic pain in central neuropathy and fibromyalgia. A supplemental delta 9-THC treatment as part of a broader pain management plan therefore may represent a promising coanalgesic therapeutic option.

  5. Neuropathic and chronic pain stimuli downregulate central mu-opioid and dopaminergic transmission.

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    Niikura, Keiichi; Narita, Minoru; Butelman, Eduardo R; Kreek, Mary Jeanne; Suzuki, Tsutomu

    2010-07-01

    Although morphine and other mu-opioid agonists are the main analgesics for severe pain, these compounds have potential for abuse and/or addiction. This has complicated the use of mu-agonists in the treatment of chronic pain. However, clinical studies show that when mu-agonist analgesics are appropriately used to control pain, actual abuse or addiction does not usually occur, although some risk factors that increase vulnerability need to be considered, including genetic variation. We review recent findings on molecular adaptations in sustained pain models, and propose how these adaptations (including sustained release of the endogenous mu-agonist beta-endorphin) can result in decreased abuse potential of mu-agonists in chronic pain states. We also review data on particular gene polymorphisms (e.g. in the mu-receptor gene) that could also influence the relative abuse potential of mu-agonists in clinical pain populations. Copyright 2010 Elsevier Ltd. All rights reserved.

  6. Central Neuropathic Pain in Spinal Cord Injury

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    Lee, Sujin; Zhao, Xing; Hatch, Maya; Chun, Sophia; Chang, Eric

    2015-01-01

    Spinal cord injury (SCI) is a devastating medical condition affecting 1.2 million people in the United States. Central neuropathic pain is one of the most common medical complications of SCI. Current treatment options include opioids, antiepileptic agents such as gabapentin, antispastic agents such as baclofen or tizanidine, and tricyclic acid. Other options include complementary, nonpharmacological treatment such as exercise or acupuncture, interventional treatments, and psychological approaches. Although these treatment options exist, central neuropathic pain in patients with SCI is still extremely difficult to treat because of its complexity. To develop and provide more effective treatment options to these patients, proper assessment of and classification tools for central neuropathic pain, as well as a better understanding of the pathophysiology, are needed. A combination of approaches, from standard general pain assessments to medically specific questions unique to SCI pathophysiology, is essential for this population. A multidisciplinary approach to patient care, in addition with a better understanding of pathophysiology and diagnosis, will lead to improved management and treatment of patients with SCI displaying central neuropathic pain. Here we summarize the most recent classification tools, pathophysiology, and current treatment options for patients with SCI with central neuropathic pain. PMID:25750485

  7. Morphine for chronic neuropathic pain in adults.

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    Cooper, Tess E; Chen, Junqiao; Wiffen, Philip J; Derry, Sheena; Carr, Daniel B; Aldington, Dominic; Cole, Peter; Moore, R Andrew

    2017-05-22

    Neuropathic pain, which is caused by a lesion or disease affecting the somatosensory system, may be central or peripheral in origin. Neuropathic pain often includes symptoms such as burning or shooting sensations, abnormal sensitivity to normally painless stimuli, or an increased sensitivity to normally painful stimuli. Neuropathic pain is a common symptom in many diseases of the nervous system. Opioid drugs, including morphine, are commonly used to treat neuropathic pain. Most reviews have examined all opioids together. This review sought evidence specifically for morphine; other opioids are considered in separate reviews. To assess the analgesic efficacy and adverse events of morphine for chronic neuropathic pain in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase for randomised controlled trials from inception to February 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trial registries. We included randomised, double-blind trials of two weeks' duration or longer, comparing morphine (any route of administration) with placebo or another active treatment for neuropathic pain, with participant-reported pain assessment. Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)), or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC). Where pooled analysis was possible, we used dichotomous data to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH). We assessed the quality of the evidence using GRADE and created 'Summary of findings' tables. We identified five randomised, double-blind, cross-over studies with treatment periods of four to

  8. Chronic Neuropathic Pain in Spinal Cord Injury: The Patient's Perspective

    Directory of Open Access Journals (Sweden)

    Penelope Henwood

    2004-01-01

    Full Text Available BACKGROUND: Chronic neuropathic pain (CNP in spinal cord injury (SCI is recognized as severely compromising, in both adjustment after injury and quality of life. Studies indicate that chronic pain in SCI is associated with great emotional distress over and above that of the injury itself. Currently, little is known about the SCI patient's perception of the impact of living with chronic neuropathic pain.

  9. Chronic neuropathic pain: mechanisms, drug targets and measurement

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix; Sindrup, Søren H.; Jensen, Troels Staehelin

    2007-01-01

    Neuropathic pain is common in many diseases or injuries of the peripheral or central nervous system, and has a substantial impact on quality of life and mood. Lesions of the nervous system may lead to potentially irreversible changes and imbalance between excitatory and inhibitory systems...... to assess various symptoms and signs in neuropathic pain and knowledge of drug mechanisms are prerequisites for pursuing this approach. The present review summarizes mechanisms of neuropathic pain, targets of currently used drugs, and measures used in neuropathic pain trials....

  10. Holistic approach to treatment of intractable central neuropathic itch.

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    Curtis, Ashley R; Tegeler, Charles; Burdette, Jonathan; Yosipovitch, Gil

    2011-05-01

    Central neuropathic itch can be a lifelong debilitating condition and treatment challenge. We report a patient with a traumatic brain injury with severe intractable pruritus who failed extensive pharmacologic and nonpharmacologic treatment but responded to a holistic approach using healing touch. We discuss the complexity of this type of neuropathic itch and present a holistic approach as an adjunct to therapy in reducing itch intensity. This case presentation along with the literature discussed suggests a therapeutic strategy for the management of complicated central neuropathic itch. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  11. [Pathophysiology of neuropathic pain: molecular mechanisms underlying central sensitization in the dorsal horn in neuropathic pain].

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    Yamanaka, Hiroki; Noguchi, Koichi

    2012-11-01

    Neuropathic pain syndromes are clinically characterized by spontaneous pain and evoked pain (hyperalgesia and allodynia). The optimal treatment approach for neuropathic pain is still under development because of the complex pathological mechanisms underlying this type of pain. The spinal cord is an important gateway thorough which peripheral pain signals are transmitted to the brain, and sensitization of the spinal neurons is one of the important mechanisms underlying neuropathic pain. Central sensitization represents enhancement of the function of neuronal circuits in nociceptive pathways and is a manifestation of the remarkable plasticity of the somatosensory nervous system after nerve injury. This review highlights the pathological features of central sensitization, which develops because of (1) injury-induced abnormal inputs from primary afferents, (2) increase in the excitability of dorsal horn neurons, and (3) activated glial cell-derived signals.

  12. PI3K/Akt Pathway is Required for Spinal Central Sensitization in Neuropathic Pain.

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    Liu, Wei; Lv, Yanling; Ren, Facheng

    2018-04-01

    Phosphatidylinositol-3-kinase (PI3K) has been identified in the expression of central sensitization after noxious inflammatory stimuli. However, its contribution in neuropathic pain remains to be determined. Here we address the role of PI3K signaling in central sensitization in a model of neuropathic pain, and propose a novel potential drug target for neuropathic pain. Chronic constriction injury (CCI) rat model was used in the study as the model for neuropathic pain. Western blotting, whole-cell patch clamp, and von Frey assay were performed to study biochemical, electrical, and behavioral changes in CCI rats, respectively. A steroid metabolite of the fungi (wortmannin) was used to block PI3K signaling and its effects on CCI rats were tested. PI3K/Akt signaling increased in the spinal cord L4-L6 sections in the CCI rats. CCI also facilitated miniature excitatory postsynaptic potential of dorsal horn substantia gelatinosa neurons, increased phosphorylation of glutamate receptor subunit GluA1 and synapsin at the synapse, and induced mechanic allodynia. Wortmannin reversed biochemical, electrical, and behavioral changes in CCI rats. This study is the first to show PI3K/Akt signaling is required for spinal central sensitization in the CCI neuropathic pain model.

  13. Cannabis-based medicines for chronic neuropathic pain in adults.

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    Mücke, Martin; Phillips, Tudor; Radbruch, Lukas; Petzke, Frank; Häuser, Winfried

    2018-03-07

    This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain. To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults. In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles. We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm. Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For

  14. Management of chronic neuropathic pain with single and compounded topical analgesics.

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    Knezevic, Nebojsa Nick; Tverdohleb, Tatiana; Nikibin, Farid; Knezevic, Ivana; Candido, Kenneth D

    2017-11-01

    The goal of our review was to emphasize important aspects that physicians should take into consideration when prescribing topical analgesics as part of chronic neuropathic pain treatment. We discuss the dermatopharmacokinetics and microstructural components of the skin, differences between topical and transdermal drug delivery, and topical medication effects on peripheral neuropathy and central sensitization. Even though the US FDA approved topical analgesics are 8%-capsaicin and 5%-lidocaine patches for treating postherpetic neuralgia, there are many other studies conducted on the efficacy of topical ketamine cream, clonidine gel, topical gabapentin, topical baclofen and topical phenytoin for peripheral neuropathic pain, either alone or in combination with other formulations. Furthermore, we discuss new compounded topical analgesics that are becoming more popular and that are showing promising results in the management of chronic peripheral neuropathies. However, more studies are needed for elucidation of the role of topical analgesics and their effects, especially when combined with other treatments.

  15. Does hemiplegic shoulder pain share clinical and sensory characteristics with central neuropathic pain? A comparative study.

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    Zeilig, Gabi; Rivel, Michal; Doron, Dana; Defrin, Ruth

    2016-10-01

    Hemiplegic shoulder pain (HSP) is a common poststroke complication and is considered to be a chronic pain syndrome. It is negatively correlated with the functional recovery of the affected arm and the quality of life of the individual. It also leads to a longer length of stay in rehabilitation. Today, there is no consensus as to the underlying mechanism causing HSP, making the syndrome difficult to treat. The aim of this study was to compare the clinical and sensory profile of individuals with HSP to that of individuals with established central neuropathic pain (CNP) in order to identify common features and the presence of neuropathic components in HSP. Cross sectional controlled study. Outpatient rehabilitation clinics. Sixteen chronic HSP patients and 18 chronic CNP patients with spinal cord injury (SCI-CNP). The chronic pain characteristics, thresholds of thermal and tactile sensations and presence of pathological sensations were compared between groups, and between painful and pain free body regions within groups. Correlations were calculated between HSP intensity and sensory and musculoskeletal characteristics. Patients with HSP and patients with SCI-CNP had similar decrease of thermal sensibility in the painful compared to intact body regions and both groups presented similar rates of pathological sensations in painful regions. HSP and SCI-CNP differed however, in the quality of pain and aggravating factors. Significant correlations were found between HSP intensity and heat-pain threshold, presence of subluxation and spasticity. The similarities between HSP and SCI-CNP and the altered spinothalamic function and sensitization suggest that HSP has neuropathic components in its mechanism. Nevertheless, the unique features of HSP point towards additional possible mechanisms. The use of specific therapy options for neuropathic pain should be considered when treating patients with HSP.

  16. Treatment of Chronic Refractory Neuropathic Pelvic Pain with High-Frequency 10-kilohertz Spinal Cord Stimulation.

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    Simopoulos, Thomas; Yong, Robert J; Gill, Jatinder S

    2017-11-06

    Chronic neuropathic pelvic pain remains a recalcitrant problem in the field of pain management. Case series on application of 10 kHz spinal cord stimulation is presented. High frequency stimulation can improve chronic neuropathic pain states that are known to be mediated at the conus medullaris and offers another avenue for the treatment of these patients. © 2017 World Institute of Pain.

  17. Chronic Orofacial Pain: Burning Mouth Syndrome and Other Neuropathic Disorders

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    Tait, Raymond C; Ferguson, McKenzie; Herndon, Christopher M

    2017-01-01

    Chronic orofacial pain is a symptom associated with a wide range of neuropathic, neurovascular, idiopathic, and myofascial conditions that affect a significant proportion of the population. While the collective impact of the subset of the orofacial pain disorders involving neurogenic and idiopathic mechanisms is substantial, some of these are relatively uncommon. Hence, patients with these disorders can be vulnerable to misdiagnosis, sometimes for years, increasing the symptom burden and delaying effective treatment. This manuscript first reviews the decision tree to be followed in diagnosing any neuropathic pain condition, as well as the levels of evidence needed to make a diagnosis with each of several levels of confidence: definite, probable, or possible. It then examines the clinical literature related to the idiopathic and neurogenic conditions that can occasion chronic orofacial pain, including burning mouth syndrome, trigeminal neuralgia, glossopharyngeal neuralgia, post-herpetic neuralgia, and atypical odontalgia. Temporomandibular disorders also are examined as are other headache conditions, even though they are not neurologic conditions, because they are common and can mimic symptoms of the latter disorders. For each of these conditions, the paper reviews literature regarding incidence and prevalence, physiologic and other contributing factors, diagnostic signs and symptoms, and empirical evidence regarding treatments. Finally, in order to improve the quality and accuracy of clinical diagnosis, as well as the efficiency with which effective treatment is initiated and delivered, criteria are offered that can be instrumental in making a differential diagnosis. PMID:28638895

  18. The mechanism of neurofeedback training for treatment of central neuropathic pain in paraplegia: a pilot study.

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    Hassan, Muhammad Abul; Fraser, Matthew; Conway, Bernard A; Allan, David B; Vuckovic, Aleksandra

    2015-10-13

    Central neuropathic pain has a prevalence of 40% in patients with spinal cord injury. Electroencephalography (EEG) studies showed that this type of pain has identifiable signatures, that could potentially be targeted by a neuromodulation therapy. The aim of the study was to investigate the putative mechanism of neurofeedback training on central neuropathic pain and its underlying brain signatures in patients with chronic paraplegia. Patients' EEG activity was modulated from the sensory-motor cortex, electrode location C3/Cz/C4/P4 in up to 40 training sessions Results. Six out of seven patients reported immediate reduction of pain during neurofeedback training. Best results were achieved with suppressing Ɵ and higher β (20-30 Hz) power and reinforcing α power at C4. Four patients reported clinically significant long-term reduction of pain (>30%) which lasted at least a month beyond the therapy. EEG during neurofeedback revealed a wide spread modulation of power in all three frequency bands accompanied with changes in the coherence most notable in the beta band. The standardized low resolution electromagnetic tomography analysis of EEG before and after neurofeedback therapy showed the statistically significant reduction of power in beta frequency band in all tested patients. Areas with reduced power included the Dorsolateral Prefrontal Cortex, the Anterior Cingulate Cortex and the Insular Cortex. Neurofeedback training produces both immediate and longer term reduction of central neuropathic pain that is accompanied with a measurable short and long term modulation of cortical activity. Controlled trials are required to confirm the efficacy of this neurofeedback protocol on treatment of pain. The study is a registered UKCRN clinical trial Nr 9824.

  19. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial.

    Science.gov (United States)

    Ware, Mark A; Wang, Tongtong; Shapiro, Stan; Robinson, Ann; Ducruet, Thierry; Huynh, Thao; Gamsa, Ann; Bennett, Gary J; Collet, Jean-Paul

    2010-10-05

    Chronic neuropathic pain affects 1%-2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood. Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. We recorded effects on mood, sleep and quality of life, as well as adverse events. We recruited 23 participants (mean age 45.4 [standard deviation 12.3] years, 12 women [52%]), of whom 21 completed the trial. The average daily pain intensity, measured on the 11-point numeric rating scale, was lower on the prespecified primary contrast of 9.4% v. 0% tetrahydrocannabinol (5.4 v. 6.1, respectively; difference = 0.7, 95% confidence interval [CI] 0.02-1.4). Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief. Participants receiving 9.4% tetrahydrocannabinol reported improved ability to fall asleep (easier, p = 0.001; faster, p sleep (less wakefulness, p = 0.01) relative to 0% tetrahydrocannabinol. We found no differences in mood or quality of life. The most common drug-related adverse events during the period when participants received 9.4% tetrahydrocannabinol were headache, dry eyes, burning sensation in areas of neuropathic pain, dizziness, numbness and cough. A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated. Further long-term safety and efficacy studies are indicated. (International Standard Randomised Controlled Trial Register

  20. Pro-inflammatory cytokines involvement in the hesperidin antihyperalgesic effects at peripheral and central levels in a neuropathic pain model.

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    Carballo-Villalobos, A I; González-Trujano, M E; Alvarado-Vázquez, N; López-Muñoz, F J

    2017-04-01

    Emerging evidence proposes a link between immune changes and pain, which is consistent with the inflammation theory and the increased incidence of neurodegenerative diseases. Flavonoids have long been used because of their anti-inflammatory potential activity and they are considered a promising alternative to alleviate neuropathic pain. The aim of this study was to investigate the antihyperalgesic effect of hesperidin and the presence of pro-inflammatory cytokines evaluated at peripheral and central levels in the chronic constriction injury as model of neuropathic pain in rats. Mechanical and thermal hyperalgesia were assessed in the aesthesiometer and plantar tests, respectively, as related to the presence of cytokines concentrations (TNF-α, IL-1β and IL-6) in sciatic nerve and segments of the spinal cord after 15 days chronic constriction injury model in rats receiving vehicle or hesperidin. Antihyperalgesic response of hesperidin (100 mg/kg) was associated to the presence of cytokines mainly at several sections of the spinal cord suggesting not only peripheral but also its involvement in central sensitization in the experimental neuropathic pain.

  1. Neuropathic pain

    Directory of Open Access Journals (Sweden)

    Giuseppe Re

    2009-02-01

    Full Text Available Neuropathic pain is the expression of a dysfunction or primary lesion of a nerve in the peripheral or central nervous system, or both, rather than the biological signal transmitted by the nerve following peripheral nociceptor activation. It represents about 20% of all painful syndromes, with an estimated prevalence of 1.5%, however is actual incidence is hard to pinpoint due to the difficulties encountered in distinguishing it from chronic pain, of which it represents a significant percentage, on account of the not infrequent concurrence of conditions. It is crucial to recognise the variety of symptoms with which it can present: these can be negative and positive and, in turn, motor, sensitive and autonomic. In public health terms, it is important to emphasise that the diagnosis of neuropathic pain does not in most cases require sophisticated procedures and does not therefore weigh on health expenditure. In clinical practice, a validated scale (the LANSS is mentioned is useful for identifying patients presenting neuropathic pain symptoms. Therapy is based on three categories of medication: tricyclic antidepressants, anti-epileptics and opioids at high doses: neuropathic pain has a bad reputation for often resisting common therapeutic approaches and responding less well that nociceptor pain to monotherapy. Therapeutic strategies are all the more adequate the more they are based on symptoms and therefore on the pain generation mechanisms, although the recommendations are dictated more by expert opinions that double-blind randomised trials.

  2. Low back pain: guidelines for the clinical classification of predominant neuropathic, nociceptive, or central sensitization pain.

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    Nijs, Jo; Apeldoorn, Adri; Hallegraeff, Hank; Clark, Jacqui; Smeets, Rob; Malfliet, Annaleen; Girbes, Enrique L; De Kooning, Margot; Ickmans, Kelly

    2015-01-01

    Low back pain (LBP) is a heterogeneous disorder including patients with dominant nociceptive (e.g., myofascial low back pain), neuropathic (e.g., lumbar radiculopathy), and central sensitization pain. In order to select an effective and preferably also efficient treatment in daily clinical practice, LBP patients should be classified clinically as either predominantly nociceptive, neuropathic, or central sensitization pain. To explain how clinicians can differentiate between nociceptive, neuropathic, and central sensitization pain in patients with LBP. Narrative review and expert opinion Universities, university hospitals and private practices Recently, a clinical method for the classification of central sensitization pain versus neuropathic and nociceptive pain was developed. It is based on a body of evidence of original research papers and expert opinion of 18 pain experts from 7 different countries. Here we apply this classification algorithm to the LBP population. The first step implies examining the presence of neuropathic low back pain. Next, the differential diagnosis between predominant nociceptive and central sensitization pain is done using a clinical algorithm. The classification criteria are substantiated by several original research findings including a Delphi survey, a study of a large group of LBP patients, and validation studies of the Central Sensitization Inventory. Nevertheless, these criteria require validation in clinical settings. The pain classification system for LBP should be an addition to available classification systems and diagnostic procedures for LBP, as it is focussed on pain mechanisms solely.

  3. Exploring acute-to-chronic neuropathic pain in rats after contusion spinal cord injury.

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    Gaudet, Andrew D; Ayala, Monica T; Schleicher, Wolfgang E; Smith, Elana J; Bateman, Emily M; Maier, Steven F; Watkins, Linda R

    2017-09-01

    Spinal cord injury (SCI) causes chronic pain in 65% of individuals. Unfortunately, current pain management is inadequate for many SCI patients. Rodent models could help identify how SCI pain develops, explore new treatment strategies, and reveal whether acute post-SCI morphine worsens chronic pain. However, few studies explore or compare SCI-elicited neuropathic pain in rats. Here, we sought to determine how different clinically relevant contusion SCIs in male and female rats affect neuropathic pain, and whether acute morphine worsens later chronic SCI pain. First, female rats received sham surgery, or 150kDyn or 200kDyn midline T9 contusion SCI. These rats displayed modest mechanical allodynia and long-lasting thermal hyperalgesia. Next, a 150kDyn (1s dwell) midline contusion SCI was performed in male and female rats. Interestingly, males, but not females showed SCI-elicited mechanical allodynia; rats of both sexes had thermal hyperalgesia. In this model, acute morphine treatment had no significant effect on chronic neuropathic pain symptoms. Unilateral SCIs can also elicit neuropathic pain that could be exacerbated by morphine, so male rats received unilateral T13 contusion SCI (100kDyn). These rats exhibited significant, transient mechanical allodynia, but not thermal hyperalgesia. Acute morphine did not exacerbate chronic pain. Our data show that specific rat contusion SCI models cause neuropathic pain. Further, chronic neuropathic pain elicited by these contusion SCIs was not amplified by our course of early post-trauma morphine. Using clinically relevant rat models of SCI could help identify novel pain management strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Neuropathic pain - Current concepts

    African Journals Online (AJOL)

    Abstract. Neuropathic pain (NP) represents a common and diverse group of disorders with peripheral and/or central nervous system damage or dysfunction. ... It is estimated that as many as one in five adults with chronic pain will have ... in daily activities and an association with depression and sleep disturbances.16,18 In a.

  5. Managing neuropathic pain in dogs

    Directory of Open Access Journals (Sweden)

    Sarah A Moore

    2016-02-01

    Full Text Available Disorders of the somatosensory system such as neuropathic pain are common in people with chronic neurologic and musculoskeletal diseases, yet these conditions remain an underappreciated morbidity in our veterinary patients. This is likely because assessment of neuropathic pain in people relies heavily on self-reporting, something our veterinary patients are not able to do. The development of neuropathic pain is a complex phenomenon, and concepts related to it are frequently not addressed in the standard veterinary medical curriculum such that veterinarians may not recognize this as a potential problem in patients. The goals of this review are to discuss basic concepts in the pathophysiology of neuropathic pain, provide definitions for common clinical terms used in association with the condition, and discuss available medical treatment options for dogs with neuropathic pain. The development of neuropathic pain involves key mechanisms such as ectopic afferent nerve activity, peripheral sensitization, central sensitization, impaired inhibitory modulation, and activation of microglia. Treatments aimed at reducing neuropathic pain are targeted at one or more of these mechanisms. Several drugs are commonly used in the veterinary clinical setting to treat neuropathic pain. These include gabapentin, pregabalin, amantadine, and amitriptyline. Proposed mechanisms of action for each drug, and known pharmacokinetic profiles in dogs are discussed. Strong evidence exists in the human literature for the utility of most of these treatments, but clinical veterinary-specific literature is currently limited. Future studies should focus on objective methods to document neuropathic pain and monitor response to therapy in our veterinary patients.

  6. Differential diagnosis of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Yu. N. Bykov

    2015-01-01

    Full Text Available Neuropathic pain is an acute or chronic pain caused by damage to or dysfunction of the peripheral and/or central nervous system. Neuropathic pain is a direct sequel of damage to or disease of the somatosensory nervous system. The paper presents the definition, international diagnostic criteria, clinical and diagnostic features, and causes of neuropathic pain syndrome, differences between nociceptive and neuropathic pain, the classification of major neuropathic pain syndromes, and the DN4 questionnaire to identify neuropathic pain. It shows a substantial clinical and pathophysiological similarity of neuropathic pain and fibromyalgia and gives preliminary diagnostic criteria for fibromyalgia. The differential diagnosis of neuropathic, nociceptive, and psychogenic pain and the determination of the level of damage to the nervous system and a leading pathogenetic mechanism of neuropathic pain syndrome require not only meticulous clinical examination of the sensory sphere, but also neurophysiological examination including electroneuromyography, somatosensory evoked potential recording, quantitative sensory testing, and, in a number of cases, neuroimaging (magnetic resonance imaging or morphological (intraepidermal nerve fiber density examination verification of injury somatosensory afferents. 

  7. Under Pressure: Applying Practice-Based Learning and Improvement to the Treatment of Chronic Neuropathic Pain in Patients with Burns.

    Science.gov (United States)

    Rapolti, Mihaela; Wu, Cindy; Schuth, Olga A; Hultman, Charles Scott

    2017-10-01

    Chronic neuropathic pain after burn injury may have multiple causes, such as direct nerve injury, nerve compression, or neuroma formation, and can significantly impair quality of life and limit functional recovery. Management includes a team-based approach that involves close collaboration between occupational and physical therapists, plastic surgeons, and experts in chronic pain, from neurology, anesthesia, psychiatry, and physiatry. Carefully selected patients with an anatomic cause of chronic neuropathic pain unequivocally benefit from surgical intervention. Self-reflection and analysis yield improvement in both efficiency and effectiveness when managing patients with burns with chronic neuropathic pain. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Study of nociceptive flexion reflex in healthy subjects and patients with chronic neuropathic pain syndrome.

    Science.gov (United States)

    Gordeev, S A; Turbina, L G; Zus'man, A A; Posokhov, S I

    2012-12-01

    Nociceptive flexion reflex was measured in healthy subjects and patients with chronic neuropathic pain (diabetic distal symmetric sensorimotor polyneuropathy). The study of nociceptive flexion reflex revealed reduction of subjective pain threshold and reflex threshold in patients compared with healthy persons reflecting deficit of descending antinociceptive influences in the CNS.

  9. Descending volleys generated by efficacious epidural motor cortex stimulation in patients with chronic neuropathic pain

    NARCIS (Netherlands)

    Lefaucheur, Jean-Pascal; Holsheimer, J.; Goujon, Colette; Keravel, Yves; Nguyen, Jean-Paul

    Epidural motor cortex stimulation (EMCS) is a therapeutic option for chronic, drug-resistant neuropathic pain, but its mechanisms of action remain poorly understood. In two patients with refractory hand pain successfully treated by EMCS, the presence of implanted epidural cervical electrodes for

  10. Neuropathic Pain Mechanisms in Patients with Chronic Sports Injuries : A Diagnostic Model Useful in Sports Medicine?

    NARCIS (Netherlands)

    van Wilgen, Cornelis P.; Keizer, Doeke

    2011-01-01

    Objective. The pathophysiology of chronic sports injuries such as overuse or tendinopathy remains largely unknown. With this exploratory study, we aim to detect signs of sensitization of the nervous system. Sensitization is an indication of the involvement of neuropathic mechanisms in patients with

  11. Self-reported somatosensory symptoms of neuropathic pain in fibromyalgia and chronic widespread pain correlate with tender point count and pressure-pain thresholds

    DEFF Research Database (Denmark)

    Amris, Kirstine; Jespersen, Anders; Bliddal, Henning

    2010-01-01

    Widespread pain and pain hypersensitivity are the hallmark of fibromyalgia, a complex pain condition linked to central sensitization. In this study the painDETECT questionnaire (PDQ), validated to identify neuropathic pain and based on pain quality items, was applied in a cross-sectional sample...... of patients with chronic widespread pain (CWP). The aims of the study were to assess the patient-reported sensory neuropathic symptoms by PDQ and to correlate these with tender point (TP) count and pressure-pain thresholds. Eighty-one patients (75 F, 6 M) with CWP (ACR-criteria) filled in the PDQ. Manual TP......-37). Mean PDT was 8.8 kPa (range: 2-36) and mean PTT 30.9 kPa (range: 4-85). Deep-tissue hyperalgesia was the predominant somatosensory symptom reported in 83%, but other neuropathic symptoms were also frequent, e.g. burning 51% and prickling 47%. Statistically significant correlations were found between...

  12. Prevalence of neuropathic pain according to the IASP grading system in patients with chronic non-malignant pain.

    Science.gov (United States)

    Vaegter, Henrik Bjarke; Andersen, Per Grunwald; Madsen, Marianne Frobøse; Handberg, Gitte; Enggaard, Thomas Peter

    2014-01-01

    The primary objective was to determine the prevalence of neuropathic pain according to the new International Association for the Study of Pain (IASP) grading system. The secondary objective was to compare the system classification of neuropathic pain with the classification of neuropathic pain according to a patient-administered screening questionnaire. A Multidisciplinary Pain Center. One hundred twenty patients with a variety of chronic pain conditions referred to a multidisciplinary pain center. Consecutively referred patients filled out the PainDETECT Questionnaire before the first consultation. During the first consultation, patients had pain history taken and bedside examination performed by a pain specialist. Patients were classified according to the score on the PainDETECT Questionnaire and graded according to the IASP grading system about the certainty of neuropathic pain. According to the IASP grading system, 22 patients (18.3%) classified as probable or definite neuropathic pain and 90 patients (75%) as unlikely neuropathic pain. According to the PainDETECT Questionnaire, 55 patients (45%) were classified as likely neuropathic pain and 13 patients (10.8%) as unlikely neuropathic pain. Eleven patients (20%) who were classified as neuropathic pain according to PainDETECT were also classified as probable or definite neuropathic pain by the new IASP grading system. According to the new IASP grading system, less than 20% of the patients referred to a multidisciplinary pain center fulfilled the criteria for neuropathic pain. The classification of neuropathic pain with the IASP system varies from the classification of neuropathic pain with the use of a self-administered screening questionnaire. Wiley Periodicals, Inc.

  13. The effects of spinal cord stimulation on the neuronal activity of the brain in patients with chronic neuropathic pain

    International Nuclear Information System (INIS)

    Kunitake, Ayumi; Hidaka, Nami; Katsuki, Hiroshi; Iwasaki, Tatsuma; Nagamachi, Shigeki; Takasaki, Mayumi; Uno, Takeshi

    2005-01-01

    The effects of spinal cord stimulation (SCS) on the neuronal activity of the brain were examined by single photon emission computed tomography (SPECT) in patients with chronic neuropathic pain. Regional cerebral blood flow (CBF) in each cortical area and the thalamus decreased in several patients without SCS. Patients with central pain due to thalamic hemorrhage showed a decrease in rCBF in the thalamus contralateral to the painful side. During the stimulation period in SCS, parietal rCBF decreased on the side contralateral to the pain. In contrast, rCBF increased in the bilateral frontal and anterior cingulate cortex and in the contralateral temporal lobe in half of the patients in whom SCS was effective in relieving pain. The decrease in thalamic rCBF in two patients with central pain was improved by the SCS therapy; however, pain was relieved in only one of them. In the majority of patients in whom SCS was not effective, there was no change in rCBF in various cortical areas, even after SCS. These results suggest that, in patients with chronic neuropathic pain, SCS modulates the neuronal activities of several brain areas that are believed to be associated with pain processing. (author)

  14. Ameliorative potential of Ocimum sanctum in chronic constriction injury-induced neuropathic pain in rats

    Directory of Open Access Journals (Sweden)

    GURPREET KAUR

    2015-03-01

    Full Text Available The present study was designed to investigate the ameliorative potential of Ocimumsanctum and its saponin rich fraction in chronic constriction injury-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, proximal to its trifurcation. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Chronic constriction injury was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with an increase in oxidative stress and calcium levels. However, administration of Ocimumsanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated chronic constriction injury-induced neuropathic pain as well as decrease the oxidative stress and calcium levels. It may be concluded that saponin rich fraction of Ocimum sanctum has ameliorative potential in attenuating painful neuropathic state, which may be attributed to a decrease in oxidative stress and calcium levels.

  15. Neuropathic pain mechanisms in patients with chronic sports injuries: a diagnostic model useful in sports medicine?

    Science.gov (United States)

    van Wilgen, Cornelis P; Keizer, Doeke

    2011-01-01

    The pathophysiology of chronic sports injuries such as overuse or tendinopathy remains largely unknown. With this exploratory study, we aim to detect signs of sensitization of the nervous system. Sensitization is an indication of the involvement of neuropathic mechanisms in patients with chronic sports injuries. Sensory descriptors were assessed by means of a neuropathic pain questionnaire (DN4-interview) and by three methods of sensory testing. The test results were integrated in a scoring system. Patients were recruited from an outpatient clinic of a University Medical Centre and at primary care physical therapy practices. Fifteen athletes with a unilateral chronic sports injury were included. All subjects filled out the seven-items of the DN4-interview to assess sensory descriptors. Next, the presence of brush-evoked allodynia was assessed and pain thresholds with Von Frey monofilaments and a pressure algometer were measured in all patients to determine signs of sensitization. Based on the scoring system, in 4 out of 15 patients (27%) the presence of sensitization could be detected. In two other patients, signs of hypoalgesia were observed. The involvement of sensitization as an explanation for the pain in chronic sports injuries is credible in a considerable proportion of patients. With respect to treatment, the establishment of such neuropathic pain mechanisms is of clinical significance. Wiley Periodicals, Inc.

  16. Central sensitization in chronic low back pain: A narrative review.

    Science.gov (United States)

    Sanzarello, Ilaria; Merlini, Luciano; Rosa, Michele Attilio; Perrone, Mariada; Frugiuele, Jacopo; Borghi, Raffaele; Faldini, Cesare

    2016-11-21

    Low back pain is one of the four most common disorders in all regions, and the greatest contributor to disability worldwide, adding 10.7% of total years lost due to this health state. The etiology of chronic low back pain is, in most of the cases (up to 85%), unknown or nonspecific, while the specific causes (specific spinal pathology and neuropathic/radicular disorders) are uncommon. Central sensitization has been recently recognized as a potential pathophysiological mechanism underlying a group of chronic pain conditions, and may be a contributory factor for a sub-group of patients with chronic low back pain. The purposes of this narrative review are twofold. First, to describe central sensitization and its symptoms and signs in patients with chronic pain disorders in order to allow its recognition in patients with nonspecific low back pain. Second, to provide general treatment principles of chronic low back pain with particular emphasis on pharmacotherapy targeting central sensitization.

  17. Chronic pain in Gaucher disease: skeletal or neuropathic origin?

    Science.gov (United States)

    Devigili, Grazia; De Filippo, Michele; Ciana, Giovanni; Dardis, Andrea; Lettieri, Christian; Rinaldo, Sara; Macor, Daniela; Moro, Alessandro; Eleopra, Roberto; Bembi, Bruno

    2017-08-31

    Pain is one of the most disabling symptoms of Gaucher disease. It is referred by the majority of Gaucher patients and often persists despite long-term enzyme replacement treatment. It has been mainly considered as nociceptive pain secondary to skeletal involvement but it is described even in the absence of bone disease without a clear explanation. In the last years an increasing number of reports have described the presence of neurological manifestation in Gaucher type 1 patients, including subclinical large fibre neuropathy. In our Gaucher clinic we have observed the recurrence of painful symptoms in a group of type 1 Gaucher patients even after a long-term enzyme replacement therapy. A cross-sectional study was designed to investigate the pathophysiology of pain in a cohort of 25 Gaucher patients (13 females, 12 males). Twenty-two patients received enzyme replacement therapy for a period of time ranging from 10 to >20 years, while three were new diagnosis. Pain was classified as bone or neurologic related on the basis of anamnestic data, clinical and electrophysilogical examinations. Intensity and quality of pain were recorded by Douleur Neuropathique en 4 questionnaire and Neuropathic Pain Symptom Inventory. Neuroalgological evaluation, quantitative sensory testing, nerve conduction studies and evaluation of epidermal nerve fibres density were performed. Comorbidities for peripheral neuropathy were excluded. Thirteen patients complained of pain suggestive of neuropathic origin with proximal patchy distribution, six manifested severe pain paroxysmal, nine pinprick hypoesthesia and 17 thermal hypoesthesia. At quantitative sensory testing, all of them showed high cold thresholds with errata sensation (burning instead of cold), paradoxical heat sensation and mechanic hypoesthesia; three patients showed pressure pain hyperalgesia. Epidermal denervation was present in 19 patients, 12 of them with non-length dependent pattern. These results confirm the role of

  18. Brain activity modifications following spinal cord stimulation for chronic neuropathic pain: A systematic review.

    Science.gov (United States)

    Bentley, L D; Duarte, R V; Furlong, P L; Ashford, R L; Raphael, J H

    2016-04-01

    Spinal cord stimulation (SCS) is believed to exert supraspinal effects; however, these mechanisms are still far from fully elucidated. This systematic review aims to assess existing neurophysiological and functional neuroimaging literature to reveal current knowledge regarding the effects of SCS for chronic neuropathic pain on brain activity, to identify gaps in knowledge, and to suggest directions for future research. Electronic databases and hand-search of reference lists were employed to identify publications investigating brain activity associated with SCS in patients with chronic neuropathic pain, using neurophysiological and functional neuroimaging techniques (fMRI, PET, MEG, EEG). Studies investigating patients with SCS for chronic neuropathic pain and studying brain activity related to SCS were included. Demographic data (age, gender), study factors (imaging modality, patient diagnoses, pain area, duration of SCS at recording, stimulus used) and brain areas activated were extracted from the included studies. Twenty-four studies were included. Thirteen studies used neuroelectrical imaging techniques, eight studies used haemodynamic imaging techniques, two studies employed both neuroelectrical and haemodynamic techniques separately, and one study investigated cerebral neurobiology. The limited available evidence regarding supraspinal mechanisms of SCS does not allow us to develop any conclusive theories. However, the studies included appear to show an inhibitory effect of SCS on somatosensory evoked potentials, as well as identifying the thalamus and anterior cingulate cortex as potential mediators of the pain experience. The lack of substantial evidence in this area highlights the need for large-scale controlled studies of this kind. © 2015 European Pain Federation - EFIC®

  19. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin: systematic review and economic evaluation.

    Science.gov (United States)

    Simpson, E L; Duenas, A; Holmes, M W; Papaioannou, D; Chilcott, J

    2009-03-01

    This report addressed the question 'What is the clinical and cost-effectiveness of spinal cord stimulation (SCS) in the management of chronic neuropathic or ischaemic pain?' Thirteen electronic databases [including MEDLINE (1950-2007), EMBASE (1980-2007) and the Cochrane Library (1991-2007)] were searched from inception; relevant journals were hand-searched; and appropriate websites for specific conditions causing chronic neuropathic/ischaemic pain were browsed. Literature searches were conducted from August 2007 to September 2007. A systematic review of the literature sought clinical and cost-effectiveness data for SCS in adults with chronic neuropathic or ischaemic pain with inadequate response to medical or surgical treatment other than SCS. Economic analyses were performed to model the cost-effectiveness and cost-utility of SCS in patients with neuropathic or ischaemic pain. From approximately 6000 citations identified, 11 randomised controlled trials (RCTs) were included in the clinical effectiveness review: three of neuropathic pain and eight of ischaemic pain. Trials were available for the neuropathic conditions failed back surgery syndrome (FBSS) and complex regional pain syndrome (CRPS) type I, and they suggested that SCS was more effective than conventional medical management (CMM) or reoperation in reducing pain. The ischaemic pain trials had small sample sizes, meaning that most may not have been adequately powered to detect clinically meaningful differences. Trial evidence failed to demonstrate that pain relief in critical limb ischaemia (CLI) was better for SCS than for CMM; however, it suggested that SCS was effective in delaying refractory angina pain onset during exercise at short-term follow-up, although not more so than coronary artery bypass grafting (CABG) for those patients eligible for that surgery. The results for the neuropathic pain model suggested that the cost-effectiveness estimates for SCS in patients with FBSS who had inadequate

  20. Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury.

    Science.gov (United States)

    Carlton, Susan M; Du, Junhui; Tan, Huai Yu; Nesic, Olivera; Hargett, Gregory L; Bopp, Anne C; Yamani, Ammar; Lin, Qing; Willis, William D; Hulsebosch, Claire E

    2009-12-15

    Central neuropathic pain (CNP) developing after spinal cord injury (SCI) is described by the region affected: above-level, at-level and below-level pain occurs in dermatomes rostral, at/near, or below the SCI level, respectively. People with SCI and rodent models of SCI develop above-level pain characterized by mechanical allodynia and thermal hyperalgesia. Mechanisms underlying this pain are unknown and the goals of this study were to elucidate components contributing to the generation of above-level CNP. Following a thoracic (T10) contusion, forelimb nociceptors had enhanced spontaneous activity and were sensitized to mechanical and thermal stimulation of the forepaws 35 days post-injury. Cervical dorsal horn neurons showed enhanced responses to non-noxious and noxious mechanical stimulation as well as thermal stimulation of receptive fields. Immunostaining dorsal root ganglion (DRG) cells and cord segments with activating transcription factor 3 (ATF3, a marker for neuronal injury) ruled out neuronal damage as a cause for above-level sensitization since few C8 DRG cells expressed AFT3 and cervical cord segments had few to no ATF3-labeled cells. Finally, activated microglia and astrocytes were present in thoracic and cervical cord at 35 days post-SCI, indicating a rostral spread of glial activation from the injury site. Based on these data, we conclude that peripheral and central sensitization as well as reactive glia in the uninjured cervical cord contribute to CNP. We hypothesize that reactive glia in the cervical cord release pro-inflammatory substances which drive chronic CNP. Thus a complex cascade of events spanning many cord segments underlies above-level CNP.

  1. Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury

    OpenAIRE

    Carlton, Susan M.; Du, Junhui; Tan, Huai Yu; Nesic, Olivera; Hargett, Gregory L.; Bopp, Anne C.; Yamani, Ammar; Lin, Qing; Willis, William D.; Hulsebosch, Claire E.

    2009-01-01

    Central neuropathic pain (CNP) developing after spinal cord injury (SCI) is described by the region affected: above-level, at-level and below-level pain occurs in dermatomes rostral, at/near, or below the SCI level, respectively. People with SCI and rodent models of SCI develop above-level pain characterized by mechanical allodynia and thermal hyperalgesia. Mechanisms underlying this pain are unknown and the goals of this study were to elucidate components contributing to the generation of ab...

  2. Experiences with spinal cord stimulator in patients with chronic neuropathic back pain.

    Science.gov (United States)

    Gjesdal, Kine; Furnes, Bodil; Dysvik, Elin

    2014-09-01

    Neuropathic pain is a complex, chronic, and disabling condition that has physical, functional, and psychosocial repercussions. Although the estimated prevalence of neuropathic pain in the general population ranges from 1.5% to 8%, neuropathic pain is frequently underdiagnosed and undertreated. The aims of this study were to examine the experience of patients treated with spinal cord stimulation as a pain-relieving treatment and how this may influence the patient's ability to participate in everyday life activities. A qualitative approach based on seven telephone interviews was performed. The participants were recruited from a university hospital in Norway, and all used spinal cord stimulation as a pain-relieving treatment. Qualitative content analysis was used. Two thematic findings emerged: (1) pain relief with spinal cord stimulation as a complex and individual experience and (2) challenges in adaptations in everyday life with spinal cord stimulation. Findings indicate that spinal cord stimulation can offer pain relief that can help patients achieve a meaningful life despite chronic pain. Spinal cord stimulation also may have disadvantages that should be considered before offering this treatment. It seems evident that extended information needs about working mechanism of SCS and precautions as well as follow-up are required to meet unexpected challenges in adaptation. Here the nurse has an important role when informing and following this patient group. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  3. Pain following cancer treatment: Guidelines for the clinical classification of predominant neuropathic, nociceptive and central sensitization pain.

    Science.gov (United States)

    Nijs, Jo; Leysen, Laurence; Adriaenssens, Nele; Aguilar Ferrándiz, Maria Encarnación; Devoogdt, Nele; Tassenoy, An; Ickmans, Kelly; Goubert, Dorien; van Wilgen, C Paul; Wijma, Amarins J; Kuppens, Kevin; Hoelen, Wouter; Hoelen, Astrid; Moloney, Niamh; Meeus, Mira

    2016-06-01

    In addition to fatigue, pain is the most frequent persistent symptom in cancer survivors. Clear guidelines for both the diagnosis and treatment of pain in cancer survivors are lacking. Classification of pain is important as it may facilitate more specific targeting of treatment. In this paper we present an overview of nociceptive, neuropathic and central sensitization pain following cancer treatment, as well as the rationale, criteria and process for stratifying pain classification. Recently, a clinical method for classifying any pain as either predominant central sensitization pain, neuropathic or nociceptive pain was developed, based on a large body of research evidence and international expert opinion. We, a team of 15 authors from 13 different centers, four countries and two continents have applied this classification algorithm to the cancer survivor population. The classification of pain following cancer treatment entails two steps: (1) examining the presence of neuropathic pain; and (2) using an algorithm for differentiating predominant nociceptive and central sensitization pain. Step 1 builds on the established criteria for neuropathic pain diagnosis, while Step 2 applies a recently developed clinical method for classifying any pain as either predominant central sensitization pain, neuropathic or nociceptive pain to the cancer survivor population. The classification criteria allow identifying central sensitization pain following cancer treatment. The recognition of central sensitization pain in practice is an important development in the integration of pain neuroscience into the clinic, and one that is relevant for people undergoing and following cancer treatment.

  4. Spinal neuropeptide expression and neuropathic behavior in the acute and chronic phases after spinal cord injury: Effects of progesterone administration.

    Science.gov (United States)

    Coronel, María F; Villar, Marcelo J; Brumovsky, Pablo R; González, Susana L

    2017-02-01

    Patients with spinal cord injury (SCI) develop chronic pain that severely compromises their quality of life. We have previously reported that progesterone (PG), a neuroprotective steroid, could offer a promising therapeutic strategy for neuropathic pain. In the present study, we explored temporal changes in the expression of the neuropeptides galanin and tyrosine (NPY) and their receptors (GalR1 and GalR2; Y1R and Y2R, respectively) in the injured spinal cord and evaluated the impact of PG administration on both neuropeptide systems and neuropathic behavior. Male rats were subjected to spinal cord hemisection at T13 level, received daily subcutaneous injections of PG or vehicle, and were evaluated for signs of mechanical and thermal allodynia. Real time PCR was used to determine relative mRNA levels of neuropeptides and receptors, both in the acute (1day) and chronic (28days) phases after injury. A significant increase in Y1R and Y2R expression, as well as a significant downregulation in GalR2 mRNA levels, was observed 1day after SCI. Interestingly, PG early treatment prevented Y1R upregulation and resulted in lower NPY, Y2R and GalR1 mRNA levels. In the chronic phase, injured rats showed well-established mechanical and cold allodynia and significant increases in galanin, NPY, GalR1 and Y1R mRNAs, while maintaining reduced GalR2 expression. Animals receiving PG treatment showed basal expression levels of galanin, NPY, GalR1 and Y1R, and reduced Y2R mRNA levels. Also, and in line with previously published observations, PG-treated animals did not develop mechanical allodynia and showed reduced sensitivity to cold stimulation. Altogether, we show that SCI leads to considerable changes in the spinal expression of galanin, NPY and their associated receptors, and that early and sustained PG administration prevents them. Moreover, our data suggest the participation of galaninergic and NPYergic systems in the plastic changes associated with SCI-induced neuropathic pain

  5. Reduction of central neuropathic pain with ketamine infusion in a patient with Ehlers–Danlos syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Lo TC

    2016-09-01

    Full Text Available Tony Chung Tung Lo,1,* Stephen Tung Yeung,2,* Sujin Lee,1 Kira Skavinski,3 Solomon Liao,4 1Department of Physical Medicine and Rehabilitation, University of California Irvine, Orange, CA, 2Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, 3Department of Palliative Medicine, University of California San Diego, La Jolla, 4Department of Palliative Medicine, University of California Irvine, Orange, CA, USA *These authors contributed equally to this work Objective: Ehlers–Danlos syndrome frequently causes acute and chronic pain because of joint subluxations and dislocations secondary to hypermobility. Current treatments for pain related to Ehlers–Danlos syndrome and central pain syndrome are inadequate. This case report discusses the therapeutic use of ketamine intravenous infusion as an alternative. Case report: A 27-year-old Caucasian female with a history of Ehlers–Danlos syndrome and spinal cord ischemic myelopathy resulting in central pain syndrome, presented with severe generalized body pain refractory to multiple pharmacological interventions. After a 7-day course of ketamine intravenous infusion under controlled generalized sedation in the intensive care unit, the patient reported a dramatic reduction in pain levels from 7–8 out of 10 to 0–3 out of 10 on a numeric rating scale and had a significant functional improvement. The patient tolerated a reduction in her pain medication regimen, which originally included opioids, gabapentin, pregabalin, tricyclic antidepressants, and nonsteroidal anti-inflammatory drugs. Conclusion: Ketamine infusion treatment has been used in various pain syndromes, including central neuropathic pain, ischemic pain, and regional pain syndrome. Reports have suggested that ketamine modulates pain by the regression of N-methyl-D-aspartate receptor to a resting state. As such, propagation of nociceptive signal to brain is interrupted allowing for the restoration of

  6. Astrocytic CX43 hemichannels and gap junctions play a crucial role in development of chronic neuropathic pain following spinal cord injury.

    Science.gov (United States)

    Chen, Michael J; Kress, Benjamin; Han, Xiaoning; Moll, Katherine; Peng, Weiguo; Ji, Ru-Rong; Nedergaard, Maiken

    2012-11-01

    Chronic neuropathic pain is a frequent consequence of spinal cord injury (SCI). Yet despite recent advances, upstream releasing mechanisms and effective therapeutic options remain elusive. Previous studies have demonstrated that SCI results in excessive ATP release to the peritraumatic regions and that purinergic signaling, among glial cells, likely plays an essential role in facilitating inflammatory responses and nociceptive sensitization. We sought to assess the role of connexin 43 (Cx43) as a mediator of CNS inflammation and chronic pain. To determine the extent of Cx43 involvement in chronic pain, a weight-drop SCI was performed on transgenic mice with Cx43/Cx30 deletions. SCI induced robust and persistent neuropathic pain including heat hyperalgesia and mechanical allodynia in wild-type control mice, which developed after 4 weeks and was maintained after 8 weeks. Notably, SCI-induced heat hyperalgesia and mechanical allodynia were prevented in transgenic mice with Cx43/Cx30 deletions, but fully developed in transgenic mice with only Cx30 deletion. SCI-induced gliosis, detected as upregulation of glial fibrillary acidic protein in the spinal cord astrocytes at different stages of the injury, was also reduced in the knockout mice with Cx43/Cx30 deletions, when compared with littermate controls. In comparison, a standard regimen of post-SCI treatment of minocycline attenuated neuropathic pain to a significantly lesser degree than Cx43 deletion. These findings suggest Cx43 is critically linked to the development of central neuropathic pain following acute SCI. Since Cx43/Cx30 is expressed by astrocytes, these findings also support an important role of astrocytes in the development of chronic pain. Copyright © 2012 Wiley Periodicals, Inc.

  7. Self-reported somatosensory symptoms of neuropathic pain in fibromyalgia and chronic widespread pain correlate with tender point count and pressure-pain thresholds

    DEFF Research Database (Denmark)

    Amris, Kirstine; Jespersen, Anders; Bliddal, Henning

    2010-01-01

    Widespread pain and pain hypersensitivity are the hallmark of fibromyalgia, a complex pain condition linked to central sensitization. In this study the painDETECT questionnaire (PDQ), validated to identify neuropathic pain and based on pain quality items, was applied in a cross-sectional sample...... of patients with chronic widespread pain (CWP). The aims of the study were to assess the patient-reported sensory neuropathic symptoms by PDQ and to correlate these with tender point (TP) count and pressure-pain thresholds. Eighty-one patients (75 F, 6 M) with CWP (ACR-criteria) filled in the PDQ. Manual TP...... examination was conducted according to ACR guidelines. Computerized cuff pressure algometry was used for the assessment of pressure-pain detection thresholds (PDT, unit: kPa) and pressure-pain tolerance thresholds (PTT, unit: kPa). Mean TP count was 14.32 (range: 2-18), mean PDQ score 22.75 (range: 5...

  8. Peripheral nerve stimulation (PNS) in the trapezius muscle region alleviate chronic neuropathic pain after lower brachial plexus root avulsion lesion: A case report

    DEFF Research Database (Denmark)

    Sørensen, Jens Christian Hedemann; Meier, Kaare; Perinpam, Larshan

    Peripheral nerve stimulation (PNS) in the trapezius muscle region alleviate chronic neuropathic pain after lower brachial plexus root avulsion lesion: A case report......Peripheral nerve stimulation (PNS) in the trapezius muscle region alleviate chronic neuropathic pain after lower brachial plexus root avulsion lesion: A case report...

  9. GLT1 overexpression reverses established neuropathic pain-related behavior and attenuates chronic dorsal horn neuron activation following cervical spinal cord injury.

    Science.gov (United States)

    Falnikar, Aditi; Hala, Tamara J; Poulsen, David J; Lepore, Angelo C

    2016-03-01

    Development of neuropathic pain occurs in a major portion of traumatic spinal cord injury (SCI) patients, resulting in debilitating and often long-term physical and psychological burdens. Following SCI, chronic dysregulation of extracellular glutamate homeostasis has been shown to play a key role in persistent central hyperexcitability of superficial dorsal horn neurons that mediate pain neurotransmission, leading to various forms of neuropathic pain. Astrocytes express the major CNS glutamate transporter, GLT1, which is responsible for the vast majority of functional glutamate uptake, particularly in the spinal cord. In our unilateral cervical contusion model of mouse SCI that is associated with ipsilateral forepaw heat hypersensitivity (a form of chronic at-level neuropathic pain-related behavior), we previously reported significant and long-lasting reductions in GLT1 expression and functional GLT1-mediated glutamate uptake in cervical spinal cord dorsal horn. To therapeutically address GLT1 dysfunction following cervical contusion SCI, we injected an adeno-associated virus type 8 (AAV8)-Gfa2 vector into the superficial dorsal horn to increase GLT1 expression selectively in astrocytes. Compared to both contusion-only animals and injured mice that received AAV8-eGFP control injection, AAV8-GLT1 delivery increased GLT1 protein expression in astrocytes of the injured cervical spinal cord dorsal horn, resulting in a significant and persistent reversal of already-established heat hypersensitivity. Furthermore, AAV8-GLT1 injection significantly reduced expression of the transcription factor and marker of persistently increased neuronal activation, ΔFosB, in superficial dorsal horn neurons. These results demonstrate that focal restoration of GLT1 expression in the superficial dorsal horn is a promising target for treating chronic neuropathic pain following SCI. © 2015 Wiley Periodicals, Inc.

  10. Analgesic effect of piracetam on peripheral neuropathic pain induced by chronic constriction injury of sciatic nerve in rats.

    Science.gov (United States)

    Mehta, Ashish K; Bhati, Yogendra; Tripathi, Chakra D; Sharma, Krishna K

    2014-08-01

    Despite immense advances in the treatment strategies, management of neuropathic pain remains unsatisfactory. Piracetam is a prototype of nootropic drugs, used to improve cognitive impairment. The present study was designed to investigate the effect of piracetam on peripheral neuropathic pain in rats. Neuropathic pain was induced by the chronic constriction injury of the sciatic nerve. Following this, piracetam was intraperitoneally administered for 2 weeks in doses of 50, 100 and 200 mg/kg, and pain was assessed by employing the behavioural tests for thermal hyperalgesia (hot plate and tail flick tests) and cold allodynia (acetone test). After the induction of neuropathic pain, significant development of thermal hyperalgesia and cold allodynia was observed. The administration of piracetam (50 mg/kg) did not have any significant effect on all the behavioural tests. Further, piracetam (100 mg/kg) also had no effect on the hot plate and tail flick tests; however it significantly decreased the paw withdrawal duration in the acetone test. Piracetam in a dose of 200 mg/kg significantly modulated neuropathic pain as observed from the increased hot plate and tail flick latencies, and decreased paw withdrawal duration (in acetone test). Therefore, the present study suggests the potential use of piracetam in the treatment of neuropathic pain, which merits further clinical investigation.

  11. Cognitive Impairment in Patients with Chronic Neuropathic or Radicular Pain: An Interaction of Pain and Age

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    Orla Moriarty

    2017-06-01

    Full Text Available A growing body of empirical research has confirmed an association between chronic pain and cognitive dysfunction. The aim of the present study was to determine whether cognitive function is affected in patients with a diagnosis of chronic neuropathic or radicular pain relative to healthy control participants matched by age, gender, and years of education. We also examined the interaction of pain with age in terms of cognitive performance. Some limitations of previous clinical research investigating the effects of chronic pain on cognitive function include differences in the pain and cognitive scale materials used, and the heterogeneity of patient participants, both in terms of their demographics and pathological conditions. To address these potential confounds, we have used a relatively homogenous patient group and included both experimental and statistical controls. We have also specifically investigated the interaction effect of pain and age on cognitive performance. Patients (n = 38 and controls (n = 38 were administered a battery of cognitive tests measuring IQ, spatial and verbal memory, attention, and executive function. Educational level, depressive symptoms, and state anxiety were assessed as were medication usage, caffeine, and nicotine consumption to control for possible confounding effects. Both the level of depressive symptoms and the state anxiety score were higher in chronic pain patients than in matched control participants. Chronic pain patients had a lower estimated IQ than controls, and showed impairments on measures of spatial and verbal memory. Attentional responding was altered in the patient group, possibly indicative of impaired inhibitory control. There were significant interactions between chronic pain condition and age on a number of cognitive outcome variables, such that older patients with chronic pain were more impaired than both age-matched controls and younger patients with chronic pain. Chronic pain did not appear

  12. Virtual Reality Hypnosis In The Treatment Of Chronic Neuropathic Pain: A Case Report

    Science.gov (United States)

    Oneal, Brent J.; Patterson, David R.; Soltani, Maryam; Teeley, Aubriana; Jensen, Mark P.

    2009-01-01

    This case report evaluates virtual reality hypnosis (VRH) in treating chronic neuropathic pain in a patient with a 5-year history of failed treatments. The patient participated in a 6-month trial of VRH, and her pain ratings of intensity and unpleasantness dropped on average 36% and 33%, respectively, over the course of 33 sessions. In addition, she reported both no pain and a reduction of pain for an average of 3.86 and 12.21 hours, respectively, after treatment sessions throughout the course of the VRH treatment. These reductions and the duration of treatment effects following VRH treatment were superior to those following a trial of standard hypnosis (non-VR) treatment. However, the pain reductions with VRH did not persist over long periods of time. The findings support the potential of VRH treatment for helping individuals with refractory chronic pain conditions. PMID:18726807

  13. A Case of Chronic Abdominal Neuropathic Pain and Burning after Female Genital Cutting

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    Vicky Hadid

    2015-01-01

    Full Text Available Introduction. Female genital cutting is prevalent in the Middle Eastern and African countries. This ritual entails not only immediate complications such as infection, pain, and haemorrhage, but also chronic ones including dysmenorrhea and dyspareunia. However, there is limited data on neuropathic pain secondary to female genital mutilation when searching the literature. Case. This case discusses a 38-year-old female with a history of infibulation who presented with a chronic burning abdominal and anterior vulvar pain including the related investigations and treatment. Discussion. This case brings to light the additional delayed complication of this ritual: sensory neuropathy. Our goal is to educate health professionals to be aware of these complications and to appropriately investigate and treat them in order to find a solution to relieve the patients’ symptoms.

  14. Percutaneous nerve stimulation in chronic neuropathic pain patients due to spinal cord injury: a pilot study.

    Science.gov (United States)

    Kopsky, David Jos; Ettema, Frank Willem Leo; van der Leeden, Marike; Dekker, Joost; Stolwijk-Swüste, Janneke Marjan

    2014-03-01

    The long-term prognosis for neuropathic pain resolution following spinal cord injury (SCI) is often poor. In many SCI patients, neuropathic pain continues or even worsens over time. Thus, new treatment approaches are needed. We conducted a pilot study to evaluate the feasibility and effect of percutaneous (electrical) nerve stimulation (P(E)NS) in SCI patients with chronic neuropathic pain. In 18 weeks, 12 P(E)NS treatments were scheduled. Assessment with questionnaires was performed at baseline (T0), after 8 weeks (T8), 18 weeks (T18), and 12 weeks post-treatment (T30). From 26 screened patients, 17 were included. In total, 91.2% questionnaires were returned, 2 patients dropped out, and 4.2% of the patients reported minor side effects. Pain scores on the week pain diary measured with the numerical rating scale improved significantly at T8, from 6.5 at baseline to 5.4, and were still significantly improved at T18. Pain reduction of ≥ 30% directly after a session was reported in 64.6% sessions. In total, 6 patients experienced reduction in size of the pain areas at T18 and T30, with a mean reduction of 45.8% at T18 and 45.3% at T30. P(E)NS is feasible as an intervention in SCI patients and might have a positive effect on pain reduction in a part of this patient group. © 2013 The Authors Pain Practice © 2013 World Institute of Pain.

  15. Contribution of microglia and astrocytes to the central sensitization, inflammatory and neuropathic pain in the juvenile rat

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    Ikeda Hiroshi

    2012-06-01

    Full Text Available Abstract Background The development of pain after peripheral nerve and tissue injury involves not only neuronal pathways but also immune cells and glia. Central sensitization is thought to be a mechanism for such persistent pain, and ATP involves in the process. We examined the contribution of glia to neuronal excitation in the juvenile rat spinal dorsal horn which is subjected to neuropathic and inflammatory pain. Results In rats subjected to neuropathic pain, immunoreactivity for the microglial marker OX42 was markedly increased. In contrast, in rats subjected to inflammatory pain, immunoreactivity for the astrocyte marker glial fibrillary acidic protein was increased slightly. Optically-recorded neuronal excitation induced by single-pulse stimulation to the dorsal root was augmented in rats subjected to neuropathic and inflammatory pain compared to control rats. The bath application of a glial inhibitor minocycline and a p38 mitogen-activated protein kinase inhibitor SB203580 inhibited the neuronal excitation in rats subjected to neuropathic pain. A specific P2X1,2,3,4 antagonist TNP-ATP largely inhibited the neuronal excitation only in rats subjected to neuropathic pain rats. In contrast, an astroglial toxin L-alpha-aminoadipate, a gap junction blocker carbenoxolone and c-Jun N-terminal kinase inhibitor SP600125 inhibited the neuronal excitation only in rats subjected to inflammatory pain. A greater number of cells in spinal cord slices from rats subjected to neuropathic pain showed Ca2+ signaling in response to puff application of ATP. This Ca2+ signaling was inhibited by minocycline and TNP-ATP. Conclusions These results directly support the notion that microglia is more involved in neuropathic pain and astrocyte in inflammatory pain.

  16. Contribution of microglia and astrocytes to the central sensitization, inflammatory and neuropathic pain in the juvenile rat.

    Science.gov (United States)

    Ikeda, Hiroshi; Kiritoshi, Takaki; Murase, Kazuyuki

    2012-06-15

    The development of pain after peripheral nerve and tissue injury involves not only neuronal pathways but also immune cells and glia. Central sensitization is thought to be a mechanism for such persistent pain, and ATP involves in the process. We examined the contribution of glia to neuronal excitation in the juvenile rat spinal dorsal horn which is subjected to neuropathic and inflammatory pain. In rats subjected to neuropathic pain, immunoreactivity for the microglial marker OX42 was markedly increased. In contrast, in rats subjected to inflammatory pain, immunoreactivity for the astrocyte marker glial fibrillary acidic protein was increased slightly. Optically-recorded neuronal excitation induced by single-pulse stimulation to the dorsal root was augmented in rats subjected to neuropathic and inflammatory pain compared to control rats. The bath application of a glial inhibitor minocycline and a p38 mitogen-activated protein kinase inhibitor SB203580 inhibited the neuronal excitation in rats subjected to neuropathic pain. A specific P2X1,2,3,4 antagonist TNP-ATP largely inhibited the neuronal excitation only in rats subjected to neuropathic pain rats. In contrast, an astroglial toxin L-alpha-aminoadipate, a gap junction blocker carbenoxolone and c-Jun N-terminal kinase inhibitor SP600125 inhibited the neuronal excitation only in rats subjected to inflammatory pain. A greater number of cells in spinal cord slices from rats subjected to neuropathic pain showed Ca2+ signaling in response to puff application of ATP. This Ca2+ signaling was inhibited by minocycline and TNP-ATP. These results directly support the notion that microglia is more involved in neuropathic pain and astrocyte in inflammatory pain.

  17. Assessment and management of pain, with particular emphasis on central neuropathic pain, in moderate to severe dementia

    NARCIS (Netherlands)

    Scherder, E.J.A.; Plooij, B.

    2012-01-01

    In patients with dementia, undertreatment of pain, irrespective of its aetiology, is widely recognized; the risk for undertreatment increases with the severity of dementia. We argue, however, that central neuropathic pain is by far the most undertreated type of pain in patients with dementia.

  18. Mechanisms of Chronic Central Neuropathic Pain after Spinal Cord Injury

    OpenAIRE

    Hulsebosch, Claire E.; Hains, Bryan C.; Crown, Eric D.; Carlton, Susan M.

    2008-01-01

    Not all spinal contusions result in mechanical allodynia, in which non-noxious stimuli become noxious. The studies presented use the NYU impactor at 12.5 mm drop or the Infinite Horizons Impactor (150 kdyne, 1 sec dwell) devices to model spinal cord injury (SCI). Both of these devices and injury parameters, if done correctly, will result in animals with above level (forelimb), at level (trunk) and below level (hindlimb) mechanical allodynia that model the changes in evoked somatosensation exp...

  19. Alpha-1 Adrenoceptor Hyperresponsiveness in Three Neuropathic Pain States: Complex Regional Pain Syndrome 1, Diabetic Peripheral Neuropathic Pain and Central Pain States Following Spinal Cord Injury

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    Robert W Teasell

    2004-01-01

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

  20. Most Relevant Neuropathic Pain Treatment and Chronic Low Back Pain Management Guidelines: A Change Pain Latin America Advisory Panel Consensus.

    Science.gov (United States)

    Amescua-Garcia, Cesar; Colimon, Frantz; Guerrero, Carlos; Jreige Iskandar, Aziza; Berenguel Cook, Maria; Bonilla, Patricia; Campos Kraychete, Durval; Delgado Barrera, William; Alberto Flores Cantisani, Jose; Hernandez-Castro, John Jairo; Lara-Solares, Argelia; Perez Hernandez, Concepcion; Rico, Maria Antonieta; Del Rocio Guillen Nunez, Maria; Sempertegui Gallegos, Manuel; Garcia, Joao Batista Santos

    2018-03-01

    Chronic pain conditions profoundly affect the daily living of a significant number of people and are a major economic and social burden, particularly in developing countries. The Change Pain Latin America (CPLA) advisory panel aimed to identify the most appropriate guidelines for the treatment of neuropathic pain (NP) and chronic low back pain (CLBP) for use across Latin America. Published systematic reviews or practice guidelines were identified by a systematic search of PubMed, the Guidelines Clearinghouse, and Google. Articles were screened by an independent reviewer, and potential candidate guidelines were selected for more in-depth review. A shortlist of suitable guidelines was selected and critically evaluated by the CPLA advisory panel. Searches identified 674 and 604 guideline articles for NP and CLBP, respectively. Of these, 14 guidelines were shortlisted for consensus consideration, with the following final selections made: "Recommendations for the pharmacological management of neuropathic pain from the Neuropathic Pain Special Interest Group in 2015-pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis."Diagnosis and treatment of low back pain: A joint clinical practice guideline from the American College of Physicians and the American Pain Society" (2007). The selected guidelines were endorsed by all members of the CPLA advisory board as the best fit for use across Latin America. In addition, regional considerations were discussed and recorded. We have included this expert local insight and advice to enhance the implementation of each guideline across all Latin American countries.

  1. An open-label, long-term study examining the safety and tolerability of pregabalin in Japanese patients with central neuropathic pain

    Directory of Open Access Journals (Sweden)

    Onouchi K

    2014-07-01

    patients with chronic central neuropathic pain. Keywords: clinical trial, spinal cord injury, multiple sclerosis, cerebral stroke

  2. Pregabalin in patients with central neuropathic pain: a randomized, double-blind, placebo-controlled trial of a flexible-dose regimen

    NARCIS (Netherlands)

    Vranken, J. H.; Dijkgraaf, M. G. W.; Kruis, M. R.; van der Vegt, M. H.; Hollmann, M. W.; Heesen, M.

    2008-01-01

    The effective treatment of patients suffering from central neuropathic pain remains a clinical challenge, despite a standard pharmacological approach in combination with anticonvulsants and antidepressants. A randomized, double-blinded, placebo-controlled trial evaluated the effects of pregabalin on

  3. Duloxetine in patients with central neuropathic pain caused by spinal cord injury or stroke: a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Vranken, J. H.; Hollmann, M. W.; van der Vegt, M. H.; Kruis, M. R.; Heesen, M.; Vos, K.; Pijl, A. J.; Dijkgraaf, M. G. W.

    2011-01-01

    The mechanisms underlying central neuropathic pain are poorly understood. Pain inhibitory mechanisms including sertononergic and norepinephrine systems may be dysfunctional. In this randomized, double-blinded, placebo-controlled trial we evaluated the effects of duloxetine on pain relief

  4. Living with chronic neuropathic pain after spinal cord injury: an interpretative phenomenological analysis of community experience.

    Science.gov (United States)

    Hearn, Jasmine H; Cotter, Imogen; Fine, Philip; A Finlay, Katherine

    2015-01-01

    This article presents an in-depth, idiographic study examining the lived experience of chronic pain following spinal cord injury (SCI). Neuropathic pain (NP) occurs in a large majority of the SCI population and is particularly intractable to treatment. It can be both psychologically and physically debilitating. This study examines how the experience of NP is mediated by its meaning to the sufferer. Semi-structured interviews were conducted with eight people with SCI and chronic NP, attending outpatient clinics at a specialist SCI Centre in the UK. Verbatim transcripts were subjected to interpretative phenomenological analysis to further understand the experience. Analysis suggested that NP has powerful consequences upon the sufferer's physical, psychological and social well-being, in line with a biopsychosocial understanding of pain. Three super-ordinate themes were identified: a perceived gap between treatments received and participants' views of what they wanted and needed; a fight for life control and acceptance; and feeling understood by others with SCI, but isolated from the non-understanding able-bodied. The results are discussed in terms of the possible application of acceptance-based therapy to NP and the potential for the alleviation of the debilitating consequences of NP. Chronic NP after SCI is often described as worse than the injury itself, often impacting upon the sufferers physical and psychological health. The experiences of persons with SCI-specific NP highlight the impact of pain on their physical, psychological and social health. This indicates that healthcare professionals should incorporate a biopsychosocial approach for managing pain post-SCI. Routine clinical follow-up of SCI patients with chronic NP, as well as comprehensive pain management treatment programmes, could address the three themes evidenced in the current study, by moving routine intervention with NP away from pain relief, towards pain management. Continued education for patients

  5. Tumor necrosis factor-alpha is a potential diagnostic biomarker for chronic neuropathic pain after spinal cord injury.

    Science.gov (United States)

    Xu, Jun; E, Xiaoqiang; Liu, Huiyong; Li, Feng; Cao, Yanhui; Tian, Jun; Yan, Jinglong

    2015-05-19

    Neuropathic pain (NP) is one of the most common complications after spinal cord injury (SCI), but no protein biomarkers has ever been introduced into clinical diagnosis. Previous studies implicated that toll-like receptor (TLR) 4 played a critical role in the development of NP in animal SCI models. Here, a total of 140 participants were recruited, 70 of them were SCI-NP subject and the rest 70 controls did not show neuropathic symptoms. TLR4 was upregulated significantly in SCI-NP patients compared with SCI-noNP subjects. Furthermore, we measured the concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), two TLR4 downstream pro-inflammatory cytokines, to assess their diagnostic values. Receiver operating characteristics (ROC) analysis revealed that TNF-α had great potential advantages to predict the progression of neuropathy, the risks of NP were strongly increased in SCI subjects with higher levels of TNF-α (odds ratio: 4.92; 95% confidence interval: 1.89-12.32). These results suggested neuro-immune activation contributed to the development of neuropathic disorder after SCI, and TNF-α could be a potential sensitive diagnostic biomarker for chronic neuropathic pain in SCI patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Percutaneous Nerve Stimulation in Chronic Neuropathic Pain Patients due to Spinal Cord Injury: A Pilot Study

    NARCIS (Netherlands)

    Kopsky, D.J.; Ettema, F.W.L.; van der Leeden, M.; Dekker, J.; Stolwijk-Swuste, J.M.

    2014-01-01

    Background: The long-term prognosis for neuropathic pain resolution following spinal cord injury (SCI) is often poor. In many SCI patients, neuropathic pain continues or even worsens over time. Thus, new treatment approaches are needed. We conducted a pilot study to evaluate the feasibility and

  7. Cognitive behavioural treatment programme for chronic neuropathic pain after spinal cord injury

    NARCIS (Netherlands)

    Heutink, M.

    2014-01-01

    People with spinal cord injury (SCI) often face serious secondary health conditions, including different types of pain. Neuropathic pain is often rated by them as the most severe type of pain. Pharmacological interventions are often insufficiently effective in providing neuropathic pain relief and,

  8. Reversed cortical over-activity during movement imagination following neurofeedback treatment for central neuropathic pain.

    Science.gov (United States)

    Hasan, Muhammad Abul; Fraser, Matthew; Conway, Bernard A; Allan, David B; Vučković, Aleksandra

    2016-09-01

    One of the brain signatures of the central neuropathic pain (CNP) is the theta band over-activity of wider cortical structures, during imagination of movement. The objective of the study was to investigate whether this over-activity is reversible following the neurofeedback treatment of CNP. Five paraplegic patients with pain in their legs underwent from twenty to forty neurofeedback sessions that significantly reduced their pain. In order to assess their dynamic cortical activity they were asked to imagine movements of all limbs a week before the first and a week after the last neurofeedback session. Using time-frequency analysis we compared EEG activity during imagination of movement before and after the therapy and further compared it with EEG signals of ten paraplegic patients with no pain and a control group of ten able-bodied people. Neurofeedback treatment resulted in reduced CNP and a wide spread reduction of cortical activity during imagination of movement. The reduction was significant in the alpha and beta band but was largest in the theta band. As a result cortical activity became similar to the activity of other two groups with no pain. Reduction of CNP is accompanied by reduced cortical over-activity during movement imagination. Understanding causes and consequences mechanism through which CNP affects cortical activity. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  9. Ameliorative effect of ethyl pyruvate in neuropathic pain induced by chronic constriction injury of sciatic nerve

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    Varsha J. Bansode

    2014-01-01

    Full Text Available Objective: The present study was designed to investigate the ameliorative effects of ethyl pyruvate (EP in chronic constriction injury (CCI-induced painful neuropathy in rats. Materials and Methods: EP 50 and 100 mg/kg was administered for 21 consecutive days starting from the day of surgery. The effects of EP in the paw pressure, acetone drop, and tail heat immersion tests were assessed, reflecting the degree of mechanical hyperalgesia, cold allodynia, and spinal thermal sensation, respectively. Axonal degeneration of the sciatic nerve was assessed histopathologically. The levels of thiobarbituric acid reactive species, reduced glutathione (GSH, catalase (CAT, and superoxide dismutase (SOD were determined to assess oxidative stress. Key Findings: Administration of 50 and 100 mg/kg EP attenuated the reduction of nociceptive threshold in the paw pressure, acetone drop, and tail heat immersion tests. EP 100 mg/kg significantly attenuated reactive changes in histopathology and increase in oxidative stress. Conclusion: EP 100 mg/kg showed beneficial activity against nerve trauma-induced neuropathy. Hence, it can be used as a better treatment option in neuropathic pain (NP. The observed antinociceptive effects of EP may possibly be attributed to its antioxidant and anti-inflammatory activity.

  10. Multidimensional study of orofacial chronic neuropathic pain: An experimental study in rats.

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    Claudia Daniela Montes-Angeles

    2017-10-01

    Full Text Available Orofacial neuropathic chronic pain (NCP is frequently attributed to lesions caused by orofacial surgeries and dental treatments. There are many experimental models available to study orofacial NCP, however, many are extremely painful for the animal due to the amplitude of the innervated region. A previously proposed mental nerve constriction model, mNC, was used in this project. Forty Wistar rats were randomly divided into two groups: one group included rats with mNC (n=20, and another rats with sham lesions (n=20. Through the use of the fixed ratio program and the progressive program, a decrease of motivation for a sweet substance, caused by the lesion, was evaluated. The possibility of alterations in cognitive learning and adaptation abilities was also assessed using the go/no-go behavioral task. The mNC group showed low induced and spontaneously evoked pain responses, as well as a decrease in the motivation for sucrose, a sign of anhedonia. This decrease does not depend on taste processing. Finally, although no alterations in the learning-memory process were observed, the mNC group did show alterations when adapting to a new rule.

  11. TRPA1 polymorphisms in chronic and complete spinal cord injury patients with neuropathic pain: a pilot study.

    Science.gov (United States)

    Vidal Rodriguez, Sonia; Castillo Aguilar, Inmaculada; Cuesta Villa, Luis; Serrano Saenz de Tejada, Francisco

    2017-01-01

    Pilot study. Single-nucleotide polymorphisms (SNPs) in TRPA1 gene are related to the etiology of chronic pain. The study is a pilot study with the primary objective of analyzing these SNPs in Spanish patients with chronic and complete spinal cord injury (SCI) and neuropathic pain (NPP). Asepeyo Hospital Department of Chronic and Complete SCI. Twelve patients with chronic and complete SCI and NPP, and 12 patients with chronic and complete SCI with no pain were reviewed. International Spinal Cord Injury Pain Classification (LANSS) and visual analog score (VAS) were chosen to classify pain syndrome. SNPs were identified by melting analysis after DNA amplification with real-time fluorescence PCR. There were differences in rs11988795 variant: GG homozygous ( p  = 0.01) and G allele ( p  = 0.001) were more frequent in SCI patients with no pain. There were differences in rs13255063 variant: TT homozygous were prevalent ( p  = 0.03) in patients with NPP. Until now this is the first study to show a description of TRPA1 SNPs in Spanish patients with chronic and complete SCI and NPP. These results suggest that GG genotype in rs11988795 variant and G allele could be protective factors against NPP. TT genotype in rs13255063 variant could be a risk factor for NPP. Neuropathic pain after spinal cord injuries may have genetic contributions.

  12. Dynamic Changes in Nociception and Pain Perception After Spinal Cord Stimulation in Chronic Neuropathic Pain Patients.

    Science.gov (United States)

    Biurrun Manresa, José A; Sörensen, Jan; Andersen, Ole K; Arendt-Nielsen, Lars; Gerdle, Björn

    2015-12-01

    Patients with an implanted spinal cord stimulation (SCS) system for pain management present an opportunity to study dynamic changes in the pain system in a situation where patients are not stimulated (ie, experiencing severe pain) compared with a situation in which patients have just been stimulated (ie, pain free or greatly reduced pain). The aims of this study were (1) to determine if there are differences in nociceptive withdrawal reflex thresholds (NWR-T) and electrical pain thresholds (EP-T) before and after SCS; and (2) to establish if these differences are related to psychological factors associated with chronic pain. Seventeen volunteers with chronic neuropathic pain participated in the experiment. Electrical stimuli were applied to assess the NWR-T and the EP-T. In addition, psychological factors (ie, pain characteristics, depression, anxiety, and disability indexes) were also recorded. The NWR-T and EP-T were assessed with the SCS system off (at least 8 h before the experiment), and then reassessed 1 hour after the SCS system was turned on. Ongoing pain intensity ratings decreased (P=0.018), whereas the NWR-T increased (P=0.028) after the SCS was turned on, whereas no significant difference was found for EP-T (P=0.324). Psychological factors were significant predictors for EP-T but not for NWR-T. The results of this study suggest that pain relief after SCS is partially mediated by a decrease in the excitability of dorsal horn neurons in the spinal cord.

  13. The oxidative response in the chronic constriction injury model of neuropathic pain.

    Science.gov (United States)

    Tan, Edward C T H; Bahrami, Soheyl; Kozlov, Andrey V; Kurvers, Harry A J M; Ter Laak, Henk J; Nohl, Hans; Redl, Heinz; Goris, R Jan A

    2009-03-01

    In the chronic constriction injury model of rat neuropathic pain, oxidative stress as well as antioxidants superoxide dismutase and reduced glutathione (GSH) are important determinants of neuropathological and behavioral consequences. Studies of the chronic constriction injury model observed (indirect) signs of inflammation. We, therefore, investigated the level of oxidative stress and antioxidant enzymes in skeletal muscle tissue of the rat hind paw and (jugular vein) plasma at d 7 after nerve injury. The level of reactive oxygen and nitrogen species (RONS) was determined as a measure of oxidative stress. Reduced GSH levels and the ceruloplasmin/transferrin ratio were determined as measures of overall antioxidant activity. RONS and overall antioxidant activity were measured in skeletal muscle tissue of the hind paw and jugular vein plasma. The level of RONS in muscle was determined using spin trapping combined with electron paramagnetic resonance spectroscopy. Using electron paramagnetic resonance spectroscopy, we also determined plasma levels of transferrin and ceruloplasmin. GSH levels were determined using high-performance liquid chromatography. In skeletal muscle tissue, the level of RONS was lower in nerve-injured hind paws than in controls. The plasma level (jugular vein) of RONS did not differ between nerve-injured and control rats. In skeletal muscle tissue, the level of GSH was higher in nerve-injured hind paws than in controls. The ceruloplasmin/transferrin ratio tended to be higher in (jugular vein) plasma of nerve-injured rats as compared to controls. This study shows that, at d 7 after nerve injury, oxidative stress-induced changes are present also in skeletal muscle tissue of the rat hind paw. Our findings of a decreased level of RONS in combination with an increased level of the antioxidant GSH suggest that an overshoot of antioxidant activity overrules initial oxidative stress.

  14. Functional and metabolic changes in the brain in neuropathic pain syndrome against the background of chronic epidural electrostimulation of the spinal cord.

    Science.gov (United States)

    Sufianov, A A; Shapkin, A G; Sufianova, G Z; Elishev, V G; Barashin, D A; Berdichevskii, V B; Churkin, S V

    2014-08-01

    Changes in functional and metabolic activities of the brain were evaluated by EEG and positron-emission/computer tomography with 18F-fluorodeoxyglucose in patients with neuropathic pain syndrome previous to and 3 months after implantation of a system for chronic epidural spinal cord stimulation. In most cases, the use of a nerve stimulator was followed by alleviation of neuropathic pain and partial normalization of functional and metabolic activities of brain structures responsible for pain perception, emotiogenic, behavioral, and autonomic responses.

  15. Dynamic oscillatory signatures of central neuropathic pain in spinal cord injury.

    Science.gov (United States)

    Vuckovic, Aleksandra; Hasan, Muhammad A; Fraser, Matthew; Conway, Bernard A; Nasseroleslami, Bahman; Allan, David B

    2014-06-01

    Central neuropathic pain (CNP) is believed to be accompanied by increased activation of the sensorimotor cortex. Our knowledge of this interaction is based mainly on functional magnetic resonance imaging studies, but there is little direct evidence on how these changes manifest in terms of dynamic neuronal activity. This study reports on the presence of transient electroencephalography (EEG)-based measures of brain activity during motor imagery in spinal cord-injured patients with CNP. We analyzed dynamic EEG responses during imaginary movements of arms and legs in 3 groups of 10 volunteers each, comprising able-bodied people, paraplegic patients with CNP (lower abdomen and legs), and paraplegic patients without CNP. Paraplegic patients with CNP had increased event-related desynchronization in the theta, alpha, and beta bands (16-24 Hz) during imagination of movement of both nonpainful (arms) and painful limbs (legs). Compared to patients with CNP, paraplegics with no pain showed a much reduced power in relaxed state and reduced event-related desynchronization during imagination of movement. Understanding these complex dynamic, frequency-specific activations in CNP in the absence of nociceptive stimuli could inform the design of interventional therapies for patients with CNP and possibly further understanding of the mechanisms involved. This study compares the EEG activity of spinal cord-injured patients with CNP to that of spinal cord-injured patients with no pain and also to that of able-bodied people. The study shows that the presence of CNP itself leads to frequency-specific EEG signatures that could be used to monitor CNP and inform neuromodulatory treatments of this type of pain. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  16. Loss of Ca(2+)-permeable AMPA receptors in synapses of tonic firing substantia gelatinosa neurons in the chronic constriction injury model of neuropathic pain.

    Science.gov (United States)

    Chen, Yishen; Derkach, Victor A; Smith, Peter A

    2016-05-01

    Synapses transmitting nociceptive information in the spinal dorsal horn undergo enduring changes following peripheral nerve injury. Indeed, such injury alters the expression of the GluA2 subunit of glutamatergic AMPA receptors (AMPARs) in the substantia gelatinosa and this predicts altered channel conductance and calcium permeability, leading to an altered function of excitatory synapses. We therefore investigated the functional properties of synaptic AMPA receptors in rat substantia gelatinosa neurons following 10-20d chronic constriction injury (CCI) of the sciatic nerve; a model of neuropathic pain. We measured their single-channel conductance and sensitivity to a blocker of calcium permeable AMPA receptors (CP-AMPARs), IEM1460 (50μM). In putative inhibitory, tonic firing neurons, CCI reduced the average single-channel conductance of synaptic AMPAR from 14.4±3.5pS (n=12) to 9.2±1.0pS (n=10, pinjury acting at synapses of inhibitory neurons to reduce their drive and therefore inhibitory tone in the spinal cord, therefore contributing to the central sensitization associated with neuropathic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Sensitization of neurons in the central nucleus of the amygdala via the decreased GABAergic inhibition contributes to the development of neuropathic pain-related anxiety-like behaviors in rats.

    Science.gov (United States)

    Jiang, Hong; Fang, Dong; Kong, Ling-Yu; Jin, Zi-Run; Cai, Jie; Kang, Xue-Jing; Wan, You; Xing, Guo-Gang

    2014-10-04

    Despite high prevalence of anxiety accompanying with chronic pain, the mechanisms underlying pain-related anxiety are largely unknown. With its well-documented role in pain and emotion processing, the amygdala may act as a key player in pathogenesis of neuropathic pain-related anxiety. Pain-related plasticity and sensitization of CeA (central nucleus of the amygdala) neurons have been shown in several models of chronic pain. In addition, firing pattern of neurons with spike output can powerfully affect functional output of the brain nucleus, and GABAergic neurons are crucial in the modulation of neuronal excitability. In this study, we first investigated whether pain-related plasticity (e.g. alteration of neuronal firing patterns) and sensitization of CeA neurons contribute to nerve injury-evoked anxiety in neuropathic rats. Furthermore, we explored whether GABAergic disinhibition is responsible for regulating firing patterns and intrinsic excitabilities of CeA neurons as well as for pain-related anxiety in neuropathic rats. We discovered that spinal nerve ligation (SNL) produced neuropathic pain-related anxiety-like behaviors in rats, which could be specifically inhibited by intra-CeA administration of anti-anxiety drug diazepam. Moreover, we found potentiated plasticity and sensitization of CeA neurons in SNL-induced anxiety rats, of which including: 1) increased burst firing pattern and early-adapting firing pattern; 2) increased spike frequency and intrinsic excitability; 3) increased amplitude of both after-depolarized-potential (ADP) and sub-threshold membrane potential oscillation. In addition, we observed a remarkable reduction of GABAergic inhibition in CeA neurons in SNL-induced anxiety rats, which was proved to be important for altered firing patterns and hyperexcitability of CeA neurons, thereby greatly contributing to the development of neuropathic pain-related anxiety. Accordantly, activation of GABAergic inhibition by intra-CeA administration of

  18. Discriminating between neuropathic pain and sensory hypersensitivity using the Chronic Pain Questions (CPQ).

    Science.gov (United States)

    Coyne, Karin S; Currie, Brooke M; Donevan, Sean; Cappelleri, Joseph C; Hegeman-Dingle, Rozelle; Abraham, Lucy; Thompson, Christine; Sadosky, Alesia; Brodsky, Marina

    2017-01-01

    The Chronic Pain Questions (CPQ) were developed for clinical use with the aim of supporting primary care physicians in the screening, assessment and monitoring of patients with chronic pain. the purpose of this study was to examine the ability of the cpq CPQ to discriminate between patients with neuropathic pain (nep) versus those with sensory hypersensitivity (sh). Adult men and women with a diagnosis of a NeP or SH condition were recruited from 5 clinical sites across the United States. Participants completed a series of self-administered questionnaires, including the CPQ. Continuous variables were compared between groups with independent t-tests; categorical variables were compared with chi-square analyses. A series of exploratory logistic regressions were performed to discern optimal screening criteria for SH using CPQ responses. 98 participants, 68 with physician-confirmed diagnoses of SH and 30 with NeP, participated. 81.6% were female, 73.5% Caucasian, and mean (± SD) age was 58.4 ± 12.6 years. SH participants included significantly more females compared to the NeP group (94.1% vs. 53.3%). Differences in CPQ responses between groups were statistically significant for six of the 14 CPQ items with SH participants having significantly lower scores on specific pain quality questions and significantly higher scores on trouble thinking/remembering (5.3 ± 3.5 vs. 3.0 ± 2.8) and sensitivity to lights/noises/smells (4.8 ± 3.5 vs. 2.7 ± 3.0). No significant differences were found between groups for chronic pain intensity, pain made worse with touch, pain limited to joints, or pain interference with usual activity, sleep or mood. Logistic regression analyses revealed strong c indices (≥0.89) for all models. Consistent findings demonstrated that younger age, female gender, and scores ≥6 for the CPQ question on sensitivity to lights/noises/smells were all predictive of SH. The CPQ can help differentiate between patients with NeP and SH. More research

  19. The Discriminative validity of "nociceptive," "peripheral neuropathic," and "central sensitization" as mechanisms-based classifications of musculoskeletal pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-02-01

    OBJECTIVES: Empirical evidence of discriminative validity is required to justify the use of mechanisms-based classifications of musculoskeletal pain in clinical practice. The purpose of this study was to evaluate the discriminative validity of mechanisms-based classifications of pain by identifying discriminatory clusters of clinical criteria predictive of "nociceptive," "peripheral neuropathic," and "central sensitization" pain in patients with low back (+\\/- leg) pain disorders. METHODS: This study was a cross-sectional, between-patients design using the extreme-groups method. Four hundred sixty-four patients with low back (+\\/- leg) pain were assessed using a standardized assessment protocol. After each assessment, patients\\' pain was assigned a mechanisms-based classification. Clinicians then completed a clinical criteria checklist indicating the presence\\/absence of various clinical criteria. RESULTS: Multivariate analyses using binary logistic regression with Bayesian model averaging identified a discriminative cluster of 7, 3, and 4 symptoms and signs predictive of a dominance of "nociceptive," "peripheral neuropathic," and "central sensitization" pain, respectively. Each cluster was found to have high levels of classification accuracy (sensitivity, specificity, positive\\/negative predictive values, positive\\/negative likelihood ratios). DISCUSSION: By identifying a discriminatory cluster of symptoms and signs predictive of "nociceptive," "peripheral neuropathic," and "central" pain, this study provides some preliminary discriminative validity evidence for mechanisms-based classifications of musculoskeletal pain. Classification system validation requires the accumulation of validity evidence before their use in clinical practice can be recommended. Further studies are required to evaluate the construct and criterion validity of mechanisms-based classifications of musculoskeletal pain.

  20. An improved behavioural assay demonstrates that ultrasound vocalizations constitute a reliable indicator of chronic cancer pain and neuropathic pain

    Directory of Open Access Journals (Sweden)

    Selvaraj Deepitha

    2010-03-01

    Full Text Available Abstract Background On-going pain is one of the most debilitating symptoms associated with a variety of chronic pain disorders. An understanding of mechanisms underlying on-going pain, i.e. stimulus-independent pain has been hampered so far by a lack of behavioural parameters which enable studying it in experimental animals. Ultrasound vocalizations (USVs have been proposed to correlate with pain evoked by an acute activation of nociceptors. However, literature on the utility of USVs as an indicator of chronic pain is very controversial. A majority of these inconsistencies arise from parameters confounding behavioural experiments, which include novelty, fear and stress due to restrain, amongst others. Results We have developed an improved assay which overcomes these confounding factors and enables studying USVs in freely moving mice repetitively over several weeks. Using this improved assay, we report here that USVs increase significantly in mice with bone metastases-induced cancer pain or neuropathic pain for several weeks, in comparison to sham-treated mice. Importantly, analgesic drugs which are known to alleviate tumour pain or neuropathic pain in human patients significantly reduce USVs as well as mechanical allodynia in corresponding mouse models. Conclusions We show that studying USVs and mechanical allodynia in the same cohort of mice enables comparing the temporal progression of on-going pain (i.e. stimulus-independent pain and stimulus-evoked pain in these clinically highly-relevant forms of chronic pain.

  1. Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice.

    Science.gov (United States)

    Castany, Sílvia; Gris, Georgia; Vela, José Miguel; Verdú, Enrique; Boadas-Vaello, Pere

    2018-03-01

    Sigma-1 receptor (σ 1 R) knockout (KO) CD1 mice, generated by homologous recombination, and separate pharmacological studies in wild type (WT) mice were done to investigate the role of this receptor in the development of pain-related behaviours (thermal hyperalgesia and mechanical allodynia) in mice after spinal cord contusion injury (SCI) - a model of central neuropathic pain. The modulatory effect of σ 1 R KO on extracellular mediators and signalling pathways in the spinal cord was also investigated. In particular, changes in the expression of inflammatory cytokines (tumour necrosis factor TNF-α, interleukin IL-1β) and both the expression and activation (phosphorylation) of the N-methyl-D-aspartate receptor subunit 2B (NR2B-NMDA) and extracellular signal-regulated kinases (ERK1/2) were analysed. Compared with WT mice, both mechanical and thermal hypersensitivity were attenuated in σ 1 R KO mice following SCI. Accordingly, treatment of WT mice with the σ 1 R antagonist MR309 (previously developed as E-52862; S1RA) after SCI exerted antinociceptive effects (i.e. reduced mechanical allodynia and thermal hyperalgesia). Attenuated nociceptive responses in σ 1 R KO were accompanied by reduced expression of TNF- α and IL-1β as well as decreased activation/phosphorylation of NR2B-NMDA receptors and ERK1/2. These findings suggest that σ 1 R may modulate central neuropathic pain and point to regulation of sensitization-related phenomena as a possible mechanism.

  2. Systemic Administration of Propentofylline, Ibudilast, and (+)-Naltrexone Each Reverses Mechanical Allodynia in a Novel Rat Model of Central Neuropathic Pain

    Science.gov (United States)

    Ellis, Amanda; Wieseler, Julie; Favret, Jacob; Johnson, Kirk W.; Rice, Kenner C.; Maier, Steven F.; Falci, Scott; Watkins, Linda R.

    2014-01-01

    Central neuropathic pain (CNP) is a debilitating consequence of central nervous system (CNS) damage for which current treatments are ineffective. To explore mechanisms underlying CNP, we developed a rat model involving T13/L1 dorsal root avulsion. The resultant dorsal horn damage creates bilateral below-level (L4-6) mechanical allodynia. This allodynia, termed spinal neuropathic avulsion pain (SNAP), occurs in the absence of confounding paralysis. To characterize this model, we undertook a series of studies aimed at defining whether SNAP could be reversed by any of 3 putative glial activation inhibitors, each with distinct mechanisms of action. Indeed, the phosphodiesterase inhibitor propentofylline, the macrophage migration inhibitory factor (MIF) inhibitor ibudilast, and the toll-like receptor 4 (TLR4) antagonist (+)-naltrexone each reversed below-level allodynia bilaterally. Strikingly, none of these impacted SNAP upon first administration but required 1–2 wk of daily administration before pain reversal was obtained. Given reversal of CNP by each of these glial modulatory agents, these results suggest that glia contribute to the maintenance of such pain and enduring release of MIF and endogenous agonists of TLR4 is important for sustaining CNP. The markedly delayed efficacy of all 3 glial modulatory drugs may prove instructive for interpretation of apparent drug failures after shorter dosing regimens. PMID:24412802

  3. Long term clinical outcome of peripheral nerve stimulation in patients with chronic peripheral neuropathic pain

    DEFF Research Database (Denmark)

    Calenbergh, F. Van; Gybels, J.; Laere, K. Van

    2009-01-01

    of the present study was to evaluate the long-term clinical efficacy of PNS in a group of patients with peripheral neuropathic pain treated with PNS since the 1980s. METHODS: Of an original series of 11 patients, 5 patients could be invited for clinical examination, detailed assessment of clinical pain and QST...

  4. Prevalence of Neuropathic Pain and Patient-Reported Outcomes in Korean Adults with Chronic Low Back Pain Resulting from Neuropathic Low Back Pain.

    Science.gov (United States)

    Kim, Jin-Hwan; Hong, Jae Taek; Lee, Chong-Suh; Kim, Keun-Su; Suk, Kyung-Soo; Kim, Jin-Hyok; Park, Ye-Soo; Chang, Bong-Soon; Jun, Deuk Soo; Kim, Young-Hoon; Lee, Jung-Hee; Min, Woo-Kie; Lee, Jung-Sub; Park, Si-Young; Oh, In-Soo; Hong, Jae-Young; Shin, Hyun-Chul; Kim, Woo-Kyung; Kim, Joo-Han; Lee, Jung-Kil; Kim, In-Soo; Ha, Yoon; Im, Soo-Bin; Kim, Sang Woo; Han, In-Ho; Shin, Jun-Jae; Rim, Byeong Cheol; Seo, Bo-Jeong; Kim, Young-Joo; Lee, Juneyoung

    2017-12-01

    A noninterventional, multicenter, cross-sectional study. We investigated the prevalence of neuropathic pain (NP) and patient-reported outcomes (PROs) of the quality of life (QoL) and functional disability in Korean adults with chronic low back pain (CLBP). Among patients with CLBP, 20%-55% had NP. Patients older than 20 years with CLBP lasting for longer than three months, with a visual analog scale (VAS) pain score higher than four, and with pain medications being used for at least four weeks before enrollment were recruited from 27 general hospitals between December 2014 and May 2015. Medical chart reviews were performed to collect demographic/clinical features and diagnosis of NP (douleur neuropathique 4, DN4). The QoL (EuroQoL 5-dimension, EQ-5D; EQ-VAS) and functional disability (Quebec Back Pain Disability Scale, QBPDS) were determined through patient surveys. Multiple linear regression analyses were performed to compare PROs between the NP (DN4≥4) and non-NP (DN4NP. The prevalence of NP was higher in male patients (46.8%; p p p NP group vs. non-NP group: 0.4±0.3 vs. 0.5±0.3; p NP group vs. non-NP group: 45.8±21.2 vs. 36.3±20.2; p NP showed lower EQ-5D (β=-0.1; p p NP. NP was highly prevalent in Korean patients with CLBP. Patients with CLBP having NP had a lower QoL and more severe dysfunction than those without NP. To enhance the QoL and functional status of patients with CLBP, this study highlights the importance of appropriately diagnosing and treating NP.

  5. A comparison of coping strategies in patients with fibromyalgia, chronic neuropathic pain, and pain-free controls

    DEFF Research Database (Denmark)

    Baastrup, S; Schultz, Rikke; Brødsgaard, I

    2016-01-01

    Patients suffering from chronic pain may benefit from learning adaptive coping strategies. Consensus on efficient strategies for this group of patients is, however, lacking, and previous studies have shown inconsistent results. The present study has examined coping strategies in two distinctly...... different groups of chronic pain patients and a group of healthy controls. Thirty neuropathic pain (NP) patients, 28 fibromyalgia (FM) patients, and 26 pain-free healthy controls completed the Coping Strategy Questionnaire (CSQ-48/27) and rated their daily pain. The results showed that FM and NP patients...... did not cope differently with pain. The only difference between the groups was that FM patients felt more in control of their pain than NP patients. Both patient groups used more maladaptive/passive coping strategies, but surprisingly also more adaptive/active coping strategies than healthy controls...

  6. A pilot study of healing touch and progressive relaxation for chronic neuropathic pain in persons with spinal cord injury.

    Science.gov (United States)

    Wardell, Diane Wind; Rintala, Diana H; Duan, Zhigang; Tan, Gabriel

    2006-12-01

    This pilot study assessed the role of Healing Touch (HT), an energy-based therapy, in modulating chronic neuropathic pain and the associated psychological distress from post spinal cord injury. Twelve veterans were assigned to either HT or guided progressive relaxation for six weekly home visits. The instruments selected showed sensitivity, although there was a large variation among the groups. There was a significant difference in the composite of interference on the Brief Pain Inventory (t = -2.71, p = .035). The mean score of the fatigue subscale of the Profile of Moods decreased (ns) in the HT group and in the subscale of confusion yet remained stable in the control group. The Diener Satisfaction With Life Scale showed increased well-being in the HT group and no change in the control group. Participants reported various experiences with HT sessions indicating that it may have benefit in the complex response to chronic pain.

  7. Peripheral and central sites of action for A-85380 in the spinal nerve ligation model of neuropathic pain.

    Science.gov (United States)

    Rueter, Lynne E; Kohlhaas, Kathy L; Curzon, Peter; Surowy, Carol S; Meyer, Michael D

    2003-06-01

    Neuronal nicotinic receptor (NNR) agonists such as ABT 594 have been shown to be effective in a wide range of preclinical models of acute and neuropathic pain. The present study, using the NNR agonist A-85380, sought to determine if NNR agonists are acting via similar or differing mechanisms to induce anti-nociception and anti-allodynia. A systemic administration of the quaternary NNR antagonist chlorisondamine (0.4 micromol/kg, intraperitoneal (i.p.)) did not alter A-85380-induced (0.75 micromol/kg, i.p.) anti-nociception in the rat paw withdrawal model of acute thermal pain. In contrast, previous studies have demonstrated that blockade of central NNRs by prior administration of chlorisondamine (10 microg i.c.v.) prevents A-85380 induced anti-nociception indicating a predominantly central site of action of NNR agonists in relieving acute pain. In the rat spinal nerve ligation model of neuropathic pain, A-85380 induced a dose-dependent anti-allodynia (0.5-1.0 micromol/kg) that was blocked by pretreatment with mecamylamine (1 micromol/kg). Interestingly, unlike acute pain, both systemic and central administration of chlorisondamine blocked A-85380-induced anti-allodynia, an effect that was determined not to be due to a non-specific effect of chlorisondamine or to chlorisondamine crossing the blood-brain barrier. The peripheral site of action was shown not to be the primary receptive field, since A-85380 had equally potent anti-allodynic effects when it was injected into either the affected or unaffected paw. In contrast, infusion of A-85380 directly onto the L5 dorsal root ganglion on the affected side resulted in a dose-dependent and marked anti-allodynia (10-20 microg) at doses that had no effect when injected systemically. This effect was blocked by pretreatment with chlorisondamine. Together these data further support the idea that different mechanisms underlie different pain states and suggest that the effects of NNR agonists in neuropathic pain may be due in

  8. Treatment of chronic intractable neuropathic pain with dronabinol: case report of two adolescents.

    Science.gov (United States)

    Rudich, Zvia; Stinson, Jennifer; Jeavons, Michael; Brown, Stephen C

    2003-01-01

    To evaluate the effectiveness of dronabinol for the treatment of neuropathic pain refractory to previous treatment. We studied the response (reduction of pain intensity and functional improvement) to dronabinol (5 mg/day to 25 mg/day) in two adolescents with neuropathic pain and depression refractory to previous treatments over two and five years, respectively. Reduction in pain intensity (45%) was achieved in patient 2 and was unchanged in patient 1. Functional improvement was markedly increased in terms of academic performance, mood and sleep in both patients over four to five months, without major adverse effects. While these improvements dissipated over time, the patients were more reconnected with rehabilitation and focused less on the intrusiveness of their pain problem in their every day lives. Dronabinol appeared to be effective in improving pain affect and psychosocial functioning in the treatment of refractory neuropathic pain and may be considered as an adjuvant medication in the rehabilitation process. Well-controlled placebo studies are required for further evaluation.

  9. The Evaluation of the Effect of Neuropathic Pain on Functional Disability in Patients with Chronic Low Back Pain

    Directory of Open Access Journals (Sweden)

    Yalkın Çalık

    2015-12-01

    Full Text Available Objective: The aim of this study was to evaluate both the prevalence of neuropathic pain (NP and the effect of functional disability of NP in patients with chronic low back pain (CLBP. Materials and Methods: In this study, outpatients data were reviewed retrospectively from January 2014 to December 2014 to determine the patients with CLBP. 190 patients with CLBP meeting the inclusion criteria were included. NP scores of the patients were assessed using Leeds Assessment of Neuropathic Symptoms and Signs (LANSS and the evaluation of pain was performed using the Visual analoque scale (VAS and functional disability scores was determined by the Oswestry disability index (ODI. Results: In this study NP was detected in 39.4% of the patients with CLBP. The number of female patients with NP (n=60, %80 was significantly higher than the number of male patients with NP (n=15, %20, (p<0.05. ODI and VAS scores of the patients with NP [(19.81±7.28, (5.08±0.76] was significantly higher than those of the patients without NP [(15.28±6.83, (4.44±1.14], (p<0,001. Conclusion: It was found that the co-existence of NP with CLBP increases pain and functional disability.

  10. Prevalence of Neuropathic Pain According to the IASP Grading System in Patients with Chronic Non-Malignant Pain

    DEFF Research Database (Denmark)

    Vægter, Henrik Bjarke; Andersen, Per Grunwald; Madsen, Marianne Frobøse

    2014-01-01

    The primary objective was to determine the prevalence of neuropathic pain according to the new International Association for the Study of Pain (IASP) grading system. The secondary objective was to compare the system classification of neuropathic pain with the classification of neuropathic pain...

  11. Altered resting state EEG in chronic pancreatitis patients: toward a marker for chronic pain

    NARCIS (Netherlands)

    Vries, M. de; Wilder-Smith, O.H.G.; Jongsma, M.L.A.; Broeke, E.N. van den; Arns, M.W.; Goor, H. van; Rijn, C.M. van

    2013-01-01

    OBJECTIVES: Electroencephalography (EEG) may be a promising source of physiological biomarkers accompanying chronic pain. Several studies in patients with chronic neuropathic pain have reported alterations in central pain processing, manifested as slowed EEG rhythmicity and increased EEG power in

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

    Science.gov (United States)

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

    2016-03-01

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

  13. Effects of chronic constriction injury and spared nerve injury, two models of neuropathic pain, on the numbers of neurons and glia in the rostral ventromedial medulla.

    Science.gov (United States)

    Leong, Mai Lan; Speltz, Rebecca; Wessendorf, Martin

    2016-03-23

    In previous studies we have reported that spinal nerve ligation (SNL), a model of neuropathic pain, results in the loss of over 20% of neurons in the rostral portion of the ventromedial medulla (RVM) in rats, 10 days after SNL. The RVM is involved in pain modulation and we have proposed that loss of pain inhibition from the RVM, including loss of RVM serotonin neurons, contributes to the increased hypersensitivity observed after SNL. In the present study we examined whether RVM neuronal loss occurs in two other models of neuropathic pain, chronic constriction injury (CCI) and spared nerve injury (SNI). We found no evidence for neuronal loss 10 days after either nerve injury, a time when robust tactile hypersensitivity is present in both CCI and SNI. We conclude that loss of RVM neurons appears not to be required for expression of tactile hypersensitivity in these models of neuropathic pain. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Characterization of chronic constriction of the saphenous nerve, a model of neuropathic pain in mice showing rapid molecular and electrophysiological changes.

    Science.gov (United States)

    Walczak, Jean-Sébastien; Pichette, Vincent; Leblond, François; Desbiens, Karine; Beaulieu, Pierre

    2006-05-15

    Neuropathic pain is one of the most inextricable problems encountered in clinics, because few facts are known about its etiology. Nerve injury often leads to allodynia and hyperalgesia, which are symptoms of neuropathic pain. The aim of this study was to understand some molecular and electrophysiological mechanisms of neuropathic pain after chronic constriction of the saphenous nerve (CCS) in mice. After surgery, CCS mice displayed significant allodynia and hyperalgesia, which were sensitive to acute systemic injection of morphine (4 mg/kg), gabapentin (50 mg/kg), amitriptyline (10 mg/kg), and the cannabinoid agonist WIN 55,212-2 (5 mg/kg). These behavioral changes were accompanied after surgery by an increase of c-Fos expression and by an overexpression of mu-opioid and cannabinoid CB1 and CB2 receptors in the spinal cord and the dorsal hind paw skin. In combination with the skin-nerve preparation, this model showed a decrease in functional receptive fields downstream to the injury and the apparition of A-fiber ectopic discharges. In conclusion, CCS injury induced behavioral, molecular, and electrophysiological rearrangements that might help us in better understanding the peripheral mechanisms of neuropathic pain. This model takes advantage of the possible use in the future of genetically modified mice and of an exclusively sensory nerve for a comprehensive study of peripheral mechanisms of neuropathic pain. Copyright 2006 Wiley-Liss, Inc.

  15. Motor Cortex Stimulation in Patients Suffering from Chronic Neuropathic Pain : Summary of Expert Meeting and Premeeting Questionnaire, Combined with Literature Review

    NARCIS (Netherlands)

    Kurt, Erkan; Henssen, Dylan J. H. A.; Steegers, Monique; Staal, Michiel; Beese, Ulrich; Maarrawi, Joseph; Pirotte, Benoit; Garcia-Larrea, Luis; Rasche, Dirk; Vesper, Jan; Holsheimer, Jan; Duyvendak, Wim; Herregodts, Patrick; van Dongen, Robert; Moens, Maarten

    2017-01-01

    BACKGROUND: Motor cortex stimulation (MCS) was introduced in the early 1990s by Tsubokawa and his group for patients diagnosed with drug-resistant, central neuropathic pain. Inconsistencies concerning the details of this therapy and its outcomes and poor methodology of most clinical essays divide

  16. Depression, anxiety, health-related quality of life and pain in patients with chronic fibromyalgia and neuropathic pain.

    Science.gov (United States)

    Gormsen, Lise; Rosenberg, Raben; Bach, Flemming W; Jensen, Troels S

    2010-02-01

    Chronic pain is often associated with comorbidities such as anxiety and depression, resulting in a low health-related quality of life. The mechanisms underlying this association are not clear, but a disturbance in the pain control systems from the brain stem has been suggested. Thirty neuropathic pain (NP) patients, 28 patients with fibromyalgia (FM), and 26 pain-free age- and gender-matched controls were included and examined with respect to mental distress (self-rated Symptom Checklist-92), depression (doctor-rated Hamilton Depression Scale and self-rated Major Depression Inventory), and anxiety (doctor-rated Hamilton Anxiety Scale and self-rated Anxiety Inventory). In addition, patients assessed their health-related quality of life (SF-36). Chronic pain patients with FM and NP had significantly more mental distress including depression and anxiety than healthy controls both by self-rating and by a professional rating. However, these scores are low compared to other studies on mental distress in chronic pain patients. Only few chronic pain patients meet the diagnostic criteria for depression (NP 3.3%, FM 7.1%), and associations between pain and mental symptoms were only found in the FM group despite similar pain intensities. The findings suggest that different mechanisms are responsible for the development of mood disorders in the two patient groups.

  17. Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ya-Qiong [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Jin, Shao-Ju [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Luohe Medical College, Luohe 462002, Henan Province (China); Liu, Ning [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Li, Yu-Xiang [College of Nursing, Ningxia Medical University, Yinchuan 750004 (China); Zheng, Jie [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Ma, Lin [Ningxia Key Lab of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan 750004 (China); Du, Juan; Zhou, Ru [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Zhao, Cheng-Jun [Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750000 (China); Niu, Yang [Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004 (China); Sun, Tao [Ningxia Key Lab of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan 750004 (China); Yu, Jian-Qiang, E-mail: Yujq910315@163.com [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Luohe Medical College, Luohe 462002, Henan Province (China)

    2014-09-05

    Highlights: • Aloperine has anti-nociceptive effects on neuropathic pain induced CCI. • Aloperine reduces ROS in neuropathic pain mice. • Aloperine down-regulates the expression of NF-κB and its downstream pro-inflammatory cytokines in neuropathic pain mice. - Abstract: Objective: To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain. Methods: Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the spinal cord (L4/5) were analyzed by using Western blot. Results: Administration of ALO (80 mg/kg and 40 mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1β at the dose of 80 mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10 mg/kg (i.p.). Conclusion: ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway.

  18. Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway

    International Nuclear Information System (INIS)

    Xu, Ya-Qiong; Jin, Shao-Ju; Liu, Ning; Li, Yu-Xiang; Zheng, Jie; Ma, Lin; Du, Juan; Zhou, Ru; Zhao, Cheng-Jun; Niu, Yang; Sun, Tao; Yu, Jian-Qiang

    2014-01-01

    Highlights: • Aloperine has anti-nociceptive effects on neuropathic pain induced CCI. • Aloperine reduces ROS in neuropathic pain mice. • Aloperine down-regulates the expression of NF-κB and its downstream pro-inflammatory cytokines in neuropathic pain mice. - Abstract: Objective: To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain. Methods: Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the spinal cord (L4/5) were analyzed by using Western blot. Results: Administration of ALO (80 mg/kg and 40 mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1β at the dose of 80 mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10 mg/kg (i.p.). Conclusion: ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway

  19. Experimental Gene Therapy with Serine-Histogranin and Endomorphin 1 for the Treatment of Chronic Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Stanislava Jergova

    2017-12-01

    Full Text Available The insufficient pain relief provided by current pharmacotherapy for chronic neuropathic pain is a serious medical problem. The enhanced glutamate signaling via NMDA receptors appears to be one of the key events in the development of chronic pain. Although effective, clinical use of systemic NMDA antagonists is limited by adverse effects such as hallucinations and motor dysfunction. Opioids are also potent analgesics but their chronic use is accompanied by tolerance and risk of addiction. However, combination of NMDA antagonists and opioids seems to provide a stable pain relieve at subthreshold doses of both substances, eliminating development of side effects. Our previous research showed that combined delivery of NMDA antagonist Serine histrogranin (SHG and endomorphin1 (EM1 leads to attenuation of acute and chronic pain. The aim of this study was to design and evaluate an analgesic potency of the gene construct encoding SHG and EM1. Constructs with 1SHG copy in combination with EM1, 1SHG/EM1, and 6SHG/EM1 were intraspinally injected to animals with peripheral nerve injury-induced pain (chronic constriction injury, CCI or spinal cord injury induced pain (clip compression model, SCI and tactile and cold allodynia were evaluated. AAV2/8 particles were used for gene delivery. The results demonstrated 6SHG/EM1 as the most efficient for alleviation of pain-related behavior. The effect was observed up to 8 weeks in SCI animals, suggesting the lack of tolerance of possible synergistic effect between SHG and EM1. Intrathecal injection of SHG antibody or naloxone attenuated the analgesic effect in treated animals. Biochemical and histochemical evaluation confirmed the presence of both peptides in the spinal tissue. The results of this study showed that the injection of AAV vectors encoding combined SHG/EM constructs can provide long term attenuation of pain without overt adverse side effects. This approach may provide better treatment options for

  20. Clonazepam for neuropathic pain and fibromyalgia in adults.

    Science.gov (United States)

    Corrigan, Ruth; Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

    2012-05-16

    Antiepileptic drugs have been used in pain management since the 1960s; some have shown efficacy in treating different neuropathic pain conditions. Clonazepam, a benzodiazepine, is an established antiepileptic drug, but its place in the treatment of neuropathic pain is unclear. To assess the analgesic efficacy and adverse effects of the antiepileptic drug clonazepam in neuropathic pain and fibromyalgia. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2). MEDLINE, and EMBASE to 28 February 2012, together with reference lists of retrieved papers and reviews, and ClinicalTrials.gov. We planned to include randomised, double-blind studies of eight weeks duration or longer, comparing clonazepam with placebo or another active treatment in chronic neuropathic pain or fibromyalgia. Two review authors would independently extract data for efficacy and adverse events, and examine issues of study quality. We did not identify any studies that satisfied the inclusion criteria. This review uncovered no evidence of sufficient quality to support the use of clonazepam in chronic neuropathic pain or fibromyalgia.

  1. Synergistic interaction between total glucosides and total flavonoids on chronic constriction injury induced neuropathic pain in rats.

    Science.gov (United States)

    Zhang, Juan; Lv, Chen; Wang, Hai-na; Cao, Yi

    2013-04-01

    Shaoyao Gancao Decoction (SGD), a famous herbal medicine, consists of two herbs (Paeoniae Radix and Glycyrrhizae Radix) and is traditionally used for the treatment of pain. To investigate the synergistic potential of total glucosides of Paeoniae Radix (TGP) and total flavonoids of Glycyrrhizae Radix (TFL). Oral administration of TGP and TFL alone at the doses of 60,120 and 240 mg/kg or in combination were given only one time to the neuropathic pain rat induced by chronic constriction injury. Paw pressure and heat immersion tests were performed to assess degrees of mechanical allodynia and thermal hyperalgesia, respectively. Synergistic interactions between TGP and TFL were characterized using isobolographic analysis. Expressions of Sirt1 protein were detected by immunohistochemistry. On day 14 after surgery, single oral administration of TGP and TFL both produced significant anti-allodynic and anti-hyperalgesic effects in dose-dependent and time-dependent manners. The ED(50) value of TGP was 249.4 ± 10.8 mg/kg while TFL was 871.4 ± 30.5 mg/kg. Isobolographic analysis revealed that the combination of TGP with TFL at the fixed ratios of 3:1 exerted the highest sub-additive (synergistic) interaction, of which the experimental ED(50) value was 95.1 ± 9.0 mg/kg. SGD could also downregulate Sirt1 protein expression, which was 4.2-fold higher than that of model rats in dorsal root ganglion. Analgesic effects of SGD may contribute to simultaneous inhibition of Sirt1 overexpression and could warrant further evaluation as a possible agent for the treatment of neuropathic pain.

  2. The characteristics of chronic pain after non-traumatic, non-compressive myelopathy: Focus on neuropathic pain.

    Science.gov (United States)

    Eom, Young In; Kim, Min; Joo, In Soo

    2017-05-01

    The aim of this study was to assess the characteristics of neuropathic pain after non-traumatic, non-compressive (NTNC) myelopathy and find potential predictors for neuropathic pain. We analyzed 54 patients with NTNC myelopathy. The Short Form McGill Pain Questionnaire (SF-MPQ) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) were used to assess pain. Health-related QOL was evaluated by the Short Form 36-item (SF-36) health survey. Out of 48 patients with pain, 16 (33.3%) patients experienced neuropathic pain. Mean age was significantly lower in patients with neuropathic pain than in patients with non-neuropathic pain (39.1 ± 12.5 vs. 49.8 ± 9.3, P = 0.002). There were no statistically significant differences in the other variables including sex, etiology of myelopathy, pain and QOL scores between the two groups. A binary logistic regression revealed that onset age under 40, and non-idiopathic etiology were independent predictors of the occurrence of neuropathic pain. Both SF-MPQ and LANSS scores were significantly correlated with SF-36 scores, adjusted by age, sex, presence of diabetes mellitus, and current EDSS scores (r = -0.624, P Neuropathic pain must be one of serious complications in patients with NTNC myelopathy and also affects their quality of life. Onset age and etiology of myelopathy are important factors in the development of neuropathic pain in NTNC myelopathy.

  3. Pharmacological Regulation of Neuropathic Pain Driven by Inflammatory Macrophages

    Directory of Open Access Journals (Sweden)

    Norikazu Kiguchi

    2017-11-01

    Full Text Available Neuropathic pain can have a major effect on quality of life but current therapies are often inadequate. Growing evidence suggests that neuropathic pain induced by nerve damage is caused by chronic inflammation. Upon nerve injury, damaged cells secrete pro-inflammatory molecules that activate cells in the surrounding tissue and recruit circulating leukocytes to the site of injury. Among these, the most abundant cell type is macrophages, which produce several key molecules involved in pain enhancement, including cytokines and chemokines. Given their central role in the regulation of peripheral sensitization, macrophage-derived cytokines and chemokines could be useful targets for the development of novel therapeutics. Inhibition of key pro-inflammatory cytokines and chemokines prevents neuroinflammation and neuropathic pain; moreover, recent studies have demonstrated the effectiveness of pharmacological inhibition of inflammatory (M1 macrophages. Nicotinic acetylcholine receptor ligands and T helper type 2 cytokines that reduce M1 macrophages are able to relieve neuropathic pain. Future translational studies in non-human primates will be crucial for determining the regulatory mechanisms underlying neuroinflammation-associated neuropathic pain. In turn, this knowledge will assist in the development of novel pharmacotherapies targeting macrophage-driven neuroinflammation for the treatment of intractable neuropathic pain.

  4. Spatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats.

    Science.gov (United States)

    Gwak, Young S; Kang, Jonghoon; Unabia, Geda C; Hulsebosch, Claire E

    2012-04-01

    In the spinal cord, neuron and glial cells actively interact and contribute to neurofunction. Surprisingly, both cell types have similar receptors, transporters and ion channels and also produce similar neurotransmitters and cytokines. The neuroanatomical and neurochemical similarities work synergistically to maintain physiological homeostasis in the normal spinal cord. However, in trauma or disease states, spinal glia become activated, dorsal horn neurons become hyperexcitable contributing to sensitized neuronal-glial circuits. The maladaptive spinal circuits directly affect synaptic excitability, including activation of intracellular downstream cascades that result in enhanced evoked and spontaneous activity in dorsal horn neurons with the result that abnormal pain syndromes develop. Recent literature reported that spinal cord injury produces glial activation in the dorsal horn; however, the majority of glial activation studies after SCI have focused on transient and/or acute time points, from a few hours to 1 month, and peri-lesion sites, a few millimeters rostral and caudal to the lesion site. In addition, thoracic spinal cord injury produces activation of astrocytes and microglia that contributes to dorsal horn neuronal hyperexcitability and central neuropathic pain in above-level, at-level and below-level segments remote from the lesion in the spinal cord. The cellular and molecular events of glial activation are not simple events, rather they are the consequence of a combination of several neurochemical and neurophysiological changes following SCI. The ionic imbalances, neuroinflammation and alterations of cell cycle proteins after SCI are predominant components for neuroanatomical and neurochemical changes that result in glial activation. More importantly, SCI induced release of glutamate, proinflammatory cytokines, ATP, reactive oxygen species (ROS) and neurotrophic factors trigger activation of postsynaptic neuron and glial cells via their own receptors

  5. Spatial and Temporal Activation of Spinal Glial Cells: Role of Gliopathy in Central Neuropathic Pain Following Spinal Cord Injury in Rats

    Science.gov (United States)

    Gwak, Young S.; Kang, Jonghoon; Unabia, Geda C.; Hulsebosch, Claire. E.

    2012-01-01

    In the spinal cord, neurons and glial cells actively interact and contribute to neurofunction. Surprisingly, both cell types have similar receptors, transporters and ion channels and also produce similar neurotransmitters and cytokines. The neuroanatomical and neurochemical similarities work synergistically to maintain physiological homeostasis in the normal spinal cord. However, in trauma or disease states, spinal glia become activated, dorsal horn neurons become hyperexcitable contributing to sensitized neuronal-glial circuits. The maladaptive spinal circuits directly affect synaptic excitability, including activation of intracellular downstream cascades that result in enhanced evoked and spontaneous activity in dorsal horn neurons with the result that abnormal pain syndromes develop. Recent literature reported that spinal cord injury produces glial activation in the dorsal horn; however, the majority of glial activation studies after SCI have focused on transient and/or acute time points, from a few hours to one month, and peri-lesion sites, a few millimeters rostral and caudal to the lesion site. In addition, thoracic spinal cord injury produces activation of astrocytes and microglia that contributes to dorsal horn neuronal hyperexcitability and central neuropathic pain in above-level, at-level and below-level segments remote from the lesion in the spinal cord. The cellular and molecular events of glial activation are not a simple event, rather it is the consequence of a combination of several neurochemical and neurophysiological changes following SCI. The ionic imbalances, neuroinflammation and alterations of cell cycle proteins after SCI are predominant components for neuroanatomical and neurochemical changes that result in glial activation. More importantly, SCI induced release of glutamate, proinfloammatory cytokines, ATP, reactive oxygen species (ROS) and neurotrophic factors trigger activation of postsynaptic neurons and glial cells via their own

  6. Topical clonidine for neuropathic pain.

    Science.gov (United States)

    Wrzosek, Anna; Woron, Jaroslaw; Dobrogowski, Jan; Jakowicka-Wordliczek, Joanna; Wordliczek, Jerzy

    2015-08-31

    Clonidine is a presynaptic alpha-2-adrenergic receptor agonist used for many years to treat hypertension and other conditions, including chronic pain. Adverse events associated with systemic use of the drug have limited its application. Topical use of drugs is currently gaining interest, as it may limit adverse events without loss of analgesic efficacy. Topical clonidine (TC) formulations have been investigated recently in clinical trials. The objectives of this review were to assess the analgesic efficacy of TC for chronic neuropathic pain in adults and to assess the frequency of adverse events associated with clinical use of TC for chronic neuropathic pain. We searched the Cochrane Register of Studies (CRS) Online (Cochrane Central Register of Controlled Trials (CENTRAL)), MEDLINE and EMBASE databases, reference lists of retrieved papers and trial registries, and we contacted experts in the field. We performed the most recent search on 17 September 2014. We included randomised, double-blind studies of at least two weeks' duration comparing TC versus placebo or other active treatment in patients with chronic neuropathic pain. Two review authors extracted data from the studies and assessed bias. We planned three tiers of evidence analysis. The first tier was designed to analyse data meeting current best standards, by which studies reported the outcome of at least 50% pain intensity reduction over baseline (or its equivalent) without use of the last observation carried forward or other imputation method for dropouts, reported an intention-to-treat (ITT) analysis, lasted eight weeks or longer, had a parallel-group design and included at least 200 participants (preferably at least 400) in the comparison. The second tier was designed to use data from at least 200 participants but in cases in which one of the above conditions was not met. The third tier of evidence was assumed in other situations. We included two studies in the review, with a total of 344 participants

  7. Rescuing Our Warriors from Chronic Pain: A Battlefield-to-Nondeployment Means to Prevent Opioid-induced Amplification of Neuropathic Pain from Traumatic Injury

    Science.gov (United States)

    2017-10-01

    agility, suggesting that the decrease in voluntary exercise is due to loss of motivation or pain amplification rather than physical disability . We... disability 15 Sep 2016 - 14 Sep 2017 15. SUBJECT TERMS chronic pain, opioid analgesics, non-opioid analgesics, toll-like receptor 4, return to duty 16...of the project? 1. Define whether deleterious effects of opioids extend beyond neuropathic pain to other indices of disability . Determine

  8. Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain.

    Science.gov (United States)

    Kim, Yu Shin; Chu, Yuxia; Han, Liang; Li, Man; Li, Zhe; LaVinka, Pamela Colleen; Sun, Shuohao; Tang, Zongxiang; Park, Kyoungsook; Caterina, Michael J; Ren, Ke; Dubner, Ronald; Wei, Feng; Dong, Xinzhong

    2014-02-19

    The peripheral terminals of primary nociceptive neurons play an essential role in pain detection mediated by membrane receptors like TRPV1, a molecular sensor of heat and capsaicin. However, the contribution of central terminal TRPV1 in the dorsal horn to chronic pain has not been investigated directly. Combining primary sensory neuron-specific GCaMP3 imaging with a trigeminal neuropathic pain model, we detected robust neuronal hyperactivity in injured and uninjured nerves in the skin, soma in trigeminal ganglion, and central terminals in the spinal trigeminal nucleus. Extensive TRPV1 hyperactivity was observed in central terminals innervating all dorsal horn laminae. The central terminal TRPV1 sensitization was maintained by descending serotonergic (5-HT) input from the brainstem. Central blockade of TRPV1 or 5-HT/5-HT3A receptors attenuated central terminal sensitization, excitatory primary afferent inputs, and mechanical hyperalgesia in the territories of injured and uninjured nerves. Our results reveal central mechanisms facilitating central terminal sensitization underlying chronic pain. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Central blood pressure and chronic kidney disease

    Science.gov (United States)

    Ohno, Yoichi; Kanno, Yoshihiko; Takenaka, Tsuneo

    2016-01-01

    In this review, we focused on the relationship between central blood pressure and chronic kidney diseases (CKD). Wave reflection is a major mechanism that determines central blood pressure in patients with CKD. Recent medical technology advances have enabled non-invasive central blood pressure measurements. Clinical trials have demonstrated that compared with brachial blood pressure, central blood pressure is a stronger risk factor for cardiovascular (CV) and renal diseases. CKD is characterized by a diminished renal autoregulatory ability, an augmented direct transmission of systemic blood pressure to glomeruli, and an increase in proteinuria. Any elevation in central blood pressure accelerates CKD progression. In the kidney, interstitial inflammation induces oxidative stress to handle proteinuria. Oxidative stress facilitates atherogenesis, increases arterial stiffness and central blood pressure, and worsens the CV prognosis in patients with CKD. A vicious cycle exists between CKD and central blood pressure. To stop this cycle, vasodilator antihypertensive drugs and statins can reduce central blood pressure and oxidative stress. Even in early-stage CKD, mineral and bone disorders (MBD) may develop. MBD promotes oxidative stress, arteriosclerosis, and elevated central blood pressure in patients with CKD. Early intervention or prevention seems necessary to maintain vascular health in patients with CKD. PMID:26788468

  10. Burden of illness associated with peripheral and central neuropathic pain among adults seeking treatment in the United States: a patient-centered evaluation.

    Science.gov (United States)

    Schaefer, Caroline; Mann, Rachael; Sadosky, Alesia; Daniel, Shoshana; Parsons, Bruce; Nieshoff, Edward; Tuchman, Michael; Nalamachu, Srinivas; Anschel, Alan; Stacey, Brett R

    2014-12-01

    The aim of this study was to evaluate patient-reported burden associated with peripheral and central neuropathic pain (NeP) by pain severity and NeP condition. Six hundred twenty-four subjects with one of six NeP conditions were recruited during routine office visits. Subjects consented to retrospective chart review and completed a one-time questionnaire (including EuroQol-5 dimensions, 12-item Short-Form Health Survey, Brief Pain Inventory-Short Form, Medical Outcomes Study Sleep Scale, Hospital Anxiety and Depression Scale, and demographic and clinical characteristics). Pain severity scores were used to stratify subjects by mild, moderate, and severe pain. Summary statistics and frequency distributions were calculated. Differences by severity level were compared using Kruskal-Wallis (continuous variables) and chi-square or Fisher's exact test (categorical variables). Effect size was computed with Cohen's d (mild vs severe). Subjects' mean age was 55.5. The majority (80.8%) had moderate or severe pain. Patient-reported outcomes (health status, physical and mental health, pain interference with function, sleep, anxiety, and depression) were significantly worse among subjects with greater pain severity (all P 0.95) for all others. The observed burden was most substantial among chronic low back pain-NeP, although the pattern of disease burden was similar across the six NeP conditions. Subjects across NeP conditions exhibited high pain levels, which were significantly associated with poor function, compromised health status and sleep, and increased anxiety and depression. Results indicate substantial patient burden across broad NeP, particularly among subjects with severe pain. Wiley Periodicals, Inc.

  11. Increased psychological distress among individuals with spinal cord injury is associated with central neuropathic pain rather than the injury characteristics.

    Science.gov (United States)

    Gruener, Hila; Zeilig, Gabi; Laufer, Yocheved; Blumen, Nava; Defrin, Ruth

    2018-02-01

    Cross-sectional study. Central neuropathic pain (CNP) is common after spinal cord injury (SCI). The psychological impact of CNP is not clear. Previous studies reported depression and pain catastrophizing among patients with SCI and CNP; however, the lack of control groups prevented discerning whether these were attributed to CNP or to the SCI itself. The aim was to examine the psychological distress among individuals with SCI with and without CNP and controls to evaluate its impact and possible source. Outpatient clinic of a large rehabilitation center. Individuals with SCI and CNP (n = 27) and without CNP (n = 23), and able-bodied controls (n = 20) participated. Data collection included sociodemographics, SCI characteristics, and level of post-traumatic stress disorder (PTSD), anxiety, stress, depression, and pain catastrophizing. The sensory, affective, and cognitive dimensions of CNP were analyzed. Individuals with SCI and CNP exhibited elevated levels of PTSD, anxiety, stress, depression, and pain catastrophizing compared to the two control groups, which presented similar levels. The psychological variables among the CNP group correlated positively only with the affective dimension of CNP. Neither CNP nor the psychological variables correlated with SCI characteristics. Irrespective of CNP intensity, the affective dimension (suffering) is associated with increased psychological distress. Perhaps individual differences in the response to SCI and/or individual traits rather than the mere exposure to SCI may have a role in the emergence of CNP and psychological distress/mood dysfunction. Rehabilitation programs should prioritize stress management and prevention among individuals with SCI and CNP.

  12. Prokineticin 2 Upregulation in the Peripheral Nervous System Has a Major Role in Triggering and Maintaining Neuropathic Pain in the Chronic Constriction Injury Model

    Directory of Open Access Journals (Sweden)

    Roberta Lattanzi

    2015-01-01

    Full Text Available The new chemokine Prokineticin 2 (PROK2 and its receptors (PKR1 and PKR2 have a role in inflammatory pain and immunomodulation. Here we identified PROK2 as a critical mediator of neuropathic pain in the chronic constriction injury (CCI of the sciatic nerve in mice and demonstrated that blocking the prokineticin receptors with two PKR1-preferring antagonists (PC1 and PC7 reduces pain and nerve damage. PROK2 mRNA expression was upregulated in the injured nerve since day 3 post injury (dpi and in the ipsilateral DRG since 6 dpi. PROK2 protein overexpression was evident in Schwann Cells, infiltrating macrophages and axons in the peripheral nerve and in the neuronal bodies and some satellite cells in the DRG. Therapeutic treatment of neuropathic mice with the PKR-antagonist, PC1, impaired the PROK2 upregulation and signalling. This fact, besides alleviating pain, brought down the burden of proinflammatory cytokines in the damaged nerve and prompted an anti-inflammatory repair program. Such a treatment also reduced intraneural oedema and axon degeneration as demonstrated by the physiological skin innervation and thickness conserved in CCI-PC1 mice. These findings suggest that PROK2 plays a crucial role in neuropathic pain and might represent a novel target of treatment for this disease.

  13. Spinal Gap Junction Channels in Neuropathic Pain

    OpenAIRE

    Jeon, Young Hoon; Youn, Dong Ho

    2015-01-01

    Damage to peripheral nerves or the spinal cord is often accompanied by neuropathic pain, which is a complex, chronic pain state. Increasing evidence indicates that alterations in the expression and activity of gap junction channels in the spinal cord are involved in the development of neuropathic pain. Thus, this review briefly summarizes evidence that regulation of the expression, coupling, and activity of spinal gap junction channels modulates pain signals in neuropathic pain states induced...

  14. Diagnostic challenges of neuropathic tooth pain.

    Science.gov (United States)

    Matwychuk, Michael J

    2004-09-01

    This article presents the clinical characteristics, epidemiology, pathophysiology and treatment of 2 neuropathic conditions: trigeminal neuralgia and atypical odontalgia. A case report highlights the complexities involved in diagnosing neuropathic pain. Neuropathic pain is chronic, diverse in quality, difficult to localize and it occurs in the absence of obvious pathology. To avoid multiple, ineffective dental treatments, general practitioners must be familiar with the signs of nonodontogenic sources of tooth pain.

  15. Dexmedetomidine attenuates neuropathic pain in chronic constriction injury by suppressing NR2B, NF-κB, and iNOS activation

    Directory of Open Access Journals (Sweden)

    Feng Liang

    2017-05-01

    Full Text Available The effective treatment of patients suffering from neuropathic pain remains challenging. Dexmedetomidine (DEX possesses anti-inflammatory activity. However, the role of DEX in neuropathic pain is still unclear. The aim of the present study was to examine DEX an α2-adrenoceptor agonist could improve pain hypersensitivity and reduce inflammatory in a chronic constriction injury (CCI model of the sciatic nerve in Sprague-Dawley rats. Dex was intrathecally administrated 1-h after operation. The paw mechanical withdrawal threshold (MWT and paw withdrawal thermal latency (PWTL were measured on day 1 before operation and on days 1, 7, 14 and 21 after operation, respectively. On day 21, all the rats were decapitated to collect the L4-6 segments of the spinal cord to examine IL-1, TNF-α, IL-6, NR2B, NF-κB, and iNOS mRNA levels using RT-PCR. The postoperative MWT and PWTL were significantly decreased in CCI, and DEX groups as compared to those before surgery and Sham group (P < 0.05. And DEX reversed this trend (P < 0.05. Interleukin 1 (IL-1, tumor necrosis factor α (TNF-α, IL-6 mRNA expression significantly increased postsurgery in CCI group as compared to that of Sham group (P < 0.05; DEX blocked increased IL-1, TNF-α, IL-6, N-methyl-D-aspartate (NMDA receptor 2B (NR2B, nuclear factor κB (NF-κB, and inducible isoform of nitric oxide synthase (iNOS mRNA levels (P < 0.05. DEX may alleviate neuropathic hypersensitivity and inflammation partially by inhibiting NR2B, NF-κB, and iNOS expression in the spinal cord of rats with neuropathic pain resulting from CCI of the sciatic nerve.

  16. Capsaicin 8% Patch for Central and Peripheral Neuropathic Pain of Persons with Incomplete Spinal Cord Injury: Two Case Reports.

    Science.gov (United States)

    Trbovich, Michelle; Yang, Huiqing

    2015-08-01

    Neuropathic pain after spinal cord injury is common and often refractory to standard treatments. The capsaicin 8% patch is a Food and Drug Administration-approved treatment of neuropathic pain in postherpetic neuralgia and has demonstrated significant efficacy in human immunodeficiency virus-autonomic neuropathy. The patch defunctionalizes transient receptor potential vanilloid 1 receptors, impairing cutaneous nociceptors for a prolonged period (i.e., 8-12 wks) with no systemic side effects. A retrospective review was conducted on the effects of the patch in two patients with spinal cord injury and neuropathic pain refractory to standard treatments. Two weeks after application, both patients reported complete pain relief. Average onset of relief of 4 days and average duration of relief of 197 days, requiring only one to four applications per year, paralleled findings reported in postherpetic neuralgia and human immunodeficiency virus-autonomic neuropathy trials. Upregulation of capsaicin-sensitive transient receptor potential vanilloid 1 receptors after spinal cord injury has been reported. The capsaicin 8% patch is a promising therapeutic agent for neuropathic pain in spinal cord injury.

  17. Effects of Saffron (Crocus sativus L.) Stigma Extract and its Active Constituent Crocin on Neuropathic Pain Responses in a Rat Model of Chronic Constriction Injury

    OpenAIRE

    Safakhah, Hossein Ali; Taghavi, Tahereh; Rashidy-Pour, Ali; Vafaei, Abbas Ali; Sokhanvar, Mina; Mohebbi, Narges; Rezaei-Tavirani, Mostafa

    2016-01-01

    This study was designed to investigate the therapeutic effects of saffron (Crocus sativus L.) and its main constituent crocin on neuropathic pain behavioral responses induced by chronic constriction injury (CCI) in rats. Adult male Wistar rats (200 to 250 g) were randomly assigned into 5 groups: Sham + saline, CCI + saline, CCI+ saffron (30 mg/kg), CCI + crocin (15 mg/kg) and CCI + crocin (30 mg/kg). CCI was induced by applying 4 loose ligatures around the sciatic nerve. Two weeks after nerve...

  18. Nortriptyline for neuropathic pain in adults.

    Science.gov (United States)

    Derry, Sheena; Wiffen, Philip J; Aldington, Dominic; Moore, R Andrew

    2015-01-08

    Antidepressants are widely used to treat chronic neuropathic pain (pain due to nerve damage), usually in doses below those at which they exert antidepressant effects. An earlier review that included all antidepressants for neuropathic pain is being replaced by new reviews of individual drugs examining individual neuropathic pain conditions.Nortriptyline is a tricyclic antidepressant that is occasionally used for treating neuropathic pain, and is recommended in European, UK, and USA guidelines. To assess the analgesic efficacy and associated adverse events of nortriptyline for chronic neuropathic pain in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from inception to 7 January 2015, and the reference lists of retrieved papers and other reviews. We also searched two clinical trials databases for ongoing or unpublished studies. We included randomised, double-blind studies of at least two weeks' duration comparing nortriptyline with placebo or another active treatment in chronic neuropathic pain. Participants were adults aged 18 years and over. We included only full journal publication articles and clinical trial summaries. Two review authors independently extracted efficacy and adverse event data, and examined issues of study quality. We considered the evidence using three tiers. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks' duration, parallel design); second tier evidence from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison; and third tier evidence from data involving small numbers of participants that was considered very likely to be biased or used outcomes of limited clinical utility

  19. Duloxetine and 8-OH-DPAT, but not fluoxetine, reduce depression-like behaviour in an animal model of chronic neuropathic pain.

    Science.gov (United States)

    Hu, Bing; Doods, Henri; Treede, Rolf-Detlef; Ceci, Angelo

    2016-04-21

    The current study assessed whether antidepressant and/or antinociceptive drugs, duloxetine, fluoxetine as well as (±)-8-hydroxy-2-[di-n-propylamino] tetralin (8-OH-DPAT), are able to reverse depression-like behaviour in animals with chronic neuropathic pain. Chronic constriction injury (CCI) of the sciatic nerve in rats was selected as neuropathic pain model. Mechanical hypersensitivity and depression-like behaviour were evaluated 4 weeks after surgery by "electronic algometer" and forced swimming test (FST), which measured the time of immobility, and active behaviours climbing and swimming. The selective noradrenergic and serotonergic uptake blocker duloxetine (20mg/kg) and the selective 5-HT1A agonist 8-OH-DPAT (0.5mg/kg) significantly reversed both mechanical hypersensitivity and depression-like behaviour in CCI animals. Duloxetine significantly reversed depression-like behaviour in CCI rats by increasing the time of climbing and swimming, while 8-OH-DPAT attenuated depression-like behaviour mainly by increasing the time of swimming. However, the selective serotonergic uptake blocker fluoxetine (20mg/kg) failed to attenuate mechanical hypersensitivity and depression-like behaviour, possibly due to confounding pro-nociceptive actions at 5-HT3 receptors. These data suggest to target noradrenergic and 5-HT1A receptors for treatment of chronic pain and its comorbidity depression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Milnacipran for neuropathic pain and fibromyalgia in adults

    Science.gov (United States)

    Derry, Sheena; Gill, Dipender; Phillips, Tudor; Moore, R Andrew

    2014-01-01

    Background Milnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI) that is sometimes used to treat chronic neuropathic pain and fibromyalgia. Objectives To evaluate the analgesic efficacy and adverse effects of milnacipran in the management of chronic neuropathic pain or fibromyalgia. Search methods We searched CENTRAL, MEDLINE, and EMBASE to 4th of January 2012, together with reference lists of retrieved papers and reviews. Selection criteria We included randomised, double-blind studies of eight weeks duration or longer, comparing milnacipran with placebo or another active treatment in chronic neuropathic pain or fibromyalgia. Data collection and analysis We extracted efficacy and adverse event data, and two study authors examined issues of study quality independently. Main results Five studies (4138 participants) were included, all of which were placebo-controlled, involved participants with fibromyalgia, and used titration to a target dose of 100 mg or 200 mg milnacipran. There were no other active comparators or studies in other neuropathic pain conditions. Study quality was generally good, although the imputation method used in analyses of the primary outcomes could overestimate treatment effect. Both doses of milnacipran provided moderate levels of pain relief to about 40% of those treated, compared to 30% with placebo, giving a number needed to treat of 8 to 10. Adverse events were common in both milnacipran (87%) and placebo (78%) groups, but serious adverse events (pain due to fibromyalgia, providing moderate levels of pain relief (at least 30%) to about 40% of participants, compared with about 30% with placebo. There were insufficient data to assess substantial levels of pain relief (at least 50%), and the use of last observation carried forward imputation may overestimate drug efficacy. Milnacipran is associated with increased adverse events and adverse event withdrawals, which were significantly greater for the higher dose. There were no

  1. Novel epigallocatechin-3-gallate (EGCG) derivative as a new therapeutic strategy for reducing neuropathic pain after chronic constriction nerve injury in mice.

    Science.gov (United States)

    Xifró, Xavier; Vidal-Sancho, Laura; Boadas-Vaello, Pere; Turrado, Carlos; Alberch, Jordi; Puig, Teresa; Verdú, Enrique

    2015-01-01

    Neuropathic pain is common in peripheral nerve injury and often fails to respond to ordinary medication. Here, we investigated whether the two novel epigallocatechin-3-gallate (EGCG) polyphenolic derivatives, compound 23 and 30, reduce the neuropathic pain in mice chronic constriction nerve injury (CCI). First, we performed a dose-response study to evaluate nociceptive sensation after administration of EGCG and its derivatives 23 and 30, using the Hargreaves test at 7 and 21 days after injury (dpi). We daily administered EGCG, 23 and 30 (10 to 100 mg/Kg; i.p.) during the first week post-CCI. None of the doses of compound 23 caused significant pain diminution, whereas 50mg/kg was optimal for both EGCG and 30 to delay the latency of paw withdrawal. With 50 mg/Kg, we showed that EGCC prevented the thermal hyperalgesia from 7 to 21 dpi and compound 30 from 14 to 56 dpi. To evaluate the molecular mechanisms underpinning why EGCG and compound 30 differentially prevented the thermal hyperalgesia, we studied several biochemical parameters in the dorsal horn of the spinal cord at 14 and 56 dpi. We showed that the effect observed with EGCG and compound 30 was related to the inhibition of fatty acid synthase (FASN), a known target of these polyphenolic compounds. Additionally, we observed that EGCG and compound 30 reduced the expression of CCI-mediated inflammatory proteins and the nuclear localization of nuclear factor-kappa B at 14 dpi, but not at 56 dpi. We also strongly detected a decrease of synaptic plasma membrane levels of N-methyl-D-asparte receptor 2B in CCI-mice treated with compound 30 at 56 dpi. Altogether, compound 30 reduced the chronic thermal hyperalgesia induced by CCI better than the natural compound EGCG. Thus, our findings provide a rationale for the preclinical development of compound 30 as an agent to treat neuropathic pain.

  2. Novel epigallocatechin-3-gallate (EGCG derivative as a new therapeutic strategy for reducing neuropathic pain after chronic constriction nerve injury in mice.

    Directory of Open Access Journals (Sweden)

    Xavier Xifró

    Full Text Available Neuropathic pain is common in peripheral nerve injury and often fails to respond to ordinary medication. Here, we investigated whether the two novel epigallocatechin-3-gallate (EGCG polyphenolic derivatives, compound 23 and 30, reduce the neuropathic pain in mice chronic constriction nerve injury (CCI. First, we performed a dose-response study to evaluate nociceptive sensation after administration of EGCG and its derivatives 23 and 30, using the Hargreaves test at 7 and 21 days after injury (dpi. We daily administered EGCG, 23 and 30 (10 to 100 mg/Kg; i.p. during the first week post-CCI. None of the doses of compound 23 caused significant pain diminution, whereas 50mg/kg was optimal for both EGCG and 30 to delay the latency of paw withdrawal. With 50 mg/Kg, we showed that EGCC prevented the thermal hyperalgesia from 7 to 21 dpi and compound 30 from 14 to 56 dpi. To evaluate the molecular mechanisms underpinning why EGCG and compound 30 differentially prevented the thermal hyperalgesia, we studied several biochemical parameters in the dorsal horn of the spinal cord at 14 and 56 dpi. We showed that the effect observed with EGCG and compound 30 was related to the inhibition of fatty acid synthase (FASN, a known target of these polyphenolic compounds. Additionally, we observed that EGCG and compound 30 reduced the expression of CCI-mediated inflammatory proteins and the nuclear localization of nuclear factor-kappa B at 14 dpi, but not at 56 dpi. We also strongly detected a decrease of synaptic plasma membrane levels of N-methyl-D-asparte receptor 2B in CCI-mice treated with compound 30 at 56 dpi. Altogether, compound 30 reduced the chronic thermal hyperalgesia induced by CCI better than the natural compound EGCG. Thus, our findings provide a rationale for the preclinical development of compound 30 as an agent to treat neuropathic pain.

  3. Neuroinflammation and Central Sensitization in Chronic and Widespread Pain.

    Science.gov (United States)

    Ji, Ru-Rong; Nackley, Andrea; Huh, Yul; Terrando, Niccolò; Maixner, William

    2018-02-19

    Chronic pain is maintained in part by central sensitization, a phenomenon of synaptic plasticity, and increased neuronal responsiveness in central pain pathways after painful insults. Accumulating evidence suggests that central sensitization is also driven by neuroinflammation in the peripheral and central nervous system. A characteristic feature of neuroinflammation is the activation of glial cells, such as microglia and astrocytes, in the spinal cord and brain, leading to the release of proinflammatory cytokines and chemokines. Recent studies suggest that central cytokines and chemokines are powerful neuromodulators and play a sufficient role in inducing hyperalgesia and allodynia after central nervous system administration. Sustained increase of cytokines and chemokines in the central nervous system also promotes chronic widespread pain that affects multiple body sites. Thus, neuroinflammation drives widespread chronic pain via central sensitization. We also discuss sex-dependent glial/immune signaling in chronic pain and new therapeutic approaches that control neuroinflammation for the resolution of chronic pain.

  4. Neuropathic pain: targeting the melatonin MT receptor

    African Journals Online (AJOL)

    Neuropathic pain is further classified as being either central. (originating from injury to the brain or spinal cord) or peripheral. (originating from injury to the peripheral nerve, plexus, dorsal root ganglion, or root). Neuropathic pain is also classified on the basis of the aetiology of the insult to the nervous system.2 In addition ...

  5. Effectiveness and Safety of Tapentadol Prolonged Release (PR) Versus a Combination of Tapentadol PR and Pregabalin for the Management of Severe, Chronic Low Back Pain With a Neuropathic Component: A Randomized, Double-blind, Phase 3b Study.

    Science.gov (United States)

    Baron, Ralf; Martin-Mola, Emilio; Müller, Matthias; Dubois, Cecile; Falke, Dietmar; Steigerwald, Ilona

    2015-06-01

    To evaluate the effectiveness and tolerability of tapentadol PR monotherapy versus tapentadol PR/pregabalin combination therapy for severe, chronic low back pain with a neuropathic component. Eligible patients had painDETECT "unclear" or "positive" ratings and average pain intensity ≥ 6 (11-point NRS-3 [average 3-day pain intensity]) at baseline. Patients were titrated to tapentadol PR 300 mg/day over 3 weeks. Patients with ≥ 1-point decrease in pain intensity and average pain intensity ≥ 4 were randomized to tapentadol PR (500 mg/day) or tapentadol PR (300 mg/day)/pregabalin (300 mg/day) during an 8-week comparative period. In the per-protocol population (n = 288), the effectiveness of tapentadol PR was clinically and statistically comparable to tapentadol PR/pregabalin based on the change in pain intensity from randomization to final evaluation (LOCF; LSMD [95% CI], -0.066 [-0.57, 0.43]; P opioids and anticonvulsants for combination therapy. The incidence of the composite of dizziness and/or somnolence was significantly lower with tapentadol PR (16.9%) than tapentadol PR/pregabalin (27.0%; P = 0.0302). Tapentadol PR 500 mg is associated with comparable improvements in pain intensity and quality-of-life measures to tapentadol PR 300 mg/pregabalin 300 mg, with improved central nervous system tolerability, suggesting that tapentadol PR monotherapy may offer a favorable treatment option for severe low back pain with a neuropathic component. © 2014 The Authors. Pain Practice published by Wiley periodicals, Inc. on behalf of World Institute of Pain.

  6. Effects of Saffron (Crocus sativus L.) Stigma Extract and its Active Constituent Crocin on Neuropathic Pain Responses in a Rat Model of Chronic Constriction Injury.

    Science.gov (United States)

    Safakhah, Hossein Ali; Taghavi, Tahereh; Rashidy-Pour, Ali; Vafaei, Abbas Ali; Sokhanvar, Mina; Mohebbi, Narges; Rezaei-Tavirani, Mostafa

    2016-01-01

    This study was designed to investigate the therapeutic effects of saffron (Crocus sativus L.) and its main constituent crocin on neuropathic pain behavioral responses induced by chronic constriction injury (CCI) in rats. Adult male Wistar rats (200 to 250 g) were randomly assigned into 5 groups: Sham + saline, CCI + saline, CCI+ saffron (30 mg/kg), CCI + crocin (15 mg/kg) and CCI + crocin (30 mg/kg). CCI was induced by applying 4 loose ligatures around the sciatic nerve. Two weeks after nerve lesion, injections of saline, saffron or crocin were started and continued until 26(th) day post-surgery. Pain behavioral responses including mechanical allodynia (von Frey filament testing) and thermal hyperalgesia were measured in 14, 17, 20, 23, 26, and 40(th) days after CCI. CCI significantly increased pain behavioral responses. Saffron and crocin (30 mg/kg) decreased thermal hyperalgesia and mechanical allodynia on day 26, and this effect continued until the day 40. Crocin at lower dose (15 mg/kg) was ineffective. These findings indicate that treatment of saffron and crocin after CCI may have a therapeutic effect against neuropathic pain, suggesting that these substances may offer new strategies for the treatment of this highly debilitating condition.

  7. Differences in Neural Mechanosensitivity Between Patients with Chronic Nonspecific Neck Pain With and Without Neuropathic Features. A Descriptive Cross-Sectional Study.

    Science.gov (United States)

    López-de-Uralde-Villanueva, Ibai; Beltran-Alacreu, Hector; Fernández-Carnero, Josué; Gil-Martínez, Alfonso; La Touche, Roy

    2016-01-01

    To assess differences in neural mechanosensitivity between patients with chronic nonspecific neck pain with and without neuropathic features (NF and No-NF, respectively). Descriptive, cross-sectional study. A primary care center, a hospital physiotherapy outpatient department, and a university campus. Chronic nonspecific neck pain patients classified by the self-completed leeds assessment of neuropathic symptoms and signs pain scale (S-LANSS; 49 patients with NF [S-LANSS ≥ 12] and 50 patients with No-NF [S-LANSS pain intensity according to the upper limb neural test 1 (ULNT1) for the median nerve and the modified passive neck flexion test (MPNFT) for the cervical region; secondary measurements included pain intensity, neck disability, kinesiophobia, and pain catastrophizing. Statistically significant differences between the NF and No-NF groups were found with respect to the onset of symptoms of ULNT1 (-15.11 [-23.19 to -7.03]) and MPNFT (-6.58 [-11.54 to -1.62]), as well as the outcomes of the visual analogue scale (Mean difference [95% Confidence Interval]; 7.12 [1.81-12.42]) and neck disability index (3.72 [1.72-5.71]). Both chronic nonspecific neck pain groups showed statistically significant differences compared with the control group for all outcomes assessed (P neck pain patients with NF have greater neural mechanosensitivity, pain intensity, and neck disability than those with No-NF. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. 2016. This work is written by US Government employees and is in the public domain in the US.

  8. Desipramine for neuropathic pain in adults.

    Science.gov (United States)

    Hearn, Leslie; Moore, R Andrew; Derry, Sheena; Wiffen, Philip J; Phillips, Tudor

    2014-09-23

    Antidepressants are widely used to treat chronic neuropathic pain (pain due to nerve damage), usually in doses below those at which they exert antidepressant effects. An earlier review that included all antidepressants for neuropathic pain is being replaced by new reviews of individual drugs examining individual neuropathic pain conditions.Desipramine is a tricyclic antidepressant that is occasionally used for treating neuropathic pain. To assess the analgesic efficacy of desipramine for chronic neuropathic pain in adults, and to assess the associated adverse events. We searched CENTRAL, MEDLINE, and EMBASE from inception to 29 April 2014, and the reference lists of retrieved papers and other reviews. We also used our own hand searched database to identify older studies, and two clinical trials databases for ongoing or unpublished studies. We included randomised, double-blind studies of at least two weeks duration comparing desipramine with placebo or another active treatment in chronic neuropathic pain. Participants were adults aged 18 years and over. We included only full journal publication articles. Two review authors independently extracted the efficacy and adverse event data, and examined issues of study quality. We performed analysis using three tiers of evidence. First tier evidence was derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts, at least 200 participants in the comparison, 8 to 12 weeks duration, parallel design); second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison; and third tier from data involving small numbers of participants and considered very likely to be biased or that used outcomes of limited clinical utility, or both. Five studies treated 177 participants with painful diabetic

  9. Imipramine for neuropathic pain in adults.

    Science.gov (United States)

    Hearn, Leslie; Derry, Sheena; Phillips, Tudor; Moore, R Andrew; Wiffen, Philip J

    2014-05-19

    Antidepressants are widely used to treat chronic neuropathic pain (pain due to nerve damage), usually in doses below those at which they exert antidepressant effects. An earlier review that included all antidepressants for neuropathic pain is being replaced by new reviews of individual drugs examining individual neuropathic pain conditions.Imipramine is a tricyclic antidepressant that is occasionally used to treat neuropathic pain. To assess the analgesic efficacy of imipramine for chronic neuropathic pain in adults, and to assess the associated adverse events. We searched CENTRAL, MEDLINE, and EMBASE on 18 November 2013, as well as the reference lists of retrieved papers and other reviews. We also used our own handsearched database for older studies, and two clinical trials databases. We included randomised, double-blind studies of at least two weeks' duration comparing imipramine with placebo or another active treatment in chronic neuropathic pain. Participants were adults aged 18 and over. We included only articles with full journal publication and extended trial abstracts and summaries. Two review authors independently extracted efficacy and adverse event data, and examined issues of study quality. We performed analysis using three tiers of evidence. First tier evidence was derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks duration, parallel design); second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison; and third tier from data involving small numbers of participants which was considered very likely to be biased or used outcomes of limited clinical utility, or both. Five studies treated 168 participants with painful diabetic neuropathy or

  10. Neural Mobilization Treatment Decreases Glial Cells and Brain-Derived Neurotrophic Factor Expression in the Central Nervous System in Rats with Neuropathic Pain Induced by CCI in Rats.

    Science.gov (United States)

    Giardini, Aline Carolina; Dos Santos, Fabio Martinez; da Silva, Joyce Teixeira; de Oliveira, Mara Evany; Martins, Daniel Oliveira; Chacur, Marucia

    2017-01-01

    Background . Glial cells are implicated in the development of chronic pain and brain-derived neurotropic factor (BDNF) released from activated microglia contributes to the nociceptive transmission. Neural mobilization (NM) technique is a method clinically effective in reducing pain sensitivity. Here we examined the involvement of glial cells and BDNF expression in the thalamus and midbrain after NM treatment in rats with chronic constriction injury (CCI). CCI was induced and rats were subsequently submitted to 10 sessions of NM, every other day, beginning 14 days after CCI. Thalamus and midbrain were analyzed for glial fibrillary acidic protein (GFAP), microglial cell OX-42, and BDNF using Immunohistochemistry and Western blot assays. Results . Thalamus and midbrain of CCI group showed increases in GFAP, OX-42, and BDNF expression compared with control group and, in contrast, showed decreases in GFAP, OX-42, and BDNF after NM when compared with CCI group. The decreased immunoreactivity for GFAP, OX-42, and BDNF in ventral posterolateral nucleus in thalamus and the periaqueductal gray in midbrain was shown by immunohistochemistry. Conclusions . These findings may improve the knowledge about the involvement of astrocytes, microglia, and BDNF in the chronic pain and show that NM treatment, which alleviates neuropathic pain, affects glial cells and BDNF expression.

  11. Peripheral Nerve Stimulation of Brachial Plexus Nerve Roots and Supra-Scapular Nerve for Chronic Refractory Neuropathic Pain of the Upper Limb.

    Science.gov (United States)

    Bouche, Bénédicte; Manfiotto, Marie; Rigoard, Philippe; Lemarie, Jean; Dix-Neuf, Véronique; Lanteri-Minet, Michel; Fontaine, Denys

    2017-10-01

    We report the outcome of a consecutive series of 26 patients suffering from chronic medically-refractory neuropathic pain of the upper limb (including 16 patients with complex regional pain syndrome), topographically limited, treated by brachial plexus (BP) nerve roots or supra-scapular nerve (SSN) peripheral nerve stimulation (PNS). The technique consisted in ultrasound-guided percutaneous implantation of a cylindrical lead (Pisces-Quad, Medtronic) close to the SSN or the cervical nerve roots within the BP, depending on the pain topography. All the patients underwent a positive trial stimulation before lead connection to a subcutaneous stimulator. Chronic bipolar stimulation mean parameters were: frequency 55.5 Hertz, voltage 1.17 Volts. The voltage was set below the threshold inducing muscle contractions or paresthesias. Two patients were lost immediately after surgery. At last follow-up (mean 27.5 months), the 20 patients still using the stimulation experienced a mean pain relief of 67.1%. Seventeen patients were improved ≥50%, including 12 improved ≥70%. In 11 patients with a follow-up >2 years, the mean pain relief was 68%. At last follow-up, respectively, six out of the nine (67%) patients treated by SSN stimulation and 10 out of 17 patients (59%) treated by BP stimulation were improved ≥50%. At last follow-up, 12 out of 20 patients still using the stimulation were very satisfied, six were satisfied, and two were poorly satisfied. Complications were: stimulation intolerance due to shock-like sensations (three cases), superficial infection (1), lead fractures (2), and migration (1). In this pilot study, SSN or BP roots PNS provided a relatively safe, durable and effective option to control upper limb neuropathic pain. © 2017 International Neuromodulation Society.

  12. Therapeutic implications of toll-like receptors in peripheral neuropathic pain.

    Science.gov (United States)

    Thakur, Krishan K; Saini, Jyoti; Mahajan, Kanika; Singh, Dhyanendra; Jayswal, Dinkar P; Mishra, Srishti; Bishayee, Anupam; Sethi, Gautam; Kunnumakkara, Ajaikumar B

    2017-01-01

    Neuropathic pain is a state of chronic pain arising after peripheral or central nerve injury. These injuries can be mediated through the activation of various cells (astrocytes, microglia and Schwann cells), as well as the dissolution of distal axons. Recent studies have suggested that after nerve injury, Toll-like receptors (TLRs) involved in Wallerian degeneration and generation of neuropathic pain. Furthermore, these TLRs are responsible for the stimulation of astrocytes and microglia that can cause induction of the proinflammatory mediators and cytokines in the spinal cord, thereby leading to the generation and maintenance of neuropathic pain. Indeed considering the prevalence of neuropathic pain and suffering of the affected patients, insights into the diverse mechanism(s) of activation of TLR signaling cascades may open novel avenues for the management of this chronic condition. Moreover, existing therapies like antidepressants, anticonvulsants, opiates and other analgesic are not sufficiently effective in reducing the pain. In this review, we present substantial evidences highlighting the diverse roles of TLRs and their signaling pathways involved in the progression of neuropathic pain. Furthermore, an elaborate discussion on various existing treatment regimens and future targets involving TLRs has also been included. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Central hypersensitivity in chronic musculoskeletal pain

    DEFF Research Database (Denmark)

    Curatolo, Michele; Arendt-Nielsen, Lars

    2015-01-01

    Clinical research has consistently detected alteration in central pain processing leading to hypersensitivity. Most methods used in humans are reliable and have face validity to detect widespread central hypersensitivity. However, construct validity is difficult to investigate due to lack of gold...... standards. Reference values in the pain-free population have been generated, but need replication. Research on pain biomarkers that reflect specific central hypersensitivity processes is warranted. Few studies have analyzed the prognostic value of central hypersensitivity. Most medications acting at central...... level and some non-pharmacological approaches, including psychological interventions, are likely to attenuate central hypersensitivity....

  14. Intrathecal Administration of Tempol Reduces Chronic Constriction Injury-Induced Neuropathic Pain in Rats by Increasing SOD Activity and Inhibiting NGF Expression.

    Science.gov (United States)

    Zhao, Baisong; Pan, Yongying; Wang, Zixin; Tan, Yonghong; Song, Xingrong

    2016-08-01

    We investigate the antinociceptive effect of intrathecal and intraperitoneal tempol administration in a rat model of chronic constriction injury (CCI)-induced neuropathic pain and explore the underlying antinociceptive mechanisms of tempol. Rats were randomly assigned to four groups (n = 8 per group): sham group, CCI group, Tem1 group (intrathecal injection of tempol), and Tem2 group (intraperitoneal injection of tempol). Neuropathic pain was induced by CCI of the sciatic nerve. Tempol was intrathecally or intraperitoneally administered daily for 7 days beginning on postoperative day one. The mechanical withdrawal threshold and thermal withdrawal latency were tested on preoperative day 3 and postoperative days 1, 3, 5, 7, 10, 14, and 21. Structural changes were examined by hematoxylin and eosin staining, toluidine blue staining, and electron microscopy. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined using the thiobarbituric acid and nitroblue tetrazolium methods, respectively. Nerve growth factor (NGF) expression levels were determined by immunohistochemistry and Western blot. Intrathecal, but not intraperitoneal, injection of tempol produced a persistent antinociceptive effect. Intraperitoneal injection of tempol did not result in high enough concentration of tempol in the cerebrospinal fluid. Intrathecal, but not intraperitoneal, injection of tempol inhibited CCI-induced structural damage in the spinal cord reduced MDA levels, and increased SOD activities in the spinal cord. Furthermore, intrathecal, but not intraperitoneal, injection of tempol further downregulated the expression of NGF in the spinal cord following CCI, and this effect was blocked by p38MAPK inhibitor. Intrathecal injection of tempol produces antinociceptive effects and reduces CCI-induced structural damage in the spinal cord by increasing SOD activities and downregulating the expression of NGF via the p38MAPK pathway. Intraperitoneal administration of tempol does

  15. Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury.

    Science.gov (United States)

    Fandel, Thomas M; Trivedi, Alpa; Nicholas, Cory R; Zhang, Haoqian; Chen, Jiadong; Martinez, Aida F; Noble-Haeusslein, Linda J; Kriegstein, Arnold R

    2016-10-06

    Neuropathic pain and bladder dysfunction represent significant quality-of-life issues for many spinal cord injury patients. Loss of GABAergic tone in the injured spinal cord may contribute to the emergence of these symptoms. Previous studies have shown that transplantation of rodent inhibitory interneuron precursors from the medial ganglionic eminence (MGE) enhances GABAergic signaling in the brain and spinal cord. Here we look at whether transplanted MGE-like cells derived from human embryonic stem cells (hESC-MGEs) can mitigate the pathological effects of spinal cord injury. We find that 6 months after transplantation into injured mouse spinal cords, hESC-MGEs differentiate into GABAergic neuron subtypes and receive synaptic inputs, suggesting functional integration into host spinal cord. Moreover, the transplanted animals show improved bladder function and mitigation of pain-related symptoms. Our results therefore suggest that this approach may be a valuable strategy for ameliorating the adverse effects of spinal cord injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Spinal cord stimulation for neuropathic pain: current perspectives.

    Science.gov (United States)

    Wolter, Tilman

    2014-01-01

    Neuropathic pain constitutes a significant portion of chronic pain. Patients with neuropathic pain are usually more heavily burdened than patients with nociceptive pain. They suffer more often from insomnia, anxiety, and depression. Moreover, analgesic medication often has an insufficient effect on neuropathic pain. Spinal cord stimulation constitutes a therapy alternative that, to date, remains underused. In the last 10 to 15 years, it has undergone constant technical advancement. This review gives an overview of the present practice of spinal cord stimulation for chronic neuropathic pain and current developments such as high-frequency stimulation and peripheral nerve field stimulation.

  17. Etiology and Pharmacology of Neuropathic Pain.

    Science.gov (United States)

    Alles, Sascha R A; Smith, Peter A

    2018-04-01

    Injury to or disease of the nervous system can invoke chronic and sometimes intractable neuropathic pain. Many parallel, interdependent, and time-dependent processes, including neuroimmune interactions at the peripheral, supraspinal, and spinal levels, contribute to the etiology of this "disease of pain." Recent work emphasizes the roles of colony-stimulating factor 1, ATP, and brain-derived neurotrophic factor. Excitatory processes are enhanced, and inhibitory processes are attenuated in the spinal dorsal horn and throughout the somatosensory system. This leads to central sensitization and aberrant processing such that tactile and innocuous thermal information is perceived as pain (allodynia). Processes involved in the onset of neuropathic pain differ from those involved in its long-term maintenance. Opioids display limited effectiveness, and less than 35% of patients derive meaningful benefit from other therapeutic approaches. We thus review promising therapeutic targets that have emerged over the last 20 years, including Na + , K + , Ca 2+ , hyperpolarization-activated cyclic nucleotide-gated channels, transient receptor potential channel type V1 channels, and adenosine A3 receptors. Despite this progress, the gabapentinoids retain their status as first-line treatments, yet their mechanism of action is poorly understood. We outline recent progress in understanding the etiology of neuropathic pain and show how this has provided insights into the cellular actions of pregabalin and gabapentin. Interactions of gabapentinoids with the α 2 δ -1 subunit of voltage-gated Ca 2+ channels produce multiple and neuron type-specific actions in spinal cord and higher centers. We suggest that drugs that affect multiple processes, rather than a single specific target, show the greatest promise for future therapeutic development. Copyright © 2018 by The Author(s).

  18. Activated microglia in the spinal cord underlies diabetic neuropathic pain.

    Science.gov (United States)

    Wang, Dongmei; Couture, Réjean; Hong, Yanguo

    2014-04-05

    Diabetes mellitus is an increasingly common chronic medical condition. Approximately 30% of diabetic patients develop neuropathic pain, manifested as spontaneous pain, hyperalgesia and allodynia. Hyperglycemia induces metabolic changes in peripheral tissues and enhances oxidative stress in nerve fibers. The damages and subsequent reactive inflammation affect structural properties of Schwann cells and axons leading to the release of neuropoietic mediators, such as pro-inflammatory cytokines and pro-nociceptive mediators. Therefore, diabetic neuropathic pain (DNP) shares some histological features and underlying mechanisms with traumatic neuropathy. DNP displays, however, other distinct features; for instance, sensory input to the spinal cord decreases rather than increasing in diabetic patients. Consequently, development of central sensitization in DNP involves mechanisms that are distinct from traumatic neuropathic pain. In DNP, the contribution of spinal cord microglia activation to central sensitization and pain processes is emerging as a new concept. Besides inflammation in the periphery, hyperglycemia and the resulting production of reactive oxygen species affect the local microenvironment in the spinal cord. All these alterations could trigger resting and sessile microglia to the activated phenotype. In turn, microglia synthesize and release pro-inflammatory cytokines and neuroactive molecules capable of inducing hyperactivity of spinal nociceptive neurons. Hence, it is imperative to elucidate glial mechanisms underlying DNP for the development of effective therapeutic agents. The present review highlights the recent developments regarding the contribution of spinal microglia as compelling target for the treatment of DNP. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Analgesic Microneedle Patch for Neuropathic Pain Therapy.

    Science.gov (United States)

    Xie, Xi; Pascual, Conrado; Lieu, Christopher; Oh, Seajin; Wang, Ji; Zou, Bende; Xie, Julian; Li, Zhaohui; Xie, James; Yeomans, David C; Wu, Mei X; Xie, Xinmin Simon

    2017-01-24

    Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain. Local analgesic effects were evaluated in rats by testing behavioral pain sensitivity in response to thermal and mechanical stimuli using neuropathic pain models such as spared-nerve injury and diabetic neuropathy pain, as well as neurogenic inflammatory pain model induced by ultraviolet B (UVB) radiation. Unlike several conventional therapies, the AMN patches produced effective analgesia on neuropathic pain without disturbing the normal nociception and motor function of the rat, resulting from the high specificity of the delivered peptide against CGRP receptors. The AMN patches did not cause skin irritation or systemic side effects. These results demonstrate that dissolvable microneedle patches delivering CGRP antagonist peptide provide an effective, safe, and simple approach to mitigate neuropathic pain with significant advantages over current treatments.

  20. Spinal cord stimulation for neuropathic pain: current perspectives

    OpenAIRE

    Wolter, Tilman

    2014-01-01

    Tilman Wolter Interdisciplinary Pain Centre, University Hospital Freiburg, Freiburg, Germany Abstract: Neuropathic pain constitutes a significant portion of chronic pain. Patients with neuropathic pain are usually more heavily burdened than patients with nociceptive pain. They suffer more often from insomnia, anxiety, and depression. Moreover, analgesic medication often has an insufficient effect on neuropathic pain. Spinal cord stimulation constitutes a therapy alternative that, to date, re...

  1. EFNS guidelines on neurostimulation therapy for neuropathic pain

    DEFF Research Database (Denmark)

    EFNS Panel on Neuropathic Pain, Vienna; Cruccu, Giorgio; Aziz, T. Z.

    2007-01-01

    Pharmacological relief of neuropathic pain is often insufficient. Electrical neurostimulation is efficacious in chronic neuropathic pain and other neurological diseases. European Federation of Neurological Societies (EFNS) launched a Task Force to evaluate the evidence for these techniques...... and to produce relevant recommendations. We searched the literature from 1968 to 2006, looking for neurostimulation in neuropathic pain conditions, and classified the trials according to the EFNS scheme of evidence for therapeutic interventions. Spinal cord stimulation (SCS) is efficacious in failed back surgery...

  2. ABSTRACT CHRONIC MYELOID LEUKAEMIA IN CENTRAL ...

    African Journals Online (AJOL)

    hi-tech

    2003-09-09

    , USA. .... anaemia (Hb ≤ 9.4g/dl recorded in 86 (57.3%) patients and ..... J.M. Chronic myeloid leukaemia. In. Haematology, Basic Principles and Practice 2nd edn., (ed.), R. Hoffman. Churchill Livingstone, New York, USA.

  3. Impact of locomotion training with a neurologic controlled hybrid assistive limb (HAL) exoskeleton on neuropathic pain and health related quality of life (HRQoL) in chronic SCI: a case study (.).

    Science.gov (United States)

    Cruciger, Oliver; Schildhauer, Thomas A; Meindl, Renate C; Tegenthoff, Martin; Schwenkreis, Peter; Citak, Mustafa; Aach, Mirko

    2016-08-01

    Chronic neuropathic pain (CNP) is a common condition associated with spinal cord injury (SCI) and has been reported to be severe, disabling and often treatment-resistant and therefore remains a clinical challenge for the attending physicians. The treatment usually includes pharmacological and/or nonpharmacological approaches. Body weight supported treadmill training (BWSTT) and locomotion training with driven gait orthosis (DGO) have evolved over the last decades and are now considered to be an established part in the rehabilitation of SCI patients. Conventional locomotion training goes along with improvements of the patients' walking abilities in particular speed and gait pattern. The neurologic controlled hybrid assistive limb (HAL®, Cyberdyne Inc., Ibraki, Japan) exoskeleton, however, is a new tailored approach to support motor functions synchronously to the patient's voluntary drive. This report presents two cases of severe chronic and therapy resistant neuropathic pain due to chronic SCI and demonstrates the beneficial effects of neurologic controlled exoskeletal intervention on pain severity and health-related quality of life (HRQoL). Both of these patients were engaged in a 12 weeks period of daily HAL®-supported locomotion training. In addition to improvements in motor functions and walking abilities, both show significant reduction in pain severity and improvements in all HRQoL domains. Although various causal factors likely contribute to abatement of CNP, the reported results occurred due to a new approach in the rehabilitation of chronic spinal cord injury patients. These findings suggest not only the feasibility of this new approach but in conclusion, demonstrate the effectiveness of neurologic controlled locomotion training in the long-term management of refractory neuropathic pain. Implications for Rehabilitation CNP remains a challenge in the rehabilitation of chronic SCI patients. Locomotion training with the HAL exoskeleton seems to improve CNP

  4. Regulation of Neurotrophin-3 and Interleukin-1β and Inhibition of Spinal Glial Activation Contribute to the Analgesic Effect of Electroacupuncture in Chronic Neuropathic Pain States of Rats

    Directory of Open Access Journals (Sweden)

    Wenzhan Tu

    2015-01-01

    Full Text Available Growing evidence indicates that neurotrophin-3, interleukin-1β, and spinal glia are involved in neuropathic pain derived from dorsal root ganglia to spinal cord. Electroacupuncture is widely accepted to treat chronic pain, but the precise mechanism underlying the analgesic effect of EA has not been fully demonstrated. In this study, the mechanical withdrawal threshold and thermal withdrawal latency were recorded. We used immunofluorescence and western blots methods to investigate the effect of EA on the expression of NT-3 and IL-1β in DRG and spinal cord of CCI rats; we also examined the expression of spinal GFAP and OX-42 in spinal cord. In present study, the MWT and TWL of CCI group rats were lower than those in the Sham CCI group rats, but EA treatment increased the pain thresholds. Furtherly, we found that EA upregulates the expression of NT-3 in DRG and spinal cord of CCI rats, while EA downregulates the expression of IL-1β. Additionally, immunofluorescence exhibited that CCI-induced activation of microglia and astrocytes was inhibited significantly by EA treatment. These results demonstrated that the analgesic effect of EA may be achieved through promoting the neural protection of NT-3 as well as the inhibition of IL-1β production and spinal glial activity.

  5. Methadone for neuropathic pain in adults.

    Science.gov (United States)

    McNicol, Ewan D; Ferguson, McKenzie C; Schumann, Roman

    2017-05-17

    This review replaces an earlier review, "Methadone for chronic non-cancer pain in adults". This review serves to update the original and includes only studies of neuropathic pain. Methadone belongs to a class of analgesics known as opioids, that are considered the cornerstone of therapy for moderate-to-severe postsurgical pain and pain due to life-threatening illnesses; however, their use in neuropathic pain is controversial. Methadone has many characteristics that differentiate it from other opioids, which suggests that it may have a different efficacy and safety profile. To assess the analgesic efficacy and adverse events of methadone for chronic neuropathic pain in adults. We searched the following databases: CENTRAL (CRSO), MEDLINE (Ovid), and Embase (Ovid), and two clinical trial registries. We also searched the reference lists of retrieved articles. The date of the most recent search was 30 November 2016. We included randomised, double-blind studies of two weeks' duration or longer, comparing methadone (in any dose, administered by any route, and in any formulation) with placebo or another active treatment in chronic neuropathic pain. We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. There were insufficient data to perform pooled analyses. We assessed the overall quality of the evidence for each outcome using GRADE and created a 'Summary of findings' table. We included three studies, involving 105 participants. All were cross-over studies, one involving 19 participants with diverse neuropathic pain syndromes, the other two involving 86 participants with postherpetic neuralgia. Study phases ranged from 20 days to approximately eight weeks. All administered methadone orally, in doses ranging from 10 mg to 80 mg daily. Comparators were primarily placebo, but one study also included morphine and tricyclic antidepressants

  6. Neuropathic pain: targeting the melatonin MT 2 receptor | Smith ...

    African Journals Online (AJOL)

    More recently, melatonin, commonly known as the neurohormone that regulates the circadian rhythm, has come to light as a therapeutic treatment option in the neuropathic pain setting. Early clinical trials showed a link between melatonin and chronic pain, which includes neuropathic pain. The MT2 receptor has also been ...

  7. Antidepressants in the treatment of neuropathic pain

    DEFF Research Database (Denmark)

    Sindrup, Søren H.; Otto, Marit; Finnerup, Nanna Brix

    2005-01-01

    Neuropathic pain is due to lesion or dysfunction of the peripheral or central nervous system. Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit...... presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated...... in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2-3 patients with peripheral...

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

    Science.gov (United States)

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

    2017-09-01

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

  9. Neuropathic sensory symptoms: association with pain and psychological factors

    Directory of Open Access Journals (Sweden)

    Shaygan M

    2014-05-01

    Full Text Available Maryam Shaygan,1 Andreas Böger,2 Birgit Kröner-Herwig11Department of Clinical Psychology and Psychotherapy, University of Göttingen, Germany; 2Pain Management Clinic at the Red Cross Hospital, Kassel, GermanyBackground: A large number of population-based studies of chronic pain have considered neuropathic sensory symptoms to be associated with a high level of pain intensity and negative affectivity. The present study examines the question of whether this association previously found in non-selected samples of chronic pain patients can also be found in chronic pain patients with underlying pathology of neuropathic sensory symptoms.Methods: Neuropathic sensory symptoms in 306 patients with chronic pain diagnosed as typical neuropathic pain, radiculopathy, fibromyalgia, or nociceptive back pain were assessed using the Pain DETECT Questionnaire. Two separate cluster analyses were performed to identify subgroups of patients with different levels of self-reported neuropathic sensory symptoms and, furthermore, to identify subgroups of patients with distinct patterns of neuropathic sensory symptoms (adjusted for individual response bias regarding specific symptoms.Results: ANOVA (analysis of variance results in typical neuropathic pain, radiculopathy, and fibromyalgia showed no significant differences between the three levels of neuropathic sensory symptoms regarding pain intensity, pain chronicity, pain catastrophizing, pain acceptance, and depressive symptoms. However, in nociceptive back pain patients, significant differences were found for all variables except pain chronicity. When controlling for the response bias of patients in ratings of symptoms, none of the patterns of neuropathic sensory symptoms were associated with pain and psychological factors.Conclusion: Neuropathic sensory symptoms are not closely associated with higher levels of pain intensity and cognitive-emotional evaluations in chronic pain patients with underlying pathology of

  10. [Central lung embolism in chronic interstitial pneumopathy].

    Science.gov (United States)

    Mordasini, C; Hess, B; Zimmermann, A

    1998-04-15

    An 80 year old patient with known interstitial pneumopathy of unknown etiology was hospitalized because of acute onset and rapid deterioration of dyspnea at rest within days. A foregoing neurologic investigation including CT and EEG because of prior syncopes and cramp attacks had not revealed pathologic findings. Thorax X-ray at admission showed homogenous loss of transparency on the left side, calcified basal plaques on both sides and prominent central pulmonary vessels with jumping caliber. A punctate of the leftsided pleural effusion revealed lymphocytic exsudate, normal pH, low glucose and an elevated LDH. The patient died shortly after a collapse at a bowel visit and pulmonary embolism was suspected in accordance to results from arterial blood gas analysis, ECG and chest X-ray. Neurologic symptoms could be explained by recurrent pulmonary embolism. Pleural plaques together with the punctate suggested a malignant etiology. A mesothelioma was taken into consideration, although there were no anamnestic reports on an exposition to asbestos. Autopsy revealed almost complete central embolism of the left pulmonary artery with acute cor pulmonale thus confirming the clinical suspicion. The embolus showed components of different ages of origin. Besides bronchitic and emphysematous alteration histology of the pulmonary tissue revealed interstitial and septal fibrosis with focal tissue consolidation. In one giant cell a typical asbestos body was found (in 1 out of 10 sections). In spite of missing information on an exposition to asbestos an abnormally high exposition must be taken into consideration because of the finding of an asbestos particle in relation to the amount of tissue studied. Apart from interstitial fibrosis asbestos may also cause consolidation of pulmonary tissue. Histology of plaquelike lesions revealed mesothelioma of fibrous type. This finding supports the suspicion that a major part of the pulmonary lesions was due to exposition to asbestos.

  11. Microglia: A Promising Target for Treating Neuropathic and Postoperative Pain, and Morphine Tolerance

    Directory of Open Access Journals (Sweden)

    Yeong-Ray Wen

    2011-08-01

    Full Text Available Management of chronic pain, such as nerve-injury-induced neuropathic pain associated with diabetic neuropathy, viral infection, and cancer, is a real clinical challenge. Major surgeries, such as breast and thoracic surgery, leg amputation, and coronary artery bypass surgery, also lead to chronic pain in 10–50% of individuals after acute postoperative pain, partly due to surgery-induced nerve injury. Current treatments mainly focus on blocking neurotransmission in the pain pathway and have only resulted in limited success. Ironically, chronic opioid exposure might lead to paradoxical pain. Development of effective therapeutic strategies requires a better understanding of cellular mechanisms underlying the pathogenesis of neuropathic pain. Progress in pain research points to an important role of microglial cells in the development of chronic pain. Spinal cord microglia are strongly activated after nerve injury, surgical incision, and chronic opioid exposure. Increasing evidence suggests that, under all these conditions, the activated microglia not only exhibit increased expression of microglial markers CD 11 b and Iba 1, but also display elevated phosphorylation of p38 mitogen-activated protein kinase. Inhibition of spinal cord p38 has been shown to attenuate neuropathic and postoperative pain, as well as morphine-induced antinociceptive tolerance. Activation of p38 in spinal microglia results in increased synthesis and release of the neurotrophin brain-derived neurotrophic factor and the proinflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α. These microglia-released mediators can powerfully modulate spinal cord synaptic transmission, leading to increased excitability of dorsal horn neurons, that is, central sensitization, partly via suppressing inhibitory synaptic transmission. Here, we review studies that support the pronociceptive role of microglia in conditions of neuropathic and postoperative pain and opioid

  12. Spinal cord stimulation for neuropathic pain: current perspectives

    Directory of Open Access Journals (Sweden)

    Wolter T

    2014-11-01

    Full Text Available Tilman Wolter Interdisciplinary Pain Centre, University Hospital Freiburg, Freiburg, Germany Abstract: Neuropathic pain constitutes a significant portion of chronic pain. Patients with neuropathic pain are usually more heavily burdened than patients with nociceptive pain. They suffer more often from insomnia, anxiety, and depression. Moreover, analgesic medication often has an insufficient effect on neuropathic pain. Spinal cord stimulation constitutes a therapy alternative that, to date, remains underused. In the last 10 to 15 years, it has undergone constant technical advancement. This review gives an overview of the present practice of spinal cord stimulation for chronic neuropathic pain and current developments such as high-frequency stimulation and peripheral nerve field stimulation. Keywords: spinal cord stimulation, neuropathic pain, neurostimulation

  13. [Nocioceptive pain, neuropathic pain and pain memory].

    Science.gov (United States)

    Montero-Homs, Jordi

    2009-01-01

    Pain is a cognitive evaluation. Its appearance in the new functional image systems is promising. Nocioceptive pain, usually acute or persistent, is useful to prevent animals from getting injured. Chronic pain is disease per se: It is due to a sensitisation phenomena and pain memory with an important relationship with emotions. Neuropathic pain is a neurological symptom due to a somatosensorial system dysfunction. In this case, axonal ectopic generation of impulses and synaptic hyperexcitability occurs. In persistent cases, sensitisation phenomenon and memory of pain appear together with neuropathic pain. Pain treatment should be physiopathologicaly orientated. Pain units, specialized in analgesic treatment and some invasive techniques, are usually competent in the treatment of nocioceptive pain. Neuropathic pain should have a neurologic diagnosis and treatment. But neurologist need to be more and more interested in the chronic pain related with memory and sensitisation: better knowledge of the cerebral mechanisms in this phenomenon can add to this pathology in our field.

  14. Effectiveness of pregabalin for the treatment of chronic low back pain with accompanying lower limb pain (neuropathic component: a non-interventional study in Japan

    Directory of Open Access Journals (Sweden)

    Taguchi T

    2015-08-01

    Full Text Available Toshihiko Taguchi,1 Ataru Igarashi,2 Stephen Watt,3 Bruce Parsons,3 Alesia Sadosky,3 Kazutaka Nozawa,4 Kazuhiro Hayakawa,4 Tamotsu Yoshiyama,4 Nozomi Ebata,4 Koichi Fujii4 1Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan; 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan; 3Pfizer Inc., New York, NY, USA; 4Pfizer Japan, Inc., Tokyo, Japan Objective: To evaluate the impact of pregabalin on sleep, pain, function, and health status in patients with chronic low back pain with accompanying neuropathic pain (CLBP-NeP under routine clinical practice. Methods: This prospective, non-interventional, observational study enrolled Japanese adults (≥18 years with CLBP-NeP of duration ≥3 months and severity ≥5 on a numerical rating scale (0= no pain, 10= worst possible pain. Treatment was 8 weeks with pregabalin (n=157 or usual care alone (n=174; choice of treatment was determined by the physician. The primary efficacy outcome was change from baseline to 8 weeks in pain-related interference with sleep, assessed using the Pain-Related Sleep Interference Scale (PRSIS; 0= did not interfere with sleep, 10= completely interferes with sleep. Secondary endpoints were changes in PRSIS at week 4, and changes at weeks 4 and 8 in pain (numerical rating scale, function (Roland-Morris Disability Questionnaire, and quality of life (EuroQol 5D-5L; global assessments of change were evaluated from the clinician and patient perspectives at the final visit. Results: Demographic characteristics were similar between cohorts, but clinical characteristics suggested greater disease severity in the pregabalin group including a higher mean (standard deviation pain score, 6.3 (1.2 versus 5.8 (1.1 (P<0.001. For the primary endpoint, pregabalin resulted in significantly greater improvements in PRSIS at week 8, least-squares mean changes of -1.3 versus

  15. Supression of chronic central pain by superoxide dismutase in rats with spinal cord injury: Inhibition of the NMDA receptor implicated.

    Science.gov (United States)

    Xie, Yong-Gang; Mu, Hong-Jie; Li, Zhen; Ma, Jia-Hai; Wang, Yue-Lan

    2014-10-01

    Superoxide dismutase (SOD) is used to manage chronic pain, including neuropathic and inflammatory pain. However, data regarding the clinical effectiveness are conflicting and the neurophysiological mechanism of SOD has yet to be elucidated. The aim of the present study was to investigate whether SOD relieved chronic central pain (CCP) following spinal cord injury (SCI) and the possible underlying mechanisms. A CCP model was established using the Allen method and the CCP of the rats was measured using the paw withdrawal threshold. SOD was administered intraperitoneally following the establishment of CCP as a result of SCI. The results demonstrated that SOD relieved CCP in rats following SCI. In addition, the expression of spinal phosphorylated N-methyl-D-aspartate(NMDA) receptor subunit 1 (pNR-1) was inhibited in the CCP rats that had been treated with SOD. These observations indicated that SOD reduced mechanical allodynia and attenuated the enhancement of spinal pNR1 expression in rats with CCP. In addition, the results indicated that superoxide, produced via xanthine oxidase, and the participation of superoxide and nitric oxide (NO) as a precursor of peroxynitrite in NMDA, were involved in the mediation of central sensitization. Therefore, the observations support the hypothesis that SOD may have a potential therapeutic role for the treatment of CCP following SCI via the manipulation of superoxide and NO.

  16. Do low levels of beta-endorphin in the cerebrospinal fluid indicate defective top-down inhibition in patients with chronic neuropathic pain? A cross-sectional, comparative study.

    Science.gov (United States)

    Bäckryd, Emmanuel; Ghafouri, Bijar; Larsson, Britt; Gerdle, Björn

    2014-01-01

    Pain medicine still lacks mechanism-specific biomarkers to guide diagnosis and treatment, and defective top-down modulation is an important factor in the pathophysiology of chronic pain conditions. Using modern analytical tools and advanced multivariate statistical analysis, the aim of this study was to revisit two classical potential biomarkers of pro- and anti-nociception in humans (substance P and beta-endorphin), focusing particularly on the cerebrospinal fluid (CSF). Cross-sectional, comparative, observational study. Patients with chronic, post-traumatic and/or post-surgical, neuropathic pain refractory to conventional treatment (N = 15) and healthy controls (N = 19) were included. Samples were taken from CSF and blood, and levels of substance P and beta-endorphin were investigated using a Luminex technology kit. We found low levels of beta-endorphin in the CSF of neuropathic pain patients (66 ± 11 pcg/mL) compared with healthy controls (115 ± 14 pcg/mL) (P = 0.017). Substance P levels in the CSF did not differ (20 ± 2 pcg/mL, 26 ± 2, P = 0.08). However, our multivariate data analysis showed that belonging to the patient group was associated with low levels of both substances in the CSF. A higher correlation between the levels of beta-endorphin and substance P in CSF was found in healthy controls than in patients (rs  = 0.725, P pain due to trauma or surgery had low levels of beta-endorphin in the CSF. We speculate that this could indicate a defective top-down modulation of pain in chronic neuropathic pain. Our results also illustrate the importance of taking a system-wide, multivariate approach when searching for biomarkers. Wiley Periodicals, Inc.

  17. Electroacupuncture attenuates neuropathic pain after brachial plexus injury

    OpenAIRE

    Zhang, Shenyu; Tang, Hailiang; Zhou, Junming; Gu, Yudong

    2014-01-01

    Electroacupuncture has traditionally been used to treat pain, but its effect on pain following brachial plexus injury is still unknown. In this study, rat models of an avulsion injury to the left brachial plexus root (associated with upper-limb chronic neuropathic pain) were given electroacupuncture stimulation at bilateral Quchi (LI11), Hegu (LI04), Zusanli (ST36) and Yanglingquan (GB34). After electroacupuncture therapy, chronic neuropathic pain in the rats’ upper limbs was significantly at...

  18. The potential role of neuropathic mechanisms in dry eye syndromes

    Directory of Open Access Journals (Sweden)

    Charles W. Mcmonnies

    2017-01-01

    Full Text Available Dry eye syndromes can involve both nociceptive and neuropathic symptoms. Nociceptive symptoms are the normal physiological responses to noxious stimuli. Neuropathic symptoms are caused by a lesion or disease of the somatosensory nervous system and can be the result of hypersensitisation of peripheral or central corneal and conjunctival somatosensory nerves. For example, inflammation could induce neuroplastic peripheral sensitisation of the ocular surface or lid wiper and exacerbate nociceptive symptoms. Neuropathic symptoms may explain the incommensurate relation between signs and symptoms in some dry eye syndromes although absence of signs of a dry eye syndrome may also be a consequence of inappropriate methods used when examining for them. Involvement of neuropathic mechanisms may also help explain dry eye symptoms which occur in association with reduced corneal sensitivity. This review includes a discussion of the potential for ocular symptoms involving neuropathic mechanisms to contribute to psychosocial problems such as depression, stress, anxiety and sleep disorders as well as for these types of psychosocial problems to contribute to neuropathic mechanisms and dry eye syndromes. Failure to consider the possibility that neuropathic mechanisms can contribute to dry eye syndromes may reduce accuracy of diagnosis and the suitability of treatment provided. Dry eye symptoms in the absence of commensurate evidence of tear dysfunction, and unsatisfactory response to tear dysfunction therapies should prompt consideration of neuropathic mechanisms being involved. Symptoms which persist after local anaesthetic instillation are more likely to be neuropathic in origin. Reducing inflammation may help limit any associated neuroplastic hypersensitivity.

  19. A retrospective study of chronic post-surgical pain following thoracic surgery: prevalence, risk factors, incidence of neuropathic component, and impact on qualify of life.

    Directory of Open Access Journals (Sweden)

    Zhiyou Peng

    Full Text Available BACKGROUND: Thoracic surgeries including thoracotomy and VATS are some of the highest risk procedures that often lead to CPSP, with or without a neuropathic component. This retrospective study aims to determine retrospectively the prevalence of CPSP following thoracic surgery, its predicting risk factors, the incidence of neuropathic component, and its impact on quality of life. METHODS: Patients who underwent thoracic surgeries including thoracotomy and VATS between 01/2010 and 12/2011 at the First Affiliated Hospital, School of Medicine, Zhejiang University were first contacted and screened for CPSP following thoracic surgery via phone interview. Patients who developed CPSP were then mailed with a battery of questionnaires, including a questionnaire referenced to Maguire's research, a validated Chinese version of the ID pain questionnaire, and a SF-36 Health Survey. Logistic regression analyses were subsequently performed to identify risk factors for CPSP following thoracic surgery and its neuropathic component. RESULTS: The point prevalence of CPSP following thoracic surgery was 24.9% (320/1284 patients, and the point prevalence of neuropathic component of CPSP was 32.5% (86/265 patients. CPSP following thoracic surgery did not improve significantly with time. Multiple predictive factors were identified for CPSP following thoracic surgery, including age<60 years old, female gender, prolonged duration of post-operative chest tube drainage (≥ 4 days, options of post-operative pain management, and pre-existing hypertension. Furthermore, patients who experienced CPSP following thoracic surgery were found to have significantly decreased physical function and worse quality of life, especially those with neuropathic component. CONCLUSIONS: Our study demonstrated that nearly 1 out of 4 patients underwent thoracic surgery might develop CPSP, and one third of them accompanied with a neuropathic component. Early prevention as well as aggressive

  20. Acupuncture for neuropathic pain in adults.

    Science.gov (United States)

    Ju, Zi Yong; Wang, Ke; Cui, Hua Shun; Yao, Yibo; Liu, Shi Min; Zhou, Jia; Chen, Tong Yu; Xia, Jun

    2017-12-02

    Neuropathic pain may be caused by nerve damage, and is often followed by changes to the central nervous system. Uncertainty remains regarding the effectiveness and safety of acupuncture treatments for neuropathic pain, despite a number of clinical trials being undertaken. To assess the analgesic efficacy and adverse events of acupuncture treatments for chronic neuropathic pain in adults. We searched CENTRAL, MEDLINE, Embase, four Chinese databases, ClinicalTrials.gov and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 14 February 2017. We also cross checked the reference lists of included studies. Randomised controlled trials (RCTs) with treatment duration of eight weeks or longer comparing acupuncture (either given alone or in combination with other therapies) with sham acupuncture, other active therapies, or treatment as usual, for neuropathic pain in adults. We searched for studies of acupuncture based on needle insertion and stimulation of somatic tissues for therapeutic purposes, and we excluded other methods of stimulating acupuncture points without needle insertion. We searched for studies of manual acupuncture, electroacupuncture or other acupuncture techniques used in clinical practice (such as warm needling, fire needling, etc). We used the standard methodological procedures expected by Cochrane. The primary outcomes were pain intensity and pain relief. The secondary outcomes were any pain-related outcome indicating some improvement, withdrawals, participants experiencing any adverse event, serious adverse events and quality of life. For dichotomous outcomes, we calculated risk ratio (RR) with 95% confidence intervals (CI), and for continuous outcomes we calculated the mean difference (MD) with 95% CI. We also calculated number needed to treat for an additional beneficial outcome (NNTB) where possible. We combined all data using a random-effects model and assessed the quality of evidence using GRADE to generate

  1. Pannexin 1: a novel participant in neuropathic pain signaling in the rat spinal cord.

    Science.gov (United States)

    Bravo, David; Ibarra, Paula; Retamal, Jeffri; Pelissier, Teresa; Laurido, Claudio; Hernandez, Alejandro; Constandil, Luis

    2014-10-01

    Pannexin 1 (panx1) is a large-pore membrane channel expressed in many tissues of mammals, including neurons and glial cells. Panx1 channels are highly permeable to calcium and adenosine triphosphatase (ATP); on the other hand, they can be opened by ATP and glutamate, two crucial molecules for acute and chronic pain signaling in the spinal cord dorsal horn, thus suggesting that panx1 could be a key component for the generation of central sensitization during persistent pain. In this study, we examined the effect of three panx1 blockers, namely, 10panx peptide, carbenoxolone, and probenecid, on C-reflex wind-up activity and mechanical nociceptive behavior in a spared nerve injury neuropathic rat model involving sural nerve transection. In addition, the expression of panx1 protein in the dorsal horn of the ipsilateral lumbar spinal cord was measured in sural nerve-transected and sham-operated control rats. Sural nerve transection resulted in a lower threshold for C-reflex activation by electric stimulation of the injured hindpaw, together with persistent mechanical hypersensitivity to pressure stimuli applied to the paw. Intrathecal administration of the panx1 blockers significantly depressed the spinal C-reflex wind-up activity in both neuropathic and sham control rats, and decreased mechanical hyperalgesia in neuropathic rats without affecting the nociceptive threshold in sham animals. Western blotting showed that panx1 was similarly expressed in the dorsal horn of lumbar spinal cord from neuropathic and sham rats. The present results constitute the first evidence that panx1 channels play a significant role in the mechanisms underlying central sensitization in neuropathic pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  2. Central Blood Pressure and Chronic Kidney Disease Progression

    Directory of Open Access Journals (Sweden)

    Debbie L. Cohen

    2011-01-01

    Full Text Available Hypertension, diabetes, and proteinuria are well-recognized risk factors for progressive kidney function loss. However, despite excellent antihypertensive and antidiabetic drug therapies, which also often lower urinary protein excretion, there remains a significant reservoir of patients with chronic kidney disease who are at high risk for progression to end-stage kidney disease. This has led to the search for less traditional cardiovascular risk factors that will help stratify patients at risk for more rapid kidney disease progression. Among these are noninvasive estimates of vascular structure and function. Arterial stiffness, manifested by the pulse wave velocity in the aorta, has been established in a number of studies as a significant risk factor for kidney disease progression and cardiovascular endpoints. Much less well studied in chronic kidney disease are measures of central arterial pressures. In this paper we cover the physiology behind the generation of the central pulse wave contour and the studies available using these approaches and conclude with some speculations on the rationale for why measurements of central pressure may be informative for the study of chronic kidney disease progression.

  3. [Central arterial pressure in patients with chronic obstructive pulmonary disease].

    Science.gov (United States)

    Gel'tser, B I; Brodskaia, T A

    2008-01-01

    To study central (aortic) arterial pressure (CAP) and aortic stiffness in patients with chronic obstructive pulmonary disease (COPD) of different severity. Non-invasive arteriography with Tensio Climo TL1 arteriograph (TensioMed, Hungary) was made to measure aortic stiffness and systolic pressure (SAP) in 54 COPD patients and 25 healthy controls. The difference between the central and peripheral SAP (delta SAP) and central/ peripheral pressure correspondence index (CI) were estimated. Indirect arteriography has found that patients with moderate and severe COPD have stable elevated central SAP which is close to brachial SAP while in healthy controls the difference between central and peripheral SAP is 10.2 +/- 2.1 mmHg. With progression of COPD severity, deltaSAP diminishes while CI rises showing growing disproportion between central and peripheral blood pressure. In severe COPD physiological difference between them disappears. In COPD increased CAP is associated with impaired mechanical properties of the arterial bed and myocardial contractility proved by significant links between CAP and left ventricular ejection fraction index and key parameters of arterial stiffness. Aortic CAP, delta SAP and CI are additional informative criteria of COPD severity and high cardiovascular risk as shown by their close correlation with hypoxemia, severity and duration of the disease.

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

    Science.gov (United States)

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

    2013-01-01

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

  5. The brain-penetrant 5-HT7receptor agonist LP-211 reduces the sensory and affective components of neuropathic pain.

    Science.gov (United States)

    Santello, Mirko; Bisco, Alberto; Nevian, Natalie Elisabeth; Lacivita, Enza; Leopoldo, Marcello; Nevian, Thomas

    2017-10-01

    Neuropathic pain is a debilitating pathological condition of high clinical relevance. Changes in neuronal excitability in the anterior cingulate cortex (ACC) play a central role in the negative emotional and affective aspects of chronic pain. We evaluated the effects of LP-211, a new serotonin-receptor-type-7 (5-HT 7 R) agonist that crosses the blood-brain barrier, on ACC neurons in a mouse model of neuropathic pain. LP-211 reduced synaptic integration in layer 5 pyramidal neurons, which was enhanced in neuropathic pain due to a dysfunction of dendritic hyperpolarization-activated-and-cyclic-nucleotide-regulated (HCN) channels. Acute injection of LP-211 had an analgesic effect, increasing the mechanical withdrawal threshold in neuropathic animals, which was partially mediated by an action in the ACC. Additionally, the acute application of LP-211 blocked the switch in the place escape/avoidance behavior induced by noxious stimuli. Thus systemic treatment with a 5-HT 7 R agonist leads to modulation of the ACC, which dampens sensory and affective aspects of chronic pain. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Effectiveness of Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR for the Management of Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open-Label, Phase 3b/4 Study.

    Science.gov (United States)

    Baron, Ralf; Likar, Rudolf; Martin-Mola, Emilio; Blanco, Francisco J; Kennes, Lieven; Müller, Matthias; Falke, Dietmar; Steigerwald, Ilona

    2016-06-01

    To evaluate the effectiveness of tapentadol prolonged release (PR) vs. oxycodone/naloxone PR in non-opioid-pretreated patients with severe chronic low back pain with a neuropathic pain component. Eligible patients (average pain intensity [numerical rating scale-3 (NRS-3)] ≥6; painDETECT positive/unclear) were randomized to twice-daily tapentadol PR 50 mg or oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or oxycodone/naloxone PR 40 mg/20 mg plus oxycodone PR 10 mg), target doses were continued for 9 weeks. The primary effectiveness endpoint was the change in NRS-3 from baseline to final evaluation; the exact repeated confidence interval (RCI) for tapentadol PR minus oxycodone/naloxone PR was used to establish noninferiority (upper limit <1.3) and superiority (confirmatory analyses). For the primary effectiveness endpoint, tapentadol PR was noninferior to oxycodone/naloxone PR (97.5% RCI: [-1.820, -0.184]; P < 0.001). This exact RCI also yielded evidence of superiority for tapentadol PR vs. oxycodone/naloxone PR (significantly greater reduction in pain intensity; P = 0.003). Improvements (baseline to final evaluation) in painDETECT and Neuropathic Pain Symptom Inventory scores were significantly greater with tapentadol PR vs. oxycodone/naloxone PR (all P ≤ 0.005). The study was formally shown to be positive and demonstrated, in the primary effectiveness endpoint, the noninferiority for tapentadol PR vs. oxycodone/naloxone PR. The effectiveness of tapentadol PR was superior to that of oxycodone/naloxone PR by means of clinical relevance and statistical significance (confirmatory evidence of superiority). Tapentadol PR was associated with significantly greater improvements in neuropathic pain-related symptoms and global health status than oxycodone/naloxone PR and with a significantly better gastrointestinal tolerability profile. Tapentadol PR may be considered a first-line option for

  7. Effectiveness and Tolerability of a Moderate Dose of Tapentadol Prolonged Release for Managing Severe, Chronic Low Back Pain with a Neuropathic Component: An Open-label Continuation Arm of a Randomized Phase 3b Study.

    Science.gov (United States)

    Baron, Ralf; Kern, Uwe; Müller, Matthias; Dubois, Cecile; Falke, Dietmar; Steigerwald, Ilona

    2015-06-01

    To evaluate the effectiveness and tolerability of tapentadol prolonged release (PR) for severe, chronic low back pain with a neuropathic component in a subpopulation that achieved adequate pain relief with tapentadol PR 300 mg/day in a randomized, double-blind, phase 3b study. Patients with painDETECT "unclear" or "positive" ratings and pain intensity ≥ 6 (11-point NRS-3 [average 3-day pain intensity]) were titrated to tapentadol PR 300 mg/day over 3 weeks. A subpopulation with pain intensity pain intensity ≥ 4 were randomized to tapentadol PR 500 mg/day or tapentadol PR 300 mg/day plus pregabalin 300 mg/day during a concurrent 8-week, double-blind comparative period. From baseline to end of titration and to final evaluation, significant improvements were observed in pain intensity (mean [SD] changes from baseline to: end of titration; - 5.3 [1.78]; final evaluation; - 5.2 [2.39]; both P pain symptoms, and quality-of-life measures in the open-label continuation arm, with greater improvements in this selected subpopulation than in either group in the primary study population. A favorable tolerability profile was observed, with incidences of all individual treatment-emergent adverse events ≤ 5.1% during the continuation period. A subpopulation of patients with low back pain with a neuropathic component responded very well to tapentadol PR 300 mg/day, with significant improvements in pain intensity, neuropathic pain-related symptoms, and quality of life. Further research is needed to identify factors associated with a very positive treatment response. © 2014 The Authors. Pain Practice published by Wiley periodicals, Inc. on behalf of World Institute of Pain.

  8. Cortical and white matter alterations in patients with neuropathic pain after spinal cord injury.

    Science.gov (United States)

    Yoon, Eun Jin; Kim, Yu Kyeong; Shin, Hyung Ik; Lee, Youngjo; Kim, Sang Eun

    2013-12-02

    Neuropathic pain is one of the major problems of patients with spinal cord injury (SCI), which remains refractory to treatment despite a variety of therapeutic approach. Multimodal neuroimaging could provide complementary information for brain mechanisms underlying neuropathic pain, which could be based on development of more effective treatment strategies. Ten patients suffering from chronic neuropathic pain after SCI and 10 healthy controls underwent FDG-PET, T1-anatomical MRI and diffusion tensor imaging. We found decreases of both metabolism and the gray matter volume in the left dorsolateral prefrontal cortex in patients compared to healthy controls, as well as hypometabolism in the medial prefrontal cortex and gray matter volume loss in bilateral anterior insulae and subgenual anterior cingulate cortices. These brain regions are generally known to participate in pain modulation by affective and cognitive processes. Decreases of mean diffusivity (MD) in the right internal capsule including, cerebral peduncle, pre-and post-central white matter, and prefrontal white matter as components of the corticospinal and thalamocortical tracts were demonstrated in patients. Further, lower MD value of prefrontal white matter was correlated with decreased metabolism of medial prefrontal cortex in patients. These results indicated that white matter changes imply abnormal pain modulation in patients as well as motor impairment. Our study showed the functional and structural multimodal imaging modality commonly identified the possible abnormalities in the brain regions participating pain modulation in neuropathic pain. Multifaceted imaging studies in neuropathic pain could be useful elucidating precise mechanisms of persistent pain, and providing future directions for treatment. © 2013 Elsevier B.V. All rights reserved.

  9. Neuropathic osteoarthropathy: iconographic essay; Osteoartropatia neurotrofica: ensaio iconografico

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Joao Luiz; Rocha, Arthemizio Antonio Lopes [Hospital Santa Lucia, Brasilia, DF (Brazil); Viana, Sergio Lopes [Clinica Radiologica Vila Rica, Brasilia DF (Brazil)]. E-mail: radiolog@uol.com.br

    2005-04-15

    Neuropathic osteoarthropathy is characterized by chronic, destructive and non-infectious bone and joint disease developing in patients with some level of loss of proprioception or pain insensitivity. Currently, diabetes mellitus is the most frequent cause of neuropathic osteoarthropathy. The classic appearance on X-rays is bone fragmentation, osteophytosis, joint effusion and joint instability, with preserved bone density. Although conventional X-rays is the most frequently used imaging modality for the evaluation of neuropathic osteoarthropathy and the role of the imaging methods are reviewed as a pictorial essay. (author)

  10. Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease.

    Science.gov (United States)

    Carroll, C Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A; Campbell, Claudia M

    2016-07-01

    Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared the severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis); central sensitization; and depression and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  11. Chronic neuropathic pain management in spinal cord injury patients. What is the efficacy of pharmacological treatments with a general mode of administration? (oral, transdermal, intravenous).

    OpenAIRE

    Attal, Nadine; Mazaltarine, Gilles; Perrouin-Verbe, Brigitte; Albert, T.

    2009-01-01

    International audience; INTRODUCTION: The pharmacological treatment of patients with spinal cord injury (SCI) pain remains challenging despite new available drugs. Such treatment should always be viewed in the context of global pain management in these patients. To date few clinical trials have been specifically devoted to this topic, and the implementation of treatments is generally based on results obtained in peripheral neuropathic pain. The aim of this review is to present evidence for ef...

  12. Orofacial neuropathic pain mouse model induced by Trigeminal Inflammatory Compression (TIC of the infraorbital nerve

    Directory of Open Access Journals (Sweden)

    Ma Fei

    2012-12-01

    Full Text Available Abstract Background Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity. Results The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild nerve trauma. Nerve edema is observed in the contacting infraorbital nerve bundle as well as macrophage infiltration in the trigeminal ganglia. Centrally in the spinal trigeminal nucleus, increased immunoreactivity for an activated microglial marker is evident (OX42, postoperative day 70. Mechanical thresholds of the affected whisker pad are significantly decreased on day 3 after chromic gut suture placement, persisting at least 10 weeks. The mechanical allodynia is reversed by suppression of microglial activation. Cold allodynia was detected at 4 weeks. Conclusions A simple, effective, and reproducible chronic mouse model mimicking clinical orofacial neuropathic pain (Type 2 is induced by placing chromic gut suture between the infraorbital nerve and the maxillary bone. The method produces mild inflammatory compression with significant continuous mechanical allodynia persisting at least 10 weeks and cold allodynia measureable at 4 weeks.

  13. Puerarin Alleviates Neuropathic Pain by Inhibiting Neuroinflammation in Spinal Cord

    OpenAIRE

    Ming Liu; Kaijun Liao; Changxi Yu; Xuejun Li; Suhuan Liu; Shuyu Yang

    2014-01-01

    Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI) and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4–100 nM) ...

  14. Platelet-rich plasma and the elimination of neuropathic pain.

    Science.gov (United States)

    Kuffler, Damien P

    2013-10-01

    Peripheral neuropathic pain typically results from trauma-induced nociceptive neuron hyperexcitability and their spontaneous ectopic activity. This pain persists until the trauma-induced cascade of events runs its full course, which results in complete tissue repair, including the nociceptive neurons recovering their normal biophysical properties, ceasing to be hyperexcitable, and stopping having spontaneous electrical activity. However, if a wound undergoes no, insufficient, or too much inflammation, or if a wound becomes stuck in an inflammatory state, chronic neuropathic pain persists. Although various drugs and techniques provide temporary relief from chronic neuropathic pain, many have serious side effects, are not effective, none promotes the completion of the wound healing process, and none provides permanent pain relief. This paper examines the hypothesis that chronic neuropathic pain can be permanently eliminated by applying platelet-rich plasma to the site at which the pain originates, thereby triggering the complete cascade of events involved in normal wound repair. Many published papers claim that the clinical application of platelet-rich plasma to painful sites, such as muscle injuries and joints, or to the ends of nerves evoking chronic neuropathic pain, a process often referred to as prolotherapy, eliminates pain initiated at such sites. However, there is no published explanation of a possible mechanism/s by which platelet-rich plasma may accomplish this effect. This paper discusses the normal physiological cascade of trauma-induced events that lead to chronic neuropathic pain and its eventual elimination, techniques being studied to reduce or eliminate neuropathic pain, and how the application of platelet-rich plasma may lead to the permanent elimination of neuropathic pain. It concludes that platelet-rich plasma eliminates neuropathic pain primarily by platelet- and stem cell-released factors initiating the complex cascade of wound healing events

  15. Neuropathic pain in primary care

    African Journals Online (AJOL)

    The operative difference is that neuropathic pain represents a delayed, ongoing response to damage that is no longer acute ... Postsurgical pain (including post- mastectomy and phantom limb pain). Spinal cord injury pain ... Management of neuropathic pain. Neuropathic pain tends to exhibit a relatively poor response.

  16. Macrophage-to-sensory neuron crosstalk mediated by Angiotensin II type-2 receptor elicits neuropathic pain

    OpenAIRE

    Krause, Eric; Shepherd, Andrew; Mickle, Aaron; Copits, Bryan; Karlsson, Pall; Kadunganattil, Suraj; Golden, Judith; Tadinada, Satya; Mack, Madison; Haroutounian, Simon; De Kloet, Annette; Samineni, Vijay; Valtcheva, Manouela; Mcilvried, Lisa; Sheahan, Tayler

    2017-01-01

    Peripheral nerve damage initiates a complex series of cellular and structural processes that culminate in chronic neuropathic pain. Our study defines local angiotensin signaling via activation of the Angiotensin II (Ang II) type-2 receptor (AT2R) on macrophages as the critical trigger of neuropathic pain. An AT2R-selective antagonist attenuates neuropathic, but not inflammatory pain hypersensitivity in mice, and requires the cell damage-sensing ion channel transient receptor potential family-...

  17. Treatment of interstitial cystitis/painful bladder syndrome as a neuropathic pain condition

    Directory of Open Access Journals (Sweden)

    Lakshmi Vas

    2014-01-01

    Full Text Available A lady of 52 years with painful bladder syndrome/interstitial cystitis (PBS/IC presented with chronic pelvic pain, irritative voiding with sphincter dominance on urodynamics. 3 yrs of oral analgesics, antispasmodics and intravesical therapy was ineffective. We surmised her pain, and irritative voiding to be secondary to constant straining against a dysfunctional pelvic floor. We treated PBS/IC as a neuropathic phenomenon with a combination of neuromodulator medications and continuous caudal epidural analgesia to reduce the pain induced peripheral and central sensitisation. Botulinum toxin type A injection into pelvic floor muscles appeared to address their dysfuction. Clinical and urodynamics response was encouraging.

  18. Anti-allodynic Effect of Nefopam and Morphine in a Rat Model of Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Taraneh Moini Zanjani

    2013-05-01

    Full Text Available Please cite this article as: Moini Zanjani T, Saghaei E, Ameli H, Sabetkasaei M. Anti-allodynic Effect of Nefopam and Morphine in a Rat Model of Neuropathic Pain. Novel Biomed 2013;1:16-22.Background: Neuropathic pain is a chronic pain due to a disorder in the peripheral or central nervous system with different pathophysiological mechanisms. Current treatments are not effective. Here we compared the analgesic effect of nefopam, and morphine in chronic constriction injury (CCI model of neuropathic pain.Methods: Male wistar rat (150-200g, n=8 were divided into 3 different groups: 1- Saline-treated CCI group, 2- Saline-treated sham group, and 3- Drug-treated CCI groups. In CCI model of neuropathic pain, the left sciatic nerve was exposed and 4 loose chromic gut ligatures were placed around the nerve proximal to the trifurcation. Ketamine 60mg/kg and xylazine 10 mg/kg were used for anesthesia. Nefopam (10, 20, 30mg/kg, and morphine (1, 3, 5mg/kg were injected 30 minutes before surgery and continued daily to day 14 post-ligation. Von Frey filaments for mechanical allodynia and acetone test for cold allodynia were respectively used as pain behavioral tests. Experiments were performed on day 0 (before surgery and days 1, 3, 5,7,10 and 14 post injury. Behavioral studies were performed in a quiet room between 9:00 to 11:00 AM. All experiments followed the IASP guidelines on ethical standards for investigation of experimental pain in animals.Results: Nefopam (20 and 30mg/kg blocked mechanical and cold allodynia during the experimental period, but the analgesic effects of morphine (5mg/kg lasted for 7 days.Conclusions: It seems that nefopam could effectively reduce pain behavior compared to morphine with reduced adverse effects.

  19. Has central sensitization become independent of nociceptive input in chronic pancreatitis patients who fail thoracoscopic splanchnicectomy?

    NARCIS (Netherlands)

    Bouwense, S.A.W.; Buscher, H.C.J.L.; Goor, H. van; Wilder-Smith, O.H.G.

    2011-01-01

    BACKGROUND AND OBJECTIVES: : Central sensitization due to visceral pancreatic nociceptive input may be important in chronic pancreatitis pain. We investigated whether bilateral thoracoscopic splanchnicectomy (BTS) to reduce nociceptive input in chronic pancreatitis patients (CPP) with poor pain

  20. Invasive and non-invasive brain stimulation for treatment of neuropathic pain in patients with spinal cord injury: a review.

    Science.gov (United States)

    Nardone, Raffaele; Höller, Yvonne; Leis, Stefan; Höller, Peter; Thon, Natasha; Thomschewski, Aljoscha; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

    2014-01-01

    Past evidence has shown that invasive and non-invasive brain stimulation may be effective for relieving central pain. To perform a topical review of the literature on brain neurostimulation techniques in patients with chronic neuropathic pain due to traumatic spinal cord injury (SCI) and to assess the current evidence for their therapeutic efficacy. A MEDLINE search was performed using following terms: "Spinal cord injury", "Neuropathic pain", "Brain stimulation", "Deep brain stimulation" (DBS), "Motor cortex stimulation" (MCS), "Transcranial magnetic stimulation" (TMS), "Transcranial direct current stimulation" (tDCS), "Cranial electrotherapy stimulation" (CES). Invasive neurostimulation therapies, in particular DBS and epidural MCS, have shown promise as treatments for neuropathic and phantom limb pain. However, the long-term efficacy of DBS is low, while MCS has a relatively higher potential with lesser complications that DBS. Among the non-invasive techniques, there is accumulating evidence that repetitive TMS can produce analgesic effects in healthy subjects undergoing laboratory-induced pain and in chronic pain conditions of various etiologies, at least partially and transiently. Another very safe technique of non-invasive brain stimulation - tDCS - applied over the sensory-motor cortex has been reported to decrease pain sensation and increase pain threshold in healthy subjects. CES has also proved to be effective in managing some types of pain, including neuropathic pain in subjects with SCI. A number of studies have begun to use non-invasive neuromodulatory techniques therapeutically to relieve neuropathic pain and phantom phenomena in patients with SCI. However, further studies are warranted to corroborate the early findings and confirm different targets and stimulation paradigms. The utility of these protocols in combination with pharmacological approaches should also be explored.

  1. The use of 10-kilohertz spinal cord stimulation in a cohort of patients with chronic neuropathic limb pain refractory to medical management.

    Science.gov (United States)

    Al-Kaisy, Adnan; Palmisani, Stefano; Smith, Tom; Harris, Stephany; Pang, David

    2015-01-01

    It is the purpose of this study to document our experience with the use of a 10-kHz high-frequency spinal cord stimulation (SCS) device for the relief of neuropathic pain of the upper and lower limbs. A retrospective chart review was performed of all patients treated with the 10-kHz high-frequency SCS system for neuropathic pain (upper or lower limb) refractory to conventional treatment. All patients underwent a trial with one or two eight-contact percutaneous leads using 50-Hz traditional stimulation. If ≥ 80% paresthesia coverage of the painful area with traditional SCS was obtained, high-frequency 10-kHz SCS was used. Patients who had a significant reduction in pain score (≥ 50%) at the end of the trial received a permanent implant and were then followed for up to six months. Outcome measures included a numeric rating scale for pain, the Brief Pain Inventory, health-related quality of life (EQ-5D), the Pain Catastrophizing Scale, and patient satisfaction. Fifteen patients completed a trial of high-frequency 10-kHz SCS. Eleven patients proceeded to permanent implantation. Ten of the 11 patients who proceeded to full implantation had significant reductions in all of the collected outcome variables at one, three, and six months. In this small cohort of patients, high-frequency 10-kHz SCS reduced pain and improved quality of life. However, before we can conclude that high-frequency 10-kHz SCS for neuropathic pain of the upper and lower extremities is efficacious, a large-scale multicenter observational study should be performed to corroborate our small retrospective study. © 2014 International Neuromodulation Society.

  2. Melanocortins and Neuropathic Pain

    NARCIS (Netherlands)

    Vrinten, Dorien Henriëtte

    2003-01-01

    Neuropathic pain (pain initiated by a lesion or dysfunction of the nervous system) is characterised by symptoms such as allodynia (pain due to a stimulus that does not normally provoke pain) and hyperalgesia (an increased response to a stimulus that is normally painful). It constitutes a major

  3. [Contribution of the sensitization of supraspinal nociceptive transmission in chronic pain].

    Science.gov (United States)

    Ohsawa, Masahiro; Yamamoto, Shohei; Ono, Hideki

    2014-01-01

    Central sensitization in the spinal cord is well known to be involved in chronic pain. Recent investigations indicated that the protein expressions involving the synaptic plasticity are changed in several brain areas under a chronic pain condition. These changes in supraspinal neural function might cause the emotional and memory dysfunction. It is also possible that these changes are involved in the chronic pain. Indeed, since the improvement of spinal and peripheral sensitization showed limited relief in the neuropathic pain, the sensitization of supraspinal nociceptive transmission might be involved in the expression of chronic pain. We recently found that intra-thalamic treatment with excitatory neurotransmitter glutamate caused hyperalgesia, which is mediated by the stimulation of glutamate N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Moreover, intracerebroventricular treatment with gabapentin, a calcium channel alpha2delta-1 subunit blocker, attenuated the hyperalgesia in the nerve-injury model of mice. These results suggest that the sensitization of supraspinal nociceptive transmission is involved in neuropathic pain. It is also indicated that neuropathic pain is resulted from the activations of spinal glial cells. Likewise, the supraspinal glial activation was observed in the neuropathic pain. Therefore, the sensitization of supraspinal nociceptive transmission might be important for a chronic pain. In this review, we would like to discuss the possible involvement of the supraspinal sensitization in neuropathic pain and in its application for the curative treatment in chronic pain.

  4. Dor neuropática central após lesão medular traumática: capacidade funcional e aspectos sociais Dolor neuropático central después de lesión medular traumática: capacidad funcional y aspectos sociales Central neuropathic pain after traumatic spinal cord injury: functional capacity and social aspects

    Directory of Open Access Journals (Sweden)

    Janaina Vall

    2005-12-01

    Full Text Available Estudo de caso comparativo com o objetivo de avaliar a capacidade funcional e os aspectos sociais de dois pacientes, ambos com lesão medular traumática, sem e com dor neuropática central associada, respectivamente. Para avaliar a capacidade funcional, foi utilizado como instrumento o Functional Independence Measure ou Escala de Independência Funcional. E para avaliar os aspectos sociais foi construído o ecomapa de cada paciente, preconizado pelo modelo Calgary de avaliação de famílias. Ambos foram aplicados no domicílio do paciente. Os resultados mostraram que o paciente com dor neuropática central secundária à lesão medular possui baixa capacidade funcional e precária rede social de apoio, quando comparado com o paciente com as mesmas condições, porém sem dor associada.Estudio de caso comparativo con el objetivo de evaluar la capacidad funcional y los aspectos sociales de dos paciente, ambos con lesión medular traumática, sin y con el dolor neuropático central, respectivamente. Para evaluar la capacidad funcional, se usó como instrumento la Escala de Independencia Funcional. Y para evaluar los aspectos sociales, el ecomapa de cada paciente fue construido, preconizado por el modelo Calgary de evaluación de familias. Los dos furon aplicados en la casa del paciente. Los resultados mostraron que el paciente con dolor neuropatico central secundario a la lesión medular posee capacidad funcional baja y precaria red social de apoyo, cuando comparado con el paciente con las mismas condiciones, pero sin el dolor asociado.Comparative study of case with the aim of evaluating the functional capacity and social aspects of two patients, both with traumatic spinal cord injury, without and with central neuropathic pain associated, respectively. To evaluate the functional capacity it was used as instrument Functional Independence Measure. And to evaluate the social aspects the ecomap of each patient one it was built, extolled by the model

  5. Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?

    Science.gov (United States)

    Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica

    2011-05-01

    Central sensitization accounts for chronic 'unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that - theoretically - desensitize the CNS in humans. To provide a comprehensive treatment for 'unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization. © 2011 Informa UK, Ltd

  6. The role of glia in the spinal cord in neuropathic and inflammatory pain.

    Science.gov (United States)

    Old, Elizabeth Amy; Clark, Anna K; Malcangio, Marzia

    2015-01-01

    Chronic pain, both inflammatory and neuropathic, is a debilitating condition in which the pain experience persists after the painful stimulus has resolved. The efficacy of current treatment strategies using opioids, NSAIDS and anticonvulsants is limited by the extensive side effects observed in patients, underlining the necessity for novel therapeutic targets. Preclinical models of chronic pain have recently provided evidence for a critical role played by glial cells in the mechanisms underlying the chronicity of pain, both at the site of damage in the periphery and in the dorsal horn of the spinal cord. Here microglia and astrocytes respond to the increased input from the periphery and change morphology, increase in number and release pro-nociceptive mediators such as ATP, cytokines and chemokines. These gliotransmitters can sensitise neurons by activation of their cognate receptors thereby contributing to central sensitization which is fundamental for the generation of allodynia, hyperalgesia and spontaneous pain.

  7. Proteomic Identification of an Upregulated Isoform of Annexin A3 in the Spinal Cords of Rats in a Neuropathic Pain Model

    Directory of Open Access Journals (Sweden)

    Wangyuan Zou

    2017-09-01

    Full Text Available Neuropathic pain (NP is induced by nerve damage or a disturbance in the peripheral or central nervous systems. Nerve damage causes the activation of sensitizing mechanisms in the peripheral and central nervous systems, which induces transcriptional and post-transcriptional alterations in sensory nerves. However, the underlying mechanisms of NP remain elusive. In the study, Two-dimensional gel electrophoresis (2DGE-based comparative proteomics identified 38 differential gel spots, and 15 differentially expressed proteins (DEPs between the sham and the chronic constriction injury (CCI-induced neuropathic pain rats. Of them, Annexin A3 (ANXA3 was significantly increased after CCI with Western blot analysis and immunofluorescence imaging. A lentivirus delivering ANXA3 shRNA (LV-shANXA3 was administered intrathecally to determine the analgesic effects of ANXA3 on allodynia and hyperalgesia in a CCI-induced neuropathic pain model in rats. Further study showed that LV-shANXA3 reversed the upregulation of ANXA3, alleviated CCI-induced mechanical allodynia and thermal hyperalgesia. The study indicated that ANXA3 may play an important role in neuropathic pain.

  8. Tapentadol extended-release for treatment of chronic pain: a review

    Directory of Open Access Journals (Sweden)

    Vadivelu N

    2011-08-01

    Full Text Available Nalini Vadivelu1, Alexander Timchenko1, Yili Huang2, Raymond Sinatra11Department of Anesthesiology, Yale University School of Medicine, New Haven, CT; 2Internal Medicine, North Shore-LIJ Plainview Hospital, Plainview, NY, USAAbstract: Tapentadol is a centrally acting analgesic with a dual mechanism of action of mu receptor agonism and norepinephrine reuptake inhibition. Tapentadol immediate-release is approved by the US Food and Drug Administration for the management of moderate-to-severe acute pain. It was developed to decrease the intolerability issue associated with opioids. Tapentadol extended-release has a 12-hour duration of effect, and has recently been evaluated for pain in patients with chronic osteoarthritis, low back pain, and pain associated with diabetic peripheral neuropathy. Tapentadol extended-release was found to provide safe and highly effective analgesia for the treatment of chronic pain conditions, including moderate-to-severe chronic osteoarthritis pain and low back pain. Initial trials demonstrating efficacy in neuropathic pain suggest that tapentadol has comparable analgesic effectiveness and better gastrointestinal tolerability than opioid comparators, and demonstrates effectiveness in settings of inflammatory, somatic, and neuropathic pain. Gastrointestinal intolerance and central nervous system effects were the major adverse events noted. Tapentadol will need to be rigorously tested in chronic neuropathic pain, cancer-related pain, and cancer-related neuropathic pain.Keywords: osteoarthritis, neuropathic pain, analgesic, opioids, norepinephrine

  9. Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults.

    Science.gov (United States)

    Gibson, William; Wand, Benedict M; O'Connell, Neil E

    2017-09-14

    Neuropathic pain, which is due to nerve disease or damage, represents a significant burden on people and society. It can be particularly unpleasant and achieving adequate symptom control can be difficult. Non-pharmacological methods of treatment are often employed by people with neuropathic pain and may include transcutaneous electrical nerve stimulation (TENS). This review supersedes one Cochrane Review 'Transcutaneous electrical nerve stimulation (TENS) for chronic pain' (Nnoaham 2014) and one withdrawn protocol 'Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults' (Claydon 2014). This review replaces the original protocol for neuropathic pain that was withdrawn. To determine the analgesic effectiveness of TENS versus placebo (sham) TENS, TENS versus usual care, TENS versus no treatment and TENS in addition to usual care versus usual care alone in the management of neuropathic pain in adults. We searched CENTRAL, MEDLINE, Embase, PsycINFO, AMED, CINAHL, Web of Science, PEDro, LILACS (up to September 2016) and various clinical trials registries. We also searched bibliographies of included studies for further relevant studies. We included randomised controlled trials where TENS was evaluated in the treatment of central or peripheral neuropathic pain. We included studies if they investigated the following: TENS versus placebo (sham) TENS, TENS versus usual care, TENS versus no treatment and TENS in addition to usual care versus usual care alone in the management of neuropathic pain in adults. Two review authors independently screened all database search results and identified papers requiring full-text assessment. Subsequently, two review authors independently applied inclusion/exclusion criteria to these studies. The same review authors then independently extracted data, assessed for risk of bias using the Cochrane standard tool and rated the quality of evidence using GRADE. We included 15 studies with 724 participants. We found a

  10. Complex Regional Pain Syndrome (CRPS/RSD and Neuropathic Pain: Role of Intravenous Bisphosphonates as Analgesics

    Directory of Open Access Journals (Sweden)

    Jennifer Yanow

    2008-01-01

    Full Text Available Neuropathic pain is a sequela of dysfunction, injuries, or diseases of the peripheral and/or central nervous system pain pathways, which has historically been extremely difficult to treat. Complex regional pain syndrome (CRPS types 1 and 2 are neuropathic pain conditions that have a long history in the medical literature but whose pathophysiology remains elusive and whose available treatment options remain few. While an exact animal model for CRPS doesn't yet exist, there are several animal models of neuropathic pain that develop behaviors of hypersensitivity, one of the hallmark signs of neuropathic pain in humans.

  11. Placebo, nocebo, and neuropathic pain

    OpenAIRE

    Vase, Lene; Skyt, Ina; Hall, Kathryn T.

    2016-01-01

    Over the last decade, the apparent increase in placebo responses in randomized controlled trials (RCTs) of neuropathic pain have complicated and potentially limited development and availability of new effective pain medication. Placebo analgesia and nocebo hyperalgesia effects are well described in nociceptive and idiopathic pain conditions, but less is known about the magnitude and mechanisms of placebo and nocebo effects in neuropathic pain. In neuropathic pain, placebo treatments have prim...

  12. Effect of NMDA NR2B antagonist on neuropathic pain in two spinal cord injury models.

    Science.gov (United States)

    Kim, Youngkyung; Cho, Hwi-young; Ahn, Young Ju; Kim, Junesun; Yoon, Young Wook

    2012-05-01

    N-Methyl-d-aspartate (NMDA) receptors are thought to play an important role in the processes of central sensitization and pathogenesis of neuropathic pain, particularly after spinal cord injury (SCI). NMDA antagonists effectively reduce neuropathic pain, but serious side effects prevent their use as therapeutic drugs. NMDA NR2B antagonists have been reported to effectively reduce inflammatory and neuropathic pain. In this study, we investigated the effects of NR2B antagonists on neuropathic pain and the expression of NR2B in the spinal cord in 2 SCI models. SCI was induced at T12 by a New York University impactor (contusion) or by sectioning of the lateral half of the spinal cord (hemisection). Ifenprodil (100, 200, 500, 1000nmol) and Ro25-6981 (20, 50, 100, 200nmol) were intrathecally injected and behavioral tests were conducted. Ifenprodil increased the paw withdrawal threshold in both models but also produced mild motor depression at higher doses. Ro25-6981 increased the mechanical nociceptive threshold in a dose-dependent manner without motor depression. NR2B expression was significantly increased on both sides at the spinal segments of L1-2 and L4-5 in the hemisection model but did not change in the contusion model. Increased expression of NR2B in the hemisection model was reduced by intrathecal ifenprodil. These results suggest that intrathecal NMDA NR2B antagonist increased the mechanical nociceptive threshold after SCI without motor depression. A selective subtype of NMDA receptor, such as NR2B, may be a more selective target for pain control because NMDA receptors play a crucial role in the development and maintenance of chronic pain. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  13. The major brain endocannabinoid 2-AG controls neuropathic pain and mechanical hyperalgesia in patients with neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Hannah L Pellkofer

    Full Text Available Recurrent myelitis is one of the predominant characteristics in patients with neuromyelitis optica (NMO. While paresis, visual loss, sensory deficits, and bladder dysfunction are well known symptoms in NMO patients, pain has been recognized only recently as another key symptom of the disease. Although spinal cord inflammation is a defining aspect of neuromyelitis, there is an almost complete lack of data on altered somatosensory function, including pain. Therefore, eleven consecutive patients with NMO were investigated regarding the presence and clinical characteristics of pain. All patients were examined clinically as well as by Quantitative Sensory Testing (QST following the protocol of the German Research Network on Neuropathic Pain (DFNS. Additionally, plasma endocannabinoid levels and signs of chronic stress and depression were determined. Almost all patients (10/11 suffered from NMO-associated neuropathic pain for the last three months, and 8 out of 11 patients indicated relevant pain at the time of examination. Symptoms of neuropathic pain were reported in the vast majority of patients with NMO. Psychological testing revealed signs of marked depression. Compared to age and gender-matched healthy controls, QST revealed pronounced mechanical and thermal sensory loss, strongly correlated to ongoing pain suggesting the presence of deafferentation-induced neuropathic pain. Thermal hyperalgesia correlated to MRI-verified signs of spinal cord lesion. Heat hyperalgesia was highly correlated to the time since last relapse of NMO. Patients with NMO exhibited significant mechanical and thermal dysesthesia, namely dynamic mechanical allodynia and paradoxical heat sensation. Moreover, they presented frequently with either abnormal mechanical hypoalgesia or hyperalgesia, which depended significantly on plasma levels of the endogenous cannabinoid 2-arachidonoylglycerole (2-AG. These data emphasize the high prevalence of neuropathic pain and hyperalgesia

  14. Neuropathic pain and cytokines: current perspectives

    Directory of Open Access Journals (Sweden)

    Clark AK

    2013-11-01

    Full Text Available Anna K Clark, Elizabeth A Old, Marzia Malcangio Wolfson Centre for Age Related Diseases, King's College London, London, UK Abstract: Neuropathic pain represents a major problem in clinical medicine because it causes debilitating suffering and is largely resistant to currently available analgesics. A characteristic of neuropathic pain is abnormal response to somatic sensory stimulation. Thus, patients suffering peripheral neuropathies may experience pain caused by stimuli which are normally nonpainful, such as simple touching of the skin or by changes in temperature, as well as exaggerated responses to noxious stimuli. Convincing evidence suggests that this hypersensitivity is the result of pain remaining centralized. In particular, at the first pain synapse in the dorsal horn of the spinal cord, the gain of neurons is increased and neurons begin to be activated by innocuous inputs. In recent years, it has become appreciated that a remote damage in the peripheral nervous system results in neuronal plasticity and changes in microglial and astrocyte activity, as well as infiltration of macrophages and T cells, which all contribute to central sensitization. Specifically, the release of pronociceptive factors such as cytokines and chemokines from neurons and non-neuronal cells can sensitize neurons of the first pain synapse. In this article we review the current evidence for the role of cytokines in mediating spinal neuron–non-neuronal cell communication in neuropathic pain mechanisms following peripheral nerve injury. Specific and selective control of cytokine-mediated neuronal–glia interactions results in attenuation of the hypersensitivity to both noxious and innocuous stimuli observed in neuropathic pain models, and may represent an avenue for future therapeutic intervention. Keywords: anti-inflammatory cytokines, proinflammatory cytokines, microglia, astrocytes, first pain synapse

  15. Central Hyperexcitability in Chronic Musculoskeletal Pain: A Conceptual Breakthrough with Multiple Clinical Implications

    Directory of Open Access Journals (Sweden)

    Jan Lidbeck

    2002-01-01

    Full Text Available Recent investigations of dysfunctional pain processing in the central nervous system have contributed much knowledge about the development of chronic musculoskeletal pain. Many common chronic musculoskeletal pain syndromes - including regional myofascial pain syndromes, whiplash pain syndromes, refractory work-related neck-shoulder pain, certain types of chronic low back pain, fibromyalgia and others - may essentially be explained by abnormalities in central pain modulation. The growing awareness of dysfunctional central pain modulation may be a conceptual breakthrough leading to a better understanding of common chronic pain disorders. A new paradigm will have multiple clinical implications, including re-evaluation of clinical practice routines and rehabilitation methods, and will focus on controversial issues of medicolegal concern. The concept of dysfunctional central pain processing will also necessitate a mechanism-based classification of pain for the selection of individual treatment and rehabilitation programs for subgroups of patients with chronic musculoskeletal pain due to different pathophysiological mechanisms.

  16. Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia.

    Science.gov (United States)

    Strati, Paolo; Uhm, Joon H; Kaufmann, Timothy J; Nabhan, Chadi; Parikh, Sameer A; Hanson, Curtis A; Chaffee, Kari G; Call, Timothy G; Shanafelt, Tait D

    2016-04-01

    Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic

  17. Antihyperalgesic Effect of Hesperidin Improves with Diosmin in Experimental Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Azucena I. Carballo-Villalobos

    2016-01-01

    Full Text Available Neuropathic pain is caused by a primary lesion, dysfunction, or transitory perturbation in the peripheral or central nervous system. In this study, we investigated the hesperidin antihyperalgesic effects alone or combined with diosmin in a model of neuropathic pain to corroborate a possible synergistic antinociceptive activity. Mechanical and thermal hyperalgesia were assessed in the aesthesiometer and plantar tests, respectively, after chronic constriction injury (CCI model in rats receiving hesperidin (HS, 5 doses from 10 to 1000 mg/kg alone or combined with diosmin (DS, 10 and 100 mg/kg in comparison to gabapentin (31.6 mg/kg. UHPLC-MS analysis of cerebral samples was used to recognize the central concentrations of these flavonoids. Participation of different receptors was also investigated in the presence of haloperidol, bicuculline, and naloxone antagonists. Acute hesperidin administration significantly decreased mechanical and thermal hyperalgesia in CCI rats. Antihyperalgesic response of hesperidin, improved by a combination with diosmin (DS10/HS100 in both stimuli, was blockaded by haloperidol, bicuculline, and naloxone, but not WAY100635, antagonists. Both flavonoids were detected in brain samples. In conclusion, hesperidin alone and combined with diosmin produces antihyperalgesic response in the CCI model in rats. Antihyperalgesic effect of DS10/HS100 combination involves central activity partially modulated by D2, GABAA, and opioids, but not by 5-HT1A, receptors.

  18. Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults.

    Science.gov (United States)

    Gill, Dipender; Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

    2011-10-05

    Valproic acid and its sodium salt (sodium valproate) are antiepileptic drugs that are sometimes used to treat chronic neuropathic pain and fibromyalgia, although they are not licensed for this use. To evaluate the analgesic efficacy and adverse effects of valproic acid and sodium valproate in the management of chronic neuropathic pain and fibromyalgia. We identified randomised controlled trials (RCTs) of valproic acid and sodium valproate in acute, and chronic pain by searching MEDLINE, EMBASE and Cochrane CENTRAL to June 2011, together with reference lists of retrieved papers and reviews. RCTs that were double blind and of eight-weeks duration or longer, reporting on analgesic effects and adverse events with valproic acid and sodium valproate in the treatment of chronic neuropathic pain and fibromyalgia. Two review authors independently extracted results and scored for quality. We extracted efficacy and adverse event data, and examined issues of study quality. We included three studies, two in diabetic neuropathy (42 participants treated with valproate, 42 with placebo), and one in post-herpetic neuralgia (23 treated with divalproex sodium, 22 with placebo). Study duration was eight or 12 weeks. No studies were found in fibromyalgia.Only one study reported one of our primary outcomes (≥ 50% pain relief), while all three reported group means for pain reduction from baseline to endpoint. In all three studies; efficacy results were given only for participants who completed the study. One study in diabetic neuropathy and the study in post-herpetic neuralgia reported significant differences between active and placebo groups, but there were insufficient data for reliable pooled analysis.More adverse events were reported with active treatment than placebo, and included nausea, drowsiness and abnormal liver function tests. One participant taking sodium valproate withdrew due to serious derangement of liver enzymes. These three studies no more than hint that sodium

  19. Neuropathic arthropathy (Charcot's joint) in dialysis patients

    International Nuclear Information System (INIS)

    Meneghello, A.; Bertoli, M.

    1984-01-01

    To the author's knowledge, uraemic neuropathy has not been previously reported as a cause of Charcot's joint. In this paper they present three cases in which the association between clinical and radiographic patterns suggest the diagnosis of neuropathic arthropathy. The features of uraemic neuropathy are stressed and the role of secondary hyperparathyroidism in the development of this type of arthropathy is discussed. The extremely severe hyperparathyroidism reported here, may cause tendon and ligament disease, especially at the site of their bone insertion. Uraemic tendon and ligament failures weaken joints and prdouce further instability, which may be a precipitating factor of uraemic Charcot's joint in patients undergoing chronic haemodialysis. (orig.) [de

  20. Chromaffin cell transplantation for neuropathic pain after spinal cord injury: a report of two cases

    Directory of Open Access Journals (Sweden)

    Chen L

    2017-02-01

    Full Text Available Lin Chen,1,2 Haitao Xi,1 Juan Xiao,1 Feng Zhang,1 Di Chen,1 Hongyun Huang,1,3 1Cell Therapy Center, Beijing Hongtianji Neuroscience Academy, 2Department of Neurosurgery, Tsinghua University Yuquan Hospital, 3Neurorestoratology Institute, General Hospital of Chinese People’s Armed Police Forces, Beijing, People’s Republic of China Abstract: Neuropathic pain (NP, a common secondary complication following spinal cord injury (SCI, presenting at or below the level of injury is largely refractory to current pharmacological, physical, and surgical treatments. Previous studies have demonstrated the promising value of cell therapy including adrenal chromaffin cells that have the capacity to act as mini-pumps that release amines and peptides for alleviating chronic pain. The paper presents the cases of two gentlemen suffering from severe central NP after thoracic SCI. Six months after chromaffin cell intrathecal injection, their pain relieved significantly. The results demonstrated the preliminary therapeutic efficacy of chromaffin cell transplants in people with NP, and support further research of this treatment strategy for the management of intractable chronic pain due to SCI. Keywords: chromaffin cell, cell transplantation, neuropathic pain, spinal cord injury

  1. Puerarin alleviates neuropathic pain by inhibiting neuroinflammation in spinal cord.

    Science.gov (United States)

    Liu, Ming; Liao, Kaijun; Yu, Changxi; Li, Xuejun; Liu, Suhuan; Yang, Shuyu

    2014-01-01

    Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI) and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4-100 nM) for 7 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models puerarin inhibited the activation of microglia and astroglia in the spinal dorsal horn. Puerarin also reduced the upregulated levels of nuclear factor-κB (NF-κB) and other proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. In summary, puerarin alleviated CCI- and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal cord. The anti-inflammation effect of puerarin might be related to the suppression of spinal NF-κB activation and/or cytokines upregulation. We conclude that puerarin has a significant effect on alleviating neuropathic pain and thus may serve as a therapeutic approach for neuropathic pain.

  2. Puerarin Alleviates Neuropathic Pain by Inhibiting Neuroinflammation in Spinal Cord

    Directory of Open Access Journals (Sweden)

    Ming Liu

    2014-01-01

    Full Text Available Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4–100 nM for 7 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models puerarin inhibited the activation of microglia and astroglia in the spinal dorsal horn. Puerarin also reduced the upregulated levels of nuclear factor-κB (NF-κB and other proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. In summary, puerarin alleviated CCI- and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal cord. The anti-inflammation effect of puerarin might be related to the suppression of spinal NF-κB activation and/or cytokines upregulation. We conclude that puerarin has a significant effect on alleviating neuropathic pain and thus may serve as a therapeutic approach for neuropathic pain.

  3. Neuropathic pain management in children.

    LENUS (Irish Health Repository)

    Hyde, Catherine

    2012-10-01

    There are difficulties in assessing, managing, and evaluating neuropathic pain in dying children, particularly those with neurological impairment. Neuropathic pain in children often presents differently to how it presents in the adult population. Comprehensive assessment as well as pharmacological and non-pharmacological interventions are crucial to its successful management and frequently require input from an interdisciplinary team. Notwithstanding the need for further research, this paper brings together research papers, reviews, and clinical guidelines to present an exploration of existing evidence regarding care for children with neuropathic pain and their families.

  4. Elucidation of pathophysiology and treatment of neuropathic pain

    NARCIS (Netherlands)

    Vranken, Jan H.

    2012-01-01

    Neuropathic pain, pain arising as a direct consequence of a lesion or disease affecting the somatosensory system, is relatively common, occurring in about 1% of the population. Studies in animal models describe a number of peripheral and central pathophysiological processes after nerve injury that

  5. Neuropathic Pain - Current Concepts | Meyer | South African Family ...

    African Journals Online (AJOL)

    Neuropathic pain (NP) represents a common and diverse group of disorders with peripheral and/or central nervous system damage or dysfunction. Many patients report intractable and severe pain that is resistant to simple analgesics. The diagnosis of NP is primarily based on clinical evaluation rather than diagnostic tests.

  6. Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial.

    NARCIS (Netherlands)

    Bouwense, S.A.W.; Olesen, S.S.; Drewes, A.M.; Poley, J.W.; Goor, H. van; Wilder-Smith, O.H.G.

    2012-01-01

    BACKGROUND: Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate the effect

  7. Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial

    NARCIS (Netherlands)

    S.A.W. Bouwense (Stefan); S.S. Olesen (Søren); A.M. Drewes (Asbjørn); J.-W. Poley (Jan-Werner); H. van Goor (Harry); O.H.G. Wilder-Smith (Oliver)

    2012-01-01

    textabstractBackground: Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate

  8. Central pain processing in chronic tension-type headache

    DEFF Research Database (Denmark)

    Lindelof, Kim; Ellrich, Jens; Jensen, Rigmor

    2009-01-01

    OBJECTIVE: Chronic tension-type headache (CTTH) affects 3% of the population. Directly and indirectly it causes high costs and considerable loss of quality of life. The mechanisms of this disorder are poorly understood and the treatment possibilities are therefore limited. The blink reflex (BR...

  9. Amelioration of chronic neuropathic pain after partial nerve injury by adeno-associated viral (AAV) vector-mediated over-expression of BDNF in the rat spinal cord

    NARCIS (Netherlands)

    Eaton, M J; Blits, B; Ruitenberg, Marc J; Verhaagen, J; Oudega, M.

    2002-01-01

    Changing the levels of neurotrophins in the spinal cord micro-environment after nervous system injury has been proposed to recover normal function, such that behavioral response to peripheral stimuli does not lead to chronic pain. We have investigated the effects of recombinant adeno-associated

  10. Evidence for central sensitization in chronic whiplash: a systematic literature review.

    Science.gov (United States)

    Van Oosterwijck, J; Nijs, J; Meeus, M; Paul, L

    2013-03-01

    It has been suggested that sensitization of the central nervous system plays an important role in the development and maintenance of chronic (pain) complaints experienced by whiplash patients. According to the PRISMA guidelines, a systematic review was performed to screen and evaluate the existing clinical evidence for the presence of central sensitization in chronic whiplash. DATABASES AND DATA TREATMENT: Predefined keywords regarding central sensitization and chronic whiplash were combined in electronic search engines PubMed and Web of Science. Full text clinical reports addressing studies of central sensitization in human adults with chronic complaints due to a whiplash trauma were included and reviewed on methodological quality by two independent reviewers. From the 99 articles that were identified, 24 met the inclusion criteria, and 22 articles achieved sufficient scores on methodological quality and were discussed. These studies evaluated the sensitivity to different types of stimuli (mechanical, thermal, electrical). Findings suggest that although different central mechanisms seem to be involved in sustaining the pain complaints in whiplash patients, hypersensitivity of the central nervous system plays a significant role. Persistent pain complaints, local and widespread hyperalgesia, referred pain and (thoracic) allodynia, decreased spinal reflex thresholds, inefficient diffuse noxious inhibitory controls activation and enhanced temporal summation of pain were established in chronic whiplash patients. Although the majority of the literature provides evidence for the presence of central sensitization in chronic whiplash, underlying mechanisms are still unclear and future studies with good methodological quality are necessary. In addition, international guidelines for the definition, clinical recognition, assessment and treatment of central sensitization are warranted. © 2012 European Federation of International Association for the Study of Pain Chapters.

  11. The Impact of Enrollment in a Specialized Interdisciplinary Neuropathic Pain Clinic

    Directory of Open Access Journals (Sweden)

    Alex Garven

    2011-01-01

    Full Text Available BACKGROUND: Chronic pain clinics have been created because of the increasing recognition of chronic pain as a very common, debilitating condition that requires specialized care. Neuropathic pain (NeP is a multifaceted, specialized form of chronic pain that often requires input from multiple disciplines for assessment and management.

  12. Self-reported pain severity, quality of life, disability, anxiety and depression in patients classified with 'nociceptive', 'peripheral neuropathic' and 'central sensitisation' pain. The discriminant validity of mechanisms-based classifications of low back (±leg) pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-04-01

    Evidence of validity is required to support the use of mechanisms-based classifications of pain clinically. The purpose of this study was to evaluate the discriminant validity of \\'nociceptive\\' (NP), \\'peripheral neuropathic\\' (PNP) and \\'central sensitisation\\' (CSP) as mechanisms-based classifications of pain in patients with low back (±leg) pain by evaluating the extent to which patients classified in this way differ from one another according to health measures associated with various dimensions of pain. This study employed a cross-sectional, between-subjects design. Four hundred and sixty-four patients with low back (±leg) pain were assessed using a standardised assessment protocol. Clinicians classified each patient\\'s pain using a mechanisms-based classification approach. Patients completed a number of self-report measures associated with pain severity, health-related quality of life, functional disability, anxiety and depression. Discriminant validity was evaluated using a multivariate analysis of variance. There was a statistically significant difference between pain classifications on the combined self-report measures, (p = .001; Pillai\\'s Trace = .33; partial eta squared = .16). Patients classified with CSP (n = 106) reported significantly more severe pain, poorer general health-related quality of life, and greater levels of back pain-related disability, depression and anxiety compared to those classified with PNP (n = 102) and NP (n = 256). A similar pattern was found in patients with PNP compared to NP. Mechanisms-based pain classifications may reflect meaningful differences in attributes underlying the multidimensionality of pain. Further studies are required to evaluate the construct and criterion validity of mechanisms-based classifications of musculoskeletal pain.

  13. Central and peripheral mechanisms in chronic tension-type headache

    OpenAIRE

    Lipchik, Gay L.; Holroyd, Kenneth A.; France, Christopher R.; Kvaal, Steven A.; Segal, David; Cordingley, Gary E.; Rokicki, Lori A.; McCool, Heidi R.

    1996-01-01

    The second exteroceptive suppression of masseter muscle activity (ES2) and tenderness in pericranial muscles were evaluated in 112 young adults who met IHS criteria in the following diagnostic classifications: 31 chronic tension headache, 31 episodic tension headache, 33 migraine without aura and 17 migraine with aura. An additional 31 subjects served as controls. Pericranial muscle tenderness better distinguished diagnostic subgroups and better distinguished recurrent headache sufferers from...

  14. Comparing the DN4 tool with the IASP grading system for chronic neuropathic pain screening after breast tumor resection with and without paravertebral blocks: a prospective 6-month validation study.

    Science.gov (United States)

    Abdallah, Faraj W; Morgan, Pamela J; Cil, Tulin; Escallon, Jaime M; Semple, John L; Chan, Vincent W

    2015-04-01

    Investigating protective strategies against chronic neuropathic pain (CNP) after breast cancer surgery entails using valid screening tools. The DN4 (Douleur Neuropathique en 4 questions) is 1 tool that offers important research advantages. This prospective 6-month follow-up study seeks to validate the DN4 and assess its responsiveness in screening for CNP that satisfies the International Association for the Study of Pain (IASP) definition and fulfills its grading system criteria after breast tumor resection with and without paravertebral blocks (PVBs). We randomized 66 females to standardized general anesthesia and sham subcutaneous injections, or PVB and total intravenous anesthesia. The 6-month CNP risk was assessed using the IASP grading system and the DN4 screening tools. We evaluated the DN4 sensitivity, specificity, and responsiveness in capturing the impact of PVB on the CNP risk relative to the IASP grading system. Data from 64 patients showed similar demographic characteristics in both groups. Twenty patients in both groups met the grading system CNP criteria; among these, 18 patients also met the DN4 CNP criteria. Furthermore, 15 patients in both groups did not meet the grading system CNP criteria; among these, 9 patients also did not meet the DN4 CNP criteria. Therefore, the sensitivity and specificity of the DN4 were estimated at 90% and 60%, respectively. Both screening tools suggested that PVB reduced the 6-month CNP risk. Our results suggest that the DN4 can reliably identify CNP at 6 months after breast tumor resection and detect the preincisional PVB effect on the risk of developing such pain.

  15. Tolerability, Safety, and Quality of Life with Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR in Patients with Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open-label, Phase 3b/4 Trial.

    Science.gov (United States)

    Baron, Ralf; Jansen, Jan-Peter; Binder, Andreas; Pombo-Suarez, Manuel; Kennes, Lieven; Müller, Matthias; Falke, Dietmar; Steigerwald, Ilona

    2016-06-01

    To evaluate tolerability, safety, and quality-of-life outcomes in non-opioid-pretreated patients with severe chronic low back pain with a neuropathic component receiving tapentadol PR vs. oxycodone/naloxone PR. Eligible patients (average pain intensity [numerical rating scale] ≥ 6; painDETECT positive/unclear ratings) were randomized to twice-daily tapentadol PR 50 mg or oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or oxycodone/naloxone PR 40 mg/20 mg plus oxycodone PR 10 mg), target doses were continued for 9 weeks. Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) total score from baseline to final evaluation was a primary endpoint. For the primary tolerability-related endpoint, the 97.5% exact repeated confidence interval for tapentadol PR minus oxycodone/naloxone PR for the PAC-SYM total score was [-0.259, 0.121], showing noninferiority (upper limit < 0.7). Incidences of constipation and vomiting were significantly lower with tapentadol PR than oxycodone/naloxone PR (P ≤ 0.045). Confirmatory superiority based on formal noninferiority was shown for the primary effectiveness endpoint (change from baseline to final evaluation in pain intensity) for tapentadol PR vs. oxycodone/naloxone PR (presented separately). Improvements in the Short Form-12 physical component summary and EuroQol-5 Dimension health status index and health state assessment were significantly greater with tapentadol PR vs. oxycodone/naloxone PR (P ≤ 0.024). Tapentadol PR had a minimal impact on bowel function (noninferior to oxycodone/naloxone PR) and, along with superior effectiveness (presented separately), was associated with significantly lower incidences of constipation and vomiting and significant improvements in quality-of-life measures vs. oxycodone/naloxone PR. © 2015 The authors. Pain Practice published by Wiley Periodicals, Inc. on behalf of World Institute of Pain.

  16. Management of chronic luxated central incisor with hopeless prognosis

    Directory of Open Access Journals (Sweden)

    Gauresh Kumar Patel

    2013-01-01

    Full Text Available Traumatic injuries are the most studied yet most challenging for a dentist. Extrusive luxation injuries are usually managed by repositioning tooth in the original position and pulp sensibility is evaluated at regular periodic intervals. However, when injuries are chronic, tooth is necrotic with compromised periodontal support, treatment is a challenge. Intentional replantation utilizing growth factors in fibrin rich network of platelet rich fibrin can be a treatment modality in such patients where other restorative modalities to establish function-esthetics rehabilitation is not possible.

  17. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis.

    Science.gov (United States)

    Langford, R M; Mares, J; Novotna, A; Vachova, M; Novakova, I; Notcutt, W; Ratcliffe, S

    2013-04-01

    Central neuropathic pain (CNP) occurs in many multiple sclerosis (MS) patients. The provision of adequate pain relief to these patients can very difficult. Here we report the first phase III placebo-controlled study of the efficacy of the endocannabinoid system modulator delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (USAN name, nabiximols; Sativex, GW Pharmaceuticals, Salisbury, Wiltshire, UK), to alleviate CNP. Patients who had failed to gain adequate analgesia from existing medication were treated with THC/CBD spray or placebo as an add-on treatment, in a double-blind manner, for 14 weeks to investigate the efficacy of the medication in MS-induced neuropathic pain. This parallel-group phase of the study was then followed by an 18-week randomized-withdrawal study (14-week open-label treatment period plus a double-blind 4-week randomized-withdrawal phase) to investigate time to treatment failure and show maintenance of efficacy. A total of 339 patients were randomized to phase A (167 received THC/CBD spray and 172 received placebo). Of those who completed phase A, 58 entered the randomized-withdrawal phase. The primary endpoint of responder analysis at the 30 % level at week 14 of phase A of the study was not met, with 50 % of patients on THC/CBD spray classed as responders at the 30 % level compared to 45 % of patients on placebo (p = 0.234). However, an interim analysis at week 10 showed a statistically significant treatment difference in favor of THC/CBD spray at this time point (p = 0.046). During the randomized-withdrawal phase, the primary endpoint of time to treatment failure was statistically significant in favor of THC/CBD spray, with 57 % of patients receiving placebo failing treatment versus 24 % of patients from the THC/CBD spray group (p = 0.04). The mean change from baseline in Pain Numerical Rating Scale (NRS) (p = 0.028) and sleep quality NRS (p = 0.015) scores, both secondary endpoints in phase B, were also statistically

  18. A randomized trial of pregabalin in patients with neuropathic pain due to spinal cord injury.

    Science.gov (United States)

    Cardenas, Diana D; Nieshoff, Edward C; Suda, Kota; Goto, Shin-Ichi; Sanin, Luis; Kaneko, Takehiko; Sporn, Jonathan; Parsons, Bruce; Soulsby, Matt; Yang, Ruoyong; Whalen, Ed; Scavone, Joseph M; Suzuki, Makoto M; Knapp, Lloyd E

    2013-02-05

    To assess the efficacy and tolerability of pregabalin for the treatment of central neuropathic pain after spinal cord injury (SCI). Patients with chronic, below-level, neuropathic pain due to SCI were randomized to receive 150 to 600 mg/d pregabalin (n = 108) or matching placebo (n = 112) for 17 weeks. Pain was classified in relation to the neurologic level of injury, defined as the most caudal spinal cord segment with normal sensory and motor function, as above, at, or below level. The primary outcome measure was duration-adjusted average change in pain. Key secondary outcome measures included the change in mean pain score from baseline to end point, the percentage of patients with ≥30% reduction in mean pain score at end point, patient global impression of change scores at end point, and the change in mean pain-related sleep interference score from baseline to end point. Additional outcome measures included the medical outcomes study-sleep scale and the Hospital anxiety and depression scale. Pregabalin treatment resulted in statistically significant improvements over placebo for all primary and key secondary outcome measures. Significant pain improvement was evident as early as week 1 and was sustained throughout the treatment period. Adverse events were consistent with the known safety profile of pregabalin and were mostly mild to moderate in severity. Somnolence and dizziness were most frequently reported. This study demonstrates that pregabalin is effective and well tolerated in patients with neuropathic pain due to SCI. This study provides class I evidence that pregabalin, 150 to 600 mg/d, is effective in reducing duration-adjusted average change in pain compared with baseline in patients with SCI over a 16-week period (p = 0.003, 95% confidence interval = -0.98, -0.20).

  19. Effect of photobiomodulation therapy (808 nm) in the control of neuropathic pain in mice.

    Science.gov (United States)

    de Andrade, Ana Laura Martins; Bossini, Paulo Sérgio; do Canto De Souza, Azair Liane Matos; Sanchez, Ariane Dutra; Parizotto, Nivaldo Antonio

    2017-05-01

    Neuropathic pain can be defined as the pain initiated or caused by a primary lesion or dysfunction of the central or peripheral nervous system. Photobiomodulation therapy (PBM) stands out among the physical therapy resources used for analgesia. However, application parameters, especially the energy density, remain controversial in the literature. Therefore, this study aimed to investigate the PBM effect, in different energy densities to control neuropathic pain in mice. Fifty (50) mice were induced to neuropathy by chronic constriction surgery of the sciatic nerve (CCI), treated with PBM (808 nm), and divided into five groups: GP (PBM simulation), GS (sham), GL10, GL20, GL40 (energy density of 10, 20, and 40 J/cm 2 , respectively). The evaluations were carried out using the hot plate test and Randall and Selitto test, before and after the CCI surgery, every 15 days during the 90 days experiment. β-Endorphin blood dosage was also tested. For both the hot plate and Randall and Selitto tests, the GL20 and GL40 groups presented reduction of the nociceptive threshold from the 30th day of treatment, the GL10 group only after day 75, and the GP group did not show any improvement throughout the experiment. The β-endorphin dosage was higher for all groups when compared to the GP group. However, only the GL20 group and GL40 presented a significant increase. This study demonstrates that PBM in higher energy density (20, 40 J/cm 2 ) is more effective in the control of neuropathic pain.

  20. Placebo, nocebo, and neuropathic pain.

    Science.gov (United States)

    Vase, Lene; Skyt, Ina; Hall, Kathryn T

    2016-02-01

    Over the last decade, the apparent increase in placebo responses in randomized controlled trials (RCTs) of neuropathic pain have complicated and potentially limited development and availability of new effective pain medication. Placebo analgesia and nocebo hyperalgesia effects are well described in nociceptive and idiopathic pain conditions, but less is known about the magnitude and mechanisms of placebo and nocebo effects in neuropathic pain. In neuropathic pain, placebo treatments have primarily been used as control conditions for active agents under investigation in RCTs and these placebo responses are typically not controlled for the natural history of pain and other confounding factors. Recently, mechanistic studies that control for the natural history of pain have investigated placebo and nocebo effects in neuropathic pain in their own right. Large placebo analgesia but no nocebo hyperalgesic effects have been found, and the underlying mechanisms are beginning to be elucidated. Here we review placebo and nocebo effects and the underlying mechanisms in neuropathic pain and compare them with those of nociceptive and idiopathic pain. This allows for a novel discussion on how knowledge of psychological, neurobiological, and genetic factors underlying well-controlled placebo effects may help improve the information that can be obtained from and potentially restore the utility of RCTs.

  1. Pharmacologic management of neuropathic pain.

    Science.gov (United States)

    Gordon, Debra B; Love, Georgette

    2004-12-01

    The mechanisms underlying the pathogenesis of neuropathic pain are complex but are gradually coming to light. Agents that have been found effective in a variety of neuropathic pain conditions include drugs that act to modulate (a) sodium or calcium channels, (b) N-methyl-D-aspartate receptors, (c) norepinephrine or serotonin reuptake, (d) opioid receptors, and (e) other cellular processes. Clinical trials have primarily evaluated these treatments for postherpetic neuralgia and painful diabetic neuropathy, the two most common types of neuropathic pain. Nonetheless, the identification of effective treatment regimens remains challenging, often because multiple mechanisms may be operating in a given patient giving rise to the same symptom. Alternatively, a single mechanism may be responsible for multiple symptoms. Currently available diagnostic tools are inadequate to determine the best treatment using a mechanism-based model. Clinically, drug treatment of neuropathic pain is often a matter of treatment trials. This article presents a summary of available clinical information on first-line and lesser-known treatments for neuropathic pain.

  2. Sensory pain qualities in neuropathic pain.

    Science.gov (United States)

    Mackey, Sean; Carroll, Ian; Emir, Birol; Murphy, T Kevin; Whalen, Ed; Dumenci, Levent

    2012-01-01

    The qualities of chronic neuropathic pain (NeP) may be informative about the different mechanisms of pain. We previously developed a 2-factor model of NeP that described an underlying structure among sensory descriptors on the Short-Form McGill Pain Questionnaire. The goal of this study was to confirm the correlated 2-factor model of NeP. Individual descriptive scores from the Short-Form McGill Pain Questionnaire were analyzed. Confirmatory factor analysis was used to test a correlated 2-factor model. Factor 1 (stabbing pain) was characterized by high loadings on stabbing, sharp, and shooting sensory items; factor 2 (heavy pain) was characterized by high loadings on heavy, gnawing, and aching items. Results of the confirmatory factor analysis strongly supported the correlated 2-factor model. This article validates a model that describes the qualities of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. These data suggest that specific pain qualities may be associated with pain mechanisms or may be useful for predicting treatment response. Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.

  3. Effectiveness of repetitive trancranial or peripheral magnetic stimulation in neuropathic pain.

    Science.gov (United States)

    Kumru, Hatice; Albu, Sergiu; Vidal, Joan; Tormos, Josep Maria

    2017-05-01

    Maladaptive plasticity in the sensorimotor system, following neurological lesions or diseases, plays a central role in the generation and maintenance of neuropathic pain. Repetitive magnetic stimulation of the central and peripheral nervous system has gained relevance as noninvasive approach for neuromodulation and pain relief. Systematic reviews that evaluate the effectiveness and specificity of different protocols of repetitive magnetic stimulation to control neuropathic pain in clinical populations have the potential to improve the therapeutic applicability of this technique. Studies whose primary goal was to evaluate the effectiveness of repetitive magnetic stimulation for the treatment of various types of neuropathic pain published in PubMed until August 2015 have been included in this systematic review. A total of 39 articles fulfilling the inclusion criteria were analyzed of which 37 studies investigated pain modulation using repetitive magnetic stimulation over the motor or non-motor cortices and two studies evaluated pain modulation using repetitive peripheral magnetic stimulation protocols. Repetitive transcranial magnetic stimulation of the primary motor cortex using high frequency stimulation protocols can effectively reduce neuropathic pain, particularly in individuals with pain related to non-cerebral lesions. The application of multiple sessions can lead to long-lasting pain modulation and cumulative effects. Implications for Rehabilitation Maladaptive plasticity plays a central role in sensitization of nociceptive pathways, generation and maintainance of neuropathic pain; Most neuropathic pain conditions are refractory to pharmacological therapies; Repetitive magnetic stimulation of the central and peripheral nervous system has gained relevance as noninvasive approach for neuromodulation and pain relief.

  4. Spinal NGF Restores Opioid Sensitivity in Neuropathic Rats: Possible Role of NGF as a Regulator of CCK-Induced Anti-Opioid Effects

    Directory of Open Access Journals (Sweden)

    Catherine M Cahill

    2000-01-01

    Full Text Available The breadth of peripheral effects produced by nerve growth factor (NGF in nociceptive processing has been well documented. However, less is known about the functional significance of central NGF in nociceptive transmission. The effect of NGF on the nervous system is dependent on the developmental stage. During the prenatal developmental period, NGF is critical for survival of nociceptors; in the postnatal period it regulates the expression of nociceptor phenotype, and in the adult it contributes to pain following an inflammatory insult. The implications for central NGF in the expression and regulation of spinal neuropeptides that are involved in pain mechanisms are reviewed. Knowledge has been gained by studies using peripheral nerve injury models that cause a deprivation of central NGF. These models also give rise to the development of pain syndromes, which encompass spontaneous pain, hyperalgesia and allodynia, routinely referred to as neuropathic pain. These models provide an approach for examining the contribution of central NGF to nociceptive transmission. Chronic pain emanating from a nerve injury is typically refractory to traditional analgesics such as opioids. Recent evidence suggests that supplementation of spinal NGF restores morphine-induced antinociception in an animal model of neuropathic pain. This effect appears to be mediated by alterations in spinal levels of cholecystokinin. The authors hypothesize that NGF is critical in maintaining neurochemical homeostasis in the spinal cord of nociceptive neurons, and that supplementation may be beneficial in restoring and/or maintaining opioid analgesia in chronic pain conditions resulting from traumatic nerve injury.

  5. Gynecologic management of neuropathic pain.

    Science.gov (United States)

    Tu, Frank F; Hellman, Kevin M; Backonja, Miroslav M

    2011-11-01

    Obstetrician/gynecologists often are the initial management clinicians for pelvic neuropathic pain. Although treatment may require comprehensive team management and consultation with other specialists, there are a few critical and basic steps that can be performed during an office visit that offer the opportunity to improve quality of life significantly in this patient population. A key first step is a thorough clinical examination to map the pain site physically and to identify potentially involved nerves. Only limited evidence exists about how best to manage neuropathic pain; generally, a combination of surgical, manipulative, or pharmacologic methods should be considered. Experimental methods to characterize more precisely the nature of the nerve dysfunction exist to diagnose and treat neuropathic pain; however, additional scientific evidence is needed to recommend these options unanimously. In the meantime, an approach that was adopted from guidelines of the International Association for the Study of Pain has been tailored for gynecologic pain. Copyright © 2011 Mosby, Inc. All rights reserved.

  6. Central pain processing in chronic tension-type headache.

    Science.gov (United States)

    Lindelof, Kim; Ellrich, Jens; Jensen, Rigmor; Bendtsen, Lars

    2009-07-01

    Chronic tension-type headache (CTTH) affects 3% of the population. Directly and indirectly it causes high costs and considerable loss of quality of life. The mechanisms of this disorder are poorly understood and the treatment possibilities are therefore limited. The blink reflex (BR) reflects neuronal excitability due to nociceptive input in the brainstem. The aim of this study was to investigate nociceptive processing at the level of the brainstem in an experimental pain model of CTTH symptoms. The effect of conditioning pain, 5 min infusion of hypertonic saline into the neck muscles, was investigated in 20 patients with CTTH and 20 healthy controls. In addition, a pilot study with isotonic saline was performed with 5 subjects in each group. The BR was elicited by electrical stimuli with an intensity of four times the pain threshold, with a superficial concentric electrode. We measured the BR, sensibility to pressure and electrical pain scores before, during and 25 min after the saline infusion. The pain rating of the electrical stimuli and the pain score of the hypertonic saline infusion were significantly higher in CTTH patients than in healthy volunteers. The primary endpoint was the relative change of the blink reflex integral immediately after hypertonic saline infusion. It was significantly smaller in CTTH patients on the contralateral side (-24.5% +/-7.0 (sem)) compared to healthy volunteers (0.4% +/-6.8), (p<0.05, Holm-Sidak), while there was no significant difference on the ipsilateral side (-5.9% +/-3.2 vs. -3.4% +/-3.0, n.s., Holm-Sidak). There was no robust difference in BR integral after conditioning tonic neck pain between CTTH patients and healthy volunteers, but CTTH patients were more sensitive to nociceptive stimuli. A combined homotopic and heterotopic effect of the conditioning pain onto the blink reflex could account for this finding.

  7. Combined approaches for the relief of spinal cord injury-induced neuropathic pain.

    Science.gov (United States)

    Gwak, Young S; Kim, Hee Young; Lee, Bong Hyo; Yang, Chae Ha

    2016-04-01

    The adequate treatment of spinal cord injury (SCI)-induced neuropathic pain still remains an unresolved problem. The current medications predominantly used in the SCI-induced neuropathic pain therapy are morphine, anticonvulsants, antidepressants, and antiepileptics, which suggests that psychiatric aspects might be important factors in the treatment of neuropathic pain. It is well documented that the modulation of the sensory events is not a unique way for achieving pain relief. In addition, pain patients still express dissatisfaction and complain of unwanted effects of the medications, suggesting that alternative approaches for the treatment of neuropathic pain are essential. In psychiatry, pain relief represents relaxation and a feeling of comfort and satisfaction, which suggests that cognitive and emotional motivations are important factors in the treatment of neuropathic pain. The comorbidity of chronic pain and psychiatric disorders, which is well recognized, suggests that the effective therapeutic relief for neuropathic pain induced by SCI can be achieved in conjunction with the management of the sensory and psychiatric aspects of patient. In this review, we address the feasibility of a combined acupuncture and pharmacotherapy treatment for the relief of neuropathic pain behavior following SCI. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents.

    Science.gov (United States)

    Gui, Wen-Shan; Wei, Xiao; Mai, Chun-Lin; Murugan, Madhuvika; Wu, Long-Jun; Xin, Wen-Jun; Zhou, Li-Jun; Liu, Xian-Guo

    2016-01-01

    Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice. Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β. Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression. © The Author(s) 2016.

  9. Neuropathic pain after spinal cord injury resistant to conventional therapies - case report

    OpenAIRE

    Andrzej Daszkiewicz; Zbigniew Gierlotka; Wojciech Nierodziński; Aleksandra Misiołek; Hanna Misiołek

    2016-01-01

    Objectives There are patients with neuropathic pain in whom the treatment is ineffective, despite the fact that is conducted with adherence to the current guidelines. In these patients alternative treatment methods such as hypnosis could be effective. Methods The paper presents a case of a 58-year-old man with central neuropathic pain after cervical spinal cord injury. The conservative treatment with antiepileptics including gabapentoids), antidepressants (tricyclic and selective no...

  10. OCT Angiography Compared to Fluorescein and Indocyanine Green Angiography in Chronic Central Serous Chorioretinopathy

    NARCIS (Netherlands)

    Teussink, M.M.; Breukink, M.B.; Grinsven, M.J.J.P. van; Hoyng, C.B.; Klevering, B.J.; Boon, C.J.F.; Jong, E.K.; Theelen, T.

    2015-01-01

    PURPOSE: Abnormal choroidal blood flow is considered important in the pathogenesis of chronic central serous chorioretinopathy (CSC). Optical coherence tomography (OCT) angiography can image ocular blood cell flow and could thus provide novel insights in disease mechanisms of CSC. We evaluated

  11. How to explain central sensitization to patients with 'unexplained' chronic musculoskeletal pain : Practice guidelines

    NARCIS (Netherlands)

    Nijs, Jo; van Wilgen, C. Paul; Van Oosterwijck, Jessica; van Ittersum, Miriam; Meeus, Mira

    2011-01-01

    Central sensitization provides an evidence-based explanation for many cases of 'unexplained' chronic musculoskeletal pain. Prior to commencing rehabilitation in such cases, it is crucial to change maladaptive illness perceptions, to alter maladaptive pain cognitions and to reconceptualise pain. This

  12. High dose ascorbic acid does not reverse central sympathetic overactivity in chronic heart failure

    NARCIS (Netherlands)

    Gomes, M.E.R.; El Messaoudi, S.; Lenders, J.W.M.; Bellersen, L.; Verheugt, F.W.A.; Smits, P.; Tack, C.J.J.

    2011-01-01

    WHAT IS KNOWN AND OBJECTIVE: The increased central sympathetic activity typically associated with chronic heart failure (CHF) is probably mediated by formation of reactive oxygen species (ROS) in the brain. Our objective was to undertake a trial to test our hypothesis that administration of the

  13. Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model.

    Science.gov (United States)

    Ryu, Tae Ha; Jung, Kyung Young; Ha, Mi Jin; Kwak, Kyung Hwa; Lim, Dong Gun; Hong, Jung Gil

    2010-03-01

    Recent studies indicate that reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Since the data suggest that ROS are involved in central sensitization, the present study examines the levels of activated N-methyl-D-aspartate (NMDA) receptors in the dorsal horn after an exogenous supply of three antioxidants in rats with chronic post-ischemia pain (CPIP). This serves as an animal model of complex regional pain syndrome type-I induced by hindpaw ischemia/reperfusion injury. The application of tight-fitting O-rings for a period of three hours produced CPIP in male Sprague-Dawley rats. Allopurinol 4 mg/kg, allopurinol 40 mg/kg, superoxide dismutase (SOD) 4,000 U/kg, N-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg and SOD 4,000 U/kg plus L-NAME 10 mg/kg were administered intraperitoneally just after O-ring application and on the first and second days after reperfusion. Mechanical allodynia was measured, and activation of the NMDA receptor subunit 1 (pNR1) of the lumbar spinal cord (L4-L6) was analyzed by the Western blot three days after reperfusion. Allopurinol reduced mechanical allodynia and attenuated the enhancement of spinal pNR1 expression in CPIP rats. SOD and L-NAME also blocked spinal pNR1 in accordance with the reduced mechanical allodynia in rats with CPIP. The present data suggest the contribution of superoxide, produced via xanthine oxidase, and the participation of superoxide and nitric oxide as a precursor of peroxynitrite in NMDA mediated central sensitization. Finally, the findings support a therapeutic potential for the manipulation of superoxide and nitric oxide in ischemia/reperfusion related pain conditions.

  14. Effect of Gabapentin and Baclofen on Histology Study in Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Fifteen A. Fajrin

    2015-12-01

    Full Text Available Neuropathic pain resulted from injury to nerves is often resistant to current treatments and can seriously cause chronic pain if no appropriate treatment is given. This study was designed to prove the effectiveness of gabapentin and baclofen in increasing latency time toward thermal stimulus and recovering the morphology of dorsal horn of spinal cord in neuropathic-induced chronic pain. Forty mice were divided into 8 groups i.e sham, negative control, gabapentin at three different doses (10, 30, 100 nmol and baclofen at three different doses (1, 10, 30 nmol. Neuropathic condition was induced by ligation of sciatic nerve with Partial Sciatic Nerve Ligation (PSNL method. Gabapentin and baclofen were administrated intrathecally once a day for seven days, a week after neuropathic induction. Latency time toward thermal stimulus was measured on days 0, 1, 3, 5, 7, 8, 10, 12 and 14 after induction. Histology of the dorsal horn of spinal cord tissue was examined by haematoxylline-eosin staining. The results showed that intrathecal injection of gabapentin and baclofen significantly increased latency time of mice toward thermal stimulus compared with negative control. Gabapentin and baclofen are effective as treatment for neuropathic pain. They can also help the recovery process of the histology in dorsal horn in neuropathic pain.

  15. TMEM16F Regulates Spinal Microglial Function in Neuropathic Pain States

    Directory of Open Access Journals (Sweden)

    Laura Batti

    2016-06-01

    Full Text Available Neuropathic pain is a widespread chronic pain state that results from injury to the nervous system. Spinal microglia play a causative role in the pathogenesis of neuropathic pain through secretion of growth factors and cytokines. Here, we investigated the contribution of TMEM16F, a protein that functions as a Ca2+-dependent ion channel and a phospholipid scramblase, to microglial activity during neuropathic pain. We demonstrate that mice with a conditional ablation of TMEM16F in microglia do not develop mechanical hypersensitivity upon nerve injury. In the absence of TMEM16F, microglia display deficits in process motility and phagocytosis. Moreover, loss of GABA immunoreactivity upon injury is spared in TMEM16F conditional knockout mice. Collectively, these data indicate that TMEM16F is an essential component of the microglial response to injury and suggest the importance of microglial phagocytosis in the pathogenesis of neuropathic pain.

  16. Neuropeptide Y and its involvement in chronic pain

    DEFF Research Database (Denmark)

    Diaz-delCastillo, Marta; Woldbye, David P D; Heegaard, Anne Marie

    2018-01-01

    Chronic pain is a serious condition that significantly impairs the quality of life, affecting an estimate of 1.5 billion people worldwide. Despite the physiological, emotional and financial burden of chronic pain, there is still a lack of efficient treatments. Neuropeptide Y (NPY) is a highly...... and Y2 receptors. Intrathecal administration of NPY in animal models of neuropathic, inflammatory or postoperative pain has been shown to cause analgesia, even though its exact mechanisms are still unclear. It remains to be seen whether these promising central antinociceptive effects of NPY can...... be transferred into a future treatment for chronic pain....

  17. Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Gui-Lin Jin

    2018-01-01

    Full Text Available Despite decades of studies, the currently available drugs largely fail to control neuropathic pain. Koumine—an alkaloidal constituent derived from the medicinal plant Gelsemium elegans Benth.—has been shown to possess analgesic and anti-inflammatory properties; however, the underlying mechanisms remain unclear. In this study, we aimed to investigate the analgesic and anti-inflammatory effects and the possible underlying mechanisms of koumine. The analgesic and anti-inflammatory effects of koumine were explored by using chronic constriction injury of the sciatic nerve (CCI neuropathic pain model in vivo and LPS-induced injury in microglia BV2 cells in vitro. Immunofluorescence staining and Western blot analysis were used to assess the modulator effect of koumine on microglia and astrocyte activation after CCI surgery. Enzyme-linked immunosorbent assay (ELISA was used to evaluate the levels of proinflammatory cytokines. Western blot analysis and quantitative real-time polymerase chain reaction (qPCR were used to examine the modulator effect of koumine on microglial M1 polarization. We found that single or repeated treatment of koumine can significantly reduce neuropathic pain after nerve injury. Moreover, koumine showed inhibitory effects on CCI-evoked microglia and astrocyte activation and reduced proinflammatory cytokine production in the spinal cord in rat CCI models. In BV2 cells, koumine significantly inhibited microglia M1 polarization. Furthermore, the analgesic effect of koumine was inhibited by a TSPO antagonist PK11195. These findings suggest that the analgesic effects of koumine on CCI-induced neuropathic pain may result from the inhibition of microglia activation and M1 polarization as well as the activation of astrocytes while sparing the anti-inflammatory responses to neuropathic pain.

  18. Transient inhibition of LIMKs significantly attenuated central sensitization and delayed the development of chronic pain.

    Science.gov (United States)

    Yang, Xiangyu; He, Guiqin; Zhang, Xiaoyun; Chen, Lu; Kong, Yue; Xie, Wei; Jia, Zhengping; Liu, Wen-Tao; Zhou, Zikai

    2017-10-01

    Central sensitization represents a key mechanism mediating chronic pain, a major clinical problem lacking effective treatment options. LIM-domain kinases (LIMKs) selectively regulate several substrates, e.g. cofilin and cAMP response element-binding protein (CREB), that profoundly affect neural activities, such as synaptogenesis and gene expression, thus critical in the consolidation of long-term synaptic potentiation and memory in the brain. In this study, we demonstrate that LIMK deficiency significantly impaired the development of multiple forms of chronic pain. Mechanistic studies focusing on spared nerve injury (SNI) model reveal a pivotal role of LIMKs in the up-regulation of spontaneous excitatory synaptic transmission and synaptogenesis after pain induction. Depending on the pain induction methods, LIMKs can be transiently activated with distinct time courses. Accordingly, pharmacological inhibition of LIMKs targeting this critical period remarkably attenuated central sensitization in the spinal cord and alleviated pain behaviors. We propose selectively targeting LIMKs during their activation phase as a potential therapeutic strategy for clinical management of chronic pain, especially for chronic pain with predictable onset and development time courses, such as chronic post-surgical pain (PSP). Copyright © 2017. Published by Elsevier Ltd.

  19. Centralization phenomenon as a prognostic factor for chronic low back pain and disability.

    Science.gov (United States)

    Werneke, M; Hart, D L

    2001-04-01

    Two hundred twenty-three consecutive adults with acute low back pain with or without referred spinal symptoms were treated conservatively and followed prospectively for 1 year. To investigate the predictive value of centralization phenomenon (CP) with psychosocial variables previously identified as important risk factors for patients with acute onset of nonserious or nonspecific low back pain who subsequently develop chronic pain or disability. Psychosocial factors have been shown to be predictors of chronic disability, but measures from physical examination rarely predict chronic behavior. The authors of the present study investigated whether dynamic assessment of changes in clinical measures during treatment could be used to classify patients and predict occurrence of chronic pain or disability. Patients with acute symptoms and no history of surgery were treated by five physical therapists trained in McKenzie evaluation/treatment methods. Seventy-three percent were receiving workers' compensation benefits. At initial evaluation and discharge, 23 independent variables were assessed representing psychosocial, clinical, and demographic factors. Pain location changes to repeated trunk movements were assessed at every visit. Patients were placed in two groups: 1) those with pain that did not centralize and 2) those who completely centralized or demonstrated partial reduction of pain location with time. Treatment was individualized and based on McKenzie methods. Patients were contacted at 12 months after discharge, and dependent variables of pain intensity, return to work status, sick leave at work, activity interference at home, and continued use of health care were assessed. Nine independent variables influenced pain symptoms or disability. Pain pattern classification (noncentralization) and leg pain at intake were the strongest predictive variables of chronicity. Dynamic assessment of change in anatomic pain location during treatment and leg pain at intake were

  20. Beyond the Joint: The Role of Central Nervous System Reorganizations in Chronic Musculoskeletal Disorders.

    Science.gov (United States)

    Roy, Jean-Sébastien; Bouyer, Laurent J; Langevin, Pierre; Mercier, Catherine

    2017-11-01

    To a large extent, management of musculoskeletal disorders has traditionally focused on structural dysfunctions found within the musculoskeletal system, mainly around the affected joint. While a structural-dysfunction approach may be effective for musculoskeletal conditions in some populations, especially in acute presentations, its effectiveness remains limited in patients with recurrent or chronic musculoskeletal pain. Numerous studies have shown that the human central nervous system can undergo plastic reorganizations following musculoskeletal disorders; however, they can be maladaptive and contribute to altered joint control and chronic pain. In this Viewpoint, the authors argue that to improve rehabilitation outcomes in patients with chronic musculoskeletal pain, a global view of the disorder that incorporates both central (neural) and peripheral (joint-level) changes is needed. The authors also discuss the challenge of evaluating and rehabilitating central changes and the need for large, high-level studies to evaluate approaches incorporating central and peripheral changes and emerging therapies. J Orthop Sports Phys Ther 2017;47(11):817-821. doi:10.2519/jospt.2017.0608.

  1. TrkB.T1 contributes to neuropathic pain after spinal cord injury through regulation of cell cycle pathways.

    Science.gov (United States)

    Wu, Junfang; Renn, Cynthia L; Faden, Alan I; Dorsey, Susan G

    2013-07-24

    Spinal cord injury (SCI) frequently causes severe, persistent central neuropathic pain that responds poorly to conventional pain treatments. Brain-derived neurotrophic factor (BDNF) signaling appears to contribute to central sensitization and nocifensive behaviors in certain animal models of chronic pain through effects mediated in part by the alternatively spliced truncated isoform of the BDNF receptor tropomyosin-related kinase B.T1 (trkB.T1). Mechanisms linking trkB.T1 to SCI-induced chronic central pain are unknown. Here, we examined the role of trkB.T1 in central neuropathic pain after spinal cord contusion. Genetic deletion of trkB.T1 in mice significantly reduced post-SCI mechanical hyperesthesia, locomotor dysfunction, lesion volumes, and white matter loss. Whole genome analysis, confirmed at the protein level, revealed that cell cycle genes were upregulated in trkB.T1(+/+) but not trkB.T1(-/-) spinal cord after SCI. TGFβ-induced reactive astrocytes from WT mice showed increased cell cycle protein expression that was significantly reduced in astrocytes from trkB.T1(-/-) mice that express neither full-length trkB nor trkB.T1. Administration of CR8, which selectively inhibits cyclin-dependent kinases, reduced hyperesthesia, locomotor deficits, and dorsal horn (SDH) glial changes after SCI, similar to trkB.T1 deletion, without altering trkB.T1 protein expression. In trkB.T1(-/-) mice, CR8 had no effect. These data indicate that trkB.T1 contributes to the pathobiology of SCI and SCI pain through modulation of cell cycle pathways and suggest new therapeutic targets.

  2. A double-blind placebo-controlled cross-over study of the vascular effects of midodrine in neuropathic compared with hyperadrenergic postural tachycardia syndrome

    OpenAIRE

    ROSS, Amanda J.; OCON, Anthony J.; MEDOW, Marvin S.; STEWART, Julian M.

    2014-01-01

    POTS (postural tachycardia syndrome) is a chronic form of OI (orthostatic intolerance). Neuropathic POTS is characterized by decreased adrenergic vasoconstriction, whereas hyperadrenergic POTS exhibits increased adrenergic vasoconstriction. We hypothesized that midodrine, an α1-adrenergic receptor agonist, would increase CVR (calf vascular resistance), decrease Cv (calf venous capacitance) and decrease orthostatic tachycardia in neuropathic POTS, but not alter haemodynamics in hyperadrenergic...

  3. Nurse’s knowledge of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Ali Yavuz Karahan

    2014-08-01

    Full Text Available The aim of our study was to determine the levels of information and awareness of the nurses who work on neuropathic pain in the departments of physical medicine and rehabilitation, neurology and neurosurgery. A total of 60 nurses (20 per each department who work in the physical medicine and rehabilitation, neurology and neurosurgery departments of Beyhekim State Hospital of Konya in Turkey took part in the study. The level of information and awareness of the nurses on neuropathic pain were assessed via a questionnaire prepared by specialists in the light of recent literature. The questionnaire was composed of 30 questions including the definition, symptoms, treatment and management of neuropathic pain. None of 60 nurses participating in the study were given any previous in-service training on neuropathic pain. According to the assessments, 80% of nurses (48 were found not to have sufficient knowledge about definition of neuropathic pain; 83.3% (50 about diseases causing neuropathic pain; 83.3% (50 about symptoms of neuropathic pain; and 90% (54 about management of neuropathic pain. The findings obtained from the nurses of these three departments showed no statistically significant relation. Our findings indicated that the knowledge of participants’ about neuropathic pain who work in these three departments seriously lack of information. Informing nurses about neuropathic pain during in-service training will be an important step towards improving the quality of services provided.

  4. Nurse’s Knowledge of Neuropathic Pain

    Science.gov (United States)

    Kucuksarac, Seher; Soran, Neslihan; Ordahan, Banu; Tekin, Levent; Basaran, Aynur

    2014-01-01

    The aim of our study was to determine the levels of information and awareness of the nurses who work on neuropathic pain in the departments of physical medicine and rehabilitation, neurology and neurosurgery. A total of 60 nurses (20 per each department) who work in the physical medicine and rehabilitation, neurology and neurosurgery departments of Beyhekim State Hospital of Konya in Turkey took part in the study. The level of information and awareness of the nurses on neuropathic pain were assessed via a questionnaire prepared by specialists in the light of recent literature. The questionnaire was composed of 30 questions including the definition, symptoms, treatment and management of neuropathic pain. None of 60 nurses participating in the study were given any previous in-service training on neuropathic pain. According to the assessments, 80% of nurses (48) were found not to have sufficient knowledge about definition of neuropathic pain; 83.3% (50) about diseases causing neuropathic pain; 83.3% (50) about symptoms of neuropathic pain; and 90% (54) about management of neuropathic pain. The findings obtained from the nurses of these three departments showed no statistically significant relation. Our findings indicated that the knowledge of participants’ about neuropathic pain who work in these three departments seriously lack of information. Informing nurses about neuropathic pain during in-service training will be an important step towards improving the quality of services provided. PMID:25309714

  5. In vitro study of the neuropathic potential of the organophosphorus compounds fenamiphos and profenofos: Comparison with mipafox and paraoxon.

    Science.gov (United States)

    Emerick, Guilherme L; Fernandes, Laís S; de Paula, Eloísa Silva; Barbosa, Fernando; dos Santos, Neife Aparecida Guinaim; dos Santos, Antonio Cardozo

    2015-08-01

    Organophosphorus-induced delayed neuropathy (OPIDN) is a central-peripheral distal axonopathy that develops 8-14 days after poisoning by a neuropathic organophosphorus compound (OP). Several OPs that caused OPIDN were withdrawn from the agricultural market due to induction of serious delayed effects. Therefore, the development of in vitro screenings able to differentiate neuropathic from non-neuropathic OPs is of crucial importance. Thus, the aim of this study was to evaluate the differences in the neurotoxic effects of mipafox (neuropathic OP) and paraoxon (non-neuropathic OP) in SH-SY5Y human neuroblastoma cells, using the inhibition and aging of neuropathy target esterase (NTE), inhibition of acetylcholinesterase (AChE), activation of calpain, neurite outgrowth, cytotoxicity and intracellular calcium as indicators. Additionally, the potential of fenamiphos and profenofos to cause acute and/or delayed effects was also evaluated. Mipafox had the lowest IC50 and induced the highest percentage of aging of NTE among the OPs evaluated. Only mipafox was able to cause calpain activation after 24 h of incubation. Concentrations of mipafox and fenamiphos which inhibited at least 70% of NTE were also able to reduce neurite outgrowth. Cytotoxicity was higher in non-neuropathic than in neuropathic OPs while the intracellular calcium levels were higher in neuropathic than in non-neuropathic OPs. In conclusion, the SH-SY5Y cellular model was selective to differentiate neuropathic from non-neuropathic OPs; fenamiphos, but not profenofos presented results compatible with the induction of OPIDN. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. R-flurbiprofen reduces neuropathic pain in rodents by restoring endogenous cannabinoids.

    Directory of Open Access Journals (Sweden)

    Philipp Bishay

    Full Text Available BACKGROUND: R-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear. METHODOLOGY/PRINCIPAL FINDINGS: We show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice. This is mediated by restoring the balance of endocannabinoids (eCB, which is disturbed following peripheral nerve injury in the DRGs, spinal cord and forebrain. The imbalance results from transcriptional adaptations of fatty acid amide hydrolase (FAAH and NAPE-phospholipase D, i.e. the major enzymes involved in anandamide metabolism and synthesis, respectively. R-flurbiprofen inhibits FAAH activity and normalizes NAPE-PLD expression. As a consequence, R-Flurbiprofen improves endogenous cannabinoid mediated effects, indicated by the reduction of glutamate release, increased activity of the anti-inflammatory transcription factor PPARgamma and attenuation of microglia activation. Antinociceptive effects are lost by combined inhibition of CB1 and CB2 receptors and partially abolished in CB1 receptor deficient mice. R-flurbiprofen does however not cause changes of core body temperature which is a typical indicator of central effects of cannabinoid-1 receptor agonists. CONCLUSION: Our results suggest that R-flurbiprofen improves the endogenous mechanisms to regain stability after axonal injury and to fend off chronic neuropathic pain by modulating the endocannabinoid system and thus constitutes an attractive, novel therapeutic agent in the treatment of chronic, intractable pain.

  7. Chronic at-level thermal hyperalgesia following rat cervical contusion spinal cord injury is accompanied by neuronal and astrocyte activation and loss of the astrocyte glutamate transporter, GLT1, in superficial dorsal horn.

    Science.gov (United States)

    Putatunda, Rajarshi; Hala, Tamara J; Chin, Jeannie; Lepore, Angelo C

    2014-09-18

    Neuropathic pain is a form of pathological nociception that occurs in a significant portion of traumatic spinal cord injury (SCI) patients, resulting in debilitating and often long-term physical and psychological burdens. While many peripheral and central mechanisms have been implicated in neuropathic pain, central sensitization of dorsal horn spinothalamic tract (STT) neurons is a major underlying substrate. Furthermore, dysregulation of extracellular glutamate homeostasis and chronic astrocyte activation play important underlying roles in persistent hyperexcitability of these superficial dorsal horn neurons. To date, central sensitization and astrocyte changes have not been characterized in cervical SCI-induced neuropathic pain models, despite the fact that a major portion of SCI patients suffer contusion trauma to cervical spinal cord. In this study, we have characterized 2 rat models of unilateral cervical contusion SCI that behaviorally result in chronic persistence of thermal hyperalgesia in the ipsilateral forepaw. In addition, we find that STT neurons are chronically activated in both models when compared to laminectomy-only uninjured rats. Finally, persistent astrocyte activation and significantly reduced expression of the major CNS glutamate transporter, GLT1, in superficial dorsal horn astrocytes are associated with both excitability changes in STT neurons and the neuropathic pain behavioral phenotype. In conclusion, we have characterized clinically-relevant rodent models of cervical contusion-induced neuropathic pain that result in chronic activation of both STT neurons and astrocytes, as well as compromise in astrocyte glutamate transporter expression. These models can be used as important tools to further study mechanisms underlying neuropathic pain post-SCI and to test potential therapeutic interventions. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Central sensitization and perceived indoor climate among workers with chronic upper-limb pain

    DEFF Research Database (Denmark)

    Sundstrup, Emil; Jakobsen, Markus D.; Brandt, Mikkel

    2015-01-01

    threshold (PPT) was measured in muscles of the arm, shoulder, and lower leg. Cross-sectional associations were determined using general linear models controlled for age, smoking, and job position. The number of indoor climate complaints was twice as high among workers with chronic pain compared with pain......Monitoring of indoor climate is an essential part of occupational health and safety. While questionnaires are commonly used for surveillance, not all workers may perceive an identical indoor climate similarly. The aim of this study was to evaluate perceived indoor climate among workers with chronic...... pain compared with pain-free colleagues and to determine the influence of central sensitization on this perception. Eighty-two male slaughterhouse workers, 49 with upper-limb chronic pain and 33 pain-free controls, replied to a questionnaire with 13 items of indoor climate complaints. Pressure pain...

  9. The paediatric neuropathic bladder

    African Journals Online (AJOL)

    A neurogenic bladder can be defined as a dysfunctinal urinary bladder caused by disease of the central nervous system or peripheral nerves involved in the control of micturition (urination). In pathophysiological terms, a neurogenic bladder is caused by a spinal reflex arc that occurs when the bladder becomes autonomous.

  10. Inflammatory mediators of neuropathic pain

    OpenAIRE

    Oliveira Júnior, José Oswaldo de; Portella Junior, Caio Sander Andrade; Cohen, Cláudia Panossian

    2016-01-01

    ABSTRACT BACKGROUND AND OBJECTIVES: Pro-inflammatory chemical mediators and algogenic substances seem to be confused by the sharing of their actions and by interactions in painful and inflammatory presentation. This study aimed at presenting a review of major inflammatory chemical mediators and place them in neuropathic pain pathophysiology. CONTENTS: Inflammation is the homeostatic response of vascularized tissues to remove harmful agents and restore their normal functions. Nervous system ...

  11. Has central sensitization become independent of nociceptive input in chronic pancreatitis patients who fail thoracoscopic splanchnicectomy?

    Science.gov (United States)

    Bouwense, Stefan A W; Buscher, Hessel C J L; van Goor, Harry; Wilder-Smith, Oliver H G

    2011-01-01

    Central sensitization due to visceral pancreatic nociceptive input may be important in chronic pancreatitis pain. We investigated whether bilateral thoracoscopic splanchnicectomy (BTS) to reduce nociceptive input in chronic pancreatitis patients (CPP) with poor pain control affects supraspinal and spinal sensitization. Seventeen CPP were studied preoperatively and 6 weeks after BTS. Pressure pain thresholds (PPT) were measured in clavicle and pancreatic dermatomes reflecting supraspinal and spinal central sensitization, respectively. Patients with increased PPT after BTS (hypoalgesic) were compared to those without (hyperalgesic) and PPT vs. pain numeric rating scale (NRS) changes compared. After BTS, ten patients showed C5 PPT increases (hypoalgesic; median change 87 kPa), 7 patients had unaltered/lower PPT (hyperalgesic; -135 kPa). Preoperative pain NRS was similar between groups (4 vs. 5, P = 0.2). After BTS hypoalgesic group NRS was lower (1 vs. 6; P = 0.008) and NRS change greater (-2 vs. 0; P = 0.005). Whole group NRS and C5 PPT change correlated significantly and negatively (r = 0.53; P central sensitization after BTS was associated with significantly reduced pain scores in a majority of CPP. A subgroup showed no reductions in supraspinal central sensitization after BTS, coupled to no significant pain NRS reduction. Our results suggest that a subgroup of CPP has altered pain processing that may be independent of ongoing peripheral nociceptive input, resulting in persisting pain despite BTS. If confirmed, these results indicate the importance of sensory testing for indications and management of pain treatments.

  12. Neuropathic pain among patients with primary knee osteoarthritis: Results of a cross-sectional study from a tertiary care center in Southern India

    Directory of Open Access Journals (Sweden)

    R Vignesh Narayan

    2017-01-01

    Conclusions: Neuropathic pain (DN4 ≥4 was seen in up to 49% patients with knee OA. Centrally acting drugs such as tricyclic antidepressants or duloxetine can be used to improve the quality of life and physical function of knee OA patients with neuropathic pain.

  13. PSD95 gene specific siRNAs attenuate neuropathic pain through modulating neuron sensibility and postsynaptic CaMKIIα phosphorylation.

    Science.gov (United States)

    Le, Shen; Xu, Li; Wen, Chen; Li, Xu; Wei, Liu; Xue-rong, Yu; Yu-guang, Huang

    2011-12-01

    To observe the effects of PSD95 gene specific siRNAs on neuropathic pain relief, neuron viability, and postsynaptic calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) phosphorylation in vitro and in vivo. Gene-specific siRNAs of rat PSD95 were synthesized chemically for transfection. Adult male Sprague-Dawley (SD) rats were randomly divided into 3 groups: naïve group (n=6), sham group (n=6), and sciatic nerve chronic constriction injury (CCI) group (n=24). The CCI group was further divided into 4 groups (n=6 in each group), which were pretreated with normal saline, transfection vehicle, negative control siRNAs, and PSD95 gene specific siRNAs respectively. All the subgroups received corresponding agents intrathecally for 3 days, started one day before the CCI of sciatic nerve. Both mechanical allodynia and thermal hyperalgesia were measured on post-operative day 3 and 7. PSD95 gene silenced NG108-15 cells were further stimulated by glutamate, with the cell viability and the expression/phosphorylation of CaMKIIα measured by MTT cell proliferation assay and Western blot, respectively. The siRNAs decreased PSD95 mRNA level significantly both in vivo and in vitro. Neuropathic pain rats pretreated with PSD95 gene specific siRNAs exhibited significant elevation in the mechanical withdrawal threshold and paw withdrawal thermal latency, without affecting the baseline nociception. PSD95 gene silencing enhanced neuronal tolerance against the glutamate excitotoxicity, meanwhile the phosphorylation of CaMKIIα Thr286 was attenuated. Pre-emptive administration of PSD95 gene specific siRNAs may attenuate the central sensitization CaMKIIα-related signaling cascades, leading to the relief of neuropathic pain.

  14. Update on uncertain etiology of chronic kidney disease in Sri Lanka's north-central dry zone.

    Science.gov (United States)

    Wanigasuriya, Kamani

    2014-04-01

    This manuscript updates a review previously published in a local journal in 2012, about a new form of chronic kidney disease that has emerged over the past two decades in the north-central dry zone of Sri Lanka, where the underlying causes remain undetermined. Disease burden is higher in this area, particularly North Central Province, and affects a rural and disadvantaged population involved in rice-paddy farming. Over the last decade several studies have been carried out to estimate prevalence and identify determinants of this chronic kidney disease of uncertain etiology. Summarize the available evidence on prevalence, clinical profile and risk factors of chronic kidney disease of uncertain etiology in the north-central region of Sri Lanka. PubMed search located 16 manuscripts published in peer-reviewed journals. Three peer-reviewed abstracts of presentations at national scientific conferences were also included in the review. Disease prevalence was 5.1%-16.9% with more severe disease seen in men than in women. Patients with mild to moderate stages of disease were asymptomatic or had nonspecific symptoms; urinary sediments were bland; 24-hour urine protein excretion was urine, and mycotoxins detected in foods were below maximum statutory limits. Calcium-bicarbonate-type water with high levels of fluoride was predominant in endemic regions. Significantly high levels of cadmium in urine of cases compared to controls, as well as the disease's dose-related response to these levels, has drawn attention to this element as a possible contributing factor. Familial clustering of patients is suggestive of a polygenic inheritance pattern comparable to that associated with diseases of multifactorial etiology. Available data suggest that chronic kidney disease of uncertain etiology is an environmentally acquired disease, but to date no definitive causal factor has been identified. Geographic distribution and research findings suggest a multifactorial etiology.

  15. Role of the spinal cord NR2B-containing NMDA receptors in the development of neuropathic pain.

    Science.gov (United States)

    Qu, Xiao-Xiu; Cai, Jie; Li, Ming-Jia; Chi, Ye-Nan; Liao, Fei-Fei; Liu, Feng-Yu; Wan, You; Han, Ji-Sheng; Xing, Guo-Gang

    2009-02-01

    Activation of N-methyl-d-aspartate (NMDA) receptors in the spinal dorsal horn has been shown to be essential for the initiation of central sensitization and the hyperexcitability of dorsal horn neurons in chronic pain. However, whether the spinal NR2B-containing NMDA (NMDA-2B) receptors are involved still remains largely unclear. Using behavioral test and in vivo extracellular electrophysiological recording in L5 spinal nerve-ligated (SNL) neuropathic rats, we investigate the roles of spinal cord NMDA-2B receptors in the development of neuropathic pain. Our study showed that intrathecal (i.t.) injection of Ro 25-6981, a selective NMDA-2B receptor antagonist, had a dose-dependent anti-allodynic effect without causing motor dysfunction. Furthermore, i.t. application of another NMDA-2B receptor antagonist ifenprodil prior to SNL also significantly inhibited the mechanical allodynia but not the thermal hyperalgesia. These data suggest that NMDA-2B receptors at the spinal cord level play an important role in the development of neuropathic pain, especially at the early stage following nerve injury. In addition, spinal administration of Ro 25-6981 not only had a dose-dependent inhibitory effect on the C-fiber responses of dorsal horn wide dynamic range (WDR) neurons in both normal and SNL rats, but also significantly inhibited the long-term potentiation (LTP) in the C-fiber responses of WDR neurons induced by high-frequency stimulation (HFS) applied to the sciatic nerve. These results indicate that activation of the dorsal horn NMDA-2B receptors may be crucial for the spinal nociceptive synaptic transmission and for the development of long-lasting spinal hyperexcitability following nerve injury. In conclusion, the spinal cord NMDA-2B receptors play a role in the development of central sensitization and neuropathic pain via the induction of LTP in dorsal horn nociceptive synaptic transmission. Therefore, the spinal cord NMDA-2B receptor is likely to be a target for

  16. Upregulation of Nuclear Factor of Activated T-Cells by Nerve Injury Contributes to Development of Neuropathic Pain

    OpenAIRE

    Cai, You-Qing; Chen, Shao-Rui; Pan, Hui-Lin

    2013-01-01

    Nerve injury induces long-term changes in gene expression in the nociceptive circuitry and can lead to chronic neuropathic pain. However, the transcriptional mechanism involved in neuropathic pain is poorly understood. Nuclear factor of activated T-cells (NFATc) is a transcriptional factor regulated by the Ca2+-dependent protein phosphatase calcineurin. In this study, we determined nerve injury–induced changes in the expression of NFATc1–c4 in the dorsal root ganglia (DRG) and spinal cords an...

  17. Peroxisome Proliferator-Activated Receptor Agonists Modulate Neuropathic Pain: a Link to Chemokines?

    Directory of Open Access Journals (Sweden)

    Caroline eFreitag

    2014-08-01

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

  18. Topical analgesics for neuropathic pain: preclinical exploration, clinical validation, future development.

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    Sawynok, J

    2014-04-01

    Topical analgesics applied locally to skin or to specialized compartments modify pain by actions on sensory nerve endings and/or adjacent cellular elements. With this approach, there are low systemic drug levels, good tolerability and few drug interactions, and combination with oral formulations is feasible. The goal of this review is to provide an overview of the potential for topical analgesics to contribute to improved management of neuropathic pain. Mechanistic and preclinical studies indicate much potential for development of novel topical analgesics for neuropathic pain. In humans, two topical analgesics are approved for use in post-herpetic neuralgia (lidocaine 5% medicated plaster, capsaicin 8% patch), and there is evidence for efficacy in other neuropathic pain conditions. Comparative trials indicate similar efficacy between topical and oral analgesics. Not all individuals respond to topical analgesics, and there is interest in determining factors (patient factors, sensory characteristics) which might predict responsiveness to topical analgesics. There is a growing number of controlled trials and case reports of investigational agents (vasodilators, glutamate receptor antagonists, α2-adrenoreceptor agonists, antidepressants, centrally acting drugs), including combinations of several agents, indicating these produce pain relief in neuropathic pain. There is interest in compounding topical analgesics for neuropathic pain, but several challenges remain for this approach. Topical analgesics have the potential to be a valuable additional approach for the management of neuropathic pain. © 2013 European Pain Federation - EFIC®

  19. Neuropathic Pain Medication Use Does Not Alter Outcomes of Spinal Cord Stimulation for Lower Extremity Pain.

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    Maher, Dermot P; Martins, Yuri Chaves; Doshi, Tina; Bicket, Mark; Zhang, Kui; Hanna, George; Ahmed, Shihab

    2018-01-01

    Spinal cord stimulation (SCS) for the treatment of lower extremity pain is believed to the result of increased activity in the descending inhibitory and decreased activity in the ascending excitatory tracts. Evidence suggests that the analgesia afforded by SCS may be altered using certain neuropathic pain medications that also modulate neurotransmitters in these sensory tracts. We hypothesize that neuropathic pain medications may alter the response to SCS therapy. One hundred and fifteen subjects undergoing SCS therapy for lower extremity pain were retrospectively examined. The pharmacologic profile, including stable use of neuropathic and opioid medications, were recorded. Three separate logistic regression models examined the odds ratio of primary outcomes; a successful SCS trial, a 50% decrease in pain or a 50% reduction in opioid use one year after implant. Neither the use of opioids or neuropathic pain medications were associated with changes in the odds of a successful SCS trial or a 50% pain reduction. A higher dose of chronic opioids use prior to a trial was associated with greater odds of having a 50% reduction in opioid use following implant. OR 1.02, 95% CI 1.01-1.02, p-value neuropathic pain medications did not change the odds of either a successful SCS trial, or of experiencing a 50% reduction in pain at one year. The association between higher opioid doses and greater odds of a 50% reduction in opioid use may be the reflective of SCS's ability to reduce opioid reliance in chronic pain patients. © 2017 International Neuromodulation Society.

  20. Chronic central serous choroidopathy with severe visual loss in hyperopic microphthalmic identical twins

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    Fabry, Annelies

    2011-01-01

    Full Text Available Objective: To report chronic central serous choroidopathy with severe visual loss in hyperopic microphthalmic identical twins. Methods: The index patient was first examined in 1994, at age 31, and has been followed up closely for 17 years. He had repeated fluorescein and indocyanine green angiograms, OCT, ultrasound biometry, and recently also autofluorescence and EDI OCT. His twin brother was first examined in 2010, at age 47, and had a similar extensive exploration. Results: The index patient had a mean refractive error of +6 D OU and VA was 20/32++ in the RE and 20/200 in the LE in 1994. Vision slowly went down to 20/800+ in the RE and 20/600 in the LE in 2011. His twin brother has a mean refractive error of +6 D OU and VA 20/400 OU. Both have a short axial length of the eye, a thick choroid with dilated vessels, and central serous choroidopathy with cystic degeneration of the macula and retina in the posterior pole. Conclusions: We add to the reported complications of microphthalmos, chronic central serous choroidopathy.

  1. ADX71943 and ADX71441, novel positive allosteric modulators of the GABABreceptor with distinct central/peripheral profiles, show efficacy in the monosodium iodoacetate model of chronic osteoarthritis pain in the rat.

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    Kalinichev, Mikhail; Donovan-Rodriguez, Tansy; Girard, Françoise; Haddouk, Hasnaá; Royer-Urios, Isabelle; Schneider, Manfred; Bate, Simon T; Marker, Cheryl; Pomonis, James D; Poli, Sonia

    2017-01-15

    We tested novel positive allosteric modulators (PAMs) of the γ-aminobutyric acid receptor B (GABA B ), ADX71943 and ADX71441in the monosodium iodoacetate model of chronic osteoarthritis pain in rats with the objective to delineate the role of peripheral versus central GABA B receptor populations in modulation of chronic pain. Anesthetized Sprague-Dawley rats received an injection of monosodium iodoacetate into the knee and were tested for hyperalgesia starting post-MIA day 14. Effects of compounds on ipsilateral joint compression threshold were evaluated on post-MIA day 14 (after acute treatment), as well as after repeated, daily treatment on days 21 and 28 (ADX71943 only) and were compared to those of celecoxib (30mg/kg, p.o.). The PAMs were also tested in the rat rotarod test for potential muscle-relaxant effects. Acutely, ADX71943 (1-30mg/kg, p.o.), the peripherally restricted PAM, resulted in similar increases in pain threshold across the doses on day 14, while showing reduced efficacy on day 21 and no efficacy on day 28. A clear reduction in the efficacy of celecoxib across testing was also noted in this experiment. Acutely ADX71441 (0.3-15mg/kg, p.o.), the central-peripheral PAM, resulted in over 2-fold increases in pain threshold at 15mg/kg (but not at lower doses) on day 14, while causing more modest effects on day 21. Celecoxib increased pain threshold after both acute and daily treatment, showing overall similar efficacy. Thus, early, presumably more inflammatory phase of osteoarthritis pain in more sensitive to GABA B PAMs with peripherally restricted profile, while later, presumably more neuropathic phase is more sensitive to PAMs with central-peripheral profile. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Lamotrigine for acute and chronic pain

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    Wiffen, Philip J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background This is an update of the original Cochrane review published in Issue 2, 2007. Some antiepileptic medicines have a place in the treatment of neuropathic pain (pain due to nerve damage). This updated review adds five new additional studies looking at evidence for Lamotrigine as an effective treatment for acute and chronic pain. Objectives To assess analgesic efficacy and adverse effects of the antiepileptic drug lamotrigine in acute and chronic pain. Search methods Randomised controlled trials (RCTs) of lamotrigine in acute, and chronic pain (including cancer pain) were identified from MEDLINE, EMBASE and CENTRAL up to January 2011. Additional studies were sought from the reference list of the retrieved papers. Selection criteria RCTs investigating the use of lamotrigine (any dose, by any route, and for any study duration) for the treatment of acute or chronic pain. Assessment of pain intensity or pain relief, or both, using validated scales. Participants were adults aged 18 and over. Only full journal publication articles were included. Data collection and analysis Dichotomous data (ideally for the outcome of at least 50% pain relief) were used to calculate relative risk with 95% confidence intervals. Meta-analysis was undertaken using a fixed-effect model. Numbers needed to treat to benefit (NNTs) were calculated as the reciprocal of the absolute risk reduction. For unwanted effects, the NNT becomes the number needed to harm (NNH) and was calculated. Main results Twelve included studies in 11 publications (1511 participants), all with chronic neuropathic pain: central post stroke pain (1), chemotherapy induced neuropathic pain (1), diabetic neuropathy (4), HIV related neuropathy (2), mixed neuropathic pain (2), spinal cord injury related pain (1), and trigeminal neuralgia (1); none investigated lamotrigine in acute pain. The update had five additional studies (1111 additional participants). Participants were aged between 26 and 77 years. Study duration

  3. Spinal SIRT1 activation attenuates neuropathic pain in mice.

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    Haijun Shao

    Full Text Available Abnormal histone acetylation occurs during neuropathic pain through an epigenetic mechanism. Silent information regulator 1 (sir2 or SIRT1, a NAD-dependent deacetylase, plays complex systemic roles in a variety of processes through deacetylating acetylated histone and other specific substrates. But the role of SIRT1 in neuropathic pain is not well established yet. The present study was intended to detect SIRT1 content and activity, nicotinamide (NAM and nicotinamide adenine dinucleotide (NAD in the spinal cord using immunoblotting or mass spectroscopy over time in mice following chronic constriction injury (CCI or sham surgery. In addition, the effect of intrathecal injection of NAD or resveratrol on thermal hyperalgesia and mechanical allodynia was evaluated in CCI mice. Finally, we investigated whether SIRT1 inhibitor EX-527 could reverse the anti-nociceptive effect of NAD or resveratrol. It was found that spinal SIRT1 expression, deacetylase activity and NAD/NAM decreased significantly 1, 3, 7, 14 and 21 days after CCI surgery as compared with sham group. In addition, daily intrathecal injection of 5 µl 800 mM NAD 1 h before and 1 day after CCI surgery or single intrathecal injection of 5 µl 90 mM resveratrol 1 h before CCI surgery produced a transient inhibitory effect on thermal hyperalgesia and mechanical allodynia in CCI mice. Finally, an intrathecal injection of 5 µl 1.2 mM EX-527 1 h before NAD or resveratrol administration reversed the anti-nociceptive effect of NAD or resveratrol. These data indicate that the reduction in SIRT1 deacetylase activity may be a factor contributing to the development of neuropathic pain in CCI mice. Our findings suggest that the enhancement of spinal NAD/NAM and/or SIRT1 activity may be a potentially promising strategy for the prevention or treatment of neuropathic pain.

  4. Multiple spots of photodynamic therapy for the treatment of severe chronic central serous chorioretinopathy

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    Tsakonas GD

    2012-10-01

    Full Text Available George D Tsakonas, Athanasios I Kotsolis, Chrysanthi Koutsandrea, Ilias Georgalas, Dimitrios Papakonstantinou, Ioannis D LadasFirst Department of Ophthalmology, Medical School of Athens University, Athens, GreecePurpose: To evaluate the efficacy and safety of fluorescein angiography (FA-guided photodynamic therapy (PDT for the treatment of severe chronic central serous chorioretinopathy (CSC.Methods: Patients presenting with chronic CSC with multiple areas of retinal pigment epithelium decompensation, with or without focal leaks, were treated with FA-guided full-fluence PDT. Best-corrected visual acuity (BCVA, optical coherence tomography (OCT, FA, indocyanine green angiography, and fundus autofluorescence were used to determine functional and anatomic outcomes.Results: Twenty-one eyes (17 patients were treated with PDT and followed for a median of 24 months (range, 12–73. In fourteen eyes (66.66%, two PDT spots were performed within the same session. In three eyes (14.28%, three PDT spots were performed, in two eyes (9.52% four spots, and in two eyes (9.52% five spots. In 17 eyes (80.95%, the leakage in FA and the subretinal fluid in OCT disappeared after only one session of PDT. In four eyes (19.05%, a second session – with only one spot – of PDT was required due to persistent or recurrent leakage and subfoveal SRF. Median BCVA improved significantly from 20/63 at baseline to 20/40 at 3 months (P = 0.0002 and 20/32 at 6 months (P < 0.0001, and remained improved until the last examination (20/25, P < 0.0001. Two patients complained of a transient central scotoma after the treatment.Conclusion: FA-guided full-fluence PDT with multiple PDT spots within the same session seems to be effective and safe for the treatment of chronic CSC cases with multiple areas of retinal pigment epithelium decompensation.Keywords: central serous chorioretinopathy, photodynamic therapy

  5. An Intensive Locomotor Training Paradigm Improves Neuropathic Pain following Spinal Cord Compression Injury in Rats.

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    Dugan, Elizabeth A; Sagen, Jacqueline

    2015-05-01

    Spinal cord injury (SCI) is often associated with both locomotor deficits and sensory dysfunction, including debilitating neuropathic pain. Unfortunately, current conventional pharmacological, physiological, or psychological treatments provide only marginal relief for more than two-thirds of patients, highlighting the need for improved treatment options. Locomotor training is often prescribed as an adjunct therapy for peripheral neuropathic pain but is rarely used to treat central neuropathic pain. The goal of this study was to evaluate the potential anti-nociceptive benefits of intensive locomotor training (ILT) on neuropathic pain consequent to traumatic SCI. Using a rodent SCI model for central neuropathic pain, ILT was initiated either 5 d after injury prior to development of neuropathic pain symptoms (the "prevention" group) or delayed until pain symptoms fully developed (∼3 weeks post-injury, the "reversal" group). The training protocol consisted of 5 d/week of a ramping protocol that started with 11 m/min for 5 min and increased in speed (+1 m/min/week) and time (1-4 minutes/week) to a maximum of two 20-min sessions/d at 15 m/min by the fourth week of training. ILT prevented and reversed the development of heat hyperalgesia and cold allodynia, as well as reversed developed tactile allodynia, suggesting analgesic benefits not seen with moderate levels of locomotor training. Further, the analgesic benefits of ILT persisted for several weeks once training had been stopped. The unique ability of an ILT protocol to produce robust and sustained anti-nociceptive effects, as assessed by three distinct outcome measures for below-level SCI neuropathic pain, suggests that this adjunct therapeutic approach has great promise in a comprehensive treatment strategy for SCI pain.

  6. Dynamics of circadian thalamocortical flow of information during a peripheral neuropathic pain condition

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    Helder eCardoso-Cruz

    2011-08-01

    Full Text Available It is known that the thalamocortical loop plays a crucial role in the encoding of sensory-discriminative features of painful stimuli. However, only a few studies have addressed the changes in thalamocortical dynamics that may occur after the onset of chronic pain. Our goal was to evaluate how the induction of chronic neuropathic pain affected the flow of information within the thalamocortical loop throughout the brain states of the sleep-wake cycle. To address this issue we recorded local field potentials – LFPs – both before and after the establishment of neuropathic pain in awake freely moving adult rats chronically implanted with arrays of multielectrodes in the lateral thalamus and primary somatosensory cortex. Our results show that the neuropathic injury induced changes in the number of wake and slow-wave-sleep state episodes, and especially in the total number of transitions between brain states. Moreover, partial directed coherence – PDC – analysis revealed that the amount of information flow between cortex and thalamus in neuropathic animals decreased significantly, indicating that the overall thalamic activity had less weight over the cortical activity. However, thalamocortical LFPs displayed higher phase-locking during awake and slow-wave-sleep episodes after the nerve lesion, suggesting faster transmission of relevant information along the thalamocortical loop. The observed changes are in agreement with the hypothesis of thalamic dysfunction after the onset of chronic pain, and may result from diminished inhibitory effect of the primary somatosensory cortex over the lateral thalamus.

  7. Identification of patients with neuropathic pain using electronic primary care records

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    Camille Gajria

    2011-05-01

    Conclusion Computerised health records offer an excellent opportunity to improve the identification of patients for clinical research in complex conditions like chronic neuropathic pain. To make full use of data from these records, standardisation of clinical coding and consensus on diagnostic criteria are needed.

  8. Neuropathic pain in spinal cord injury.

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    Nakipoglu-Yuzer, Guidal F; Atçı, Nermin; Ozgirgin, Nese

    2013-01-01

    Several studies have described pain prevalence, risk factors, pain and medical variables in spinal cord injury (SCI) populations. In this study on traumatic SCI in Turkey, we surveyed the neuropathic pain experiences during in-patient rehabilitation and defined the relationships between neuropathic pain and demographic and SCI characteristics of patients. To survey the neuropathic pain experiences during in-patient rehabilitation in traumatic SCI and to define the relationships between neuropathic pain and demographic and SCI-related characteristics of patients. Descriptive study. Physicial Medicine and Rehabilitation inpatient clinic, Ankara, Turkey Sixty-nine SCI patients as inpatients were included in this descriptive study. All patients demographic and SCI-related characteristics were enrolled. The diagnosis of neuropathic pain was made with the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale. Location of pain and pain description, relation to time and severity according to McGill Pain Questionnaire (MPQ) were enrolled. The neuropathic pain localization was below the lesion level in 67 (97.1%) and at the lesion level in 2 (2.9%) patients. The pain was at the hip and leg regions in 36 (52.2%) patients. The neuropathic pain was defined as burning in 27 (39.1%), aching in 26 (37.7%), sharp in 4 (5.8%), stinging in 3 (4.3%), and cramping in 3 (4.3%). We did not find a significant difference between demographic and SCI-related characteristics and the localization of neuropathic pain for the patients (P > 0.05). There was no significant difference according to pain description by MPQ and pain localization (P > 0.05). We found a significant relationship between the patient's lesion level and the region of pain (P neuropathic pain due to SCI to be mostly below the lesion level with a burning or aching character and we did not find a significant relationship between the demographic and SCI-related characteristics of the patient and the pain

  9. [Toothache with a neuropathic background].

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    Khatchaturian, V; de Wijer, A; Kalaykova, S I; Steenks, M H

    2015-03-01

    A 48-year old woman in good general health was referred to the orofacial pain clinic in a centre for special dentistry with a toothache in the premolar region of the left maxillary quadrant. The complaints had existed for 15 years and various dental treatments, including endodontic treatments, apical surgery, extraction and splint therapy, had not helped to alleviate the complaints. As a result of the fact that anti-epileptic drugs were able to reduce the pain it was concluded that this 'toothache' satisfied the criteria of an atypical odontalgia: 'toothache' with a neuropathic background.

  10. Caloric Vestibular Stimulation Reduces Pain and Somatoparaphrenia in a Severe Chronic Central Post-Stroke Pain Patient: A Case Study.

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    Grazia Fernanda Spitoni

    Full Text Available Central post-stroke pain is a neuropathic syndrome characterized by intolerable contralesional pain and, in rare cases, somatic delusions. To date, there is limited evidence for the effective treatments of this disease. Here we used caloric vestibular stimulation to reduce pain and somatoparaphrenia in a 57-year-old woman suffering from central post-stroke pain. Resting-state functional magnetic resonance imaging was used to assess the neurological effects of this treatment. Following vestibular stimulation we observed impressive improvements in motor skills, pain, and somatic delusions. In the functional connectivity study before the vestibular stimulation, we observed differences in the patient's left thalamus functional connectivity, with respect to the thalamus connectivity of a control group (N = 20, in the bilateral cingulate cortex and left insula. After the caloric stimulation, the left thalamus functional connectivity with these regions, which are known to be involved in the cortical response to pain, disappeared as in the control group. The beneficial use of vestibular stimulation in the reduction of pain and somatic delusion in a CPSP patient is now documented by behavioral and imaging data. This evidence can be applied to theoretical models of pain and body delusions.

  11. Photodynamic therapy combined with antivascular endothelial growth factor treatment for recalcitrant chronic central serous chorioretinopathy

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    Asahi MG

    2017-11-01

    Full Text Available Masumi G Asahi,1 Andrew T Chon,1 Esmeralda Gallemore,1 Ron P Gallemore1,2 1Clinical Research Department, Retina Macula Institute, Torrance, CA, USA; 2Jules Stein Eye Institute, University of California, Los Angeles, CA, USA Purpose: To determine whether combination photodynamic therapy (PDT and antivascular endothelial growth factor (VEGF therapy is effective in the management of chronic central serous chorioretinopathy (CSC recalcitrant to conventional therapy. Methods: This was a retrospective analysis of eight patients with chronic CSC unresponsive to topical nonsteroidal anti-inflammatory drugs, focal photocoagulation, anti-VEGF alone, or PDT alone. All patients were evaluated with a full ophthalmic examination, spectral-domain optical coherence tomography (OCT, fluorescein angiography (FA, and most with indocyanine green angiography (ICGA followed by treatment with half-fluence PDT and intravitreal anti-VEGF injection (seven bevacizumab, one aflibercept. Patients were seen in follow-up 1 month after treatment. Results: All eight patients achieved complete resolution in subretinal fluid following combination treatment. Average duration of CSC prior to initiation of combination therapy was 7.5 months. Mean central macular thickness on OCT decreased significantly from 401.2±52.7 µm to 297.9±18.2 µm (p=0.0010 by 4 months after treatment (1.63±1.18 months. Seven of eight patients were followed up for an average of 13 months with no recurrence during that time. One case recurred at 8 months and was treated with repeat combination at that time. Frank choroidal neovascularization (CNV was not identified in these cases on FA or ICGA studies. Eight of eight patients showed significant improvement in vision from a logMAR of 0.1125±0.099 to 0.0125±0.064 (p=0.019. Conclusion: Combination PDT and anti-VEGF is effective for chronic CSC which has failed conventional therapy. Associated CNV and/or inflammation may be reasons for greater success in

  12. The chronically inflamed central nervous system provides niches for long-lived plasma cells.

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    Pollok, Karolin; Mothes, Ronja; Ulbricht, Carolin; Liebheit, Alina; Gerken, Jan David; Uhlmann, Sylvia; Paul, Friedemann; Niesner, Raluca; Radbruch, Helena; Hauser, Anja Erika

    2017-11-25

    Although oligoclonal bands in the cerebrospinal fluid have been a hallmark of multiple sclerosis diagnosis for over three decades, the role of antibody-secreting cells in multiple sclerosis remains unclear. T and B cells are critical for multiple sclerosis pathogenesis, but increasing evidence suggests that plasma cells also contribute, through secretion of autoantibodies. Long-lived plasma cells are known to drive various chronic inflammatory conditions as e.g. systemic lupus erythematosus, however, to what extent they are present in autoimmune central nervous system inflammation has not yet been investigated. In brain biopsies from multiple sclerosis patients and other neurological diseases, we could detect non-proliferating plasma cells (CD138 + Ki67 - ) in the parenchyma. Based on this finding, we hypothesized that long-lived plasma cells can persist in the central nervous system (CNS). In order to test this hypothesis, we adapted the multiple sclerosis mouse model experimental autoimmune encephalomyelitis to generate a B cell memory response. Plasma cells were found in the meninges and the parenchyma of the inflamed spinal cord, surrounded by tissue areas resembling survival niches for these cells, characterized by an up-regulation of chemokines (CXCL12), adhesion molecules (VCAM-1) and survival factors (APRIL and BAFF). In order to determine the lifetime of plasma cells in the chronically inflamed CNS, we labeled the DNA of proliferating cells with 5-ethynyl-2'-deoxyuridine (EdU). Up to five weeks later, we could detect EdU + long-lived plasma cells in the murine CNS. To our knowledge, this is the first study describing non-proliferating plasma cells directly in the target tissue of a chronic inflammation in humans, as well as the first evidence demonstrating the ability of plasma cells to persist in the CNS, and the ability of the chronically inflamed CNS tissue to promote this persistence. Hence, our results suggest that the CNS provides survival niches for

  13. Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling

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    Enrique J. Cobos

    2018-01-01

    Full Text Available Chronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia in a model of partial nerve injury, and this temporal divergence was associated with major differences in global gene expression in innervating dorsal root ganglia. Transcripts whose expression change correlates with the onset of cold allodynia were nociceptor related, whereas those correlating with tactile hypersensitivity were immune cell centric. Ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity, whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain incorporates reactive processes of sensory neurons and immune cells, each leading to distinct forms of hypersensitivity, potentially allowing drug development targeted to each pain type.

  14. A novel use for testosterone to treat central sensitization of chronic pain in fibromyalgia patients.

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    White, Hillary D; Robinson, Thomas D

    2015-08-01

    Fibromyalgia is a diffuse chronic pain condition that occurs predominantly in women and may be under-reported in men. Symptoms include a loss of feeling of well-being and generalized widespread flu-like muscle aches and pain that fail to resolve due to central sensitization of nociceptive neurons. It has commonalities with a myriad of other chronic pain conditions which include PTSD, "Gulf War Syndrome", and various stress-induced conditions caused, for example, by viral infection, emotional or physical stress, trauma, combat, accident or surgery. It is not understood why some individuals are susceptible to this condition and others are not. White et al., elsewhere in this issue, present a clinical feasibility study designed to test the hypothesis that 1) low or deficient testosterone serum levels are linked to a high risk for an inflamed nociceptive nervous system and resultant chronic pain states, and 2) a testosterone transdermal gel applied once a day by fibromyalgia patients can be an effective therapeutic against chronic pain. Here, a short profile of fibromyalgia is provided along with a brief summary of best practices currently recommended by clinical specialists. The link between testosterone and pain is then discussed, with an overview of scientific studies that lay the foundation for testosterone as a possible important additional therapeutic that has the potential to be safely administered and effective but also avoid the adverse effects of other therapeutics. Finally, novel mechanisms by which testosterone therapy is likely to down-modulate pain signaling are proposed. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  15. The neurosurgical treatment of neuropathic facial pain.

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    Brown, Jeffrey A

    2014-04-01

    This article reviews the definition, etiology and evaluation, and medical and neurosurgical treatment of neuropathic facial pain. A neuropathic origin for facial pain should be considered when evaluating a patient for rhinologic surgery because of complaints of facial pain. Neuropathic facial pain is caused by vascular compression of the trigeminal nerve in the prepontine cistern and is characterized by an intermittent prickling or stabbing component or a constant burning, searing pain. Medical treatment consists of anticonvulsant medication. Neurosurgical treatment may require microvascular decompression of the trigeminal nerve. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Central sensitization in urogynecological chronic pelvic pain: a systematic literature review.

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    Kaya, Serap; Hermans, Linda; Willems, Tine; Roussel, Nathalie; Meeus, Mira

    2013-01-01

    Chronic pelvic pain (CPP) is a complex pain syndrome. Since its pathogenesis is still poorly understood and structural alterations in pain related brain regions may be present, there is a greater acceptance that sensitization of the central nervous system (CNS) plays an important role in the development and maintenance of chronicity. The purpose of this study is to systematically review the scientific evidence regarding central sensitization (CS) in female patients with urogynecological CPP. Systematic review of the literature. A systematic literature search was conducted in PubMed and Web of Science using different keyword combinations related to urogynecological CPP and central sensitization. Full text clinical reports addressing CS in adult women with urogynecological CPP were included and assessed for methodological quality by 2 independent reviewers. After screening for the eligibility, a total of 29 full-text articles with low to good methodological quality were retained. All studies were observational, 27 of which were case-control and 2 of which were cohorts. Sensitivity of the CNS was investigated by using a variety of methods. Although different central mechanisms seem to be involved in pain processing, the present evidence suggests hyperexcitability of the CNS in patients with urogynecological CPP. Altered brain morphology and function, generalized hyperalgesia to different type of stimuli, overactive bottom-up nociceptive mechanisms, and autonomic dysregulation were established in patients with urogynecological CPP. Nevertheless, diffuse noxious inhibitory control seemed normal, and therefore the contribution of an impaired endogenous pain inhibition mechanism to CPP requires further study. The same goes for the contribution of psychological factors. The level of evidence of retained studies is low due to the observational study designs and a wide range of diagnoses and assessment methods. Although the majority of the literature provides evidence for

  17. Central Sensitization in Functional Chronic Pain Syndromes: Overview and Clinical Application.

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    Bettini, Liz; Moore, Ki

    2016-10-01

    The purpose of this review and clinical application article is to offer nurses up-to-date knowledge on peripheral and central sensitization in chronic functional pain syndromes, and to discuss therapies that have shown efficacy in treating various aspects of these disorders. Central sensitization is a result of changes in the peripheral and central nervous system due to noxious stimuli, such as illness or trauma. Once these changes occur, treatment for the associated syndromes requires a multimodal approach that includes behavioral pain psychology, physical therapy, and pharmacological agents that specifically target neuroinflammation, pain modulation, and amplification of pain pathways. More research needs to be conducted on the basis and patient perception of functional pain syndromes to reduce the morbidity and significant disability associated with these illnesses. Nurses have the opportunity to be at the forefront of this research because of their holistic and multidimensional approach to patient care, assessment, and symptom management. Copyright © 2016 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  18. Prevalence, Causes, and Treatment of Neuropathic Pain in Dutch Nursing Home Residents : A Retrospective Chart Review

    NARCIS (Netherlands)

    van Kollenburg, Esther G. P.; Lavrijsen, Jan C. M.; Verhagen, Stans C.; Zuidema, Sytse U.; Schalkwijk, Annelies; Vissers, Kris C. P.

    Objectives To identify the prevalence and causes of neuropathic pain in Dutch nursing home residents; to establish the prevalence of painful and nonpainful diabetic polyneuropathy in a subsample of individuals with diabetes mellitus and central poststroke pain (CPSP) in a subsample of individuals

  19. PHARMACOTHERAPY IN ELDERLY NEUROPATHIC PAIN

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    Thomas Eko P

    2013-10-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 The incidence of pain increases with age. Neuropathic pain are common in elderly patients and pose challenges in both their diagnosis and treatment. The most common neuropathic pain in elderly are radiculopathy due to foraminal or spinal stenosis, diabetic neuropathy, and postherpetic neuralgia. Pain in the elderly is often unrecognized and undertreated. The main problem with pain in older adults relates to impaired quality of life secondary to pain which may be expressed by depression (including increased suicide risk, anxiety, sleep disruption, appetite disturbance, and weight loss, cognitive impairment, and limitations in the performance of daily activities. Pain management in elderly patients requires a different perspective from that of younger patients. Causes, comorbidities, and responses to both pain and its treatment differ between young healthy and older patients. Effective pain management in elderly patients should include both pharmacologic and nonpharmacologic strategies. Pharmacological approaches are the first line of pain management in older person for neuropathic pain. Pharmacologic strategies call for administration of nonopioid analgesics, opioid analgesics, and adjuvant medication. Polypharmacy, drug-drug and drug-disease interactions, age-associated changes in drug metabolism, and the high frequency of adverse drug reactions need to be carefully considered in using medications in this population /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso

  20. How to diagnose neuropathic pain? The contribution from clinical examination, pain questionnaires and diagnostic tests.

    Science.gov (United States)

    La Cesa, S; Tamburin, S; Tugnoli, V; Sandrini, G; Paolucci, S; Lacerenza, M; Marchettini, P; Cruccu, G; Truini, A

    2015-12-01

    Patients with peripheral and central nervous system diseases may suffer from different types of pain, namely nociceptive, neuropathic and mixed pain. Although in some cases, the distinction between these types of pain is clinically evident, yet in some patients an accurate differential diagnosis requires dedicated clinical examination, screening questionnaires and diagnostic techniques some of which are available only in specialized pain centres. This review briefly addresses the currently agreed definitions of the different types of pain and shows how clinical examination, pain questionnaires and diagnostic tests can help the clinicians in identifying neuropathic pain.

  1. Hindfoot Arthrodesis for Neuropathic Deformity

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    Peng-Ju Huang

    2007-03-01

    Full Text Available Acquired neurologic disorders of the foot lead to arthrosis, deformities, instabilities, and functional disabilities. Hindfoot arthrodesis is the current option available for irreducible or nonbraceable deformities of neuropathic feet. However, the role of ankle arthrodesis in these patients has been questioned because of high nonunion and complication rates. From 1990 to 2001, 17 cases of acquired neuropathic foot deformities were treated by four tibiotalocalcaneal (TTC arthrodeses and 13 ankle arthrodeses. TTC arthrodesis was performed on cases with combined ankle and subtalar arthritis or cases whose deformities or instabilities could not be corrected by ankle fusion alone. There was no nonunion of TTC arthrodesis and seven ununited ankle arthrodeses were salvaged by two TTC-attempted arthrodeses and five revision ankle-attempted arthrodeses. Eventually in these cases, there was one nonunion in TTC arthrodesis and one nonunion in revision ankle arthrodesis. The final fusion rate was 88% (15 of 17 cases with average union time of 6.9 months (range, 2.5–18 months. The American Orthopaedic Foot and Ankle Society ankle hind-foot functional scores were evaluated: one was excellent (5.8%, seven were good (41%, eight were fair (53.3%, and one was poor (5.8% in terms of total functional outcome. We conclude that TTC arthrodesis is indicated for cases with ankle and subtalar involvement and ankle arthrodesis is an alternative for cases with intact subtalar joint. We recommend revision ankle arthrodesis if the ankle fails to fuse and the bone stock of the talus is adequate. TTC arthrodesis is reserved for ankles with poor bone stock of the talus with fragmentation.

  2. Psychometric validation of the Portuguese version of the Neuropathic Pain Symptoms Inventory

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    de Andrade Daniel

    2011-11-01

    Full Text Available Abstract Backgroud It has been shown that different symptoms or symptom combinations of neuropathic pain (NeP may correspond to different mechanistic backgrounds and respond differently to treatment. The Neuropathic Pain Symptom Inventory (NPSI is able to detect distinct clusters of symptoms (i.e. dimensions with a putative common mechanistic background. The present study described the psychometric validation of the Portuguese version (PV of the NPSI. Methods Patients were seen in two consecutive visits, three to four weeks apart. They were asked to: (i rate their mean pain intensity in the last 24 hours on an 11-point (0-10 numerical scale; (ii complete the PV-NPSI; (iii provide the list of pain medications and doses currently in use. VAS and Global Impression of Change (GIC were filled out in the second visit. Results PV-NPSI underwent test-retest reliability, factor analysis, analysis of sensitivity to changes between both visits. The PV-NPSI was reliable in this setting, with a good intra-class correlation for all items. The factorial analysis showed that the PV-NPSI inventory assessed different components of neuropathic pain. Five different factors were found. The PV-NPSI was adequate to evaluate patients with neuropathic pain and to detect clusters of NeP symptoms. Conclusions The psychometric properties of the PV-NPSI rendered it adequate to evaluate patients with both central and peripheral neuropathic pain syndromes and to detect clusters of NeP symptoms.

  3. Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients

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    Bouwense SA

    2015-07-01

    -generating study provides the first evidence that pain relief with pregabalin is associated with anti-hyperalgesic effects and increased endogenous inhibitory modulation. No such effects were observed in patients experiencing pain relief with the placebo treatment. The mechanisms underlying analgesic response to placebo vs drug treatments are different and, together with their interactions, deserve further study.Keywords: chronic pancreatitis, pregabalin, placebo, chronic pain treatment, quantitative sensory testing, central sensitization

  4. Neuropathic pain after spinal cord injury resistant to conventional therapies - case report.

    Science.gov (United States)

    Daszkiewicz, Andrzej; Gierlotka, Zbigniew; Nierodziński, Wojciech; Misiołek, Aleksandra; Misiołek, Hanna

    There are patients with neuropathic pain in whom the treatment is ineffective, despite the fact that is conducted with adherence to the current guidelines. In these patients alternative treatment methods such as hypnosis could be effective. The paper presents a case of a 58-year-old man with central neuropathic pain after cervical spinal cord injury. The conservative treatment with antiepileptics including gabapentoids), antidepressants (tricyclic and selective noradrenaline and serotonin inhibitor - SNRI) and opioids was not effective. In the pain management centre the celiac plexus stimulation and neuromodulation was performed, however, with no positive results. The patient was referred to the psychiatrist using hypnosis in his medical practice. The psychiatrist qualified the patient to pain treatment with hypnosis. After several hypnotic sessions the pain intensity score in numeric rating scale (NRS) decreased from NRS 7 to NRS 5 points and became acceptable for the patient. Hypnosis can be considered an effective method of neuropathic pain treatment in some patients.

  5. Neuropathic pain. Redefinition and a grading system for clinical and research purposes

    DEFF Research Database (Denmark)

    Treede, R.-D.; Jensen, Troels Staehelin; Campbell, J.N.

    2008-01-01

    potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as "pain...... initiated or caused by a primary lesion or dysfunction in the nervous system." While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate...... affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific...

  6. Persistent at-level thermal hyperalgesia and tactile allodynia accompany chronic neuronal and astrocyte activation in superficial dorsal horn following mouse cervical contusion spinal cord injury.

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    Jaime L Watson

    Full Text Available In humans, sensory abnormalities, including neuropathic pain, often result from traumatic spinal cord injury (SCI. SCI can induce cellular changes in the CNS, termed central sensitization, that alter excitability of spinal cord neurons, including those in the dorsal horn involved in pain transmission. Persistently elevated levels of neuronal activity, glial activation, and glutamatergic transmission are thought to contribute to the hyperexcitability of these dorsal horn neurons, which can lead to maladaptive circuitry, aberrant pain processing and, ultimately, chronic neuropathic pain. Here we present a mouse model of SCI-induced neuropathic pain that exhibits a persistent pain phenotype accompanied by chronic neuronal hyperexcitability and glial activation in the spinal cord dorsal horn. We generated a unilateral cervical contusion injury at the C5 or C6 level of the adult mouse spinal cord. Following injury, an increase in the number of neurons expressing ΔFosB (a marker of chronic neuronal activation, persistent astrocyte activation and proliferation (as measured by GFAP and Ki67 expression, and a decrease in the expression of the astrocyte glutamate transporter GLT1 are observed in the ipsilateral superficial dorsal horn of cervical spinal cord. These changes have previously been associated with neuronal hyperexcitability and may contribute to altered pain transmission and chronic neuropathic pain. In our model, they are accompanied by robust at-level hyperaglesia in the ipsilateral forepaw and allodynia in both forepaws that are evident within two weeks following injury and persist for at least six weeks. Furthermore, the pain phenotype occurs in the absence of alterations in forelimb grip strength, suggesting that it represents sensory and not motor abnormalities. Given the importance of transgenic mouse technology, this clinically-relevant model provides a resource that can be used to study the molecular mechanisms contributing to

  7. Persistent at-level thermal hyperalgesia and tactile allodynia accompany chronic neuronal and astrocyte activation in superficial dorsal horn following mouse cervical contusion spinal cord injury.

    Science.gov (United States)

    Watson, Jaime L; Hala, Tamara J; Putatunda, Rajarshi; Sannie, Daniel; Lepore, Angelo C

    2014-01-01

    In humans, sensory abnormalities, including neuropathic pain, often result from traumatic spinal cord injury (SCI). SCI can induce cellular changes in the CNS, termed central sensitization, that alter excitability of spinal cord neurons, including those in the dorsal horn involved in pain transmission. Persistently elevated levels of neuronal activity, glial activation, and glutamatergic transmission are thought to contribute to the hyperexcitability of these dorsal horn neurons, which can lead to maladaptive circuitry, aberrant pain processing and, ultimately, chronic neuropathic pain. Here we present a mouse model of SCI-induced neuropathic pain that exhibits a persistent pain phenotype accompanied by chronic neuronal hyperexcitability and glial activation in the spinal cord dorsal horn. We generated a unilateral cervical contusion injury at the C5 or C6 level of the adult mouse spinal cord. Following injury, an increase in the number of neurons expressing ΔFosB (a marker of chronic neuronal activation), persistent astrocyte activation and proliferation (as measured by GFAP and Ki67 expression), and a decrease in the expression of the astrocyte glutamate transporter GLT1 are observed in the ipsilateral superficial dorsal horn of cervical spinal cord. These changes have previously been associated with neuronal hyperexcitability and may contribute to altered pain transmission and chronic neuropathic pain. In our model, they are accompanied by robust at-level hyperaglesia in the ipsilateral forepaw and allodynia in both forepaws that are evident within two weeks following injury and persist for at least six weeks. Furthermore, the pain phenotype occurs in the absence of alterations in forelimb grip strength, suggesting that it represents sensory and not motor abnormalities. Given the importance of transgenic mouse technology, this clinically-relevant model provides a resource that can be used to study the molecular mechanisms contributing to neuropathic pain

  8. Development and statistical optimization of nefopam hydrochloride loaded nanospheres for neuropathic pain using Box–Behnken design

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    S. Sukhbir

    2016-09-01

    Full Text Available Nefopam hydrochloride (NFH is a non-opioid centrally acting analgesic drug used to treat chronic condition such as neuropathic pain. In current research, sustained release nefopam hydrochloride loaded nanospheres (NFH-NS were auspiciously synthesized using binary mixture of eudragit RL 100 and RS 100 with sorbitan monooleate as surfactant by quasi solvent diffusion technique and optimized by 35 Box–Behnken designs to evaluate the effects of process and formulation variables. Fourier transform infrared spectroscopy (FTIR, differential scanning calorimetric (DSC and X-ray diffraction (XRD affirmed absence of drug–polymer incompatibility and confirmed formation of nanospheres. Desirability function scrutinized by design-expert software for optimized formulation was 0.920. Optimized batch of NFH-NS had mean particle size 328.36 nm ± 2.23, % entrapment efficiency (% EE 84.97 ± 1.23, % process yield 83.60 ± 1.31 and % drug loading (% DL 21.41 ± 0.89. Dynamic light scattering (DLS, zeta potential analysis and scanning electron microscopy (SEM validated size, charge and shape of nanospheres, respectively. In-vitro drug release study revealed biphasic release pattern from optimized nanospheres. Korsmeyer Peppas found excellent kinetics model with release exponent less than 0.45. Chronic constricted injury (CCI model of optimized NFH-NS in Wistar rats produced significant difference in neuropathic pain behavior (p < 0.05 as compared to free NFH over 10 h indicating sustained action. Long term and accelerated stability testing of optimized NFH-NS revealed degradation rate constant 1.695 × 10−4 and shelf-life 621 days at 25 ± 2 °C/60% ± 5% RH.

  9. Development and statistical optimization of nefopam hydrochloride loaded nanospheres for neuropathic pain using Box-Behnken design.

    Science.gov (United States)

    Sukhbir, S; Yashpal, S; Sandeep, A

    2016-09-01

    Nefopam hydrochloride (NFH) is a non-opioid centrally acting analgesic drug used to treat chronic condition such as neuropathic pain. In current research, sustained release nefopam hydrochloride loaded nanospheres (NFH-NS) were auspiciously synthesized using binary mixture of eudragit RL 100 and RS 100 with sorbitan monooleate as surfactant by quasi solvent diffusion technique and optimized by 3 5 Box-Behnken designs to evaluate the effects of process and formulation variables. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetric (DSC) and X-ray diffraction (XRD) affirmed absence of drug-polymer incompatibility and confirmed formation of nanospheres. Desirability function scrutinized by design-expert software for optimized formulation was 0.920. Optimized batch of NFH-NS had mean particle size 328.36 nm ± 2.23, % entrapment efficiency (% EE) 84.97 ± 1.23, % process yield 83.60 ± 1.31 and % drug loading (% DL) 21.41 ± 0.89. Dynamic light scattering (DLS), zeta potential analysis and scanning electron microscopy (SEM) validated size, charge and shape of nanospheres, respectively. In-vitro drug release study revealed biphasic release pattern from optimized nanospheres. Korsmeyer Peppas found excellent kinetics model with release exponent less than 0.45. Chronic constricted injury (CCI) model of optimized NFH-NS in Wistar rats produced significant difference in neuropathic pain behavior ( p  < 0.05) as compared to free NFH over 10 h indicating sustained action. Long term and accelerated stability testing of optimized NFH-NS revealed degradation rate constant 1.695 × 10 -4 and shelf-life 621 days at 25 ± 2 °C/60% ± 5% RH.

  10. Central blood circulation in children at chronic combined low dose radiation and chemical action

    International Nuclear Information System (INIS)

    Arinchin, A.N.

    2000-01-01

    The state of central blood circulation and its hormonal regulation were studied in 1465 children living permanently under chronic low dose radiation and chemical action. Basic group consisted of 1093 children (579 boys and 514 girls) . 372 children (115 boys and 227 girls permanently living on 'clean' areas) were investigated in control group. Average age was 10,8 years old in basic group and 10,4 years old in the control group. Such parameters as arterial pressure, level of lead in blood and urine, adrenaline, noradrenaline and dophamine content in urine, thyroxine, iodothyronine, prostaglandins and cyclic AMP content in the blood serum has been controlled. Hypotensive states were determined to prevail in children living permanently under chronic low dose radiation and chemical action. The main pathogenic mechanism of this defeat is consider to be a reduction of the sympathoadrenal system activity combined with a decreasing of the thyroid system activity and of cyclic AMP level as well as predominance of prostaglandin depressive activity

  11. Molecular Hydrogen Attenuates Neuropathic Pain in Mice

    Science.gov (United States)

    Kawaguchi, Masanori; Satoh, Yasushi; Otsubo, Yukiko; Kazama, Tomiei

    2014-01-01

    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. PMID:24941001

  12. Medical management of trigeminal neuropathic pains.

    Science.gov (United States)

    Zakrzewska, Joanna M

    2010-06-01

    Although trigeminal neuralgia has traditionally been considered the prime neuralgic condition in the face region, other forms of neuropathic pain are now being more frequently recognized and require recognition and a different management approach. This review principally covers medical management of trigeminal neuralgia; but also included is glossopharyngeal neuralgia, trigeminal neuropathic pain (atypical odontalgia) and burning mouth syndrome. Systematic reviews and guidelines will be discussed. An update will be provided of drug therapy for these relatively rare facial pains. Trigeminal neuralgia continues to be best managed using anticonvulsant drugs, the primary ones being carbamazepine and oxcarbazepine; baclofen may be helpful and, of the newly emerging drugs, pregabalin has potential. Glossopharyngeal neuralgia remains managed in the same way as trigeminal neuralgia. Trigeminal neuropathic pain is probably best managed according to guidelines used for the management of neuropathic pain, which include the use of tricyclic antidepressants, gabapentin, pregabalin, duloxetine, venalafaxine and topical lidocaine. Burning mouth syndrome is a neuropathic pain managed initially with topical clonazepam and then with other neuropathic drugs. Patients need to be involved in their management.

  13. Recognition and Treatment of Central Sensitization in Chronic Pain Patients: Not Limited to Specialized Care.

    Science.gov (United States)

    Nijs, Jo; Goubert, Dorien; Ickmans, Kelly

    2016-12-01

    Modern pain neuroscience has substantially improved our understanding of the (development of) chronic musculoskeletal pain. The time has come for orthopaedic and sports physical therapists to implement modern pain neuroscience in specialized, but definitely also in primary, care settings, including the role of central sensitization (CS) in amplifying and explaining the presence of the pain experience. Central sensitization dominates the clinical picture in a subgroup of the musculoskeletal pain population, ranging from tennis elbow over shoulder pain to osteoarthritis and whiplash. Applying modern pain neuroscience to clinical practice implies (1) recognizing those patients having predominant CS pain, and (2) accounting for CS when designing the treatment plan in those with predominant CS pain. Future work in this area should (1) examine the validity of the proposed clinical classification algorithm for identifying CS pain in patients with orthopaedic and sports injuries, and (2) explore evidence-based treatment options for patients having predominant CS pain. J Orthop Sports Phys Ther 2016;46(12):1024-1028. doi:10.2519/jospt.2016.0612.

  14. Protein Kinase C γ Contributes to Central Sensitization in a Rat Model of Chronic Migraine.

    Science.gov (United States)

    Wu, Baixue; Wang, Sha; Qin, Guangcheng; Xie, Jingmei; Tan, Ge; Zhou, Jiying; Chen, Lixue

    2017-10-01

    Protein kinase C γ (PKCγ) is a critical regulator of central sensitization and is widely recognized to be involved in the pathogenesis of chronic migraine (CM). However, the function of PKCγ in CM remains unknown. This study investigated the role of PKCγ on pathogenesis of CM. We repeated infusions of inflammatory soup (IS) on the intact dura of conscious rats to model recurrent trigeminovascular or dural nociceptor activation assumed to occur in patients with CM. The von Frey test was then used to detect changes in pain threshold. QT-PCR, western blotting, and double immunofluorescence staining were performed to detect the expression and location of PKCγ in the trigeminal nucleus caudalis (TNC) and the expressions of calcitonin gene-related peptide (CGRP), c-Fos, and phosphorylation level of GluR1 subunit at serine 831. Chelerythrine chloride (CHE) and phorbol 12-myristate 13-acetate (PMA) were administrated to investigate the role of PKCγ in central sensitization. We found that repeated infusions of IS induced mechanical allodynia. PKCγ was significantly increased in TNC after CM. Furthermore, inhibition of PKCγ by CHE relieved allodynia and reduced the expression of CGRP and c-Fos. Activation of PKCγ by PMA aggravated allodynia and increased the expression of CGRP and c-Fos. In addition, inhibition of PKCγ reduced the phosphorylation level of GluR1; in contrast, activation of PKCγ increased the phosphorylation level of GluR1. These results suggest PKCγ-induced GluR1 phosphorylation might participate in central sensitization in a rat model of CM. We suggest that PKCγ is a potential therapeutic target for CM.

  15. Analgesic efficacy of CR4056, a novel imidazoline-2 receptor ligand, in rat models of inflammatory and neuropathic pain

    Directory of Open Access Journals (Sweden)

    Ferrari F

    2011-04-01

    Full Text Available Flora Ferrari1, Simonetta Fiorentino1, Laura Mennuni1, Paolo Garofalo1, Ornella Letari1, Stefano Mandelli2, Antonio Giordani3, Marco Lanza1, Gianfranco Caselli11Department of Pharmacology and Toxicology; 2Department of Medicinal Chemistry; 3R&D Chemistry Drug Development and OS, Rottapharm S.p.A., Monza (MB, ItalyAbstract: Two decades of investigations have failed to unequivocally clarify the functions and the molecular nature of imidazoline-2 receptors (I2R. However, there is robust pharmacological evidence for the functional modulation of monoamino oxidase (MAO and other important enzyme activities by I2 site ligands. Some compounds of this class proved to be active experimental tools in preventing both experimental pain and opioid tolerance and dependence. Unfortunately, even though these compounds bind with high potency to central I2 sites, they fail to represent a valid clinical opportunity due to their pharmacokinetic, selectivity or side-effects profile. This paper presents the preclinical profile of a novel I2 ligand (2-phenyl-6-(1H-imidazol-1ylquinazoline; [CR4056] that selectively inhibits the activity of human recombinant MAO-A in a concentration-dependent manner. A sub-chronic four day oral treatment of CR4056 increased norepinephrine (NE tissue levels both in the rat cerebral cortex (63.1% ± 4.2%; P<0.05 and lumbar spinal cord (51.3% ± 6.7%; P < 0.05. In the complete Freund's adjuvant (CFA rat model of inflammatory pain, CR4056 was found to be orally active (ED50 = 5.8 mg/kg, by mouth [p.o.]. In the acute capsaicin model, CR4056 completely blocked mechanical hyperalgesia in the injured hind paw (ED50 = 4.1 mg/kg, p.o.; ED100 = 17.9 mg/kg, p.o.. This effect was dose-dependently antagonized by the non-selective imidazoline I2/α2 antagonist idazoxan. In rat models of neuropathic pain, oral administration of CR4056 significantly attenuated mechanical hyperalgesia and allodynia. In summary, the present study suggests a novel

  16. Frequency, character, intensity and impact of neuropathic pain in a cohort of spinal cord injury patients

    International Nuclear Information System (INIS)

    Ullah, H.; Akhtar, N.; Matee, S.; Butt, A.W.

    2015-01-01

    The purpose of this study was to determine frequency, character, approximate location and intensity of neuropathic pain in spinal cord injury and its impact on the quality of life. Study Design: A cross-sectional survey Place and Duration of Study: Armed Forces Institute of Rehabilitation Medicine (AFIRM), Rawalpindi from Feb 2009 to Feb 2010. Material and Methods: Through non-probability convenience sampling 87 patients of both genders diagnosed with spinal cord injury based on American Spinal Injury Association criteria and admitted within a year of injury were included. Those in spinal shock, having poor cognition, inability to communicate, concurrent brain injury and history of chronic pain before injury were excluded. The history, localization and characteristics of the pain and interference with life activities were recorded. Neuropathic pain of patients was evaluated with Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale. Visual analogue scale was used to measure the severity of pain. Results: Out of 87 patients (mean age 36.9 years) seventy four were male and 13 were female. Seventy patients (80%) were AIS-A, 6 (7%) were AIS-B and 11 (13%) were AIS-C. Neuropathic pain was present in 57.5% (n=50). Most of the patients localized their pain below the neurological level of injury (78%) and rated pain intensity as moderate pain (54%). Majority (48%) described the pain as burning followed by electric shock like (42%), stabbing (8%) and pricking (2%). 48% patients reported that their quality of life was affected due to pain. 52% required two analgesics of different groups to relieve pain followed by 40% requiring three analgesics and 8% requiring one analgesic. Conclusion: Neuropathic pain is prevalent in people with spinal cord injury and adversely affects life quality. Neuropathic pain is primarily described as a burning sensation of moderate intensity mostly referred to below the neurological level of injury. (author)

  17. The astrocyte-targeted therapy by Bushi for the neuropathic pain in mice.

    Directory of Open Access Journals (Sweden)

    Keisuke Shibata

    Full Text Available BACKGROUND: There is accumulating evidence that the activation of spinal glial cells, especially microglia, is a key event in the pathogenesis of neuropathic pain. However, the inhibition of microglial activation is often ineffective, especially for long-lasting persistent neuropathic pain. So far, neuropathic pain remains largely intractable and a new therapeutic strategy for the pain is still required. METHODS/PRINCIPAL FINDINGS: Using Seltzer model mice, we investigated the temporal aspect of two types of neuropathic pain behaviors, i.e., thermal hyperalgesia and mechanical allodynia, as well as that of morphological changes in spinal microglia and astrocytes by immunohistochemical studies. Firstly, we analyzed the pattern of progression in the pain behaviors, and found that the pain consisted of an "early induction phase" and subsequent "late maintenance phase". We next analyzed the temporal changes in spinal glial cells, and found that the induction and the maintenance phase of pain were associated with the activation of microglia and astrocytes, respectively. When Bushi, a Japanese herbal medicine often used for several types of persistent pain, was administered chronically, it inhibited the maintenance phase of pain without affecting the induction phase, which was in accordance with the inhibition of astrocytic activation in the spinal cord. These analgesic effects and the inhibition of astrocytic activation by Bushi were mimicked by the intrathecal injection of fluorocitrate, an inhibitor of astrocytic activation. Finally, we tested the direct effect of Bushi on astrocytic activation, and found that Bushi suppressed the IL-1β- or IL-18-evoked ERK1/2-phosphorylation in cultured astrocytes but not the ATP-evoked p38- and ERK1/2-phosphorylation in microglia in vitro. CONCLUSIONS: Our results indicated that the activation of spinal astrocytes was responsible for the late maintenance phase of neuropathic pain in the Seltzer model mice and

  18. The astrocyte-targeted therapy by Bushi for the neuropathic pain in mice.

    Science.gov (United States)

    Shibata, Keisuke; Sugawara, Takeshi; Fujishita, Kayoko; Shinozaki, Youichi; Matsukawa, Takashi; Suzuki, Tsutomu; Koizumi, Schuichi

    2011-01-01

    There is accumulating evidence that the activation of spinal glial cells, especially microglia, is a key event in the pathogenesis of neuropathic pain. However, the inhibition of microglial activation is often ineffective, especially for long-lasting persistent neuropathic pain. So far, neuropathic pain remains largely intractable and a new therapeutic strategy for the pain is still required. Using Seltzer model mice, we investigated the temporal aspect of two types of neuropathic pain behaviors, i.e., thermal hyperalgesia and mechanical allodynia, as well as that of morphological changes in spinal microglia and astrocytes by immunohistochemical studies. Firstly, we analyzed the pattern of progression in the pain behaviors, and found that the pain consisted of an "early induction phase" and subsequent "late maintenance phase". We next analyzed the temporal changes in spinal glial cells, and found that the induction and the maintenance phase of pain were associated with the activation of microglia and astrocytes, respectively. When Bushi, a Japanese herbal medicine often used for several types of persistent pain, was administered chronically, it inhibited the maintenance phase of pain without affecting the induction phase, which was in accordance with the inhibition of astrocytic activation in the spinal cord. These analgesic effects and the inhibition of astrocytic activation by Bushi were mimicked by the intrathecal injection of fluorocitrate, an inhibitor of astrocytic activation. Finally, we tested the direct effect of Bushi on astrocytic activation, and found that Bushi suppressed the IL-1β- or IL-18-evoked ERK1/2-phosphorylation in cultured astrocytes but not the ATP-evoked p38- and ERK1/2-phosphorylation in microglia in vitro. Our results indicated that the activation of spinal astrocytes was responsible for the late maintenance phase of neuropathic pain in the Seltzer model mice and, therefore, the inhibition of astrocytic activation by Bushi could be a

  19. Interventional management of neuropathic pain: NeuPSIG recommendations

    Science.gov (United States)

    Dworkin, Robert H.; O’Connor, Alec B.; Kent, Joel; Mackey, Sean C.; Raja, Srinivasa N.; Stacey, Brett R.; Levy, Robert M.; Backonja, Miroslav; Baron, Ralf; Harke, Henning; Loeser, John D.; Treede, Rolf-Detlef; Turk, Dennis C.; Wells, Christopher D.

    2015-01-01

    Neuropathic pain (NP) is often refractory to pharmacologic and non-interventional treatment. On behalf of the International Association for the Study of Pain Neuropathic Pain Special Interest Group (NeuPSIG), the authors evaluated systematic reviews, clinical trials, and existing guidelines for the interventional management of NP. Evidence is summarized and presented for neural blockade, spinal cord stimulation (SCS), intrathecal medication, and neurosurgical interventions in patients with the following peripheral and central NP conditions: herpes zoster and postherpetic neuralgia (PHN); painful diabetic and other peripheral neuropathies; spinal cord injury NP; central post-stroke pain; radiculopathy and failed back surgery syndrome (FBSS); complex regional pain syndrome (CRPS); and trigeminal neuralgia and neuropathy. Due to the paucity of high-quality clinical trials, no strong recommendations can be made. Four weak recommendations based on the amount and consistency of evidence, including degree of efficacy and safety, are: (1) epidural injections for herpes zoster; (2) steroid injections for radiculopathy; (3) SCS for FBSS; and (4) SCS for CRPS type 1. Based on the available data, we recommend not to use sympathetic blocks for PHN nor RF lesions for radiculopathy. No other conclusive recommendations can be made due to the poor quality of available of data. Whenever possible, these interventions should either be part of randomized clinical trials or documented in pain registries. Priorities for future research include randomized clinical trials; long-term studies; and head-to-head comparisons among different interventional and non-interventional treatments. PMID:23748119

  20. Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

    Science.gov (United States)

    Nijs, Jo; Loggia, Marco L; Polli, Andrea; Moens, Maarten; Huysmans, Eva; Goudman, Lisa; Meeus, Mira; Vanderweeën, Luc; Ickmans, Kelly; Clauw, Daniel

    2017-08-01

    The mechanism of sensitization of the central nervous system partly explains the chronic pain experience in many patients, but the etiological mechanisms of this central nervous system dysfunction are poorly understood. Recently, an increasing number of studies suggest that aberrant glial activation takes part in the establishment and/or maintenance of central sensitization. Areas covered: This review focused on preclinical work and mostly on the neurobiochemistry studied in animals, with limited human studies available. Glial overactivation results in a low-grade neuroinflammatory state, characterized by high levels of BDNF, IL-1β, TNF-α, which in turn increases the excitability of the central nervous system neurons through mechanisms like long-term potentiation and increased synaptic efficiency. Aberrant glial activity in chronic pain might have been triggered by severe stress exposure, and/or sleeping disturbances, each of which are established initiating factors for chronic pain development. Expert opinion: Potential treatment avenues include several pharmacological options for diminishing glial activity, as well as conservative interventions like sleep management, stress management and exercise therapy. Pharmacological options include propentofylline, minocycline, β -adrenergic receptor antagonists, and cannabidiol. Before translating these findings from basic science to clinical settings, more human studies exploring the outlined mechanisms in chronic pain patients are needed.

  1. Neuroplasticity of ascending and descending pathways after somatosensory system injury: reviewing knowledge to identify neuropathic pain therapeutic targets.

    Science.gov (United States)

    Boadas-Vaello, P; Castany, S; Homs, J; Álvarez-Pérez, B; Deulofeu, M; Verdú, E

    2016-05-01

    This is a narrative review of the literature. This review aims to be useful in identifying therapeutic targets. It focuses on the molecular and biochemical neuroplasticity changes that occur in the somatosensory system, including ascending and descending pathways, during the development of neuropathic pain. Furthermore, it highlights the latest experimental strategies, based on the changes reported in the damaged nociceptive neurons during neuropathic pain states. This study was conducted in Girona, Catalonia, Spain. A MEDLINE search was performed using the following terms: descending pain pathways; ascending pain pathways; central sensitization; molecular pain; and neuropathic pain pharmacological treatment. Neuropathic pain triggered by traumatic lesions leads to sensitization and hyperexcitability of nociceptors and projection neurons of the dorsal horn, a strengthening in the descendent excitatory pathway and an inhibition of the descending inhibitory pathway of pain. These functional events are associated with molecular plastic changes such as overexpression of voltage-gated ion channels, algogen-sensitive receptors and synthesis of several neurotransmitters. Molecular studies on the plastic changes in the nociceptive somatosensory system enable the development of new pharmacological treatments against neuropathic pain, with higher specificity and effectiveness than classical drug treatments. Although research efforts have already focused on these aspects, additional research may be necessary to further explore the potential therapeutic targets in neuropathic pain involved in the neuroplasticity changes of neuropathological pathways from the injured somatosensory system.

  2. Pregabalin in acute and chronic pain

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    Dalim Kumar Baidya

    2011-01-01

    Full Text Available Pregabalin is a gamma-amino-butyric acid analog shown to be effective in several models of neuropathic pain, incisional injury, and inflammatory injury. In this review, the role of pregabalin in acute postoperative pain and in chronic pain syndromes has been discussed. Multimodal perioperative analgesia with the use of gabapentinoids has become common. Based on available evidence from randomized controlled trials and meta-analysis, the perioperative administration of pregabalin reduces opioid consumption and opioid-related adverse effects in the first 24 h following surgery. Postoperative pain intensity is however not consistently reduced by pregabalin. Adverse effects like visual disturbance, sedation, dizziness, and headache are associated with higher doses. The advantage of the perioperative use of pregabalin is so far limited to laparoscopic, gynecological, and daycare surgeries which are not very painful. The role of the perioperative administration of pregabalin in preventing chronic pain following surgery, its efficacy in more painful surgeries and surgeries done under regional anesthesia, and the optimal dosage and duration of perioperative pregabalin need to be studied. The efficacy of pregabalin in chronic pain conditions like painful diabetic neuropathy, postherpetic neuralgia, central neuropathic pain, and fibromyalgia has been demonstrated.

  3. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice.

    Science.gov (United States)

    Bercik, Premysl; Verdu, Elena F; Foster, Jane A; Macri, Joseph; Potter, Murray; Huang, Xiaxing; Malinowski, Paul; Jackson, Wendy; Blennerhassett, Patricia; Neufeld, Karen A; Lu, Jun; Khan, Waliul I; Corthesy-Theulaz, Irene; Cherbut, Christine; Bergonzelli, Gabriela E; Collins, Stephen M

    2010-12-01

    Clinical and preclinical studies have associated gastrointestinal inflammation and infection with altered behavior. We investigated whether chronic gut inflammation alters behavior and brain biochemistry and examined underlying mechanisms. AKR mice were infected with the noninvasive parasite Trichuris muris and given etanercept, budesonide, or specific probiotics. Subdiaphragmatic vagotomy was performed in a subgroup of mice before infection. Gastrointestinal inflammation was assessed by histology and quantification of myeloperoxidase activity. Serum proteins were measured by proteomic analysis, circulating cytokines were measured by fluorescence activated cell sorting array, and serum tryptophan and kynurenine were measured by liquid chromatography. Behavior was assessed using light/dark preference and step-down tests. In situ hybridization was used to assess brain-derived neurotrophic factor (BDNF) expression in the brain. T muris caused mild to moderate colonic inflammation and anxiety-like behavior that was associated with decreased hippocampal BDNF messenger RNA (mRNA). Circulating tumor necrosis factor-α and interferon-γ, as well as the kynurenine and kynurenine/tryptophan ratio, were increased. Proteomic analysis showed altered levels of several proteins related to inflammation and neural function. Administration of etanercept, and to a lesser degree of budesonide, normalized behavior, reduced cytokine and kynurenine levels, but did not influence BDNF expression. The probiotic Bifidobacterium longum normalized behavior and BDNF mRNA but did not affect cytokine or kynurenine levels. Anxiety-like behavior was present in infected mice after vagotomy. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry, which can be normalized by inflammation-dependent and -independent mechanisms, neither of which requires the integrity of the vagus nerve. Copyright © 2010 AGA Institute. Published by Elsevier Inc

  4. Applying modern pain neuroscience in clinical practice: criteria for the classification of central sensitization pain.

    Science.gov (United States)

    Nijs, Jo; Torres-Cueco, Rafael; van Wilgen, C Paul; Girbes, Enrique Lluh; Struyf, Filip; Roussel, Nathalie; van Oosterwijck, Jessica; Daenen, Liesbeth; Kuppens, Kevin; Vanwerweeen, Luc; Hermans, Linda; Beckwee, David; Voogt, Lennard; Clark, Jacqui; Moloney, Niamh; Meeus, Mira

    2014-01-01

    The awareness is growing that central sensitization is of prime importance for the assessment and management of chronic pain, but its classification is challenging clinically since no gold standard method of assessment exists. Designing the first set of classification criteria for the classification of central sensitization pain. A body of evidence from original research papers was used by 18 pain experts from 7 different countries to design the first classification criteria for central sensitization pain. It is proposed that the classification of central sensitization pain entails 2 major steps: the exclusion of neuropathic pain and the differential classification of nociceptive versus central sensitization pain. For the former, the International Association for the Study of Pain diagnostic criteria are available for diagnosing or excluding neuropathic pain. For the latter, clinicians are advised to screen their patients for 3 major classification criteria, and use them to complete the classification algorithm for each individual patient with chronic pain. The first and obligatory criterion entails disproportionate pain, implying that the severity of pain and related reported or perceived disability are disproportionate to the nature and extent of injury or pathology (i.e., tissue damage or structural impairments). The 2 remaining criteria are 1) the presence of diffuse pain distribution, allodynia, and hyperalgesia; and 2) hypersensitivity of senses unrelated to the musculoskeletal system (defined as a score of at least 40 on the Central Sensitization Inventory). Although based on direct and indirect research findings, the classification algorithm requires experimental testing in future studies. Clinicians can use the proposed classification algorithm for differentiating neuropathic, nociceptive, and central sensitization pain.

  5. Reduced basal ganglia μ-opioid receptor availability in trigeminal neuropathic pain: A pilot study

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    DosSantos Marcos

    2012-09-01

    Full Text Available Abstract Background Although neuroimaging techniques have provided insights into the function of brain regions involved in Trigeminal Neuropathic Pain (TNP in humans, there is little understanding of the molecular mechanisms affected during the course of this disorder. Understanding these processes is crucial to determine the systems involved in the development and persistence of TNP. Findings In this study, we examined the regional μ-opioid receptor (μOR availability in vivo (non-displaceable binding potential BPND of TNP patients with positron emission tomography (PET using the μOR selective radioligand [11C]carfentanil. Four TNP patients and eight gender and age-matched healthy controls were examined with PET. Patients with TNP showed reduced μOR BPND in the left nucleus accumbens (NAc, an area known to be involved in pain modulation and reward/aversive behaviors. In addition, the μOR BPND in the NAc was negatively correlated with the McGill sensory and total pain ratings in the TNP patients. Conclusions Our findings give preliminary evidence that the clinical pain in TNP patients can be related to alterations in the endogenous μ-opioid system, rather than only to the peripheral pathology. The decreased availability of μORs found in TNP patients, and its inverse relationship to clinical pain levels, provide insights into the central mechanisms related to this condition. The results also expand our understanding about the impact of chronic pain on the limbic system.

  6. Glial role in oxaliplatin-induced neuropathic pain.

    Science.gov (United States)

    Di Cesare Mannelli, Lorenzo; Pacini, Alessandra; Micheli, Laura; Tani, Alessia; Zanardelli, Matteo; Ghelardini, Carla

    2014-11-01

    Oxaliplatin, a platinum-based chemotherapeutic agent, has become a standard treatment for advanced colorectal cancer. The dose-limiting toxicity of this compound is the development of peripheral neuropathy. A tangled panel of symptoms, sensory loss, paresthesia, dysesthesia and pain, may be disabling for patients and adversely affect their quality of life. Recently, we described a characteristic glial activation profile in a rat model of oxaliplatin-induced neuropathy. Glial cells are considered a new pharmacological target for neuropathic pain relief but its relevance in chemotherapy-dependent neuropathies is debated. Aimed to evaluate the significance of glial activation in pain generated by oxaliplatin, the microglial inhibitor minocycline or the astrocyte inhibitor fluorocitrate were continuously infused by intrathecal route in oxaliplatin-treated rats. Both compounds significantly reduced oxaliplatin-evoked pain though the efficacy of fluorocitrate was higher revealing a prominent role of astrocytes. Immunohistochemical analysis of the dorsal horn confirmed the specific Iba1-positive cell inhibition caused by minocycline as well as the selectivity of fluorocitrate on GFAP-positive cells. The activation of astrocytes in minocycline-treated rats suggests a microglia-independent modulation of astrocytes by oxaliplatin neurotoxicity. Neither the selective activation of astrocyte after minocycline treatment nor the exclusive microglial response after fluorocitrate is able to evoke pain. Morphometric and morphological determinations performed on dorsal root ganglia evidenced that the glial inhibitors did not prevent the oxaliplatin-dependent increase of eccentric nucleoli and multinucleolated neurons. The decrease of soma area was also unaltered. In summary, these data highlight the role of central glial cells in oxaliplatin-dependent neuropathic pain. On the other hand, glial inhibition is not associated with neuroprotective effects suggesting the need for careful

  7. A Review of Neuropathic Pain: From Diagnostic Tests to Mechanisms

    OpenAIRE

    Truini, Andrea

    2017-01-01

    Neuropathic pain develops when the somatosensory nervous system is affected by a lesion or disease. Diagnostic tests aimed at assessing somatosensory afferent pathway damage are therefore useful for diagnosing neuropathic pain. Neuropathic pain manifests with a range of different symptoms such as ongoing burning pain, squeezing or pressure pain, paroxysmal electric shock-like sensations, stabbing pain, or mechanical dynamic allodynia. The various types of neuropathic pain are associated with ...

  8. Botulinum Toxin for Neuropathic Pain: A Review of the Literature

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    Hyun-Mi Oh

    2015-08-01

    Full Text Available Botulinum neurotoxin (BoNT, derived from Clostridium botulinum, has been used therapeutically for focal dystonia, spasticity, and chronic migraine. Its spectrum as a potential treatment for neuropathic pain has grown. Recent opinions on the mechanism behind the antinociceptive effects of BoNT suggest that it inhibits the release of peripheral neurotransmitters and inflammatory mediators from sensory nerves. There is some evidence showing the axonal transport of BoNT, but it remains controversial. The aim of this review is to summarize the experimental and clinical evidence of the antinociceptive effects, mechanisms, and therapeutic applications of BoNT for neuropathic pain conditions, including postherpetic neuralgia, complex regional pain syndrome, and trigeminal neuralgia. The PubMed and OvidSP databases were searched from 1966 to May 2015. We assessed levels of evidence according to the American Academy of Neurology guidelines. Recent studies have suggested that BoNT injection is an effective treatment for postherpetic neuralgia and is likely efficient for trigeminal neuralgia and post-traumatic neuralgia. BoNT could also be effective as a treatment for diabetic neuropathy. It has not been proven to be an effective treatment for occipital neuralgia or complex regional pain syndrome.

  9. Effects of Glutathione on Mechanical Allodynia and Central Sensitization in Chronic Postischemic Pain Rats

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    Jinseok Yeo

    2017-01-01

    Full Text Available Background. The chronic postischemia pain (CPIP model is an animal model using ischemia/reperfusion injury that mimics the symptoms of complex regional pain syndrome type I. Glutathione (GSH prevents ischemia/reperfusion injury by scavenging free radicals. We conducted this study to investigate the protective effect of GSH in CPIP rats via changes of mechanical allodynia and phospholyration of the N-methyl-D-aspartate receptor subunit GluN1. Methods. We divided 45 rats into 5 groups: sham, CPIP, CPIP + GSH 100 mg/kg, CPIP + GSH 200 mg/kg, and CPIP + GSH 500 mg/kg. Rats in the sham and CPIP groups received normal saline and rats in the other groups received GSH at the designated doses thirty minutes prior to reperfusion. Withdrawal thresholds were evaluated before sugery as well as 1, 3, and 7 days after surgery. pGluN1 level in the spinal cord was also measured. Results. GSH treated rats show a significant increase in the withdrawal thresholds of both hind paws as compared with the CPIP group dose-dependently. The expression of pGluN1 in the GSH treated rats significantly decreased as compared to the CPIP group (all P < 0.05. Conclusion. These findings suggest that GSH inhibited the development of mechanical allodynia and central sensitization in CPIP rats.

  10. Effects of Glutathione on Mechanical Allodynia and Central Sensitization in Chronic Postischemic Pain Rats.

    Science.gov (United States)

    Yeo, Jinseok; Jung, Hoon; Lee, Hyerim

    2017-01-01

    The chronic postischemia pain (CPIP) model is an animal model using ischemia/reperfusion injury that mimics the symptoms of complex regional pain syndrome type I. Glutathione (GSH) prevents ischemia/reperfusion injury by scavenging free radicals. We conducted this study to investigate the protective effect of GSH in CPIP rats via changes of mechanical allodynia and phospholyration of the N-methyl-D-aspartate receptor subunit GluN1. We divided 45 rats into 5 groups: sham, CPIP, CPIP + GSH 100 mg/kg, CPIP + GSH 200 mg/kg, and CPIP + GSH 500 mg/kg. Rats in the sham and CPIP groups received normal saline and rats in the other groups received GSH at the designated doses thirty minutes prior to reperfusion. Withdrawal thresholds were evaluated before sugery as well as 1, 3, and 7 days after surgery. pGluN1 level in the spinal cord was also measured. GSH treated rats show a significant increase in the withdrawal thresholds of both hind paws as compared with the CPIP group dose-dependently. The expression of pGluN1 in the GSH treated rats significantly decreased as compared to the CPIP group (all P central sensitization in CPIP rats.

  11. The role of the immune system in the generation of neuropathic pain.

    Science.gov (United States)

    Calvo, Margarita; Dawes, John M; Bennett, David L H

    2012-07-01

    Persistent pain is a sequela of several neurological conditions with a primary immune basis, such as Guillain-Barré syndrome and multiple sclerosis. Additionally, diverse forms of injury to the peripheral or the central nervous systems--whether traumatic, metabolic, or toxic--result in substantial recruitment and activation of immune cells. This response involves the innate immune system, but evidence also exists of T-lymphocyte recruitment, and in some patient cohorts antibodies to neuronal antigens have been reported. Mediators released by immune cells, such as cytokines, sensitise nociceptive signalling in the peripheral and central nervous systems. Preclinical data suggest an immune pathogenesis of neuropathic pain, but clinical evidence of a central role of the immune system is less clear. An important challenge for the future is to establish to what extent this immune response initiates or maintains neuropathic pain in patients and thus whether it is amenable to therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. A Review of Select Centralized Pain Syndromes

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    David R. Spiegel

    2015-01-01

    Full Text Available Pain can be broadly divided into 3 classes, including nociceptive or inflammatory pain (protective, neuropathic (pathological, occurring after damage to the nervous system, or centralized (pathological, due to abnormal function but with no damage or inflammation to the nervous system. The latter has been posited to occur when descending analgesic pathways are attenuated and/or glutamatergic transmission is facilitated. Additionally, this “pain prone phenotype” can be associated with early life trauma and a suboptimal response to opiates. This article will review the relationships between centralized pain syndromes (ie, fibromyalgia, chronic low back pain, childhood sexual abuse, and opiate misuse. Finally, treatment implications, potentially effecting primary care physicians, will be discussed.

  13. Somatosensory Profiles but Not Numbers of Somatosensory Abnormalities of Neuropathic Pain Patients Correspond with Neuropathic Pain Grading

    NARCIS (Netherlands)

    Konopka, Karl-Heinz; Harbers, Marten; Houghton, Andrea; Kortekaas, Rudie; van Vliet, Andre; Timmerman, Wia; den Boer, Johan A.; Struys, Michel M. R. F.; van Wijhe, Marten

    2012-01-01

    Due to the lack of a specific diagnostic tool for neuropathic pain, a grading system to categorize pain as 'definite', 'probable', 'possible' and 'unlikely' neuropathic was proposed. Somatosensory abnormalities are common in neuropathic pain and it has been suggested that a greater number of

  14. Bioinformatic Analysis of Potential Biomarkers for Spinal Cord Injured Patients With Intractable Neuropathic Pain.

    Science.gov (United States)

    Wang, Yimin; Ye, Fang; Huang, Chanyan; Xue, Faling; Li, Yingyuan; Gao, Shaowei; Qiu, Zeting; Li, Si; Chen, Qinchang; Zhou, Huaqiang; Song, Yiyan; Huang, Wenqi; Tan, Wulin; Wang, Zhongxing

    2018-03-15

    Neuropathic pain is one of the common complications after spinal cord injury (SCI), affecting patients' life quality. The molecular mechanism for neuropathic pain after SCI is still unclear. We aimed to discover potential genes and MicroRNAs(miRNAs) related to neuropathic pain by bioinformatics method. Microarray data of GSE69901 were obtained from Gene Expression Omnibus (GEO) database. Peripheral blood samples from patients with or without neuropathic pain after spinal cord injury (SCI) were collected. 12 samples with neuropathic pain and 13 samples without pain as control were included in the downloaded microarray. Differentially expressed genes (DEGs) between neuropathic pain group and control group were detected using GEO2R online tool. Functional enrichment analysis of DEGs was performed using DAVID database. Protein-protein interaction (PPI) network was constructed from STRING database. MiRNAs targeting these DEGs were obtained from miRNet database. A merged miRNA-DEG network was constructed and analyzed with Cytoscape software. Total 1134 DEGs were identified between patients with or without neuropathic pain(case and control) and 454 biological processes were enriched. We identified 4 targeted miRNAs, including mir-204-5p, mir-519d-3p, mir-20b-5p, mir-6838-5p, which may be the potential biomarker for SCI patients. Protein modification and regulation biological process of central nervous system may be a risk factor of in SCI patients. Certain genes and miRNAs may be potential biomarkers for the prediction of and potential targets for prevention and treatment of neuropathic pain after SCI.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http

  15. Differential transcriptional profiling of damaged and intact adjacent dorsal root ganglia neurons in neuropathic pain.

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    A K Reinhold

    Full Text Available Neuropathic pain, caused by a lesion in the somatosensory system, is a severely impairing mostly chronic disease. While its underlying molecular mechanisms are not thoroughly understood, neuroimmune interactions as well as changes in the pain pathway such as sensitization of nociceptors have been implicated. It has been shown that not only are different cell types involved in generation and maintenance of neuropathic pain, like neurons, immune and glial cells, but, also, intact adjacent neurons are relevant to the process. Here, we describe an experimental approach to discriminate damaged from intact adjacent neurons in the same dorsal root ganglion (DRG using differential fluorescent neuronal labelling and fluorescence-activated cell sorting (FACS. Two fluorescent tracers, Fluoroemerald (FE and 1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate (DiI, were used, whose properties allow us to distinguish between damaged and intact neurons. Subsequent sorting permitted transcriptional analysis of both groups. Results and qPCR validation show a strong regulation in damaged neurons versus contralateral controls as well as a moderate regulation in adjacent neurons. Data for damaged neurons reveal an mRNA expression pattern consistent with established upregulated genes like galanin, which supports our approach. Moreover, novel genes were found strongly regulated such as corticotropin-releasing hormone (CRH, providing novel targets for further research. Differential fluorescent neuronal labelling and sorting allows for a clear distinction between primarily damaged neuropathic neurons and "bystanders," thereby facilitating a more detailed understanding of their respective roles in neuropathic processes in the DRG.

  16. Systematic administration of B vitamins attenuates neuropathic hyperalgesia and reduces spinal neuron injury following temporary spinal cord ischaemia in rats.

    Science.gov (United States)

    Yu, C-Z; Liu, Y-P; Liu, S; Yan, M; Hu, S-J; Song, X-J

    2014-01-01

    B vitamins have been demonstrated to be effective in treating chronic pain due to peripheral nerve injury. We investigated whether B vitamins could alleviate neuropathic pain and reduce neuron injury following temporary ischaemia in a rat model of spinal cord ischaemia-reperfusion injury (SCII). SCII was produced by transiently blocking the unilateral lumbar arteries in adult male Sprague-Dawley rats. Behavioural and neurochemical signs of neuropathic pain and spinal neuron injury were analysed with and without B vitamin treatment. SCII caused behavioural thermal hyperalgesia and mechanical allodynia and neurochemical alterations, including increased expression of the vanilloid receptor 1 (VR1) and induction of c-Fos, as well as activation of the astrocytes and microglial cells in the spinal cord. Repetitive systemic administration of vitamin B complex (B1/B6/B12 at 33/33/0.5 mg/kg, i.p., daily, for 7-14 consecutive days) significantly reduced thermal hyperalgesia and the increased expression of VR1 and c-Fos, as well as activation of the astrocytes and microglial cells. SCII caused a dramatic decrease of the expression of the rate-limiting enzyme glutamic acid decarboxylase-65 (GAD65), which synthesizes γ-aminobutyric acid (GABA) in the axonal terminals, and β-III-tubulin, and also caused loss of Nissl bodies in the spinal cord. These alterations were largely prevented and rescued by the B vitamin treatment. These findings support the idea that the B vitamins are capable of neuroprotection and antinociception during spinal cord injury due to temporary ischaemia. Rescuing the loss of inhibitory GABAergic tone may reduce spinal central sensitization and contribute to B vitamin-induced analgesia. © 2013 European Pain Federation - EFIC®

  17. Chronic whiplash and central sensitization; an evaluation of the role of a myofascial trigger points in pain modulation

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    Freeman Michael D

    2009-04-01

    Full Text Available Abstract Objective it has been established that chronic neck pain following whiplash is associated with the phenomenon of central sensitization, in which injured and uninjured parts of the body exhibit lowered pain thresholds due to an alteration in central pain processing. it has furthermore been hypothesized that peripheral sources of nociception in the muscles may perpetuate central sensitization in chronic whiplash. the hypothesis explored in the present study was whether myofascial trigger points serve as a modulator of central sensitization in subjects with chronic neck pain. Design controlled case series. Setting outpatient chronic pain clinic. Subjects seventeen patients with chronic and intractable neck pain and 10 healthy controls without complaints of neck pain. Intervention symptomatic subjects received anesthetic infiltration of myofascial trigger points in the upper trapezius muscles and controls received the anesthetic in the thigh. Outcome measures: pre and post injection cervical range of motion, pressure pain thresholds (ppt over the infraspinatus, wrist extensor, and tibialis anterior muscles. sensitivity to light (photophobia and subjects' perception of pain using a visual analog scale (vas were also evaluated before and after injections. only the ppt was evaluated in the asymptomatic controls. Results immediate (within 1 minute alterations in cervical range of motion and pressure pain thresholds were observed following an average of 3.8 injections with 1–2 cc of 1% lidocaine into carefully identified trigger points. cervical range of motion increased by an average of 49% (p = 0.000 in flexion and 44% (p = 0.001 in extension, 47% (p = 0.000 and 28% (p Conclusion the present data suggest that myofascial trigger points serve to perpetuate lowered pain thresholds in uninjured tissues. additionally, it appears that lowered pain thresholds associated with central sensitization can be immediately reversed, even when associated

  18. Ascending central canal dilation and progressive ependymal disruption in a contusion model of rodent chronic spinal cord injury

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    Keirstead Hans S

    2007-09-01

    Full Text Available Abstract Background Chronic spinal cord injury (SCI can lead to an insidious decline in motor and sensory function in individuals even years after the initial injury and is accompanied by a slow and progressive cytoarchitectural destruction. At present, no pathological mechanisms satisfactorily explain the ongoing degeneration. Methods Adult female Sprague-Dawley rats were anesthetized laminectomized at T10 and received spinal cord contusion injuries with a force of 250 kilodynes using an Infinite Horizon Impactor. Animals were randomly distributed into 5 groups and killed 1 (n = 4, 28 (n = 4, 120 (n = 4, 450 (n = 5, or 540 (n = 5 days after injury. Morphometric and immunohistochemical studies were then performed on 1 mm block sections, 6 mm cranial and 6 mm caudal to the lesion epicenter. The SPSS 11.5 t test was used to determine differences between quantitative measures. Results Here, we document the first report of an ascending central canal dilation and progressive ependymal disruption cranial to the epicenter of injury in a contusion model of chronic SCI, which was characterized by extensive dural fibrosis and intraparenchymal cystic cavitation. Expansion of the central canal lumen beyond a critical diameter corresponded with ependymal cell ciliary loss, an empirically predictable thinning of the ependymal region, and a decrease in cell proliferation in the ependymal region. Large, aneurysmal dilations of the central canal were accompanied by disruptions in the ependymal layer, periependymal edema and gliosis, and destruction of the adjacent neuropil. Conclusion Cells of the ependymal region play an important role in CSF homeostasis, cellular signaling and wound repair in the spinal cord. The possible effects of this ascending pathology on ependymal function are discussed. Our studies suggest central canal dilation and ependymal region disruption as steps in the pathogenesis of chronic SCI, identify central canal dilation as a marker of

  19. Mast cells in chronic inflammation, pelvic pain and depression in women.

    Science.gov (United States)

    Graziottin, Alessandra; Skaper, Stephen D; Fusco, Mariella

    2014-07-01

    Inflammatory and neuroinflammatory processes are increasingly recognized as critical pathophysiologic steps in the development of multiple chronic diseases and in the etiology of persistent pain and depression. Mast cells are immune cells now viewed as cellular sensors in inflammation and immunity. When stimulated, mast cells release an array of mediators to orchestrate an inflammatory response. These mediators can directly initiate tissue responses on resident cells, and may also regulate the activity of other immune cells, including central microglia. New evidence supports the involvement of peripheral and central mast cells in the development of pain processes as well as in the transition from acute, to chronic and neuropathic pain. That behavioral and endocrine states can increase the number and activation of peripheral and brain mast cells suggests that mast cells represent the immune cells that peripherally and centrally coordinate inflammatory processes in neuropsychiatric diseases such as depression and anxiety which are associated with chronic pelvic pain. Given that increasing evidence supports the activated mast cell as a director of common inflammatory pathways/mechanisms contributing to chronic and neuropathic pelvic pain and comorbid neuropsychiatric diseases, mast cells may be considered a viable target for the multifactorial management of both pain and depression.

  20. Preemptive analgesic effect of lidocaine in a chronic neuropathic pain model Efeito analgésico preemptivo da lidocaína em modelo de dor crônica neuropática

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    Leonardo M. Batista

    2009-12-01

    Full Text Available Preemptive analgesia inhibits the progression of pain caused by surgical lesions. To analyze the effect of lidocaine on postoperative pain relief, we performed compression of the right sciatic nerve in Wistar rats and observed the differences on behavior between the group that received lidocaine and the group that was not treated with the local anesthetics pre-operatively. Group 1 was not operated (control; group 2 underwent the sciatic nerve ligature without lidocaine; group 3, underwent surgery with previous local infiltration of lidocaine. Group 2 showed significantly longer scratching times with a peak on day 14 post-operative (p=0.0005 and reduction in the latency to both noxious (p=0.003 and non-noxious (p=0.004 thermal stimulus. Group 3 presented significantly shorter scratching times (p=0.004 and longer latency times when compared to Group 2. Preemptive use of lidocaine 2% can potentially reduce the postoperative neuropathic pain associated with sciatic nerve compression.A analgesia preemptiva inibe a progressão da dor causada por lesão cirúrgica. Para analisar o efeito da lidocaína na diminuição da dor pós-operatória, submetemos ratos Wistar a compressão cirúrgica do nervo ciático e observamos diferenças em alguns padrões de comportamento entre o grupo tratado com lidocaína pré-operatória e o grupo não-tratado com o anestésico local. O grupo 1 não foi operado (controle; o grupo 2, submetido a ligadura do nervo ciático sem lidocaína, apresentou significativo aumento do tempo de coçar-se com um pico no 14º pós-operatório (p=0.0005 e redução na latência para os estímulos térmicos nocivo (p=0.003 e não-nocivo (p=0.004; o grupo 3, operado com a droga preemptiva, demonstrou significativo decréscimo no tempo de coçar-se (p=0.004 e maiores tempos de latência quando comparados aos do grupo 2. O uso preemptivo da lidocaína 2% pode, potencialmente, reduzir a dor neuropática pós-operatória associada à compress

  1. Possible analgesic effect of vigabatrin in animal experimental chronic neuropathic pain Possível efeito analgésico da vigabatrina na dor neuropática crônica experimental animal

    Directory of Open Access Journals (Sweden)

    NILZA D. ALVES

    1999-12-01

    Full Text Available Since anticonvulsants have been used for treating neuralgias, an interest has arisen to experimentally test vigabatrin for its gabaergic mechanism of action. For this, 41 Wistar rats were used, and in 25 of them a constrictive sciatic neuropathy was induced (Bennet & Xie model. For testing pain symptoms, spontaneous (scratching and evoked behaviors to noxious (46o C and non-noxious (40o C thermal stimuli were quantified. Moreover, a comparative pharmacological study of vigabatrin with other analgesic anticonvulsant drugs was also performed. The results showed a possible dose-dependent analgesic effect of vigabatrin (gamma-vinyl-GABA on experimental neuropathic pain, as shown by the significant (pO uso de anticonvulsivantes no tratamento de neuralgias despertou um interesse em testar novas drogas anticonvulsivantes, e dentre essas a vigabatrina por possuir mecanismo de ação gabaérgico. Para isso, foram usados 41 ratos Wistar e em 25 deles induziu-se neuropatia ciática constritiva (modelo de Bennett & Xie. Para testar sintomas de dor, foram quantificados comportamentos espontâneos (coçar-se e evocados, por meio de estímulos térmicos nocivos (46oC e não-nocivos (40oC. Além disso, realizou-se estudo comparativo da vigabatrina com outros anticonvulsivantes analgésicos. Os resultados mostraram um possível efeito analgésico, dose-dependente, de vigabatrina (gama-vinil-GABA em dor neuropática experimental. Isso foi evidenciado pela diminuição significativa (p<0,05 do comportamento de coçar-se e pelo aumento significativo (p<0,05 da latência de retirada da pata posterior direita a estímulos térmicos nocivos. Isso foi corroborado por achados semelhantes em experimentos com anticonvulsivantes (carbamazepina, fenitoína e ácido valpróico analgésicos. Esse possível efeito analgésico da vigabatrina (ainda não descrito na literatura não é mediado pelo sistema opióide.

  2. Inducible nitric oxide synthase inhibition by 1400W limits pain hypersensitivity in a neuropathic pain rat model.

    Science.gov (United States)

    Staunton, C A; Barrett-Jolley, R; Djouhri, L; Thippeswamy, T

    2018-02-13

    What is the central question of this study? Can modulation of inducible NO synthase reduce pain behaviour and pro-inflammatory cytokine signalling in a rat model of neuropathic pain? What is the main finding and its importance? Nitric oxide synthase-based therapies could be effective for the treatment of peripheral neuropathic pain. Peripheral neuropathic pain (PNP), resulting from injury to or dysfunction of a peripheral nerve, is a major health problem that affects 7-8% of the population. It is inadequately controlled by current drugs and is characterized by pain hypersensitivity, which is believed to be attributable to sensitization of peripheral and CNS neurons by various inflammatory mediators. Here we examined, in a rat model of PNP: (i) whether reducing levels of nitric oxide (NO) with 1400W, a highly selective inhibitor of inducible NO synthase (iNOS), would prevent or attenuate pain hypersensitivity; and (ii) the effects of 1400W on plasma concentrations of several cytokines that are secreted after iNOS upregulation during chronic pain states. The L5 spinal nerve axotomy (SNA) model of PNP was used, and 1400W (20 mg kg -1 ) was administered i.p. at 8 h intervals for 3 days starting at 18 h post-SNA. Changes in plasma concentrations of 12 cytokines in SNA rats treated with 1400W were examined using multiplex enzyme-linked immunosorbent assay. The SNA rats developed behavioural signs of mechanical and heat hypersensitivity. Compared with the vehicle/control, 1400W significantly: (i) limited development of mechanical hypersensitivity at 66 h post-SNA and of heat hypersensitivity at 42 h and at several time points tested thereafter; and (ii) increased the plasma concentrations of interleukin (IL)-1α, IL-1β and IL-10 in the SNA rats. The findings suggest that 1400W might exert its analgesic effects by reducing iNOS and altering the balance between the pro-inflammatory (IL-1β and IL-1α) and anti-inflammatory (IL-10) cytokines and that therapies

  3. The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.

    Science.gov (United States)

    Caspani, Ombretta; Zurborg, Sandra; Labuz, Dominika; Heppenstall, Paul A

    2009-10-08

    Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP) channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG) and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI) model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI) of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.

  4. Management of neuropathic pain following treatment for breast cancer in the absence of recurrence: a challenge for the radiation oncologist

    International Nuclear Information System (INIS)

    Clubb, B.

    2004-01-01

    This report reviews various management options for treatment-induced neuropathic pain in breast cancer. First-line options include tricyclic antidepressants and anticonvulsant drugs. Opioids should be prescribed according to published guidelines. Second-line treatments include lignocaine, mexiletine and ketamine. Sympatholytic therapies are available to patients with features of chronic regional pain syndrome. Anti-inflammatory agents are used for neurogenic inflammation. Surgical interventions are considered for refractory neuropathic pain. Interdisciplinary management is appropriate when persisting pain causes physical and psychosocial disabilities. Copyright (2004) Blackwell Science Pty Ltd

  5. Reaction to topical capsaicin in spinal cord injury patients with and without central pain

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix; Pedersen, Louise H.; Terkelsen, Astrid J.

    2007-01-01

    of a spinal cord injury which already is hyperexcitable, would cause enhanced responses in patients with central pain at the level of injury compared to patients without neuropathic pain and healthy controls. Touch, punctuate stimuli, cold stimuli and topical capsaicin was applied above, at, and below injury......Central neuropathic pain is a debilitating and frequent complication to spinal cord injury (SCI). Excitatory input from hyperexcitable cells around the injured grey matter zone is suggested to play a role for central neuropathic pain felt below the level of a spinal cord injury. Direct evidence...... at the level of injury. Keywords: Spinal cord injury; Neuropathic pain; Capsaicin; Neuronal hyperexcitability; Hyperalgesia; Blood flow...

  6. Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment.

    Science.gov (United States)

    Gur, Ali; Oktayoglu, Pelin

    2008-01-01

    Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are poorly understood disorders that share similar demographic and clinical characteristics. The etiology and pathophysiology of these diseases remain unclear. Because of the similarities between both disorders it was suggested that they share a common pathophysiological mechanisms, namely, central nervous system (CNS) dysfunction. Current hypotheses center on atypical sensory processing in the CNS and dysfunction of skeletal muscle nociception and the hypothalamic-pituitary-adrenal (HPA) axis. Researches suggest that the (CNS) is primarily involved in both disorders in regard to the pain, fatigue and sleep disturbances. Many patients experience difficulty with concentration and memory and many others have mood disturbance, including depression and anxiety. Although fibromyalgia is common and associated with substantial morbidity and disability, there are no US Food and Drug Administration (FDA)-approved treatments except pregabalin. Recent pharmacological treatment studies about fibromyalgia have focused on selective serotonin and norepinephrine (NE) reuptake inhibitors, which enhance serotonin and NE neurotransmission in the descending pain pathways and lack many of the adverse side effects associated with tricyclic medications. CFS is a descriptive term used to define a recognisable pattern of symptoms that cannot be attributed to any alternative condition. The symptoms are currently believed to be the result of disturbed brain function. To date, no pharmacological agent has been reliably shown to be effective treatment for CFS. Management strategies are therefore primarily directed at relief of symptoms and minimising impediments to recovery. This chapter presents data demonstrating CFS, abnormal pain processing and autonomic nervous system (ANS) dysfunction in FM and CFS and concludes by reviewing the new concepts in treatments in CFS and FM.

  7. Assessment of the treatment of chronic hepatitis C in the state of Mato Grosso, central Brazil

    Directory of Open Access Journals (Sweden)

    Francisco Kennedy Scofoni Faleiros de Azevedo

    2012-03-01

    Full Text Available In Brazil, the treatment of hepatitis C virus (HCV infection is funded by the national public health system (SUS. To evaluate treatment results in the state of Mato Grosso, central Brazil, we have consulted the files of the office of the State Department of Health responsible for supplying such medications. We obtained information on 232 treatments of 201 patients who underwent treatment in or prior to 2008. The study was conducted by reviewing medical records, making telephone calls and interviewing the assistant physicians. Thirty-nine patients (19.4% had cirrhosis and HCV genotype 1 predominated (64.3%. Excluding patients with comorbidities or treatment without ribavirin we analysed 175 treatments (sustained virologic response occurred in 32.6% of cases. Twenty-six of these 175 were retreatments and the sustained virological response (SVR rate among them was 30.8%; the SVR rate was 32.9% among those receiving treatment for the first time. The SVR rate of genotype 1 patients was 27.8%, whereas it was 37.5% in non-1 genotype patients. The adjusted multivariate analysis showed association of SVR with the absence of cirrhosis [odds ratio (OR: 7.7; confidence interval (CI 95%: 2.5, 33.3], the use of pegylated interferon (OR: 5.8; CI 95%: 1.5, 21.4, non-1 genotype (OR: 5.3; CI 95%: 1.7, 16.7 and uninterrupted treatment (OR: 9.0; CI 95%: 3.3, 45.4. The SVR rates were similar to those found in other Brazilian studies about HCV, but lower than those found in national and international clinical trials. These data suggest that the treatments of chronic hepatitis C that are made available by SUS does not, under normal conditions, work as well as the original controlled studies indicated.

  8. Neuropathic Pain: Delving into the Oxidative Origin and the Possible Implication of Transient Receptor Potential Channels

    Directory of Open Access Journals (Sweden)

    Cristina Carrasco

    2018-02-01

    Full Text Available Currently, neuropathic pain is an underestimated socioeconomic health problem affecting millions of people worldwide, which incidence may increase in the next years due to chronification of several diseases, such as cancer and diabetes. Growing evidence links neuropathic pain present in several disorders [i.e., spinal cord injury (SCI, cancer, diabetes and alcoholism] to central sensitization, as a global result of mitochondrial dysfunction induced by oxidative and nitrosative stress. Additionally, inflammatory signals and the overload in intracellular calcium ion could be also implicated in this complex network that has not yet been elucidated. Recently, calcium channels namely transient receptor potential (TRP superfamily, including members of the subfamilies A (TRAP1, M (TRPM2 and 7, and V (TRPV1 and 4, have demonstrated to play a role in the nociception mediated by sensory neurons. Therefore, as neuropathic pain could be a consequence of the imbalance between reactive oxygen species and endogen antioxidants, antioxidant supplementation may be a treatment option. This kind of therapy would exert its beneficial action through antioxidant and immunoregulatory functions, optimizing mitochondrial function and even increasing the biogenesis of this vital organelle; on balance, antioxidant supplementation would improve the patient's quality of life. This review seeks to deepen on current knowledge about neuropathic pain, summarizing clinical conditions and probable causes, the relationship existing between oxidative stress, mitochondrial dysfunction and TRP channels activation, and scientific evidence related to antioxidant supplementation.

  9. Characteristics of neuropathic pain in patients with spinal cord injury.

    Science.gov (United States)

    Jang, Joon Young; Lee, Seung Hoon; Kim, MinYoung; Ryu, Ju Seok

    2014-06-01

    To characterize neuropathic pain in patients with spinal cord injury (SCI) according to classification used in the study by Baron et al. (Baron classification), a classification of neuropathic pain based on the mechanism. To also compare the patterns of neuropathic pain in SCI patients with those in patients with other etiologies and to determine the differences in patterns of neuropathic pain between the etiologies. This was a descriptive cross-sectional study. We used the Baron classification to investigate the characteristics of neuropathic pain in SCI. Sixty-one SCI patients with neuropathic pain (The Leeds assessment of neuropathic symptoms and signs score ≥12) were enrolled in this study between November 2012 and August 2013, after excluding patients patients with visual analog scale (VAS) score patients, and patients with systemic disease or pain other than neuropathic pain. The most common pain characteristic was pricking pain followed by electrical pain and numbness. The mean VAS score of at-level neuropathic pain was 7.51 and that of below-level neuropathic pain was 6.83. All of the patients suffered from rest pain, but 18 (54.6%) patients with at-level neuropathic pain and 20 (50.0%) patients with below-level neuropathic pain suffered from evoked pain. There was no significant difference in between at-level and below-level neuropathic pains. The result was quite different from the characteristics of post-herpetic neuralgia, but it was similar to the characteristics of diabetic neuropathy as shown in the study by Baron et al., which means that sensory nerve deafferentation may be the most common pathophysiologic mechanism of neuropathic pain after SCI. Since in our study, we included short and discrete symptoms and signs based on diverse mechanisms, our results could be helpful for determining further evaluation and treatment.

  10. The β-lactam clavulanic acid mediates glutamate transport-sensitive pain relief in a rat model of neuropathic pain

    DEFF Research Database (Denmark)

    Kristensen, P J; Gegelashvili, G; Munro, G

    2017-01-01

    , ceftriaxone, displays analgesic effects in rodent chronic pain models. METHODS: Here, the antinociceptive actions of another β-lactam clavulanic acid, which possesses negligible antibiotic activity, were compared with ceftriaxone in rats with chronic constriction injury (CCI)-induced neuropathic pain......-dependent manner. CONCLUSIONS: Thus, clavulanic acid up-regulates GluTs in cultured rodent- and human astroglia and alleviates CCI-induced hypersensitivity, most likely through up-regulation of GLT1b in spinal dorsal horn. SIGNIFICANCE: Chronic dosing of clavulanic acid alleviates neuropathic pain in rats and up......-regulates glutamate transporters both in vitro and in vivo. Crucially, a similar up-regulation of glutamate transporters in human spinal astrocytes by clavulanic acid supports the development of novel β-lactam-based analgesics, devoid of antibacterial activity, for the clinical treatment of chronic pain....

  11. Scrambler therapy for the treatment of neuropathic pain related to leukemia in a pediatric patient: A case report.

    Science.gov (United States)

    Park, Hahck Soo; Kim, Won-Joong; Kim, Hyung Gon; Yoo, Seung Hee

    2017-11-01

    Cancer-related neuropathic pain often responds poorly to standard pain treatments. Scrambler therapy has relieved refractory chronic pain in several uncontrolled clinical trials. An 11-year-old female patient was suffering from left groin and medial thigh pain after irradiation to the knee. The girl was diagnosed with precursor B-cell lymphoblastic leukemia 2 years ago. Extramedullary relapse of leukemia developed 1 month ago and pain had started. She was treated with oral medications, but she was continuously complaining of severe pain. Neuropathic pain caused by obturator nerve involvement in leukemia. Scrambler therapy. Pain reduction. Scrambler therapy is noninvasive, is not associated with any complications, causes minimal discomfort during treatment, and is very effective in a pediatric patient with cancer-related neuropathic pain.

  12. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain

    Science.gov (United States)

    Guasti, Leonardo; Richardson, Denise; Jhaveri, Maulik; Eldeeb, Khalil; Barrett, David; Elphick, Maurice R; Alexander, Stephen PH; Kendall, David; Michael, Gregory J; Chapman, Victoria

    2009-01-01

    Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord. Selective spinal nerve ligation (SNL) in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P endocannabinoids and related compounds in neuropathic pain states. PMID:19570201

  13. Chronic kidney disease of nontraditional etiology in Central America: a provisional epidemiologic case definition for surveillance and epidemiologic studies.

    Science.gov (United States)

    Lozier, Matthew; Turcios-Ruiz, Reina Maria; Noonan, Gary; Ordunez, Pedro

    2016-11-01

    SYNOPSIS Over the last two decades, experts have reported a rising number of deaths caused by chronic kidney disease (CKD) along the Pacific coast of Central America, from southern Mexico to Costa Rica. However, this specific disease is not associated with traditional causes of CKD, such as aging, diabetes, or hypertension. Rather, this disease is a chronic interstitial nephritis termed chronic kidney disease of nontraditional etiology (CKDnT). According to the Pan American Health Organization (PAHO) mortality database, there are elevated rates of deaths related to kidney disease in many of these countries, with the highest rates being reported in El Salvador and Nicaragua. This condition has been identified in certain agricultural communities, predominantly among male farmworkers. Since CKD surveillance systems in Central America are under development or nonexistent, experts and governmental bodies have recommended creating standardized case definitions for surveillance purposes to monitor and characterize this epidemiological situation. A group of experts from Central American ministries of health, the U.S. Centers for Disease Control and Prevention (CDC), and PAHO held a workshop in Guatemala to discuss CKDnT epidemiologic case definitions. In this paper, we propose that CKD in general be identified by the standard definition internationally accepted and that a suspect case of CKDnT be defined as a person age diseases, and other well-known causes of CKD. A probable case of CKDnT is defined as a suspect case with the same findings confirmed three or more months later.

  14. Evaluation of Analgesic Effects of Hydroalcoholic Extract of Allium cepa L. in Animal Model of Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Sanaz Mahdipour

    2017-05-01

    Full Text Available Abstract Background: Neuropathic pain is a chronic pain that affects on the patient’s quality of life. Use of herbal instead of synthetic drugs recently has been increased due to side effects of synthetic drugs and herbal effective components. Flavonoids are herbal compounds that have analgesic and anti-inflammatory effects. Because Allium cepa L. has a great amount of flavonoids, this study has been designed to evaluate analgesic effects of alcoholic extract of Allium cepa L. on neuropathic pain behavior in chronic constriction injury model in rats. Materials and Methods: In this experimental study, neuropathic pain induced by chronic constriction injury (CCI model in Rats. Animals were randomly divided into 4 groups (n=10 for each: Sham, CCI model, receiving red onion hydroalcoholic extract at a dose of 100 mg/kg and a group receiving gabapentin (100 mg/kg. Red onion extract and gabapentin were administered by gavage for 21 days. Using thermal hyperalgesia, mechanical and thermal allodynia tests, the analgesic effects of extract have been measured. Results: Findings of this study revealed that CCI surgery on rats induced hyperalgesia, mechanical and thermal allodynia. Daily intakes of alcoholic extract of red onion and gabapentin significantly increase the paw withdrawal latency; increase the threshold to mechanical allodynia and decrease in response to acetone. Conclusion: Oral use of alcoholic extract of Allium cepa L. reduces neuropathic pain behavior in CCI model in rats.

  15. Duloxetine Inhibits Microglial P2X4 Receptor Function and Alleviates Neuropathic Pain after Peripheral Nerve Injury.

    Directory of Open Access Journals (Sweden)

    Tomohiro Yamashita

    Full Text Available P2X4 receptors (P2X4R are a family of ATP-gated non-selective cation channels. We previously demonstrated that activation of P2X4R in spinal microglia is crucial for neuropathic pain, a highly debilitating chronic pain condition, suggesting that P2X4R is a potential therapeutic target for treating neuropathic pain. Thus, the identification of a compound that has a potent inhibitory effect on P2X4R is an important clinical challenge. In the present study, we screened a chemical library of clinically approved drugs and show for the first time that duloxetine, a serotonin and noradrenaline reuptake inhibitor, has an inhibitory effect on rodent and human P2X4R. In primary cultured microglial cells, duloxetine also inhibited P2X4R-, but not P2X7R-, mediated responses. Moreover, intrathecal administration of duloxetine in a model of neuropathic pain produced a reversal of nerve injury-induced mechanical allodynia, a cardinal symptom of neuropathic pain. In rats that were pretreated with a serotonin-depleting agent and a noradrenaline neurotoxin, the antiallodynic effect of duloxetine was reduced, but still remained. Based on these results, we suggest that, in addition to duloxetine's primary inhibitory action on serotonin and noradrenaline transporters, an inhibitory effect on P2X4R may be involved at least in part in an antiallodynic effect of intrathecal duloxetine in a model of neuropathic pain.

  16. [Effects of intrathecal escin and clonidine in the treatment of neuropathic pain in rats].

    Science.gov (United States)

    Yao, Xin-hua; Zhou, Pu; Huang, Ying; Wang, Bao; Chen, Chen-yan; Qing, Zhao-hui

    2009-09-01

    To investigate the effects of intrathecal escin and clonidine, used alone or in combination, in the treatment of neuropathic pain in rats and the possible mechanism. Ninety-six male SD rats weighing 250-300 g were chronically implanted with lumbar intrathecal catheters. One week later, the left L5 and L6 spinal nerve roots were ligated to establish the model of spinal nerve ligation neuropathic pain (SNL). The rats were then randomly divided into 16 groups (n=6), including the control (saline), escin, clonidine, escin+clonidine, and the antagonist groups. Mechanical withdrawal threshold was assessed before and at 5, 10, 20, 30, 40, 50 and 60 min after intrathecal administration was evaluated. The maximal possible effect (MPE) was calculated and the effect of the treatments on the neuropathic pain. Isobolographic analysis was performed to characterize any potential interactions between the drugs. MPE was significantly higher in escin group (20, 40 microg), clonidine group (2, 5, 10 microg) and escin+clonidine group [1/4, 1/2 (escin ED(50)+clonidine ED(50))] than in the saline group (Pescin (5-40 microg) or clonidine (1-10 microg) alone dose-dependently alleviated neuropathic pain. Isobolographic analysis suggested a synergistic effect between escin and clonidine. Intrathecal pretreatment with yohimbine (20 microg) antagonized the effects of clonidine (Pescin and clonidine (Pescin and clonidine alone can dose-dependently relieve neuropathic pain. Escin and clonidine produce a synergistic effect for pain relief, which may involve the actions of alpha(2) receptor and Ca(2+) channel.

  17. NEUROPATHIC PAIN-INDUCED DEPRESSIVE-LIKE BEHAVIOR AND HIPPOCAMPAL NEUROGENESIS AND PLASTICITY ARE DEPENDENT ON TNFR1 SIGNALING

    Science.gov (United States)

    Anna, Dellarole; Paul, Morton; Roberta, Brambilla; Winston, Walters; Spencer, Summer; Danielle, Bernardes; Mariagrazia, Grilli; R, Bethea John

    2014-01-01

    Patients suffering from neuropathic pain have a higher incidence of mood disorders such as depression. Increased expression of tumor necrosis factor (TNF) has been reported in neuropathic pain and depressive-like conditions and most of the pro-inflammatory effects of TNF are mediated by the TNF receptor 1 (TNFR1). Here we sought to investigate: 1) the occurrence of depressive-like behavior in chronic neuropathic pain and the associated forms of hippocampal plasticity, and 2) the involvement of TNFR1-mediated TNF signaling as a possible regulator of such events. Neuropathic pain was induced by chronic constriction injury of the sciatic nerve in wild-type and TNFR1−/− mice. Anhedonia, weight loss and physical state were measured as symptoms of depression. Hippocampal neurogenesis, neuroplasticity, myelin remodeling and TNF/TNFRs expression were analyzed by immunohistochemical analysis and western blot assay. We found that neuropathic pain resulted in the development of depressive symptoms in a time dependent manner and was associated with profound hippocampal alterations such as impaired neurogenesis, reduced expression of neuroplasticity markers and myelin proteins. The onset of depressive-like behavior also coincided with increased hippocampal levels of TNF, and decreased expression of TNF receptor 2 (TNFR2), which were all fully restored after mice spontaneously recovered from pain. Notably, TNFR1−/− mice did not develop depressive-like symptoms after injury, nor were there changes in hippocampal neurogenesis and plasticity. Our data show that neuropathic pain induces a cluster of depressive-like symptoms and profound hippocampal plasticity that are dependent on TNF signaling through TNFR1. PMID:24938671

  18. Promoting Gait Recovery and Limiting Neuropathic Pain After Spinal Cord Injury

    OpenAIRE

    Mercier, Catherine; Roosink, Meyke; Bouffard, Jason; Bouyer, Laurent J.

    2016-01-01

    Most persons living with a spinal cord injury experience neuropathic pain in the months following their lesion, at the moment where they receive intensive gait rehabilitation. Based on studies using animal models, it has been proposed that central sensitization in nociceptive pathways (maladaptive plasticity) and plasticity related to motor learning (adaptive plasticity) share common neural mechanisms and compete with each other. This article aims to address the discrepancy between the growin...

  19. Chronic Cardiovascular Disease Mortality in Mountaintop Mining Areas of Central Appalachian States

    Science.gov (United States)

    Esch, Laura; Hendryx, Michael

    2011-01-01

    Purpose: To determine if chronic cardiovascular disease (CVD) mortality rates are higher among residents of mountaintop mining (MTM) areas compared to mining and nonmining areas, and to examine the association between greater levels of MTM surface mining and CVD mortality. Methods: Age-adjusted chronic CVD mortality rates from 1999 to 2006 for…

  20. CENTRAL SENSITIZATION AND MEDICATION IN SPINAL CORD INJURED IN-PATIENTS. A CROSS-SECTIONAL CLINICAL STUDY

    DEFF Research Database (Denmark)

    Rosendahl, A; Kasch, Helge

    Background and aims: A major proportion of spinal cord injured subjects (SCIS) suffers from chronic pain. A majority with neuropathic pain, being: shooting, burning and stabbing. Neurological examination reveals signs of central sensitization (CS) e.g. allodynia and hyperalgesia. CS plays...... an important role in maintained neuropathic pain conditions and may lead to or be induced by analgesics. Medication-overuse-headaches (MOH) alter CNS pain processing systems, and the situation is reversed after discontinuation of headache medication. Aim: To determine the occurrence of CS and conditions...... pressure algometry, Von Frey filaments and pinprick test. Patients fulfill McGill Pain Questionnaire and the International SCI pain data-set. All participants undergo examination of the Pressure Pain Detection Threshold, Pressure Pain Tolerance Threshold, Mechanical Detection Threshold, and Wind...

  1. Functional brain imaging: what has it brought to our understanding of neuropathic pain? A special focus on allodynic pain mechanisms.

    Science.gov (United States)

    Peyron, Roland

    2016-02-01

    Brain responses to nociception are well identified. The same is not true for allodynic pain, a strong painful sensation in response to touch or innocuous cold stimuli that may be experienced by patients with neuropathic pain. Brain (or spinal cord) reorganization that may explain this paradoxical perception still remains largely unknown. Allodynic pain is associated with abnormally increased activity in SII and in the anterior insular cortex, contralateral and/or ipsilateral to allodynia. Because a bilateral increase in activity has been repeatedly reported in these areas in nociceptive conditions, the observed activation during allodynia can explain that a physiologically nonpainful stimulus could be perceived by the damaged nervous system as a painful one. Both secondary somatosensory and insular cortices receive input from the thalamus, which is a major relay of sensory and spinothalamic pathways, the involvement of which is known to be crucial for the development of neuropathic pain. Both thalamic function and structure have been reported to be abnormal or impaired in neuropathic pain conditions including in the basal state, possibly explaining the spontaneous component of neuropathic pain. A further indication as to how the brain can create neuropathic pain response in SII and insular cortices stems from examples of diseases, including single-case reports in whom a focal brain lesion leads to central pain disappearance. Additional studies are required to certify the contribution of these areas to the disease processes, to disentangle abnormalities respectively related to pain and to deafferentation, and, in the future, to guide targeting of stimulation studies.

  2. Cervical Spinal Cord and Dorsal Nerve Root Stimulation for Neuropathic Upper Limb Pain.

    Science.gov (United States)

    Levine, Adrian B; Parrent, Andrew G; MacDougall, Keith W

    2017-01-01

    Spinal cord stimulation (SCS) is a well-established treatment for chronic neuropathic pain in the lower limbs. Upper limb pain comprises a significant proportion of neuropathic pain patients, but is often difficult to target specifically and consistently with paresthesias. We hypothesized that the use of dorsal nerve root stimulation (DNRS), as an option along with SCS, would help us better relieve pain in these patients. All 35 patients trialed with spinal stimulation for upper limb pain between July 1, 2011, and October 31, 2013, were included. We performed permanent implantation in 23/35 patients based on a visual analogue scale pain score decrease of ≥50% during trial stimulation. Both the SCS and DNRS groups had significant improvements in average visual analogue scale pain scores at 12 months compared with baseline, and the majority of patients in both groups obtained ≥50% pain relief. The majority of patients in both groups were able to reduce their opioid use, and on average had improvements in Short Form-36 quality of life scores. Complication rates did not differ significantly between the two groups. Treatment with SCS or DNRS provides meaningful long-term relief of chronic neuropathic pain in the upper limbs.

  3. What Are the Predictors of Altered Central Pain Modulation in Chronic Musculoskeletal Pain Populations? A Systematic Review.

    Science.gov (United States)

    Clark, Jacqui; Nijs, Jo; Yeowell, Gillian; Goodwin, Peter Charles

    2017-09-01

    Altered central pain modulation is the predominant pain mechanism in a proportion of chronic musculoskeletal pain disorders and is associated with poor outcomes. Although existing studies predict poor outcomes such as persistent pain and disability, to date there is little consensus on what factors specifically predict altered central pain modulation. To review the existing literature on the predictive factors specifically for altered central pain modulation in musculoskeletal pain populations. This is a systematic review in accordance with supplemented PRISMA guidelines. A systematic search was performed by 2 mutually blinded reviewers. Relevant articles were screened by title and abstract from Medline, Embase, PubMed, CINAHL, and Web of Science electronic databases. Alternative sources were also sought to locate missed potential articles. Eligibility included studies published in English, adults aged 18 to 65, musculoskeletal pain, baseline measurements taken at the pre-morbid or acute stage, > 3-month follow-up time after pain onset, and primary outcome measures specific to altered central pain modulation. Studies were excluded where there were concurrent diseases or they were non-predictive studies. Risk of bias was assessed using the quality in prognostic studies (QUIPS) tool. Study design, demographics, musculoskeletal region, inclusion/exclusion criteria, measurement timelines, predictor and primary outcome measures, and results were extracted. Data were synthesized qualitatively and strength of evidence was scored using the grading of recommendations, assessment, development, and evaluations (GRADE) scoring system. Nine eligible articles were located, in various musculoskeletal populations (whiplash, n = 2; widespread pain, n = 5; temporomandibular disorder, n = 2). Moderate evidence was found for 2 predictive factors of altered central pain modulation: 1) high sensory sensitivity (using genetic testing or quantitative sensory tests), and 2) psychological

  4. Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity

    Science.gov (United States)

    Latremoliere, Alban; Woolf, Clifford J.

    2009-01-01

    Central sensitization represents an enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition and is a manifestation of the remarkable plasticity of the somatosensory nervous system in response to activity, inflammation, and neural injury. The net effect of central sensitization is to recruit previously subthreshold synaptic inputs to nociceptive neurons, generating an increased or augmented action potential output: a state of facilitation, potentiation, augmentation, or amplification. Central sensitization is responsible for many of the temporal, spatial, and threshold changes in pain sensibility in acute and chronic clinical pain settings and exemplifies the fundamental contribution of the central nervous system to the generation of pain hypersensitivity. Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled, as acute nociceptive pain is, to the presence, intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations. Perspective In this article, we review the major triggers that initiate and maintain central sensitization in healthy individuals in response to nociceptor input and in patients with inflammatory and neuropathic pain, emphasizing the fundamental contribution and multiple mechanisms of synaptic plasticity caused by changes in the density, nature, and properties of ionotropic and metabotropic glutamate receptors. PMID:19712899

  5. Processos inflamatorios cronicos do sistema nervoso central: aspectos neurocirurgicos Inflamatory chronic processes of the central nervous system: neurosurgical aspects

    Directory of Open Access Journals (Sweden)

    Nubor Orlando Facure

    1976-03-01

    Full Text Available São relatados 35 casos de pacientes com síndrome de hipertensão intra-craniana causada por processos inflamatórios crônicos do sistema nervoso central. Apesar da multiplicidade dos agentes etiológicos, a conduta neuro-cirúrgica para a solução da hipertensão intracraniana é semelhante nestes processos. Os pacientes foram divididos em dois grupos. O grupo 1 inclui 7 pacientes nos quais o quadro clínico e neuro-radiológico era de lesão expansiva intracerebral. Estes pacientes foram submetidos a cranotomia com exerese do processo expansivo: tratava-se de cisticercos múltiplos em 5 casos, tuberculoma em um e granuloma blastomicótico em outro. A mortalidade foi nula e não houve recidiva da hipertensão intracraniana. Nos pacientes do grupo 2 as lesões fundamentais são representadas pela ependimite granulosa e leptomeningite crônica das cisternas basais. Os quadros clínico e neuro-radiológico são de hidrocefalia com dilatação ventricular e frequentemente sem sintais neurológicos focais. O prognóstico nestes casos é mais grave devido quase sempre à progressão da doença. Nos 28 pacientes incluídos neste grupo o tratamento de escolha foi a derivação ventriculoatrial ou ventrículoperitonial. A mortalidade foi de 39,2%.A study into the neurosurgical approach to thirty-five patients with increased intracranial pressure due to inflamatory diseases affecting the central nervous system and meninges is reported. The entities under consideration were found to have similar surgical aspects despite the heterogeneity of etiologic agents. As regards the surgical treatment, two groups of cases were recognized. Group 1 comprises 7 patientes with symptoms of a space-occupying lesion; in these patients craniotomies were perfomed with good results. Group 2 included the remainder 28 cases with acquired hydrocephalus. In this group differents methods for ventricular drainage were used, but ventriculo-auriculostomy and specially ventriculo

  6. Central role of T helper 17 cells in chronic hypoxia-induced pulmonary hypertension.

    Science.gov (United States)

    Maston, Levi D; Jones, David T; Giermakowska, Wieslawa; Howard, Tamara A; Cannon, Judy L; Wang, Wei; Wei, Yongyi; Xuan, Weimin; Resta, Thomas C; Gonzalez Bosc, Laura V

    2017-05-01

    Inflammation is a prominent pathological feature in pulmonary arterial hypertension, as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension caused by chronic hypoxia. CD4 + T cells are required for initiating and maintaining inflammation, suggesting that these cells could play an important role in the pathogenesis of hypoxic pulmonary hypertension. Our objective was to test the hypothesis that CD4 + T cells, specifically the T helper 17 subset, contribute to chronic hypoxia-induced pulmonary hypertension. We compared indices of pulmonary hypertension resulting from chronic hypoxia (3 wk) in wild-type mice and recombination-activating gene 1 knockout mice (RAG1 -/- , lacking mature T and B cells). Separate sets of mice were adoptively transferred with CD4 + , CD8 + , or T helper 17 cells before normoxic or chronic hypoxic exposure to evaluate the involvement of specific T cell subsets. RAG1 -/- mice had diminished right ventricular systolic pressure and arterial remodeling compared with wild-type mice exposed to chronic hypoxia. Adoptive transfer of CD4 + but not CD8 + T cells restored the hypertensive phenotype in RAG1 -/- mice. Interestingly, RAG1 -/- mice receiving T helper 17 cells displayed evidence of pulmonary hypertension independent of chronic hypoxia. Supporting our hypothesis, depletion of CD4 + cells or treatment with SR1001, an inhibitor of T helper 17 cell development, prevented increased pressure and remodeling responses to chronic hypoxia. We conclude that T helper 17 cells play a key role in the development of chronic hypoxia-induced pulmonary hypertension. Copyright © 2017 the American Physiological Society.

  7. Pain matrices and neuropathic pain matrices: a review.

    Science.gov (United States)

    Garcia-Larrea, Luis; Peyron, Roland

    2013-12-01

    The pain matrix is conceptualised here as a fluid system composed of several interacting networks. A nociceptive matrix receiving spinothalamic projections (mainly posterior operculoinsular areas) ensures the bodily specificity of pain and is the only one whose destruction entails selective pain deficits. Transition from cortical nociception to conscious pain relies on a second-order network, including posterior parietal, prefrontal and anterior insular areas. Second-order regions are not nociceptive-specific; focal stimulation does not evoke pain, and focal destruction does not produce analgesia, but their joint activation is necessary for conscious perception, attentional modulation and control of vegetative reactions. The ensuing pain experience can still be modified as a function of beliefs, emotions and expectations through activity of third-order areas, including the orbitofrontal and perigenual/limbic networks. The pain we remember results from continuous interaction of these subsystems, and substantial changes in the pain experience can be achieved by acting on each of them. Neuropathic pain (NP) is associated with changes in each of these levels of integration. The most robust abnormality in NP is a functional depression of thalamic activity, reversible with therapeutic manoeuvres and associated with rhythmic neural bursting. Neuropathic allodynia has been associated with enhancement of ipsilateral over contralateral insular activation and lack of reactivity in orbitofrontal/perigenual areas. Although lack of response of perigenual cortices may be an epiphenomenon of chronic pain, the enhancement of ipsilateral activity may reflect disinhibition of ipsilateral spinothalamic pathways due to depression of their contralateral counterpart. This in turn may bias perceptual networks and contribute to the subjective painful experience. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  8. Duloxetine in the management of diabetic peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Boomershine CS

    2011-07-01

    Full Text Available Michelle J Ormseth, Beth A Sholz, Chad S BoomershineDivision of Rheumatology and Immunology, Vanderbilt University, Nashville, TN, USAAbstract: Diabetic neuropathy affects up to 70% of diabetics, and diabetic peripheral neuropathic pain (DPNP is the most common and debilitating of the diabetic neuropathies. DPNP significantly reduces quality of life and increases management costs in affected patients. Despite the impact of DPNP, management is poor with one-quarter of patients receiving no treatment and many treated with medications having little or no efficacy in managing DPNP. Duloxetine is one of two drugs approved by the United States Food and Drug Administration for DPNP management. Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI proven safe, effective, and cost-saving in reducing DPNP symptoms at a dose of 60 mg/day. Duloxetine doses greater than 60 mg/day for DPNP management are not recommended since they are no more efficacious and associated with more side effects; addition of pregabalin or gabapentin for these patients may be beneficial. Side effects of duloxetine are generally mild and typical for the SNRI class including nausea, dizziness, somnolence, fatigue, sweating, dry mouth, constipation, and diarrhea. Given its other indications, duloxetine is a particularly good choice for DPNP treatment in patients with coexisting depression, anxiety, fibromyalgia, or chronic musculoskeletal pain. Duloxetine treatment had no clinically significant effect on glycemic control and did not increase the risk of cardiovascular events in diabetes patients. However, duloxetine use should be avoided in patients with hepatic disease or severe renal impairment. Given its safety, efficacy, and tolerability, duloxetine is an excellent choice for DPNP treatment in many patients.Keywords: duloxetine, diabetic peripheral neuropathic pain, review, treatment

  9. Hedonic and motivational responses to food reward are unchanged in rats with neuropathic pain.

    Science.gov (United States)

    Okun, Alec; McKinzie, David L; Witkin, Jeffrey M; Remeniuk, Bethany; Husein, Omar; Gleason, Scott D; Oyarzo, Janice; Navratilova, Edita; McElroy, Brian; Cowen, Stephen; Kennedy, Jeffrey D; Porreca, Frank

    2016-12-01

    Rewards influence responses to acute painful stimuli, but the relationship of chronic pain to hedonic or motivational aspects of reward is not well understood. We independently evaluated hedonic qualities of sweet or bitter tastants and motivation to seek food reward in rats with experimental neuropathic pain induced by L5/6 spinal nerve ligation. Hedonic response was measured by implantation of intraoral catheters to allow passive delivery of liquid solutions, and "liking/disliking" responses were scored according to a facial reactivity scale. Spinal nerve ligation rats did not differ from controls in either "liking" or "disliking" reactions to intraoral sucrose or quinine, respectively, at postsurgery day 21, suggesting no differences in perceived hedonic value of sweet or bitter tastants. To assess possible motivational deficits during acute and chronic pain, we used fixed- and progressive-ratio response paradigms of sucrose pellet presentation in rats with transient inflammatory or chronic neuropathic pain. Assessment of response acquisition and break points under the progressive ratio schedule revealed no differences between sham and spinal nerve ligation rats for up to 120 days after injury. However, rats with inflammation showed decrements in lever pressing and break points on days 1 and 2 after complete Freund adjuvant injection that normalized by day 4, consistent with transient ongoing pain. Thus, although acute ongoing inflammatory pain may transiently reduce reward motivation, we did not detect influences of chronic neuropathic pain on hedonic or motivational responses to food rewards. Adaptations that allow normal reward responding to food regardless of chronic pain may be of evolutionary benefit to promote survival.

  10. Classification of neuropathic pain in cancer patients

    DEFF Research Database (Denmark)

    Brunelli, Cinzia; Bennett, Michael I; Kaasa, Stein

    2014-01-01

    Neuropathic pain (NP) in cancer patients lacks standards for diagnosis. This study is aimed at reaching consensus on the application of the International Association for the Study of Pain (IASP) special interest group for neuropathic pain (NeuPSIG) criteria to the diagnosis of NP in cancer patients...... was found on the statement "the pathophysiology of NP due to cancer can be different from non-cancer NP" (MED=9, IQR=2). Satisfactory consensus was reached for the first 3 NeuPSIG criteria (pain distribution, history, and sensory findings; MEDs⩾8, IQRs⩽3), but not for the fourth one (diagnostic test....../imaging; MED=6, IQR=3). Agreement was also reached on clinical examination by soft brush or pin stimulation (MEDs⩾7 and IQRs⩽3) and on the use of PRO descriptors for NP screening (MED=8, IQR=3). Based on the study results, a clinical algorithm for NP diagnostic criteria in cancer patients with pain...

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

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    Junying Wang

    2016-01-01

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

  12. Virtual reality-augmented neurorehabilitation improves motor function and reduces neuropathic pain in patients with incomplete spinal cord injury.

    Science.gov (United States)

    Villiger, Michael; Bohli, Dominik; Kiper, Daniel; Pyk, Pawel; Spillmann, Jeremy; Meilick, Bruno; Curt, Armin; Hepp-Reymond, Marie-Claude; Hotz-Boendermaker, Sabina; Eng, Kynan

    2013-10-01

    Neurorehabilitation interventions to improve lower limb function and neuropathic pain have had limited success in people with chronic, incomplete spinal cord injury (iSCI). We hypothesized that intense virtual reality (VR)-augmented training of observed and executed leg movements would improve limb function and neuropathic pain. Patients used a VR system with a first-person view of virtual lower limbs, controlled via movement sensors fitted to the patient's own shoes. Four tasks were used to deliver intensive training of individual muscles (tibialis anterior, quadriceps, leg ad-/abductors). The tasks engaged motivation through feedback of task success. Fourteen chronic iSCI patients were treated over 4 weeks in 16 to 20 sessions of 45 minutes. Outcome measures were 10 Meter Walking Test, Berg Balance Scale, Lower Extremity Motor Score, Spinal Cord Independence Measure, Locomotion and Neuropathic Pain Scale (NPS), obtained at the start and at 4 to 6 weeks before intervention. In addition to positive changes reported by the patients (Patients' Global Impression of Change), measures of walking capacity, balance, and strength revealed improvements in lower limb function. Intensity and unpleasantness of neuropathic pain in half of the affected participants were reduced on the NPS test. Overall findings remained stable 12 to 16 weeks after termination of the training. In a pretest/posttest, uncontrolled design, VR-augmented training was associated with improvements in motor function and neuropathic pain in persons with chronic iSCI, several of which reached the level of a minimal clinically important change. A controlled trial is needed to compare this intervention to active training alone or in combination.

  13. Neuropathic pain: A personal case reflection on a critical incident

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    Balaji P Duraisamy

    2011-01-01

    Full Text Available Neuropathic pain is a distressing symptom for the patient and a difficult symptom for the physician to treat. There is lack of evidence-based clinical guidelines for the management of malignant neuropathic pain. The case reflection is a personal account of what has been learnt from a critical incident in a particular patient in the management of neuropathic pain. Psychological issues are known to increase pain percetion and affect the quality of life. The case reflection explores problem areas, defines lacunae in knowledge, and demonstrates active learning of the management of neuropathic pain through reflective practice.

  14. Neuropathic orofacial pain: Facts and fiction.

    Science.gov (United States)

    Baad-Hansen, Lene; Benoliel, Rafael

    2017-06-01

    Definition and taxonomy This review deals with neuropathic pain of traumatic origin affecting the trigeminal nerve, i.e. painful post-traumatic trigeminal neuropathy (PTTN). Symptomatology The clinical characteristics of PTTN vary considerably, partly due to the type and extent of injury. Symptoms involve combinations of spontaneous and evoked pain and of positive and negative somatosensory signs. These patients are at risk of going through unnecessary dental/surgical procedures in the attempt to eradicate the cause of the pain, due to the fact that most dentists only rarely encounter PTTN. Epidemiology Overall, approximately 3% of patients with trigeminal nerve injuries develop PTTN. Patients are most often female above the age of 45 years, and both physical and psychological comorbidities are common. Pathophysiology PTTN shares many pathophysiological mechanisms with other peripheral neuropathic pain conditions. Diagnostic considerations PTTN may be confused with one of the regional neuralgias or other orofacial pain conditions. For intraoral PTTN, early stages are often misdiagnosed as odontogenic pain. Pain management Management of PTTN generally follows recommendations for peripheral neuropathic pain. Expert opinion International consensus on classification and taxonomy is urgently needed in order to advance the field related to this condition.

  15. Chronic kidney disease of nontraditional etiology in Central America: a provisional epidemiologic case definition for surveillance and epidemiologic studies

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    Matthew Lozier

    Full Text Available SYNOPSIS Over the last two decades, experts have reported a rising number of deaths caused by chronic kidney disease (CKD along the Pacific coast of Central America, from southern Mexico to Costa Rica. However, this specific disease is not associated with traditional causes of CKD, such as aging, diabetes, or hypertension. Rather, this disease is a chronic interstitial nephritis termed chronic kidney disease of nontraditional etiology (CKDnT. According to the Pan American Health Organization (PAHO mortality database, there are elevated rates of deaths related to kidney disease in many of these countries, with the highest rates being reported in El Salvador and Nicaragua. This condition has been identified in certain agricultural communities, predominantly among male farmworkers. Since CKD surveillance systems in Central America are under development or nonexistent, experts and governmental bodies have recommended creating standardized case definitions for surveillance purposes to monitor and characterize this epidemiological situation. A group of experts from Central American ministries of health, the U.S. Centers for Disease Control and Prevention (CDC, and PAHO held a workshop in Guatemala to discuss CKDnT epidemiologic case definitions. In this paper, we propose that CKD in general be identified by the standard definition internationally accepted and that a suspect case of CKDnT be defined as a person age < 60 years with CKD, without type 1 diabetes mellitus, hypertensive diseases, and other well-known causes of CKD. A probable case of CKDnT is defined as a suspect case with the same findings confirmed three or more months later.

  16. Sleep Deprivation Aggravates Median Nerve Injury-Induced Neuropathic Pain and Enhances Microglial Activation by Suppressing Melatonin Secretion

    Science.gov (United States)

    Huang, Chun-Ta; Chiang, Rayleigh Ping-Ying; Chen, Chih-Li; Tsai, Yi-Ju

    2014-01-01

    Study Objectives: Sleep deprivation is common in patients with neuropathic pain, but the effect of sleep deprivation on pathological pain remains uncertain. This study investigated whether sleep deprivation aggravates neuropathic symptoms and enhances microglial activation in the cuneate nucleus (CN) in a median nerve chronic constriction injury (CCI) model. Also, we assessed if melatonin supplements during the sleep deprived period attenuates these effects. Design: Rats were subjected to sleep deprivation for 3 days by the disc-on-water method either before or after CCI. In the melatonin treatment group, CCI rats received melatonin supplements at doses of 37.5, 75, 150, or 300 mg/kg during sleep deprivation. Melatonin was administered at 23:00 once a day. Participants: Male Sprague-Dawley rats, weighing 180-250 g (n = 190), were used. Measurements: Seven days after CCI, behavioral testing was conducted, and immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analyses of microglial activation and measurements of proinflammatory cytokines. Results: In rats who underwent post-CCI sleep deprivation, microglia were more profoundly activated and neuropathic pain was worse than those receiving pre-CCI sleep deprivation. During the sleep deprived period, serum melatonin levels were low over the 24-h period. Administration of melatonin to CCI rats with sleep deprivation significantly attenuated activation of microglia and development of neuropathic pain, and markedly decreased concentrations of proinflammatory cytokines. Conclusions: Sleep deprivation makes rats more vulnerable to nerve injury-induced neuropathic pain, probably because of associated lower melatonin levels. Melatonin supplements to restore a circadian variation in melatonin concentrations during the sleep deprived period could alleviate nerve injury-induced behavioral hypersensitivity. Citation: Huang CT, Chiang RP, Chen CL, Tsai YJ. Sleep

  17. Dor neuropática central após lesão medular traumática: capacidade funcional e aspectos sociais Dolor neuropático central después de lesión medular traumática: capacidad funcional y aspectos sociales Central neuropathic pain after traumatic spinal cord injury: functional capacity and social aspects

    OpenAIRE

    Janaina Vall; Violante Augusta Batista Braga

    2005-01-01

    Estudo de caso comparativo com o objetivo de avaliar a capacidade funcional e os aspectos sociais de dois pacientes, ambos com lesão medular traumática, sem e com dor neuropática central associada, respectivamente. Para avaliar a capacidade funcional, foi utilizado como instrumento o Functional Independence Measure ou Escala de Independência Funcional. E para avaliar os aspectos sociais foi construído o ecomapa de cada paciente, preconizado pelo modelo Calgary de avaliação de famílias. Ambos ...

  18. Neuropathic pain as a process: reversal of chronification in an animal model

    Directory of Open Access Journals (Sweden)

    Dableh LJ

    2011-09-01

    Full Text Available Liliane J Dableh1,2, Kiran Yashpal1,2, James L Henry1,21Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada; 2Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, CanadaAbstract: Peripheral neuropathic pain arises from trauma to sensory nerves. Other types of acute neurotrauma such as stroke and spinal cord injury are treated immediately, largely to prevent secondary damage. To pursue the possibility that neuropathic pain may also be amenable to early treatment, a rat model of neuropathic pain was induced using a 2-mm polyethylene cuff implanted around one sciatic nerve. Within 24 hours, hypersensitivity to von Frey hair stimulation appeared, as indicated by decreased paw withdrawal thresholds. When the cuff was removed 24 hours after implantation, readings returned to pre-implantation levels starting as early as day 18. When the cuff was removed after 4 days, there was a period of initial hypersensitivity, and then an increase toward baseline at two time points near the end of the study; therefore, only a partial recovery toward pre-implantation values occurred. Having established that a temporal reversal can occur, the next step examined possible pharmacological reversal. The tachykinin NK1 receptor antagonist, CP-96,345, produced a minor increase in withdrawal thresholds in animals with the cuff left permanently implanted. To determine the effect of early and repeated administration of CP-96,345, it was given daily on days 1–4. The cuff was removed on day 4. Six days later, readings showed reversal of tactile hypersensitivity. We suggest that persistent neuropathic pain occurs from processes that develop over several hours and days, and that some of these processes may be prevented by early medical intervention. Thus, nerve injury in the context of chronic neuropathic pain should be treated in a similar manner to nerve injury resulting from stroke, spinal cord

  19. Ketamine for chronic pain: risks and benefits

    Science.gov (United States)

    Niesters, Marieke; Martini, Christian; Dahan, Albert

    2014-01-01

    The anaesthetic ketamine is used to treat various chronic pain syndromes, especially those that have a neuropathic component. Low dose ketamine produces strong analgesia in neuropathic pain states, presumably by inhibition of the N-methyl-D-aspartate receptor although other mechanisms are possibly involved, including enhancement of descending inhibition and anti-inflammatory effects at central sites. Current data on short term infusions indicate that ketamine produces potent analgesia during administration only, while three studies on the effect of prolonged infusion (4–14 days) show long-term analgesic effects up to 3 months following infusion. The side effects of ketamine noted in clinical studies include psychedelic symptoms (hallucinations, memory defects, panic attacks), nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity. The recreational use of ketamine is increasing and comes with a variety of additional risks ranging from bladder and renal complications to persistent psychotypical behaviour and memory defects. Blind extrapolation of these risks to clinical patients is difficult because of the variable, high and recurrent exposure to the drug in ketamine abusers and the high frequency of abuse of other illicit substances in this population. In clinical settings, ketamine is well tolerated, especially when benzodiazepines are used to tame the psychotropic side effects. Irrespective, close monitoring of patients receiving ketamine is mandatory, particularly aimed at CNS, haemodynamic, renal and hepatic symptoms as well as abuse. Further research is required to assess whether the benefits outweigh the risks and costs. Until definite proof is obtained ketamine administration should be restricted to patients with therapy-resistant severe neuropathic pain. PMID:23432384

  20. Tryptophan and Kynurenic Acid May Produce an Amplified Effect in Central Fatigue Induced by Chronic Sleep Disorder

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    Masatoshi Yamashita

    2014-01-01

    Full Text Available Tryptophan (TRP and its neuroactive metabolite, kynurenic acid (KYNA, are thought to play key roles in central fatigue, but the specifics are still unknown. To clarify their roles in the brain, we developed a rat model of central fatigue induced by chronic sleep disorder (CFSD by disturbing the sleep-wake cycle. Results showed that while 5-hydroxytryptamine (5-HT concentration did not differ between control and CFSD groups, levels of TRP and KYNA in the CFSD group were about 2 and 5 times higher in the hypothalamus, and 2 and 3.5 times higher in the hippocampus, respectively. Moreover, CFSD-induced fatigue led to abnormal running performance (via treadmill test and social interaction (via social-interaction test. These results support a TRP-KYNA hypothesis in central fatigue in which increased TRP concentration in the brain and subsequently synthesized KYNA may produce an amplified effect on central fatigue, with enhanced concentrations being a possible mechanism by which social-interaction deficits are generated.

  1. Motor cortex stimulation for neuropathic pain: From phenomenology to mechanisms.

    Science.gov (United States)

    Garcia-Larrea, Luis; Peyron, Roland

    2007-01-01

    Motor cortex stimulation (MCS) is relatively recent neurosurgical technique for pain control, the use of which is growing steadily since its description in the last decade. While clinical series show that at least 50% of patients with chronic, pharmacoresistant neuropathic pain may benefit from this technique, the mechanisms of action of MCS remain elusive. In this review, we synthesise a number of studies that, combining electrophysiology and functional imaging, have permitted to proceed from phenomenology to models that may account for part of such mechanisms. MCS appears to trigger rapid and phasic activation in the lateral thalamus, which leads to a cascade of events of longer time-course in medial thalamus, anterior cingulate/orbitofrontal cortices and periaqueductal grey matter. Activity in these latter structures is delayed relative to actual cortical neurostimulation and becomes maximal during the hours that follow MCS arrest. Current hypotheses suggest that MCS may act through at least two mechanisms: activation of perigenual cingulate and orbitofrontal areas may modulate the emotional appraisal of pain, rather than its intensity, while top down activation of brainstem PAG may lead to descending inhibition toward the spinal cord. Recent evidence also points to a possible secretion of endogenous opioids triggered by chronic MCS. This, along with the delayed and long-lasting activation of several brain structures, is consistent with the clinical effects of MCS, which may also last for hours or days after MCS discontinuation.

  2. Mitogen activated protein kinase phosphatase-1 prevents the development of tactile sensitivity in a rodent model of neuropathic pain

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    Ndong Christian

    2012-04-01

    Full Text Available Abstract Background Neuropathic pain due to nerve injury is one of the most difficult types of pain to treat. Following peripheral nerve injury, neuronal and glial plastic changes contribute to central sensitization and perpetuation of mechanical hypersensitivity in rodents. The mitogen activated protein kinase (MAPK family is pivotal in this spinal cord plasticity. MAPK phosphatases (MKPs limit inflammatory processes by dephosphorylating MAPKs. For example, MKP-1 preferentially dephosphorylates p-p38. Since spinal p-p38 is pivotal for the development of chronic hypersensitivity in rodent models of pain, and p-p38 inhibitors have shown clinical potential in acute and chronic pain patients, we hypothesize that induction of spinal MKP-1 will prevent the development of peripheral nerve-injury-induced hypersensitivity and p-p38 overexpression. Results We cloned rat spinal cord MKP-1 and optimize MKP-1 cDNA in vitro using transfections to BV-2 cells. We observed that in vitro overexpression of MKP-1 blocked lipopolysaccharide-induced phosphorylation of p38 (and other MAPKs as well as release of pro-algesic effectors (i.e., cytokines, chemokines, nitric oxide. Using this cDNA MKP-1 and a non-viral, in vivo nanoparticle transfection approach, we found that spinal cord overexpression of MKP-1 prevented development of peripheral nerve-injury-induced tactile hypersensitivity and reduced pro-inflammatory cytokines and chemokines and the phosphorylated form of p38. Conclusions Our results indicate that MKP-1, the natural regulator of p-p38, mediates resolution of the spinal cord pro-inflammatory milieu induced by peripheral nerve injury, resulting in prevention of chronic mechanical hypersensitivity. We propose that MKP-1 is a potential therapeutic target for pain treatment or prevention.

  3. Political instability, chronic poverty and food production systems in Central Chad

    NARCIS (Netherlands)

    Dijk, van J.W.M.

    2008-01-01

    In many parts of the world long-term political instability combined with frequent droughts results in chronic poverty and high levels of malnutrition and child mortality. Despite the magnitude and importance of the problem in these areas, the relation between political instability, resource tenure

  4. Central Sensitization and Perceived Indoor Climate among Workers with Chronic Upper-Limb Pain

    DEFF Research Database (Denmark)

    Sundstrup, Emil; Jakobsen, Markus D; Brandt, Mikkel

    2015-01-01

    threshold (PPT) was measured in muscles of the arm, shoulder, and lower leg. Cross-sectional associations were determined using general linear models controlled for age, smoking, and job position. The number of indoor climate complaints was twice as high among workers with chronic pain compared with pain...

  5. Chronic cardiovascular disease mortality in mountaintop mining areas of central Appalachian states.

    Science.gov (United States)

    Esch, Laura; Hendryx, Michael

    2011-01-01

    To determine if chronic cardiovascular disease (CVD) mortality rates are higher among residents of mountaintop mining (MTM) areas compared to mining and nonmining areas, and to examine the association between greater levels of MTM surface mining and CVD mortality. Age-adjusted chronic CVD mortality rates from 1999 to 2006 for counties in 4 Appalachian states where MTM occurs (N = 404) were linked with county coal mining data. Three groups of counties were compared: MTM, coal mining but not MTM, and nonmining. Covariates included smoking rate, rural-urban status, percent male population, primary care physician supply, obesity rate, diabetes rate, poverty rate, race/ethnicity rates, high school and college education rates, and Appalachian county. Linear regression analyses examined the association of mortality rates with mining in MTM areas and non-MTM areas and the association of mortality with quantity of surface coal mined in MTM areas. Prior to covariate adjustment, chronic CVD mortality rates were significantly higher in both mining areas compared to nonmining areas and significantly highest in MTM areas. After adjustment, mortality rates in MTM areas remained significantly higher and increased as a function of greater levels of surface mining. Higher obesity and poverty rates and lower college education rates also significantly predicted CVD mortality overall and in rural counties. MTM activity is significantly associated with elevated chronic CVD mortality rates. Future research is necessary to examine the socioeconomic and environmental impacts of MTM on health to reduce health disparities in rural coal mining areas. © 2011 National Rural Health Association.

  6. Event-related cortical processing in neuropathic pain under long-term spinal cord stimulation.

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    Weigel, Ralf; Capelle, H Holger; Flor, Herta; Krauss, Joachim K

    2015-01-01

    Several mechanisms were suggested in the past to explain the beneficial effect of spinal cord stimulation (SCS) in patients suffering from neuropathic pain. Little is known about potential supraspinal mechanisms. In this study cortical signaling of patients with neuropathic pain and successful long-term treatment with SCS was analyzed. Observational study. University hospital, neurosurgical department, outpatient clinic for movement disorders and pain, institute for cognitive and clinical neuroscience. Nine patients with neuropathic pain of a lower extremity with a lasting response to chronic SCS were included. Cortical activity was analyzed using event-related potentials of the electroencephalogram after non-painful and painful stimulation. Each patient was tested under the effect of long-term SCS and 24 hours after cessation of SCS. Cortical areas involved in the peaks of evoked potentials were localized using a source localization method based on a fixed dipole model. Detection threshold and intensity of non-painful stimulation did not differ significantly on both sides. Pain threshold was significantly lower on the neuropathic side under the effect of SCS (P = 0.03). Bilateral pain thresholds were significantly lower (P = 0.03 healthy side, P = 0.003 neuropathic side) in 5 patients with increased pain after cessation of SCS. Under the effect of SCS cortical negativities (N1, N2, N3) and positivities (P1) demonstrated bilaterally comparable amplitudes. After cessation of SCS, decreased threshold for peripheral stimulation resulted in lowered negativities on both sides. The positivity P1 was differentially regulated and was reduced more contralateral to the unaffected side. N2 was localized at the sensory representation of the leg within the homunculus. The main vector of P1 was localized within the cingular cortex (CC) and moved more anteriorly under the effect of SCS. The exact time span that SCS continues to have an effect is not known. However, due to patient

  7. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

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    Karine Thibault

    Full Text Available Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.

  8. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

    Science.gov (United States)

    Thibault, Karine; Calvino, Bernard; Rivals, Isabelle; Marchand, Fabien; Dubacq, Sophie; McMahon, Stephen B; Pezet, Sophie

    2014-01-01

    Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.

  9. The analgesic effect on neuropathic pain of retrogradely transported botulinum neurotoxin A involves Schwann cells and astrocytes.

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    Sara Marinelli

    Full Text Available In recent years a growing debate is about whether botulinum neurotoxins are retrogradely transported from the site of injection. Immunodetection of cleaved SNAP-25 (cl-SNAP-25, the protein of the SNARE complex targeted by botulinum neurotoxin serotype A (BoNT/A, could represent an excellent approach to investigate the mechanism of action on the nociceptive pathways at peripheral and/or central level. After peripheral administration of BoNT/A, we analyzed the expression of cl-SNAP-25, from the hindpaw's nerve endings to the spinal cord, together with the behavioral effects on neuropathic pain. We used the chronic constriction injury of the sciatic nerve in CD1 mice as animal model of neuropathic pain. We evaluated immunostaining of cl-SNAP-25 in the peripheral nerve endings, along the sciatic nerve, in dorsal root ganglia and in spinal dorsal horns after intraplantar injection of saline or BoNT/A, alone or colocalized with either glial fibrillar acidic protein, GFAP, or complement receptor 3/cluster of differentiation 11b, CD11b, or neuronal nuclei, NeuN, depending on the area investigated. Immunofluorescence analysis shows the presence of the cl-SNAP-25 in all tissues examined, from the peripheral endings to the spinal cord, suggesting a retrograde transport of BoNT/A. Moreover, we performed in vitro experiments to ascertain if BoNT/A was able to interact with the proliferative state of Schwann cells (SC. We found that BoNT/A modulates the proliferation of SC and inhibits the acetylcholine release from SC, evidencing a new biological effect of the toxin and further supporting the retrograde transport of the toxin along the nerve and its ability to influence regenerative processes. The present results strongly sustain a combinatorial action at peripheral and central neural levels and encourage the use of BoNT/A for the pathological pain conditions difficult to treat in clinical practice and dramatically impairing patients' quality of life.

  10. Identifying Predictors of Central Sleep Apnea/Cheyne-Stokes Breathing in Chronic Heart Failure: a Pathophysiological Approach.

    Science.gov (United States)

    Draganova, Aneliya I; Terziyski, Kiril V; Kostianev, Stefan S

    2016-12-01

    Chronic heart failure (CHF) is a major health problem associated with increased mortality, despite modern treatment options. Central sleep apnea (CSA)/Cheyne-Stokes breathing (CSB) is a common and yet largely under-diagnosed co-morbidity, adding significantly to the poor prognosis in CHF because of a number of acute and chronic effects, including intermittent hypoxia, sympathetic overactivation, disturbed sleep architecture and impaired physical tolerance. It is characterized by repetitive periods of crescendo-decrescendo ventilatory pattern, alternating with central apneas and hypopneas. The pathogenesis of CSA/CSB is based on the concept of loop gain, comprising three major components: controller gain, plant gain and feedback gain. Laboratory polysomnography, being the golden standard for diagnosing sleep-disordered breathing (SDB) at present, is a costly and highly specialized procedure unable to meet the vast diagnostic demand. Unlike obstructive sleep apnea, CSA/CSB has a low clinical profile. Therefore, a reliable predictive system is needed for identifying CHF patients who are most likely to suffer from CSA/CSB, optimizing polysomnography use. The candidate predictors should be standardized, easily accessible and low-priced in order to be applied in daily medical routine. The present review focuses on a pathophysiological approach to the selection of some predictors based on parameters reflecting the etiology, the pathogenesis and the consequences of CSA/CSB in CHF.

  11. Identifying Predictors of Central Sleep Apnea/Cheyne-Stokes Breathing in Chronic Heart Failure: a Pathophysiological Approach

    Directory of Open Access Journals (Sweden)

    Draganova Aneliya I.

    2016-12-01

    Full Text Available Chronic heart failure (CHF is a major health problem associated with increased mortality, despite modern treatment options. Central sleep apnea (CSA/Cheyne-Stokes breathing (CSB is a common and yet largely under-diagnosed co-morbidity, adding significantly to the poor prognosis in CHF because of a number of acute and chronic effects, including intermittent hypoxia, sympathetic overactivation, disturbed sleep architecture and impaired physical tolerance. It is characterized by repetitive periods of crescendo-decrescendo ventilatory pattern, alternating with central apneas and hypopneas. The pathogenesis of CSA/CSB is based on the concept of loop gain, comprising three major components: controller gain, plant gain and feedback gain. Laboratory polysomnography, being the golden standard for diagnosing sleep-disordered breathing (SDB at present, is a costly and highly specialized procedure unable to meet the vast diagnostic demand. Unlike obstructive sleep apnea, CSA/CSB has a low clinical profile. Therefore, a reliable predictive system is needed for identifying CHF patients who are most likely to suffer from CSA/CSB, optimizing polysomnography use. The candidate predictors should be standardized, easily accessible and low-priced in order to be applied in daily medical routine.

  12. Long term outcomes for patients treated with half-fluence photodynamic therapy for chronic central serous chorioretinopathy: a case series

    Science.gov (United States)

    Doyle, Jennifer; Gupta, Bhaskar; Tahir, Irfan

    2018-01-01

    A case series was used to evaluate the efficacy of half-fluence photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSCR). Patients were treated with standard-dose verteporfin and half-fluence PDT. Totally 13 eyes from 11 patients were included. The mean patient age was 52.0y. There was a mean reduction in central retinal thickness of 107.0 microns. Totally 7/13 eyes (53.8%) achieved resolution of subretinal fluid (SRF) on optical coherence tomography (OCT) scan after 1 treatment with PDT. Four eyes had further treatment with PDT; of these 1 eye achieved resolution of SRF. Seven of the 13 eyes (53.8%) achieved an improvement of more than 5 ETDRS letters. One patient experienced acute macula oedema 1d post PDT treatment. These results support the hypothesis that half-fluence PDT can have a positive effect in chronic CSCR for a gain in visual acuity and reduction in sub-retinal fluid. Acute macula oedema is a rare but potential adverse effect of half-fluence PDT. PMID:29487828

  13. Effect of Patient Education on Reducing Medication in Spinal Cord Injury Patients With Neuropathic Pain.

    Science.gov (United States)

    Shin, Ji Cheol; Kim, Na Young; Chang, Shin Hye; Lee, Jae Joong; Park, Han Kyul

    2017-08-01

    To determine whether providing education about the disease pathophysiology and drug mechanisms and side effects, would be effective for reducing the use of pain medication while appropriately managing neurogenic pain in spinal cord injury (SCI) patients. In this prospective study, 109 patients with an SCI and neuropathic pain, participated in an educational pain management program. This comprehensive program was specifically created, for patients with an SCI and neuropathic pain. It consisted of 6 sessions, including educational training, over a 6-week period. Of 109 patients, 79 (72.5%) initially took more than two types of pain medication, and this decreased to 36 (33.0%) after the educational pain management program was completed. The mean pain scale score and the number of pain medications decreased, compared to the baseline values. Compared to the non-response group, the response group had a shorter duration of pain onset (p=0.004), and a higher initial number of different medications (ppain management program, can be a valuable complement to the treatment of spinal cord injured patients with neuropathic pain. Early intervention is important, to prevent patients from developing chronic SCI-related pain.

  14. Effects of Ginkgo Biloba Extract EGb-761 on Neuropathic Pain in Mice: Involvement of Opioid System.

    Science.gov (United States)

    Zhu, Chao; Li, Wei; Xu, Fan; Li, Mo; Yang, Liu; Hu, Xue-Yu; Ye, Zheng-Xu; Wang, Zhe; Luo, Zhuo-Jing

    2016-11-01

    Neuropathic pain is considered as one of the most difficult types of pain to manage with conventional analgesics. EGb-761 is extracted from leaves of Ginkgo biloba and has analgesia and anti-inflammatory properties. This study aimed to examine the effect of EGb-761 on chronic constriction injury (CCI)-induced neuropathic pain behaviors, including thermal hyperalgesia and mechanical allodynia, and to explore the possible mechanisms underlying this action. To this end, CCI mice were intraperitoneally injected with EGb-761 (10, 20, 40, and 80 mg/kg), and thermal hyperalgesia, mechanical allodynia, cytokines, and mu-opioid receptor expression were measured. Results showed that EGb-761 attenuated thermal hyperalgesia and mechanical allodynia dose-dependently and the best delivery time window was from day 7 to day 14 after CCI. Additionally, EGb-761 treatment significantly decreased pro-inflammatory cytokines and enhanced mu opioid receptor (MOR) expression in the sciatic nerve. Moreover, the opioid antagonist naloxone prevented the effect of EGb-761 on thermal hyperalgesia and mechanical allodynia but did not influence the effect of EGb-761 on inflammatory cytokines. In conclusion, this study suggests that the potential of EGb-761 as a new analgesic for neuropathic pain treatment, and opioid system may be involved in the EGb-761-induced attenuation of thermal hyperalgesia and mechanical allodynia. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Prevalence of acute neuropathic pain after cancer surgery: A prospective study

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    P N Jain

    2014-01-01

    Full Text Available Background and Aims: Acute neuropathic pain (ANP is an under-recognised and under-diagnosed condition and often difficult to treat. If left untreated, it may further transform into persistent post-operative chronic pain leading to a disability. Aims: This prospective study was undertaken on 300 patients to identify the prevalence of ANP in the post-operative period by using a neuropathic pain detection questionnaire tool. Methods: This is an open-label study in which patients with six different types of cancer surgeries (Thoracic, gastro-intestinal, gynae/urology, bone/soft-tissue, head and neck and breast subgroups-50 each were included for painDETECT questionnaire tool on the 2 nd and 7 th day surgery. Results: This study found a 10% point prevalence of ANP. Analysis showed that 25 patients had ′possible′ ANP, the maximum from urological cancer surgery (6 followed by thoracic surgery (5. Five patients were found to have ′positive′ ANP including 2 groin node dissection, 2 hemipelvectomy and 1 oesophagectomy. Conclusion: Significant relationship between severity of post-operative pain was found with the occurrence of ANP in the post-operative period requiring a special attention to neuropathic pain assessment. Larger studies are required with longer follow-up to identify accurately the true prevalence and causative factors of ANP after surgery.

  16. Magnetic resonance imaging of sequelae of central pontine myelinolysis in chronic alcohol abusers

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, Akira; Kudo, Sho [Department of Radiology, Saga Medical School, 5-1-1 Nabeshima, 849-8501, Saga (Japan); Yuzuriha, Takefumi; Murakami, Masaru; Endoh, Koichi; Hiejima, Shigeto; Koga, Hiroshi [Center for Emotional and Behavional Disorders, Hizen National Hospital, 160 Mitsu, Higashisefuri, Kanzaki, 842-0192, Saga (Japan)

    2003-12-01

    Central pontine myelinolysis (CPM) is one of the serious neurological complications of alcoholism. This study evaluated magnetic resonance images of sequelae of CPM. Approximately 600 alcoholic patients were examined by a 1.0-T magnetic resonance imaging device, and 11 patients were retrospectively found to have a central pontine lesion, a presumed sequela of CPM. The lesions had various shapes and most were cavitary. In 3 of the 11 patients bilateral symmetrical oval lesions were faintly visible in the middle cerebellar peduncles. These middle cerebellar peduncular lesions were diagnosed as having Wallerian degeneration of the pontocerebellar tract secondary to CPM. (orig.)

  17. Src-family kinases activation in spinal microglia contributes to central sensitization and chronic pain after lumbar disc herniation.

    Science.gov (United States)

    Huang, Yangliang; Li, Yongyong; Zhong, Xiongxiong; Hu, Yuming; Liu, Pan; Zhao, Yuanshu; Deng, Zhen; Liu, Xianguo; Liu, Shaoyu; Zhong, Yi

    2017-01-01

    Background Lumbar disc herniation is a major cause of radicular pain, but the underlying mechanisms remain largely unknown. Spinal activation of src-family kinases are involved in the development of chronic pain from nerve injury, inflammation, and cancer. In the present study, the role of src-family kinases activation in lumbar disc herniation-induced radicular pain was investigated. Results Lumbar disc herniation was induced by implantation of autologous nucleus pulposus, harvest from tail, in lumbar 4/5 spinal nerve roots of rat. Behavior test and electrophysiologic data showed that nucleus pulposus implantation induced persistent mechanical allodynia and thermal hyperalgesia and increased efficiency of synaptic transmission in spinal dorsal horn which underlies central sensitization of pain sensation. Western blotting and immunohistochemistry staining revealed that the expression of phosphorylated src-family kinases was upregulated mainly in spinal microglia of rats with nucleus pulposus. Intrathecal delivery of src-family kinases inhibitor PP2 alleviated pain behaviors, decreased efficiency of spinal synaptic transmission, and reduced phosphorylated src-family kinases expression. Furthermore, we found that the expression of ionized calcium-binding adapter molecule 1 (marker of microglia), tumor necrosis factor-α, interleukin 1 -β in spinal dorsal horn was increased in rats with nucleus pulposus. Therapeutic effect of PP2 may be related to its capacity in reducing the expression of these factors. Conclusions These findings suggested that central sensitization was involved in radicular pain from lumbar disc herniation; src-family kinases-mediated inflammatory response may be responsible for central sensitization and chronic pain after lumbar disc herniation.

  18. Effect the exercise program on neuropathic pain intensity in patients with paraplegia Spinal Cord Injury

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    Sedghi Goyaghaj N

    2015-11-01

    Full Text Available Background and Objective: Patients with spinal cord injury suffer from continuous and persistent neuropathic pain that has a destructive impact on their quality of life. Exercise therapy is one of the non-pharmacological interventions that is recommended to control chronic pain, This study aimed to determine the effect of exercise program on neuropathic pain intensity in patients with paraplegia Spinal Cord Injury. Materials and Method: This study is a clinical trial.that population was the all of the patients with spinal cord injury, who referred to one of the educational hospitals in Tehran in 2014, 40 patient were selected based on purposive sampling and were randomly allocated into two groups of experimental and control. Exercise program for paraplegia spinal cord injury was implemented in experimental group during twelve 45-60minutes sessions, twice a week. Data collection was done before and one week after the intervention through using personal information form and, The International Spinal Cord Injury Pain Basic Data Set. Data were analyzed with statistical software SPSS19 and Fisher's exact test, Independent samples T-test Paired T-test and Chi square. Results: The mean score of neuropathic pain intensity before the intervention was 8.05 ± 1.51 in intervention group and 7.57 ± 1.21 in the control group. These amounts after the intervention were 5.55 ± 1.61 and 7.37 ± 1.05 respectively (p < 0.001. Conclusion: Results showed that the regular exercise program can reduce neuropathic pain severity in patients with spinal cord injuries and it can be recommended as a non-pharmacological method of pain control in these patients.

  19. Neuropathic pain prevalence following spinal cord injury: A systematic review and meta-analysis.

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    Burke, D; Fullen, B M; Stokes, D; Lennon, O

    2017-01-01

    Following spinal cord injury (SCI), chronic pain is a common secondary complication with neuropathic pain (NP) cited as one of the most distressing and debilitating conditions leading to poor quality of life, depression and sleep disturbances. Neuropathic pain presenting at or below the level of injury is largely refractory to current pharmacological and physical treatments. No consensus on the prevalence of NP post SCI currently exists, hence this systematic review was undertaken. The review comprised three phases: a methodological assessment of databases [PubMed, Embase, Web of Knowledge, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library and Physiotherapy Evidence Database (PEDro)] identifying potential papers and screening for inclusion criteria by two independent reviewers; data extraction; and finally rating of internal validity and strength of the evidence, using a published valid and reliable scale. Meta-analysis estimated pooled point prevalence rates using a random effects model. In total, 17 studies involving 2529 patients were included in the review. Overall point prevalence rates for NP were established at 53% (38.58-67.47); 19% (13.26-26.39) for at-level NP and 27% (19.89-34.61) for below-level NP, with high heterogeneity noted (I 2  = 84-93%). Prevalence rates for NP following SCI are high. Future studies should include established definitions, classification systems and assessment tools for NP at defined time points post SCI to follow the trajectory of this problem across the lifespan and include indices of sleep, mood and interference to allow for appropriate, optimal and timely NP management for each patient. WHAT DOES THIS REVIEW ADD?: This is the first systematic review and meta-analysis to record pooled point prevalence of neuropathic pain post spinal cord injury at 53%. Additional pooled analysis shows that neuropathic pain is more common below the level of lesion, in patients with tetraplegia, older patients

  20. Thalamic deep brain stimulation for neuropathic pain after amputation or brachial plexus avulsion.

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    Pereira, Erlick A C; Boccard, Sandra G; Linhares, Paulo; Chamadoira, Clara; Rosas, Maria José; Abreu, Pedro; Rebelo, Virgínia; Vaz, Rui; Aziz, Tipu Z

    2013-09-01

    Fifteen hundred patients have received deep brain stimulation (DBS) to treat neuropathic pain refractory to pharmacotherapy over the last half-century, but few during the last decade. Deep brain stimulation for neuropathic pain has shown variable outcomes and gained consensus approval in Europe but not the US. This study prospectively evaluated the efficacy at 1 year of DBS for phantom limb pain after amputation, and deafferentation pain after brachial plexus avulsion (BPA), in a single-center case series. Patient-reported outcome measures were collated before and after surgery, using a visual analog scale (VAS) score, 36-Item Short-Form Health Survey (SF-36), Brief Pain Inventory (BPI), and University of Washington Neuropathic Pain Score (UWNPS). Twelve patients were treated over 29 months, receiving contralateral, ventroposterolateral sensory thalamic DBS. Five patients were amputees and 7 had BPAs, all from traumas. A postoperative trial of externalized DBS failed in 1 patient with BPA. Eleven patients proceeded to implantation and gained improvement in pain scores at 12 months. No surgical complications or stimulation side effects were noted. In the amputation group, after 12 months the mean VAS score improved by 90.0% ± 10.0% (p = 0.001), SF-36 by 57.5% ± 97.9% (p = 0.127), UWNPS by 80.4% ± 12.7% (p stimulation demonstrated efficacy at 1 year for chronic neuropathic pain after traumatic amputation and BPA. Clinical trials that retain patients in long-term follow-up are desirable to confirm findings from prospectively assessed case series.

  1. Synaptic Homeostasis and Allostasis in the Dentate Gyrus Caused by Inflammatory and Neuropathic Pain Conditions

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    Rui-Rui Wang

    2018-01-01

    Full Text Available It has been generally accepted that pain can cause imbalance between excitation and inhibition (homeostasis at the synaptic level. However, it remains poorly understood how this imbalance (allostasis develops in the CNS under different pain conditions. Here, we analyzed the changes in both excitatory and inhibitory synaptic transmission and modulation of the dentate gyrus (DG under two pain conditions with different etiology and duration. First, it was revealed that the functions of the input-output (I/O curves for evoked excitatory postsynaptic currents (eEPSCs following the perforant path (PP stimulation were gained under both acute inflammatory and chronic neuropathic pain conditions relative to the controls. However, the functions of I/O curves for the PP-evoked inhibitory postsynaptic currents (eIPSCs differed between the two conditions, namely it was greatly gained under inflammatory condition, but was reduced under neuropathic condition in reverse. Second, both the frequency and amplitude of miniature IPSCs (mIPSCs were increased under inflammatory condition, however a decrease in frequency of mIPSCs was observed under neuropathic condition. Finally, the spike discharge of the DG granule cells in response to current injection was significantly increased by neuropathic pain condition, however, no different change was found between inflammatory pain condition and the control. These results provide another line of evidence showing homeostatic and allostatic modulation of excitatory synaptic transmission by inhibitory controls under different pathological pain conditions, hence implicating use of different therapeutic approaches to maintain the homeostasis between excitation and inhibition while treating different conditions of pathological pain.

  2. Altered central sensitization and pain modulation in the CNS in chronic joint pain

    DEFF Research Database (Denmark)

    Arendt-Nielsen, Lars; Skou, Søren Thorgaard; Nielsen, Thomas Arendt

    2015-01-01

    and central pain mechanisms are not fully understood, and safe and efficient analgesic drugs are not available. The pain associated with joint pain is highly individual, and features from radiological imaging have not demonstrated robust associations with the pain manifestations. In recent years, a variety...

  3. Early systemic granulocyte-colony stimulating factor treatment attenuates neuropathic pain after peripheral nerve injury.

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    Po-Kuan Chao

    Full Text Available Recent studies have shown that opioid treatment can reduce pro-inflammatory cytokine production and counteract various neuropathic pain syndromes. Granulocyte colony-stimulating factor (G-CSF can promote immune cell differentiation by increasing leukocytes (mainly opioid-containing polymorphonuclear (PMN cells, suggesting a potential beneficial role in treating chronic pain. This study shows the effectiveness of exogenous G-CSF treatment (200 µg/kg for alleviating thermal hyperalgesia and mechanical allodynia in rats with chronic constriction injury (CCI, during post-operative days 1-25, compared to that of vehicle treatment. G-CSF also increases the recruitment of opioid-containing PMN cells into the injured nerve. After CCI, single administration of G-CSF on days 0, 1, and 2, but not on day 3, relieved thermal hyperalgesia, which indicated that its effect on neuropathic pain had a therapeutic window of 0-48 h after nerve injury. CCI led to an increase in the levels of interleukin-6 (IL-6 mRNA and tumor necrosis factor-α (TNF-α protein in the dorsal root ganglia (DRG. These high levels of IL-6 mRNA and TNF-α were suppressed by a single administration of G-CSF 48-144 h and 72-144 h after CCI, respectively. Furthermore, G-CSF administered 72-144 h after CCI suppressed the CCI-induced upregulation of microglial activation in the ipsilateral spinal dorsal horn, which is essential for sensing neuropathic pain. Moreover, the opioid receptor antagonist naloxone methiodide (NLXM reversed G-CSF-induced antinociception 3 days after CCI, suggesting that G-CSF alleviates hyperalgesia via opioid/opioid receptor interactions. These results suggest that an early single systemic injection of G-CSF alleviates neuropathic pain via activation of PMN cell-derived endogenous opioid secretion to activate opioid receptors in the injured nerve, downregulate IL-6 and TNF-α inflammatory cytokines, and attenuate microglial activation in the spinal dorsal horn. This

  4. Pregabalin in chemotherapy induced neuropathic pain

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    Shrikant Atreya

    2016-01-01

    Full Text Available Chemotherapeutic agents belonging to vinca alkaloids, taxanes, and antitubulins produce peripheral neuropathy for which there is no validated treatment. Pregabalin, a gamma-aminobutyric acid analog, is known to inhibit theα2δ subunit of the voltage-gated calcium channel. Earlier studies and case reports have shown pregabalin to be effective in treating neuropathic pain. We present a case series of patients with chemotherapy-induced peripheral neuropathy who were successfully treated with pregabalin with reduction in the hyperalgesia, allodynia, and improvement in the quality of life.

  5. Glial TNFα in the spinal cord regulates neuropathic pain induced by HIV gp120 application in rats

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    Ouyang Handong

    2011-05-01

    Full Text Available Abstract Background HIV-associated sensory neuropathy (HIV-SN is one of the most common forms of peripheral neuropathy, affecting about 30% of people with acquired immune deficiency syndrome (AIDS. The symptoms of HIV-SN are dominated by neuropathic pain. Glia activation in the spinal cord has become an attractive target for attenuating chronic pain. This study will investigate the role of spinal TNFα released from glia in HIV-related neuropathic pain. Results Peripheral gp120 application into the rat sciatic nerve induced mechanical allodynia for more than 7 weeks, and upregulated the expression of spinal TNFα in the mRNA and the protein levels at 2 weeks after gp120 application. Spinal TNFα was colocalized with GFAP (a marker of astrocytes and Iba1 (a marker of microglia in immunostaining, suggesting that glia produce TNFα in the spinal cord in this model. Peripheral gp120 application also increased TNFα in the L4/5 DRG. Furthermore, intrathecal administration of TNFα siRNA or soluble TNF receptor reduced gp120 application-induced mechanical allodynia. Conclusions Our results indicate that TNFα in the spinal cord and the DRG are involved in neuropathic pain, following the peripheral HIV gp120 application, and that blockade of the glial product TNFα reverses neuropathic pain induced by HIV gp120 application.

  6. The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.

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    Ombretta Caspani

    Full Text Available Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.

  7. Evaluating Sativex® in Neuropathic Pain Management: A Clinical and Neurophysiological Assessment in Multiple Sclerosis.

    Science.gov (United States)

    Russo, Margherita; Naro, Antonino; Leo, Antonino; Sessa, Edoardo; D'Aleo, Giangaetano; Bramanti, Placido; Calabrò, Rocco Salvatore

    2016-06-01

    The aim of our study was to better investigate the role of Sativex(®) in improving pain in multiple sclerosis (MS) patients by means of either clinical or neurophysiological assessment. Pain is a common symptom of MS, affecting up to 70% of patients. Pain treatment is often unsatisfactory, although emerging drugs (including cannabinoids) are giving encouraging results. Clinical pain assessment in MS is very difficult, and more objective tools are necessary to better quantify this symptom and its potential response to the treatments. We enrolled 20 MS patients (10 with and 10 without neuropathic pain), who underwent a specific clinical (such as visual analog scale) and neurophysiological assessment (by means of laser-evoked potentials and transcranial magnetic stimulation), before and after 4 weeks of Sativex administration. One month of drug administration in MS patients with neuropathic pain successfully reduced pain rating and improved quality of life. Interestingly, such effects were paralleled by an increase of fronto-central γ-band oscillation and of pain-motor integration strength. Our data suggest that Sativex may be effective in improving MS-related neuropathic pain, maybe through its action on specific cortical pathways. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Reappraising neuropathic pain in humans--how symptoms help disclose mechanisms.

    Science.gov (United States)

    Truini, Andrea; Garcia-Larrea, Luis; Cruccu, Giorgio

    2013-10-01

    Neuropathic pain--that is, pain arising directly from a lesion or disease that affects the somatosensory system--is a common clinical problem, and typically causes patients intense distress. Patients with neuropathic pain have sensory abnormalities on clinical examination and experience pain of diverse types, some spontaneous and others provoked. Spontaneous pain typically manifests as ongoing burning pain or paroxysmal electric shock-like sensations. Provoked pain includes pain induced by various stimuli or even gentle brushing (dynamic mechanical allodynia). Recent clinical and neurophysiological studies suggest that the various pain types arise through distinct pathophysiological mechanisms. Ongoing burning pain primarily reflects spontaneous hyperactivity in nociceptive-fibre pathways, originating from 'irritable' nociceptors, regenerating nerve sprouts or denervated central neurons. Paroxysmal sensations can be caused by several mechanisms; for example, electric shock-like sensations probably arise from high-frequency bursts generated in demyelinated non-nociceptive Aβ fibres. Most human and animal findings suggest that brush-evoked allodynia originates from Aβ fibres projecting onto previously sensitized nociceptive neurons in the dorsal horn, with additional contributions from plastic changes in the brainstem and thalamus. Here, we propose that the emerging mechanism-based approach to the study of neuropathic pain might aid the tailoring of therapy to the individual patient, and could be useful for drug development.

  9. Tumor suppressor menin mediates peripheral nerve injury-induced neuropathic pain through potentiating synaptic plasticity.

    Science.gov (United States)

    Xu, S; Wu, H; Wang, X; Shen, X; Guo, X; Shen, R; Wang, F

    2012-10-25

    Synaptic plasticity is a crucial step in the development of central sensitization in the pathogenesis of neuropathic hyperalgesia. Menin, the product of the multiple endocrine neoplasia type 1 (MEN1) gene, possesses the property of synaptogenesis which plays an essential role in neuronal activity. We tested the contributing role of spinal menin in peripheral nerve injury-induced neuropathic hypersensitivity through modulating neuronal synaptic plasticity. After approval by the Institutional Animal Care and Use Committee, nociceptive responses were detected with von Frey filaments and thermal plate after spared nerve injury in C57BL/6 mice who were treated with either intrathecal antisense oligonucleotide of MEN1 (ASO) or vehicle. Extracellular spontaneous discharge frequency, field excitatory postsynaptic potential (fEPSP), and monosynaptic excitatory postsynaptic currents (EPSCs) were measured electrophysiologically. Intrathecal ASO alleviated nerve injury-induced mechanical and thermal hypersensitivity. Upregulated spinal menin after nerve injury colocalized with NeuN in the superficial laminae; genetic knockdown of spinal menin reduced nerve injury induced in vivo spontaneous activity and instantaneous frequency and in vitro field potentials; ASO decreased the frequency and amplitude of monosynaptic EPSCs, and reduced synaptic strength and total charge. Collectively, these findings highlight the role of upregulated neuronal menin in the spinal cord in potentiating spinal synaptic plasticity in peripheral nerve injury-induced neuropathic hypersensitivity. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Chronic inorganic mercury exposure induces sex-specific changes in central TNFα expression: Importance in autism?

    OpenAIRE

    Curtis, J. Thomas; Chen, Yue; Buck, Daniel J.; Davis, Randall L.

    2011-01-01

    Mercury is neurotoxic and increasing evidence suggests that environmental exposure to mercury may contribute to neuropathologies including Alzheimer's disease and autism spectrum disorders. Mercury is known to disrupt immunocompetence in the periphery, however, little is known about the effects of mercury on neuroimmune signaling. Mercury-induced effects on central immune function are potentially very important given that mercury exposure and neuroinflammation both are implicated in certain n...

  11. Central mechanisms of chronic pain (neuralgias and certain other neurogenic pain).

    Science.gov (United States)

    Sweet, W H

    1980-01-01

    Almost all supratentorial intracranial lesions which may effectively control chronic pain in man are ineffective for acute pain. There are at least 10 sites at which lesions producing no somatic sensory loss have often stopped the peculiarly agonizing chronic pain of advanced cancer. They include: (a) inferior posteromedial or subcaudate (preinnominate) frontal white matter; (b) supracallosal portion of cingulum; (c) thalamotomy of centrum medianum and parafascicularis nuclei; (d) thalamotomy of linear parasagittal type separating connections between lateral specific and medial nonspecific sensory relay nuclei; (e) thalamotomy of pulvinar; (f) amygdalotomy; (g) frontothalamic tractotomy; (h) hypothalamotomy-posteromedial nuclei; (i) hypothalamotomy-periventricular nuclei; (j) hypophysectomy. It is indeed remarkable that such diversely situated lesions may many times be so successful. We understand poorly the mechanisms by which this control is often (though at times only temporarily) achieved. Hence, we are in real need of animal models to permit critical analysis. The problem of devising an ethically acceptable modus operandi is formidable. However, an ethicist who would demand that every time an experimental animal is showing some distress the experiment must be terminated, must also bear some responsibility for continuing disabling pain in hundreds of thousands of people.

  12. Neuropathic pain and use of PainDETECT in patients with fibromyalgia: a cohort study

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    Gauffin Jarno

    2013-02-01

    Full Text Available Abstract Backround Fibromyalgia has a plethorae of symptoms, which can be confusing and even misleading. Accurate evaluation is necessary when patients with fibromyalgia are treated. Different types of instruments are available for the clinicians to supplement evaluation. Our objective was to study the applicability of the PainDETECT instrument to screen neuropathic pain in patients with fibromyalgia. Methods 158 patients with primary fibromyalgia underwent a neurological examination including bedside sensory testing. They also fulfilled four questionnaires: PainDETECT, Beck depression inventory IA (BDI IA, Fibromyalgia Impact Questionnaire (FIQ and a self-made questionnaire regarding present pain and pain relieving methods of the patients. The results of the clinical evaluation and questionnaires were then compared. Results Clinically verified neuropathic pain was diagnosed in 53/158 [34% (95% Cl: 26 to 41] patients. The ROC curve achieved a maximum Youden´s index at score of 17 when sensitivity was 0.79 (95% Cl: 0.66 to 0.89 and specificity 0.53 (95% Cl: 0.43 to 0.63. The PainDETECT total score (OR: 1.14 95% Cl: 1.06 to 1.22, FM as the worst current pain (OR: 0.31; 95% 0.16 to 0.62, body mass index (BMI (OR: 1.05; 95% Cl: 1.00 to 1.11 and the intensity of current pain (OR: 1.20; 95% Cl: 1.01 to 1.41 were significantly associated with the presence of neuropathic pain in univariate analyses. Conclusion This study highlights the importance of thorough clinical examination. The Neuropathic pain screening tool PainDETECT is not as useful in patients with fibromyalgia as in patients with uncompromised central pain control.

  13. The effect of exercise frequency on neuropathic pain and pain-related cellular reactions in the spinal cord and midbrain in a rat sciatic nerve injury model

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    Sumizono M

    2018-02-01

    Full Text Available Megumi Sumizono,1,2 Harutoshi Sakakima,1 Shotaro Otsuka,1 Takuto Terashi,1 Kazuki Nakanishi,1,2 Koki Ueda,1,2 Seiya Takada,1,2 Kiyoshi Kikuchi3 1Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan; 2Kirishima Orthopedics, Kirishima, Japan; 3Division of Brain Science, Department of Physiology, Kurume University School of Medicine, Kurume, Japan Background: Exercise regimens are established methods that can relieve neuropathic pain. However, the relationship between frequency and intensity of exercise and multiple cellular responses of exercise-induced alleviation of neuropathic pain is still unclear. We examined the influence of exercise frequency on neuropathic pain and the intracellular responses in a sciatic nerve chronic constriction injury (CCI model. Materials and methods: Rats were assigned to four groups as follows: CCI and high-frequency exercise (HFE group, CCI and low-frequency exercise (LFE group, CCI and no exercise (No-Ex group, and naive animals (control group. Rats ran on a treadmill, at a speed of 20 m/min, for 30 min, for 5 (HFE or 3 (LFE days a week, for a total of 5 weeks. The 50% withdrawal threshold was evaluated for mechanical sensitivity. The activation of glial cells (microglia and astrocytes, expression of brain-derived neurotrophic factor (BDNF and μ-opioid receptor in the spinal dorsal horn and endogenous opioid in the midbrain were examined using immunohistochemistry. Opioid receptor antagonists (naloxone were administered using intraperitoneal injection. Results: The development of neuropathic pain was related to the activation of glial cells, increased BDNF expression, and downregulation of the μ-opioid receptor in the ipsilateral spinal dorsal horn. In the No-Ex group, neuropathic pain showed the highest level of mechanical hypersensitivity at 2 weeks, which improved slightly until 5 weeks after CCI. In both exercise groups, the alleviation of

  14. Microsurgical Drezotomy for Neuropathic Pain after Spinal Cord Injury: Long Term Results in a Patient

    OpenAIRE

    Acevedo González, Juan Carlos; López Cárdenas, Gloria Viviana; Berbeo Calderón, Miguel Enrique; Zorro Guio, Óscar; Díaz Orduz, Roberto Carlos; Feo Lee, Óscar

    2012-01-01

    70 % of patients with spinal cord injuries are chronic and disabling neuropathic pain. This article presents the 23 years-old patient case, who suffered an infrasegmentary severe pain by spinal cord trauma. We performed neurosurgical treatment of pain. Drezotomy is selective section of nociceptive fibers in the spinal segments involved. The patient has 24 months of complete improvement and discontinuation of analgesics. Un 70 % de pacientes con lesión medular tiene dolor neuropático crónic...

  15. Comparison of efficacy between low-fluence and half-dose verteporfin photodynamic therapy for chronic central serous chorioretinopathy

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    Alkin Z

    2014-04-01

    Full Text Available Zeynep Alkin,1 Irfan Perente,1 Abdullah Ozkaya,1 Dilek Alp,1 Alper Agca,1 Ebru Demet Aygit,1 Selcuk Korkmaz,2 Ahmet Taylan Yazici,1 Ahmet Demirok1 1Beyoglu Eye Training and Research Hospital, Istanbul, Turkey; 2Hacettepe University Faculty of Science, Department of Statistics, Ankara, Turkey Purpose: To compare the efficacy of low-fluence photodynamic therapy (PDT and PDT with half-dose verteporfin in chronic central serous chorioretinopathy (CSC. Patients and methods: The medical records of 64 eyes from 60 patients with chronic CSC were retrospectively reviewed; 36 eyes received low-fluence PDT (25 J/cm2 and 28 eyes received half-dose verteporfin PDT (3 mg/m2. The primary outcome measure was the proportion of eyes with complete resolution of subretinal fluid. Secondary outcome measures were the changes in best corrected visual acuity (BCVA and central foveal thickness, and the proportion of eyes that showed an increase of ≥5 letters in BCVA at the last visit. Results: The mean follow-up period was12.5±4.3 months and 13.1±4 months in the low-fluence group and half-dose group, respectively (P=0.568. Thirty-three eyes (91.6% in the low-fluence group and 26 eyes (92.8% in the half-dose verteporfin group showed complete resolution of subretinal fluid (P=0.703. BCVA increased by a mean of 7.4 letters and 4.8 letters in the low-fluence group and half-dose group, respectively (P=0.336. Seventeen eyes (52.8% in the low-fluence group and 14 eyes (50% in the half-dose group experienced a gain of ≥5 letters in BCVA (P=0.825. In the low-fluence and half-dose verteporfin group, the mean baseline central foveal thickness was 351±90 µm and 341±96 µm, and significantly decreased to 188±61 µm and 181±47 µm, respectively (P<0.01. Conclusion: Both treatments resulted in complete subretinal fluid resolution in most of the eyes, with significantly better visual acuity outcomes compared to baseline at the last visit. Keywords: low-fluence, half

  16. A double-blind placebo-controlled cross-over study of the vascular effects of midodrine in neuropathic compared with hyperadrenergic postural tachycardia syndrome.

    Science.gov (United States)

    Ross, Amanda J; Ocon, Anthony J; Medow, Marvin S; Stewart, Julian M

    2014-02-01

    POTS (postural tachycardia syndrome) is a chronic form of OI (orthostatic intolerance). Neuropathic POTS is characterized by decreased adrenergic vasoconstriction, whereas hyperadrenergic POTS exhibits increased adrenergic vasoconstriction. We hypothesized that midodrine, an α1-adrenergic receptor agonist, would increase CVR (calf vascular resistance), decrease C(v) (calf venous capacitance) and decrease orthostatic tachycardia in neuropathic POTS, but not alter haemodynamics in hyperadrenergic POTS. A total of 20 POTS patients (12 neuropathic and eight hyperadrenergic), ages 12-20 years, participated in this randomized placebo-controlled double-blind cross-over study. Of these subjects, 15 were female. POTS subjects received 2 weeks of treatment with midodrine or placebo, with increased dosing from 2.5 to 10 mg three times daily. Following a 7-day drug-washout period, subjects received the cross-over treatment. HR (heart rate), MAP (mean arterial pressure), Q(calf) (calf blood flow) and CVR were measured supine and during 35° HUT (head-up tilt). C(v) was measured supine. In neuropathic POTS, midodrine decreased supine HR, Q(calf) and C(v), while increasing MAP and CVR compared with placebo. During HUT, in neuropathic POTS, midodrine decreased HR, Q(calf) and C(v), while increasing MAP and CVR. In hyperadrenergic POTS, placebo and midodrine both decreased upright HR and increased supine CVR. Placebo also increased supine C(v), compared with midodrine in hyperadrenergic POTS. Therefore midodrine improved postural tachycardia in neuropathic POTS by increasing CVR and decreasing Q(calf) and C(v), whereas these effects were not seen in hyperadrenergic POTS patients who experienced a placebo effect. This suggests that midodrine is probably an effective treatment for neuropathic POTS, but not for hyperadrenergic POTS.

  17. An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain From Spinal Cord Injury and Disease.

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas D; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

    2016-09-01

    Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, most of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta 9-THC on 3 separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was used to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model showed a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (eg, good drug effect, feeling high, etc) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all P patients with neuropathic pain associated with injury or disease of the spinal cord. A crossover, randomized, placebo-controlled human laboratory experiment involving administration of vaporized cannabis was performed in patients with neuropathic pain related to spinal cord injury and disease. This study supports consideration of future research that would include longer duration studies over weeks to months to evaluate the efficacy of medicinal cannabis in patients with central neuropathic pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  18. Central pontine myelinolysis in a chronic alcoholic: A clinical and brain magnetic resonance imaging follow-up

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    Dujmović Irena

    2013-01-01

    Full Text Available Introduction. Central pontine myelinolysis (CPM is a noninflammatory, demyelinating lesion usually localised in the basis pontis. Chronic alcoholism is frequently associated with this condition which may have a variable clinical outcome. Until now, brain magnetic resonance imaging (MRI follow-up in alcoholic CPM cases after alcohol withdrawal has been rarely described. Case report. We reported a 30- year-old male with a 12-year history of alcohol abuse, who presented with inability to stand and walk, nausea, vomiting and somnolence. Neurological examination revealed: impared fixation on lateral gaze, dysarthria, mild spastic quadriparesis, truncal and extremity ataxia, sock-like hypesthesia and moderate decrease in vibration sense in legs. Brain MRI showed a trident-shaped non-enhancing pontine lesion highly suggestive of CPM. After an eight-month alcoholfree follow-up period, the patient’s clinical status significantly improved, while the extent of MRI pontine lesion was merely slightly reduced. Conclusion. The presented case demonstrates that CPM in chronic alcoholics may have a benign clinical course after alcohol withdrawal, which is not necessarily associated with the reduction of lesions on brain MRI. [Projekat Ministarstva nauke Republike Srbije, br. 175031

  19. Improved dexterity after chronic electrical stimulation of the motor cortex for central pain: a special relevance for thalamic syndrome.

    Science.gov (United States)

    Nuti, Christophe; Vassal, François; Mertens, Patrick; Lemaire, Jean-Jacques; Magnin, Michel; Peyron, Roland

    2012-01-01

    To demonstrate that motor cortex stimulation (MCS) could improve motor function in patients with neuropathic pain. In this prospective clinical study of 38 patients referred for MCS as treatment for their neuropathic pain, we collected any declaration of improvement in motor performance that could be attributed to MCS. Ten patients (26%) declared a benefit in their motor function. Eight presented objective evidence of recovered dexterity for rapid alternating movements. A minor proportion had improvement in dystonic posture (n = 2), but none had detectable increased motor strength or tonus changes. Overall, 73% of the patients with limb ataxia declared a benefit after MCS. In 6 out of 10 patients (60%), the anatomic lesion responsible for pain was restricted to the lateral aspect of the thalamus. All of them had either clinical or electrophysiological evidence of lemniscal dysfunction (proprioceptive ataxia). No correlation was found between the scores of pain relief and the modification of motor status. The correlation between thalamic lesions and benefits in motor performance was significant (Fisher's exact test, two-tailed, p = 0.0017). Up to 26% of patients estimated that MCS improved their motor outcome through recovered dexterity and in cases of lateral thalamic lesions. Copyright © 2012 S. Karger AG, Basel.

  20. Use of Methadone as an Adjuvant Medication to Low-Dose Opioids for Neuropathic Pain in the Frail Elderly: A Case Series.

    Science.gov (United States)

    Vu Bach, Tammy; Pan, Jonathan; Kirstein, Anne; Grief, Cindy Joanne; Grossman, Daphna

    2016-12-01

    Palliative care clinicians are increasingly involved in the care of elderly patients suffering from chronic malignant and nonmalignant illnesses, of which neuropathic pain is a prevalent problem. As a person becomes more frail, pain medications such as opioid analgesics and adjuvant pain medications can result in unwanted effects such as sedation, confusion, and increased risk of falls. Treating pain in patients with advanced dementia or neurodegenerative diseases that can affect swallowing is particularly challenging because most adjuvant pain medications used to ameliorate neuropathic pain must be taken orally. Furthermore, dosing of neuropathic medications is limited by renal function, which is often impaired in the elderly due to both normal aging and renal disease. Methadone is an opioid analgesic that is effective in the treatment of neuropathic pain, is excreted by the bowels, is highly lipophilic, and can be administered through the oral, buccal, or sublingual routes. We present three cases highlighting the use of low-dose adjuvant methadone to manage complex neuropathic pain in the frail elderly.

  1. Microbiology of chronic suppurative otitis media at Queen Elizabeth Central Hospital, Blantyre, Malawi: A cross-sectional descriptive study.

    Science.gov (United States)

    Chirwa, M; Mulwafu, W; Aswani, J M; Masinde, P W; Mkakosya, R; Soko, D

    2015-12-01

    Chronic suppurative otitis media (CSOM) is still a significant health problem in developing countries. Therefore, it was pertinent to determine the local Malawian microbiology in order to guide adequate treatment, avoid complications, and provide records for future reference. The study sought to determine the CSOM-causing microorganisms at Queen Elizabeth Central Hospital in Blantyre, Malawi, and establish their relationship signs and symptoms, and with the demographic pattern of the study. This was a hospital-based cross-sectional descriptive study carried out at the ENT outpatient clinic and the Microbiology Department of Queen Elizabeth Central Hospital.The sample comprised 104 patients with unilateral or bilateral active CSOM, who met the inclusion criteria. All patients were evaluated through a detailed history and clinical examination. Pus samples from draining ears were collected by aspiration with a sterile pipette. The specimens were immediately sent for microbiological analysis. Data were analyzed using SPSS.version 20. The study found that Proteus mirabilis, Pseudomonas aeruginosa, and Staphylococcus aureus were the most prevalent aerobic bacteria, while Bacteroides spp. and Peptostreptococcus spp. were the commonest anaerobic bacteria causing CSOM. These CSOM-causing microorganisms were predominant among males aged 18 years and below. Some CSOM-causing microorganisms were-significantly more so than the others-characteristically associated with each of the following clinical features: quantity of pus drainage, mode of onset, otalgia, hearing loss, location of tympanic membrane perforation, and mucosal appearance.

  2. Preclinical evidence supporting the clinical development of central pattern generator-modulating therapies for chronic spinal cord-injured patients

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    Pierre eGuertin

    2014-05-01

    Full Text Available Ambulation or walking is one of the main gaits of locomotion. In terrestrial animals, it may be defined as a series of rhythmic and bilaterally coordinated movement of the limbs which creates a forward movement of the body. This applies regardless of the number of limbs - from arthropods with six or more limbs to bipedal primates. These fundamental similarities among species may explain why comparable neural systems and cellular properties have been found, thus far, to control in similar ways locomotor rhythm generation in most animal models. The aim of this article is to provide a comprehensive review of the known structural and functional features associated with central nervous system (CNS networks that are involved in the control of ambulation and other stereotyped motor patterns - specifically Central Pattern Generators (CPGs that produce basic rhythmic patterned outputs for locomotion, micturition, ejaculation, and defecation. Although there is compelling evidence of their existence in humans, CPGs have been most studied in reduced models including in vitro isolated preparations, genetically-engineered mice and spinal cord-transected animals. Compared with other structures of the CNS, the spinal cord is generally considered as being well-preserved phylogenetically. As such, most animal models of SCI should be considered as valuable tools for the development of novel pharmacological strategies aimed at modulating spinal activity and restoring corresponding functions in chronic spinal cord-injured patients.

  3. Central pain processing in chronic chemotherapy-induced peripheral neuropathy: a functional magnetic resonance imaging study.

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    Elaine G Boland

    Full Text Available Life expectancy in multiple myeloma has significantly increased. However, a high incidence of chemotherapy induced peripheral neuropathy (CIPN can negatively influence quality of life during this period. This study applied functional magnetic resonance imaging (fMRI to compare areas associated with central pain processing in patients with multiple myeloma who had chemotherapy induced peripheral neuropathy (MM-CIPN with those from healthy volunteers (HV. Twenty-four participants (n = 12 MM-CIPN, n = 12 HV underwent Blood Oxygen Level-Dependent (BOLD fMRI at 3T whilst noxious heat-pain stimuli were applied to the foot and then thigh. Patients with MM-CIPN demonstrated greater activation during painful stimulation in the precuneus compared to HV (p = 0.014, FWE-corrected. Patients with MM-CIPN exhibited hypo-activation of the right superior frontal gyrus compared to HV (p = 0.031, FWE-corrected. Significant positive correlation existed between the total neuropathy score (reduced version and activation in the frontal operculum (close to insular cortex during foot stimulation in patients with MM-CIPN (p = 0.03, FWE-corrected; adjusted R2 = 0.87. Painful stimuli delivered to MM-CIPN patients evoke differential activation of distinct cortical regions, reflecting a unique pattern of central pain processing compared with healthy volunteers. This characteristic activation pattern associated with pain furthers the understanding of the pathophysiology of painful chemotherapy induced peripheral neuropathy. Functional MRI provides a tool for monitoring cerebral changes during anti-cancer and analgesic treatment.

  4. Antinociceptive effects of fisetin against diabetic neuropathic pain in mice: Engagement of antioxidant mechanisms and spinal GABAA receptors.

    Science.gov (United States)

    Zhao, Xin; Li, Xin-Lin; Liu, Xin; Wang, Chuang; Zhou, Dong-Sheng; Ma, Qing; Zhou, Wen-Hua; Hu, Zhen-Yu

    2015-12-01

    Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Fisetin, a naturally occurring flavonoid, has been reported to exert antidepressant-like effect in previous studies. As antidepressant drugs are employed clinically to treat neuropathic pain, this work aimed to investigate whether fisetin possess beneficial effect on diabetic neuropathic pain and explore the mechanism(s). We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (200mg/kg), and von Frey test or Hargreaves test was used to assess mechanical allodynia or thermal hyperalgesia, respectively. Chronic treatment of diabetic mice with fisetin not only ameliorated the established symptoms of thermal hyperalgesia and mechanical allodynia, but also arrested the development of neuropathic pain when given at low doses. Although chronic fisetin administration did not impact on the symptom of hyperglycemia in diabetic mice, it reduced exacerbated oxidative stress in tissues of spinal cord, dorsal root ganglion (DRG) and sciatic verve. Furthermore, the analgesic actions of fisetin were abolished by repetitive co-treatment with the reactive oxygen species (ROS) donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the ROS scavenger phenyl-N-tert-butylnitrone (PBN). Finally, acute blockade of spinal GABAA receptors by bicuculline totally counteracted such fisetin analgesia. These findings indicate that chronic fisetin treatment can delay or correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the present fisetin analgesia may be associated with its antioxidant activity, and spinal GABAA receptors are likely rendered as downstream targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Sleep deprivation aggravates median nerve injury-induced neuropathic pain and enhances microglial activation by suppressing melatonin secretion.

    Science.gov (United States)

    Huang, Chun-Ta; Chiang, Rayleigh Ping-Ying; Chen, Chih-Li; Tsai, Yi-Ju

    2014-09-01

    Sleep deprivation is common in patients with neuropathic pain, but the effect of sleep deprivation on pathological pain remains uncertain. This study investigated whether sleep deprivation aggravates neuropathic symptoms and enhances microglial activation in the cuneate nucleus (CN) in a median nerve chronic constriction injury (CCI) model. Also, we assessed if melatonin supplements during the sleep deprived period attenuates these effects. Rats were subjected to sleep deprivation for 3 days by the disc-on-water method either before or after CCI. In the melatonin treatment group, CCI rats received melatonin supplements at doses of 37.5, 75, 150, or 300 mg/kg during sleep deprivation. Melatonin was administered at 23:00 once a day. Male Sprague-Dawley rats, weighing 180-250 g (n = 190), were used. Seven days after CCI, behavioral testing was conducted, and immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analyses of microglial activation and measurements of proinflammatory cytokines. In rats who underwent post-CCI sleep deprivation, microglia were more profoundly activated and neuropathic pain was worse than those receiving pre-CCI sleep deprivation. During the sleep deprived period, serum melatonin levels were low over the 24-h period. Administration of melatonin to CCI rats with sleep deprivation significantly attenuated activation of microglia and development of neuropathic pain, and markedly decreased concentrations of proinflammatory cytokines. Sleep deprivation makes rats more vulnerable to nerve injury-induced neuropathic pain, probably because of associated lower melatonin levels. Melatonin supplements to restore a circadian variation in melatonin concentrations during the sleep deprived period could alleviate nerve injury-induced behavioral hypersensitivity. © 2014 Associated Professional Sleep Societies, LLC.

  6. Evaluation of the Effect of Duration on the Efficacy of Pulsed Radiofrequency in an Animal Model of Neuropathic Pain.

    Science.gov (United States)

    Ramzy, Eiad A; Khalil, Khaled I; Nour, Eman M; Hamed, Mohammed F; Taha, Mohamed A

    2018-03-01

    Pulsed radiofrequency (PRF) is increasingly used in clinical practice, especially in neuropathic pain disorders. Although PRF is not new to clinical use, there are significant gaps in knowledge regarding its effectiveness. The current study was conducted to evaluate the effect of duration of application of PRF on its analgesic efficacy in improvement of neuropathic pain. A randomized experimental trial. An animal research facility at the College of Veterinary Medicine at Mansoura University in Egypt. Chronic constriction of the sciatic nerve of 36 male Sprague-Dawley rats was performed to induce neuropathic pain. The rats were divided into 6 groups (6 rats each) in which PRF was applied for 2, 4, 6, or 8 minutes or not at all. In one group, RF cannula was applied without performing PRF intervention. The pain was assessed through observation of resting paw posture (RPP) at 3, 10, and 21 days. Nerve damage was assessed by histopathological evaluation of the sciatic nerve. Immunohistochemical localization of proinflammatory cytokines (interleukin 6 [IL-6] and tumor necrosis factor alpha [TNF-alpha]) was also done. RPP was improved in rats treated with PRF. This improvement was significant only in rats treated for 8 minutes. Increased duration for PRF application was associated with a significant decrease in IL-6 and TNF-alpha contents in all groups when compared with the control group. Histopathological evaluation of the constricted sciatic nerve revealed no statistical significance among the different study groups. The study was limited by the lack of measurement of other inflammatory markers that may help elucidate other relevant mechanisms. Increased duration of PRF application resulted in better analgesic efficacy without any increase in tissue injury in an animal model of neuropathic pain. This effect may be attributed to decreased production of pro-inflammatory cytokines. Pulsed radiofrequency, analgesic, rats, sciatic nerve, duration, neuropathic pain.

  7. Cholinergic Neurotransmission in the Posterior Insular Cortex Is Altered in Preclinical Models of Neuropathic Pain: Key Role of Muscarinic M2 Receptors in Donepezil-Induced Antinociception

    Science.gov (United States)

    Ferrier, Jérémy; Bayet-Robert, Mathilde; Dalmann, Romain; El Guerrab, Abderrahim; Aissouni, Youssef; Graveron-Demilly, Danielle; Chalus, Maryse; Pinguet, Jérémy; Eschalier, Alain; Richard, Damien; Daulhac, Laurence; Balayssac, David

    2015-01-01

    Neuropathic pain is one of the most debilitating pain conditions, yet no therapeutic strategy has been really effective for its treatment. Hence, a better understanding of its pathophysiological mechanisms is necessary to identify new pharmacological targets. Here, we report important metabolic variations in brain areas involved in pain processing in a rat model of oxaliplatin-induced neuropathy using HRMAS 1H-NMR spectroscopy. An increased concentration of choline has been evidenced in the posterior insular cortex (pIC) of neuropathic animal, which was significantly correlated with animals' pain thresholds. The screening of 34 genes mRNA involved in the pIC cholinergic system showed an increased expression of the high-affinity choline transporter and especially the muscarinic M2 receptors, which was confirmed by Western blot analysis in oxaliplatin-treated rats and the spared nerve injury model (SNI). Furthermore, pharmacological activation of M2 receptors in the pIC using oxotremorine completely reversed oxaliplatin-induced mechanical allodynia. Consistently, systemic treatment with donepezil, a centrally active acetylcholinesterase inhibitor, prevented and reversed oxaliplatin-induced cold and mechanical allodynia as well as social interaction impairment. Intracerebral microdialysis revealed a lower level of acetylcholine in the pIC of oxaliplatin-treated rats, which was significantly increased by donepezil. Finally, the analgesic effect of donepezil was markedly reduced by a microinjection of the M2 antagonist, methoctramine, within the pIC, in both oxaliplatin-treated rats and spared nerve injury rats. These findings highlight the crucial role of cortical cholinergic neurotransmission as a critical mechanism of neuropathic pain, and suggest that targeting insular M2 receptors using central cholinomimetics could be used for neuropathic pain treatment. SIGNIFICANCE STATEMENT Our study describes a decrease in cholinergic neurotransmission in the posterior insular

  8. A preliminary report on stem cell therapy for neuropathic pain in humans

    Directory of Open Access Journals (Sweden)

    Vickers ER

    2014-05-01

    Full Text Available E Russell Vickers,1 Elisabeth Karsten,2 John Flood,3 Richard Lilischkis21Sydney Oral and Maxillofacial Surgery, NSW, Australia; 2Regeneus Ltd, Gordon, NSW, Australia; 3St Vincents Hospital, Sydney, NSW, AustraliaObjective: Mesenchymal stem cells (MSCs have been shown in animal models to attenuate chronic neuropathic pain. This preliminary study investigated if: i injections of autologous MSCs can reduce human neuropathic pain and ii evaluate the safety of the procedure.Methods: Ten subjects with symptoms of neuropathic trigeminal pain underwent liposuction. The lipoaspirate was digested with collagenase and washed with saline three times. Following centrifugation, the stromal vascular fraction was resuspended in saline, and then transferred to syringes for local injections into the pain fields. Outcome measures at 6 months assessed reduction in: i pain intensity measured by standard numerical rating scale from 0–10 and ii daily dosage requirements of antineuropathic pain medication.Results: Subjects were all female (mean age 55.3 years ± standard deviation [SD] 14.67; range 27–80 years with pain symptoms lasting from 4 months to 6 years and 5 months. Lipoaspirate collection ranged from 102–214 g with total cell numbers injected from 33 million to 162 million cells. Cell viability was 62%–91%. There were no systemic or local tissue side effects from the stem cell therapy (n=41 oral and facial injection sites. Clinical pain outcomes showed that at 6 months, 5/9 subjects had reduced both pain intensity scores and use of antineuropathic medication. The mean pain score pre-treatment was 7.5 (SD 1.58 and at 6 months had decreased to 4.3 (SD 3.28, P=0.018, Wilcoxon signed-rank test. Antineuropathic pain medication use showed 5/9 subjects reduced their need for medication (gabapentin, P=0.053, Student's t-test.Conclusion: This preliminary open-labeled study showed autologous administration of stem cells for neuropathic trigeminal pain

  9. Combined inhibition of monoacylglycerol lipase and cyclooxygenases synergistically reduces neuropathic pain in mice

    Science.gov (United States)

    Crowe, Molly S; Leishman, Emma; Banks, Matthew L; Gujjar, Ramesh; Mahadevan, Anu; Bradshaw, Heather B; Kinsey, Steven G

    2015-01-01

    Background and Purpose Neuropathic pain is commonly treated with GABA analogues, steroids or non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibit one or more COX isozymes but chronic COX inhibition paradoxically increases gastrointestinal inflammation and risk of unwanted cardiovascular events. The cannabinoids also have analgesic and anti-inflammatory properties and reduce neuropathic pain in animal models. The present study investigated the analgesic effects of inhibiting both monoacylglycerol lipase (MAGL) and COX enzymes, using low doses of both inhibitors. Experimental Approach Mice subjected to chronic constriction injury (CCI) were tested for mechanical and cold allodynia after administration of the MAGL inhibitor, JZL184, or the non-selective COX inhibitor diclofenac. Then, both drugs were co-administered at fixed dose proportions of 1:3, 1:1 and 3:1, based on their ED50 values. PGs, endocannabinoids and related lipids were quantified in lumbar spinal cord. Key Results Combining low doses of JZL184 and diclofenac synergistically attenuated mechanical allodynia and additively reduced cold allodynia. The cannabinoid CB1 receptor antagonist, rimonabant, but not the CB2 receptor antagonist, SR144528, blocked the analgesic effects of the JZL184 and diclofenac combination on mechanical allodynia, implying that CB1 receptors were primarily responsible for the anti-allodynia. Diclofenac alone and with JZL184 significantly reduced PGE2 and PGF2α in lumbar spinal cord tissue, whereas JZL184 alone caused significant increases in the endocannabinoid metabolite, N-arachidonoyl glycine. Conclusions and Implications Combining COX and MAGL inhibition is a promising therapeutic approach for reducing neuropathic pain with minimal side effects. PMID:25393148

  10. A burden of illness study for neuropathic pain in Europe

    Directory of Open Access Journals (Sweden)

    Liedgens H

    2016-04-01

    countries: €7,098 in France, €11,232 in Germany, €6,382 in Italy, €7,066 in Spain, and €5,492 in the UK. In the subgroup analysis, total annual direct costs per patient were highest for neuropathic back pain and radiculopathy, and lowest for fibromyalgia. Mean WPAI score range was 34.4–56.1; BPI interference was 4.1–4.8; and EQ-5D was 0.57–0.74. The results suggest that a significant proportion of the patient's work time in the previous week was affected by NP, and these are relatively high compared with other diseases such as diabetes, respiratory conditions, and arthritis. Implications: Despite differences in practice between countries, these findings suggest a high opportunity cost for society in terms of lost work and productivity due to NP. The wider costs appear significantly higher to patients, carers/families, and society as a whole than to the health system alone. Keywords: neuropathic pain, burden of illness, chronic lower back pain, productivity

  11. Frida Kahlo: Portrait of Chronic Pain.

    Science.gov (United States)

    Courtney, Carol A; O'Hearn, Michael A; Franck, Carla C

    2017-01-01

    The Mexican artist Frida Kahlo (1907-1954) is one of the most celebrated artists of the 20th century. Although famous for her colorful self-portraits and associations with celebrities Diego Rivera and Leon Trotsky, less known is the fact that she had lifelong chronic pain. Frida Kahlo developed poliomyelitis at age 6 years, was in a horrific trolley car accident in her teens, and would eventually endure numerous failed spinal surgeries and, ultimately, limb amputation. She endured several physical, emotional, and psychological traumas in her lifetime, yet through her art, she was able to transcend a life of pain and disability. Of her work, her self-portraits are conspicuous in their capacity to convey her life experience, much of which was imbued with chronic pain. Signs and symptoms of chronic neuropathic pain and central sensitization of nociceptive pathways are evident when analyzing her paintings and medical history. This article uses a narrative approach to describe how events in the life of this artist contributed to her chronic pain. The purpose of this article is to discuss Frida Kahlo's medical history and her art from a modern pain sciences perspective, and perhaps to increase our understanding of the pain experience from the patient's perspective. © 2017 American Physical Therapy Association.

  12. Central venous catheters for chronic hemodialysis: Is "last choice" never the "right choice"?

    Science.gov (United States)

    Dumaine, Chance S; Brown, Robert S; MacRae, Jennifer M; Oliver, Matthew J; Ravani, Pietro; Quinn, Robert R

    2018-01-01

    Since the publication of the first vascular access clinical practice guidelines in 1997, the global nephrology community has dedicated significant time and resources toward increasing the prevalence of arteriovenous fistulas and decreasing the prevalence of central venous catheters for hemodialysis. These efforts have been bolstered by observational studies showing an association between catheter use and increased patient morbidity and mortality. To date, however, no randomized comparisons of the outcomes of different forms of vascular access have been conducted. There is mounting evidence that much of the difference in patient outcomes may be explained by patient factors, rather than choice of vascular access. Some have called into question the appropriateness of fistula creation for certain patient populations, such as those with limited life expectancy and those at high risk of fistula-related complications. In this review, we explore the extent to which catheters and fistulas exhibit the characteristics of the "ideal" vascular access and highlight the significant knowledge gaps that exist in the current literature. Further studies, ideally randomized comparisons of different forms of vascular access, are required to better inform shared decision making. © 2017 Wiley Periodicals, Inc.

  13. Lowering of blood pressure by chronic suppression of central sympathetic outflow: insight from prolonged baroreflex activation

    Science.gov (United States)

    Iliescu, Radu

    2012-01-01

    Device-based therapy for resistant hypertension by electrical activation of the carotid baroreflex is currently undergoing active clinical investigation, and initial findings from clinical trials have been published. The purpose of this mini-review is to summarize the experimental studies that have provided a conceptual understanding of the mechanisms that account for the long-term lowering of arterial pressure with baroreflex activation. The well established mechanisms mediating the role of the baroreflex in short-term regulation of arterial pressure by rapid changes in peripheral resistance and cardiac function are often extended to long-term pressure control, and the more sluggish actions of the baroreflex on renal excretory function are often not taken into consideration. However, because clinical, experimental, and theoretical evidence indicates that the kidneys play a dominant role in long-term control of arterial pressure, this review focuses on the mechanisms that link baroreflex-mediated reductions in central sympathetic outflow with increases in renal excretory function that lead to sustained reductions in arterial pressure. PMID:22797307

  14. The evidence for pharmacological treatment of neuropathic pain

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix; Sindrup, Søren Hein; Jensen, Troels Staehelin

    2010-01-01

    Randomized, double-blind, placebo-controlled trials on neuropathic pain treatment are accumulating, so an updated review of the available evidence is needed. Studies were identified using MEDLINE and EMBASE searches. Numbers needed to treat (NNT) and numbers needed to harm (NNH) values were used...... to compare the efficacy and safety of different treatments for a number of neuropathic pain conditions. One hundred and seventy-four studies were included, representing a 66% increase in published randomized, placebo-controlled trials in the last 5 years. Painful poly-neuropathy (most often due to diabetes...... are the drug classes for which there is the best evidence for a clinical relevant effect. Despite a 66% increase in published trials only a limited improvement of neuropathic pain treatment has been obtained. A large proportion of neuropathic pain patients are left with insufficient pain relief. This fact...

  15. Neuropathic pain and spasticity: intricate consequences of spinal cord injury

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix

    2017-01-01

    STUDY DESIGN: The 2016 International Spinal Cord Society Sir Ludwig Guttmann Lecture. OBJECTIVES: The aim of this review is to identify different symptoms and signs of neuropathic pain and spasticity after spinal cord injury (SCI) and to present different methods of assessing them. The objective......', 'neuropathic', 'spasticity', 'spasms' and 'spinal cord injury'. RESULTS: This review identified different domains of neuropathic pain and spasticity after SCI and methods to assess them in preclinical and clinical research. Different factors important for pain description include location, onset, pain...... of SCI, and a careful examination and characterization of the symptoms and signs, are a prerequisite for understanding the relationship between neuropathic pain and spasticity and the intricate underlying mechanisms.Spinal Cord advance online publication, 11 July 2017; doi:10.1038/sc.2017.70....

  16. Prevalence of Neuropathic Pain and the Need for Treatment

    Directory of Open Access Journals (Sweden)

    Pat Morley-Forster

    2006-01-01

    There is an unmet need for the treatment of neuropathic pain as evidenced by reports of pain despite the use of opioids and anticonvulsants, continuing psychological difficulties, lack of access to treatments and patients seeking access to complementary therapy.

  17. Botulinum Toxin B Affects Neuropathic Pain but Not Functional Recovery after Peripheral Nerve Injury in a Mouse Model

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    Alba Finocchiaro

    2018-03-01

    Full Text Available Clinical use of neurotoxins from Clostridium botulinum is well established and is continuously expanding, including in treatment of pain conditions. Background: The serotype A (BoNT/A has been widely investigated, and current data demonstrate that it induces analgesia and modulates nociceptive processing initiated by inflammation or nerve injury. Given that data concerning the serotype B (BoNT/B are limited, the aim of the present study was to verify if also BoNT/B is able not only to counteract neuropathic pain, but also to interfere with inflammatory and regenerative processes associated with the nerve injury. Methods: As model of neuropathic pain, chronic constriction injury (CCI of the sciatic nerve was performed in CD1 male mice. Mice were intraplantarly injected with saline (control or BoNT/B (5 or 7.5 pg/mouse into the injured hindpaw. For comparison, another mouse group was injected with BoNT/A (15 pg/mouse. Mechanical allodynia and functional recovery of the injured paw was followed for 101 days. Spinal cords and sciatic nerves were collected at day 7 for immunohistochemistry. Results and Conclusions: The results of this study show that BoNT/B is a powerful biological molecule that, similarly to BoNT/A, can reduce neuropathic pain over a long period of time. However, the analgesic effects are not associated with an improvement in functional recovery, clearly highlighting an important difference between the two serotypes for the treatment of this chronic pain state.

  18. Botulinum Toxin B Affects Neuropathic Pain but Not Functional Recovery after Peripheral Nerve Injury in a Mouse Model

    Science.gov (United States)

    Finocchiaro, Alba; Marinelli, Sara; De Angelis, Federica; Vacca, Valentina; Pavone, Flaminia

    2018-01-01

    Clinical use of neurotoxins from Clostridium botulinum is well established and is continuously expanding, including in treatment of pain conditions. Background: The serotype A (BoNT/A) has been widely investigated, and current data demonstrate that it induces analgesia and modulates nociceptive processing initiated by inflammation or nerve injury. Given that data concerning the serotype B (BoNT/B) are limited, the aim of the present study was to verify if also BoNT/B is able not only to counteract neuropathic pain, but also to interfere with inflammatory and regenerative processes associated with the nerve injury. Methods: As model of neuropathic pain, chronic constriction injury (CCI) of the sciatic nerve was performed in CD1 male mice. Mice were intraplantarly injected with saline (control) or BoNT/B (5 or 7.5 pg/mouse) into the injured hindpaw. For comparison, another mouse group was injected with BoNT/A (15 pg/mouse). Mechanical allodynia and functional recovery of the injured paw was followed for 101 days. Spinal cords and sciatic nerves were collected at day 7 for immunohistochemistry. Results and Conclusions: The results of this study show that BoNT/B is a powerful biological molecule that, similarly to BoNT/A, can reduce neuropathic pain over a long period of time. However, the analgesic effects are not associated with an improvement in functional recovery, clearly highlighting an important difference between the two serotypes for the treatment of this chronic pain state. PMID:29562640

  19. Spinal NF-κB and chemokine ligand 5 expression during spinal glial cell activation in a neuropathic pain model.

    Directory of Open Access Journals (Sweden)

    Qin Yin

    Full Text Available BACKGROUND: The NF-κB pathway and chemokine (C-C motif ligand 5 (CCL5 are involved in pain modulation; however, the precise mechanisms of their interactions in chronic neuropathic pain have yet to be established. METHODS: The present study examined the roles of spinal NF-κB and CCL5 in a neuropathic pain model after chronic constriction injury (CCI surgery. CCI-induced pain facilitation was evaluated using the Plantar and von Frey tests. The changes in NF-κB and CCL5 expression were analyzed by immunohistochemistry and Western blot analyses. RESULTS: Spinal NF-κB and CCL5 expression increased after CCI surgery. Repeated intrathecal infusions of pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor decreased CCL5 expression, inhibited the activation of microglia and astrocytes, and attenuated CCI-induced allodynia and hyperalgesia. Intrathecal injection of a CCL5-neutralizing antibody attenuated CCI-induced pain facilitation and also suppressed spinal glial cell activation after CCI surgery. However, the CCL5-neutralizing antibody did not affect NF-κB expression. Furthermore, selective glial inhibitors, minocycline and fluorocitrate, attenuated the hyperalgesia induced by intrathecal CCL5. CONCLUSIONS: The inhibition of spinal CCL5 expression may provide a new method to prevent and treat nerve injury-induced neuropathic pain.

  20. Lipo-endomorphin-1 derivatives with systemic activity against neuropathic pain without producing constipation.

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    Pegah Varamini

    Full Text Available To enhance the drug-like properties of the endogenous opioid peptide endomorphin-1 (1 = Tyr-Pro-Trp-Phe-NH(2, the N-terminus of the peptide was modified with 2-aminodecanoic acid, resulting in compound 3. Tyr in compound 1 was replaced with 2,6-dimethyltyrosine yielding compound 2. Derivative 2 was also substituted with 2-aminodecanoic acid producing compound, 4. Lipoamino acid-modified derivatives showed improved metabolic stability and membrane permeability while maintaining high μ-opioid (MOP receptor binding affinity and acting as a potent agonist. In vivo studies showed dose-dependent antinociceptive activity following intravenous (i.v. administration of compounds 3 and 4 in a chronic constriction injury (CCI-rat model of neuropathic pain with ED(50 values of 1.22 (± 0.93 and 0.99 (± 0.89 µmol/kg, respectively. Pre-treatment of animals with naloxone hydrochloride significantly attenuated the anti-neuropathic effects of compound 3, confirming the key role of opioid receptors in mediating antinociception. In contrast to morphine, no significant constipation was produced following i.v. administration of compound 3 at 16 µmol/kg. Furthermore, following chronic administration of equi-potent doses of compound 3 and morphine to rats, there was less antinociceptive tolerance for compound 3 compared with morphine.

  1. Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's

    OpenAIRE

    Liu, Ganqiang; Boot, Brendon; Locascio, Joseph J.; Jansen, Iris E.; Winder?Rhodes, Sophie; Eberly, Shirley; Elbaz, Alexis; Brice, Alexis; Ravina, Bernard; van Hilten, Jacobus J.; Cormier?Dequaire, Florence; Corvol, Jean?Christophe; Barker, Roger A.; Heutink, Peter; Marinus, Johan

    2016-01-01

    Objective We hypothesized that specific mutations in the ??glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non?neuropathic GD mutations confer intermediate progression rates. Methods A total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential effects of four types of geneti...

  2. Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's

    OpenAIRE

    Liu, Ganqiang; Boot, Brendon; Locascio, Joseph J.; Jansen, Iris E.; Winder‐Rhodes, Sophie; Eberly, Shirley; Elbaz, Alexis; Brice, Alexis; Ravina, Bernard; van Hilten, Jacobus J.; Cormier‐Dequaire, Florence; Corvol, Jean‐Christophe; Barker, Roger A.; Heutink, Peter; Marinus, Johan

    2016-01-01

    Objective: We hypothesized that specific mutations in the β‐glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non‐neuropathic GD mutations confer intermediate progression rates. Methods: A total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential effects of four types of gene...

  3. A behavioral and pharmacological validation of the acetone spray test in gerbils with a chronic constriction injury.

    NARCIS (Netherlands)

    Vissers, K.C.P.; Meert, T.F.

    2005-01-01

    Cold and mechanical allodynia are important symptoms in patients with neuropathic pain. The study of cold allodynia in animals can help us to understand the underlying pathophysiological mechanisms of neuropathic pain and to validate drugs. The evaluation of cold allodynia in gerbils with a chronic

  4. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Elphick Maurice R

    2009-07-01

    Full Text Available Abstract Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG, and the related compound N-palmitoylethanolamine (PEA, in neuropathic spinal cord. Selective spinal nerve ligation (SNL in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P P P P P

  5. Topical amitriptyline and ketamine for the treatment of neuropathic pain.

    Science.gov (United States)

    Mercadante, Sebastiano

    2015-01-01

    A neuropathy is a disturbance of function or pathological change in nerves. In some cases, peripheral neuropathic pain may occur due to a lesion or disease of the peripheral somatosensory nervous system. Efficacy of different agents for peripheral neuropathic pain conditions is less than optimal. The administration of topical analgesics might be an option, due to the potential of reduced adverse effects and increased patient compliance. There is major interest in compounding topical analgesics for peripheral neuropathic pain, but several challenges remain for this approach. Topical analgesics have the potential to be a valuable additional approach for the management of peripheral neuropathic pain. Topical amitriptyline-ketamine combination (AK) is a promising agent for peripheral neuropathic pain conditions. Some studies have shown its efficacy in neuropathic pain conditions. However, this data was not uniformely obtained and its role remains still controversial. Efficacy may depend on many factors, including the choice of the vehicle, the concentration, the pain site, and specific diseases. More studies are necessary to support the use of AK in clinical practice.

  6. Neonicotinoid concentrations in urine from chronic kidney disease patients in the North Central Region of Sri Lanka.

    Science.gov (United States)

    Kabata, Risako; Nanayakkara, Shanika; Senevirathna, Stmld; Harada, Kouji H; Chandrajith, Rohana; Hitomi, Toshiaki; Abeysekera, Tilak; Takasuga, Takumi; Koizumi, Akio

    2016-01-01

    Neonicotinoid insecticides have been widely used around the world since the 1990s. Reports have been made since the 1990s of rice paddy farmers in the North Central Region (NCR) of Sri Lanka suffering from chronic kidney disease with unknown etiology (CKDu). A preliminary evaluation of the exposure of local farmers in the NCR of Sri Lanka to neonicotinoids was performed. We analyzed neonicotinoid and neonicotinoid metabolite concentrations in spot urine samples. We selected 40 samples, 10 from farmers with CKDu and 10 from controls from each of two areas, Medawachchiya and Girandurukotte. Imidacloprid and desmethyl-acetamiprid were found at significantly higher concentrations in the control samples (with medians of 51 ng/l and 340 ng/l, respectively) than in the CKDu samples (medians of 15 ng/l and 150 ng/l, respectively) when the results were not adjusted for the creatinine contents. None of the six compounds that were measured in the urine samples were found at significantly higher concentrations in the CKDu samples than in the control samples. None of the neonicotinoid concentrations in the samples analyzed in this study exceeded the concentrations that have been found in samples from the general population of Japan. Farmers (both with and without CKDu) living in CKDu-endemic areas in the NCR of Sri Lanka are exposed to lower neonicotinoid concentrations than non-occupationally exposed residents of Japan.

  7. Are There Abnormalities in Peripheral and Central Components of Somatosensory Evoked Potentials in Non-Specific Chronic Low Back Pain?

    Science.gov (United States)

    Puta, Christian; Franz, Marcel; Blume, Kathrin R; Gabriel, Holger H W; Miltner, Wolfgang H R; Weiss, Thomas

    2016-01-01

    Chronic low back pain (CLBP) was shown to be associated with longer reflex response latencies of trunk muscles during external upper limb perturbations. One theoretical, but rarely investigated possibility for longer reflex latencies might be related to modulated somatosensory information processing. Therefore, the present study investigated somatosensory evoked potentials (SEPs) to median nerve stimulation in CLBP patients and healthy controls (HC). Latencies of the peripheral N9 SEP component were used as the primary outcome. In addition, latencies and amplitudes of the central N20 SEP component, sensory thresholds, motor thresholds and nerve conduction velocity were also analyzed in CLBP patients and HC. There is a trend for the CLBP patients to exhibit longer N9 latencies at the ipsilateral Erb's point compared to HC. This trend is substantiated by significantly longer N9 latencies in CLBP patients compared to normative data. None of the other parameters showed any significant difference between CLBP patients and HC. Overall, our data indicate small differences of the peripheral N9 SEP component; however, these differences cannot explain the reflex delay observed in CLBP patients. While it was important to rule out the contribution of early somatosensory processing and to elucidate its contribution to the delayed reflex responses in CLBP patients, further research is needed to find the primary source(s) of time-delayed reflexes in CLBP.

  8. Are there abnormalities in peripheral and central components of somatosensory evoked potentials in non - specific chronic low back pain ?

    Directory of Open Access Journals (Sweden)

    Christian Puta

    2016-10-01

    Full Text Available Chronic low back pain (CLBP was shown to be associated with longer reflex response latencies of trunk muscles during external upper limb perturbations. One theoretical, but rarely investigated possibility for longer reflex latencies might be related to modulated somatosensory information processing. Therefore, the present study investigated somatosensory evoked potentials (SEPs to median nerve stimulation in CLBP patients and healthy controls (HC. Latencies of the peripheral N9 SEP component were used as primary outcome. In addition, latencies and amplitudes of the central N20 SEP component, sensory thresholds, motor thresholds, and nerve conduction velocity were also analyzed in CLBP patients and HC. There is a trend for the CLBP patients to exhibited longer N9 latencies at the ipsilateral Erb’s point compared to HC. This trend is substantiated by significantly longer N9 latencies in CLBP patients compared to normative data. None of the other parameters showed any significant difference between CLBP patients and HC. Overall, our data indicate small differences of the peripheral N9 SEP component; however, these differences cannot explain the reflex delay observed in CLBP patients. While it was important to rule out the contribution of early somatosensory processing and to elucidate its contribution to the delayed reflex responses in CLBP patients, further research is needed to find the primary source(s of time-delayed reflexes in CLBP.

  9. Effects of chronic furosemide on central neural hyperactivity and cochlear thresholds after cochlear trauma in guinea pig

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    Wilhelmina eMulders

    2014-08-01

    Full Text Available Increased neuronal spontaneous firing rates have been observed throughout the central auditory system after trauma to the cochlea and this hyperactivity is believed to be associated with the phantom perception of tinnitus. Previously we have shown in an animal model of hearing loss, that an acute injection with furosemide can significantly decrease hyperactivity after cochlear trauma and eliminate behavioural evidence of tinnitus of early onset. However, furosemide also has the potential to affect cochlear thresholds. In this paper we measured the effects of a chronic (daily injections for 7 days furosemide treatment on the spontaneous firing rate of inferior colliculus neurons and on cochlear thresholds in order to establish whether a beneficial effect on hyperactivity can be obtained without causing additional hearing loss. Guinea pigs were exposed to a 10 kHz, 124dB, 2 hour acoustic trauma, and after 5 days of recovery, were given daily i.p. injections of 80mg/kg furosemide or an equivalent amount of saline. The activity of single IC neurons was recorded 24 hours following the last injection. The furosemide treatment had no effect on cochlear thresholds compared to saline injections but did result in significant reductions in spontaneous firing rates recorded in inferior colliculus. These results that suggest a long term beneficial effect of furosemide on hyperactivity after cochlear trauma may be achievable without detrimental effects on hearing, which is important when considering therapeutic potential.

  10. Mutation Status and Immunoglobulin Gene Rearrangements in Patients from Northwest and Central Region of Spain with Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    I. González-Gascón y Marín

    2014-01-01

    Full Text Available The aim of this study was to investigate the frequency and mutation status of the immunoglobulin heavy variable chain (IGHV in a cohort of 224 patients from northwest and central region of Spain diagnosed with chronic lymphocytic leukemia (CLL, and to correlate it with cytogenetic abnormalities, overall survival (OS and time to first treatment (TTFT. 125 patients had mutated IGHV, while 99 had unmutated IGHV. The most frequently used IGHV family was IGHV3, followed by IGHV1 and IGHV4. The regions IGHV3-30, IGHV1-69, IGHV3-23, and IGHV4-34 were the most commonly used. Only 3.1% of the patients belonged to the subfamily IGHV3-21 and we failed to demonstrate a worse clinical outcome in this subgroup. The IGHV4 family appeared more frequently with mutated pattern, similar to IGHV3-23 and IGHV3-74. By contrast, IGHV1-69 was expressed at a higher frequency in unmutated CLL patients. All the cases from IGHV3-11 and almost all from IGHV5-51 subfamily belonged to the group of unmutated CLL.

  11. The relationship between chronic lymphocytic thyroiditis and central neck lymph node metastasis in North American patients with papillary thyroid carcinoma.

    Science.gov (United States)

    Jara, Sebastian M; Carson, Kathryn A; Pai, Sara I; Agrawal, Nishant; Richmon, Jeremy D; Prescott, Jason D; Dackiw, Alan; Zeiger, Martha A; Bishop, Justin A; Tufano, Ralph P

    2013-12-01

    Several studies have reported that concurrent chronic lymphocytic thyroiditis (CLT) with papillary thyroid carcinoma (PTC) is associated with improved prognosis of the PTC, including decreased lymph node metastasis. We sought to assess the incidence of central nodal metastasis (CNM) in patients with PTC and concurrent CLT. We studied 495 consecutive patients who underwent thyroidectomy with nodal excision for PTC. Pathology reports identified the presence of CLT and the extent of CNM. There were 226 patients (46%) with CLT and 220 (44%) with CNM. Patients with CLT were more often female (88% vs. 71%; P CLT was associated with a 39% decreased odds of CNM after adjusting for age, gender, tumor size, PTC histopathologic subtype, and presence of lymphovascular invasion (odds ratio, 0.61; 95% confidence interval, 0.38-0.99; P = .046). Predicted probability modeling showed that all females with CLT and no suspicious nodal findings on ultrasonography had a 9-11% risk of CNM with pT1a tumors. Female patients of all ages with CLT and small PTCs have the least incidence of CNM. Copyright © 2013 Mosby, Inc. All rights reserved.

  12. Validation of the Malayalam version of Leeds assessment of neuropathic symptoms and signs pain scale in cancer patients in the Regional Cancer Centre, Thiruvananthapuram, Kerala, India

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    Shoukkathali Anzar

    2017-01-01

    Full Text Available Objective: The Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS is a 7-item self-report scale developed to identify pain which is of predominantly neuropathic origin. The aim of this study was to develop a Malayalam version of the LANSS and to test its validity and reliability in chronic pain patients. Methodology: We enrolled 101 Malayalam-speaking chronic pain patients who visited the Division of Palliative Medicine, Regional Cancer Centre, Thiruvananthapuram, Kerala, India. The translated version of S- LANSS was constructed by standard means. Fifty-one neuropathic pain and fifty nociceptive pain patients were identified by an independent pain physician and were subjected to the new pain scale by a palliative care nurse who was blinded to the diagnosis. The “gold standard diagnosis” is what the physician makes after clinical examination. Its validation, sensitivity, specificity, and positive and negative predictive values were determined. Results: Fifty-one neuropathic pain and fifty nociceptive pain patients were subjected to the Malayalam version of S-LANSS pain scale for validity testing. The agreement by Cohen's Kappa 0.743, Chi-square test P < 0.001, sensitivity 89.58, specificity 84.91, positive predictive value 84.31, negative predictive value 90.00, accuracy by 87.13, and likelihood ratio 5.94. Conclusion: The Malayalam version of S-LANSS pain scale is a validated screening tool for identifying neuropathic pain in chronic pain patients in Malayalam-speaking regions.

  13. CCL-1 in the spinal cord contributes to neuropathic pain induced by nerve injury.

    Science.gov (United States)

    Akimoto, N; Honda, K; Uta, D; Beppu, K; Ushijima, Y; Matsuzaki, Y; Nakashima, S; Kido, M A; Imoto, K; Takano, Y; Noda, M

    2013-06-20

    Cytokines such as interleukins are known to be involved in the development of neuropathic pain through activation of neuroglia. However, the role of chemokine (C-C motif) ligand 1 (CCL-1), a well-characterized chemokine secreted by activated T cells, in the nociceptive transmission remains unclear. We found that CCL-1 was upregulated in the spinal dorsal horn after partial sciatic nerve ligation. Therefore, we examined actions of recombinant CCL-1 on behavioural pain score, synaptic transmission, glial cell function and cytokine production in the spinal dorsal horn. Here we show that CCL-1 is one of the key mediators involved in the development of neuropathic pain. Expression of CCL-1 mRNA was mainly detected in the ipsilateral dorsal root ganglion, and the expression of specific CCL-1 receptor CCR-8 was upregulated in the superficial dorsal horn. Increased expression of CCR-8 was observed not only in neurons but also in microglia and astrocytes in the ipsilateral side. Recombinant CCL-1 injected intrathecally (i.t.) to naive mice induced allodynia, which was prevented by the supplemental addition of N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801. Patch-clamp recordings from spinal cord slices revealed that application of CCL-1 transiently enhanced excitatory synaptic transmission in the substantia gelatinosa (lamina II). In the long term, i.t. injection of CCL-1 induced phosphorylation of NMDA receptor subunit, NR1 and NR2B, in the spinal cord. Injection of CCL-1 also upregulated mRNA level of glial cell markers and proinflammatory cytokines (IL-1β, TNF-α and IL-6). The tactile allodynia induced by nerve ligation was attenuated by prophylactic and chronic administration of neutralizing antibody against CCL-1 and by knocking down of CCR-8. Our results indicate that CCL-1 is one of the key molecules in pathogenesis, and CCL-1/CCR-8 signaling system can be a potential target for drug development in the treatment for neuropathic pain.

  14. Botulinum toxin type A for neuropathic pain in patients with spinal cord injury.

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    Han, Zee-A; Song, Dae Heon; Oh, Hyun-Mi; Chung, Myung Eun

    2016-04-01

    To evaluate the analgesic effect of botulinum toxin type A (BTX-A) on patients with spinal cord injury-associated neuropathic pain. The effect of BTX-A on 40 patients with spinal cord injury-associated neuropathic pain was investigated using a randomized, double-blind, placebo-controlled design. A 1-time subcutaneous BTX-A (200U) injection was administered to the painful area. Visual analogue scale (VAS) scores (0-100mm), the Korean version of the short-form McGill Pain Questionnaire, and the World Health Organization WHOQOL-BREF quality of life assessment were evaluated prior to treatment and at 4 and 8 weeks after the injection. At 4 and 8 weeks after injection, the VAS score for pain was significantly reduced by 18.6 ± 16.8 and 21.3 ± 26.8, respectively, in the BTX-A group, whereas it was reduced by 2.6 ± 14.6 and 0.3 ± 19.5, respectively, in the placebo group. The pain relief was associated with preservation of motor or sensory function below the neurological level of injury. Among the responders in the BTX-A group, 55% and 45% reported pain relief of 20% or greater at 4 and 8 weeks, respectively, after the injection, whereas only 15% and 10% of the responders in the placebo group reported a similar level of pain relief. Improvements in the score for the physical health domain of the WHOQOL-BREF in the BTX-A group showed a marginal trend toward significance (p = 0.0521) at 4 weeks after the injection. These results indicate that BTX-A may reduce intractable chronic neuropathic pain in patients with spinal cord injury. © 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

  15. A3 adenosine receptor agonist prevents the development of paclitaxel-induced neuropathic pain by modulating spinal glial-restricted redox-dependent signaling pathways.

    Science.gov (United States)

    Janes, Kali; Esposito, Emanuela; Doyle, Timothy; Cuzzocrea, Salvatore; Tosh, Dillip K; Jacobson, Kenneth A; Salvemini, Daniela

    2014-12-01

    Chemotherapy-induced peripheral neuropathy accompanied by chronic neuropathic pain is the major dose-limiting toxicity of several anticancer agents including the taxane paclitaxel (Taxol). A critical mechanism underlying paclitaxel-induced neuropathic pain is the increased production of peroxynitrite in spinal cord generated in response to activation of the superoxide-generating enzyme, NADPH oxidase. Peroxynitrite in turn contributes to the development of neuropathic pain by modulating several redox-dependent events in spinal cord. We recently reported that activation of the Gi/Gq-coupled A3 adenosine receptor (A3AR) with selective A3AR agonists (ie, IB-MECA) blocked the development of chemotherapy induced-neuropathic pain evoked by distinct agents, including paclitaxel, without interfering with anticancer effects. The mechanism or mechanisms of action underlying these beneficial effects has yet to be explored. We now demonstrate that IB-MECA attenuates the development of paclitaxel-induced neuropathic pain by inhibiting the activation of spinal NADPH oxidase and two downstream redox-dependent systems. The first relies on inhibition of the redox-sensitive transcription factor (NFκB) and mitogen activated protein kinases (ERK and p38) resulting in decreased production of neuroexcitatory/proinflammatory cytokines (TNF-α, IL-1β) and increased formation of the neuroprotective/anti-inflammatory IL-10. The second involves inhibition of redox-mediated posttranslational tyrosine nitration and modification (inactivation) of glia-restricted proteins known to play key roles in regulating synaptic glutamate homeostasis: the glutamate transporter GLT-1 and glutamine synthetase. Our results unravel a mechanistic link into biomolecular signaling pathways employed by A3AR activation in neuropathic pain while providing the foundation to consider use of A3AR agonists as therapeutic agents in patients with chemotherapy-induced peripheral neuropathy. Copyright © 2014

  16. Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain

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    Ellis Connie L

    2010-03-01

    Full Text Available Abstract Background Despite the frequency of diabetes mellitus and its relationship to diabetic peripheral neuropathy (DPN and neuropathic pain (NeP, our understanding of underlying mechanisms leading to chronic pain in diabetes remains poor. Recent evidence has demonstated a prominent role of microglial cells in neuropathic pain states. One potential therapeutic option gaining clinical acceptance is the cannabinoids, for which cannabinoid receptors (CB are expressed on neurons and microglia. We studied the accumulation and activation of spinal and thalamic microglia in streptozotocin (STZ-diabetic CD1 mice and the impact of cannabinoid receptor agonism/antagonism during the development of a chronic NeP state. We provided either intranasal or intraperitoneal cannabinoid agonists/antagonists at multiple doses both at the initiation of diabetes as well as after establishment of diabetes and its related NeP state. Results Tactile allodynia and thermal hypersensitivity were observed over 8 months in diabetic mice without intervention. Microglial density increases were seen in the dorsal spinal cord and in thalamic nuclei and were accompanied by elevation of phosphorylated p38 MAPK, a marker of microglial activation. When initiated coincidentally with diabetes, moderate-high doses of intranasal cannabidiol (cannaboid receptor 2 agonist and intraperitoneal cannabidiol attenuated the development of an NeP state, even after their discontinuation and without modification of the diabetic state. Cannabidiol was also associated with restriction in elevation of microglial density in the dorsal spinal cord and elevation in phosphorylated p38 MAPK. When initiated in an established DPN NeP state, both CB1 and CB2 agonists demonstrated an antinociceptive effect until their discontinuation. There were no pronociceptive effects demonstated for either CB1 or CB2 antagonists. Conclusions The prevention of microglial accumulation and activation in the dorsal spinal

  17. The peripheral and central mechanisms of transition of acute to chronic pain and the possible role of cyclooxygenase-2 inhibition in the prevention of pain syndrome chronization

    Directory of Open Access Journals (Sweden)

    O. S. Davydov

    2016-01-01

    Full Text Available Chronic pain syndromes as a cause of suffering, short-term or persistent disability, and social losses greatly worsen quality of life. The mechanisms leading to the occurrence and maintenance of chronic pain are traditionally of interest for in-depth study since each of them is potentially a target for pharmacotherapy. Peripheral and central sensitizations, as well as disinhibition make different contributions to the development of chronic pain. The fact that cyclooxygenase-2 (COX-2 inhibitors may affect at both the peripheral and central, spinal levels, by modulating such a phenomenon as central sensitization, has been recently discussed. There are theoretical prerequisites for a discussion of this action of COX-2 inhibitors; however, clinical findings supporting this hypothesis have been scarce so far. In this connection, of interest is the clinical trial published in 2016, which may suggest to a high degree of accuracy that some analgesic effect of the selective COX-2 inhibitor etoricoxib is realized through the central mechanisms of pain modulation. 

  18. Neuropathic orofacial pain part 1--prevalence and pathophysiology.

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    Vickers, E R; Cousins, M J

    2000-04-01

    Neuropathic pain is defined as "pain initiated or caused by a primary lesion or dysfunction in the nervous system". Neuropathic orofacial pain has previously been known as "atypical odontalgia" (AO) and "phantom tooth pain". The patient afflicted with neuropathic oral/orofacial pain may present to the dentist with a persistent, severe pain, yet there are no clearly identifiable clinical or radiographic abnormalities. Accordingly, multiple endodontic procedures may be instigated to remove the likely anatomical source of the pain, yet the pain persists. There have been few studies and limited patient numbers investigating the condition. Two retrospective studies revealed the incidence of persistent pain following endodontic treatment to be 3-6% and 5% of patients; one author with wide experience in assessing the condition estimated its prevalence at 125,000 individuals in the USA alone. In one study, 50% of neuropathic orofacial pain patients reported persistent pain specifically following endodontic treatment. Patients predisposed to the condition may include those suffering from recurrent cluster or migraine headaches. Neuropathic pain states include postherpetic neuralgia (shingles) and phantom limb/stump pain. The aberrant developmental neurobiology leading to this pain state is complex. Neuropathic pain serves no protective function, in contrast to physiological pain that warns of noxious stimuli likely to result in tissue damage. The relevant clinical features of neuropathic pain include: (i) precipitating factors such as trauma or disease (infection), and often a delay in onset after initial injury (days-months), (ii) typical complaints such as dysaesthesias (abnormal unpleasant sensations), pain that may include burning, and paroxysmal, lancinating or sharp qualities, and pain in an area of sensory deficit, (iii) on physical examination there may be hyperalgesia, allodynia and sympathetic hyperfunction, and (iv) the pathophysiology includes deafferentation

  19. Botulinum Toxin Type A for the Treatment of Neuropathic Pain in Neuro-Rehabilitation

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    Domenico Intiso

    2015-06-01

    Full Text Available Pain is a natural protective mechanism and has a warning function signaling imminent or actual tissue damage. Neuropathic pain (NP results from a dysfunction and derangement in the transmission and signal processing along the nervous system and it is a recognized disease in itself. The prevalence of NP is estimated to be between 6.9% and 10% in the general population. This condition can complicate the recovery from stroke, multiple sclerosis, spinal cord lesions, and several neuropathies promoting persistent disability and poor quality of life. Subjects suffering from NP describe it as burning, itching, lancing, and numbness, but hyperalgesia and allodynia represent the most bothersome symptoms. The management of NP is a clinical challenge and several non-pharmacological and pharmacological interventions have been proposed with variable benefits. Botulinum toxin (BTX as an adjunct to other interventions can be a useful therapeutic tool for the treatment of disabled people. Although BTX-A is predominantly used to reduce spasticity in a neuro-rehabilitation setting, it has been used in several painful conditions including disorders characterized by NP. The underlying pharmacological mechanisms that operate in reducing pain are still unclear and include blocking nociceptor transduction, the reduction of neurogenic inflammation by inhibiting neural substances and neurotransmitters, and the prevention of peripheral and central sensitization. Some neurological disorders requiring rehabilitative intervention can show neuropathic pain resistant to common analgesic treatment. This paper addresses the effect of BTX-A in treating NP that complicates frequent disorders of the central and peripheral nervous system such as spinal cord injury, post-stroke shoulder pain, and painful diabetic neuropathy, which are commonly managed in a rehabilitation setting. Furthermore, BTX-A has an effect in relief pain that may characterize less common neurological disorders

  20. Assessment of economic effectiveness in treatment of neuropathic pain and refractory angina pectoris using spinal cord stimulation.

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    Harat, Aleksandra; Sokal, Paweł; Zieliński, Piotr; Harat, Marek; Rusicka, Teresa; Herbowski, Leszek

    2012-01-01

    The implementation of new diagnostic and therapeutic technologies is related to expanding financial needs. The escalation of expenses for health protection and simultaneous economic problems has resulted in an interest in the subject of economic assessment. Decision makers in the health sector should have reasonable tools that will allow them to make complex evaluations of the economic suitability of health technologies. Economic analysis should also prove that launching new procedures can save money. Numerous studies indicate that chronic pain and psycho-sociological variables lead to a worse quality of life. Chronic pain issues are a major public health problem, by virtue of the difficulties in efficient therapy and the social costs reflected in incapability of work and disability. Spinal cord stimulation is the most efficacious procedure in the treatment of chronic pain. The aim of the study was to estimate the costs of treatment of 37 patients suffering from refractory angina pectoris and neuropathic pain who underwent SCS surgery between 2002 and 2008 in the Neurosurgery Clinic of the 10th Military Hospital in Bydgoszcz in the period of two years before and two years after spinal cord stimulation. The authors also assessed quality of life, using the SF 36 questionnaire, and degree of pain using VAS. The issue was examined with a cost-benefit analysis. Cost was understood as the expenses made two years before and two years after the SCS procedure. The benefits were health care expenses saved by implementation of the SCS procedure. All the costs included in both alternative treatment techniques in a period of 5 years underwent a discounting procedure. The authors also included the price of the neurostimulator under a sensitivity analysis. To assess the quality of life before and after the SCS procedure, a SF 36 questionnaire was used, and to assess the level of pain before and after the SCS procedure, the VAS scale. The costs of treatment of refractory angina

  1. Use of 5% lidocaine medicated plaster to treat localized neuropathic pain secondary to traumatic injury of peripheral nerves

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    Correa-Illanes G

    2012-07-01

    Full Text Available Gerardo Correa-Illanes,1 Ricardo Roa,2 José Luis Piñeros,2 Wilfredo Calderón31Rehabilitation Department, 2Burns and Plastic Surgery Department, Hospital del Trabajador, 3Plastic Surgery Department, Hospital del Salvador, Santiago, ChileObjective: The efficacy of 5% lidocaine medicated plaster (LMP has previously been demonstrated in post-traumatic localized neuropathic pain. This study evaluated the use of LMP in localized neuropathic pain secondary to traumatic peripheral nerve injury.Patients and methods: This prospective observational study enrolled patients with traumatic injuries to peripheral nerves that were accompanied by localized neuropathic pain of more than 3 months duration. Demographic variables, pain intensity (measured using the numeric rating scale; NRS, answers to the Douleur Neuropathique 4 (DN4 questionnaire, and the size of the painful area were recorded.Results: Nineteen patients were included, aged (mean ± standard deviation 41.4 ± 15.7 years. Nerve injuries affected the upper (eight patients or lower (11 patients limbs. The mean duration of pain before starting treatment with LMP was 22.6 ± 43.5 months (median 8 months. Mean baseline values included: NRS 6.7 ± 1.6, painful area 17.8 ± 10.4 cm2 (median 18 cm2, and DN4 score 6.7 ± 1.4. The mean duration of treatment with LMP was 19.5 ± 10.0 weeks (median 17.4 weeks. Mean values after treatment were: NRS 2.8 ± 1.5 (≥3 point reduction in 79% of patients, ≥50% reduction in 57.9% of patients and painful area 2.1 ± 2.3 cm2 (median 1 cm2, ≥50% reduction in 94.7% of patients. Functional improvement after treatment was observed in 14/19 patients (73.7%.Conclusion: LMP effectively treated traumatic injuries of peripheral nerves which presented with chronic localized neuropathic pain, reducing both pain intensity and the size of the painful area.Keywords: chronic post-surgical pain, chronic post-traumatic pain, 5% lidocaine medicated plaster, neuropathic pain

  2. Mechanisms of disease: mechanism-based classification of neuropathic pain - a critical analysis

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix; Jensen, Troels Staehelin

    2006-01-01

    Classification of neuropathic pain according to etiology or localization has clear limitations. The discovery of specific molecular and cellular events following experimental nerve injury has raised the possibility of classifying neuropathic pain on the basis of the underlying neurobiological mec...

  3. Pain severity and the economic burden of neuropathic pain in the United States: BEAT Neuropathic Pain Observational Study

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    Schaefer C

    2014-10-01

    Full Text Available Caroline Schaefer,1 Alesia Sadosky,2 Rachael Mann,3 Shoshana Daniel,4 Bruce Parsons,2 Michael Tuchman,5 Alan Anschel,6 Brett R Stacey,7 Srinivas Nalamachu,8 Edward Nieshoff9 1Covance Market Access Services Inc., Gaithersburg, MD, 2Pfizer, Inc., New York, NY, 3Covance Market Access Services Inc., San Diego, CA, 4Covance Market Access Services Inc., Conshohocken, PA, 5Palm Beach Neurological Center, Palm Beach Gardens, FL, 6Rehabilitation Institute of Chicago, Chicago, IL, 7Oregon Health and Science University, Portland, OR, 8International Clinical Research Institute, Overland Park, KS, 9Rehabilitation Institute of Michigan/Wayne State University, Detroit, MI, USABackground: As with many chronic conditions, patients with neuropathic pain (NeP are high consumers of health care resources. However, limited literature exists on the economic burden of NeP, including its impact on productivity. The aim of this study was to characterize health care resource utilization, productivity, and costs associated with NeP by pain severity level in US adults.Methods: Subjects (n=624 with painful diabetic peripheral neuropathy, human immunodeficiency virus-related peripheral NeP, post-trauma/post-surgical NeP, spinal cord injury with NeP, chronic low back pain with NeP, and small fiber neuropathy were recruited during routine office visits to US community-based general practitioners and specialists. Clinicians captured clinical characteristics, NeP-related medications, and health care resource utilization based on 6-month retrospective medical chart review. Subjects completed questionnaires on demographics, pain/symptoms, costs, and productivity. Brief Pain Inventory pain severity scores were used to classify subjects by mild, moderate, or severe pain. Annualized NeP-related costs (adjusted for covariates were estimated, and differences across pain severity groups were evaluated.Results: In total, 624 subjects were recruited (mean age 55.5±13.7 years; 55.4% male

  4. Perspectives on physiotherapy guidelines for chronic low back pain

    Directory of Open Access Journals (Sweden)

    P. Berger

    2007-01-01

    disability. The modalities used in conjunction with active exercises include thermal, massage, electrical stimulation, traction, transcutaneous electrical nerve stimulation (Tens, myofascial release, dry needling, mobilization and acupuncture. An algorithm is provided with the intention of developing protocols for breaking the pain cycle in both nociceptive and neuropathic pain states and in reducing inflammation which is a component of both peripheral and central sensitization. Pain rehabilitation is a useful and cost-effective approach to chronic pain management and makes patients’ responsible partners in their own progress. It encourages planning, pacing of activities and activity related goal setting into a clear and goal-oriented context that provides the patient with control and improved quality of life.

  5. Analyzing implementation dynamics using theory-driven evaluation principles: lessons learnt from a South African centralized chronic dispensing model.

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    Magadzire, Bvudzai Priscilla; Marchal, Bruno; Mathys, Tania; Laing, Richard O; Ward, Kim

    2017-12-04

    Centralized dispensing of essential medicines is one of South Africa's strategies to address the shortage of pharmacists, reduce patients' waiting times and reduce over-crowding at public sector healthcare facilities. This article reports findings of an evaluation of the Chronic Dispensing Unit (CDU) in one province. The objectives of this process evaluation were to: (1) compare what was planned versus the actual implementation and (2) establish the causal elements and contextual factors influencing implementation. This qualitative study employed key informant interviews with the intervention's implementers (clinicians, managers and the service provider) [N = 40], and a review of policy and program documents. Data were thematically analyzed by identifying the main influences shaping the implementation process. Theory-driven evaluation principles were applied as a theoretical framework to explain implementation dynamics. The overall participants' response about the CDU was positive and the majority of informants concurred that the establishment of the CDU to dispense large volumes of medicines is a beneficial strategy to address healthcare barriers because mechanical functions are automated and distribution of medicines much quicker. However, implementation was influenced by the context and discrepancies between planned activities and actual implementation were noted. Procurement inefficiencies at central level caused medicine stock-outs and affected CDU activities. At the frontline, actors were aware of the CDU's implementation guidelines regarding patient selection, prescription validity and management of non-collected medicines but these were adapted to accommodate practical realities and to meet performance targets attached to the intervention. Implementation success was a result of a combination of 'hardware' (e.g. training, policies, implementation support and appropriate infrastructure) and 'software' (e.g. ownership, cooperation between healthcare

  6. The L-kynurenine-probenecid combination reduces neuropathic pain in rats.

    Science.gov (United States)

    Pineda-Farias, J B; Pérez-Severiano, F; González-Esquivel, D F; Barragán-Iglesias, P; Bravo-Hernández, M; Cervantes-Durán, C; Aguilera, P; Ríos, C; Granados-Soto, V

    2013-10-01

    l-Kynurenine has antinociceptive effects in acute and inflammatory pain. This study determined the effect of l-kynurenine and its metabolite (kynurenic acid) on rats subjected to neuropathic pain. L5/L6 spinal nerve ligation induced tactile allodynia as measured with von Frey filaments using the up-down method. High-performance liquid chromatography and Western blot analysis determined kynurenic acid levels and expression of kynurenine amino transferase II (KAT II), respectively. l-Kynurenine (50-200 mg/kg, i.p.) or probenecid (100 mg/kg, i.p.) did not affect allodynia in neuropathic rats. In contrast, l-kynurenine (50-200 mg/kg, i.p.) in combination with probenecid (100 mg/kg, i.p.), an inhibitor of organic anion transport, reversed allodynia. Furthermore, intrathecal kynurenic acid (1-30 μg) reversed allodynia. Probenecid (100 mg/kg, i.p.) supplementation enhanced the maximal antiallodynic effect of intrathecal kynurenic acid (10 μg). Only the combined administration of l-kynurenine (200 mg/kg)/probenecid (100 mg/kg) increased the kynurenic acid concentration in cerebrospinal fluid. KAT II is expressed in dorsal root ganglia and dorsal spinal cord. KAT II expression was unchanged by the spinal nerve ligation or l-kynurenine/probenecid combination. The kynurenine/probenecid combination did not affect motor activity. l-Kynurenine produces its antiallodynic effect in the central nervous system through kynurenic acid. This effect may result from blockade of N-methyl-d-aspartate receptors. KAT II is expressed in dorsal root ganglion and dorsal spinal cord. Combined l-kynurenine and probenecid therapy has the potential to reduce neuropathic pain in humans. © 2013 European Federation of International Association for the Study of Pain Chapters.

  7. Population pharmacokinetics of tamsulosin hydrochloride in paediatric patients with neuropathic and non-neuropathic bladder

    Science.gov (United States)

    Tsuda, Yasuhiro; Tatami, Shinji; Yamamura, Norio; Tadayasu, Yusuke; Sarashina, Akiko; Liesenfeld, Karl-Heinz; Staab, Alexander; Schäfer, Hans-Günter; Ieiri, Ichiro; Higuchi, Shun

    2010-01-01

    AIMS The main objective of this study was to characterize the population pharmacokinetics of tamsulosin hydrochloride (HCl) in paediatric patients with neuropathic and non-neuropathic bladder. A secondary objective was to compare the pharmacokinetics in paediatric patients and adults. METHODS Tamsulosin HCl plasma concentrations in 1082 plasma samples from 189 paediatric patients (age range 2–16 years) were analyzed with NONMEM, applying a one compartment model with first-order absorption. Based on the principles of allometry, body weight was incorporated in the base model, along with fixed allometric exponents. Covariate analysis was performed by means of a stepwise forward inclusion and backward elimination procedure. Simulations based on the final model were used to compare the pharmacokinetics with those in adults. RESULTS Beside the priori-implemented body weight, only α1-acid glycoprotein had an effect on both apparent clearance and apparent volume of distribution. No other investigated covariates, including gender, age, race, patient population and concomitant therapy with anti-cholinergics, significantly affected the pharmacokinetics of tamsulosin HCl (P tamsulosin HCl in paediatric patients was established and it described the data well. There was no major difference in the pharmacokinetics of tamsulosin HCl between paediatric patients (age range 2–16 years) and adults when the effect of body weight was taken into consideration. PMID:20642551

  8. Chronic kidney disease impairs renal nerve and haemodynamic reflex responses to vagal afferent input through a central mechanism.

    Science.gov (United States)

    Salman, Ibrahim M; Hildreth, Cara M; Phillips, Jacqueline K

    2017-05-01

    We investigated age- and sex-related changes in reflex renal sympathetic nerve activity (RSNA) and haemodynamic responses to vagal afferent stimulation in a rodent model of chronic kidney disease (CKD). Using anaesthetised juvenile (7-8weeks) and adult (12-13weeks) Lewis Polycystic Kidney (LPK) and Lewis control rats of either sex (n=63 total), reflex changes in RSNA, heart rate (HR) and mean arterial pressure (MAP) to vagal afferent stimulation (5-s train, 4.0V, 2.0-ms pulses, 1-16Hz) were measured. In all groups, stimulation of the vagal afferents below 16Hz produced frequency-dependent reductions in RSNA, HR and MAP, while a 16Hz stimulus produced an initial sympathoinhibition followed by sympathoexcitation. In juvenile LPK versus age-matched Lewis, sympathoinhibition was reduced when responses were expressed as % baseline (P<0.05), but not as microvolts, while bradycardic responses were greater. Reflex depressor responses were greater (P=0.015) only in juvenile female LPK. In adult LPK, reflex sympathoinhibition (%) was blunted (P<0.05), and an age-related decline apparent (when expressed as microvolts). Reflex reductions in HR and MAP were only diminished (P<0.05) in adult female LPK versus age-matched Lewis. Peak reflex sympathoexcitation at 16Hz did not differ between groups; however, area under the curve values were greater in the LPK versus Lewis (overall, 9±1 versus 19±3μVs, P<0.05) irrespective of age, suggestive of enhanced sympathoexcitatory drive in the LPK. Our data demonstrates a progressive deficit in the central processing of vagal afferent input and a differential sex influence on reflex regulation of autonomic function and blood pressure homeostasis in CKD. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  9. Antinociceptive effects of topical mepivacaine in a rat model of HIV-associated peripheral neuropathic pain

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    Sagen J

    2016-06-01

    tail of mice significantly increased tail withdrawal latencies in the tail flick test, demonstrating that both local anesthetics attenuate responding to a brief noxious stimulus.Conclusion: These findings showed that mepivacaine, rather than lidocaine, consistently attenuated two distinct symptoms of neuropathic pain and suggest that topical formulations of this local anesthetic could have utility in the alleviation of clinical HIV neuropathic pain. Keywords: chronic pain, acute pain, analgesia, AIDs-related pain, distal sensory neuropathy, local anesthetics

  10. Persistent orodental pain, atypical odontalgia, and phantom tooth pain: when are they neuropathic disorders?

    Science.gov (United States)

    Clark, Glenn T

    2006-08-01

    Patients with unrelenting pain in the teeth, gingival, palatal or alveolar tissues often see multiple dentists and have multiple irreversible procedures performed and still have their pain. Up to one-third of patients attending a chronic facial pain clinic have undergone prior irreversible dental procedures for their pain without success. In these cases, if no local source of infectious, inflammatory, or other pathology can be found, then the differential diagnosis must include a focal neuropathic pain disorder. The common diagnoses given include the terms atypical odontalgia, persistent orodental pain, or if teeth have been extracted, phantom tooth pain. One possibility is that these pain complaints are due to a neuropathic alteration of the trigeminal nerve. There are several diagnostic procedures that need to be performed in any patient suspected of having a trigeminal neuropathic disorder including (1) cold testing of involved teeth for pulpal nonvitality; (2) a periapical radiograph examining the teeth for apical change; (3) a panoramic radiograph examining for other maxillofacial disease; (4) a thorough head and neck examination also looking for abnormality; (5) a cranial nerve examination including anesthetic testing which documents any increased or decreased nerve trigeminal nerve sensitivity and rules out other neurologic changes outside the trigeminal nerve; and (6) MRI imaging in some cases. Finally, when a nonobvious atypical toothache first presents, direct microscopic examination of the tooth for incomplete tooth fracture is also suggested. The majority of these patients are women over the age 30 with pain in the posterior teeth/alveolar arch. Multiple causes exist for sustained neuropathic pain including direct nerve injury (e.g., associated with fracture or surgical treatment), nerve injection injury, nerve compression injury (e.g., implant, osseous growth, neoplastic invasion) and infection-inflammation damage to the nerve itself. Sustained nerve

  11. Effects of riluzole on P2X7R expression in the spinal cord in rat model of neuropathic pain.

    Science.gov (United States)

    Jiang, Kai; Zhuang, Ying; Yan, Ming; Chen, Hui; Ge, An-Qi; Sun, Li; Miao, Bei

    2016-04-08

    Neuropathic pain is becoming an intractable health threat, with its profound effect on quality of life, thus posing a major challenge to clinical therapy. Despite the reported efficacy of riluzole in some pain models, the underlying mechanism remains largely unknown. The present study aimed to assess the effects of riluzole in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Subsequent to model establishment, paw withdrawal latencies (PWLs) and the paw withdrawal mecha threshold (PWT) rapidly decreased, coupled with inhibited microglial activation and upregulated P2X7R expression in the spinal cord dorsal horn (SCDH). Following intraperitoneal administration of riluzole (4mg/kg) once daily for 5 consecutive days as from day 3 after surgery, the mechanical allodynia and thermal hyperalgesia in the hind limbs were significantly attenuated. In addition, riluzole downregulated P2X7R expression and inhibited microglial activation in SCDH. Our results indicated that riluzole is effective in alleviating neuropathic pain and inhibiting microglial activation, presumably via the downregulated P2X7R expression in SCDH. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. The management of neuropathic ulcers of the foot in diabetes by shock wave therapy

    Directory of Open Access Journals (Sweden)

    Pascone Michele

    2009-05-01

    Full Text Available Abstract Background Diabetes is becoming one of the most common chronic diseases, and ulcers are its most serious complication. Beginning with neuropathy, the subsequent foot wounds frequently lead to lower extremity amputation, even in the absence of critical limb ischemia. In recent years, some researchers have studied external shock wave therapy (ESWT as a new approach to soft tissue wound healing. The rationale of this study was to evaluate if ESWT is effective in the management of neuropathic diabetic foot ulcers. Methods We designed a randomized, prospective, controlled study in which we recruited 30 patients affected by neuropathic diabetic foot ulcers and then divided them into two groups based on different management strategies. One group was treated with standard care and shock wave therapy. The other group was treated with only standard care. The healing of the ulcers was evaluated over 20 weeks by the rate of re-epithelization. Results After 20 weeks of treatment, 53.33% of the ESWT-treated patients had complete wound closure compared with 33.33% of the control patients, and the healing times were 60.8 and 82.2 days, respectively (p 2/die in the ESWT-group and 1.30 mm2/die in the control group (p