Neuropatic Pain Research Articles

How to treat complex regional pain syndrome in rehabilitation settings?

Complex regional pain syndrome is chronic neuropatic pain condition which usually arise after trauma. It is associated with some of the sensory, vasomotor, sudomotor, motor and trophic symptoms and sings. Due to variability of symptoms and long-lasting pain, these patients are hard to rehabilitate. They exhibit activity related fear and so have pronounced functional limitations. Adequate rehabilitation procedures, frequently long lasting, are essential for their optimal recovery, so rehabilitation specialist should constantly update their knowledge on this issue. Emerging researches on pathophysiology, diagnosis and treatment of CRPS created a need for systematization of current body of evidence. Available researches on efficacy of different treatment options are still insufficient to create precise therapy guidelines, so future researches are needed in order to promote better rehabilitation outcomes.

Genetic polymorphisms of SCNA9 as predictive markers of oxaliplatin-induced neuropathy.

9073 Background: Oxaliplatin (OXL) is an active drug in digestive tumors. Oxaliplatin induced peripheral neuropathy (OIN) is the main dose limiting toxicity. Around 60-80% of patients developed a mild cold-induced neurotoxicity that used to disappear few days after but in 15% became a persistent neuropathy. The pathophysiology of oxaliplatin-induced neuropathy (OIN) remains unclear, preclinical studies suggest involvement of voltage Na channels. SCN9A gene codifies to Na channels α subunit highly expressed in nociceptive neurons. Mutations in SCN9A are involved in alterations in neuropatic pain perception. This study tried to identify if variants in SCN9A could be associated to a higher risk to OIN. Methods: Serum were obtained from 100 patients with digestive cancer (colorectal, gastric, pancreatic and bile duct) treated with OXL (adjuvant or advanced setting) in Infanta Sofía University Hospital. No diabetes or hypotiroidism were detected. Patients were divided in two groups according to the development of OIN: Arm A 50 patients diagnosed of grade 2-3 OIN after 6 courses and Arm B 50 with no OIN. The evaluation of severity of the OIN by a neurologist included a classification according to NCI-CTC and OSNS scales and conduction studies. Genomic DNA was isolated from serum and variants of SCN9A were analyzed by PCR-RFLP. The relation between SCN9A genotype and the development of severe OIN was the primary aim Results: One hundred patients were enrolled between May 2010-November 2011. 56 (56%) females and 44 (44%) males; mean age was 62; mean ECOG was 1; primary tumor were colorectal 81 pts (81%), gastric 10 (10%); 8 (8%) pancreto-biliar and anus 1(1%). Stage were classified in localized 65 (65%) and advanced (35%). The chemotherapy regimen included: 94 (94%) XELOX, 1 (1%) XELOX-Herceptin and 5 (5%) EOX regimen. The mean of cycles were 7 (1-14). Mean OXL dose intensity was 100mg/m2.The mean PFS was 23 months. High expression of SCN9A variants were detected in patients 26/50, 52% arm A and in 5/50, 10% arm B patients, suggesting a possible relationship beetwen the development of OIN and SCN9A genotype (p=0.04). Conclusions: SCN9A polimorphysms may help to identify those patients with a higher risk to develop oxaliplatin induced neuropathy.

Chronic postoperative pain and sensory changes following reduction mammaplasty

Background Few studies have examined persistent pain after reduction mammaplasty, and sensory changes remain a controversial subject with studies reporting both reduced, improved, and unchanged skin sensitivity following surgery. The aim of the present study was to describe the prevalence, character, and impact of sensory changes and persistent pain following breast reduction surgery and to assess possible causes and predictors of persistent sensory changes and chronic pain. Methods In May 2010, a detailed questionnaire was mailed to all 109 patients who underwent reduction mammaplasty at the Department of Plastic Surgery, Aalborg Hospital from September 2004 to February 2010. Ninety patients (83%) returned the questionnaire; mean age was 48.7 years (SD 14.7); and mean time since surgery was 27.7 months. Results Eight patients reported that they had sensory abnormalities in the breasts before surgery, which normalized or improved in four, remained unchanged in one, and worsened in three patients following surgery. Forty-nine patients (54%) reported sensory changes in the nipple–areola complex or skin as a consequence of surgery. Sixty-nine patients reported having pain before surgery (most often in the neck/back), which was completely relieved in 42% and partially in 43%. Twenty-five patients (28%) reported having pain in the breasts as a consequence of the operation: 20% had chronic pain (defined as constant pain or pain at least once weekly for at least 3 months) and 7% had moderate to severe pain. In more than half of the patients, the pain was compatible with neuropathic pain. Patients with pain tended to be less satisfied with the surgery than those without pain ( p = 0.07, Mann–Whitney U test). Young age, time since surgery, complications to surgery and sensory abnormalities before surgery were significantly related to pain. Conclusion Reduction mammaplasty relieved neck and back pain in most patients, but the surgery is associated with a risk of developing new sensory abnormalities and persistent neuropatic pain. Implications The clinical implication of this study is that reduction mammaplasty may sooth preexisting neck- and back pain, but may lead to a new condition in the patient with chronic sensory changes and pain in the breasts.

P02-549 - Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Medication-Resistant Neuropatic Pain

IntroductionTranscranial magnetic stimulation (TMS) is a non-invasive method that induces functional changes in a relatively small area of the cerebral cortex. It is supposed that the effect of the method in therapy of neuropatic pain is based on the induction of spinothalamic tract inhibiton, which leads to the symptom withdrawal.AimTo prove the clinical and electrophysiological effect of rTMS in the therapy of chronic neuropatic pain.Methods29 patients with medication-resistant neuropatic pain were examined by Visual analog scale (VAS), McGill Pain Questionnaire (MPQ) and QST(Quantitative sensory Testing, consisted of von Frey and thermic treshold examination),then treated by high frequency rTMS in the study using double-blind randomized sham-controlled parallel design. rTMS parameters: 5 rTMS sessions (2 weeks treatment), where each session consisted of three 10 Hz rTMS series using:1)85%MT (motor treshold),2)90%MT and3)95%MT.Each rTMS série consisted of 20 pulses in 12 trains. Location of the active coil was administered over the contralateral motor cortex, directed specifically to facial area of homunculus (according to funcional location). Sham coil was angled 90° degrees away from the skull.ResultsConfirmation of a significant decrease of VAS item in active group, trend to improvement in tactile sensation of severed patient faces. The changes of thermic treshold were not found. Sham rTMS did not show any trend for improvement.ConclusionAlthough no general recommendations can be drawn based on our result, our study is another one that suggest rTMS should be considered as an effective and safe treatment option for chronic neuropatic pain.

Antihyperalgesic activity of salvianolic acid B and its formulations in the chronic constriction injury of the sciatic nerve (CCI) model of neuropatic pain

Salvianolic acid B (Sal B) is the most abundant and the major active antioxidant from S. miltiorrhiza preventing Aβ25–35-induced reduction in BPRP in PC12 cells [1], having neuronprotective effect against hydrogen peroxide (H2O2)-induced rat pheochromocytoma line PC12 injury [2] and inhibiting HIV-1 replication [3]. In the framework of a large screening of natural constituents, the antihyperalgesic activity of Sal B was tested by the Paw-pressure test, in a model of neuropathic pain produced by a chronic constriction injury of the sciatic nerve. Size exclusion chromatography (Sephadex LH-20) was used for a rapid separation and refinement of Sal B from the crude extract of the roots of S. miltiorrizha Bunge (danshen). Hydroalchoholic solutions were used as eluents for a safe and convenient separation obtaining Sal B almost pure by NMR (>96%). Liposomial formulations were prepared using egg phosphatydil choline, cholesterol and 18:0/18:0 PEG 2000 in the case of long circulationg liposome. Encapsulation efficacy of Sal B was evaluated by HPLC-DAD, while size, polydispersion index and zeta potential by dynamic light scattering. Sal B and two formulations, liposomes and long circulating liposomes, administered intraperitoneally at the dose of 100mg/kg, reverted the mechanical hyperalgesia in CCI treated rats, evaluated in the Paw-pressure test. The antihyperalgesic effect started 15min. after administration and in the case of long circulating liposomes the antihyperalgesic effect was still significant at 45min. The prolonged, delayed and increased therapeutic effect of the long circulating liposomes was also supported by preliminary pharmacokinetic studies.

Retrospective Evaluation of Pain and Pain Management in Lung Cancer Patients

We investigated nature of pain and effectiveness of pain management methods applied of the primary lung cancer patients, if their pain's due to primary cancer or metastasis. In this retrospective study, patients with primary lung cancer who treated in our pain clinic were included in this study between January 2004 and January 2009. They were questionared for the pain localisation, onset time and exacerbation period of pain, characteristics of the pain(neuropatic or visserral), VAS, metastasis of cancer, related to cancer treatment. In addition pain affects on sleep, quality of life were questionared. Analgesic therapy and interventional methods applied were examined. One hundered twenty one patients (11 women, 110 men) had applied to pain clinic between the years 2004 -2008. Age range of the patients was 30-80 years. 92 patients defined neuropatic pain, 29 patients defined visseral pain. The localization of pain were mostly at back, shoulder, upper abdomen, lib and legs. In 25 patients pain were primary due to lung cancer, 96 patients' were due to metastasis. Visseral pain had acute onset, within 2 weeks of duration. Onset time of neuropatic pain was 3 months. Exacerbation period of visseral pain was meanly a week, and neuropatic pain was meanly 3 months. We started appropriate treatment from WHO ladder treatments according to their pains. We applicated central or peripheral nevre blockade when medical treatment didn't work in 24 hours. In 95 patients (78.5%) medical treatment worked. But in 26 (21.5 %) patients pain was under-control with central or blockade additional to medical treatment. In 16 of 26 nerve blockade patients, we inserted epidural catheter and in the other 10 patients we applicated intercostal nevre blockade. We applicated suprascapular blockade to 7 patients having shoulder pain. Almost every patients had mood and sleep disorders. We determined that patients with primary lung cancer who admitted to our pain clinic have mostly neuropatic pain usually secondary to metastasis. On the other hand, patients who described visceral pain have shorter duration of pain onset. Pain was controlled with either medical or interventional methods in all patients.

468 SPANISH GUIDELINES FOR THE TREATMENT OF SEVERE PERIPHERAL NEUROPATIC PAIN

European Journal of Pain SupplementsVolume 4, Issue S1 p. 132-133 468 SPANISH GUIDELINES FOR THE TREATMENT OF SEVERE PERIPHERAL NEUROPATIC PAIN M.D. Lopez Alarcon, Pain Unit, Department of Anesthesia, Critical Care and Pain Unit, ValenciaSearch for more papers by this authorM.L. Franco Gay, Pain Unit, Cruces Hospital, VizcayaSearch for more papers by this authorJ.M. Lopez Millan, Pain Unit, Department of Anesthesia, Critical Care and Pain Unit, SevillaSearch for more papers by this authorV. Monsalve Dolz, Pain Unit, Department of Anesthesia, Critical Care and Pain Unit, ValenciaSearch for more papers by this authorJ. Perez-Cajaraville, Pain Unit, Department of Anesthesia, Critical Care and Pain Unit, Pamplona, SpainSearch for more papers by this author M.D. Lopez Alarcon, Pain Unit, Department of Anesthesia, Critical Care and Pain Unit, ValenciaSearch for more papers by this authorM.L. Franco Gay, Pain Unit, Cruces Hospital, VizcayaSearch for more papers by this authorJ.M. Lopez Millan, Pain Unit, Department of Anesthesia, Critical Care and Pain Unit, SevillaSearch for more papers by this authorV. Monsalve Dolz, Pain Unit, Department of Anesthesia, Critical Care and Pain Unit, ValenciaSearch for more papers by this authorJ. Perez-Cajaraville, Pain Unit, Department of Anesthesia, Critical Care and Pain Unit, Pamplona, SpainSearch for more papers by this author First published: 06 January 2012 https://doi.org/10.1016/S1754-3207(10)70473-9Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume4, IssueS1April 2010Pages 132-133 RelatedInformation

Antihyperalgesic activity of verbascoside in the chronic constriction injury of the sciatic nerve (CCI) and intra-articular injection of sodium monoiodoacetate (MIA) models of neuropatic pain

Antihyperalgesic activity of verbascoside in the chronic constriction injury of the sciatic nerve (CCI) and intra-articular injection of sodium monoiodoacetate (MIA) models of neuropatic pain

Methadone rotation and initiation in outpatient cancer pain

e20734 Background: Methadone is an effective mu opioid agonist. Delta receptor affinity, monoamine reuptake inhibition an antagonism in N-methyl-D-aspartate receptor have been described. Because of itst long half-life and lack of standart conversion ratio outpatient use is chalinging. Methods: Retrospective review of consecutive medical reports were performed from 2002 to 2007. Patients with methadone as exclusive drug for the first two months were selected. A total of 143 patients were analyzed. Symptoms, toxicities, clinical caraceristics rotation e neuropatic pain were acessed. Results: 89 (62.2%) were female, 54 (37.7%) were male, all patients had solid tumors and were under palliative care only. 52 (36.6%) had neuropathic pain. Median age was 67 years. Median pain score at baseline was 7. After four follow-up with intervals of four days in average, 78% patients had score zero. At the end of two months we found a median (range) of 18 follow-ups performed. 127 (88.8%) patients had score zero. The remaining patients were rotated to other opioid. Neuropathic pain was improved in 36 (73%) of patients only with methadone. 16 (17%) had to use adjuvant drugs. Mean methadone dose was 10mg/day at baseline and 20mg/day at the end of two months.Sedation, obstipation and neurologic symptoms were mild and no major complication was observed. Conclusions: Methadone as initial opioid opyion showed excelent and safe response rates. Its capacity of blocking NMDA receptors may explain the high rate control for neuropathic pain. This finding was not observed in others studies. The low cost, lack of active metabolites, good tolerance in older patents and the finding in neuropathic pain should be better explored in well prospective randomized future clinical trials. No significant financial relationships to disclose.

Pain and the pharmacogenetics at the fuzzy border between pain physiopathology and pain treatment

Nociceptive pain is time limited and severe nociceptive pain normally responds well to treatment with opioids, On the contrary, neuropatic pain is frequently chronic, and tends to have a less robust response to treatment with opioids. The unsolved problem of insufficient pain treatment at clinical level, including both wanted analgesic effects and unwanted side effects, is a stimulus to expand the knowledge on the physiophatology of pain and on the involved molecular mechanisms. In particular, it is important not only to better understand the molecular mechanisms associated to drugs effects but also to characterize the genetic traits underlying pharmacokinetic (PK) and pharmacodynamic (PD) mechanisms related to drugs. Literature analysis reveals that there are interesting genetic polymorphisms that are associated either to the sensitivity to pain and to PD response to drugs, or to the metabolic and excretion pathways. Pharmacogenetics/pharmacogenomics holds the promise that drugs might in the next future be tailor-made for individuals and adapted to each person's own genetic background. Collected information, allowing to design combined therapies and to dissect analgesic from addictive properties of opioids within a given patient, will also contribute to contrast the persisting opiophobia in medical practice.

Lesiones del plexo braquial. A propósito de un caso

The brachial plexus injuries are more frequent that it can be thought. Young people used to suffer it more frequently than other people. They compromise seriously the function of the upper limb causing a sensitive, motor and vegetative paralysis that, frequently, it is accompanied by an intense neuropatic pain with repercussion in the psychological condition of the patient. The key concepts of the treatment are a good election of the moment of the surgery and the establishment of the priorities when the function were recovered. The surgical techniques include neurolysis, nervous grafts, neurotizations and free muscular transfers. It is presented a case of brachial plexus injury as an example about the aetiology and the surgical techniques of reparation in the different stages of the clinical evolution.

Causas de reintervención quirúrgica en pacientes con fijación lumbar intervenidos por estenosis de canal

In present study we analyze the causes leading to reoperation patients treated for lumbar spinal stenosis with laminectomy and lumbar instrumentation. 74 patients operated between January of 1996 and December of 2000 with a minimum 4 year follow-up were seleted for the study. 16 patients (21.1%) underwent a new surgical intervention. The main cause for reoperation was stenosis of the adjacent level superiorly to the instrumentation (in 50%). Other causes were radicular fibrosis, persistence of stenosis after the surgery, neuropatic pain, failure of the instrumentation system, transpedicular screws misplacement and break of screws. Complications related with the initial surgical procedure are low, as half of the reoperations were due to stenosis of the segment superior to the fixation.

Pregabalin versus gabapentin nel trattamento dei pazienti con neuropatia periferica: adattamento di un modello internazionale per la valutazione di costo/efficacia e costo/utilità alla realtà nazionale

OBJECTIVE: To compare the economic impact of treating neuropathic pain with pregabalin versus gabapentin. DESIGN: A cost effectiveness analysis comparing costs and effects of pregabalin 375 mg/die versus gabapentin 1800 mg/die in the perspective of the Italian National Healthcare Service was developed. The cost effectiveness analysis is examined alternatively in terms of the incremental cost per additional day with no or mild pain, and the incremental cost per quality-adjusted life-year (QALY) gained. Effects were derived from a pregabalin randomised clinical study 1008-155 and gabapentin 645-210 and 945-211 studies. Effects are expressed as reduction score of the VAS pain scale. Pharmacological costs were quantified according to the Italian market price of the drugs; healthcare procedure and hospitalisation costs were quantified on the basis of the National Tariff. Other healthcare services consumption data were derived from a Delphi Panel. To estimate the impact of pregabalin and gabapentin on daily pain experience in patients with neuropatic pain a Markov model is used. The dynamic simulation focuses on a hypothetical cohort of 1000 patients and simulates their daily pain experience over 12 weeks, to estimate clinical and economic outcomes for the group as a whole. MAIN OUTCOME MEASURES AND RESULTS: The cost-effectiveness ratio for the use of pregabalin is less than 1 euro per additional day with no or mild pain and 468 euros per QALY. The sensitivity analysis conducted to examine the effects of decreasing gabapentin dose to 1200 mg/die showes the consistency of the model results. CONCLUSIONS AND RESULTS: Although pregabalin pure costs are higher than gabapentin costs, the analyses prove pregabalin to be more effective with a small additional cost per day with no or mild pain.

Bortezomib-Induced Severe Hepatitis in Multiple Myeloma

Bortezomib is a novel proteasome inhibitor with significant antimyeloma activity. Its toxicity is manageable, and the most frequent adverse effects mainly consist of gastrointestinal symptoms, peripheral neuropathy, neuropatic pain, and thrombocytopenia. Severe liver toxicity has not been previously recognized. A patient with relapsed multiple myeloma who developed bortezomib-induced severe recurrent hepatitis is described. The importance of recognizing this rare potential toxicity is highlighted in order to discontinue this agent if liver adverse reaction is suspected.

P–509 - Neurogenic inframmation in a neuropatic pain model in the rat

P–509 - Neurogenic inframmation in a neuropatic pain model in the rat

The Effects of NMDA Antagonists and Sympathectomy on the c-Fos mRNA Expression in the Neuropathic Rat

Background: Neuropathic pain produced by nerve injury has the characteristics of enhanced pain responses allodynia. To understand the pathophysiology of the neuropathic pain, We evaluated the effect of NMDA antagonists and chemical sympathectomy on the c-fos mRNA expression. Methods: We have divided rats(Sprague-Dawley, N=24) that their left L5 and L6 nerve were tightly ligated into two groups. In NMDA antagonist group(N=17), We injected 10 μg MK801 and 10 μg 5-amino-phosphonovalerate in three ways, intrathecally before the ligation, after ligation and subcutaneous continuously. Then behavioral tests for mechanical allodynia and cold allodynia were performed. After the test of allodynia,the expression of c-fos were assessed by Northern blot hybridization. In chemical sympathectomy group(N=7), We injected 70 mg/kg guanethidine into the peritoneum in two ways, before the ligation and after ligation. Then same methods were performed in NMDA antagonist group as well. Results: Intrathecal NMDA antagonists before the ligation supressed the elevation of c-fos mRNA expression. Intrathecal NMDA antagonists on the 7 days after the ligation reduced the c-fos mRNA expression and neuropathic pain. Continuous treatment of subcutaneous NMDA antagonists supressed the development of neuropathic pain and the elevation of c-fos mRNA expression. Chemical sympathectomy before the ligation did not supress the elevation of c-fos mRNA expression. Chemical sympathectomy on the 7 days after the ligation reduced neuropathic pain and the elevation of c-fos mRNA expression. Conclusions: NMDA receptor is related to the induction and maitenance of neuropatic pain, and

Management of cancer pain in Denmark: a nationwide questionnaire survey

A questionnaire survey was carried out with the aim of evaluating knowledge about and practice of cancer pain treatment in Denmark. A questionnaire was sent out to a 10% random sample of Danish physicians. Of these 1411 physicians, 1068 (76%) returned the questionnaires and after exclusion of those doctors who never treated cancer patients, 577 (54%) were analyzed. Their knowledge of the principles and pratice of cancer pain treatment was evaluated by means of 14 multiple-choice and open questions. Their ability to apply their knowledge in practice was evaluated by analyzing their suggested treatment of 3 simulated patient cases. The results show that a vast majority (97%) of the physicians were prepared to use opioids conventionally administered for severe pain and that 39% reported the use of other treatment modalities (psychological treatment, antineoplastic therapy, transcutaneous nerve stimulation/acupuncture, etc.). Ninety-seven percent of the physicians recognized difficulties in cancer pain treatment, the most frequent being side effects of drugs and inadequate pain relief. Seventy-five percent considered that their knowledge about pain treatment was fair or better. The overall evaluation of the proposals for pain treatment of the patient cases was primarily based on drug therapy. Adequate doses, correct dose intervals and selection of drugs, routes of administration and other treatments were the requirements for satisfactory answers. It appears that the majority the physicians could treat both pain from bone metastasis (75%) and visceral pain (78%) satisfactorily, while very few suggested co-analgesics for neuropatic pain conditions (20%). Older physicians performed less well than their younger colleagues. Basic pain treatment skills have been acquired by the Danish physicians but, in the future, emphasis should be placed on the treatment of neuropathic pain with co-analgesics and the management of opioid side effects.