Articles: neuropathic-pain.
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Glutamate neurotoxicity and pro-inflammatory cytokines have an important role in the central sensitization of neuropathic pain. The purpose of the present study was to evaluate anti-hyperalgesic effect of repeated administration of ceftriaxone, which selectively activates and increases the expression of glutamate transporter, as well as minocycline, a selective inhibitor of microglia activation, either alone or together in Wistar rats subjected to the chronic constriction injury (CCI) of sciatic nerve. Ceftriaxone (100, 150 and 200 mg/kg) and minocycline (25, 50 and 100 mg/kg) were administered intraperitoneally from the day of surgery for seven consecutive days. ⋯ None of the administered doses of minocycline affected the CCI induced-thermal hyperalgesia in neuropathic animals. A fixed dose of minocycline (50 mg/kg) combined with three different doses of ceftriaxone administered for 7 consecutive days yielded a potentiating effect in the enhancing latency time to noxious thermal stimulus remaining until the 14th day post-surgery. The results suggest that modulation of microglia activity could have a supportive role in the improvement of CCI-induced thermal hyperalgesia and combination of such classes of drugs which have no antibiotic effects could be a new and promising therapeutic strategy for treatment.
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Etifoxine (etafenoxine, Stresam®) is a non-benzodiazepine anxiolytic with an anticonvulsant effect. It was developed in the 1960s for anxiety disorders and is currently being studied for its ability to promote peripheral nerve healing and to treat chemotherapy-induced pain. In addition to being mediated by GABAAα2 receptors like benzodiazepines, etifoxine appears to produce anxiolytic effects directly by binding to β2 or β3 subunits of the GABAA receptor complex. ⋯ In conclusion, etifoxine shows less adverse effects of anterograde amnesia, sedation, impaired psychomotor performance, and withdrawal syndromes than those of benzodiazepines. It potentiates GABAA receptor-function by a direct allosteric effect and by an indirect mechanism involving the activation of TSPO. It seems promising that non-benzodiazepine anxiolytics including etifoxine will replenish shortcomings of benzodiazepines and selective serotonin reuptake inhibitors according to animated studies related to TSPO.
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Journal of neurology · Jan 2015
Randomized Controlled Trial Multicenter StudyA multicentre, open-label, follow-on study to assess the long-term maintenance of effect, tolerance and safety of THC/CBD oromucosal spray in the management of neuropathic pain.
Peripheral neuropathic pain (PNP) poses a significant clinical challenge. The long-term efficacy of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray was investigated in this 38-week open-label extension study. In total, 380 patients with PNP associated with diabetes or allodynia entered this study from two parent randomised, controlled trials. ⋯ Improvements were observed for all secondary efficacy outcomes, including sleep quality 0-10 NRS scores, neuropathic pain scale scores, subject global impression of change and EQ-5D questionnaire scores. THC/CBD spray was well tolerated for the study duration and patients did not seek to increase their dose with time, with no new safety concerns arising from long-term use. In this previously difficult to manage patient population, THC/CBD spray was beneficial for the majority of patients with PNP associated with diabetes or allodynia.
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Expert Opin. Ther. Targets · Jan 2015
ReviewTargeting angiotensin II type 2 receptor pathways to treat neuropathic pain and inflammatory pain.
Neuropathic pain and chronic inflammatory pain are large unmet medical needs. Over the past two decades, numerous 'pain targets' have been identified for analgesic drug discovery. Despite promising results in rodent pain models, many compounds modulating such targets lacked efficacy in clinical trials. An exception is oral EMA401, a small-molecule angiotensin II type 2 receptor (AT2R) antagonist. ⋯ The functional importance of angiotensin II/AT2R signaling has remained enigmatic for decades, and there are no clinically available medications that target the AT2R. However, on the basis of preclinical findings and recent clinical trial data showing that the peripherally restricted, small-molecule AT2R antagonist, EMA401, successfully alleviated neuropathic pain in a Phase II clinical trial, the AT2R is receiving considerable attention as a new therapeutic target with human validation for the relief of peripheral neuropathic and chronic inflammatory pain conditions.
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Top Spinal Cord Inj Rehabil · Jan 2015
Meta AnalysisAntidepressants Are Effective in Decreasing Neuropathic Pain After SCI: A Meta-Analysis.
To systematically review and assess the effectiveness and safety of antidepressants for neuropathic pain among individuals with spinal cord injury (SCI). ⋯ The current meta-analysis demonstrates that antidepressants are effective in reducing neuropathic SCI pain. However, this should be interpreted with caution due to the limited number of studies. Further evaluation of long-term therapeutic options may be required.