Articles: neuralgia.
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Although neuropathic pain is one of the most intractable diseases, recent studies indicate that systemic or local injection of bone marrow stromal cells (BMSCs) decreases pro-inflammatory cytokines release and alleviates neuropathic pain. However, it is still not clear whether pre-treated BMSCs have a strong anti-inflammatory and/or analgesia effect. Using the spinal nerve ligation model of neuropathic pain, IL-1β pre-treated BMSCs (IL-1β-BMSCs) were injected into rats followed by SNL in order to determine possible effects. ⋯ Results also showed that IL-1β-BMSCs had a stronger inhibitory effect on astrocyte activation as well as CCL7 release, which was found to be mediated by IL-10 not transforming growth factor-β1. In addition, we also found directional migration of IL-1β-BMSCs was mediated by inceased C-X-C motif chemokine ligand (CXCL) 13 expression following SNL. In conclusion, our results indicated IL-1β-BMSCs could inhibit microglia activation and neuropathic pain by decreasing CCL7 level in spinal cord.
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Neurochemical research · Feb 2017
Upregulated TLR3 Promotes Neuropathic Pain by Regulating Autophagy in Rat With L5 Spinal Nerve Ligation Model.
Microglia, rapidly activated following peripheral nerve injury (PNI), accumulate within the spinal cord and adopt inflammation that contributes to development and maintenance of neuropathic pain. Microglia express functional Toll-like receptors (TLRs), which play pivotal roles in regulating inflammatory processes. However, little is known about the role of TLR3 in regulating neuropathic pain after PNI. ⋯ Poly (I:C) treatment promotes the expression of proinflammatory mediators, whereas 3-MA (a specific inhibitor of autophagy) suppresses Poly (I:C)-induced secretion of proinflammatory cytokines. Autophagy inhibition further inhibits TLR3-mediated mechanical and cold hypersensitivity following SNL. These results suggest that inhibition of TLR3/autophagy signaling contributes to alleviate neurophathic pain triggered by SNL.
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Review Meta Analysis
Different doses of gabapentin formulations for postherpetic neuralgia: A systematical review and meta-analysis of randomized controlled trials.
Gabapentin, extended-release gabapentin (gabapentin ER), and gabapentin enacarbil (GEn), play an important role in relieving pain associated with postherpetic neuralgia (PHN). Although previous systematic reviews have assessed the efficacy and safety of gabapentin formulations for PHN, they have failed to take formulation differences and dose differences into account. Aiming at assessing the efficacy and safety of different doses of gabapentin formulations for PHN, this study performed a systematical review and meta-analysis of randomized controlled trials (RCTs). ⋯ An increasing gabapentin dose may not provide a good pharmacological therapy, whereas it can increase the risk of adverse events. Gabapentin ER, 1800 mg/day once daily treatment is significantly effective in pain relief, following high incidence of adverse events, but twice daily treatment shows no significant differences in both efficacy and safety compared with placebo. GEn 1200 mg/day and 2400 mg/day doses are more effective and safe in treating PHN. The long-term efficacy and safety of different doses of gabapentin formulations remain to be determined.
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Pharmacol. Biochem. Behav. · Feb 2017
HYP-17, a novel voltage-gated sodium channel blocker, relieves inflammatory and neuropathic pain in rats.
Clinical and experimental studies suggest that voltage-gated sodium channels (VGSCs) play a key role in the pathogenesis of neuropathic pain and that blocking agents against these channels can be potentially therapeutic. In the current study, we investigated whether a novel compound, (-)-2-Amino-1-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)-propan-1-one(HYP-17), binds to VGSCs and evaluated its inhibitory effect on Na+ currents of the rat dorsal root ganglia (DRG) sensory neurons and its analgesic effect on inflammatory and neuropathic pain. HYP-17 (10μM) reduced both the tetrodotoxin-sensitive (TTX-S) and the TTX-resistant (TTX-R) currents in DRG sensory neurons. ⋯ Electrophysiological study showed that HYP-17 significantly attenuated the hyper-responsiveness of lumbar dorsal horn neurons. In addition, HYP-17 significantly reduced the levels of pp38MAPK and p-JNK in microglia and astrocytes, respectively, in the L4-L5 spinal dorsal horn. Therefore, our results indicate that HYP-17 has potential analgesic activities against nociceptive, inflammatory and neuropathic pain.
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Randomized Controlled Trial
Fulranumab in Patients with Pain Associated with Postherpetic Neuralgia and Postraumatic Neuropathy: Efficacy, Safety and Tolerability Results from a Randomized, Double-blind, Placebo-controlled, Phase-2 Study.
Fulranumab is an antibody that specifically neutralizes the biological activity of human nerve growth factor. This multicenter, phase-2, randomized, double-blind (DB), placebo-controlled study evaluated the analgesic efficacy and safety of fulranumab in postherpetic neuralgia (PHN) and posttraumatic neuropathy (PTN) patients. ⋯ Fulranumab did not demonstrate efficacy in either PHN or PTN patients, but was generally well-tolerated in this small underpowered and abbreviated study.