Inhibiting BDNF/TrkB.T1 receptor improves resiniferatoxin-induced postherpetic neuralgia through decreasing ASIC3 signaling in dorsal root ganglia

Abstract Background Postherpetic neuralgia (PHN) is a devastating complication after varicella-zoster virus infection. Brain-derived neurotrophic factor (BDNF) has been shown to participate in the pathogenesis of PHN. A truncated isoform tropomyosin receptor kinase B (TrkB) TrkB.T1, as high-affinity BDNF, upregulated multiple nervous system injuries, and such upregulation associated with pain. Acid-sensitive ion channel 3 (ASIC3) involved chronic neuropathic pain, but its relation BDNF/TrkB.T1 peripheral (PNS) during PHN unclear. This study aimed investigate whether contributes through regulating ASIC3 signaling dorsal root ganglia (DRGs). Methods Resiniferatoxin (RTX) was used induce rat models. Mechanical allodynia assessed by measuring paw withdrawal thresholds (PWTs). Thermal hyperalgesia determined detecting latencies (PWLs). We evaluated effects TrkB.T1-ASIC3 inhibition on behavior, neuronal excitability, inflammatory response RTX-induced short hairpin RNA (shRNA) transfection effect exogenous BDNF cultured PC-12 cells. Results RTX injection induced mechanical protein expression ASIC3, TRAF6, nNOS, c-Fos, well increased excitability DRGs. Inhibition reversed abovementioned RTX, except for TrkB.T1 expression. In addition, blocked allodynia, activation signaling, hyperexcitability neurons. found both neurons satellite glia cells Furthermore, activated NO level, enhanced IL-6, IL-1?, TNF-? levels cells, which shRNA-ASIC3 transfection. Conclusion These findings demonstrate that inhibiting reduced inflammation, decreased hyperexcitability, improved pathway DRGs, may provide novel therapeutic target patients