Visceral and somatic pain modalities reveal NaV1.7-independent visceral nociceptive pathways

摘要: Voltage-gated sodium channel NaV 1.7 is required for acute and inflammatory pain in mice humans but its significance visceral unknown. Here we examine the role of processing development referred hyperalgesia using a conditional nociceptor-specific knockout mouse (NaV 1.7(Nav1.8) ) selective small-molecule antagonist PF-5198007. showed normal nociceptive behaviours to intracolonic application either capsaicin or mustard oil, stimuli known evoke sustained nociceptor activity sensitization following tissue damage, respectively. Normal responses induction cystitis by cyclophosphamide were also observed both littermate controls. Loss, blockade, did not affect afferent noxious mechanical chemical nerve-gut preparations mouse, antagonism resected human appendix stimulated distending pressures. However, expression analysis voltage-gated α subunits revealed mRNA transcripts nearly all retrogradely-labelled colonic neurons suggesting redundancy function. By contrast, comparative somatic behavioral models identify that genetic deletion (in 1.8-expressing neurons) regulates heat threshold this can be recapitulated Our data demonstrates contributes defined pathways modality-dependent manner, modulating processing, advocates pharmacological block alone viscera may insufficient targeting chronic pain. This article protected copyright. All rights reserved.