Activation of TRPV1 by capsaicin induces functional Kinin B 1receptor in rat spinal cord microglia

Background: the kinin b 1receptor (b 1r) is upregulated by pro-inflammatory cytokines and oxydative stress,which are enhanced by transient receptor potential vanilloid subtype 1 (trpv1) activation. to examine the link between trpv1 and b 1r in inflammatory pain,this study aimed to determine the ability of trpv1 to regulate microglial b 1r expression in the spinal cord dorsal horn,and the underlying mechanism.methods: b 1r expression (mrna,protein and binding sites) was measured in cervical,thoracic and lumbar spinal cord in response to trpv1 activation by systemic capsaicin (1-50 mg/kg,s.c) in rats pre-treated with trpv1 antagonists (capsazepine or sb-366791),the antioxidant n-acetyl-l-cysteine (nac),or vehicle. b 1r function was assessed using a tail-flick test after intrathecal (i.t.) injection of a selective b 1r agonist (des-arg 9-bk),and its microglial localization was investigated by confocal microscopy with the selective fluorescent b 1r agonist,[n α-bodipy]-des-arg 9-bk. the effect of i.t. capsaicin (1 μg/site) was also investigated.results: capsaicin (10 to 50 mg/kg,s.c.) enhanced time-dependently (0-24h) b 1r mrna levels in the lumbar spinal cord; this effect was prevented by capsazepine (10 mg/kg,i.p.; 10 μg/site,i.t.) and sb-366791 (1 mg/kg,i.p.; 30 μg/site,i.t.). increases of b 1r mrna were correlated with il-1β mrna levels,and they were significantly less in cervical and thoracic spinal cord. intrathecal capsaicin (1 μg/site) also enhanced b 1r mrna in lumbar spinal cord. nac (1 g/kg/d × 7 days) prevented b 1r up-regulation,superoxide anion production and nf-kb activation induced by capsaicin (15 mg/kg). des-arg 9-bk (9.6 nmol/site,i.t.) decreased by 25-30% the nociceptive threshold at 1 min post-injection in capsaicin-treated rats (10-50 mg/kg) while it was without effect in control rats. des-arg 9-bk-induced thermal hyperalgesia was blocked by capsazepine,sb-366791 and by antagonists/inhibitors of b 1r (ssr240612,10 mg/kg,p.o.),glutamate nmda receptor (dl-ap5,10 μg/site,i.t.),substance p nk-1 receptor (rp-67580,10 μg/site,i.t.) and nitric oxide synthase (l-nna,10 μg/site,i.t.). the b 1r fluorescent agonist was co-localized with an immunomarker of microglia (iba-1) in spinal cord dorsal horn of capsaicin-treated rats.conclusion: this study highlights a new mechanism for b 1r induction via trpv1 activation and establishes a link between these two pro-nociceptive receptors in inflammatory pain. © 2012 talbot et al; licensee biomed central ltd.