Key role for spinal dorsal horn microglial kinin B1receptor in early diabetic pain neuropathy

Background: the pro-nociceptive kinin b1receptor (b1r) is upregulated on sensory c-fibres,astrocytes and microglia in the spinal cord of streptozotocin (stz)-diabetic rat. this study aims at defining the role of microglial kinin b1r in diabetic pain neuropathy.methods: sprague-dawley rats were made diabetic with stz (65 mg/kg,i.p.),and 4 days later,two specific inhibitors of microglial cells (fluorocitrate,1 nmol,i.t.; minocycline,10 mg/kg,i.p.) were administered to assess the impact on thermal hyperalgesia,allodynia and mrna expression (qrt-pcr) of b1r and pro-inflammatory markers. spinal b1r binding sites ((125i)-hpp-desarg10-hoe 140) were also measured by quantitative autoradiography. inhibition of microglia was confirmed by confocal microscopy with the specific marker iba-1. effects of intrathecal and/or systemic administration of b1r agonist (des-arg9-bk) and antagonists (ssr240612 and r-715) were measured on neuropathic pain manifestations.results: stz-diabetic rats displayed significant tactile and cold allodynia compared with control rats. intrathecal or peripheral blockade of b1r or inhibition of microglia reversed time-dependently tactile and cold allodynia in diabetic rats without affecting basal values in control rats. microglia inhibition also abolished thermal hyperalgesia and the enhanced allodynia induced by intrathecal des-arg9-bk without affecting hyperglycemia in stz rats. the enhanced mrna expression (b1r,il-1β,tnf-α,trpv1) and iba-1 immunoreactivity in the stz spinal cord were normalized by fluorocitrate or minocycline,yet b1r binding sites were reduced by 38%.conclusion: the upregulation of kinin b1r in spinal dorsal horn microglia by pro-inflammatory cytokines is proposed as a crucial mechanism in early pain neuropathy in stz-diabetic rats. © 2010 talbot et al; licensee biomed central ltd.