Evidence that DHPG-induced nociception depends on glutamate release from primary afferent C-fibres

We examined whether enhanced glutamate release contributes to the expressio n of persistent spontaneous nociceptive behaviours (SNBs) in rats induced b y intrathecal (i.t.) administration of the selective group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine ((RS)-DHPG). Pretreatment with drugs that have been shown to inhibit glutamate release, including a group II metabotr opic glutamate receptor (mGluR) agonist (2R,4R)-4-aminopyrrolidine-2,4-dica rboxylate ((2R,4R)-APDC), a group III mGluR agonist L-2-amino-4-phosphonobu tyrate (L-AP4), or the use-dependent sodium channel blockers 3,5-diamino-6- (2,3-diclorophenyl)-1,2,4-triazine (lamotrigine) and 2-amino-6-trifluoromet hoxybenzothiazole (riluzole), produced dose-dependent reductions in (RS)-DH PG-induced SNBs. We have also shown that incubation of rat lumbar spinal co rd slices with (RS)-DHPG potentiates 4-aminopyridine-evoked (4-AP) release of glutamate. Furthermore, we found that destruction of unmyelinated primar y afferent C-fibres by neonatal capsaicin treatment significantly reduced ( RS)-DHPG-induced SNBs in adult rats. Together, these results suggest that ( RS)-DHPG-induced nociception is dependent on spinal glutamate release, prob ably from primary afferent C-fibres. NeuroReport 11:1631-1635 (C) 2000 Lipp incott Williams & Wilkins.