Evidence that DHPG-induced nociception depends on glutamate release from primary afferent C-fibres.
We examined whether enhanced glutamate release contributes to the expression of persistent spontaneous nociceptive behaviours (SNBs) in rats induced by 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 metabotropic glutamate receptor (mGluR) agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R,4R)-APDC), a group III mGluR agonist L-2-amino-4-phosphonobutyrate (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-trifluoromethoxybenzothiazole (riluzole), produced dose-dependent reductions in (RS)-DHPG-induced SNBs. We have also shown that incubation of rat lumbar spinal cord slices with (RS)-DHPG potentiates 4-aminopyridine-evoked (4-AP) release of glutamate. Furthermore, we found that destruction of unmyelinated primary 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, probably from primary afferent C-fibres.
Lefebvre
C
C
Pain Mechanisms Laboratory, Clinical Research Institute of Montreal, Quebec, Canada.
Fisher
K
K
Cahill
C M
CM
Coderre
T J
TJ
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D007278:Injections, Spinal; D000077213:Lamotrigine; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D019782:Riluzole / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology
C114785:2-amino-4-phosphono-propinate; C097299:4-aminopyrrolidine-2,4-dicarboxylic acid; D018690:Excitatory Amino Acid Agonists; D011422:Propionates; D014227:Triazines; D018698:Glutamic Acid; D008734:Methoxyhydroxyphenylglycol; D019782:Riluzole; D011392:Proline; D015761:4-Aminopyridine; D002211:Capsaicin; D000077213:Lamotrigine; C010117:3,4-dihydroxyphenylglycol