mGlu and NMDA receptor contributions to capsaicin-induced thermal and mechanical hypersensitivity.
Metabotropic glutamate (mGlu) receptors are G protein-coupled receptors, some of which are localized in the spinal cord dorsal horn, and are involved with pain perception. The anti-nociceptive effects of intrathecal (i.t.) pretreatment with various mGlu receptor agonists and antagonists were assessed in Long Evans rats with mechanical and thermal hypersensitivity after sub-dermal injection of capsaicin in the hindpaw. Selective group II (aminopyrrolidine-2R,4R-dicarboxylate, APDC) and group III (l-2-amino-4-phosphonobutyrate, L-AP4) agonists, as well as selective mGlu(1) (1-aminoindan-1,5(R,S)-dicarboxylic acid, AIDA) and mGlu(5) (2-methyl-6-(phenylethynyl)-pyridine, MPEP) receptor subtype antagonists were compared with that of an NMDA receptor antagonist (dizocilipine maleate, MK-801). The rats were observed for signs of capsaicin-induced mechanical and thermal hypersensitivity 15 min after capsaicin injection, and 20 min following i.t. drug administration. Results indicate there was a dose-dependent reduction in capsaicin-induced mechanical hypersensitivity for all mGlu receptor agents; with maximal increases in mechanical thresholds that were 7-fold for AIDA and APDC, 7.5-fold for L-AP4 and 5.6-fold for MPEP. However, only a weak reduction (often non-significant) in thermal hypersensitivity was observed with each of the mGlu receptor drugs; thermal latencies were maximally increased by 125% (AIDA), 0% (MPEP), 8% APDC and 205% (L-AP4). By contrast, the highest dose of MK-801 was able to significantly reduce both mechanical (maximal 6.67-fold increase in threshold) and thermal (maximal 3-fold increase in latencies) hyperalgesia. We conclude that mGlu receptors contribute to the development of mechanical allodynia, but not thermal hyperalgesia, following capsaicin injury; while iGluRs may contribute to both thermal and mechanical hypersensitivity.
Soliman
Alexandra C
AC
Department of Neurology & Neurosurgery, McGill University, 3801 University st., Montreal, Quebec H3A 2B4.
Yu
Jonathan S C
JS
Coderre
Terence J
TJ
D000818:Animals; D002211:Capsaicin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006358:Hot Temperature / Q000009:adverse effects*; D008297:Male; D010146:Pain / Q000139:chemically induced; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D020318:Rats, Long-Evans; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D002211:Capsaicin