title: Interaction between vanilloid and glutamate receptors in the central modulation of nociception.
abstract: This study investigates the effect of microinjections of capsaicin in the periaqueductal grey matter of rats on nociceptive behaviour and the possible interactions with NMDA and mGlu receptors. Intra-periaqueductal grey microinjection of capsaicin (1-3-6 nmol/rat) increased the latency of the nociceptive reaction in the plantar test. This effect was prevented by pretreatment with capsazepine (6 nmol/rat), which had no effect per se on the latency of the nociceptive reaction. 7-(Hydroxyimino)cyclopropa[b]chromen-1alpha-carboxylate ethyl ester (CPCCOEt, 50 nmol/rat) and 2-Methyl-6-(phenylethynyl)pyridine (MPEP, 50 nmol/rat), antagonists of mGlu(1) and mGlu(5) receptors, respectively, completely blocked the effect of capsaicin. Similarly, pretreatment with DL-2-Amino-5-phosphonovaleric acid (DL-AP5, 5 nmol/rat) and riluzole (4 nmol/rat), an NMDA receptor antagonist and a voltage-dependent Na(+) channels blocker which inhibits glutamate release, respectively, completely antagonized the effect of capsaicin. However, pretreatment with (2S)-alpha-Ethylglutamic acid (30 nmol/rat) and (RS)-alpha-Methylserine-O-phosphate (MSOP, 30 nmol/rat), antagonists of group II and group III mGlu receptors, respectively, had no effects on capsaicin-induced analgesia. Similarly, pretreatment with N-(piperidin-1-yl)-5-(4-chlophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR 141716A, 5 pmol/rat), a selective cannabinoid CB(1) receptor antagonist, did not affect the capsaicin-induced antinociception. In conclusion, this study shows that capsaicin might produce antinociception at the periaqueductal grey level by increasing glutamate release, which activates postsynaptic group I mGlu and NMDA receptors.
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology Leonardo Donatelli, Faculty of Medicine and Surgery, II University of Naples, via Costantinopoli 16, 80138, Naples, Italy.
authors.forename: Enza
authors.initials: E
authors.lastname: Palazzo
authors.forename: Vito
authors.initials: V
authors.lastname: de Novellis
authors.forename: Ida
authors.initials: I
authors.lastname: Marabese
authors.forename: Dario
authors.initials: D
authors.lastname: Cuomo
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossi
authors.forename: Liberato
authors.initials: L
authors.lastname: Berrino
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000378:metabolism* / Q000517:prevention & control; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism*; D010768:Phosphoserine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011485:Protein Binding; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D019782:Riluzole / Q000494:pharmacology; D000077285:Rimonabant; D013997:Time Factors
chemical_list: C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; D002867:Chromones; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D011720:Pyrazoles; D011725:Pyridines; D011955:Receptors, Drug; D017470:Receptors, Glutamate; C120877:methylserine phosphate; D010768:Phosphoserine; D015763:2-Amino-5-phosphonovalerate; D019782:Riluzole; C121465:6-methyl-2-(phenylethynyl)pyridine; C071423:capsazepine; D000077285:Rimonabant; D002211:Capsaicin