Interaction between vanilloid and glutamate receptors in the central modulation of nociception.
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.
Palazzo
Enza
E
Department of Experimental Medicine, Section of Pharmacology Leonardo Donatelli, Faculty of Medicine and Surgery, II University of Naples, via Costantinopoli 16, 80138, Naples, Italy.
de Novellis
Vito
V
Marabese
Ida
I
Cuomo
Dario
D
Rossi
Francesca
F
Berrino
Liberato
L
Rossi
Francesco
F
Maione
Sabatino
S
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
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