Interaction between vanilloid and glutamate receptors in the central modulation of nociception

• Published in: European journal of pharmacology 2002-03, Vol.439 (1), p.69-75
• Main Authors: Palazzo, Enza, de Novellis, Vito, Marabese, Ida, Cuomo, Dario, Rossi, Francesca, Berrino, Liberato, Rossi, Francesco, Maione, Sabatino
• Format: Article
• Language: English
• Subjects: 2-Amino-5-phosphonovalerate - pharmacology; Analgesics; Animals; Biological and medical sciences; Capsaicin; Capsaicin - analogs & derivatives; Capsaicin - pharmacology; Chromones - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Glutamate; Glutamatergic system (aspartate and other excitatory aminoacids); Male; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Nociception; Pain - metabolism; Pain - prevention & control; Periaqueductal Gray - drug effects; Periaqueductal Gray - metabolism; Periaqueductal grey; Pharmacology. Drug treatments; Phosphoserine - pharmacology; Piperidines - pharmacology; Protein Binding; Pyrazoles - pharmacology; Pyridines - pharmacology; Rats; Rats, Wistar; Receptors, Drug - agonists; Receptors, Drug - antagonists & inhibitors; Receptors, Drug - metabolism; Receptors, Glutamate - drug effects; Receptors, Glutamate - metabolism; Riluzole - pharmacology; Rimonabant; Time Factors
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)01367-5

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-1α-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 (2 S)-α-Ethylglutamic acid (30 nmol/rat) and ( RS)-α-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-1 H-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.