Role of periaqueductal grey prostaglandin receptors in formalin-induced hyperalgesia.

Author(s): Oliva P, Berrino L, de Novellis V, Palazzo E, Marabese I, Siniscalco D, Scafuro M, Mariani L, Rossi F, Maione S

Affiliation(s): Department of Experimental Medicine, Section of Pharmacology L. Donatelli, The Second University of Naples, Italy.

Publication date & source: 2006-01-13, Eur J Pharmacol., 530(1-2):40-7. Epub 2005 Dec 19.

Publication type: Comparative Study ; Research Support, Non-U.S. Gov't

In this study we have investigated the role of periaqueductal grey prostaglandin receptors in formalin-induced hyperalgesia in mice. Glutamate and GABA release changes have been monitored by in vivo microdialysis. Intra-periaqueductal grey microinjections of misoprostol, a non-selective prostaglandin receptor agonist, increased nociceptive responses in the formalin test only during the late phase. Prostanoid EP(1) (L-335677), EP(2) (AH 6809), EP(3) (L-826266) and EP(4) (L-161982) receptor antagonists prevented the nociceptive response induced by misoprostol in formalin-injected mice. Prostanoid EP(1), EP(2), EP(3) and EP(4) antagonists reduced, per se, the late hyperalgesic phase. Intra-periaqueductal grey perfusion with misoprostol increased periaqueductal grey glutamate, whereas it produced an increase followed by a decrease in GABA. Likewise, formalin increased glutamate and produced a biphasic response on GABA. When misoprostol was perfused in combination with the peripheral injection of formalin, we observed an increase of glutamate and an increase followed by a stronger decrease in GABA release. These data show that periaqueductal grey prostaglandin receptor stimulation increased formalin-induced nociceptive response in the late phase by increasing glutamate release and by producing a biphasic change in GABA release.