Role of periaqueductal grey prostaglandin receptors in formalin-induced hyperalgesia.
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.
Oliva
Patrizia
P
Department of Experimental Medicine, Section of Pharmacology L. Donatelli, The Second University of Naples, Italy.
Berrino
Liberato
L
de Novellis
Vito
V
Palazzo
Enza
E
Marabese
Ida
I
Siniscalco
Dario
D
Scafuro
Mariantonietta
M
Mariani
Loredana
L
Rossi
Francesco
F
Maione
Sabatino
S
D000085:Acetates / Q000494:pharmacology; D000178:Acrylamides / Q000494:pharmacology; D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000633:toxicity; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D005557:Formaldehyde; D018698:Glutamic Acid / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D017551:Microdialysis; D016595:Misoprostol / Q000008:administration & dosage / Q000633:toxicity; D009281:Naphthalenes / Q000494:pharmacology; D010147:Pain Measurement / Q000379:methods; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000502:physiology*; D013876:Thiophenes / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D044004:Xanthones / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000085:Acetates; D000178:Acrylamides; D001593:Benzyl Compounds; C508711:L-161982; C508709:L-335677; C508710:L-826266; D009281:Naphthalenes; D011448:Prostaglandin Antagonists; D018078:Receptors, Prostaglandin E; D013876:Thiophenes; D014230:Triazoles; D044004:Xanthones; D016595:Misoprostol; D005557:Formaldehyde; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D004121:Dimethyl Sulfoxide