A novel model of pain sensation using superfused gastrosplenic omentum preparation of anesthetized rats.
A pain model for screening analgesics was established in anesthetized rats. The omenta of urethane-anesthetized rats were exteriorized, fixed in a plastic chamber, and superfused with Tyrode solution. Administration of bradykinin (BK) in the chamber elicited the reflex hypertensive response (RHR). Modification of the RHR was tested by topical (in the chamber) or intravenous administration of drugs. The BK dose-response curve was shifted to the right by topical indomethacin. The RHR by BK was inhibited by topical application of a BK B(2) antagonist, (Thi(5,8)-D-Phe(7)-BK), a local anesthetic (2% carbocaine), and by intravenous administration of a ganglion blocker (hexamethonium) or an alpha-adrenergic blocker (dibenamine). The RHR by topical BK was almost completely inhibited by morphine and the suppression was largely reversed by naloxone. The RHR, induced by a threshold dose of BK and inhibited by indomethacin, was potentiated by pretreatment of the omentum with prostaglandin (PG) E(2) or PGI(2). PGE(2) was less potent, but the effect lasted longer than that of PGI(2). Topical administration of a non-acidic analgesic, mepirizole, inhibited the RHR by topical BK by only 20%, but intravenous mepirizole inhibited topical BK by 96.2%, indicating its major central action. This model may be useful for studying analgesics.
Yang
Shi-Jie
SJ
Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Katori
Makoto
M
Majima
Masataka
M
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000503:physiopathology; D009852:Omentum / Q000187:drug effects / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2 / Q000502:physiology
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010879:Piperazines; D043782:Receptor, Bradykinin B2; C008351:mepiprazole; D011464:Epoprostenol; D015232:Dinoprostone; D001920:Bradykinin; D007213:Indomethacin