The Effects of Intrathecally Administered FK480, a Cholecystokinin-A Receptor Antagonist, and YM022, a Cholecystokinin-B Receptor Antagonist, on the Formalin Test in the Rat

Abstract

Cholecystokinin (CCK) is located in the brain and the spinal cord, and CCK antagonist is reported to enhance the analgesic effect of morphine.It has been suggested that, during inflammation, the level of endogenous opioid peptides increases in the spinal cord. Intrathecally administered CCK antagonist may have some analgesic effect during inflammation via the activated spinal opioid system. To gain a better understanding of the roles of CCK-A and CCK-B receptors in spinal nociceptive transmission during inflammation, this study evaluated the effects of intrathecally administered FK480 (a CCK-A receptor antagonist) and YM022 (a CCK-B receptor antagonist). Inflammation was induced by paw formalin injection (formalin test) in rats. The subcutaneous injection of formalin into the hind paw evoked biphasic flinching (Phase 1, 0-9 min; Phase 2, 10-60 min) of the injected paw. Drugs were administered intrathecally 10 min before (pretreatment) or 7 min after (posttreatment) the formalin injection. Neither pretreatment nor posttreatment with FK480 has any effect on the formalin test. Pretreatment, but not posttreatment, with YM022 depressed the Phase 1 and Phase 2 flinching behavior in a dose-dependent manner, and this YM022 effect was stereospecific and was not antagonized by naloxone. These data indicate that a CCK-B receptor antagonist, but not a CCK-A receptor antagonist, produces an antinociceptive effect in the rat formalin test. This effect of a CCK-B receptor antagonist was not mediated by the spinal opioid receptor activation. (Anesth Analg 1996;83:107-13)