Effects of spinal cholecystokinin receptor antagonists on morphine antinociception in a model of visceral pain in the rat

The objective of the present study was to determine the effects of spinal c holecystokinin (CCK) receptor antagonists on morphine antinociception in a model of visceral nociception, colorectal distension, in rats with chronic colonic inflammation and vehicle-treated controls. Three to five days after intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS), an enhanced visceromotor response to all pressures of colorectal distension ( 10-80 mm Hg) was evident. The ED50 of intrathecal morphine (0.93 mu g) in v ehicle-treated rats produced significantly greater antinociception in TNBS- treated rats. Intrathecal proglumide, a nonselective CCK receptor antagonis t, dose dependently enhanced the antinociceptive effect of morphine in vehi cle-treated rats, but not in TNBS-treated rats. Similarly, L-365,260, a spe cific CCKB receptor antagonist, dose dependently increased morphine's antin ociceptive effects in vehicle-treated rats but had no effect in rats with T NBS-induced colonic inflammation. L-364,718, a specific CCKA receptor antag onist, had no effect on morphine antinociception in either vehicle-treated or TNBS-treated rats. These data indicate that CCK, acting at the CCKB rece ptor, is involved in modulating morphine antinociception following a noxiou s visceral stimulus. However, CCK receptor antagonists no longer enhance mo rphine antinociception after instillation of intracolonic TNBS, suggesting that visceral inflammation may lead to a reduction in spinal CCK release.