PT  - JOURNAL ARTICLE
AU  - Ann E. Friedrich
AU  - Gerald F. Gebhart
TI  - Effects of Spinal Cholecystokinin Receptor Antagonists on Morphine Antinociception in a Model of Visceral Pain in the Rat
DP  - 2000 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 538--544
VI  - 292
IP  - 2
4099  - http://jpet.aspetjournals.org/content/292/2/538.short
4100  - http://jpet.aspetjournals.org/content/292/2/538.full
SO  - J Pharmacol Exp Ther2000 Feb 01; 292
AB  - The objective of the present study was to determine the effects of spinal cholecystokinin (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 μg) in vehicle-treated rats produced significantly greater antinociception in TNBS-treated rats. Intrathecal proglumide, a nonselective CCK receptor antagonist, dose dependently enhanced the antinociceptive effect of morphine in vehicle-treated rats, but not in TNBS-treated rats. Similarly, L-365,260, a specific CCKBreceptor antagonist, dose dependently increased morphine's antinociceptive effects in vehicle-treated rats but had no effect in rats with TNBS-induced colonic inflammation. L-364,718, a specific CCKA receptor antagonist, had no effect on morphine antinociception in either vehicle-treated or TNBS-treated rats. These data indicate that CCK, acting at the CCKB receptor, is involved in modulating morphine antinociception following a noxious visceral stimulus. However, CCK receptor antagonists no longer enhance morphine antinociception after instillation of intracolonic TNBS, suggesting that visceral inflammation may lead to a reduction in spinal CCK release. The American Society for Pharmacology and Experimental Therapeutics