ROLE OF VAGAL AFFERENTS IN THE ANTINOCICEPTION PRODUCED BY MORPHINE AND U-50,488H IN THE COLONIC PAIN REFLEX IN RATS

The mechanisms underlying the antinociception induced by morphine or U-50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)benzeneacetamide) against painful colonic distension were examined in anaesthetized rats. The respective ED(50) values for morphine and U-50,488H were 0.34 and 0.35 mg/kg for the i.v. route, and 1.68 and 167 mu g/rat for the i.c.v. route. Morphine was active by the intrathecal route (ED(50) = 7.8 mu g) whereas U-50,488H had no effect at doses up to 100 mu g/rat. The morphine response was selectively antagonized by naloxone (30 mu g/kg i.v.) whereas that of U-50,488H was blocked by nor-binaltorphimine (10 mg/kg s.c.). Bilateral vagotomy abolished the response to morphine at 0.35 mg/kg i.v. and reduced by 41.3% that to 1 mg/kg morphine, but had no effect on that to U-50,488H or i.c.v. morphine (10 mu g/rat). It is concluded that peripheral mu- and kappa-opioid receptors may produce antinociception for colonic pain and that vagal integrity is required for mu-opioid but not kappa-opioid peripheral antinociception.