OPIOID ANTINOCICEPTION IN A RAT MODEL OF VISCERAL PAIN - SYSTEMIC VERSUS LOCAL-DRUG ADMINISTRATION

Antinociceptive effects of systemically or locally administered opioid mu, kappa and delta agonists were evaluated in a rat model of viscera l pain. Resiniferatoxin (RTX, 3 nmol), a capsaicin-like irritant, prod uced abdominally directed grooming behavior after direct administratio n into the urinary bladder (intravesical, i.ves.) by indwelling cannul a. Systemic (s.c. or i.p.) pretreatment with the mu agonists morphine or [D-Ala(2), NMePhe(4), Gly-ol]enkephalin (Damgo), the kappa agonists trans-3,4-dichloro-N-methy-N-[2-(1-pyrrolidinyl) -cyclohexyl]benzenea cetamide (U50,488) or nyl)1-oxaspiro[4,5]dec-8-yl]-4-benzofuranacetami de (CI-977), or the nonpeptidic delta agonist yl-2,5-dimethyl-1-pipera zinyl)-3-hydroxybenzyl)-N, N-diethylbenzamide (BW373U86) dose-dependen tly decreased RTX-induced abdominal licking; such antinociception was selectively blocked by the appropriate receptor-selective antagonists beta-funaltrex-amine (mu), nor-binaltorphimine (kappa) and naltrindole (delta). Local (i.ves.) BW373U86, [D-Ala(2), Glu(4)]deltorphin (DELT II) and CI-977 also significantly decreased RTX-induced licking. Intra cerabroventricular quaternary naloxone partially blocked the effects o f systemic morphine, but not that of CI-977 or BW373U86. Intraperitone al quaternary naloxone blocked the effect of local and systemic BW373U 86 but not that of local or systemic CI-977; systemic morphine was par tially blocked, Thus, systemic mu, kappa and delta agonists all produc ed antinociception against a novel visceral chemical stimulus in the r at. Local CI-977 also produced antinociception, but the only compound clearly acting at peripheral opioid receptors was BW373U86, a delta ag onist, This study suggests that opioid delta receptors may be present on bladder nociceptive afferents and may be activated for production o f peripheral analgesia.