Opioid antinociception in a rat model of visceral pain: Systemic versus local drug administration

Antinociceptive effects of systemically or locally administered opioid μ, κ and δ agonists were evaluated in a rat model of visceral pain. Resiniferatoxin (RTX, 3 nmol), a capsaicin-like irritant, produced abdominally directed grooming behavior after direct administration into the urinary bladder (intravesical, i.ves.) by indwelling cannula. Systemic (s.c. or i.p.) pretreatment with the μ agonists morphine or [D-Ala², NMePhe⁴, Gly-ol]enkephalin (Damgo), the κ agonists trans-3,4-dichloro-N-methyl-N-[2- (1-pyrrolidinyl)-cyclohexyl]benzeneacetamide (U50,488) or [5R-(5,7,8-β)]-N- methyl-N-[7-(1-pyrrolidinyl)1-oxaspiro-[4,5]dec-8-yl]-4-benzofuranacetamide (CI-977), or the nonpeptidic δ agonist (±)-4-((α-R*)-α-((2S*,5R(*)-4- Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N, N-diethylbenzamide (BW373U86) dose-dependently decreased RTX-induced abdominal licking; such antinociception was selectively blocked by the appropriate receptor-selective antagonists β-funaltrexamine (μ), norbinaltorphimine (κ) and naltrindole (δ). Local (i.ves.) BW373U86, [D-Ala², Glu⁴]deltorphin (DELT II) and CI- 977 also significantly decreased RTX-induced licking. Intracerebroventricular quaternary naloxone partially blocked the effects of systemic morphine, but not that of CI-977 or BW373U86. Intraperitoneal quaternary naloxone blocked the effect of local and systemic BW373U86 but not that of local or systemic CI-977; systemic morphine was partially blocked. Thus, systemic μ, κ and δ agonists all produced antinociception against a novel visceral chemical stimulus in the rat. Local CI-977 also produced antinociception, but the only compound clearly acting at peripheral opioid receptors was BW373U86, a δ agonist. This study suggests that opioid δ receptors may be present on bladder nociceptive afferents and may be activated for production of peripheral analgesia.