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 visceral pain. Resiniferatoxin (RTX, 3 nmol), a capsaicin-like mutant, produced abdominally directed grooming behavior after direct administration into the urinary bladder (intravesical, Lves.) by indwelling cannula. Systemic (s.c. or i.p.) pretreatment with the mu agonists morphine or [D-Ala2, NMePhe4, Gly-ol]enkephalin (Damgo), the kappa agonists trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide (U50,488) or [5R-(5,7,8-beta)]-N-methyl-N-[7-(1-pyrrolidinyl)1-oxaspiro[4,5]dec - 8-yl]-4-benzofuranacetamide (CI-977), or the nonpeptidic delta agonist (+/-)-4-((alpha-R*)-alpha-((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 beta-funaltrexamine (mu), nor-binaltorphimine (kappa) and naltrindole (delta). Local (i.ves.) BW373U86, [D-Ala2,Glu4]deltorphin (DELT II) and Cl-977 also significantly decreased RTX-induced licking. Intracerabroventricular 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 mu, kappa and delta 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 delta agonist. This study suggests that opioid delta receptors may be present on bladder nociceptive afferents and may be activated for production of peripheral analgesia.
Craft
R M
RM
Department of Pharmacology, University of Arizona, Tucson, USA.
Henley
S R
SR
Haaseth
R C
RC
Hruby
V J
VJ
Porreca
F
F
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004224:Diterpenes / Q000633:toxicity; D004333:Drug Administration Routes; D005260:Female; D006120:Grooming / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists; D014781:Viscera / Q000473:pathology*
D000701:Analgesics, Opioid; D004224:Diterpenes; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone; C024353:resiniferatoxin