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.
Department of Pharmacology, University of Arizona, Tucson, USA.
R M
RM
Craft
S R
SR
Henley
R C
RC
Haaseth
V J
VJ
Hruby
F
F
Porreca
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