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

R M Craft; S R Henley; R C Haaseth; V J Hruby; F Porreca

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

Accepted manuscript

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Peer reviewed

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

R M Craft, S R Henley, R C Haaseth, V J Hruby and F Porreca

The Journal of pharmacology and experimental therapeutics, Vol.275(3), pp.1535-1542

12/1995

Handle:

https://hdl.handle.net/2376/109060

PMID: 8531126

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Abstract

Drug Administration Routes

Receptors, Opioid - agonists

Diterpenes - toxicity

Grooming - drug effects

Analgesics, Opioid - pharmacology

Rats

Analgesics, Opioid - therapeutic use

Pain - chemically induced

Viscera - pathology

Rats, Sprague-Dawley

Analgesics, Opioid - administration & dosage

Naloxone - pharmacology

Pain - drug therapy

Narcotic Antagonists - pharmacology

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.

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Title: Opioid antinociception in a rat model of visceral pain: systemic versus local drug administration
Creators: R M Craft - Department of Pharmacology, University of Arizona, Tucson, USA
S R Henley
R C Haaseth
V J Hruby
F Porreca
Publication Details: The Journal of pharmacology and experimental therapeutics, Vol.275(3), pp.1535-1542
Academic Unit: Psychology, Department of
Publisher: United States
Identifiers: 99900547597401842
Language: English
Resource Type: Accepted manuscript