PT  - JOURNAL ARTICLE
AU  - C Stein
AU  - M J Millan
AU  - T S Shippenberg
AU  - K Peter
AU  - A Herz
TI  - Peripheral opioid receptors mediating antinociception in inflammation. Evidence for involvement of mu, delta and kappa receptors.
DP  - 1989 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1269--1275
VI  - 248
IP  - 3
4099  - http://jpet.aspetjournals.org/content/248/3/1269.short
4100  - http://jpet.aspetjournals.org/content/248/3/1269.full
SO  - J Pharmacol Exp Ther1989 Mar 01; 248
AB  - This study examined a possible peripheral site of action of opioids in the modulation of the response to noxious pressure on inflamed tissue. Rats developed a unilateral localized inflammation upon injection of Freund's complete adjuvant into one hindpaw. 4-6 days after inoculation, intraplantar administration of mu, delta and kappa selective agonists [D-Ala2,N-methyl-Phe4,Gly-ol5]-en-kephalin (1 micrograms), [D-Pen2,5]-enkephalin (40 micrograms) and U-50, 488H (50 micrograms) produced marked antinociceptive effects in inflamed but not noninflamed paws. Equivalent doses applied systemically (s.c. and i.v.) were without effect. Dose dependency and stereospecificity of these effects were demonstrated using (-)- and (+)-morphine and (-)- and (+)-tifluadom. Furthermore, by use of (-)- and (+)-naloxone, dose-dependent and stereospecific antagonism was shown. Lastly, reversal of effects of [D-Ala2,N-methyl-Phe4,Gly-Ol5]-enkephalin, [D-Pen2,5]-enkephalin and U-50,488H by mu, delta and kappa selective antagonists D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, ICI 174,864 and nor-BNI, respectively, indicated that these agents interact with discriminable populations of receptors. These observations suggest that several selective opioid agonists can modulate responses to noxious pressure through a peripheral opioid receptor-specific site of action in inflammation and that these receptors possess distinguishable pharmacological characteristics resembling those of mu, delta and kappa receptors.