INVIVO STUDIES ON SPINAL OPIATE RECEPTOR SYSTEMS MEDIATING ANTINOCICEPTION .2. PHARMACOLOGICAL PROFILES SUGGESTING A DIFFERENTIAL ASSOCIATION OF MU-RECEPTOR, DELTA-RECEPTOR AND KAPPA-RECEPTOR WITH VISCERAL CHEMICAL AND CUTANEOUS THERMAL STIMULI IN THE RAT

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 228  (1) , 1-12
Abstract
The intrathecal administration of .mu. (morphine) and .delta. (D-Ala2-D-Leu5-enkephalin) but not .kappa. agonists (ethylketocyclazocine, bremazocine and U50488H [trans-(+)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide methane sulfonate hydrate]) or partial agonists (nalbuphine and buprenorphine)produced a dose-dependent inhibition of all cutaneous thermal (hot plate and tail-flick) responses in the rat. On visceral chemical tests (writhing), .mu. and .kappa. agonists, but not .delta. agonists, exerted a powerful suppression of the response. Whereas the ED50 of morphine on the cutaneous thermal tests did not differ from that observed on the visceral chemical test, agents with significant .mu. and .delta. activity (metkephamid and .beta.-endorphin) showed a prominent reduction in activity on the writhing as compared with the hot plate and tail-flick. Systemic naloxone resulted in a dose-dependent antagonism of the effect of all intrathecal agents. Estimation of the pA2 [competitive antagonistic activity] of .mu. agents indicated no difference on the hot plate/tail-flick and writhing (pA2 approximately 7). .kappa.-Ligands were selectively resistant to antagonism with naloxone pA2 values for those agonists ranging from 5.9-6.6. There apparently are 3 discriminable populations of receptors in the spinal cord whose activation results in a selective modulation of the response of the animal to noxious stimuli. The selective effects of the .delta. agonists on cutaneous thermal and .kappa. agonists on visceral chemical suggests a differential coding of spinal afferents through which these stimuli are transmitted.