PMID: 8987795Jan 15, 1997Paper

Multiple receptors involved in peripheral alpha 2, mu, and A1 antinociception, tolerance, and withdrawal

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
K O Aley, J D Levine

Abstract

We examined the interactions among three classes of peripherally-acting antinociceptive agents (mu-opioid, alpha 2-adrenergic, and A1-adenosine) in the development of tolerance and dependence to their antinociceptive effects. Antinociception was determined by assessing the degree of inhibition of prostaglandin E2 (PGE2)-induced mechanical hyperalgesia, using the Randall-Selitto paw-withdrawal test. Tolerance developed within 4 hr to the antinociceptive effect of the alpha 2-adrenergic agonist clonidine; dependence also occurred at that time, demonstrated as a withdrawal hyperalgesia that was precipitated by the alpha 2-receptor antagonist yohimbine. These findings are similar to those reported previously for tolerance and dependence to mu and A1 peripheral antinociception (Aley et al., 1995). Furthermore, cross-tolerance and cross-withdrawal between mu, A1, and alpha 2 agonists occurred. The observations of cross-tolerance and cross-withdrawal suggest that all three receptors are located on the same primary afferent nociceptors. In addition, the observations suggest that the mechanisms of tolerance and dependence to the antinociceptive effects of mu, A1, and alpha 2 are mediated by a common mechanism. Although any of the agonis...Continue Reading

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