CB 2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids

• DOI: 10.1073/pnas.0409888102
• Publication Date: 2005-02-10T20:24:39Z
• Authors: Mohab M. Ibrahim; Frank Porreca; Josephine Lai; Phillip J. Albrecht; Frank L. Rice; Alla Khodorova; Gudarz Davar; Alexandros Makriy...; Todd W. Vanderah; Heriberto P. Mata; T. Philip Malan
• Keywords: DAMGO; Endogenous opioid

CB(2) cannabinoid receptor-selective agonists are promising candidates for the treatment of pain. receptor activation inhibits acute, inflammatory, and neuropathic pain responses but does not cause central nervous system (CNS) effects, consistent with lack receptors in normal CNS. To date, there has been virtually no information regarding mechanism receptor-mediated inhibition responses. Here, we test hypothesis that stimulates release from keratinocytes endogenous opioid beta-endorphin, which then acts at on primary afferent neurons to inhibit nociception. The antinociceptive effects agonist AM1241 were prevented rats when naloxone or antiserum beta-endorphin was injected hindpaw where noxious thermal stimulus applied, suggesting is necessary antinociception. Further, did nociception mu-opioid receptor-deficient mice. Hindpaw injection sufficient produce stimulated rat skin tissue cultured human keratinocytes. This stimulation by AM630, a antagonist observed These data suggest local neuronal Supporting this possibility, immunolabeling detected beta-endorphin-containing stratum granulosum throughout epidermis hindpaw. allows present, leading anatomical specificity effects.