“Cannabinoid receptor agonists diminish responses to painful stimuli. Extensive evidence implicates the CB(1) receptor in the production of antinociception. However, the capacity of CB(2) receptors, which are located outside the central nervous system (CNS), to produce antinociception is not known. Using AM1241, a CB(2) receptor-selective agonist, we demonstrate that CB(2) receptors produce antinociception to thermal stimuli… Peripheral antinociception without CNS effects is consistent with the peripheral distribution of CB(2) receptors. CB(2) receptor agonists may have promise clinically for the treatment of pain without CNS cannabinoid side effects.”
Tag Archives: antinociception
CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids.
“CB(2) cannabinoid receptor-selective agonists are promising candidates for the treatment of pain. CB(2) receptor activation inhibits acute, inflammatory, and neuropathic pain responses but does not cause central nervous system (CNS) effects, consistent with the lack of CB(2) receptors in the normal CNS…
We have demonstrated that antinociception produced by CB2 receptor-selective agonists may be mediated by stimulation of β-endorphin release from CB2-expressing cells. The β-endorphin released thus appears to act at μ-opioid receptors, probably on the terminals of primary afferent neurons, to produce peripheral antinociception. This mechanism allows for the local release of endogenous opioids limited to sites where CB2 receptors are present, thereby leading to anatomical specificity of opioid effects. In this way, CB2 receptor activation may produce peripheral antinociception without CNS side effects.”
Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception.
“BACKGROUND:
β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis. The present study investigated the contribution of peripheral cannabinoid (CB) and opioid systems in the antinociception produced by intraplantar (i.pl.) injection of BCP. The interaction between peripheral BCP and morphine was also examined.”
“CONCLUSIONS:
The present results demonstrate that antinociception produced by i.pl. BCP is mediated by activation of CB(2) receptors, which stimulates the local release from keratinocytes of the endogenous opioid β-endorphin. The combined injection of morphine and BCP may be an alternative in treating chemogenic pain.”
Inhibitors of monoacylglycerol lipase, fatty-acid amide hydrolase and endocannabinoid transport differentially suppress capsaicin-induced behavioral sensitization through peripheral endocannabinoid mechanisms
“Monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH) degrade the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA), respectively… peripheral inhibition of enzymes hydrolyzing 2-AG and AEA suppresses capsaicin-evoked behavioral sensitization with distinct patterns of pharmacological specificity… Modulation of endocannabinoids in the periphery suppressed capsaicin-evoked nocifensive behavior and thermal hyperalgesia through either CB1 or CB2 receptor mechanisms but suppressed capsaicin-evoked mechanical allodynia through CB1 mechanisms only. Inhibition of endocannabinoid transport was more effective in suppressing capsaicin-induced sensitization compared to inhibition of either FAAH or MGL alone. These studies are the first to unveil the effects of pharmacologically increasing peripheral endocannabinoid levels on capsaicin-induced behavioral hypersensitivities. Our data suggest that 2-AG, the putative product of MGL inhibition, and AEA, the putative product of FAAH inhibition, differentially suppress capsaicin-induced nociception through peripheral cannabinoid mechanisms.”
“Cannabis has been used for centuries for its pain-relieving properties. The main active ingredient of cannabis, Δ9-tetrahydrocannabinol, produces antinociception by binding to G protein-coupled CB1 and CB2 receptors. Cannabinoids produce antinociception in animal models of both acute and chronic pain.”
Read more: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900457/