Endocannabinoids and Peripheral Pain

For centuries cannabis has been used for the management of pain, however, clinical studies have not led to a uniform idea regarding the analgesic effectiveness of cannabis and its constituent Δ9-tetrahydrocannabinol (Δ9-THC). The discovery of anandamide and 2-arachidonylglycerol, two endogenous ligands for cannabinoid receptors, has aroused interest about the possible role for these molecules in modulation of pain perception. The analgesic effects observed are mediated through cannabinoid receptors, localized in the brain, that interact with the noradrenergic and κ-opioid system; in the spinal cord, modulating the nociceptive perception, and on peripheral sensory neurons regulating the afferent stimulations. Anandamide is an effective antinociceptive agent, acting centrally as well as on peripheral neurons, modulating pain perception and initiation.