Effects of the endogenous agent anandamidein on nociceptive primary sensory neurons
Increasing the tissue level of the endovanilloid/endocannabinoid ligand anandamide, through inhibiting its hydrolysis by the fatty acid amide hydrolase (FAAH), has been shown to produce a significant cannabinoid 1 (CB1) receptor-mediated antinociceptive effect in various animal models of pain. However, anandamide, in addition to being an endocannabinoid, is also an endovanilloid, which activates the transient receptor potential vanilloid type 1 (TRPV1) ion channel. The inhibitory CB1 receptor, the excitatory TRPV1, anandamide-synthesising enzymes and FAAH show significant co-expression in various neurons including a major sub-population of nociceptive primary sensory neurons (PSN). Hence FAAH inhibitors through modifying anandamide-mediated signalling in nociceptive PSN may compromise the CB1 receptor-mediated inhibitory effect via TRPV1-mediated excitation. Here, we will describe membrane currents induced by exogenous and endogenous anandamide and mediated by TRPV1 and other ion channels. Further we will also describe an intricate cross-talk between the CB1 receptor and TRPV1, which might represent a novel target drug development.
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