Cannabinoids, endogenous and exogenous, have a dramatic effect on the pain pathway. To date, the most common use of these natural substances is for analgesic purposes. However, little is known about their cellular and molecular mechanism(s) inducing pain relief. A possible mechanism that recently emerged from different physiological and pathophysiological studies points to the somatosensory TRP channels as potential targets of cannabinoids. Two main TRP channels are expressed on pain fibers: TRPV1 and TRPA1. Although different compounds of the cannabinoids family modulate both channels, the exact activation mechanism is not known. Our main goal is elucidating the molecular mechanism(s) by which the active components of cannabis bind and activate TRPV1 and TRPA1. This mechanism is highly intriguing taking in account that all other TRPV1 and TRPA1 activators evoke pain sensation while exogenous cannabinoids induce pain relief. Understanding the molecular mechanism of cannabinoids’ evoked activation of somatosensory TRP channels could provide a strategy for the development of highly specific analgesics - an as yet unmet medical need.
Keywords: TRPV1; TRPA1; CBD; THC; Pain; Molecular biology; Binding sites; Activation mechanism