Naturally occurring cannabinoids in the cannabis plant and capsaicin in chili peppers activate cannabinoid (CB) receptors and transient receptor potential vanilloid type 1 (TRPV1), respectively. Both receptors have a key role in nociception, which results in pain perception. Chronic pain treatment is one of the essential tasks of medicine worldwide, whereas CB1 and TRPV1 receptors represent promising targets for analgesic treatment. Both receptors are co-expressed on central endings of primary afferent neurons, which form the 1st nociceptive synapses on the pain pathway. They are involved in the modulation of nociceptive signaling at the spinal cord level. Interestingly, anandamide (AEA) activates both the CB1 and TRPV1 receptors. The lecture will concentrate on our results studying the interaction between these two receptors in the modulation of spinal cord synaptic transmission. We have shown that anandamide is produced from precursor N-arachidonoylphosphatidylethanolamine (20:4-NAPE) in the spinal cord. In contrast, to direct AEA application, the precursor 20:4-NAPE application inhibits nociceptive synaptic transmission at 1st nociceptive synapses mediated by both CB1 and TRPV1 receptors, whereas peripheral inflammation changes the underlying mechanism. Our results indicate that increasing the anandamide level nearby the target receptor by applying substrate for its synthesis may be more effective for analgesic purposes than systemic anandamide application or inhibition of its degradation.
Diana Spicarova is a senior researcher in the Laboratory of Pain Research at IPHYS. She is interested in the modulation of nociceptive synaptic transmission at the spinal cord level as an underlying mechanism of neuropathic pain states.
IPHYS contact person: Jiří Paleček, firstname.lastname@example.org