Analgesic effect of dl-THP on inflammatory pain mediated by suppressing spinal TRPV1 and P2X3 receptors in rats

Tetrahydropalmatine (dl-THP) demonstrates an analgesic effect in animal models of neuropathic and inflammatory pain, however, the underlying mechanisms of its pharmacological action within the spinal cord remains unclear. Both P2X3 receptor and TRPV1 are associated with the development and progression of such neuropathic and inflammatory pain. Here, we found that both pre-treatment and post-treatment with dl-THP could attenuate Bee Venom (BV)-induced persistent spontaneous pain-related behaviors in rats. Further, the dl-THP also exerted both preventive and therapeutic analgesic effects in BV-induced primary thermal and mechanical pain hypersensitivity as well as in mirror-image thermal pain hypersensitivity. The Rota-Rod treadmill test revealed that the dl-THP administration did not alter the rats' motor coordinating performance. The TRPV1 and P2X3 receptor proteins increased markedly in the spinal cord of the rats following s.c. BV injection, which was significantly suppressed by dl-THP. These results suggest that dl-THP exerts a robust antihyperalgesia effect through down-regulation of P2X3 receptors and TRPV1 in inflammatory pain, providing a scientific basis for the translation of dl-THP treatment in clinics.