Abstract
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.
Highlights
Tetrahydropalmatine, one of the main active ingredients isolated from C. yanhuso plant, has been demonstrated to have excellent analgesic effects in both experimental and clinical studies
We found that the i.g. pre-treatment of dl-THP at high dose (40, 60 mg/kg) suppress the primary thermal (n = 6, P < 0.001) and mechanical pain hypersensitivity (n = 6, P < 0.001) as well as the mirrorimage thermal pain hypersensitivity (n = 6, P < 0.01)
We found that posttreatment with dl-THP at 40 and 60 mg/kg could prevent the primary mechanical pain hypersensitivity, which peaked at 2 h and continued to 6 h after the administration (Fig. 2C,F)
Summary
Tetrahydropalmatine (dl-THP), one of the main active ingredients isolated from C. yanhuso plant, has been demonstrated to have excellent analgesic effects in both experimental and clinical studies. Previous reports from preclinical studies have shown that dl-THP has potential therapeutic effects against inflammatory and neuropathic pain [2, 3, 5]. Our previous study showed that dl-THP has antihyperalgesic and antiallodynic effects against the BV induced inflammatory pain. Pre-treatment with dl-THP produced significant inhibition of persistent spontaneous nociception, primary heat and mechanical hyperalgesia and mirror-image heat hyperalgesia identified in the BV test [3]. It is still unclear whether post-treatment with dl-THP influences BVinduced hypersensitivity and, if so, what could be its underlying mechanism?
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