L-Tetrahydropalmatine alleviates mechanical hyperalgesia in models of chronic inflammatory and neuropathic pain in mice

Chronic pain is categorized as inflammatory and neuropathic, and there are common mechanisms underlying the generation of each pain state. Such pain is difficult to treat and the treatment at present is inadequate. Corydalis yanhusuo is a traditional Chinese medicine with demonstrated analgesic efficacy in humans. The potential antihyperalgesic effect of its active component is L-tetrahydropalmatine (L-THP). L-THP has been used for the treatment of headache and other mild pain. However, little is known about its analgesic effect on chronic pain and its mechanism. Here, we report that L-THP exerts remarkable antihyperalgesic effects on neuropathic and inflammatory pain in animal models. Neuropathic hypersensitivity was induced by segmental spinal nerve ligation and inflammatory hypersensitivity was induced by an intraplantar injection of complete Freund's adjuvant. To determine the receptor mechanism underlying the antihyperalgesic actions of L-THP, we used SCH23390, an antagonist of a dopamine D1 receptor, in an attempt to block the antihyperalgesic effects of L-THP. We found that L-THP (1-4 mg/kg, i.p.) produced a dose-dependent antihyperalgesic effect in spinal nerve ligation and complete Freund's adjuvant models. The antihyperalgesic effects of L-THP were abolished by a dopamine D1 receptor antagonist SCH23390 (0.02 mg/kg). Furthermore, L-THP (4 mg/kg, i.p.) did not influence motor function. These findings suggest that L-THP may ameliorate mechanical hyperalgesia by enhancing dopamine D1 receptor-mediated dopaminergic transmission.