Role of Dehydrocorybulbine in Neuropathic Pain After Spinal Cord Injury Mediated by P2X4 Receptor.

Chronic neuropathic pain is one of the primary causes of disability subsequent to spinal cord injury. Patients experiencingneuropathic pain after spinal cord injury suffer from poor quality of life, so complementary therapy is seriously needed.Dehydrocorybulbine is an alkaloid extracted from Corydalis yanhusuo. It effectively alleviates neuropathic pain. In thepresent study, we explored the effect of dehydrocorybulbine on neuropathic pain after spinal cord injury and delineated itspossible mechanism. Experiments were performed in rats to evaluate the contribution of dehydrocorybulbine to P2X4signaling in the modulation of pain-related behaviors and the levels of pronociceptive interleukins and proteins after spinalcord injury. In a rat contusion injury model, we confirmed that chronic neuropathic pain is present on day 7 after spinal cordinjury and P2X4R expression is exacerbated after spinal cord  injury. We also found that administration of dehydrocorybulbine by tail vein injection relieved pain behaviors in rat contusion injury models without affecting motor functions. The elevation in the levels of pronociceptive interleukins (IL-1β, IL-18, MMP-9) after spinal cord injury was mitigated by dehydrocorybulbine. Dehydrocorybulbine significantly mitigated the upregulation of P2X4 receptor and reduced ATP-evoked intracellular Ca2+ concentration. Both P2XR and dopamine receptor2 agonists antagonized dehydrocorybulbine's antinociceptive effects. In conclusion, we propose that dehydrocorybulbine produced antinociceptive effects in spinal cord injury models by inhibiting P2X4R.