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

• Published in: Molecules and cells Vol. 42; no. 2; pp. 143 - 150
• Main Authors: Wang, Zhongwei, Mei, Wei, Wang, Qingde, Guo, Rundong, Liu, Peilin, Wang, Yuqiang, Zhang, Zijuan, Wang, Limin
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 28.02.2019; 한국분자세포생물학회
• Subjects: Animals; Cell Line; Down-Regulation - drug effects; Interleukins - metabolism; Isoquinolines - pharmacology; Isoquinolines - therapeutic use; Male; Mice; Motor Activity - drug effects; Neuralgia - drug therapy; Neuralgia - etiology; Neuralgia - physiopathology; Nociception - drug effects; Rats, Sprague-Dawley; Receptors, Dopamine D2 - metabolism; Receptors, Purinergic P2X4 - metabolism; Spinal Cord Injuries - complications; Spinal Cord Injuries - physiopathology; 생물학; dehydrocorybulbine; Pain; P2X4; Spinal cord injury
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2018.0028

Chronic neuropathic pain is one of the primary causes of disability subsequent to spinal cord injury. Patients experiencing neuropathic pain after spinal cord injury suffer from poor quality of life, so complementary therapy is seriously needed. Dehydrocorybulbine is an alkaloid extracted from . It effectively alleviates neuropathic pain. In the present study, we explored the effect of dehydrocorybulbine on neuropathic pain after spinal cord injury and delineated its possible mechanism. Experiments were performed in rats to evaluate the contribution of dehydrocorybulbine to P2X4 signaling in the modulation of pain-related behaviors and the levels of pronociceptive interleukins and proteins after spinal cord injury. In a rat contusion injury model, we confirmed that chronic neuropathic pain is present on day 7 after spinal cord injury 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 Ca concentration. Both P2XR and dopamine receptor2 agonists antagonized dehydrocorybulbine's antinociceptive effects. In conclusion, we propose that dehydrocorybulbine produces antinociceptive effects in spinal cord injury models by inhibiting P2X4R.