Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China; Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Ocean University, Lianyungang, 222005, China.
Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China.
Eur J Pharmacol. 2023 Sep 5;954:175870. doi: 10.1016/j.ejphar.2023.175870. Epub 2023 Jun 22.
Chronic pain is a common public health problem and remains an unmet medical need. Currently available analgesics usually have limited efficacy for the treatment of chronic pain, including neuropathic pain and persistent inflammatory pain, or they are accompanied by many adverse side effects. The voltage-gated calcium channel blocker (pregabalin) and potassium channel openers (flupirtine and retigabine) have been widely used for the management of chronic pain, but their effectiveness in combination is unclear. In this research, we evaluated the antinociceptive effects of pregabalin in combination with flupirtine or retigabine in carrageenan-induced inflammatory pain and paclitaxel-induced peripheral neuropathy in mice using the von Frey test. Isobolographic analysis indicated that pregabalin exerted synergistic antinociceptive effects when combined with flupirtine or retigabine in neuropathic and inflammatory pain models. Furthermore, the antinociceptive effects of pregabalin, flupirtine/retigabine, and their combinations were significantly attenuated by the Kv7 channel blocker XE991. The favored dose ratio between pregabalin and flupirtine/retigabine in combinations was also investigated. Finally, we evaluated the motor coordination of their combinations using the rotarod test, and the outcomes underpinned their safety. Collectively, our results support the potential use of pregabalin in combination with flupirtine or retigabine to alleviate chronic pain.
慢性疼痛是一种常见的公共卫生问题，也是未满足的医学需求。目前可用的镇痛药通常对慢性疼痛（包括神经性疼痛和持续性炎症性疼痛）的治疗效果有限，或者伴有许多不良反应。电压门控钙通道阻滞剂（普瑞巴林）和钾通道开放剂（氟吡汀和瑞替加滨）已广泛用于慢性疼痛的管理，但它们联合使用的效果尚不清楚。在这项研究中，我们使用von Frey 测试评估了普瑞巴林与氟吡汀或瑞替加滨联合用于角叉菜胶诱导的炎症性疼痛和紫杉醇诱导的周围神经病变的小鼠中的镇痛效果。等辐射分析表明，普瑞巴林与氟吡汀或瑞替加滨联合在神经病理性和炎症性疼痛模型中表现出协同的镇痛作用。此外，Kv7 通道阻滞剂 XE991 显著减弱了普瑞巴林、氟吡汀/瑞替加滨及其组合的镇痛作用。还研究了组合中普瑞巴林和氟吡汀/瑞替加滨的优选剂量比。最后，我们使用转棒试验评估了它们组合的运动协调能力，结果支持了它们的安全性。总之，我们的研究结果支持了普瑞巴林与氟吡汀或瑞替加滨联合使用以缓解慢性疼痛的潜力。
