Ma Yurong, Liu Wenwen, Liang Lingzhi, Ye Jiaqi, Huang Chaonan, Zhuang Tao, Zhang Guisen
Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, China.
Jiangsu Key Laboratory of Marine Biological Resources and Environment, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, China.
Biomedicines. 2022 Jun 15;10(6):1413. doi: 10.3390/biomedicines10061413.
Neuropathic pain is often closely associated with nerve injury or inflammation, and the role of traditional nonsteroidal anti-inflammatory drugs as adjuvants for treating chemotherapy-induced peripheral neuropathic pain remains unclear. In this study, the potential synergistic antinociceptive effects of indomethacin-pregabalin and meloxicam-pregabalin were evaluated in paclitaxel-induced neuropathic pain and carrageenan-induced inflammatory pain in rodents. Although indomethacin and meloxicam alone only slightly relieved mechanical allodynia in the above two models, isobolographic analysis showed that the combination of indomethacin or meloxicam with pregabalin produced significant synergistic antinociceptive effects for paclitaxel-induced neuropathic pain (IN-PGB, experimental ED = [4.41 (3.13-5.82)] mg/kg, theoretical ED = [8.50 (6.62-10.32)] mg/kg; MEL-PGB, experimental ED = [3.96 (2.62-5.46)] mg/kg, theoretical ED = [7.52 (5.73-9.39)] mg/kg). In addition, MEL-PGB dosed via intraplantar injection into the left paw, intragastric injection, or intraperitoneal injection reversed paclitaxel-induced allodynia, indicating that they may act at multiple sites in the neuroaxis and periphery. However, indomethacin-pregabalin and meloxicam-pregabalin exerted antagonistic antiallodynic interactions in carrageenan-induced inflammatory pain in rats. Taken together, coadministration of indomethacin or meloxicam with pregabalin may possess potential therapeutic advantages for treating chemotherapy-induced neuropathic pain.
神经性疼痛通常与神经损伤或炎症密切相关，传统非甾体抗炎药作为治疗化疗引起的周围神经性疼痛辅助药物的作用仍不明确。在本研究中，评估了吲哚美辛-普瑞巴林和美洛昔康-普瑞巴林在紫杉醇诱导的神经性疼痛和角叉菜胶诱导的炎症性疼痛大鼠模型中的潜在协同镇痛作用。虽然单独使用吲哚美辛和美洛昔康仅能轻微缓解上述两种模型中的机械性异常性疼痛，但等效应线图分析表明，吲哚美辛或美洛昔康与普瑞巴林联合使用对紫杉醇诱导的神经性疼痛产生了显著的协同镇痛作用（吲哚美辛-普瑞巴林，实验ED = [4.41（3.13 - 5.82）]mg/kg，理论ED = [8.50（6.62 - 10.32）]mg/kg；美洛昔康-普瑞巴林，实验ED = [3.96（2.62 - 5.46）]mg/kg，理论ED = [7.52（5.73 - 9.39）]mg/kg）。此外，通过足底注射、胃内注射或腹腔注射给予美洛昔康-普瑞巴林可逆转紫杉醇诱导的异常性疼痛，表明它们可能在神经轴和外周的多个部位起作用。然而，吲哚美辛-普瑞巴林和美洛昔康-普瑞巴林在角叉菜胶诱导的大鼠炎症性疼痛中表现出拮抗抗异常性疼痛的相互作用。综上所述，吲哚美辛或美洛昔康与普瑞巴林联合给药可能对治疗化疗引起的神经性疼痛具有潜在的治疗优势。
