Chemotherapy-induced neuropathic pain (CIPN) is a common side effect of antitumor chemotherapeutic agents. It describes a pathological state of pain related to the cumulative dosage of the drug, significantly limiting the efficacy of antitumor treatment. Sofas strategies alleviating CIPN still lack. Calcitonin gene-related peptide (CGRP) is a neuropeptide involved in many pathologic pains. In this study, we explored the effects of CGRP blocking on CIPN and potential mechanisms. Total dose of 20.7 mg/kg cisplatin was used to establish a CIPN mouse model. Mechanical and thermal hypersensitivity was measured using von Frey hairs and tail flick test. Western blot and immunofluorescence were utilized to evaluate the levels of CGRP and activated astrocytes in mouse spinal cord, respectively. In addition, real-time quantitative PCR (RT-qPCR) was used to detect the level of inflammatory cytokines such as IL-6, IL-1β, and NLRP3 in vitro and in vivo. There are markedly increased CGRP expression and astrocyte activation in the spinal cord of mice following cisplatin treatment. Pretreatment with a monoclonal antibody targeting CGRP (ZR8 mAb) effectively reduced cisplatin-induced mechanical hypersensitivity and thermal nociceptive sensitization and attenuated neuroinflammation as marked by downregulated expression of IL-6, IL-1β, and NLRP3 in the mice spinal cord and spleen. Lastly, ZR8 mAb does not interfere with the antitumor effects of cisplatin in tumor-bearing mice. Our findings indicate that neutralizing CGRP with monoclonal antibody could effectively alleviate CIPN by attenuating neuroinflammation. CGRP is a promising therapeutic target for CIPN.

化疗引起的神经性疼痛（CIPN）是抗肿瘤化疗药物的常见副作用。它描述了与药物累积剂量相关的疼痛病理状态，显着限制了抗肿瘤治疗的功效。缓解 CIPN 的沙发策略仍然缺乏。降钙素基因相关肽（CGRP）是一种神经肽，与许多病理疼痛有关。在本研究中，我们探讨了 CGRP 阻断对 CIPN 的影响及其潜在机制。采用总剂量20.7 mg/kg顺铂建立CIPN小鼠模型。使用冯弗雷毛发和甩尾测试来测量机械和热超敏反应。Western blot和免疫荧光分别用于评估小鼠脊髓中CGRP和活化星形胶质细胞的水平。此外，采用实时定量PCR（RT-qPCR）检测体外和体内IL-6、IL-1β、NLRP3等炎症细胞因子的水平。顺铂治疗后，小鼠脊髓中 CGRP 表达和星形胶质细胞活化显着增加。使用靶向 CGRP 的单克隆抗体 (ZR8 mAb) 进行预处理，可有效降低顺铂诱导的机械超敏反应和热伤害性敏化，并减弱小鼠脊髓和脾脏中 IL-6、IL-1β 和 NLRP3 表达下调的神经炎症。最后，ZR8 mAb 不会干扰顺铂对荷瘤小鼠的抗肿瘤作用。我们的研究结果表明，用单克隆抗体中和 CGRP 可以通过减轻神经炎症来有效缓解 CIPN。CGRP 是 CIPN 的一个有前途的治疗靶点。