Abstract

Chemotherapy-induced peripheral neuropathy has an important impact on the quality of life of cancer patients. Vincristine-induced neuropathy is a major dose-limiting side effect. Symptoms of peripheral neuropathy are spontaneous pain, allodynia, and hyperalgesia. To analyze the contribution of substance P to the development of vincristine-induced mechanical allodynia/hyperalgesia, substance P levels in the rat spinal dorsal horn were analyzed after vincristine treatment. Mechanical allodynia/hyperalgesia was tested with the von Frey filaments 14 days after intraperitoneal (i.p.) administration of vincristine 0.1 mg/kg/day in rats. Vincristine-induced mechanical allodynia/hyperalgesia after day 14 was significantly inhibited by the neurokinin 1 receptor antagonist, aprepitant (20 mg/kg, s.c.). Immunohistochemistry showed that vincristine treatment significantly increased substance P expression (30.3% ± 2.4%) compared to saline treatment in the superficial layers of the spinal dorsal horn. Moreover, vincristine treatment significantly increased the substance P level in the spinal cord. These results suggest that vincristine treatment increases substance P in the spinal dorsal horn, and that aprepitant attenuates mechanical allodynia/hyperalgesia in vincristine-induced neuropathic rats.

摘要

化疗引起的周围神经病变对癌症患者的生活质量具有重要影响。长春新碱诱导的神经病变是主要的剂量限制性副作用。周围神经病变的症状是自发性疼痛、异常性疼痛和痛觉过敏。为了分析 P 物质对长春新碱引起的机械性异常性疼痛/痛觉过敏发展的贡献，在长春新碱治疗后分析了大鼠脊髓背角中 P 物质的水平。在大鼠腹膜内 (ip) 施用 0.1 mg/kg/天的长春新碱 14 天后，用 von Frey 细丝测试机械异常性疼痛/痛觉过敏。第 14 天后长春新碱诱导的机械性异常性疼痛/痛觉过敏被神经激肽 1 受体拮抗剂阿瑞匹坦 (20 mg/kg, sc) 显着抑制。免疫组织化学显示，与生理盐水处理相比，长春新碱处理显着增加了脊髓背角浅层的 P 物质表达（30.3% ± 2.4%）。此外，长春新碱治疗显着增加了脊髓中 P 物质的水平。这些结果表明，长春新碱治疗增加了脊髓背角中的 P 物质，并且阿瑞匹坦减轻了长春新碱诱导的神经病大鼠的机械性异常性疼痛/痛觉过敏。