Vincristine increased spinal cord substance P levels in a peripheral neuropathy rat model

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.