S. A. MALEKIANI, W. HU, S. F. DAVIS, T. HANANIA
Paclitaxel (Taxol ®) is a widely-used anticancer agent for treatment of ovarian, breast, lung, head, and neck cancer with two serious side effects: myelosuppression and peripheral sensory neurotoxicity which limits its use in high/cumulative doses or in combination with other anticancer agents. In patients, the peripheral neuropathy is characterized by degeneration of sensory axons and is clinically manifested as numbness, pain, and thermohyperesthesia in hands and feet. This poses a growing, significant clinical problem as the average life span improves and cancer becomes more prevalent. In rodents, administration of paclitaxel causes neuropathic pain that comprises of thermal hyperalgesia and mechanical allodynia, which can be reversed by different analgesic agents. In this study Sprague Dawley rats were injected intraperitoneally with either vehicle or paclitaxel (2 mg/kg). All rats received a total of 4 injections on days 1, 3, 5 and 7. Mechanical allodynia using von Frey filaments was assessed one week after the first injection. The time course suggests that neuropathy manifests at 12 days after the first injection and continues until the end of the study on day 44. Acute, oral administration of gabapentin (100 mg/kg) reversed mechanical induced allodynia in paclitaxel-injected rats tested on day 23 and on day 35. In addition, chronic oral administration of gabapentin (from day 24 – day 44) also reversed paclitaxel-induced mechanical hyperalgesia when administered at 100mg/kg but not 50 mg/kg. Therefore, this model could be used as a potential screen for novel analgesic compounds for treatment of taxol-induced peripheral neuropathy. The effects of other analgesic and antidepressant compounds will be discussed.