Experimental Studies of Potential Analgesics for the Treatment of Chemotherapy-Evoked Painful Peripheral Neuropathies

Abstract

OBJECTIVE: We investigated potential analgesics for chemotherapy-evoked neuropathic pain using rats treated with paclitaxel. DESIGN: Drugs were tested in a repeated dosing paradigm (four daily injections). Topiramate was tested with a long-term treatment paradigm (12 days). A literature search was performed to summarize prior data. MEASURES: Mechanical stimulation of the hind paw was used to assay antiallodynic and antihyperalgesic effects acutely and 24 hours after injection. RESULTS: Amitriptyline produced significant analgesia, but this was not apparent until after the second injection. Baclofen produced significant effects, but the response varied erratically. Mexiletine and NMED-126 (a mixed N- and T-type calcium channel blocker) produced consistent, significant analgesia when tested acutely, but the pain relief did not persist at 24 hours postinjection. Oxcarbazepine had no effect at any time. Tramadol produced consistent, near-complete analgesia when tested acutely, but the analgesia did not persist to 24 hours postinjection. Topiramate produced significant effects that were first evident after 6-8 days of dosing. CONCLUSIONS: The present data and data from the literature review suggest that there are several potential treatments for chemotherapy-evoked neuropathic pain. Nonsteroidal anti-inflammatory drugs have little or no efficacy. Opioids have an effect, but probably only with high doses. At least some antidepressants are analgesic in these conditions. Some, but clearly not all, anticonvulsants and sodium channel blockers have efficacy. Tramadol is a particularly promising candidate. Topiramate, acetyl-L-carnitine, carbamazepine, and venlafaxine may have protective or restorative effects. Clinical trials of these candidates are needed to advance the treatment of chemotherapy-evoked pain.