Mechanism-based treatment for chemotherapy-induced peripheral neuropathic pain

Chemotherapy-induced peripheral neuropathic pain (CIPNP)-a severe adverse effect observed in up to 80% of patients during treatment with antineoplastic drugs-limits the tolerable dose of cytostatics, and can lead to discontinuation of chemotherapy. Many drugs that are approved for the treatment of other neuropathic pain states have shown little or no analgesic effect on CIPNP in large randomized, placebo-controlled clinical trials. Here, we review the known mechanisms of CIPNP induced by the three most commonly used cytostatics: paclitaxel, oxaliplatin and vincristine. These substances have distinct neurotoxic and neuroinflammatory properties, but they also have overlapping contributions to pathogenesis of CIPNP that could potentially be targeted for prevention or treatment of CIPNP. We discuss the failure of previously tested antioxidants, neuroprotective agents, anticonvulsants and antidepressants as therapeutic or preventative strategies, and suggest individualized, mechanism-based therapeutic options for CIPNP associated with each of the three main drug groups. We point out the necessity to assess drug efficacy in CIPNP independently of other neuropathic pain states, and emphasize the need for delineation of subpopulations of patients with CIPNP for more-efficient treatment. Finally, we discuss novel therapeutic strategies and recent progress in treatment of CIPNP, and evaluate the potential benefits of these recent proceedings for future therapies.