Sphingolipid metabolism products: potential new players in the pathogenesis of bortezomib-induced neuropathic pain

Abstract

Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the major dose-limiting adverse events of widely used drugs in both the oncologic and hematologic setting (1). Among its cardinal symptoms, neuropathic pain is frequently present (2). In particular, the incidence of bortezomib-induced peripheral neurotoxicity (BIPN) and neuropathic pain ranges from 14–45% and 5–39%, respectively, in myeloma multiple patients. BIPN is more frequently developed in pretreated patients, compared to those being chemotherapy-naïve (3,4), and this difference mostly accounts for the wide variability in the observed incidence rates. Bortezomib is the first proteasome inhibitor introduced in clinical practice. The mechanisms underlying the pathogenesis of peripheral neurotoxicity in bortezomib- treated patients are, yet, not fully elucidated (3,4).