Work

A rat model of mild, reversible bortezomib-induced peripheral neuropathy: behavioral resolution despite persistent glial activation

Year: 2026

Type: article

Abstract: Background and aims Bortezomib as a first-line treatment for multiple myeloma leads to bortezomib-induced peripheral neuropathy (BIPN), a dose-limiting side effect. We aimed to characterize the temporal course of BIPN and to investigate molecular and cellular changes associated with its development and resolution. Methods Male Wistar rats received intraperitoneal injections of either 5% dimethyl sulfoxide (DMSO, vehicle) or bortezomib (0.2 mg/kg) on days 1, 4, 8, and 11 and hypersensitivity was monitored. Sciatic nerves were assessed for morphological changes and levels of interleukin (IL)-6 and IL-1β, and skin was examined for innervation density. Serum was analysed for neurofilament light (NfL) and BTZ concentrations. Dorsal root ganglia were examined for neuronal and satellite glial cell (SGC) activation. Results Bortezomib induced mild mechanical allodynia that peaked at day 12 and resolved by day 25, whereas DMSO caused transient hypersensitivity. No reduction of skin innervation was detected in either group. Serum bortezomib was detectable within 30 min post-injection until day 25. The sciatic nerves showed moderate macrophage presence, but no elevated levels of IL-6 and IL-1β. Dorsal root ganglion calcitonin gene-related peptide immunoreactive neurons increased on day 12 in the bortezomib group. Serum NfL remained unchanged across groups. SGC activation was present in both bortezomib and DMSO-treated rats and persisted at day 25. Interpretation This low-dose, reversible BIPN model entailed transient hypersensitivity and neuronal activation without axonal loss. Persistent activation of SGC indicated a glial response despite the absence of detectable structural neuronal damage. DMSO effects should be considered when interpreting preclinical pain models.

Source: Neurobiology of Pain

DOI: 10.1016/j.ynpai.2026.100240