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Updated: Jun 15, 2026
Cell Subtype-specific Analysis of Neuronal Membrane Proteasome in Somatosensory Neurons
Published on: October 10, 2025
Neurophysiological, histological and immunohistochemical characterization of bortezomib-induced neuropathy in mice
Jordi Bruna1, Esther Udina, Albert Alé
1Group of Neuroplasticity and Regeneration, Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Abstract:
Bortezomib, a proteasome inhibitor, is an antineoplastic drug to treat multiple myeloma and mantle cell lymphoma. Its most clinically significant adverse event is peripheral sensory neuropathy. Our objective was to characterize the neuropathy induced by bortezomib in a mouse model. Two groups were used; one group received vehicle solution and another bortezomib (1mg/kg/twice/week) for 6weeks (total dose as human schedule). Tests were performed during treatment and for 4weeks post dosing to evaluate electrophysiological, autonomic, pain sensibility and sensory-motor function changes. At the end of treatment and after washout, sciatic and tibial nerves, dorsal ganglia and intraepidermal innervation were analyzed. Bortezomib induced progressive significant decrease of sensory action potential amplitude, mild reduction of sensory velocities without effect in motor conductions. Moreover, it significantly increased pain threshold and sensory-motor impairment at 6weeks. According to these data, histopathological findings shown a mild reduction of myelinated (-10%; p=0.001) and unmyelinated fibers (-27%; p=0.04), mostly involving large and C fibers, with abnormal vesicular inclusion body in unmyelinated axons. Neurons were also involved as shown by immunohistochemical phenotypic switch. After washout, partial recovery was observed in functional, electrophysiological and histological analyses. These results suggest that axon and myelin changes might be secondary to an initial dysfunctional neuronopathy.
Insights
Bortezomib, used for cancer treatment, causes peripheral sensory neuropathy in mice, affecting nerve function and structure. These changes may stem from initial neuron damage, with partial recovery observed after treatment cessation.
Area of Science:
- Neuroscience
- Pharmacology
- Oncology
Background:
- Bortezomib is a proteasome inhibitor used to treat multiple myeloma and mantle cell lymphoma.
- Peripheral sensory neuropathy is a significant adverse event associated with bortezomib treatment.
Purpose of the Study:
- To characterize the neuropathy induced by bortezomib in a mouse model.
- To evaluate functional, electrophysiological, and histological changes in response to bortezomib.
Main Methods:
- Mice received bortezomib (1mg/kg/twice/week) or vehicle for 6 weeks.
- Electrophysiological, autonomic, pain sensibility, and sensory-motor functions were assessed during and after treatment.
- Sciatic nerves, tibial nerves, dorsal root ganglia, and intraepidermal innervation were analyzed histopathologically.
Main Results:
- Bortezomib significantly decreased sensory action potential amplitude and sensory nerve conduction velocities.
- Sensory-motor impairment and increased pain threshold were observed.
- Histopathology revealed reductions in myelinated and unmyelinated nerve fibers, with abnormal axonal inclusions and neuronal phenotypic switching.
Conclusions:
- Bortezomib induces progressive peripheral neuropathy in mice, characterized by sensory nerve dysfunction and axonal/myelin damage.
- Evidence suggests that axon and myelin changes may be secondary to an initial neuronopathy.
- Partial functional, electrophysiological, and histological recovery occurred after bortezomib withdrawal.
