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Updated: Jun 2, 2026
Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
Comparison of neuropathy-inducing effects of eribulin mesylate, paclitaxel, and ixabepilone in mice
Krystyna M Wozniak1, Kenichi Nomoto, Rena G Lapidus
1Johns Hopkins Brain Science Institute, Baltimore, Maryland 21205, USA. kwoznia3@jhmi.edu
Abstract:
Chemotherapy-induced neurotoxicity is a significant problem associated with successful treatment of many cancers. Tubulin is a well-established target of antineoplastic therapy; however, tubulin-targeting agents, such as paclitaxel and the newer epothilones, induce significant neurotoxicity. Eribulin mesylate, a novel microtubule-targeting analogue of the marine natural product halichondrin B, has recently shown antineoplastic activity, with relatively low incidence and severity of neuropathy, in metastatic breast cancer patients. The mechanism of chemotherapy-induced neuropathy is not well understood. One of the main underlying reasons is incomplete characterization of pathology of peripheral nerves from treated subjects, either from patients or preclinically from animals. The current study was conducted to directly compare, in mice, the neuropathy-inducing propensity of three drugs: paclitaxel, ixabepilone, and eribulin mesylate. Because these drugs have different potencies and pharmacokinetics, we compared them on the basis of a maximum tolerated dose (MTD). Effects of each drug on caudal and digital nerve conduction velocity, nerve amplitude, and sciatic nerve and dorsal root ganglion morphology at 0.25 × MTD, 0.5 × MTD, 0.75 × MTD, and MTD were compared. Paclitaxel and ixabepilone, at their respective MTDs, produced significant deficits in caudal nerve conduction velocity, caudal amplitude and digital nerve amplitudes, as well as moderate to severe degenerative pathologic changes in dorsal root ganglia and sciatic nerve. In contrast, eribulin mesylate produced no significant deleterious effects on any nerve conduction parameter measured and caused milder, less frequent effects on morphology. Overall, our findings indicate that eribulin mesylate induces less neuropathy in mice than paclitaxel or ixabepilone at equivalent MTD-based doses.
Insights
Eribulin mesylate causes less chemotherapy-induced nerve damage in mice compared to paclitaxel and ixabepilone. This study evaluated neurotoxicity by comparing nerve function and morphology after maximum tolerated doses (MTD).
Area of Science:
- Neuroscience
- Pharmacology
- Oncology
Background:
- Chemotherapy-induced neurotoxicity is a major challenge in cancer treatment.
- Tubulin-targeting agents like paclitaxel and epothilones cause significant neuropathy.
- Eribulin mesylate, a novel agent, shows antineoplastic activity with lower neuropathy incidence.
Purpose of the Study:
- To directly compare the neuropathy-inducing potential of eribulin mesylate, paclitaxel, and ixabepilone in mice.
- To assess the effects of these drugs on nerve conduction and morphology at equivalent maximum tolerated doses (MTD).
Main Methods:
- Mice were treated with paclitaxel, ixabepilone, or eribulin mesylate at doses up to their respective MTDs.
- Nerve conduction velocity, nerve amplitude, and sciatic nerve/dorsal root ganglion morphology were evaluated.
- Comparisons were made at 0.25, 0.5, 0.75, and 1x MTD for each drug.
Main Results:
- Paclitaxel and ixabepilone at MTDs caused significant deficits in nerve conduction and moderate to severe nerve/ganglion pathology.
- Eribulin mesylate at MTDs did not produce significant nerve conduction deficits.
- Eribulin mesylate induced milder and less frequent morphological changes compared to the other agents.
Conclusions:
- Eribulin mesylate demonstrates a lower propensity for inducing neuropathy in mice compared to paclitaxel and ixabepilone at equivalent MTD-based doses.
- These findings suggest eribulin mesylate may offer a safer therapeutic option regarding neurotoxicity.
