Abstract
Taxol, a type of antimitotic agent, could modulate local inflammatory conditions in peripheral nerves, which may impair their regeneration and recovery when injured. This study provided in vivo trials of silicone rubber chambers to bridge a long 10 mm sciatic nerve defect in taxol-treated rats. It was aimed to determine the effects of electrical stimulation at various frequencies on regeneration of the sciatic nerves in the bridging conduits. Taxol-treated rats were divided into four groups (n = 10/group): sham control (no current delivered from the stimulator); and electrical stimulation (3 times/week for 3 weeks at 2, 20, and 200 Hz with 1 mA current intensity). Neuronal electrophysiology, animal behavior, neuronal connectivity, macrophage infiltration, calcitonin gene-related peptide (CGRP) expression levels, and morphological observations were evaluated. At the end of 4 weeks, animals in the low- (2 Hz) and medium-frequency (20 Hz) groups had dramatic higher rates of successful regeneration (90% and 80%) across the wide gap as compared to the groups of sham and high-frequency (200 Hz) (60% and 50%). In addition, the 2 Hz group had significantly larger amplitudes and evoked muscle action potentials compared to the sham and the 200 Hz group, respectively (P < 0.05). Heat, cold plate licking latencies, motor coordination, and neuronal connectivity were unaffected by the electrical stimulation. Macrophage density, CGRP expression level, and axon number were all significantly increased in the 20 Hz group compared to the sham group (P < 0.05). This study suggested that low- (2 Hz) to medium-frequency (20 Hz) electrical stimulation could ameliorate local inflammatory conditions to augment recovery of regenerating nerves by accelerating their regrowth and improving electrophysiological function in taxol-treated peripheral nerve injury repaired with the silicone rubber conduit.
Highlights
IntroductionTaxol (paclitaxel) is a common microtubule-binding antineoplastic drug used to treat solid tumors
Chemotherapy induces peripheral neuropathy [1,2]
Right sciatic nerves of anesthetized female Sprague-Dawley rats were severed into proximal and distal segments. Both of the stumps were fixed in a silicone rubber chamber
Summary
Taxol (paclitaxel) is a common microtubule-binding antineoplastic drug used to treat solid tumors. It binds to and stabilizes the length of microtubules, which results in microtubule dynamics suppression, leading to mitotic arrest and dividing cancer cell apoptosis [3]. Exposure to taxol may cause neurodegeneration, resulting in serious side effects including myelosuppression and peripheral neurotoxicity [4]. Taxol could induce clinical sensory neuropathy with symptoms of tingling, numbness, or burning pain. Those symptoms in most patients could resolve within months after treatment, sensory pain may occasionally become a chronic problem [5]
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