Effects of Taxol on Regeneration in a Rat Sciatic Nerve Transection Model

Abstract

Recent studies describe taxol as a candidate treatment for promoting central nerve regeneration. However, taxol has serious side effects including peripheral neurotoxicity, and little information is known about the effect of taxol on peripheral nerve regeneration. We investigated the effects of taxol on regeneration in a rat sciatic nerve transection model. Rats were divided into four groups (n = 10): normal saline (i.p.) as the control, Cremophor EL vehicle, and 2 or 6 mg/kg of taxol in the Cremophor EL solution (four times in day-2, 4, 6, and 8), respectively. We evaluated neuronal electrophysiology, animal behaviour, neuronal connectivity, macrophage infiltration, location and expression levels of calcitonin gene-related peptide (CGRP), and expression levels of both nerve growth factors and immunoregulatory factors. In the high-dose taxol group (6 mg/kg), neuronal electrophysiological function was significantly impaired. Licking latencies were significantly changed while motor coordination was unaffected. Neuronal connectivity, macrophage density, and expression levels of CGRP was dramatically reduced. Expression levels of nerve growth factors and immunoregulatory factors was also reduced, while it was increased in the low-dose taxol group (2 mg/kg). These results indicate that taxol can modulate local inflammatory conditions, impair nerve regeneration, and impede recovery of a severe peripheral nerve injury.

Fracture repair requires TrkA signaling by skeletal sensory nerves

“…Thus, PTX has been shown to induce distal axonal degeneration, a reduction in intraepidermal nerve frequency, and thermal hypoalgesia characteristic of sensory neuropathy (23,24). PTX has been shown to impair nerve growth after experimental injury, accompanied by reduced NGF at the injury site (48). In clinical scenarios, chemotherapeutic agents are well known to reduce bone mineral density in patients, even after stratification for hormonal changes or disease stage (49).…”

Effects of Electrical Stimulation on Peripheral Nerve Regeneration in a Silicone Rubber Conduit in Taxol-Treated Rats

“…A variety of neuroprotective drugs have been developed to reduce the occurrence of neurotoxicity due to taxol [33]. Our previous study demonstrated that taxol could cause worsening of local inflammation and hinder peripheral nerve regeneration [10]. In our other study, we found that regenerated nerves in normal rats receiving electrical treatment, especially at 2 Hz, had a more mature structure with increased myelinated fibers and blood vessels compared with the controls receiving no electrical stimulation [28].…”

“…After the behavior test, electrophysiological examinations were performed, including nerve conduction velocity (NCV), amplitude, latency, and evoked muscle action potentials (MAPs) of the gastrocnemius muscles using BIOPAC Systems, Inc. (Goleta, CA, USA) [10].…”

“…Taxol treatment has been found to notably increases microtubule acetylation [9]. My group found that excessive taxol injected in rats may hinder peripheral nerve regeneration by decreasing expression of immunoregulatory factors, macrophage invasion, and calcitonin gene-related peptide (CGRP) expression in the spine [10].…”

Attenuation of TRPV1 by AMG-517 after nerve injury promotes peripheral axonal regeneration in rats

“…Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a well-known nociception-mediating ion channel that is abundantly expressed in peripheral sensory system, especially in the terminals and cell bodies of sensory dorsal root ganglion (DRG) neurons, trigeminal ganglion neurons, and vagal neurons. 1 – 3 It is activated by several physical stimuli, including temperature, voltage, protons, pH, and chemical ligands such as resiniferatoxin and capsaicin. 2 – 5 TRPV1 is regarded as a nociceptor, meaning that it plays an important role in peripheral neuropathic pain.…”