Andrea M Park1, Reena Dhanda Patil1, Randal C Paniello1. 1. Department of Otolaryngology-Head and Neck Surgery at the Washington University School of Medicine, St. Louis, MO, and the St. Louis V.A. Medical Center, St. Louis, Missouri, U.S.A.
Abstract
OBJECTIVES/HYPOTHESIS: Functional recovery after a recurrent laryngeal nerve or facial nerve injury may be impaired due to aberrant reinnervation. Previous work in a rat peripheral nerve injury model found vincristine to be a potent inhibitor of reinnervation, and it has since been used to effectively block neural regeneration in other animal models. However, vincristine's narrow therapeutic index may limit its utility; therefore, another microtubule inhibitor, paclitaxel, which has a higher therapeutic index, was tested. STUDY DESIGN: Animal (rat) study. METHODS: After controlled injury to the rat posterior tibial (PT) nerve, the gastrocnemius/soleus complex was injected with saline (control, n = 14), vincristine (n = 30), or paclitaxel (n = 20). Injections without a crush injury were performed using saline (n = 5) or paclitaxel (n = 9). The functional recovery (FR) of the PT nerve was assessed using walking track analysis. RESULTS: At 6 weeks, controls had already recovered to baseline (FR = 1.0), whereas the paclitaxel group had FR = 0.724 ± 0.064 and the vincristine group had FR = 0.709 ± 0.078. At 6 months, the paclitaxel rats had FR = 0.798 ± 0.167 and the vincristine rats had FR = 0.754 ± 0.240. These differences were significantly different from baseline, but the two agents were not different from each other. Paclitaxel did not affect the FR in the absence of a nerve injury. CONCLUSIONS: Intramuscular paclitaxel and vincristine both significantly inhibit regeneration of the PT nerve after crush injury for at least 6 months. Potential clinical uses of inhibition of reinnervation are discussed. LEVEL OF EVIDENCE: NA
OBJECTIVES/HYPOTHESIS: Functional recovery after a recurrent laryngeal nerve or facial nerve injury may be impaired due to aberrant reinnervation. Previous work in a rat peripheral nerve injury model found vincristine to be a potent inhibitor of reinnervation, and it has since been used to effectively block neural regeneration in other animal models. However, vincristine's narrow therapeutic index may limit its utility; therefore, another microtubule inhibitor, paclitaxel, which has a higher therapeutic index, was tested. STUDY DESIGN: Animal (rat) study. METHODS: After controlled injury to the rat posterior tibial (PT) nerve, the gastrocnemius/soleus complex was injected with saline (control, n = 14), vincristine (n = 30), or paclitaxel (n = 20). Injections without a crush injury were performed using saline (n = 5) or paclitaxel (n = 9). The functional recovery (FR) of the PT nerve was assessed using walking track analysis. RESULTS: At 6 weeks, controls had already recovered to baseline (FR = 1.0), whereas the paclitaxel group had FR = 0.724 ± 0.064 and the vincristine group had FR = 0.709 ± 0.078. At 6 months, the paclitaxelrats had FR = 0.798 ± 0.167 and the vincristinerats had FR = 0.754 ± 0.240. These differences were significantly different from baseline, but the two agents were not different from each other. Paclitaxel did not affect the FR in the absence of a nerve injury. CONCLUSIONS: Intramuscular paclitaxel and vincristine both significantly inhibit regeneration of the PT nerve after crush injury for at least 6 months. Potential clinical uses of inhibition of reinnervation are discussed. LEVEL OF EVIDENCE: NA
Authors: Hans Gelderblom; Klaus Mross; Albert J ten Tije; Dirk Behringer; Stephan Mielke; Desirée M van Zomeren; Jaap Verweij; Alex Sparreboom Journal: J Clin Oncol Date: 2002-01-15 Impact factor: 44.544
Authors: Hans Gelderblom; Jaap Verweij; Desirée M van Zomeren; Dirk Buijs; Linda Ouwens; Kees Nooter; Gerrit Stoter; Alex Sparreboom Journal: Clin Cancer Res Date: 2002-04 Impact factor: 12.531