title: Prevention of post-traumatic reinnervation with microtubule inhibitors.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  NA
authors.affiliation: 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.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Park
authors.affiliation: 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.
authors.forename: Reena
authors.initials: R
authors.lastname: Dhanda Patil
authors.affiliation: 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.
authors.forename: Randal C
authors.initials: RC
authors.lastname: Paniello
mesh_terms: D000818:Animals; D008297:Male; D008870:Microtubules / Q000187:drug effects*; D009416:Nerve Regeneration / Q000187:drug effects*; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use*; D059348:Peripheral Nerve Injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D050257:Tubulin Modulators / Q000494:pharmacology* / Q000627:therapeutic use*; D014750:Vincristine / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D050257:Tubulin Modulators; D014750:Vincristine; D017239:Paclitaxel
keywords: Unilateral vocal fold paralysis; laryngeal nerve; larynx; neural regeneration; neurotoxin; paclitaxel; vincristine