Functional study of four neurotoxins as inhibitors of post-traumatic nerve regeneration.
OBJECTIVE
Chemical inhibition of nerve regeneration was studied as a potential adjunct in the treatment of injuries to the facial or recurrent laryngeal nerve. We propose that by treating selected muscles with an inhibitor of nerve regeneration shortly after injury, synkinesis may be controlled.


METHODS
Nerve regeneration after crush injury was studied in the rat posterior tibial and sciatic nerves, well-established models for the study of peripheral nerve injuries.


METHODS
Four days after controlled crush injury to the posterior tibial nerve, the gastrocnemius muscle was injected with saline (control, n = 8), phenol (n = 6), doxorubicin (n = 6), or vincristine (n = 11). Injection without crush injury was performed using vincristine (n = 4) or botulinum toxin (n = 4). Four rats underwent crush injury to the sciatic nerve followed 4 days later by botulinum toxin injection to the gastrocnemius muscle. The percent of functional recovery (%FR) of the nerve was assessed using walking track analysis.


RESULTS
Vincristine significantly retarded nerve regeneration. Five weeks after injury, %FR returned to normal in controls, as well as in the phenol, doxorubicin, and botulinum toxin groups, while in the vincristine group %FR was less than 60% of baseline (P <.0001). Vincristine injections without crush injury showed no significant reduction in print length factor. Functional recovery in the botulinum/crush group was more rapid than the botulinum without crush group.


CONCLUSIONS
Application of vincristine to the gastrocnemius muscle significantly inhibits regeneration of the posterior tibial nerve after crush injury. Botulinum toxin does not prolong functional recovery after nerve injury; rather, crush injury protects against the prolonged chemodenervation seen with botulinum toxin. Doxorubicin and phenol injection did not prolong functional recovery at the doses tested.
Paydarfar
J A
JA
Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Paniello
R C
RC
D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D020220:Facial Nerve Injuries / Q000628:therapy; D005260:Female; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D019800:Phenol / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D061226:Recurrent Laryngeal Nerve Injuries; D013979:Tibial Nerve / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology*
D009498:Neurotoxins; D019800:Phenol; D014750:Vincristine; D004317:Doxorubicin; D001905:Botulinum Toxins