The therapeutic use of botulinum toxin (Botox) is increasing in popula
rity. Previous studies have shown that various drugs, especially when
injected intrafascicularly, can cause major nerve damage. This study e
valuates the potential for neurotoxicity of botulinum toxin in a rat s
ciatic nerve model. Lewis rats were randomly assigned to one of six gr
oups (n = 10/group). Group 1, 2, and 3 rats received, respectively, an
intrafascicular, extrafascicular, and extraneural injection of 50 mu
l of botulinum toxin (50 UI/ml). Group 4, 5, and 6 rats received 50 mu
l of 10% phenol as a positive control. Five animals received saline a
s a negative control. Animals were sacrificed at 2 and 7 weeks. Nerves
were harvested and processed for histology and morphometry. Nerves in
all botulinum toxin groups retained a normal architecture without cel
lular infiltration or demyelination. The number and diameter of fibers
, the thickness of myelin, and the percentage of neural tissue were co
mparable with normal controls. Nerves injected intraneurally with phen
ol presented with severe damage, demyelination, and inflammation at 2
weeks and showed signs of early regeneration at 7 weeks. This study de
monstrates that in a rat model, even direct intraneural injection of b
otulinum toxin caused no damage. This information should encourage the
reconstructive surgeon to consider broader applications of this drug.