Antiemetics are widely used drugs, frequently administered to alleviate pos
toperative and postchemotherapeutic nausea and vomiting. While antiemetics
do not induce peripheral neurotoxicity when administered systemically, it i
s not known whether peripheral nerve injury can occur as a result of inadve
rtent intraneural injection during intramuscular administration. The purpos
e of this study was to characterize the neurotoxic effect of three commonly
used antiemetic agents (promethazine, dimenhydrinate, and prochlorperazine
) as compared to saline in the rat sciatic nerve model. Intrafascicular and
extrafascicular injection as well as direct application of the antiemetic
drugs were performed, Nerves were harvested at 2 weeks postoperatively for
histology and morphometry, with an additional sacrifice point at 8 weeks fo
r the intrafascicular injection group, Injection injuries caused by antieme
tic drugs differed depending on the agent injected and the location of inje
ction. Extrafascicular injection and direct application caused no damage. I
ntrafascicular injection caused diffuse axonal injury in the promethazine a
nd dimenhydrinate groups, while prochlorperazine caused only focal injury.
Regeneration was prominent at 8 weeks in all intrafascicular injection grou
ps in this rat model. Prochlorperazine thus appears to be less neurotoxic w
hen injected intraneurally and should preferentially be used for intramuscu
lar injections.