Levetiracetam reduces anesthetic-induced hyperalgesia in rats.
BACKGROUND
As part of an increase in excitability, small doses of pentobarbital, propofol, and midazolam induce an increased sensitivity to pain. Specific therapy to prevent or reduce this excitability may offer advantages over current clinical management with analgesics and sedatives. The pharmacological profile of the novel antiepileptic drug, levetiracetam, suggests that it may reduce the intensity of the excitatory stages of anesthesia.


METHODS
We examined the influence of levetiracetam on the reduction of the nociceptive reflex threshold in rats by sedative doses of pentobarbital, propofol, and midazolam. Measurements of nociceptive reflex threshold to pressure and heat were made and then repeated after intraperitoneal injection of saline or one of three doses of levetiracetam (100, 200, 500 mg/kg). Pentobarbital (30 mg/kg), propofol (30 mg/kg), or midazolam (1.9 mg/kg) were then administered. The reflex threshold was measured every 10 min, starting at 5 min after the sedative injection, until 65 min had elapsed.


RESULTS
Levetiracetam did not alter nociceptive reflex threshold in nonsedated animals (P = 0.11) or influence the degree or duration of sedation. The three anesthetic/sedative drugs reduced the nociceptive reflex threshold by 20%-30% of control values. Levetiracetam reduced the hyperreflexia associated with pentobarbital and midazolam (P < 0.05), but not propofol.


CONCLUSIONS
These findings support further investigation into the role of levetiracetam in the prevention of anesthetic-induced excitability.
Archer
David P
DP
Department of Anesthesiology, Faculty of Medicine, University of Calgary, Calgary, Canada. david.archer@calgaryhealthregion.ca
Lamberty
Yves
Y
Wang
Bing
B
Davis
Melinda J
MJ
Samanani
Naaznin
N
Roth
Sheldon H
SH
D000758:Anesthesia / Q000009:adverse effects*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced* / Q000517:prevention & control*; D000077287:Levetiracetam; D008297:Male; D023421:Models, Animal; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam