Effects of various antiepileptics used to alleviate neuropathic pain on compound action potential in frog sciatic nerves: comparison with those of local anesthetics.
Antiepileptics used for treating neuropathic pain have various actions including voltage-gated Na(+) and Ca(2+) channels, glutamate-receptor inhibition, and GABA(A)-receptor activation, while local anesthetics are also used to alleviate the pain. It has not been fully examined yet how nerve conduction inhibitions by local anesthetics differ in extent from those by antiepileptics. Fast-conducting compound action potentials (CAPs) were recorded from frog sciatic nerve fibers by using the air-gap method. Antiepileptics (lamotrigine and carbamazepine) concentration dependently reduced the peak amplitude of the CAP (IC50 = 0.44 and 0.50 mM, resp.). Carbamazepine analog oxcarbazepine exhibited an inhibition smaller than that of carbamazepine. Antiepileptic phenytoin (0.1 mM) reduced CAP amplitude by 15%. On the other hand, other antiepileptics (gabapentin, sodium valproate, and topiramate) at 10 mM had no effect on CAPs. The CAPs were inhibited by local anesthetic levobupivacaine (IC50 = 0.23 mM). These results indicate that there is a difference in the extent of nerve conduction inhibition among antiepileptics and that some antiepileptics inhibit nerve conduction with an efficacy similar to that of levobupivacaine or to those of other local anesthetics (lidocaine, ropivacaine, and cocaine) as reported previously. This may serve to know a contribution of nerve conduction inhibition in the antinociception by antiepileptics.
Department of Physiology, Saga Medical School, Saga 849-8501, Japan ; Department of Anesthesiology & Critical Care Medicine, Saga Medical School, Saga 849-8501, Japan.
Yuhei
0000-0003-1636-2105
Y
Uemura
Department of Physiology, Saga Medical School, Saga 849-8501, Japan.
Tsugumi
T
Fujita
Department of Physiology, Saga Medical School, Saga 849-8501, Japan.
Sena
S
Ohtsubo
Department of Anesthesiology & Critical Care Medicine, Saga Medical School, Saga 849-8501, Japan.
Naomi
N
Hirakawa
Department of Anesthesiology & Critical Care Medicine, Saga Medical School, Saga 849-8501, Japan.
Yoshiro
0000-0003-0750-1046
Y
Sakaguchi
Department of Physiology, Saga Medical School, Saga 849-8501, Japan.
Eiichi
0000-0002-2365-1768
E
Kumamoto
D000200:Action Potentials / Q000187:drug effects*; D000779:Anesthetics, Local / Q000008:administration & dosage; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage; D002045:Bupivacaine / Q000008:administration & dosage / Q000031:analogs & derivatives; D002220:Carbamazepine / Q000008:administration & dosage; D006801:Humans; D000077213:Lamotrigine; D000077554:Levobupivacaine; D009437:Neuralgia / Q000188:drug therapy*; D011898:Ranidae; D012584:Sciatic Nerve / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000008:administration & dosage
D000779:Anesthetics, Local; D000927:Anticonvulsants; D014227:Triazines; D002220:Carbamazepine; D000077554:Levobupivacaine; D000077213:Lamotrigine; D002045:Bupivacaine