Effects of carbamazepine and amitriptyline on tetrodotoxinresistant Na+ channels in immature rat trigeminal ganglion neurons.
Although anticonvulsant drugs that block voltage-dependent Na+ channels have been widely used for neuropathic pain, including peripheral nerve injury-induced pain, much less is known about the actions of these drugs on immature trigeminal ganglion (TG) neurons. Here we report the effects of carbamazepine (CBZ) and amitriptyline (ATL) on tetrodotoxin-resistant (TTX-R) Na' channels expressed on immature rat TG neurons. TTX-R Na+ currents (I(Na)) were recorded in the presence of 300 nM TTX by use of a conventional whole-cell patch clamp method. Both CBZ and ATL inhibited TTX-R I(Na) in a concentration-dependent manner, but ATL was more potent. While CBZ and ATL did not affect the overall voltage-activation relationship of TTX-R Na+ channels, both drugs shifted the voltage-activation relationship to the left, indicating that they inhibited TTX-R Na+ channels more efficiently at depolarized membrane potentials. ATL showed a profound use-dependent blockade of TTX-R I(Na), but CBZ had little effect. The present results suggest that both CBZ and ATL, common drugs used for treating neuropathic pain, efficiently inhibit TTX-R Na+ channels expressed on immature TG neurons, and that these drugs might be useful for the treatment of trigeminal nerve injury-induced neuropathic pain, as well as the inhibition of ongoing central sensitization, even during immature periods.
Hur
Yun-Kyung
YK
Department of Oral Medicine, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
Choi
In-Sun
IS
Cho
Jin-Hwa
JH
Park
Eun-Joo
EJ
Choi
Jae-Kap
JK
Choi
Byung-Ju
BJ
Jang
Il-Sung
IS
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology*; D004351:Drug Resistance; D004594:Electrophysiology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D059348:Peripheral Nerve Injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D015222:Sodium Channels; D000639:Amitriptyline; D002220:Carbamazepine; D013779:Tetrodotoxin