Mexiletine suppresses nodal persistent sodium currents in sensory axons of patients with neuropathic pain.
OBJECTIVE
To investigate changes in axonal persistent Na(+) currents in patients with neuropathic pain and the effects of mexiletine, an analogue of lidocaine, on axonal excitability properties.


METHODS
The technique of latent addition was used to estimate nodal persistent Na(+) currents in superficial radial sensory axons of 17 patients with neuropathic pain/paresthesias before and after mexiletine treatment. Brief hyperpolarizing conditioning currents were delivered, and threshold change at the conditioning-test interval of 0.2 ms was measured as an indicator of the magnitude of persistent Na(+) currents.


RESULTS
Threshold changes at 0.2 ms in latent addition were greater in the neuropathic patients than in the normal controls (p<0.001). After mexiletine treatment, there was a reduction in clinical pain scores (p<0.001), associated with decreased threshold changes at 0.2 ms (p<0.001).


CONCLUSIONS
In patients with neuropathy, nodal persistent Na(+) currents in large sensory fibers increase, and the abnormal currents can be suppressed by mexiletine. Pain reduction after mexiletine treatment raises the possibility that excessive Na(+) currents are also suppressed in small fibers mediating neuropathic pain.


CONCLUSIONS
Latent addition can be used for indirect in vivo monitoring of nodal Na(+) currents in large sensory fibers, and future studies using this approach in small fibers would provide new insights into the peripheral mechanism of neuropathic pain.
Isose
Sagiri
S
Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, Japan.
Misawa
Sonoko
S
Sakurai
Kenichi
K
Kanai
Kazuaki
K
Shibuya
Kazumoto
K
Sekiguchi
Yukari
Y
Nasu
Saiko
S
Noto
Yuichi
Y
Fujimaki
Yumi
Y
Yokote
Koutaro
K
Kuwabara
Satoshi
S
D000328:Adult; D000368:Aged; D001369:Axons / Q000378:metabolism*; D004553:Electric Conductivity; D055724:Electrophysiological Phenomena; D005260:Female; D006801:Humans; D008012:Lidocaine / Q000031:analogs & derivatives; D008297:Male; D008801:Mexiletine / Q000627:therapeutic use*; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D010292:Paresthesia / Q000188:drug therapy / Q000503:physiopathology*; D011826:Radial Nerve / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism
D015222:Sodium Channels; D008801:Mexiletine; D008012:Lidocaine