Neuropathic pain is associated with increased nodal persistent Na(+) currents in human diabetic neuropathy.
Peripheral nerve injury alters function and expression of voltage gated Na(+) channels on the axolemma, leading to ectopic firing and neuropathic pain/paresthesia. Hyperglycemia also affects nodal Na(+) currents, presumably due to activation of polyol pathway and impaired Na(+)-K(+) pump. We investigated changes in nodal Na(+) currents in peripheral sensory axons and their relation with pain in human diabetic neuropathy. Latent addition using computerized threshold tracking was used to estimate nodal persistent Na(+) currents in radial sensory axons of 81 diabetic patients. Of these, 36 (44%) had chronic neuropathic pain and severe paresthesia. Compared to patients without pain, those with pain had greater nodal Na(+) currents (p = 0.001), smaller amplitudes of sensory nerve action potentials (SNAP) (p = 0.0003), and lower hemoglobin A1c levels (p = 0.006). Higher axonal Na(+) conductance was associated with smaller SNAP amplitudes (p = 0.03) and lower hemoglobin A1c levels (p = 0.008). These results suggest that development of neuropathic pain depends on axonal hyperexcitability due to increased nodal Na(+) currents associated with structural changes, but the currents could also be affected by the state of glycemic control. Our findings support the view that altered Na(+) channels could be responsible for neuropathic pain/paresthesia in diabetic neuropathy.
Misawa
Sonoko
S
Department of Neurology, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan. sonoko.m@mb.infoweb.ne.jp
Sakurai
Kenichi
K
Shibuya
Kazumoto
K
Isose
Sagiri
S
Kanai
Kazuaki
K
Ogino
Jun
J
Ishikawa
Ko
K
Kuwabara
Satoshi
S
D000200:Action Potentials; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001369:Axons / Q000502:physiology*; D002908:Chronic Disease; D003929:Diabetic Neuropathies / Q000097:blood / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000097:blood / Q000503:physiopathology*; D010292:Paresthesia / Q000503:physiopathology; D010525:Peripheral Nerves / Q000503:physiopathology*; D011984:Sensory Receptor Cells / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D055815:Young Adult
D006442:Glycated Hemoglobin; D012964:Sodium; C517652:hemoglobin A1c protein, human