Neuropathic pain is associated with increased nodal persistent Na(+) currents in human diabetic neuropathy.

Abstract

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.

• Authors: Sonoko Misawa, Kenichi Sakurai, Kazumoto Shibuya, Sagiri Isose, Kazuaki Kanai, Jun Ogino, Ko Ishikawa, Satoshi Kuwabara
• Journal: Journal of the peripheral nervous system : JPNS (J Peripher Nerv Syst) Vol. 14 Issue 4 Pg. 279-84 (Dec 2009) ISSN: 1529-8027 [Electronic] United States
• PMID: 20021569 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycated Hemoglobin A
• hemoglobin A1c protein, human
• Sodium

Topics

• Action Potentials
• Adult
• Aged
• Aged, 80 and over
• Axons (physiology)
• Chronic Disease
• Diabetic Neuropathies (blood, physiopathology)
• Female
• Glycated Hemoglobin (metabolism)
• Humans
• Male
• Middle Aged
• Neuralgia (blood, physiopathology)
• Paresthesia (physiopathology)
• Peripheral Nerves (physiopathology)
• Sensory Receptor Cells (physiology)
• Sodium (metabolism)
• Young Adult