• Sonoko Misawa.
• Department of Neurology, Graduate School of Medicine, Chiba University, Chuo-ku, Japan.
• Brain Nerve. 2012 Nov 1; 64 (11): 1249-53.

AbstractNeuropathic pain occurs as a result of peripheral neuropathy or peripheral nerve injury. Voltage-gated Na⁺ channels are assumed to play a major role in the pathophysiology of neuropathic pain and have become important therapeutic targets, because they are critical determinants of the excitability of sensory neurons. Nerve injury or disease could induce changes in trafficking, gene expression, and kinetics of Na⁺ channels, resulting in ectopic discharge and increased neuronal excitability. Hyperexcitability of neurons and excess discharge lead to neuropathic pain and trigger central sensitization. Four isoforms of Na⁺ channels, Na⁺1.3, 1.7, 1.8, and 1.9, have been implicated in the pathogenesis of neuropathic pain. However, it is unclear whether the pharmacological target should be a single isoform or a complex of isoforms. Na⁺ channel blockers could stabilize the axonal membrane and suppress pain sensation. However, adverse side effects, such as somnolence, nausea, and vertigo, resulting from the suppression of neural activity in the central nervous system, are practical limitations on the systemic administration of Na⁺ channel blockers. Agents such as subtype-specific antagonists or drugs that cannot cross the blood-brain barrier could be candidates for novel drugs in pain treatment. Na⁺ channels are attractive targets for studying the pathophysiology of neuropathic pain and for drug development. However, recent advances have been mostly based on basic research. Overcoming the challenges in directly approaching patients with neuropathic pain might advance our understanding of the pathophysiology of pain and aid the development of therapeutic strategies.

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