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The Journal of Neuroscience, September 12, 2007, 27(37):9855-9865; doi:10.1523/JNEUROSCI.0604-07.2007

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Neurobiology of Disease
Reduced Expression of A-Type Potassium Channels in Primary Sensory Neurons Induces Mechanical Hypersensitivity

Li-Ying Chien,^1 * Jen-Kun Cheng,^2,5 * Dachen Chu,³ Chau-Fu Cheng,¹ and Meei-Ling Tsaur^1,4

¹Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan, ²Department of Anesthesiology, Mackay Memorial Hospital, Taipei, Taiwan, ³Department of Neurosurgery in Hoping Branch and ⁴Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, and ⁵Department of Anesthesiology, Taipei Medical University, Taipei, Taiwan

Correspondence should be addressed to Meei-Ling Tsaur, Institute of Neuroscience, National Yang-Ming University, 155 Li-Nong Street, Sec 2, Taipei, Taiwan. Email: mltsaur{at}ym.edu.tw

A-type K⁺ channels (A-channels) are crucial in controlling neuronal excitability, and their downregulation in pain-sensing neurons may increase pain sensation. To test this hypothesis, we first characterized the expression of two A-channels, Kv3.4 and Kv4.3, in rat dorsal root ganglion (DRG) neurons. Kv3.4 was expressed mainly in the nociceptive DRG neurons, in their somata, axons, and nerve terminals innervating the dorsal horn of spinal cord. In contrast, Kv4.3 appeared selectively in the somata of a subset of nonpeptidergic nociceptive DRG neurons. Most Kv4.3(+) DRG neurons also expressed Kv3.4. In a neuropathic pain model induced by spinal nerve ligation in rats, the protein levels of Kv3.4 and Kv4.3 in the DRG neurons were greatly reduced. After Kv3.4 or Kv4.3 expression in lumbar DRG neurons was suppressed by intrathecal injections of antisense oligodeoxynucleotides, mechanical but not thermal hypersensitivity developed. Together, our data suggest that reduced expression of A-channels in pain-sensing neurons may induce mechanical hypersensitivity, a major symptom of neuropathic pain.

Key words: antisense oligodeoxynucleotides; dorsal root ganglion neurons; intrathecal injection; neuropathic pain; potassium channels; spinal nerve ligation

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Received Feb. 13, 2007; revised July 12, 2007; accepted July 13, 2007.

Correspondence should be addressed to Meei-Ling Tsaur, Institute of Neuroscience, National Yang-Ming University, 155 Li-Nong Street, Sec 2, Taipei, Taiwan. Email: mltsaur{at}ym.edu.tw

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