Reduced expression of A-type potassium channels in primary sensory neurons induces mechanical hypersensitivity.
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.
Chien
Li-Ying
LY
Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan.
Cheng
Jen-Kun
JK
Chu
Dachen
D
Cheng
Chau-Fu
CF
Tsaur
Meei-Ling
ML
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism*; D010146:Pain / Q000235:genetics / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D051672:Shal Potassium Channels / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D051670:Shaw Potassium Channels / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism
C492014:Kcnc4 protein, rat; D051672:Shal Potassium Channels; D051670:Shaw Potassium Channels