• Katsunori Ohno, Atsushi Yokota, Shinji Hirofuji, Kiyoto Kanbara, Hisashi Ohtsuka, and Mitsuo Kinoshita.
• Department of Orthopedic Surgery, Osaka Medical College, 2-7, Daigaku-machi, Takatsuki 569-8686, Japan.
• J. Orthop. Res. 2010 Apr 1; 28 (4): 481-6.

AbstractTo elucidate the pathophysiological mechanisms underlying chronic nerve-stretch injury, we gradually lengthened rat femurs by 15 mm at the rate of 0.5 mm/day (group L, n = 13). The control groups comprised sham-operated (group S, n = 10) and naive (group N, n = 8) rats. Immediately after the lengthening, we performed a conduction study on their sciatic nerves and harvested samples. Electrophysiological and histological analyses showed mild conduction slowing and axonal degeneration of unmyelinated fibers in group L rats. Altered mRNA expression of the voltage-gated sodium channels in the dorsal root ganglion was also observed. Tetrodotoxin-resistant (TTX-R) sodium-channel Nav1.8 mRNA expression was significantly decreased and TTX-R sodium-channel Nav1.9 mRNA expression showed a tendency to decrease when compared with the mRNA expressions in the control groups. However, tetrodotoxin-sensitive (TTX-S) sodium-channel Nav1.3 mRNA expression remained unaltered. The immunohistochemical alteration of Nav1.8 protein expression was parallel to the results of the mRNA expression. Previous studies involving neuropathic states have suggested that pain/paresthesia is modulated by a subset of sodium channels, including downregulation and/or upregulation of TTX-R and TTX-S sodium channels, respectively. Our findings indicate that Nav1.8 downregulation may be one of the pathophysiological mechanisms involved in limb lengthening-induced neuropathy.

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