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Front Mol Neurosci. 2018 Feb 8;11:24. doi: 10.3389/fnmol.2018.00024. eCollection 2018.

Accumulation of Cav3.2 T-type Calcium Channels in the Uninjured Sural Nerve Contributes to Neuropathic Pain in Rats with Spared Nerve Injury.

Chen W1,2,3, Chi YN1,4, Kang XJ1, Liu QY1, Zhang HL1, Li ZH5, Zhao ZF1, Yang Y1, Su L1,6, Cai J1, Liao FF1, Yi M1, Wan Y1,2,3, Liu FY1,2.

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Neuroscience Research Institute, Peking University, Beijing, China.
Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.
Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China.
Department of Anesthesiology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
Center of Medical and Health Analysis, Peking University, Beijing, China.


Injuries to peripheral nerve fibers induce neuropathic pain. But the involvement of adjacent uninjured fibers to pain is not fully understood. The present study aims to investigate the possible contribution of Cav3.2 T-type calcium channels in uninjured afferent nerve fibers to neuropathic pain in rats with spared nerve injury (SNI). Aβ-, Aδ- and C-fibers of the uninjured sural nerve were sensitized revealed by in vivo single-unit recording, which were accompanied by accumulation of Cav3.2 T-type calcium channel proteins shown by Western blotting. Application of mibefradil, a T-type calcium channel blocker, to sural nerve receptive fields increased mechanical thresholds of Aβ-, Aδ- and C-fibers, confirming the functional involvement of accumulated channels in the sural nerve in SNI rats. Finally, perineural application of mibefradil or TTA-P2 to the uninjured sural nerve alleviated mechanical allodynia in SNI rats. These results suggest that axonal accumulation of Cav3.2 T-type calcium channels plays an important role in the uninjured sural nerve sensitization and contributes to neuropathic pain.


Cav3.2 T-type calcium channels; mechanical allodynia; neuropathic pain; spared nerve injury; uninjured nerve sensitization

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