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

Wen Chen,Fei-Fei Liao,Hao-Lin Zhang,Qing-Ying Liu,You Wan,Zi-Fang Zhao,Zhi-Hua Li,Li Su,Feng-Yu Liu,Ming Yi,Jie Cai,Ye-Nan Chi,Xue-Jing Kang,Yin Yang

doi:10.3389/fnmol.2018.00024

Abstract

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.

Highlights

Peripheral neuropathic pain is characterized by spontaneous pain, mechanical allodynia and thermal hyperalgesia and results from lesions to the peripheral nervous system
Our results showed that uninjured sural nerves were sensitized in spared nerve injury (SNI) rats, and that accumulated Cav3.2 T-type calcium channels in uninjured sural nerve contributed to peripheral sensitization and neuropathic pain
We investigated the characteristics of Aβ, Aδ- and C-fibers in the uninjured sural nerves on day 14 after SNI or sham operation

Summary

Introduction

Peripheral neuropathic pain is characterized by spontaneous pain, mechanical allodynia and thermal hyperalgesia and results from lesions to the peripheral nervous system Maladaptive plasticity, such as peripheral and central sensitization, is a core mechanism of neuropathic pain (Fields et al, 1998; Woolf and Salter, 2000; Latremoliere and Woolf, 2009; Anderson et al, 2017; Colloca et al, 2017). In a mouse model of spared nerve injury (SNI), Aδ-mechanoreceptors and C-fibers in the spared sural nerve produce significantly more action potentials in response to suprathreshold mechanical stimulation (Smith et al, 2013). All these studies indicate possible contribution of the uninjured afferent sensitization to neuropathic pain

Methods

Results

Conclusion