Botulinum toxin type A counteracts neuropathic pain by countering the increase of GlyT2 expression in the spinal cord of CCI rats

Jian Wang; Zhuofeng Ding; Wei Xu; Liqiong He; Jiangju Huang; Chengliang Zhang; Qulian Guo; Wangyuan Zou

doi:10.1016/j.brainres.2022.148095

Botulinum toxin type A counteracts neuropathic pain by countering the increase of GlyT2 expression in the spinal cord of CCI rats

Brain Res. 2022 Dec 1:1796:148095. doi: 10.1016/j.brainres.2022.148095. Epub 2022 Sep 19.

Authors

Jian Wang¹, Zhuofeng Ding², Wei Xu³, Liqiong He², Jiangju Huang⁴, Chengliang Zhang⁵, Qulian Guo¹, Wangyuan Zou⁶

Affiliations

¹ Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
² Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
³ Department of Anesthesiology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan 410008, China.
⁴ Department of Anesthesiology, The First Hospital of Changsha, Changsha, Hunan 410008, China.
⁵ Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
⁶ Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: wangyuanzou@csu.edu.cn.

PMID: 36165874
DOI: 10.1016/j.brainres.2022.148095

Abstract

Botulinum toxin type A (BoNT/A) is a potent toxin, acts by cleaving synaptosome-associated-protein-25 (SNAP-25) to regulate the release of the neural transmitter and shows analgesic effect in neuropathic pain. However, the mechanisms of BoNT/A actions involved in nociceptions remain unclear. Glycine transporter 2 (GlyT2) is an isoform of glycine transporters, which plays an important role in the regulation of glycinergic neurotransmission. Inhibition of GlyTs could decrease pain sensation in neuropathic pain, the role of GlyT2 in the analgesic effect of BoNT/A has not been studied yet. In our present study, we demonstrated that the protein levels of GlyT2 and SNAP-25 were upregulated in the spinal cord after the development of chronic constriction injury (CCI)-induced neuropathic pain. Intraplantar application of BoNT/A (20 U/kg) attenuated mechanical allodynia induced by CCI and downregulated GlyT2 expression in the spinal cord. The application of BoNT/A s also decreased the expression of GlyT2 in pheochromocytoma (PC12) cells. Moreover, intrathecal application of lentivirus-mediated GlyT2 reversed the antinociceptive effect of BoNT/A in CCI rats. These findings indicate that GlyT2 contributes to the antinociceptive effect of BoNT/A and suggest a novel mechanism underlying BoNT/A's antinociception action.

Keywords: BoNT/A; CCI; GlyT2; Neuropathic pain; SNAP-25.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analgesics / pharmacology
Animals
Botulinum Toxins, Type A* / metabolism
Botulinum Toxins, Type A* / pharmacology
Crush Injuries* / metabolism
Glycine / metabolism
Glycine Plasma Membrane Transport Proteins / metabolism
Hyperalgesia / drug therapy
Hyperalgesia / metabolism
Neuralgia* / drug therapy
Neuralgia* / metabolism
Rats
Spinal Cord / metabolism

Substances

Analgesics
Glycine Plasma Membrane Transport Proteins
Botulinum Toxins, Type A
Glycine