Research Paper Volume 13, Issue 10 pp 13615—13625

The effect of IL-6/Piezo2 on the trigeminal neuropathic pain

MingXing Liu1, , Yan Li1, , Jun Zhong2, , Lei Xia2, , NingNing Dou2, ,

  • 1 Department of Neurosurgery, Qingdao Municipal Hospital, Qingdao 266000, China
  • 2 Department of Neurosurgery, XinHua Hospital, The Cranial Nerve Disease Center of Shanghai, Shanghai JiaoTong University School of Medicine, Shanghai 200092, China

Received: December 2, 2020       Accepted: March 4, 2021       Published: April 23, 2021
How to Cite

Copyright: © 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The nature of trigeminal neuropathic pain (TN) attacks is regarded as the ignition of ectopic action potentials from the trigeminal root following vascular compression, which seemed to be related to transmembrane proteins and inflammation factors. This study focused on the mechanosensitive channel Piezo2 and cytokine IL-6.

The chronic constriction injury of infraorbital nerve in SD rats was used to establish the TN model. The trigeminal ganglion was then achieved to perform immunocytochemistry studies.

A significant upregulation of Piezo2 and IL-6 was showed in the TN model rats. The Piezo2 positive accounted for 72.3±9.5% in those IL-6 positive neurons. The Piezo2 co-localized with CGRP, IB4 and NF-200 but not with GFAP, which implied that it was expressed in both the C-type and the A-type neurons. After administration of GsMTx4 or anti-rat IL-6 antibody in the TN model, the dynamic allodynia and pinprick hyperalgesia scores as well as the mechanical threshold changed significantly. In the sham-operation rates, with local administration of IL-6, an upregulation of Piezo2 was also exhibited.

Our study demonstrated that the up-regulation of Piezo2 in the pain afferent neurons following trigeminal nerve injury may play a role in the development of the neuralgia. Meanwhile, the expression of Piezo2 may be modulated by inflammatory cytokines, such as IL-6.


TN: trigeminal neuropathic pain; IL-6: interleukin-6; TG: trigeminal ganglion; DRG: dorsal root ganglion; RI: rapidly inactivating.