Articles

Article

Original Article

Exp Neurobiol 2018; 27(4): 267-276

Published online August 30, 2018

https://doi.org/10.5607/en.2018.27.4.267

© The Korean Society for Brain and Neural Sciences

Dexmedetomidine Attenuates Neuropathic Pain by Inhibiting P2X7R Expression and ERK Phosphorylation in Rats

Jia-Piao Lin1,†, Chao-Qin Chen1,†, Ling-Er Huang1, Na-Na Li1, Yan Yang2, Sheng-Mei Zhu1, and Yong-Xing Yao1*

1Department of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, P.R. China.

2Centre for Neuroscience, Zhejiang University School of Medicine, Hangzhou 310016, P.R. China.

Correspondence to: *To whom correspondence should be addressed.
TEL: 86-136-5666-8373, FAX: 86-571-8723-6169
e-mail: yaoyongxing@zju.edu.cn
These authors are contributed equally

Received: May 28, 2018; Revised: August 21, 2018; Accepted: August 23, 2018

α2-Adrenoceptor agonists attenuate hypersensitivity under neuropathic conditions. However, the mechanisms underlying this attenuation remain largely unknown. In the present study, we explored the potential roles of purinergic receptor 7 (P2X7R)/extracellular signal-regulated kinase (ERK) signaling in the anti-nociceptive effect of dexmedetomidine in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. An animal model of CCI was adopted to mimic the clinical neuropathic pain state. Behavioral hypersensitivity to mechanical and thermal stimuli was determined by von Frey filament and Hargreaves' tests, and the spinal P2X7R expression level and ERK phosphorylation were analyzed using western blot analysis and immunohistochemistry. In parallel with the development of mechanical and thermal hyperalgesia, a significant increase in P2X7R expression was noted in the ipsilateral spinal cord on day 7 after CCI. Intrathecal administration of dexmedetomidine (2.5 µg) for 3 days not only attenuated neuropathic pain but also inhibited the CCI-induced P2X7R upregulation and ERK phosphorylation. Intrathecal dexmedetomidine administration did not produce obvious effects on locomotor function. The present study demonstrated that dexmedetomidine attenuates the neuropathic pain induced by CCI of the sciatic nerve in rats by inhibiting spinal P2X7R expression and ERK phosphorylation, indicating the potential therapeutic implications of dexmedetomidine administration for the treatment of neuropathic pain.

Graphical Abstract


Keywords: Dexmedetomidine, Neuropathic pain, Chronic constriction injury, Spinal cord, Purinergic receptor, Extracellular signal-regulated kinase