Exp Neurobiol.  2018 Aug;27(4):267-276. 10.5607/en.2018.27.4.267.

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

• Lin JP
• Chen CQ
• Huang LE
• Li NN
• Yang Y
• Zhu SM
• Yao YX

• KMID: 2419336
• DOI: http://doi.org/10.5607/en.2018.27.4.267

Abstract

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.

Keyword

Dexmedetomidine; Neuropathic pain; Chronic constriction injury; Spinal cord; Purinergic receptor; Extracellular signal-regulated kinase

MeSH Terms

Animals
Blotting, Western
Constriction
Dexmedetomidine*
Hyperalgesia
Hypersensitivity
Immunohistochemistry
Models, Animal
Neuralgia*
Phosphorylation*
Phosphotransferases
Rats*
Sciatic Nerve
Spinal Cord
Up-Regulation
Dexmedetomidine
Phosphotransferases