Effect of dexmedetomidine on the development of mechanical allodynia and central sensitization in chronic post-ischemia pain rats

Jinseok Yeo,1 Sungsik Park2 1Department of Anesthesiology and Pain Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea; 2Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea Purpose: Complex regional pain syndrome type 1 (CRPS I) is an intractable neuropathic pain syndrome. Chronic post-ischemia pain (CPIP) model is an animal model of CRPS I which is produced by ischemia-reperfusion (IR) injury of the hind limb. Dexmedetomidine (DEX) is a selective and potent α2 adrenergic receptor agonist with analgesic and protective effects following an IR injury. We hypothesized that DEX protects the development of mechanical allodynia and central sensitization in CRPS I. Therefore, we evaluated the dose-related protective effect of DEX in a CPIP model.Methods: We divided 45 rats into five groups: sham, CPIP, CPIP + DEX 10 µg/kg, CPIP + DEX 50 µg/kg, and CPIP + DEX 100 µg/kg. Rats in the sham group underwent sham surgery, and the other rats received CPIP injury. One hour before reperfusion or end of sham surgery, normal saline was injected into the rats in the sham and CPIP groups, and DEX (designated dose) was injected into the rats in the other groups. All rats were evaluated for the withdrawal threshold of both hind paws before surgery and 1, 3, and 7 days after surgery. Phosphorylation of N-methyl-d-aspartate receptor subunits (pGluN1) and phosphorylation of extracellular signal-regulated kinases (pERK) in the spinal cord were measured 3 days after surgery.Results: Administration of DEX before reperfusion showed a significant increase in the withdrawal threshold in both hind paws and a significant decrease of the expressions of pGluN1 and pERK in CPIP rats dose dependently (P<0.05).Conclusion: DEX may inhibit the development of mechanical allodynia and central sensitization in CPIP rats. Keywords: allodynia, central sensitization, chronic post-ischemia pain, dexmedetomidin