Dexmedetomidine blocks hyperalgesia and dorsal root ganglia ERK signal activation in a rat model of neuropathic pain

Objective To investigate the effect of systemic administration of dexmedetomidine, a selective alpha 2 adrenergic receptor agonist, on mechanical and thermal hyperalgesia and dorsal root ganglia ERK activation induced by neuropathic pain. Methods Intraperitoneal injection of dexmedetomidine was repeatedly given once daily for 7 days or 14 days with the first injection one day before partial sciatic nerve ligation ( PSNL) surgery. Mechanical and thermal nociceptive thresholds were assessed in all animals. Then, animals were killed at corresponding time points, and the L5 DRG was removed for L5 DRG ERK activation status analysis by using immunoflurecence and Western blotting. Results (1) Partial sciatic never ligation produced a robust mechanical and thermal hyperalgisia and ERK activation of the L5 DRG in P7 and P14 groups. At the dose of 40 μg/kg, dexmedetomidine significantly attenuated PSNL-induced ipsilateral hyperalgesia on the day 7 and 14 after surgery. But the dose of 20 μg/kg of dexmedetomidine had no effect on pain behaviorl; (2) PSNL-induced up-regulation of mean fluorescence intensity of pERK on ipsilateral side of the L5 DRG was significantly suppressed by day 7, 14 post-PSNL following 40 μg/kg dexmedetomidine application, whereas 20 μg/kg dexmedetomidine had no effect; (3) Western blotting revealed that up-regulation of the protein expression of p-ERK on ipsilateral side of the L5 DRG was significantly inhibited on the day 7, 14 post-PSNL following 40 μg/kg dexmedetomidine application,whereas 20 μg/kg dexmedetomidine had no effect. Conclusion Systemic dexmedetomidine inhibits the activation of ERK signals in L5 DRG, which is possibly associated with its antihyperalgesia in rats with neuropathtic pain. Key words: Dexmedetomidine; Neuropathtic pain; DRG; ERK; Astrocyte