Mechanism of dexmedetomidine-induced reduction of acute visceral pain in rats: relationship between alpha2 adrenergic receptors and expression of Nav1.8 in dorsal root ganglion neurons

Abstract

Objective To evaluate the relationship between alpha2 adrenergic receptors and expression of Nav1.8 in dorsal root ganglion(DRG)neurons, and to illuminate the mechanism of dexmedetomidine-induced reduction of acute visceral pain in rats. Methods Thirty-two clean-grade healthy adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 180-220 g, were divided into 4 groups (n=8 each) using a random number table method: control group (group C), acute visceral pain group (group VP), dexmedetomidine group (group D), and dexmedetomidine plus atipamezole group (group DA). In VP, D and DA groups, 10-3 mmol/L capsaicin 1.3 ml was injected into the rectum at a dose of 10-3 mmol/L to establish the acute visceral pain model, while the equal volume of normal saline was given instead in group C. Atipamezole 1 mg/kg was subcutaneously injected through the back of the neck at 20 min before establishing the model in group DA.Dexmedetomidine 10 μg/kg was injected through the tail vein at 15 min before establishing the model in D and DA groups, while the equal volume of normal saline was given instead at the correspording time points in C and VP groups.The visceral pain behavior score was recorded at 1 h after establishing the model.The animals were then sacrificed, and DRGs of the lumbar segment (L3-6) were removed for determination of the number of Nav1.8 positive DRG neurons (by immunohistochemistry) and expression of Nav1.8 mRNA (by quantitative real-time polymerase chain reaction). Results Compared with group C, the visceral behavior scores and the number of Nav1.8 positive DRG neurons were significantly increased, and the expression of Nav1.8 mRNA was up-regulated in VP, D and DA groups (P<0.05). Compared with group VP, the visceral behavior score and the number of Nav1.8 positive DRG neurons were significantly decreased, and the expression of Nav1.8 mRNA was down-regulated in D and DA groups (P<0.05). Compared with group D, the visceral behavior scores and the number of Nav1.8 positive DRG neurons were significantly increased, and the expression of Nav1.8 mRNA was up-regulated in group DA (P<0.05). Conclusion The mechanism by which dexmedetomidine reduces acute visceral pain is related to activating alpha2 adrenergic receptors and to down-regulating the expression of Nav1.8 in DRG neurons of rats. Key words: Dexmedetomidine; Visceral pain; Receptors, adrenergic, alpha-2; Ganglia, spinal; NAV1.8 voltage-gated sodium channel