Effects of dexmedetomidine on neuronal apoptosis in spinal dorsal horn in a rat model of chronic neuropathic pain

Abstract

Objective To investigate the effects of dexmedetomidine (Dex) on the neuronal apoptosis in spinal dorsal horn in a rat model of chronic neuropathic pain.Methods Seventy-two adult male SD rats weighing 180-220 g were randomly divided into 3 groups ( n =24 each):sham operation group (group S) ; chronic constrictive injury (CCI) group; Dex + CCI group (group D).Two ligatures were placed on right sciatic nerve at 1 mm intervals with 4-0 silk thread in groups CCI and D.In group D Dex 50 μg/kg was injected intraperitoneally once a day starting from the end of operation until the animals were sacrificed.Paw withdrawal threshold to mechanical stimulation with yon Frey filament (PWT) and paw withdrawal latency to thermal stimulation (PWL) were measured at one day before (T0,baseline) and on the 3rd,7th and 14th day after operation (T1,2,3).Six animals were sacrificed at each time points (T1,2,3) after the measurement of PWT and PWL.Their lumbar segments (L4,5)were removed for examination with transmission electron microscope and detection of Bcl-2 and caspase-3 expression (by immune-histochemistry).Results CCI significantly decreased PWT and PWL,increased Bcl-2 and caspase-3 expression at T1,2,3 and induced apoptosis in spinal dorsal horn neurons in group CCI as compared with group S.Intraperitoneal Dex significantly attenuated CCI-induced mechanical and thermal hyperalgesia and neuronal apoptosis in group D as compared with group CCI.Dex injected intraperitoneally further increased Bcl-2 expression but decreased caspase-3 expression in group D as compared with group CCI.Conclusion Reduction in neuronal apoptosis in spinal dorsal horn is involved in the attenuation of neuropathic pain by Dex. Key words: Dexmedetomidine; Apoptosis; Posterior horn cells; Neuralgia