Effects Of Dexmedetomidine On Neuronal Apoptosis In Spinal Dorsal Horn In A Rat Model Of Chronic Neuropathic Pain

Objective To investigate the effects of dexmedetomidine (Dex) on the neuronal apoptosis in spinal dorsal horn and the expressions of caspase-3and Bcl-2which are the two genes closely related with apoptosis in a rat model of chronic neuropathic pain,and to explore the therapeutic effects and potential mechanism of dexmedetomidine in the neuropathic pain,which may provide theoretial basis for treatment.Methods Seventy-two adult male SD rats weighing180-220g were randomly divided into3groups (n=24each):group I sham operation (S); group II chronic constrictive injury (CCI); group III Dex+CCI(D). Two ligatures were placed on right sciatic nerve at1mm intervals with4-0silk thread in group II and III. In group III Dex50μg/kg was injected intraperitoneally (IP) once a day starting from the end of operation until the animals were sacrificed. Paw withdrawal threshold to mechanical stimulation with von Frey filament (PWT) and paw withdrawal latency to thermal stimulation (PWL) were measured at one day before (To baseline) and on the3rd,7th and14th day after operation (T1,2.3). Six animals were killed 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-2and caspase-3expression (by immune-histochemistry). Other two rats were observed the spinal cord dorsal horn neuron by transmission electron microscopy.Results CCI significantly decreased PWT and PWL, increased Bcl-2and caspase-3expression at T1,2,3and induced apoptosis in spinal dorsal horn neurons in group II as compared with group S (I). Intraperitoneal Dex significantly attenuated CCI-induced mechanical and thermal hyperalgesia and neuronal apoptosis in group D (III) as compared with group II. Dex IP further increased Bcl-2expression but decreased caspase-3expression in group III as compared with group II.Conclusions Reduction in neuronal apoptosis in spinal dorsal horn is involved in the attenuation of neuropathic pain by dexmedetomidine.