Analgesic effcacy andspinal neurotoxicity of intrathecal different doses of dexmedetomidine in rats

Abstract

：Objective To investigatethe analgesic efficacy and spinal neurotoxicity of intrathecal (IT) different doses ofdexmedetomidine in rats. Methods Sixty male SD rats weighing 180-220 g were randomlydivided into 5 groups ( n = 12 each): groupnormal control (group C); group IT normalsaline (group N); different doses of dexmedetomidine groups received IT dexmedetomidine0.75, 1.50 and 3.00 μg/kg respectively (groups D1.3). Paw withdrawalthreshold to mechanical stimulation (PWMT)with yon Frey filaments and tail flick latency(TFL) to a thermal nociceptive stimulus were measured before (To, baseline) and at 30 or60rin after IT dexmedetomidine or normal saline administration (T1, T2 ) and the percentageof the maximum possible effect ( MPE ) was calculated. Lumbar segment of the spinal cord (L4-6 ) was removed for microscopic examination and determination of c-Fos expression (byimmuno-histochemistry) at 7, 24 and 48 h after IT dexmedetomidine or normal salineadministration. Results PWMT, TFL and the percentage of MPE were significantly increasedafter IT dexmedetomidine as compared with the baseline values at T0 in groups D1-3 ( P＜ 0.05). PWMT was significantly higher at T1 and TFLand the percentage of MPE were higher at T2 in groups D1-3 than in groups C and N,and ingroup D3 than in groups D1,2 ( P ＜ 0.05). At 7,24 h after ITdexmedetomidine c-Fos protein expression was significantly higher in group D3 than ingroups C and N( P ＜ 0.05). There was nosignificant difference in c-Fos expression at 48 h after IT dexmedetomidine between groupD3 and groups C and N ( P ＞ 0.05 ). At 24 h after ITdexmedetomidine c-Fos protein expression was significantly higher in group D3 than inother 4 groups( P ＜ 0.05). Slight spinal cord injury was observed at 24 h after IT dexmedetomidine ingroup D3. Conclusion IT dexmedetomidine has antinociceptive effect. High dosedexmedetomidine IT can produce transient reversible toxicity to the spinal cord. Key words: Dexmedetomidine; Injections, spinal; Analgesia; Drugtoxicity