摘要
目的探讨背根神经节和脊髓背角磷酸化cAMP反应元件结合蛋白(pCREB)表达在慢性压迫性神经损伤(CCI)致神经病理性疼痛大鼠痛觉过敏中的作用。方法成年雌性SD大鼠32只, 体重230-270 g,随机分为4组(n=8):空白组、sham组、CCI 2w组和CCI 4w组。CCI前测定痛阈[机械缩足反射阈值(MWT)和热缩足反射潜伏期(TWL)]基础值,CCI后(空白组、sham组和CCI 2w组于 CCI 14 d;CCI 4w组于CCI 28 d)再次测定痛阈。最后一次测定痛阈后次日,取k4,5脊髓和L5背根神经节,免疫组织化学染色,计数pCREB免疫反应阳性(pCREB-IR)神经细胞数量。结果 MWT:CCI后 sham组、CCI 2w组、CCI 4w组均低于基础值,CCI后sham组低于空白组,CCI 2w组低于sham组(P< 0．01);TWL:CCI 2w组短于基础值,CCI 2w组短于sham组,CCI后CCI 4w组长于CCI 2w组(P<0.01)。 sham组背根神经节pCREB-IR神经细胞数量多于空白组,CCI 2w组背根神经节及脊髓背角pCREB-IR 神经细胞数量多于sham组,CCI 4w组背根神经节及脊髓背角pCREB-IR神经细胞数量少于CCI 2w组 (P<0．05或0．01)。结论 CCI致慢性神经病理性疼痛大鼠背根神经节和脊髓背角pCREB表达增加,这可能是外周神经损伤后中枢和外周敏感化的分子机制。
Objective To determine whether chronic constriction injury （CCI） to sciatic nerve is associated with changes in the phosphorylation of CREB in dorsal root ganglia （DRG） and superficial dorsal horn neurons of the spinal cord. Methods Thirty-two adult female SD rats weighing 230-270 g were randomly divided into4 groups （n=8 each）： Ⅰ blank control; Ⅱ sham operation; Ⅲ CCI 2w and IV CCI 4w. The animals were anesthetized with intraperitoneal pentobarbital 40 mg·kg^- 1 . Right sciatic nerve was exposed and 4 ligatures were placed on the fight sciatic nerve at 1 mm interspace with 3-0 silk suture. Paw withdrawal threshold to mechanical stimulation （von Frey filament） applied to plantar surface （MWT） and paw withdrawal latency to thermal stimulation （radiant heat） （TWL） were measured before operation （baseline） and 14 days （group Ⅰ ,Ⅱ and Ⅲ ） or 28 days （group Ⅳ ） after nerve ligation. The animals were killed the next day and the L4-5 segment of the spinal cord and I4-5 dorsal root ganglion were removed for determination of expression of phosphorylated-CREB-immunoreaction（pCREB-IR） using immuno-histochemistry. The pCREB-IR cells both in DRG and superficial dorsal horn neurons were quantified and analyzed. Results The animals developed mechanical and thermal hyperalgesia on the 14th day after CCI （in group CCI 2w）. The hyperalgesia was greatly attenuated on the 28th day after CCI. Interestingly enough the animals in sham operation group （ Ⅱ ） also developed mechanical hyperalgesia to some extent on the 14th day after operation. The number of pCREB-IR ceils was significantly increased in the ipsilateral L5 DRG and superficial dorsal horn in group Ⅲ （CCI 2w） as compared to sham operation group （P 〈 0.01 ）, but was significantly decreased in group Ⅳ （CCI 4w）. The number of phosphorylated CREB-IR cell was also significantly larger in the ipsilateral DRGs in sham operation group than in blank control group. Conclusion CCI to sciatic nerve increases CREB phosphorylation both in DRG and in superficial dorsal horn neurons of the spinal cord, which may partly explain the molecular mechanisms underlying central and peripheral sensitization following peripheral nerve injury.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2006年第2期173-176,共4页
Chinese Journal of Anesthesiology
基金
江苏省教育厅省级重点实验室开放课题(KJS01082)
关键词
神经痛
神经节
脊
脊髓
DNA结合蛋白
环AMP反应性
Neuralgia
＇ Ganglia, spinal
Spinal cord
DNA-Binding protein, cyclic AMP-responsive
