Munglani R, Hudspith M J, Fleming B, Harrisson S, Smith G, Bountra C, Elliot P J, Birch P J, Hunt S P
University Department of Anaesthesia, University of Cambridge Clinical School, Addenbrookes Hospital, Hills Road, Box 93, Cambridge, CB2 2QQ, UK.
Brain Res. 1999 Mar 20;822(1-2):210-9. doi: 10.1016/s0006-8993(99)01160-9.
The unilateral sciatic nerve chronic constriction injury (CCI) model of Bennett and Xie [G.J. Bennett, Y.-K. Xie, A peripheral neuropathy in rat that produces disorders of pain sensation like those seen in man, Pain, 33 (1988) 87-108] shows features of a neuropathic pain state. We examined mechanical hyperalgesia and Fos protein staining in the lumbar spinal cord 1, 7, 14 and 28 days after unilateral CCI to the sciatic nerve or sham operation. In addition, we examined the effect of the NMDA antagonist MK-801 (0.3 mg/kg s.c. administered 30 min prior to and 6 h following operation) on Fos expression and hyperalgesia at 28 days. CCI animals were hyperalgesic compared to the sham operated animals at 14 and 28 days post injury. MK-801 reduced hyperalgesia by 68% in CCI animals on day 28 (p=0.0001). In the spinal cord, Fos positive cells were present bilaterally in deeper laminae in both sham and CCI animals at all time points examined. Relatively few Fos positive cells were present in laminae 1-2 at any time point examined. At days 1 and 7, there were increased numbers of Fos positive cells ipsilaterally in the deeper laminae of the spinal cord in CCI animals compared to sham animals, but by 14 and 28 days Fos counts were similar in sham and CCI despite the obvious behavioural differences between the two groups. Fos counts ipsilateral to the injury in laminae 3-10 correlated with hyperalgesia scores in the CCI but not sham animals. Analysis at the 28-day time point showed that MK-801 differentially affected Fos expression: MK-801 significantly reduced the Fos count bilaterally in laminae 3-10 in the CCI but not in the sham group animals. These results indicate that Fos expression is initiated by different peripheral and central mechanisms following nerve injury or sham operation.
贝内特和谢的单侧坐骨神经慢性压迫损伤（CCI）模型[G.J. 贝内特、Y.-K. 谢，一种在大鼠中产生类似人类疼痛感觉障碍的周围神经病变，《疼痛》，33（1988）87 - 108]呈现出神经性疼痛状态的特征。我们在单侧坐骨神经CCI或假手术后1、7、14和28天，检测了腰椎脊髓中的机械性痛觉过敏和Fos蛋白染色情况。此外，我们还检测了NMDA拮抗剂MK - 801（在手术前30分钟和手术后6小时皮下注射0.3 mg/kg）对28天时Fos表达和痛觉过敏的影响。与假手术动物相比，CCI动物在损伤后14天和28天出现痛觉过敏。在第28天，MK - 801使CCI动物的痛觉过敏降低了68%（p = 0.0001）。在脊髓中，在所有检测时间点，假手术和CCI动物的深层板层双侧均存在Fos阳性细胞。在任何检测时间点，第1 - 2层中存在的Fos阳性细胞相对较少。在第1天和第7天，与假手术动物相比，CCI动物脊髓深层板层同侧的Fos阳性细胞数量增加，但到第14天和28天，尽管两组动物存在明显的行为差异，但假手术组和CCI组的Fos计数相似。CCI动物第3 - 10层损伤同侧的Fos计数与痛觉过敏评分相关，而假手术动物则不然。在第28天时间点的分析表明，MK - 801对Fos表达有不同影响：MK - 801显著降低了CCI组动物第3 - 10层双侧的Fos计数，但对假手术组动物无此作用。这些结果表明，神经损伤或假手术后，Fos表达由不同的外周和中枢机制启动。
