Hudspith M J, Harrisson S, Smith G, Bountra C, Elliot P J, Birch P J, Hunt S P, Munglani R
Anaesthesia and Pain Relief, University Department of Anaesthesia, Box 93, University of Cambridge Clinical School, Addenbrookes Hospital, Hills Road, Cambridge, CB2 2QQ,
Brain Res. 1999 Mar 20;822(1-2):220-7. doi: 10.1016/s0006-8993(99)01161-0.
Chronic constriction injury (CCI) of the sciatic nerve results in persistent mechanical hyperalgesia together with Fos protein expression in the lumbar spinal cord. We have examined the relationship between mechanical hyperalgesia and Fos expression within the lumbar spinal cord on days 14, 35 and 55 after either CCI or sham operation. To determine the role of NMDA receptor mechanisms in the maintenance of hyperalgesia and Fos expression, the NMDA antagonist MK-801 (0.3 mg kg-1 s.c.) was administered daily on days 28 to 34 after operation. CCI animals developed unilateral hind limb hyperalgesia that persisted unchanged from days 14 to 55 of the study. MK-801 treatment reduced hyperalgesia by 57% (p=0.02) on day 35 in CCI animals but did influence hyperalgesia at day 55. In the spinal cord, Fos positive cells were present bilaterally throughout laminae 3-10 at all time points examined in both CCI and sham group animals. Fos counts ipsilateral to the side of injury in laminae 3-10 correlated significantly with hyperalgesia scores in the CCI but not sham animals. MK-801 treatment resulted in a suppression of Fos expression in ipsilateral laminae 3-4 (p=0.0017) and laminae 5-10 (p=0.0026) of CCI animals on day 35. Fos expression in sham group animals was not inhibited by MK-801 treatment at day 35. These results indicate that Fos expression is maintained by differing mechanisms following nerve injury or sham operation. The functional consequences of Fos expression following nerve injury and sham operation are discussed.
坐骨神经慢性压迫损伤（CCI）会导致持续的机械性痛觉过敏以及腰椎脊髓中Fos蛋白的表达。我们研究了在CCI或假手术后第14、35和55天，腰椎脊髓内机械性痛觉过敏与Fos表达之间的关系。为了确定NMDA受体机制在维持痛觉过敏和Fos表达中的作用，在术后第28至34天每天给予NMDA拮抗剂MK-801（0.3mg/kg皮下注射）。CCI动物出现单侧后肢痛觉过敏，在研究的第14至55天持续不变。MK-801治疗在第35天使CCI动物的痛觉过敏降低了57%（p=0.02），但在第55天对痛觉过敏没有影响。在脊髓中，在CCI组和假手术组动物的所有检查时间点，双侧第3 - 10层均存在Fos阳性细胞。在CCI组而非假手术组动物中，第3 - 10层损伤侧同侧的Fos计数与痛觉过敏评分显著相关。MK-801治疗导致第35天CCI动物同侧第3 - 4层（p=0.0017）和第5 - 10层（p=0.0026）的Fos表达受到抑制。在第35天，MK-801治疗未抑制假手术组动物的Fos表达。这些结果表明，神经损伤或假手术后Fos表达由不同机制维持。本文讨论了神经损伤和假手术后Fos表达的功能后果。
