Kupers R, Yu W, Persson J K, Xu X J, Wiesenfeld-Hallin Z
Karolinska Institute, Department of Medical Laboratory Sciences and Technology, Huddinge University Hospital, Sweden.
Pain. 1998 May;76(1-2):45-59. doi: 10.1016/s0304-3959(98)00022-0.
Sensory abnormalities and changes in spontaneous behavior were examined after a photochemically induced ischemic lesion of the rat sciatic nerve. Male adult rats were anesthetized and the sciatic nerve was exposed. After the intravenous injection of a photosensitizing dye, erythrosin B, the exposed nerve was irradiated just proximal to the nerve trifurcation with light from an argon laser. Three different irradiation times were used, 30 s, 1 and 2 min. In sham-operated rats, the exposed sciatic nerve was irradiated for 2 min without prior injection of the erythrosin B. Rats were tested for the presence of mechanical, cold and heat allodynia or hyperalgesia. All the animals in the 1- and 2-min irradiation groups developed mechanical, cold and heat allodynia after nerve irradiation. A significant dose-dependent effect of laser exposure time was observed for all modalities tested (2 min > 1 min > 30 s = sham). The maximum effects were observed at 3 and 7 days postirradiation and remained present for up to 10 weeks. No significant contralateral effects were observed in any of the groups. In three separate groups of rats (1, 2 and 4 min of laser exposure), the presence of possible signs of spontaneous pain (paw shaking, paw elevation and freezing behavior) was tested. A significant and exposure time-dependent increase in spontaneous paw elevation and paw shaking was observed which was maximal at week 1, but resolved at 4 weeks (4 min > 2 min > 1 min > sham). In addition, animals in all ischemic groups, but not in the sham group, showed a significant increase in freezing behavior up to 4 weeks after nerve irradiation. Light microscopic evaluation of nerves removed 7 days post-irradiation, i.e. when maximal allodynia was observed, showed clear evidence of demyelination of large myelinated fibers. These data indicate that photochemically-induced peripheral nerve ischemia is associated with abnormal pain-related behaviors, including mechanical, thermal and cold allodynia and signs of spontaneous pain. The incidence and severity of the behavioral changes are clearly dependent on the exposure time and are probably due to, at least in part, a demyelinaton. These results partly confirm previous data using a similar technique and suggest that this may represent a new animal model for peripheral neuropathy of ischemic origin. The advantages of the present model are its good reproducibility and the fact that the nerve injury can be easily quantified and graded.
在大鼠坐骨神经进行光化学诱导缺血性损伤后，检测感觉异常和自发行为的变化。将成年雄性大鼠麻醉后暴露坐骨神经。静脉注射光敏染料赤藓红B后，用氩激光发出的光在神经三叉分支近端对暴露的神经进行照射。使用了三种不同的照射时间，分别为30秒、1分钟和2分钟。在假手术大鼠中，对暴露的坐骨神经照射2分钟，但事先不注射赤藓红B。对大鼠进行机械性、冷和热痛觉过敏或痛觉超敏检测。1分钟和2分钟照射组的所有动物在神经照射后均出现机械性、冷和热痛觉过敏。对于所有测试的感觉模式，均观察到激光照射时间具有显著的剂量依赖性效应（2分钟>1分钟>30秒=假手术组）。在照射后3天和7天观察到最大效应，并且这种效应持续长达10周。在任何组中均未观察到明显的对侧效应。在三组单独的大鼠中（激光照射1分钟、2分钟和4分钟），检测是否存在自发疼痛的可能迹象（爪子抖动、爪子抬起和僵住行为）。观察到自发爪子抬起和爪子抖动显著且与照射时间相关地增加，在第1周时达到最大值，但在第4周时恢复（4分钟>2分钟>1分钟>假手术组）。此外，所有缺血组的动物在神经照射后长达4周均表现出僵住行为显著增加，而假手术组则未出现这种情况。对照射后7天取出的神经进行光镜评估，即在观察到最大痛觉过敏时，发现有明显的大髓鞘纤维脱髓鞘证据。这些数据表明，光化学诱导的周围神经缺血与异常的疼痛相关行为有关，包括机械性、热和冷痛觉过敏以及自发疼痛迹象。行为变化的发生率和严重程度明显取决于照射时间，并且可能至少部分归因于脱髓鞘。这些结果部分证实了先前使用类似技术获得的数据，并表明这可能代表一种新的缺血性周围神经病动物模型。本模型的优点是其良好的可重复性以及神经损伤易于量化和分级这一事实。
