Pathphysiologic mechanism of radicular pain in lumbar disc herniation.

本研究旨在探讨腰椎间盘突出症神经根性疼痛的病理生理机制。在该实验模型中，自体髓核（NP）和纤维环（AF）移植到腰神经根产生机械和热痛觉过敏，这是大鼠的疼痛相关行为。分别硬膜外注射选择性磷脂酶A_2（PLA_2）抑制剂可使伤害性机械刺激的超敏反应消失。应用AF产生的热痛觉过敏减轻和废除硬膜外注射生理盐水和一氧化氮（NO）合酶的抑制剂之一，分别。应用逆转录聚合酶链反应技术，检测神经根和背根神经节中白细胞介素1 β（IL-1 β）、白细胞介素6（IL-6）、磷脂酶A_2（PLA_2）和诱导型一氧化氮合酶（iNOS）基因的表达。术后1周，仅NP组大鼠IL-1 β、PLA_2和iNOS mRNA表达明显升高，术后2、4周降至基础水平。而NP组术后4周时IL-6的表达已检测到。本研究还旨在阐明机械压迫神经根和NP所产生的疼痛机制。NP组和蚕丝+NP组，其中机械压迫是通过蚕丝结扎产生的，分别表现出机械和热痛觉过敏的证据。组织学分析显示，与NP组相比，丝和丝+NP组的神经根上有较少的较大直径的有髓轴突和较多的较小直径的有髓轴突。这些结果提示，椎间盘诱导的IL、PLA_2和NO等化学介质参与了腰椎间盘突出症痛性神经根病的病理生理机制，而与神经根的组织学改变无关。

The purpose of this study was to determine pathophysiological mechanism of radicular pain in lumbar disc herniation. In this experimental model, autologous nucleus pulposus (NP) and anulus fibrosus (AF) transplanted to lumbar nerve roots produced mechanical and thermal hyperalgesia, which is a pain related behavior in the rat., respectively. Epidural injection of a selective inhibitor for phospholipase A_2 (PLA_2) resulted in the disappearance of hypersensitivity to noxious mechanical stimuli. Thermal hyperalgesia produced by application of the AF was abated and abolished by epidural injections of saline and one of the inhibitors for nitric oxide (NO) synthase, respectively. Utilizing a reverse transcription polymerase chain treaction echnique, the expression of interleukin-1beta (IL-1beta), interleukin-6(IL-6), PLA_2 and inducible NO synthase (iNOS) genes was evaluated in the nerve root and dorsal root ganglion. The expression of IL-1beta, PLA_2 and iNOS messenger RNAs only in rats treated with the NP were clearly increased at 1 week postoperatively and decreased to the basal level at 2 and 4 weeks postoperatively. However, the expression of IL-6 in the NP group were detected by 4 weeks postoperatively. This study was also designed to elucidate the pain mechanism produced by mechanical compression of the nerve root and NP.Rats in the NP group and the silk+NP group, which mechanical compression was produced by silk ligation, showed evidence of mechanical and thermal hyperalgesia, respectively. Histological analysis revealed that there were less of the larger and more of the smaller diameter myelinated axons on the nerve roots in both of the silk and silk+NP groups, compared with that in the NP groups. These results suggest that chemical mediators such as ILs, PLA_2 and NO,induced by intervertebral discs, are involved in the pathophysiological mechanisms of painful radiculopathy in lumbar disc herniations but not histological changes of the nerve root.