Ringkamp M, Eschenfelder S, Grethel E J, Häbler H J, Meyer R A, Jänig W, Raja S N
Department of Neurosurgery, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Pain. 1999 Feb;79(2-3):143-53. doi: 10.1016/s0304-3959(98)00186-9.
The L5 spinal nerve ligation model of neuropathic pain in rats has been proposed as a model for sympathetically maintained pain (SMP) based on the effects of surgical or chemical sympathectomy on nerve injury induced behavior. In an attempt to confirm that the lesion produces an animal model of SMP, surgical sympathectomies were independently conducted in two different laboratories (Johns Hopkins and University Kiel) using male Sprague-Dawley (n = 30) or Wistar rats (n = 14). The L5 spinal nerve was ligated or cut and ligated. Using von Frey hairs, paw withdrawal threshold and incidence of paw withdrawal were tested concurrently before and after the sympathectomy. The sympathectomy was either verified by (a) glyoxylic acid staining of peripheral blood vessels of the hindpaw or (b) skin temperature measurements of the hindpaws. To blind the experimenter, surgeries and behavioral tests were performed by two different investigators and a sham sympathectomy was performed at Johns Hopkins. Decreased paw withdrawal thresholds and increased frequencies of paw withdrawal on the lesioned side were observed after the L5 lesion. Thus, the L5 spinal nerve ligation resulted in behavioral signs of allodynia and hyperalgesia to mechanical stimuli. Lumbar surgical sympathectomy 1-3 weeks after the lesion or prior to lesion with bilateral removal of the sympathetic ganglia L2-L4, however, did not reverse or prevent the behavioral changes induced by the nerve injury. The lack of effect of the sympathectomies was independent of the testing paradigm used. Experiments in Wistar and Sprague-Dawley rats yielded the same results. Potential reasons for the discrepancies between the present study and earlier reports are discussed. These results indicate that an L5 spinal nerve injury rat model is not a reliable model for SMP.
基于手术或化学性交感神经切除术对神经损伤诱导行为的影响,大鼠L5脊髓神经结扎性神经病理性疼痛模型已被提出作为交感神经维持性疼痛(SMP)的模型。为了证实该损伤产生了SMP动物模型,在两个不同实验室(约翰霍普金斯大学和基尔大学)分别使用雄性Sprague-Dawley大鼠(n = 30)或Wistar大鼠(n = 14)进行了手术性交感神经切除术。结扎或切断并结扎L5脊髓神经。在交感神经切除术前和术后同时使用von Frey毛发测试爪部撤离阈值和爪部撤离发生率。通过(a)后爪外周血管的乙醛酸染色或(b)后爪皮肤温度测量来验证交感神经切除术。为使实验者不知情,手术和行为测试由两名不同的研究人员进行,并且在约翰霍普金斯大学进行了假交感神经切除术。L5损伤后,观察到损伤侧爪部撤离阈值降低和爪部撤离频率增加。因此,L5脊髓神经结扎导致对机械刺激的异常性疼痛和痛觉过敏的行为体征。然而,在损伤后1 - 3周或在损伤前双侧切除交感神经节L2 - L4进行腰部手术性交感神经切除术,并未逆转或预防神经损伤诱导的行为变化。交感神经切除术无效与所使用的测试范式无关。在Wistar大鼠和Sprague-Dawley大鼠中进行的实验得出了相同的结果。讨论了本研究与早期报告之间差异的潜在原因。这些结果表明,L5脊髓神经损伤大鼠模型不是SMP的可靠模型。