Obata Koichi, Yamanaka Hiroki, Dai Yi, Mizushima Toshiyuki, Fukuoka Tetsuo, Tokunaga Atsushi, Yoshikawa Hideki, Noguchi Koichi
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Exp Neurol. 2004 Jul;188(1):149-60. doi: 10.1016/j.expneurol.2004.03.012.
To elucidate the role of the degeneration of motor and sensory fibers in neuropathic pain, we examined the pain-related behaviors and the changes of brain-derived neurotrophic factor (BDNF) in the L4/5 dorsal root ganglion (DRG) and the spinal cord after L5 ventral rhizotomy. L5 ventral rhizotomy, producing a selective lesion of motor fibers, produced thermal hyperalgesia and increased BDNF expression in tyrosine kinase A-containing small- and medium-sized neurons in the L5 DRG and their central terminations within the spinal cord, but not in the L4 DRG. Furthermore, L5 ventral rhizotomy up-regulated nerve growth factor (NGF) protein in small to medium diameter neurons in the L5 DRG and also in ED-1-positive cells in the L5 spinal nerve, suggesting that NGF synthesized in the degenerative fibers is transported to the L5 DRG and increases BDNF synthesis. On the other hand, L5 ganglionectomy, producing a selective lesion of sensory fibers, produced heat hypersensitivity and an increase in BDNF and NGF in the L4 DRG. These data indicate that degeneration of L5 sensory fibers distal to the DRG, but not motor fibers, might influence the neighboring L4 nerve fibers and induce neurotrophin changes in the L4 DRG. We suggest that these changes of neurotrophins in the intact primary afferents of neighboring nerves may be one of many complex mechanisms, which can explain the abnormal pain behaviors after nerve injury. The ventral rhizotomy and ganglionectomy models may be useful to investigate the pathophysiological mechanisms of neuropathic pain after Wallerian degeneration in motor or sensory or mixed nerve.
为了阐明运动和感觉纤维变性在神经性疼痛中的作用,我们在L5腹侧神经根切断术后,检测了疼痛相关行为以及L4/5背根神经节(DRG)和脊髓中脑源性神经营养因子(BDNF)的变化。L5腹侧神经根切断术造成运动纤维的选择性损伤,导致热痛觉过敏,并使L5 DRG中含酪氨酸激酶A的中小神经元及其在脊髓内的中枢终末中的BDNF表达增加,但L4 DRG中未出现这种情况。此外,L5腹侧神经根切断术上调了L5 DRG中小至中等直径神经元以及L5脊神经中ED-1阳性细胞中的神经生长因子(NGF)蛋白,这表明变性纤维中合成的NGF被转运至L5 DRG并增加BDNF的合成。另一方面,L5神经节切除术造成感觉纤维的选择性损伤,导致热超敏反应以及L4 DRG中BDNF和NGF增加。这些数据表明,DRG远端的L5感觉纤维而非运动纤维的变性,可能会影响相邻的L4神经纤维,并诱导L4 DRG中的神经营养因子变化。我们认为,相邻神经完整初级传入纤维中神经营养因子的这些变化可能是众多复杂机制之一,这可以解释神经损伤后的异常疼痛行为。腹侧神经根切断术和神经节切除术模型可能有助于研究沃勒变性后运动或感觉或混合神经神经性疼痛的病理生理机制。