Holmes Gregory M, Hebert Sadie L, Rogers Richard C, Hermann Gerlinda E
Laboratory of Autonomic Neuroscience, Pennington Biomedical Research Center, 6400 Perkins Road, Louisiana State University, Baton Rouge, LA 70808, USA.
Brain Res. 2004 Oct 29;1025(1-2):210-9. doi: 10.1016/j.brainres.2004.08.020.
Tumor necrosis factor-alpha (TNF-alpha) is secreted in numerous pathophysiological situations by a variety of cell types. Tactile hypersensitivity (allodynia) is one component of a constellation of "illness behaviors" triggered by TNF-alpha. TNF-alpha is also implicated in neuropathic pain after peripheral nerve injury and apoptosis after spinal cord injury (SCI). It is possible that SCI, illness- and peripheral injury-induced hypersensitivity may share a similar spinal mediated etiology. These studies identify the locus of type-1 TNF (TNFR1 or p55) and type-2 TNF (TNFR2 or p75) receptors within the spinal cord. At all spinal levels, TNFR1 receptor immunoreactivity (TNFR1-ir) was constitutively expressed on cells and afferent fibers within the dorsal root ganglia, afferent fibers of the dorsal root, dorsal root entry zone (REZ) and within lamina I and II of the dorsal horn. Unilateral dorsal rhizotomy eliminated the characteristic pattern of TNFR1-ir at the rhizotomized REZ. In contrast, TNFR2-ir was consistently absent from dorsal root fibers and the region of the root entry zone. Consistent with our previous report, medullary afferent fibers in the solitary tract and spinal trigeminal tract labelled for TNF1-ir, but did not express TNFR2-ir. The presence TNFR1-ir on dorsal horn afferents, suggests that TNF-alpha may be a mechanism responsible for tactile hypersensitivity during illness. The presence of TNFR1 receptors, and perhaps their long-term activation or plasticity, may also play a critical role in the chronic allodynia and hyperreflexia observed after SCI or peripheral nerve damage.
肿瘤坏死因子-α（TNF-α）在多种病理生理情况下由多种细胞类型分泌。触觉超敏反应（异常性疼痛）是由TNF-α引发的一系列“疾病行为”的一个组成部分。TNF-α还与周围神经损伤后的神经性疼痛以及脊髓损伤（SCI）后的细胞凋亡有关。SCI、疾病和周围损伤引起的超敏反应可能具有相似的脊髓介导病因。这些研究确定了脊髓内1型TNF（TNFR1或p55）和2型TNF（TNFR2或p75）受体的位置。在所有脊髓节段，TNFR1受体免疫反应性（TNFR1-ir）在背根神经节内的细胞和传入纤维、背根传入纤维、背根进入区（REZ）以及背角I层和II层内持续表达。单侧背根切断术消除了切断侧REZ处TNFR1-ir的特征性模式。相比之下，背根纤维和根进入区区域始终不存在TNFR2-ir。与我们之前的报告一致，孤束和脊髓三叉束中的延髓传入纤维标记为TNF1-ir，但不表达TNFR2-ir。背角传入纤维上存在TNFR1-ir，表明TNF-α可能是疾病期间触觉超敏反应的一种机制。TNFR1受体的存在，以及它们可能的长期激活或可塑性，也可能在SCI或周围神经损伤后观察到的慢性异常性疼痛和反射亢进中起关键作用。
