Immunocytochemical localization of TNF type 1 and type 2 receptors in the rat spinal cord.
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.
Holmes
Gregory M
GM
Laboratory of Autonomic Neuroscience, Pennington Biomedical Research Center, 6400 Perkins Road, Louisiana State University, Baton Rouge, LA 70808, USA. HolmesGM@pbrc.edu
Hebert
Sadie L
SL
Rogers
Richard C
RC
Hermann
Gerlinda E
GE
D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000737:chemistry / Q000293:injuries / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000032:analysis* / Q000096:biosynthesis; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000032:analysis* / Q000096:biosynthesis; D013116:Spinal Cord / Q000737:chemistry* / Q000378:metabolism
D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II