title: Expression of monocyte chemoattractant protein-1 and its induction by tumor necrosis factor receptor 1 in sensory neurons in the ventral rhizotomy model of neuropathic pain.
abstract: The expression and role of monocyte chemoattractant protein-1 (MCP-1) in the rat dorsal root ganglion (DRG) and spinal cord was evaluated in the lumbar 5 ventral rhizotomy (L5 VR) model of neuropathic pain. MCP-1 protein expression in the L4/L5 DRG neurons following L5 VR peaked after 3 days, and then declined. Immunohistochemistry showed that no MCP-1 immunoreactivity was observed in the spinal cord after L5 VR, while enzyme-linked immunosorbent assay (ELISA) revealed a small but significant increase in MCP-1 protein content. L5 VR resulted in robust and prolonged mechanical allodynia and thermal hyperalgesia. Administration of anti-MCP-1 neutralizing antibody before and at early time points after L5 VR resulted in a significant attenuation of mechanical allodynia and thermal hyperalgesia, while post-treatment had a weaker effect on established neuropathic pain. Extensive colocalization of tumor necrosis factor receptor 1 (TNFR1) and MCP-1 was observed in the L5 DRG following L5 VR, and treatment with TNFR1 antisense oligonucleotide reduced L5 VR-induced MCP-1 expression in L5 DRG neurons and neuropathic pain behaviors. MCP-1/chemokine (C-C motif) receptor 2 signaling has been proposed as a major regulator of macrophage trafficking. In contrast to the effect on pain behaviors, however, intrathecal administration of anti-MCP-1 neutralizing antibody had no effect on the L5 VR-induced increase in ED-1-immunoreactive macrophages in the L5 DRG and the distal stump of the transected L5 ventral root. These data indicate that increased MCP-1 in DRG neurons might participate in the initiation, rather than the maintenance, of neuropathic pain induced by L5 VR. Furthermore, increased MCP-1 in the DRG is induced by TNF-α/TNFR1 and has no effect on the infiltration of macrophages into the DRG following L5 VR.
authors.affiliation: Department of Anatomy, School of Medicine, Kyungpook National University, 2-101, Dongin Dong, Daegu 700-422, South Korea.
authors.forename: S-M
authors.initials: SM
authors.lastname: Jeon
authors.forename: J-K
authors.initials: JK
authors.lastname: Sung
authors.forename: H-J
authors.initials: HJ
authors.lastname: Cho
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000503:physiopathology; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D019051:Rhizotomy; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D018932:Chemokine CCL2; D047888:Receptors, Tumor Necrosis Factor, Type I