Enhanced production of monocyte chemoattractant protein-1 in the dorsal root ganglia in a rat model of neuropathic pain: possible involvement in the development of neuropathic pain.
Chemokines are a family of peptides originally identified as the factors regulating the migration of leukocytes in inflammatory and immune responses. Recently, they have been shown to be produced in the central and peripheral nervous systems under various pathological conditions and act on neuronal and glial cells. In this study, we examined the production of monocyte chemoattractant protein-1 (MCP-1), a well-characterized chemokine, in dorsal root ganglia (DRG) in a rat model of neuropathic pain. Partial ligation of the sciatic nerve induced mechanical allodynia in the ipsilateral hindpaw with weaker allodynia in the contralateral one. Immunohistochemical analyses revealed that the number of MCP-1 immunoreactivity (ir)-positive cells was increased in the ipsilateral DRG. The increase started by 4h after the ligation, peaked at 24h and continued to at least 48 h. The weaker but significant increase was observed in the contralateral DRG. Double immunofluorescent staining demonstrated that almost all of the MCP-1ir-positive cells were neuronal cells. In situ hybridization histochemistry showed that MCP-1 mRNA expression was markedly upregulated in the ipsilateral DRG with weaker increase in the contralateral one at 24 h after the ligation, indicating that the elevation in MCP-1ir detected by immunohistochemistry was due to an upregulation of MCP-1 production by the DRG neurons themselves. Furthermore, intrathecal administration of MCP-1 induced mechanical allodynia. These results suggest that MCP-1 produced in the DRG neurons is involved in the development of mechanical allodynia induced by nerve injury.
Tanaka
Takahiro
T
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Minami
Masabumi
M
Nakagawa
Takayuki
T
Satoh
Masamichi
M
D000818:Animals; D018932:Chemokine CCL2 / Q000008:administration & dosage / Q000096:biosynthesis*; D004195:Disease Models, Animal; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000378:metabolism*; D006614:Hindlimb / Q000294:innervation; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007278:Injections, Spinal; D008026:Ligation; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries
D018932:Chemokine CCL2; D012333:RNA, Messenger