Early cytokine gene expression in mouse CNS after peripheral nerve lesion.
The generation and maintenance of pain after peripheral nerve injury are thought to be influenced by cytokine signaling. Chronic constriction injury (CCI) to mouse sciatic nerve leads to an early local upregulation of pro-inflammatory cytokines already 1 h after the lesion. The early regulation of cytokines in pain related CNS areas is largely unknown. We investigated cytokine regulation in the lumbar spinal cord, hypothalamus, thalamus, hippocampus, and frontal cortex in C57Bl/6J mice after lesioning the right sciatic nerve by CCI. The gene expression of tumor necrosis factor-alpha (TNF), interleukin (IL)-1beta, IL-4, and IL-10 was analyzed by quantitative real-time-PCR from 1 to 12 h after surgery or until values were back to baseline. CCI led to an early downregulation of TNF and IL-1beta mRNA in distinct brain areas and in the lumbar spinal cord with a maximum decrease within the first 6h after CCI. The reduction of TNF mRNA was inhibited by the NMDA receptor antagonist (+)-MK-801, while the calpain inhibitor MDL-28170 had no effect. Our results suggest an early cytokine regulation in the CNS after peripheral nerve lesion, which is opposite in direction to that in the periphery and which is partly mediated by the NMDA receptor system.
Uçeyler
Nurcan
N
Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany. ueceyler n@klinik.uni-wuerzburg.de
Tscharke
Andreas
A
Sommer
Claudia
C
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D016207:Cytokines / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000473:pathology* / Q000517:prevention & control; D013997:Time Factors
D016207:Cytokines; D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D016291:Dizocilpine Maleate