Tumor necrosis factor-alpha induces long-term potentiation of C-fiber evoked field potentials in spinal dorsal horn in rats with nerve injury: the role of NF-kappa B, JNK and p38 MAPK.
Compelling evidence has shown that in hippocampus tumor necrosis factor alpha (TNF-alpha) at pathological concentration inhibits long-term potentiation (LTP), a synaptic model of learning and memory. In the present work we investigated the role of TNF-alpha in LTP of C-fiber evoked field potentials in spinal dorsal horn, which is relevant to pathological pain. We showed that spinal application of TNF-alpha affected neither basal synaptic transmission mediated by C-fibers nor spinal LTP of C-fiber evoked field potentials induced by tetanic stimulation in intact rats. However, in rats with neuropathic pain, produced by either lumbar 5 ventral root transection (L5 VRT) or spared nerve injury (SNI), spinal application of TNF-alpha induced LTP of C-fiber evoked field potentials. Spinal application of JNK inhibitor (SP600125) or p38 MAPK inhibitor (SB203580) did not affect the spinal LTP induced by tetanic stimulation in intact rats, but completely blocked LTP induced by TNF-alpha in L5 VRT rats. NF-kappa B (NF-kappaB) inhibitor (PDTC) also blocked LTP induced by TNF-alpha. These results suggest that TNF-alpha and its downstream molecules may have no acute effect on spinal synaptic transmission in intact animals and induce LTP in rats with neuropathic pain produced by nerve injury.
Liu
Yan-Ling
YL
Pain Research Center, Zhongshan Medical School of Sun Yat-sen University, 510089 Guangzhou, PR China.
Zhou
Li-Jun
LJ
Hu
Neng-Wei
NW
Xu
Ji-Tian
JT
Wu
Chang-You
CY
Zhang
Tong
T
Li
Yong-Yong
YY
Liu
Xian-Guo
XG
D000818:Animals; D001522:Behavior, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007839:Functional Laterality; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000473:pathology* / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D020929:Mitogen-Activated Protein Kinase Kinases