title: Src/p38 MAPK pathway in spinal microglia is involved in mechanical allodynia induced by peri-sciatic administration of recombinant rat TNF-α.
abstract: Our previous work has shown that peri-sciatic administration of recombinant rat TNF-α (rrTNF) induces mechanical allodynia and up-regulation of TNF-α in the spinal dorsal horn of rats; however, the underlying mechanisms remain unknown. In the current study, we found that the levels of phosphorylated Src-family kinases (p-SFKs) and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) were significantly increased in bilateral lumbar spinal dorsal horn on day 3 after rrTNF administration. Double immunofluorescence staining revealed that p-SFKs and p-p38 MAPK were nearly restricted to the microglia. Intrathecal delivery of SFKs inhibitor PP2 or p38 MAPK inhibitor SB203580, started 30 min before rrTNF administration and given once daily thereafter for 7 days, blocked mechanical allodynia in bilateral hind paws and increase of TNF-α expression in the spinal dorsal horn. Moreover, PP2 inhibited the up-regulation of p-p38 MAPK induced by rrTNF. We also found that intrathecal injection of TNF-α neutralization antibody alleviated mechanical allodynia in bilateral hind paws and suppressed up-regulation of p-SFKs and p-p38 MAPK. These results suggest that activation of the SFKs/p38 MAPK pathway in microglia and subsequent TNF-α expression in the spinal dorsal horn may contribute to the mechanical hyperalgesic state induced by peri-sciatic administered rrTNF.
authors.affiliation: School of Medical Technology & Nursing, Shenzhen Polytechnic, Xili Lake, Nanshan District, Shenzhen 518055, China.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Li
authors.forename: Xu-Hong
authors.initials: XH
authors.lastname: Wei
authors.forename: Zhen-He
authors.initials: ZH
authors.lastname: Lu
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: Chen
authors.forename: Qiao-Dong
authors.initials: QD
authors.lastname: Huang
authors.forename: Qing-Juan
authors.initials: QJ
authors.lastname: Gong
mesh_terms: D000818:Animals; D006930:Hyperalgesia / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007278:Injections, Spinal; D020935:MAP Kinase Signaling System; D008297:Male; D017628:Microglia / Q000378:metabolism*; D010146:Pain / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D019061:src-Family Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: Microglia; Pathological pain; Src-family kinases; TNF-α; p38 mitogen-activated protein kinase