The upregulation of translocator protein (18 kDa) promotes recovery from neuropathic pain in rats.
At present, effective drug for treatment of neuropathic pain is still lacking. Recent studies have shown that the ligands of translocator protein (TSPO, 18 kDa), a peripheral receptor for benzodiazepine, modulate inflammatory pain. Here, we report that TSPO was upregulated in astrocytes and microglia in the ipsilateral spinal dorsal horn of rats following L5 spinal nerve ligation (L5 SNL), lasting until the vanishing of the behavioral signs of neuropathic pain (∼50 d). Importantly, a single intrathecal injection of specific TSPO agonists Ro5-4864 or FGIN-1-27 at 7 and 21 d after L5 SNL depressed the established mechanical allodynia and thermal hyperalgesia dramatically, and the effect was abolished by pretreatment with AMG, a neurosteroid synthesis inhibitor. Mechanically, Ro5-4864 substantially inhibited spinal astrocytes but not microglia, and reduced the production of tumor necrosis factor-α (TNF-α) in vivo and in vitro. The anti-neuroinflammatory effect was also prevented by AMG. Interestingly, TSPO expression returned to control levels or decreased substantially, when neuropathic pain healed naturally or was reversed by Ro5-4864, suggesting that the role of TSPO upregulation might be to promote recovery from the neurological disorder. Finally, the neuropathic pain and the upregulation of TSPO by L5 SNL were prevented by pharmacological blockage of Toll-like receptor 4 (TLR4). These data suggested that TSPO might be a novel therapeutic target for the treatment of neuropathic pain.
Pain Research Center and Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
Xu-Hong
XH
Wei
Xiao
X
Wei
Feng-Ying
FY
Chen
Ying
Y
Zang
Wen-Jun
WJ
Xin
Rui-Ping
RP
Pang
Yuan
Y
Chen
Jun
J
Wang
Yong-Yong
YY
Li
Kai-Feng
KF
Shen
Li-Jun
LJ
Zhou
Xian-Guo
XG
Liu
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D006930:Hyperalgesia / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009437:Neuralgia / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000096:biosynthesis*; D013127:Spinal Nerves / Q000293:injuries / Q000378:metabolism; D015854:Up-Regulation
D002352:Carrier Proteins; D011963:Receptors, GABA-A; C069997:Tspo protein, rat