The upregulation of translocator protein (18 kDa) promotes recovery from neuropathic pain in rats.

Abstract

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.

• Authors: Xu-Hong Wei, Xiao Wei, Feng-Ying Chen, Ying Zang, Wen-Jun Xin, Rui-Ping Pang, Yuan Chen, Jun Wang, Yong-Yong Li, Kai-Feng Shen, Li-Jun Zhou, Xian-Guo Liu
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 33 Issue 4 Pg. 1540-51 (Jan 23 2013) ISSN: 1529-2401 [Electronic] United States
• PMID: 23345228 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Receptors, GABA-A
• Tspo protein, rat

Topics

• Animals
• Astrocytes (metabolism)
• Blotting, Western
• Carrier Proteins (biosynthesis)
• Cells, Cultured
• Coculture Techniques
• Enzyme-Linked Immunosorbent Assay
• Hyperalgesia (metabolism)
• Immunohistochemistry
• Male
• Neuralgia (metabolism)
• Neuroglia (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, GABA-A (biosynthesis)
• Spinal Nerves (injuries, metabolism)
• Up-Regulation