| Abstract No.: | C-C3075 |
| Country: | Canada |
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| Title: | INHIBITION OF SPINAL MICROGLIOSIS ATTENUATES NERVE INJURY INDUCED-HYPERSENSITIVITY S ECHEVERRY, XQ SHI, J ZHANG
THE ALAN EDWARDS CENTRE FOR RESEARCH ON PAIN, MCGILL UNIVERSITY, MONTREAL, QC, CANADA
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| Authors/Affiliations: | 1 Stefania Echeverry*;
1 McGill University, Montreal, QC, Canada
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| Content: | Objectives: Increasing evidence suggested that spinal microglia could be an important player in the pathogenesis of neuropathic pain. In this study, we sought to investigate the effect of TGF-beta, an anti-inflammatory cytokine on the spinal microglial reaction following peripheral nerve injury and the impact on nerve injury-induced hypersensitivity.
Materials and methods: Recombinant TGF-beta has been infused intrathecally in rats having a partial sciatic nerve ligation (Seltzer model). Spinal microglial activation was monitored by expression of Iba-1 (a marker for microglia activation) and the number of BrdU+ cells (index of cell proliferation). We assessed the animal mechanical allodynia using the Von Frey hair test and thermal hyperalgesia with the Hargreaves paw withdrawal test in response to heat beam stimulation.
Results: We observed that sciatic nerve injury induced a pronounced microgliosis on the lumbar spinal cord dorsal and ventral horns, ipsilateral to the side of nerve injury, which was evidenced by: 1) a significant increase of Iba-1 immunoreactivity (ir) and 2) a significant increase of BrdU+ cells colocalized with Iba-1. Both the paw withdrawal threshold to von Frey hair stimuli and the paw withdrawal latency to heat stimuli were decreased shortly after surgery, and maintained at a low level until the end of testing period (d14 post-injury). Intrathecal infusion of TGF-beta from d0-d14 post sciatic nerve lesion successfully limited spinal microgliosis with a reduction on Iba-1 ir and on the number of BrdU+ cells on the ipsilateral side spinal cord. In parallel, inhibition of microglial activation with a central treatment of TGF-beta resulted in a partial reduction of nerve injury induced-mechanical allodynia and thermal hyperalgesia.
Conclusion: We examined the impact of TGF-β1 on the central inflammatory response in relation to nerve injury-induced neuropathic pain. TGF-beta is effective in limiting spinal microgliosis following peripheral nerve injury. Inhibition of the central immune response mediated by activated microglia attenuates nerve injury induced-hypersensitivity.
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