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Peri-sciatic administration of recombinant rat IL-1beta induces mechanical allodynia by activation of src-family kinases in spinal microglia in rats.

Authors: Wei, XH  Yang, T  Wu, Q  Xin, WJ  Wu, JL  Wang, YQ  Zang, Y  Wang, J  Li, YY  Liu, XG 
Citation: Wei XH, etal., Exp Neurol. 2012 Apr;234(2):389-97. Epub 2012 Jan 12.
Pubmed: (View Article at PubMed) PMID:22265659
DOI: Full-text: DOI:10.1016/j.expneurol.2012.01.001

Previous studies have shown that Interleukin-1 beta (IL-1beta) is implicated in the modulation of pain sensitivity. In the present study, we found that a single peri-sciatic administration of rat recombinant IL-1beta (rrIL-1beta) at doses of 20 and 200 pg (100, 1000 ng/l, in 200 mul volume) induced mechanical allodynia in bilateral hindpaws in rats, lasting for about 50 days. No axonal or Schwann cell damage at the drug administration site was found following 1000 ng/l rrIL-1beta administration. The results of immunofluorescence showed that microglial cells in bilateral spinal dorsal horn were activated after peri-sciatic administration of rrIL-1beta (1000 ng/l). The immunoreactivity (IR) of Iba1 (a marker for microglia) and phosphorylated src-family kinases (p-SFKs) increased significantly in the ipsilateral and contralateral lumbar spinal dorsal horn on day 1 and day 3 after rrIL-1beta administration, respectively. Double immunofluorescence staining revealed that the increased p-SFKs-IR was almost restricted within the microglia. Intrathecal delivery of minocycline (100 mug in 10 mul volume), a selective inhibitor of microglia, started 30 min before rrIL-1beta administration and once daily thereafter for 7 days, blocked mechanical allodynia induced by rrIL-1beta completely and inhibited the upregulation of p-SFKs. Intrathecal delivery of SFKs inhibitor PP2 (12 mug in 10 mul volume) also blocked mechanical allodynia induced by rrIL-1beta completely. These data suggest that activation of SFKs in spinal microglia mediates mechanical allodynia induced by peri-sciatic administration of rrIL-1beta.

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RGD Object Information
RGD ID: 6482671
Created: 2012-04-25
Species: All species
Last Modified: 2012-04-25
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.