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. 2012 Apr;234(2):389-97.
doi: 10.1016/j.expneurol.2012.01.001. Epub 2012 Jan 12.

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

Xu-Hong Wei  1 , Tao Yang, Qiang Wu, Wen-Jun Xin, Jin-Lang Wu, Ya Qiong Wang, Ying Zang, Jun Wang, Yong-Yong Li, Xian-Guo Liu
Affiliations

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

Xu-Hong Wei et al. Exp Neurol. 2012 Apr.

Abstract

Previous studies have shown that Interleukin-1 beta (IL-1β) is implicated in the modulation of pain sensitivity. In the present study, we found that a single peri-sciatic administration of rat recombinant IL-1β (rrIL-1β) at doses of 20 and 200 pg (100, 1000 ng/l, in 200 μl 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-1β administration. The results of immunofluorescence showed that microglial cells in bilateral spinal dorsal horn were activated after peri-sciatic administration of rrIL-1β (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-1β administration, respectively. Double immunofluorescence staining revealed that the increased p-SFKs-IR was almost restricted within the microglia. Intrathecal delivery of minocycline (100 μg in 10 μl volume), a selective inhibitor of microglia, started 30 min before rrIL-1β administration and once daily thereafter for 7 days, blocked mechanical allodynia induced by rrIL-1β completely and inhibited the upregulation of p-SFKs. Intrathecal delivery of SFKs inhibitor PP2 (12 μg in 10 μl volume) also blocked mechanical allodynia induced by rrIL-1β completely. These data suggest that activation of SFKs in spinal microglia mediates mechanical allodynia induced by peri-sciatic administration of rrIL-1β.

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