title: Peri-sciatic administration of recombinant rat IL-1β induces mechanical allodynia by activation of src-family kinases in spinal microglia in rats.
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.
authors.affiliation: Pain Research Center and Department of Physiology, Zhongshan Medical School of Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangdong, China.
authors.forename: Xu-Hong
authors.initials: XH
authors.lastname: Wei
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Xin
authors.forename: Jin-Lang
authors.initials: JL
authors.lastname: Wu
authors.forename: Ya Qiong
authors.initials: YQ
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Yong-Yong
authors.initials: YY
authors.lastname: Li
authors.forename: Xian-Guo
authors.initials: XG
authors.lastname: Liu
mesh_terms: D000818:Animals; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D011994:Recombinant Proteins; D019061:src-Family Kinases