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

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 200pg (100, 1000ng/l, in 200μl volume) induced mechanical allodynia in bilateral hindpaws in rats, lasting for about 50days. No axonal or Schwann cell damage at the drug administration site was found following 1000ng/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 (1000ng/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 (100μg in 10μl volume), a selective inhibitor of microglia, started 30min before rrIL-1β administration and once daily thereafter for 7days, blocked mechanical allodynia induced by rrIL-1β completely and inhibited the upregulation of p-SFKs. Intrathecal delivery of SFKs inhibitor PP2 (12μg in 10μl 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. ► Peri-sciatic administration of rrIL-1β induced mechanical allodynia. ► RrIL-1β activated SFKs in microglia in lumbar spinal dorsal horn. ► Minocycline or SFKs inhibitor prevented allodynia induced by rrIL-1β.