Experimental neurology
-
Experimental neurology · Apr 2012
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 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. ⋯ 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.
-
Experimental neurology · Apr 2012
ReviewPurinergic systems, neuropathic pain and the role of microglia.
We have learned various data on the role of purinoceptors (P2X4, P2X7, P2Y6 and P2Y12) expressed in spinal microglia and several factors that presumably activate microglia in neuropathic pain after peripheral nerve injury. Purinergic receptor-mediated spinal microglial functions make a critical contribution to pathologically enhanced pain processing in the dorsal horn. Microglial purinoceptors might be promising targets for treating neuropathic pain. A predicted therapeutic benefit of interfering with microglial purinergic receptors may be that normal pain sensitivity would be unaffected since expression or activity of most of these receptors are upregulated or enhanced predominantly in activated microglia in the spinal cord where damaged sensory fibers project.