Experimental neurology
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Experimental neurology · Apr 2012
Increased atypical PKC expression and activity in the phrenic motor nucleus following cervical spinal injury.
Atypical protein kinase C (aPKC) isoforms are expressed in phrenic motor neurons, a group of motor neurons critical for breathing. Following C2 cervical hemisection (C2HS), spontaneous plasticity occurs in crossed-spinal synaptic pathways to phrenic motor neurons, at least partially restoring inspiratory phrenic activity below the injury. Since aPKCs are necessary for synaptic plasticity in other systems, we tested the hypothesis that C2HS increases aPKC expression and activity in spinal regions associated with the phrenic motor nucleus. ⋯ Ipsilateral aPKC activity and expression were strongly correlated (r(2)=0.675, p<0.001). In a distinct group of rats, immunohistochemistry confirmed that aPKCs are expressed in neurons 28 days post-C2HS, including large, presumptive phrenic motor neurons; aPKCs were not detected in adjacent microglia (OX-42 positive cells) or astrocytes (GFAP positive cells). Changes in aPKC expression in the phrenic motor nucleus following C2HS suggests that aPKCs may contribute to functional recovery following cervical spinal injury.
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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.
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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.
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Experimental neurology · Apr 2012
ReviewImmune responses of microglia in the spinal cord: contribution to pain states.
The role of microglia and their contribution to the development and maintenance of pain states has emerged as an attractive field of study. Sensitization of central nociceptors and interneurons is thought to be responsible for the symptoms of chronic neuropathic pain states. Microglia interact with these neurons at the site of injury or disease as well as remotely. ⋯ Activated microglia also exhibit a modulated cell surface receptor and ion channel profile. The activation of several intracellular pathways in microglia has also been implicated in pain states. Attenuation of microglia activity is being presented as a viable therapeutic approach with regard to not only the reduction of pain symptoms but also in preventing the development of chronic pain states.