Expression of @entity13766 in both resident and bone marrow-derived microglia plays a critical role in XXXX .

@entity1931 @entity66 @entity1750 @entity19 @entity128 @entity13766 @entity1897 @entity56 @entity1118 @entity9
@entity9 resulting from @entity66 of peripheral nerves is not well understood and difficult to treat. Although CNS hyperexcitability is a critical component, recent findings challenge the neuron-centric view of @entity9 etiology and pathology. Indeed, glial cells were shown to play an active role in the initiation and maintenance of pain @entity56 . However, the origins of these cells and the triggers that induce their activation have yet to be elucidated. Here we show that, after @entity1897 induced by a partial ligation on the sciatic nerve, in addition to activation of microglia resident to the CNS, hematogenous macrophage/monocyte infiltrate the spinal cord, proliferate, and differentiate into microglia. Signaling from chemokine @entity1750 ( @entity1750 , @entity1750 ) to its receptor @entity13766 is critical in the spinal microglial activation. Indeed, intrathecal injection of @entity1750 caused activation of microglia in wild-type but not in @entity13766 -deficient @entity19 . Furthermore, treatment with an @entity1750 neutralizing antibody prevented bone marrow-derived microglia (BMDM) infiltration into the spinal cord after @entity128 . In addition, using selective knock-out of @entity13766 in resident microglia or BMDM, we found that, although total @entity13766 knock-out @entity19 did not develop microglial activation or mechanical @entity1931 , @entity13766 expression in either resident microglia or BMDM is sufficient for the development of mechanical @entity1931 . Thus, to effectively relieve @entity9 , both CNS resident microglia and blood-borne macrophages need to be targeted. These findings also open the door for a novel therapeutic strategy: to take advantage of the natural ability of bone marrow-derived cells to infiltrate selectively affected CNS regions by using these cells as vehicle for targeted drug delivery to inhibit @entity56 and @entity1118 .
