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MAP kinase and cell signaling in DRG neurons and spinal microglia in neuropathic pain

Publication ,  Journal Article
Ji, RR
January 1, 2009

Nerve injury is known to produce neuropathic pain by inducing changes not only in neurons such as primary sensory neurons in the dorsal root ganglion (DRG), but also in non-neuronal cells such as microglia in the spinal cord. Increasing evidence suggests that mitogen-activated protein kinases (MAPKs) play important roles in neuropathic pain sensitization by regulating intracellular signaling in both DRG neurons and spinal cord microglia. Intrathecal injection of MAPK inhibitors for the extracellular signal-regulated kinase (ERK), p38, or c-Jun N-terminal kinase (JNK) pathway targets the MAPK pathways at both DRG and spinal cord levels and has been shown to attenuate neuropathic pain in different animal models. In particular, activation of p38 in DRG neurons by nerve growth factor and cytokines contributes to thermal hypersensitivity by increasing the expression and activity of sodium channels (e.g., Nav1.7/Nav1.8) and TRP channels (e.g., TRPV1 and TRPA1). Activation of p38 in spinal microglia by chemokines, cytokines, ATP, and proteases also contributes to neuropathic pain symptoms such as mechanical allodynia. Thus, activation of MAPK pathways in both neurons and glia and in both the peripheral and central nervous system is important for neuropathic pain sensitization, and blocking these pathways at multiple sites may lead to effective therapies for neuropathic pain.

Duke Scholars

DOI

Publication Date

January 1, 2009

Start / End Page

425 / 438
 

Citation

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Ji, R. R. (2009). MAP kinase and cell signaling in DRG neurons and spinal microglia in neuropathic pain, 425–438. https://doi.org/10.1007/978-1-4419-0226-9_20
Ji, R. R. “MAP kinase and cell signaling in DRG neurons and spinal microglia in neuropathic pain,” January 1, 2009, 425–38. https://doi.org/10.1007/978-1-4419-0226-9_20.
Ji, R. R. MAP kinase and cell signaling in DRG neurons and spinal microglia in neuropathic pain. Jan. 2009, pp. 425–38. Scopus, doi:10.1007/978-1-4419-0226-9_20.

DOI

Publication Date

January 1, 2009

Start / End Page

425 / 438