MAP Kinase and Cell Signaling in DRG Neurons and Spinal Microglia in Neuropathic Pain



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.


Dorsal Root Ganglion Neuropathic Pain Nerve Injury Dorsal Root Ganglion Neuron Mechanical Allodynia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



α-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanic acid


brain-derived neurotrophic factor


cysteine protease cathepsin S


dorsal root ganglion


gamma aminobutyric acid


extracelllular signal-regulated kinase


basic fibroblast growth factor






c-Jun-N-terminal kinase


mitogen-activated protein kinases


monocyte chemoattractant protein-1




matrix metalloproteinase-9


nerve growth factor


neurotrophin 3


prostaglandin E2


pain transmission neurons STZ, streptozotocin


tumor necrosis factor


transient receptor potential



The work was supported in part by NIH grants NS40698, DE17794, and TW7180.


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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Anesthesiology, Pain Research CenterBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA

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