[Mechanisms underlying the pathogenesis of neuropathic pain revealing by the role of glial cells]. 2015

Makoto Tsuda

Injury to the nervous system results in debilitating chronic pain states (called neuropathic pain) whose mechanisms remain unclear. Emerging lines of evidence indicate the pivotal role of spinal glial cells in neuropathic pain. Spinal microglia rapidly respond to peripheral nerve injury (PNI) and become activated with changing expression of a variety of genes. The best known example is purinergic P2X4 receptors, an ATP-gated cation channel. The expression of P2X4 receptors is upregulated in spinal microglia after PNI, and inhibition of P2X4 activity suppresses neuropathic pain. Furthermore, interferon regulatory factor-8 (IRF8) and IRF5 are identified as microglial transcription factors whose expression is upregulated in spinal microglia after PNI, and the IRF8-IRF5 transcriptional cascade is the core process for shifting spinal microglia toward a state with high expression of P2X4 receptors. Astrocytes in the spinal cord show a delayed onset of activation and play an important role in the maintenance of neuropathic pain via the transcription factor STAT3 and the intracellular kinase JNK. These results obtained from glial cell research will advance our understanding of the development and maintenance of neuropathic pain and provide a new target for treating this pain.

UI MeSH Term Description Entries
D009437 Neuralgia Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. Nerve Pain,Neurodynia,Paroxysmal Nerve Pain,Neuralgia, Atypical,Neuralgia, Iliohypogastric Nerve,Neuralgia, Ilioinguinal,Neuralgia, Perineal,Neuralgia, Stump,Neuralgia, Supraorbital,Neuralgia, Vidian,Neuropathic Pain,Atypical Neuralgia,Atypical Neuralgias,Iliohypogastric Nerve Neuralgia,Iliohypogastric Nerve Neuralgias,Ilioinguinal Neuralgia,Ilioinguinal Neuralgias,Nerve Neuralgia, Iliohypogastric,Nerve Neuralgias, Iliohypogastric,Nerve Pain, Paroxysmal,Nerve Pains,Nerve Pains, Paroxysmal,Neuralgias,Neuralgias, Atypical,Neuralgias, Iliohypogastric Nerve,Neuralgias, Ilioinguinal,Neuralgias, Perineal,Neuralgias, Stump,Neuralgias, Supraorbital,Neuralgias, Vidian,Neurodynias,Neuropathic Pains,Pain, Nerve,Pain, Neuropathic,Pain, Paroxysmal Nerve,Pains, Nerve,Pains, Neuropathic,Pains, Paroxysmal Nerve,Paroxysmal Nerve Pains,Perineal Neuralgia,Perineal Neuralgias,Stump Neuralgia,Stump Neuralgias,Supraorbital Neuralgia,Supraorbital Neuralgias,Vidian Neuralgia,Vidian Neuralgias
D009457 Neuroglia The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. Bergmann Glia,Bergmann Glia Cells,Bergmann Glial Cells,Glia,Glia Cells,Satellite Glia,Satellite Glia Cells,Satellite Glial Cells,Glial Cells,Neuroglial Cells,Bergmann Glia Cell,Bergmann Glial Cell,Cell, Bergmann Glia,Cell, Bergmann Glial,Cell, Glia,Cell, Glial,Cell, Neuroglial,Cell, Satellite Glia,Cell, Satellite Glial,Glia Cell,Glia Cell, Bergmann,Glia Cell, Satellite,Glia, Bergmann,Glia, Satellite,Glial Cell,Glial Cell, Bergmann,Glial Cell, Satellite,Glias,Neuroglial Cell,Neuroglias,Satellite Glia Cell,Satellite Glial Cell,Satellite Glias
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013116 Spinal Cord A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER. Coccygeal Cord,Conus Medullaris,Conus Terminalis,Lumbar Cord,Medulla Spinalis,Myelon,Sacral Cord,Thoracic Cord,Coccygeal Cords,Conus Medullari,Conus Terminali,Cord, Coccygeal,Cord, Lumbar,Cord, Sacral,Cord, Spinal,Cord, Thoracic,Cords, Coccygeal,Cords, Lumbar,Cords, Sacral,Cords, Spinal,Cords, Thoracic,Lumbar Cords,Medulla Spinali,Medullari, Conus,Medullaris, Conus,Myelons,Sacral Cords,Spinal Cords,Spinali, Medulla,Spinalis, Medulla,Terminali, Conus,Terminalis, Conus,Thoracic Cords
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D015854 Up-Regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Up-Regulation,Upregulation,Up-Regulation (Physiology),Up Regulation
D015870 Gene Expression The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION. Expression, Gene,Expressions, Gene,Gene Expressions
D017628 Microglia The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. Microglial Cell,Cell, Microglial,Microglial Cells,Microglias
D048670 MAP Kinase Kinase 4 A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress. JN Kinase Kinase,JNK Kinase,JNK-Activating Protein Kinase,JNKK1 Protein Kinase,Jun Amino-Terminal Kinase Kinase,MEK4 Protein Kinase,Mitogen-Activated Protein Kinase Kinase 4,SAP Kinase Kinase 1,SAP Kinase-Extracellular Signal-Regulated Kinase Kinase 1,SAPK-ERK Kinase 1,SEK1 Protein Kinase,Stress-Activated Protein Kinase Kinase 1,JNK Activating Protein Kinase,Jun Amino Terminal Kinase Kinase,Kinase, JNKK1 Protein,Mitogen Activated Protein Kinase Kinase 4,Protein Kinase, JNK-Activating,Protein Kinase, JNKK1,Protein Kinase, MEK4,Protein Kinase, SEK1,SAP Kinase Extracellular Signal Regulated Kinase Kinase 1,SAPK ERK Kinase 1,Stress Activated Protein Kinase Kinase 1

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