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Article
Open AccessMacrophages play a leading role in determining the direction of astrocytic migration in spinal cord injury via ADP-P2Y1R axis
After spinal cord injury (SCI), inflammatory cells such as macrophages infiltrate the injured area, and astrocytes migrate, forming a glial scar around macrophages. The glial scar inhibits axonal regeneration,...
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Article
The Role of ATP Receptors in Pain Signaling
Since new roles of nucleotides as neurotransmitters were proposed by Geoffrey Burnstock, the roles of ATP and P2 receptors (P2Rs) have been extensively studied in pain signaling. Chronic pain is a debilitating...
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Article
Open AccessImprovement of the affinity of an anti-rat P2X4 receptor antibody by introducing electrostatic interactions
We have recently developed a mouse monoclonal antibody (12–10H) binding to the head domain region in rat P2X4 receptor (rP2X4R, which is crucial for the pathogenesis of neuropathic pain) expressed on the cell ...
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Article
Nociceptive signaling of P2X receptors in chronic pain states
P2X3 monomeric receptors (P2X3Rs) and P2X2/3 heteromeric receptors (P2X2/3Rs) in primary sensory neurons and microglial P2X4 monomeric receptors (P2X4Rs) in the spinal dorsal horn (SDH) play important roles in...
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Article
Spinal astrocytes in superficial laminae gate brainstem descending control of mechanosensory hypersensitivity
Astrocytes are critical regulators of CNS function and are proposed to be heterogeneous in the develo** brain and spinal cord. Here we identify a population of astrocytes located in the superficial laminae o...
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Article
Open AccessHyperactivation of proprioceptors induces microglia-mediated long-lasting pain in a rat model of chronic fatigue syndrome
Patients diagnosed with chronic fatigue syndrome (CFS) or fibromyalgia experience chronic pain. Concomitantly, the rat model of CFS exhibits microglial activation in the lumbar spinal cord and pain behavior wi...
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Article
Evidence for detection of rat P2X4 receptor expressed on cells by generating monoclonal antibodies recognizing the native structure
P2X purinergic receptors are ATP-driven ionic channels expressed as trimers and showing various functions. A subtype, the P2X4 receptor present on microglial cells is highly involved in neuropathic pain. In th...
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Article
Open AccessTop-down descending facilitation of spinal sensory excitatory transmission from the anterior cingulate cortex
Spinal sensory transmission is under descending biphasic modulation, and descending facilitation is believed to contribute to chronic pain. Descending modulation from the brainstem rostral ventromedial medulla...
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Article
Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential
Neuropathic pain that results from damage to the nervous system results from the pathological operation of the nervous system
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Article
Open AccessFibromyalgia and microglial TNF-α: Translational research using human blood induced microglia-like cells
Fibromyalgia is a refractory disease characterized by chronic intractable pain and psychological suffering, the cause of which has not yet been elucidated due to its complex pathology. Activation of immune cel...
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Article
Open AccessChemogenetic silencing of GABAergic dorsal horn interneurons induces morphine-resistant spontaneous nocifensive behaviours
Inhibitory interneurons in the spinal dorsal horn (SDH) are crucial for processing somatosensory information originating in the periphery. However, the effects of the acute and selective inactivation of GABAer...
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Article
Open AccessGlucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia
Diurnal variations in pain hypersensitivity are common in chronic pain disorders, but the underlying mechanisms are enigmatic. Here, we report that mechanical pain hypersensitivity in sciatic nerve-injured mic...
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Article
Open AccessA novel P2X4 receptor-selective antagonist produces anti-allodynic effect in a mouse model of herpetic pain
Accumulating evidence indicates that purinergic P2X4 receptors (P2X4R: cation channels activated by extracellular ATP) expressed in spinal microglia are crucial for pathological chronic pain caused by nerve da...
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Article
Open AccessDorsal horn neurons release extracellular ATP in a VNUT-dependent manner that underlies neuropathic pain
Activation of purinergic receptors in the spinal cord by extracellular ATP is essential for neuropathic hypersensitivity after peripheral nerve injury (PNI). However, the cell type responsible for releasing AT...
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Article
Open AccessBK channels in microglia are required for morphine-induced hyperalgesia
Although morphine is a gold standard medication, long-term opioid use is associated with serious side effects, such as morphine-induced hyperalgesia (MIH) and anti-nociceptive tolerance. Microglia-to-neuron si...
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Article
Open AccessBone marrow-derived cells in the population of spinal microglia after peripheral nerve injury
Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that aft...
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The Research for the Mechanism of Chronically Intractable Pain Based on the Functions of Microglia as Brain Immunocompetent Cell
Injury to the nervous system often causes a debilitating chronic pain syndrome, termed neuropathic pain. Neuropathic pain is refractory to currently available analgesics. Accumulating evidence indicates that s...
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Article
Open AccessA new minimally-invasive method for microinjection into the mouse spinal dorsal horn
Noninvasive gene delivery to the spinal dorsal horn (SDH) remains challenging because existing methods to directly microinject vectors require laminectomy, which leads to tissue damage and inflammation. Such r...
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Article
STAT3-dependent reactive astrogliosis in the spinal dorsal horn underlies chronic itch
In response to signals from afferent TRPV1+ C-fibers, STAT3-dependent upregulation of LCN2 in reactive astrocytes of the spinal dorsal horn amplifies itch signaling in multiple rodent models of atopic and contact...
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Article
IRF8 is a transcriptional determinant for microglial motility
Microglia, the resident immune cells of the central nervous system, are constitutively mobile cells that undergo rapid directional movement toward sites of tissue disruption. However, transcriptional regulator...
