Neuroscience bulletin
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Neuroscience bulletin · Aug 2019
Increased CXCL13 and CXCR5 in Anterior Cingulate Cortex Contributes to Neuropathic Pain-Related Conditioned Place Aversion.
Pain consists of sensory-discriminative and emotional-affective components. The anterior cingulate cortex (ACC) is a critical brain area in mediating the affective pain. However, the molecular mechanisms involved remain largely unknown. ⋯ Finally, superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs. Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmission induced by SNL. Collectively, these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.
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Neuroscience bulletin · Jun 2019
ReviewSpinal Cord Stimulation for Pain Treatment After Spinal Cord Injury.
In addition to restoration of bladder, bowel, and motor functions, alleviating the accompanying debilitating pain is equally important for improving the quality of life of patients with spinal cord injury (SCI). Currently, however, the treatment of chronic pain after SCI remains a largely unmet need. Electrical spinal cord stimulation (SCS) has been used to manage a variety of chronic pain conditions that are refractory to pharmacotherapy. ⋯ We begin with an overview of its manifestations, classification, potential underlying etiology, and current challenges for its treatment. The clinical evidence for using SCS in SCI pain is then reviewed. Finally, future perspectives of pre-clinical research and clinical study of SCS for SCI pain treatment are discussed.
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Neuroscience bulletin · Feb 2018
Chemokine Receptor CXCR3 in the Spinal Cord Contributes to Chronic Itch in Mice.
Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also contributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. ⋯ Furthermore, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3 -/- mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3 -/- mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.
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Neuroscience bulletin · Feb 2018
Involvement of NF-κB and the CX3CR1 Signaling Network in Mechanical Allodynia Induced by Tetanic Sciatic Stimulation.
Tetanic stimulation of the sciatic nerve (TSS) triggers long-term potentiation in the dorsal horn of the spinal cord and long-lasting pain hypersensitivity. CX3CL1-CX3CR1 signaling is an important pathway in neuronal-microglial activation. Nuclear factor κB (NF-κB) is a key signal transduction molecule that regulates neuroinflammation and neuropathic pain. ⋯ In addition, blockade of NF-κB down-regulated the expression of CX3CL1-CX3CR1 signaling, and conversely the CX3CR1-neutralizing antibody also down-regulated pNF-κB. These findings suggest an involvement of NF-κB and the CX3CR1 signaling network in the development and maintenance of TSS-induced mechanical allodynia. Our work suggests the potential clinical application of NF-κB inhibitors or CX3CR1-neutralizing antibodies in treating pathological pain.
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Neuroscience bulletin · Feb 2018
ReviewCombining Human and Rodent Genetics to Identify New Analgesics.
Most attempts at rational development of new analgesics have failed, in part because chronic pain involves multiple processes that remain poorly understood. To improve translational success, one strategy is to select novel targets for which there is proof of clinical relevance, either genetically through heritable traits, or pharmacologically. Such an approach by definition yields targets with high clinical validity. ⋯ Systemic SPR inhibition in mice has not revealed any safety concerns to date, and available genetic and pharmacologic data suggest similar responses in humans. Finally, because it is present in vivo only when SPR is inhibited, sepiapterin serves as a reliable biomarker of target engagement, allowing potential quantification of drug efficacy. The emerging development of therapeutics that target BH4 synthesis to treat chronic pain illustrates the power of combining human and mouse genetics: human genetic studies for clinical selection of relevant targets, coupled with causality studies in mice, allowing the rational engineering of new analgesics.