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Involvement of NF-κB and the CX3CR1 Signaling Network in Mechanical Allodynia Induced by Tetanic Sciatic Stimulation / 神经科学通报·英文版
Neuroscience Bulletin ; (6): 64-73, 2018.
Article in English | WPRIM | ID: wpr-777070
ABSTRACT
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. Here, we set out to determine whether and how NF-κB and CX3CR1 are involved in the mechanism underlying the pathological changes induced by TSS. After unilateral TSS, significant bilateral mechanical allodynia was induced, as assessed by the von Frey test. The expression of phosphorylated NF-κB (pNF-κB) and CX3CR1 was significantly up-regulated in the bilateral dorsal horn. Immunofluorescence staining demonstrated that pNF-κB and NeuN co-existed, implying that the NF-κB pathway is predominantly activated in neurons following TSS. Administration of either the NF-κB inhibitor ammonium pyrrolidine dithiocarbamate or a CX3CR1-neutralizing antibody blocked the development and maintenance of 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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Full text: Available Index: WPRIM (Western Pacific) Main subject: Physical Stimulation / Physiology / Sciatic Nerve / Spinal Cord / Thiocarbamates / Proline / Signal Transduction / Up-Regulation / Cytokines / Rats, Sprague-Dawley Type of study: Prognostic study Limits: Animals Language: English Journal: Neuroscience Bulletin Year: 2018 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Physical Stimulation / Physiology / Sciatic Nerve / Spinal Cord / Thiocarbamates / Proline / Signal Transduction / Up-Regulation / Cytokines / Rats, Sprague-Dawley Type of study: Prognostic study Limits: Animals Language: English Journal: Neuroscience Bulletin Year: 2018 Type: Article