Mol Pain
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Noncoding microRNAs have emerged as critical players of gene expression in the nervous system, where they contribute to regulating nervous disease. As stated in previous research, the miR-155-5p upregulation happens in the spinal cord at the nociceptive state. It was unclear if miR-155-5p is linked to bone cancer pain (BCP). Herein, we aimed at investigating the miR-155-5p functional regulatory function in BCP process and delineating the underlying mechanism. ⋯ The study findings stated the miR-155-5p pivotal role in regulating BCP by directly targeting TCF4 in spinal neurons and suggested that miR-155-5p could be a promising target in treating BCP.
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Bone cancer pain (BCP) is a clinically intractable mixed pain, involving inflammation and neuropathic pain, and its mechanisms remain unclear. CXC chemokine receptor 1 (CXCR1, IL-8RA) and 2 (CXCR2, IL-8RB) are high-affinity receptors for interleukin 8 (IL8). According to previous studies, CXCR2 plays a crucial role in BCP between astrocytes and neurons, while the role of CXCR1 remains unclear. ⋯ Intrathecal injection of CXCR1-siRNA reduced phosphorylated JAK2/STAT3 protein levels and the NLRP3 inflammasome (NLRP3, caspase1, and IL-1β) levels. Furthermore, in vitro cytological experiments confirmed this conclusion. The study results suggest that the spinal chemokine receptor CXCR1 activation mediates BCP through JAK2/STAT3 signaling pathway and NLRP3 inflammasome (NLRP3, caspase1, and IL-1β).
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Effects of Fu's Subcutaneous Needling on Mitochondrial Structure and Function in Rats with Sciatica.
To observe the effects of Fu's subcutaneous needling (FSN) and acupuncture treatment on the mitochondrial structure and function of the skeletal muscle tissue of rats with sciatica. Forty Sprague-Dawley rats were divided into control, model, acupuncture, and FSN groups (10 each) according to a random number table. The control group was left untreated. ⋯ The state of mitochondria in the FSN group was close to that in the control group and was remarkably better than that in the acupuncture group. The activities of mitochondrial CS and respiratory chain complex II in the skeletal muscle of the treated rats decreased compared with the control group (p < 0.05), and their levels were better in the FSN group than in the acupuncture group (p < 0.05). FSN treatment for 1 week considerably improved the pain thresholds and improved the skeletal muscle mitochondrial ultrastructure and mitochondrial function in rats with sciatica.
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The devastating chronic central post stroke pain is associated with variety of comorbidities. Disrupted sleep is a severe comorbidity, causing an increase in the suicide rate, due to CPSP's pain symptom. Melatonin is a well-known jet-lag compound, which helps in entrainment of sleep cycle. ⋯ The low levels of melatonin in blood plasma due to CPSP were restored after 3 weeks of melatonin administration. After 30 mg/kg melatonin administrations for 3 weeks, all the disrupted resting and activity behaviors were reduced during light and dark periods. The results suggested that melatonin significantly ameliorated CPSP's pain symptoms and comorbid sleep disturbance showing in activity behavior.
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Chronic pain increases the risk of developing anxiety, with limbic areas being likely neurological substrates. Despite high clinical relevance, little is known about the precise behavioral, hormonal, and brain neuroplastic correlates of anxiety in the context of persistent pain. Previous studies have shown that decreased nociceptive thresholds in chronic pain models are paralleled by anxiety-like behavior in rats, but there are conflicting ideas regarding its effects on the stress response and circulating corticosterone levels. ⋯ Global DNA methylation was decreased in the amygdala, with no changes in DNMT3a abundance in any of the regions examined. Persistent inflammatory pain promotes anxiety -like behaviors, HPA axis activation, and epigenetic regulation through DNA methylation in the amygdala. These findings describe a molecular mechanism that links pain and stress in a well-characterized rodent model.