Mol Pain
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Spinal neuroinflammation plays a critical role in the genesis of neuropathic pain. Accumulating data suggest that abscisic acid (ABA), a phytohormone, regulates inflammatory processes in mammals. In this study, we found that reduction of the LANCL2 receptor protein but not the agonist ABA in the spinal cord is associated with the genesis of neuropathic pain. ⋯ These changes are ameliorated when ABA is added with LPS. The anti-inflammatory effects induced by ABA do not requires Gi protein activity. Our study reveals that the ABA/LANCL2 system is a powerful endogenous system regulating spinal neuroinflammation and nociceptive processing, suggesting the potential utility of ABA as the management of neuropathic pain.
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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.
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Osteoarthritis (OA) is a common osteoarthropathy with chronic inflammatory pain as the core symptom in middle-aged and elderly people. LncRNA MEG3 (Maternally expressed gene 3) is involved in the development of OA via regulation of angiogenesis, which causes the activation and overexpression of transient receptor potential vanilloid type-1 (TRPV1). In this study, we investigated the mechanism of MEG3-TRPV1 signaling in chronic inflammatory pain (CIP) of rat model. ⋯ Treatment with a TRPV1 antagonist also significantly relieved chronic inflammatory pain in CFA-induced rats. In general, our results reveal that MEG3 alleviates chronic inflammatory pain by downregulating TRPV1 expression. These findings may provide new therapeutic targets in the treatment of patients with OA.
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Chronic pain is the predominant problem for rheumatoid arthritis patients, and negatively affects quality of life. Arthritis pain management remains largely inadequate, and developing new treatment strategies are urgently needed. Spinal inflammation and oxidative stress contribute to arthritis pain and represent ideal targets for the treatment of arthritis pain. ⋯ Further, AutoDock data showed that emodin bind to Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) through two electrovalent bonds. And emodin treatment increased the phosphorylated AMPK at threonine 172. In summary, emodin treatment activates AMPK, suppresses NLRP3 inflammasome response, elevates antioxidant response, inhibits spinal inflammatory reaction and alleviates arthritis pain.