Pain
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Neuropathic pain genesis is related to gene alterations in the dorsal root ganglion (DRG) after peripheral nerve injury. Transcription factors control gene expression. In this study, we investigated whether octamer transcription factor 1 (OCT1), a transcription factor, contributed to neuropathic pain caused by chronic constriction injury (CCI) of the sciatic nerve. ⋯ Mechanistically, OCT1 participated in CCI-induced increases in Dnmt3a mRNA and its protein and DNMT3a-mediated decreases in Oprm1 and Kcna2 mRNAs and their proteins in the injured DRG. These findings indicate that OCT1 may participate in neuropathic pain at least in part by transcriptionally activating Dnmt3a and subsequently epigenetic silencing of Oprm1 and Kcan2 in the DRG. OCT1 may serve as a potential target for therapeutic treatments against neuropathic pain.
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The objective of this study was to investigate whether incident opioid use is associated with an increased risk of hip fractures among community-dwelling persons with Alzheimer disease (AD) and to assess the association in terms of duration of use and opioid strength. Among community-dwelling persons with AD diagnosed in 2010 to 2011 (N = 23,100), a matched cohort study comparing incident opioid users (N = 4750) with opioid nonusers (N = 4750) was constructed. Matching was based on age, sex, and time since AD diagnosis at opioid initiation. ⋯ The risk was observed during the first 2 months of use (IPT-weighted HR 2.37, 1.04-5.41) and attenuated after that. The results suggest an increase in the risk of hip fracture by increasing opioid strength; weak opioids IPT-weighted HR 1.75 (0.91-3.35), buprenorphine IPT-weighted HR 2.10 (1.41-3.13), and strong opioids IPT-weighted HR 2.89 (1.32-6.32). Further research is needed to find out whether the risk of injurious falls is avoidable by slow titration of opioid doses in the beginning of treatment.
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Juvenile-onset fibromyalgia (JFM) is typically diagnosed in adolescence and characterized by widespread pain and marked functional impairment. The long-term impact of JFM into adulthood is poorly understood. The objectives of this study were to describe physical and psychosocial outcomes of youth diagnosed with JFM in early adulthood (∼8-year follow-up), examine longitudinal trajectories of pain and depressive symptoms from adolescence to young adulthood, and examine the impact of pain and depressive symptoms on physical functioning over time. ⋯ This study offers evidence that although JFM symptoms persist for most individuals, pain severity tends to decrease over time. However, depressive symptoms follow distinct trajectories that indicate subgroups of JFM. In particular, JFM patients with worsening depressive symptoms showed decreasing physical functioning and may require more intensive and consistent intervention to prevent long-term disability.
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Neuropathic pain represents a challenge to clinicians because it is resistant to commonly prescribed analgesics due to its largely unknown mechanisms. Here, we investigated a descending dopaminergic pathway-mediated modulation of trigeminal neuropathic pain. We performed chronic constriction injury of the infraorbital nerve from the maxillary branch of trigeminal nerve to induce trigeminal neuropathic pain in mice. ⋯ Specific excitation of dopaminergic neurons in the A11 nucleus attenuated the trigeminal neuropathic pain through the activation of D2 receptors in the spinal trigeminal nucleus caudalis. Conversely, specific ablation of the A11 dopaminergic neurons exacerbated such pain. Our results suggest that the descending A11-spinal trigeminal nucleus caudalis dopaminergic projection is critical for the modulation of trigeminal neuropathic pain and could be manipulated to treat such pain.