Articles: chronic.
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Research has shown that pain and sleep disturbance often co-occur and influence each other over time in children and adolescents with chronic pain. Longitudinal studies examining the underlying mechanisms of this association are scarce and have focused primarily on the role of internalizing mental health symptoms and mood. This longitudinal study aimed to determine whether fatigue underlies the co-occurrence and mutual maintenance of sleep disturbance and pain over time in children and adolescents with chronic pain. ⋯ Higher levels of pain interference at first assessment predicted higher levels of sleep disturbance at follow-up while controlling for initial levels of sleep disturbance. Furthermore, fatigue was found to mediate the association between first assessment and follow-up sleep disturbance, the association between first assessment and follow-up pain interference, and the association between first assessment pain interference and follow-up sleep disturbance. The findings highlight the need to assess and address fatigue in children and adolescents with chronic pain and sleep disturbance.
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Anesthesia and analgesia · Oct 2024
The Effect of Pexidartinib on Neuropathic Pain via Influences on Microglia and Neuroinflammation in Mice.
Chronic pain is a debilitating medical condition that lacks effective treatments. Increasing evidence suggests that microglia and neuroinflammation underlie pain pathophysiology, which therefore supports a potential strategy for developing pain therapeutics. Here, our study is testing the hypothesis that the promise of pain amelioration can be achieved using the small-molecule pexidartinib (PLX-3397), a previously food and drug administration (FDA)-approved cancer medicine and a colony-stimulating factor-1 receptor (CSF-1R) inhibitor that display microglia-depleting properties. ⋯ Collectively, our study showed PLX-3397-related efficacy in ameliorating pain linked to the reduction of microglia and neuroinflammation in mice. Furthermore, our research provided new proof-of-concept data supporting the promise of testing PLX-3397 as an analgesic.
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The higher incidence of migraines in women compared with men has led to the inclusion of female animals in pain research models. However, the critical role of the hormonal cycle is frequently overlooked, despite its clear correlation with migraine occurrences. In this study, we show in a rat model of migraine induced by repeated dural infusions of an inflammatory soup (IS) that a second IS (IS2) injection performed in proestrus/estrus (PE, high estrogen) female rats evokes higher cephalic mechanical hypersensitivities than when performed in metestrus/diestrus (MD, low estrogen) or ovariectomized (OV) rats. ⋯ Second inflammatory soup depolarizes neurons in PE and MD but not in OV rats and enhances excitatory synaptic inputs in PE animals to a greater extent compared with MD and OV rats. These findings show that central TCC sensitization triggered by meningeal nociceptor activation and the resulting cephalic hypersensitivity are modulated by the estrous cycle. This highlights the crucial need to account for not just sex, but also the female estrous cycle in pain research.