Pain
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Evidence linking adverse childhood experiences and chronic pain in adulthood is largely cross-sectional, potentially subject to recall bias and does not allow exploration of mediating pathways. We analysed a large population-based cohort (UK Biobank) using a causal framework, to determine if childhood maltreatment is related to chronic "all over" body pain in adulthood. We used doubly robust estimation with inverse probability weights to estimate the difference in risk of chronic pain "all over" between those exposed/not exposed to childhood maltreatment (abuse or neglect). ⋯ In mediation analyses, the total effect was a relative risk of 1.57 (95% CI 1.49-1.66), while the estimated indirect effect via all mediators was relative risk 1.16 (95% CI 1.14-1.18). Reducing childhood maltreatment would likely prevent cases of chronic widespread pain in adulthood. Stressful adult events and mediators may offer opportunities for intervention.
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Voltage-gated potassium channel subfamily q member 4 (Kcnq4) is predominantly expressed by hair cells and auditory neurons and regulates the neuronal excitability in the auditory pathway. Although it is further detected in myelinated large-diameter dorsal root ganglia (DRG) neurons in the periphery, the expression and function of Kcnq4 channel in nociceptors remains unknown. ⋯ Moreover, genetic ablation of Kcnq4 in Trpv1-positive neurons exacerbates both acute and chronic itch behavior in mice. Taken together, our results uncover a functional role of Trpv1-lineage neuron-expressing Kcnq4 channel in the modulation of itch-specific neuronal excitation in the periphery.