Pain
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Chronic pain conditions are highly comorbid with insufficient sleep. While the mechanistic relationships between the 2 are not understood, chronic insufficient sleep may be 1 pathway through which central pain-modulatory circuits deteriorate, thereby contributing to chronic pain vulnerability over time. To test this hypothesis, an in-laboratory model of 3 weeks of restricted sleep with limited recovery (5 nights of 4-hour sleep per night followed by 2 nights of 8-hour sleep per night) was compared with 3 weeks of 8-hour sleep per night (control protocol). ⋯ These changes may reflect abnormalities in central pain-modulatory processes. Limited recovery sleep did not completely resolve these alterations in pain-modulatory processes, indicating that more extensive recovery sleep is required. Results suggest that exposure to chronic insufficient sleep may increase vulnerability to chronic pain by altering processes of pain habituation and sensitization.
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Heart rate variability (HRV) and baroreflex sensitivity (BRS) are indexes reflecting the ability to maintain cardiovascular homeostasis amidst changing conditions. Evidence primarily from small studies suggests that both HRV and BRS may be reduced in individuals with chronic pain (CP), with potential implications for cardiovascular risk. We compared HRV and BRS between individuals with CP (broadly defined) and pain-free controls in a large unselected population sample. ⋯ Results were somewhat weaker for the post-CPT period. Mediation analyses indicated that for 6 of 7 HRV and BRS measures tested, there were significant indirect (mediated) effects of CP status on the presence of comorbid hypertension via reduced HRV or BRS. Results confirm in the largest and broadest sample tested to date that the presence of CP is linked to impaired cardiovascular regulation and for the first time provide support for the hypothesis that links between CP and comorbid hypertension reported in previous population studies may be due in part to CP-related decrements in cardiovascular regulation.
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To develop a simple, valid model to identify patients at high risk of opioid overdose-related hospitalization and mortality, Oregon prescription drug monitoring program, Vital Records, and Hospital Discharge data were linked to estimate 2 logistic models; a first model that included a broad range of risk factors from the literature and a second simplified model. Receiver operating characteristic curves, sensitivity, and specificity of the models were analyzed. Variables retained in the final model were categories such as older than 35 years, number of prescribers, number of pharmacies, and prescriptions for long-acting opioids, benzodiazepines or sedatives, or carisoprodol. ⋯ The positive predictive value of the model was low. Computationally simple models can identify high-risk patients based on prescription history alone, but improvement of the predictive value of models may require information from outside the prescription drug monitoring program. Patient or prescription features that predict opioid overdose may differ from those that predict diversion.
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Pyrethroid insecticides are widely used for pest control in agriculture or in human public health commonly as a topical treatment for scabies and head lice. Exposure to pyrethroids such as permethrin or tetramethrin (TM) causes sensory alterations such as transient pain, burning, stinging sensations, and paraesthesias. Despite the well-known effects of pyrethroids on sodium channels, actions on other channels that control sensory neuron excitability are less studied. ⋯ In TRESK knockout mice, pain-associated behaviors elicited by TM were enhanced, providing further evidence for a role of this channel in preventing excessive neuronal activation. Our results indicate that inhibition of K2P channels facilitates sensory neuron activation and increases their excitability. These effects contribute to the generation of paraesthesias and pain after pyrethroid exposure.
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There is an urgent need for better treatments for chronic pain, which affects more than 1 billion people worldwide. Antisense oligonucleotides (ASOs) have proven successful in treating children with spinal muscular atrophy, a severe infantile neurological disorder, and several ASOs are currently being tested in clinical trials for various neurological disorders. Here, we characterize the pharmacodynamic activity of ASOs in spinal cord and dorsal root ganglia (DRG), key tissues for pain signaling. ⋯ Furthermore, we confirm that ASOs are selective and do not modulate basal pain sensation. We also demonstrate that ASOs targeting the sodium channel Nav1.7 induce sustained analgesia up to 4 weeks. Taken together, our findings support the idea that ASOs possess the required pharmacodynamic properties, along with a long duration of action beneficial for treating pain.