Articles: cations.
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Prescription opioids for noncancer pain in the United Kingdom have increased over the past 2 decades, alongside associated harms. Policies addressing opioid prescribing must be tailored to individual patient needs with specific disease systems. The aim of this study was to evaluate clinical conditions associated with new opioid initiation in noncancer pain using nationally representative UK data. ⋯ This is the first study in the United Kingdom evaluating large-scale national data to assess indications associated with opioid initiation. Nearly 3 quarters of new opioid prescriptions for noncancer pain were in patients with musculoskeletal conditions, often for conditions with limited evidence for opioid efficacy. These findings could inform targeted interventions and future policies to support nonpharmacological interventions in the most common conditions where opioid harms outweigh benefits.
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The development of nonopioid analgesics for the treatment of abdominal pain is a pressing clinical problem. To address this, we examined the expression of G i/o -coupled receptors, which typically inhibit nociceptor activation, in colonic sensory neurons. This led to the identification of the orphan receptor GPR35 as a visceral analgesic drug target because of its marked coexpression with transient receptor potential ankyrin 1 (TRPA1), a mediator of noxious mechanotransduction in the bowel. ⋯ Consistent with this mechanism of action, we confirmed that TRPA1-mediated colonic contractions evoked by SP release were abolished by CS pretreatment in a GPR35-dependent manner. Our data demonstrate that GPR35 agonists prevent the activation and sensitisation of colonic nociceptors through the inhibition of TRPA1-mediated SP release. These findings highlight the potential of GPR35 agonists to deliver nonopioid analgesia for the treatment of abdominal pain.
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Beauty judgments are common in daily life, but rarely studied in cognitive neuroscience. Here, in three studies, we searched for the neural mechanisms of musical beauty using a naturalistic free-listening paradigm applied to behavioral and neuroimaging recordings and validated by experts' judgments. In Study 1, 30 adults continuously rated the perceived beauty of three musical pieces using a motion sensor. ⋯ Effective connectivity analysis discovered inhibition of auditory activation and neural communication with the right orbitofrontal cortex for listening to beautiful passages vs. intrinsic activation of auditory cortices and decreased coupling to orbitofrontal cortex for not-beautiful passages. Experts' questionnaires indicated that the beautiful passages were more melodic, calm, sad, slow, tonal, traditional, and simple than the ones rated negatively. In sum, we identified neural and psychological underpinnings of musical beauty, irrespectively of individual taste and listening biography.