Articles: treatment.
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Randomized Controlled Trial Multicenter Study
Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.
Obstructive sleep apnea is characterized by disordered breathing during sleep and is associated with major cardiovascular complications; excess adiposity is an etiologic risk factor. Tirzepatide may be a potential treatment. ⋯ Among persons with moderate-to-severe obstructive sleep apnea and obesity, tirzepatide reduced the AHI, body weight, hypoxic burden, hsCRP concentration, and systolic blood pressure and improved sleep-related patient-reported outcomes. (Funded by Eli Lilly; SURMOUNT-OSA ClinicalTrials.gov number, NCT05412004.).
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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 Gi/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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Understanding the development of chronic pain (CP) is challenging due to its multifactorial etiology. Child maltreatment (CM), encompassing various types of neglect and abuse affecting more than one-third of the population, is a critical aspect of early-life adversity with long-lasting impacts. It is increasingly recognized for its role in altering biopsychosocial processes, potentially increasing vulnerability to CP. ⋯ Importantly, biopsychosocial factors are found to explain over 60% of the association between CM and CP, with psychological factors playing a key role. This study not only characterizes the relationship between CM and CP but also underscores the influence of psychosocial elements in this dynamic interplay. These findings offer important insights into the long-term impacts of CM and provide a foundation for developing targeted therapeutic and preventive strategies for CP.