Pain
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Understanding how large language model (LLM) recommendations vary with patient race/ethnicity provides insight into how LLMs may counter or compound bias in opioid prescription. Forty real-world patient cases were sourced from the MIMIC-IV Note dataset with chief complaints of abdominal pain, back pain, headache, or musculoskeletal pain and amended to include all combinations of race/ethnicity and sex. Large language models were instructed to provide a subjective pain rating and comprehensive pain management recommendation. ⋯ Race/ethnicity and sex did not influence LLM recommendations. This study suggests that LLMs do not preferentially recommend opioid treatment for one group over another. Given that prior research shows race-based disparities in pain perception and treatment by healthcare providers, LLMs may offer physicians a helpful tool to guide their pain management and ensure equitable treatment across patient groups.
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Treating bone cancer pain (BCP) continues to be a clinical challenge, and the underlying mechanisms of BCP remain elusive. This study reports that Wnt5a/Ryk signaling in the dorsal root ganglion neurons is critical to the development of BCP. Tibia bone cavity tumor cell implantation produces spontaneous and evoked behaviorally expressed pain as well as ectopic sprouting and activity of Wnt5a/Ryk signaling in the neural soma and peripheral terminals and the tumor-affected bone tissues. ⋯ Blocking Ryk receptor activation suppresses Wnt5a-induced mechanical allodynia and thermal hyperalgesia. Wnt5a facilitation of transient receptors potential vanilloid type-1 sensitization is blocked by inhibiting c-Jun N-terminal kinase activation. These findings indicate a critical peripheral mechanism of Wnt5a/Ryk signaling underlying the pathogenesis of BCP and suggest that targeting Wnt5a/Ryk in the primary sensory neurons and the tumor-invasive area may be an effective approach for the prevention and treatment of BCP.
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Memory biases for pain-related information may contribute to the development and maintenance of chronic pain; however, evidence for when (and for whom) these biases occur is mixed. Therefore, we examined neural, stress, and psychological factors that could influence memory bias, focusing on memories that motivate disabling behaviors: pain perception, conditioned responses to threat-and-safety cues, and responses to aversive nonnoxious stimuli. Two studies were conducted with adolescents with and without chronic pain. ⋯ However, no memory bias was present for the emotional response to an aversive stimulus (US; loud scream) or for the recall of pain intensity. Functional connectivity of the amygdala and hippocampus with memory circuits related to the degree of memory bias, but the specific connections varied between the studies, and we observed no relationship between memory bias and brain morphology. Our findings highlight the value of considering the interaction between implicit and explicit memory systems, contributing to a more comprehensive understanding of emotional memory biases in the context of chronic pain.
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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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Although the behavioral response to pain is complex and involves supraspinal processes, assessment of pain symptoms in animal models still mainly relies on reflex-based nociceptive tests, which do not account for the affective-motivational nor cognitive components of pain. We introduce a double avoidance place preference paradigm, an integrated testing procedure in freely moving rats that relies on the conflict between the avoidance of a dark compartment in which a thermal ramp is activated, and the escape towards an aversive brightly lit compartment. We were able to differentiate the first nociceptive threshold from the temperature of definitive escape from the dark compartment, conveying information on the adaptive behavior of animals. ⋯ In animals exhibiting hyperalgesia following intraplantar complete Freund adjuvant injection, escape thresholds were significantly higher than that of control animals, hinting at a maladaptive affective-motivational response to noxious stimulation. However, in cuff animals, we failed to reveal any hot nociceptive hypersensitivity, but animals exhibited a strong adaptive response to cold simulation upon reexposure. Overall, the proposed paradigm allows for an integrated cortical response leading to a proactive avoidance behavior, while fully complying with ethical standards in animal experimentation.