Pain
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Urocortin 3 is a neuropeptide that belongs to the corticotropin-releasing hormone family and is involved in mechanosensation and stress regulation. In this study, we show that Urocortin 3 marks a population of excitatory neurons in the mouse spinal cord, divided into 2 nonoverlapping subpopulations expressing protein kinase C gamma or calretinin/calbindin 2, populations previously associated with mechanosensation. ⋯ Chemogenetic activation of lumbar Urocortin 3-Cre neurons evoked a targeted biting/licking behavior towards the corresponding dermatome and chemogenetic inhibition decreased Compound 48/80-induced behavior. Hence, spinal lumbar Urocortin 3 neurons represent a mechanically associated population with roles in both scratching and Compound 48/80-induced sensations.
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Lower socioeconomic position (SEP) is associated with increased risk of developing chronic pain, experiencing more severe pain, and suffering greater pain-related disability. However, SEP is a multidimensional construct; there is a dearth of research on which SEP features are most strongly associated with high-impact chronic pain, the relative importance of SEP predictive features compared to established chronic pain correlates, and whether the relative importance of SEP predictive features differs by race and sex. This study used 3 machine learning algorithms to address these questions among adults in the 2019 National Health Interview Survey. ⋯ Whereas the relative importance of body mass index and owning/renting a residence was higher for non-Hispanic Black adults, the relative importance of working adults in the family and housing stability was higher for non-Hispanic White adults. Anxiety symptom severity, body mass index, and cigarette smoking had higher relevance for women, while housing stability and frequency of anxiety and depression had higher relevance for men. Results highlight the potential for machine learning algorithms to advance health equity research.
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Given the negative impact of opioid use on population health, prescriptions for alternative pain-relieving medications, including gabapentin, have increased. We wanted to determine whether people who filled gabapentin and opioid prescriptions concurrently ("gabapentin + opioids") had greater mortality than those who filled an active control medication (tricyclic antidepressants [TCAs] or duloxetine) and opioids concurrently ("TCAs/duloxetine + opioids"). In this population-based, propensity score-matched cohort study, we identified Medicare beneficiaries with spine-related diagnoses from 2017 to 2019. ⋯ However, people treated with gabapentin + opioids were at slightly increased risk of a major medical complication (1.02 [1.00-1.04]; P = 0.03) compared to those treated with TCAs/duloxetine + opioids. Results were similar in analyses (1) restricted to ≤30-day follow-up and (2) that required ≥2 fills of each prescription. When treating pain in older adults taking opioids, the addition of gabapentin did not increase mortality risk relative to addition of TCAs or duloxetine.
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Repetitive ischemia with reperfusion (I/R) injury is a common cause of myalgia. Ischemia with reperfusion injuries occur in many conditions that differentially affect males and females including complex regional pain syndrome and fibromyalgia. Our preclinical studies have indicated that primary afferent sensitization and behavioral hypersensitivity caused by I/R injury may be due to sex-specific gene expression in the dorsal root ganglia (DRG) and distinct upregulation of growth factors and cytokines in the affected muscles. ⋯ AUF1 knockdown was able to specifically inhibit repeated I/R-induced gene expression in females potentially downstream of prolactin receptor signaling. Data suggest RNA-binding proteins such as pAUF1 may underlie the sex-specific effects on DRG gene expression that modulates behavioral hypersensitivity after repeated I/R injury through prolactin signaling. This study may aid in finding distinct receptor differences related to the evolution of acute to chronic ischemic muscle pain development between sexes.