Pain
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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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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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The sodium-activated potassium channel Slack (KNa1.1, Kcnt1) plays a critical role in tuning neuronal excitability. Previous studies have revealed that Slack is expressed in neurons of the superficial dorsal horn of the spinal cord. However, the precise role of Slack in spinal dorsal horn neurons is unclear. ⋯ Unexpectedly, Lbx1-Slack-/- mice demonstrated increased scratching after intradermal injection of chloroquine, LY344864, and histamine. Moreover, neuromedin B receptors are coexpressed with Slack in the dorsal horn, and scratching after intrathecal delivery of neuromedin B was increased in Lbx1-Slack-/- mice. Our study provides in vivo evidence that Slack expressed in spinal dorsal horn neurons inhibits nerve injury-induced allodynia and acute itch induced by various pruritogens.
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The 2 tetrodotoxin-resistant (TTXr) voltage-gated sodium channel subtypes NaV1.8 and NaV1.9 are important for peripheral pain signaling. As determinants of sensory neuron excitability, they are essential for the initial transduction of sensory stimuli, the electrogenesis of the action potential, and the release of neurotransmitters from sensory neuron terminals. NaV1.8 and NaV1.9, which are encoded by SCN10A and SCN11A, respectively, are predominantly expressed in pain-sensitive (nociceptive) neurons localized in the dorsal root ganglia (DRG) along the spinal cord and in the trigeminal ganglia. ⋯ Successful knockout of both channels was verified by whole-cell recordings demonstrating the absence of NaV1.8- and NaV1.9-mediated Na+ currents in NaV1.8/NaV1.9 DKO DRG neurons. Global RNA sequencing identified significant deregulation of C-LTMR marker genes as well as of pain-modulating neuropeptides in NaV1.8/NaV1.9 DKO DRG neurons, which fits to the overall only moderately impaired acute pain behavior observed in DKO mice. Besides addressing the function of both sodium channels in pain perception, we further demonstrate that the null-background is a very valuable tool for investigations on the functional properties of individual human disease-causing variants in NaV1.8 or NaV1.9 in their native physiological environment.
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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.