Pain
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It is often assumed that there are 2 types of pain patients: those who respond well to efficacious pain therapies and those who do not respond at all, with few people in the middle. This assumption is based on research that claims that changes in pain intensity have a bimodal distribution. The claim of bimodality has led to calls for a change in how pain clinical trials are designed and analyzed, eg, performing "responder" analyses instead of comparing group mean values to evaluate the treatment effect. ⋯ We found that the improper construction of histograms, using unequal bin widths, was the principal flaw leading to the bimodality claim, along with the use of the oft-criticized baseline observation carried forward method for imputing missing data also serving as a contributing factor. Properly constructed histograms of absolute change in pain intensity using equal bin widths, combined with more principled methods for handling missing data, resulted in distributions that had a more unimodal appearance. Although our findings neither support nor refute the hypothesis that distinct populations of "responders" and "nonresponders" to pain interventions exist, the analyses presented in earlier work do not provide support for this hypothesis, nor for the recommendation that pain clinical trials prioritize "responder" analyses, a less efficient analysis strategy.
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An imbalance between excitatory and inhibitory neurotransmission has been linked to fibromyalgia (FM). Magnetic resonance spectroscopy has shown increased levels of glutamate in the insula and posterior cingulate cortex in FM as well as reduced insular levels of gamma-aminobutyric acid (GABA). Both of these changes have been associated with increased pain sensitivity. ⋯ The changes were widespread and not restricted to pain-processing regions. These findings suggest that the GABAergic system is altered, possibly indicating an imbalance between excitatory and inhibitory neurotransmission. Future studies should try to understand the nature of the dysregulation of the GABAergic system in FM and in other pain syndromes.
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Posttraumatic widespread pain (PTWP) and posttraumatic stress symptoms (PTSS) are frequent comorbid sequelae of trauma that occur at different rates in women and men. We sought to identify microRNA (miRNA) that may contribute to sex-dependent differences in vulnerability to these outcomes. Monte Carlo simulations (x10,000) identified miRNA in which predicted targeting of PTWP or PTSS genes was most enriched. ⋯ Furthermore, in support of increasing evidence indicating a role for the circadian rhythm (CR) in PTWP and PTSS pathogenesis, miR-19b targets were enriched in CR gene transcripts. Human cohort and in vitro analyses assessing miR-19b regulation of key CR transcripts, CLOCK and RORA, supported the potential importance of miR-19b to regulating the CR pathway. Together, these results highlight the potential role that sex-dependent expression of miR-19b might play in PTWP and PTSS development after trauma/stress exposure.
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Early life stress (ELS) can significantly influence biological pathways associated with nociception, increasing vulnerability to future heightened pain sensitivity and subsequent risk of pain events. However, very little human research has investigated the association of ELS, measured across multiple domains, with future pain sensitivity. Data from Gen1 and Gen2 of the Raine Study were used to assess the association between a wide range of early life stressors, including antenatally, and pressure and cold pain sensitivity at young adulthood. ⋯ More problematic behaviour at age 2 years was associated with less pressure pain sensitivity at 22 years (13.7 kPa, 95% CI: 1.0-27.0, P = 0.037), with no interaction between problematic behaviour and pain experience at 22 years. For those reporting a moderate/high pain experience at 22 years, poor family functioning increased the odds ratio for high cold pain sensitivity (3.0, 95% CI: 1.6-5.6), but for those reporting no/low pain experience, it did not (OR:1.2, 95% CI: 0.8-1.8). This study provides the most comprehensive investigation of the relationship between ELS and pressure and cold pain sensitivity in young adults supporting early life as a critical period of development influencing future nociceptive processing.