Pain
-
The persistence of inflammatory and neuropathic pain is poorly understood. We investigated a novel therapeutic paradigm by targeting gene networks that sustain or reverse persistent pain states. Our prior observations found that Sp1-like transcription factors drive the expression of TRPV1, a pain receptor, that is blocked in vitro by mithramycin A (MTM), an inhibitor of Sp1-like factors. ⋯ Mithramycin-dependent changes in gene expression following oxaliplatin treatment were largely opposite to and rarely overlapped with changes in gene expression induced by oxaliplatin alone. Notably, RNAseq analysis revealed MTM rescue of oxaliplatin-induced dysregulation of mitochondrial electron transport chain genes that correlated with in vivo reversal of excess reactive oxygen species in DRG neurons. This finding suggests that the mechanism(s) driving persistent pain states such as CIPN are not fixed but are sustained by ongoing modifiable transcription-dependent processes.
-
The coronavirus disease 19 (COVID-19) pandemic negatively affected children's health in the United States (US), with more severe disruption for marginalized groups. However, potential impact on pediatric chronic pain has not been assessed at the population level. This study aimed to (1) estimate differences in the US national prevalence of pediatric chronic pain during the first year of the COVID-19 pandemic (2020), relative to one year earlier (2019); (2) determine whether differences in prevalence varied across sociodemographic groups; and (3) explore changes in child, caregiver, and family factors associated with chronic pain prevalence. ⋯ Contrary to hypotheses, the adjusted prevalence of chronic pain was 31% lower in 2020 than in 2019 (aPR = 0.69, 95% CI: 0.61, 0.79), adjusting for child age, sex, race or ethnicity, caregiver education, neighborhood park or playground, and census region. The 2019 to 2020 change in chronic pain prevalence was similar by age ( P = 0.34), sex ( P = 0.94), race or ethnicity ( P = 0.41), caregiver education ( P = 0.49), neighborhood park or playground ( P = 0.22), and census region ( P = 0.20). Exploratory analyses identified 3 potential contributors to the unexpected decrease in the national prevalence of pediatric chronic pain: lower prevalence of bullying, more frequent family meals, and higher family resilience.