Major thermal burn injuries result in approximately 40,000 hospitalizations in the United States each year. Chronic pain affects up to 60% of burn survivors, and Black Americans have worse chronic pain outcomes than White Americans. Mechanisms of chronic pain pathogenesis after burn injury, and accounting for these racial differences, remain poorly understood. Due to socioeconomic disadvantage and differences in skin absorption, Black Americans have an increased prevalence of Vitamin D deficiency. We hypothesized that peritraumatic Vitamin D levels predict chronic pain outcomes after burn injury and contribute to racial differences in pain outcomes. Among burn survivors (n = 77, 52% White, 48% Black, 77% male), peritraumatic Vitamin D levels were more likely to be deficient in Blacks vs Whites (27/37 [73%] vs 14/40 [35%], P < .001). Peritraumatic Vitamin D levels were inversely associated with chronic post-burn pain outcomes across all burn injury survivors, including those who were and were not Vitamin D deficient, and accounted for approximately one-third of racial differences in post-burn pain outcome. Future studies are needed to evaluate potential mechanisms mediating the effect of Vitamin D on post-burn pain outcomes and the potential efficacy of Vitamin D in improving pain outcomes and reducing racial differences.

Chronic pain is a significant comorbidity of burn injury affecting up to 60% of survivors. Currently, no treatments are available to prevent chronic pain after burn injury. Accumulating evidence suggests that omega-3 fatty acids (O3FAs) improve symptoms across a range of painful conditions. In this study, we evaluated whether low peritraumatic levels of O3FA predict greater pain severity during the year after burn injury. Burn survivors undergoing skin autograft were recruited from three participating burn centers. Plasma O3FA (n = 77) levels were assessed in the early aftermath of burn injury using liquid chromatography/mass spectrometry, and pain severity was assessed via the 0 to 10 numeric rating scale for 1 year following burn injury. Repeated-measures linear regression analyses were used to evaluate the association between peritraumatic O3FA concentrations and pain severity during the year following burn injury. Peritraumatic O3FA concentration and chronic pain severity were inversely related; lower levels of peritraumatic O3FAs predicted worse pain outcomes (β = −0.002, P = .020). Future studies are needed to evaluate biological mechanisms mediating this association and to assess the ability of O3FAs to prevent chronic pain following burn injury.

Fisetin is a natural flavonoid that possesses antioxidant, anti-inflammatory, anti-senescence, and neuroprotective effects in preclinical studies. This double-blind randomized clinical trial investigated the effects of two fisetin dosing regimens on senescent gene expression in peripheral blood mononuclear cells (PBMCs) in elderly humans (> 55 years old). Participants were randomized to Daily dose (100mg/day, N = 41) or Bolus dose (20mg/kg for two consecutive days on and 28 days off, N = 40) for 60 days. Blood draw, PBMC isolation, RNA extraction and quantitative polymerase chain reaction (Q-PCR) for 5 target genes were performed at baseline, and days 15, 35, 45 and 60. At the primary endpoint, day 45, both fisetin dosing regimens significantly decreased galactosidase beta 1 (GLB1) and P16 ^INK4A (P16) gene expression. Bolus dose also significantly reduced macrophage migration inhibition factor (MIF) and alpha-L-fucosidase 1 (FUCA1) compared to baseline and decreased MIF compared to daily dose. Further, Bolus dose significantly decreased GLB1 and MIF at days 15, 35, 60, and P16 at days 15, 35 as well as FUCA1 at day 35 compared to baseline. Hence, Bolus dosing of fisetin is more effective than Daily dosing for reducing cellular senescent genes in PBMCs isolated from elderly human blood.