Alleviating Social Pain: A Double-Blind, Randomized, Placebo-Controlled Trial of Forgiveness and Acetaminophen.

BACKGROUND: Research has suggested that physical pain (e.g., caused by injury) and social pain (e.g., caused by social rejection) are modulated by some of the same biological systems. Consequently, it is possible that acetaminophen, which is commonly used to alleviate physical pain through neurochemical pathways, may have social pain-relieving effects that interact with forgiveness, which reduces social pain through psychological pathways. To date, however, only a few studies have examined how experiences of social pain change over time, and none have examined how acetaminophen and forgiveness interact to influence these effects. PURPOSE: We addressed these issues by investigating how acetaminophen administration and daily forgiveness are associated with experiences of social pain over 21 days. We hypothesized that acetaminophen-related reductions in social pain across the 21-day study period would be greatest on days following high levels of forgiveness. METHOD: To test this hypothesis, we conducted a double-blind, randomized, placebo-controlled trial in which we randomly assigned 42 healthy young adults to an acetaminophen condition (1,000 mg of acetaminophen daily), placebo-control condition (400 mg of potassium daily), or empty-control (no pill) condition. We then assessed their levels of forgiveness and social pain for 20 consecutive days. RESULTS: As hypothesized, acetaminophen reduced participants' social pain levels over time but only for those exhibiting high levels of forgiveness (i.e., 18.5% reduction in social pain over 20 days). CONCLUSIONS: These data are the first to show that forgiveness and acetaminophen have interactive effects on experiences of social pain, which is one of the most common and impactful of all human experiences.

Spinal Angulation: A Limitation of the Fetal Lamb Model of Myelomeningocele.

INTRODUCTION: The surgically induced fetal lamb model is the most commonly used large animal model of myelomeningocele (MMC) but is subject to variation due to surgical technique during defect creation. MATERIAL AND METHODS: Thirty-one fetal lambs underwent creation of the MMC defect, followed by defect repair with either an extracellular matrix (ECM) patch (n = 10) or ECM seeded with placental mesenchymal stromal cells (n = 21). Postnatal hindlimb function was assessed using the Sheep Locomotor Rating (SLR) scale. Postmortem magnetic resonance imaging of the lumbar spine was used to measure the level and degree of spinal angulation, as well as cross-sectional area of remaining vertebral bone. RESULTS: Median level of angulation was between the 2nd and 3rd lumbar vertebrae, with a median angle of 24.3 degrees (interquartile range 16.2-35.3). There was a negative correlation between angulation degree and SLR (r = -0.44, p = 0.013). Degree of angulation also negatively correlated with the normalized cross-sectional area of remaining vertebral bone (r = -0.75, p < 0.0001). DISCUSSION: Surgical creation of fetal MMC leads to varying severity of spinal angulation in the ovine model, which affects postnatal functional outcomes. Postnatal assessment of spinal angulation aids in standardization of the surgical model of fetal MMC repair.

High density placental mesenchymal stromal cells provide neuronal preservation and improve motor function following in utero treatment of ovine myelomeningocele.

PURPOSE: The purpose of this study was to determine whether seeding density of placental mesenchymal stromal cells (PMSCs) on extracellular matrix (ECM) during in utero repair of myelomeningocele (MMC) affects motor function and neuronal preservation in the ovine model. METHODS: MMC defects were surgically created in 33 fetuses and repaired following randomization into four treatment groups: ECM only (n = 10), PMSC-ECM (42 K cells/cm2) (n = 8), PMSC-ECM (167 K cells/cm2) (n = 7), or PMSC-ECM (250-300 K cells/cm2) (n = 8). Motor function was evaluated using the Sheep Locomotor Rating Scale (SLR). Serial sections of the lumbar spinal cord were analyzed by measuring their cross-sectional areas which were then normalized to normal lambs. Large neurons (LN, diameter 30-70 µm) were counted manually and density calculated per mm2 gray matter. RESULTS: Lambs treated with PMSCs at any density had a higher median SLR score (15 [IQR 13.5-15]) than ECM alone (6.5 [IQR 4-12.75], p = 0.036). Cross-sectional areas of spinal cord and gray matter were highest in the PMSC-ECM (167 K/cm2) group (p = 0.002 and 0.006, respectively). LN density was highest in the greatest density PMSC-ECM (250-300 K/cm2) group (p = 0.045) which positively correlated with SLR score (r = 0.807, p < 0.0001). CONCLUSIONS: Fetal repair of myelomeningocele with high density PMSC-ECM resulted in increased large neuron density, which strongly correlated with improved motor function. TYPE OF STUDY: Basic science. LEVEL OF EVIDENCE: N/A.