Chronic paternal morphine exposure increases sensitivity to morphine-derived pain relief in male progeny

Abstract

Parental history of opioid exposure is seldom considered when prescribing opioids for pain relief. To explore whether parental opioid exposure may affect sensitivity to morphine in offspring, we developed a “rat pain scale” with high-speed imaging, machine learning, and mathematical modeling in a multigenerational model of paternal morphine self-administration. We find that the most commonly used tool to measure mechanical sensitivity in rodents, the von Frey hair, is not painful in rats during baseline conditions. We also find that male progeny of morphine-treated sires had no baseline changes in mechanical pain sensitivity but were more sensitive to the pain-relieving effects of morphine. Using RNA sequencing across pain-relevant brain regions, we identify gene expression changes within the regulator of G protein signaling family of proteins that may underlie this multigenerational phenotype. Together, this rat pain scale revealed that paternal opioid exposure increases sensitivity to morphine’s pain-relieving effects in male offspring.

Fear conditioning biases olfactory stem cell receptor fate

“…Parental stressors, such as chronic defeat or maternal separation, result in hormonal disturbances and behavioral phenotypes in the offspring (Deitz et al, 2011; Morgan & Bale, 2011; Gapp et al, 2014). Finally, toxins and addictive drugs result in an array of metabolic disturbances in the F1 population that recapitulate the paternal state (Toussaint et al, 2022). These paternal stressors are associated with metabolic and hormonal disturbances that can readily act at a distance to affect the gamete.…”

Endothelial PDGF-BB/PDGFR-β signaling promotes osteoarthritis by enhancing angiogenesis-dependent abnormal subchondral bone formation

“…Mechanical allodynia was assessed using a digital electronic von Frey anesthesiometer, as previously described (IITC Life Science, CA, USA). 64 , 65 This exam was performed five times with a 15 min inter-test delay between each repetition. Each mouse was hung above a wire grid in a clear plastic container.…”

Towards understanding and halting legacies of trauma

“…To probe mechanisms underlying how detrimental influences of trauma echo across generations, researchers have sought to model multi-generational legacies of salient environmental experiences (SEEs). These experiences have included exposure to psychosocial stress (21)(22)(23)(24)(25)(26)(27)(28)(29), dietary perturbations (30)(31)(32)(33)(34)(35)(36), immune, and chemical challenges (15)(16)(17)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). Broadly, these studies have examined physiology and behavior in future G1, G2…Gn generations after exposing the G0 generation of a variety of species that include rodents, worms, flies, and fish to stressors as diverse as maternal separation, access to limited nesting material, low protein or high fat diets, social defeat, predation, fungicides, endocrine disrupting chemicals, and viral mimetics.…”