Chronic opioid use impacts brain functionRelated to the immune system during cancer treatment

Current treatments for opioid use disorders are often ineffective for chronic opioid use disorders as well as other serious mental health conditions according to a study published in the current issue of Biological Psychiatry. The study is the first of its kind to evaluate the lifespan effects of chronic low dose opioid treatment in normal mouse models.

Researchers at the Virginia Commonwealth Universitys Anderson Cancer Center analyzed chronic low dose opioid use and treatment responses of a mouse model of elevated blood pressure. They used a novel delivery system for the study being published in Biological Psychiatry. The mice were treated with chronic low dose opioid over a one-week period.

We found that chronic low dose opioid treatment of the mouse model resulted in an increase in the endothelial cell survival a marker of an environment in which endothelial cells are set up to protect against inflammation and provide a better quality of life said senior author Andrew Ewald MD director of the Anderson Center for Brain Metastases and the Department of Human Genetics and Genomic Biology at VCU. That endogenous survival resulted in reduced activation of the interneurons which were in turn linked to increased expression of two oscillatory signals one that is inhibited when the prefrontal cortex is suppressed and one that enhances when the neocortex is suppressed.

The physiological response to chronic low dose opioid treatment was inverted in the hypothalamus a brain region that is important for the regulation of feeding and craving. Estrogen levels rose somewhat following treatment but only after significantly longer than after the initiation of maintenance opioid use.

The findings suggest that acetaminophen can boost the integrity of the hypothalamus and decrease the impact of opioid treatment on the treatment-dependent behavior of rodents. The oxidative stress reduction effect of chronic low dose opioid treatment on endothelial cell survival are more pronounced in the hypothalamus a region where most chronic low dose opioid use occurs. Chronic low dose treatment does not appear to directly impact the gut microbiota suggesting a functional challenge that likely requires further study.

Now that we have identified one of opioids potential side effects we need to study this more said first author and postdoctoral fellow Pieta van Leina Ph. D. who initiated the study as a postdoctoral fellow in Ewalds laboratory. We currently need to determine if chronic low dose treatment is not followed up with tolerance remission or neuroprotection. In addition the therapeutic relevance of the interventions will be evaluated using animal models and human clinical trials.