A high fat anti-inflammatory diet improves widespread allodynia despite worsening metabolic outcomes in adult mice exposed to neonatal maternal separation

Abstract

Inflammation plays a key role in the progression and maintenance of chronic pain, which impacts the lives of millions of Americans. Despite growing evidence that chronic pain can be improved by treating underlying inflammation, successful treatments are lacking and pharmaceutical interventions are limited due to drug side effects. Here we are testing whether an anti-inflammatory diet (AID) containing a combination of key anti-inflammatory compounds, at clinically relevant doses, improves pain-like behaviors in a preclinical model of chronic widespread hypersensitivity induced by neonatal maternal separation (NMS). Our results demonstrate a benefit of the AID on pain-like behaviors, despite the diet being high in fat, which led to increased caloric intake, adiposity, and weight gain. The AID specifically increased measures of metabolic syndrome and inflammation in female mice, compared to an isocaloric, macronutrient-matched diet lacking the anti-inflammatory compounds. Male mice, especially those exposed to NMS, were equally susceptible to both diets worsening metabolic measures. This work highlights important sexual dimorphic outcomes related to early life stress exposure and dietary interventions, as well as a potential disconnect between improvements in pain-like behaviors and metabolic measures.