Physical Activity Induces Nucleus Accumbens Genes Expression Changes Preventing Chronic Pain Susceptibility Promoted by High-Fat Diet and Sedentary Behavior in Mice

Abstract

4High-fat diet (HFD)-induced obesity was reported to increase pain behavior independent of obesity 5 status in rats, whereas weight loss interventions such as voluntary physical activity (PA) for adults 6 with overweight or obesity was reported to promote pain reduction in humans with chronic pain (CP). 7 However, is unknown whether an HFD and sedentary (SED) behavior is underlying to CP 8 susceptibility and whether voluntary PA can prevent it. Moreover, differential gene expression in the 9 nucleus accumbens (NAc) is considered to play a crucial role in CP susceptibility. The present study 10 used an adapted model of the inflammatory prostaglandin E2 (PGE)-induced persistent hyperalgesia 11 (PH-ST) protocol for mice, an HFD, and a voluntary PA paradigm to test these hypotheses. In 12 addition, we performed a transcriptome in the NAc and a gene ontology enrichment tools to 13 investigate the differential gene expression and identify the biological processes associated with CP 14 susceptibility tested here. Our results demonstrated that HFD and sedentary behavior promoted CP 15 susceptibility, which in turn was prevented by voluntary PA, even when the animals were fed an 16 HFD. Transcriptome in the NAc found 2,204 differential expression genes related CP susceptibility 17 promoted by HFD and sedentary behavior and prevented by voluntary PA. The gene ontology 18 enrichment revealed 41 biological processes implicated in CP susceptibility. Analyzing collectively 19 those biological processes, our results suggested that genes related to metabolic and mitochondria 20 stress were up-regulated in the CP susceptibility group, whereas genes related to neuroplasticity and 21 axonogenesis were up-regulated in the CP prevented group. These findings provide pieces of 22 evidence that an HFD and sedentary behavior promoted gene expression changes in the NAc related 23 to neurodegeneration and those changes were also underlying to CP susceptibility. Additionally, our 24 findings confirmed other findings supporting the crucial role of voluntary PA to prevent CP 25 susceptibility and add novel insights of differential gene expression in the NAc related to 26 neuroplasticity. 27 28

Running wheel exercise induces therapeutic and preventive effects on inflammatory stimulus-induced persistent hyperalgesia in mice

“…It is well established that, in this model, mice show persistent hyperalgesia up to 30 days after ending the PGE 2 injections [ 24 ] and this data was replicated in the present study. This is an appropriate model to study susceptibility and resilience to pain chronification [ 26 , 27 ], allowing us to assess the central hypothesis of the present study that physical exercise promotes resilience to chronic pain and can be used as a non-pharmacological therapeutic and preventive tool for this condition.…”