Metabolomics: Impact of Comorbidities and Inflammation on Sickness Behaviors for Individuals with Chronic Wounds.

Significance: Approximately 6.5 million people in the United States suffer from chronic wounds. The chronic wound population is typically older and is characterized by a number of comorbidities associated with inflammation. In addition to experiencing wound-related pain, individuals with chronic wounds commonly experience multiple concurrent psychoneurological symptoms such as fatigue and depression, which delay wound healing. However, these distressing symptoms have been relatively overlooked in this population, although their adverse effects on morbidity are well established in other chronic disease populations. Recent Advances: Inflammation is involved in multiple pathways, which activate brain endothelial and innate immune cells that release proinflammatory cytokines, which produce multiple symptoms known as sickness behaviors. Inflammation-based activation of the kynurenine (KYN) pathway and its metabolites is a mechanism associated with chronic illnesses. Critical Issues: Although putative humoral and neuronal routes have been identified, the specific metabolic variations involved in sickness behaviors in chronic wound patients remain unclear. To improve health outcomes in the chronic wound population, clinicians need to have better understanding of the mechanisms underlying sickness behaviors to provide appropriate treatments. Future Directions: This article presents a synthesis of studies investigating associations between inflammation, metabolic pathways, and sickness behaviors in multiple chronic diseases. The presentation of a theoretical framework proposes a mechanism underlying sickness behaviors in the chronic wound population. By mediating the immune system response, dysregulated metabolites in the KYN pathway may play an important role in sickness behaviors in chronic inflammatory conditions. This framework may guide researchers in developing new treatments to reduce the disease burden in the chronic wound population.