How environmental enrichment balances out neuroinflammation in chronic pain and comorbid depression and anxiety disorders

Depression and anxiety commonly occur in chronic pain states and the coexistence of these diseases worsens outcomes for both disorders and may reduce treatment adherence and response. Despite the advances in the knowledge of chronic pain mechanisms, pharmacological treatment is still unsatisfactory. Research based on exposure to environmental enrichment is currently under investigation and seems to offer a promising low-cost strategy with no side effects. In this review, we discuss the role of inflammation as a major biological substrate and aetiological factor of chronic pain and depression/anxiety and report a collection of preclinical evidence of the effects and mechanisms of environmental enrichment. As microglia participates in the development of both conditions, we also discuss microglia as a potential target underlying the beneficial actions of environmental enrichment in chronic pain and comorbid depression/anxiety. We also discuss how alternative interventions under clinical guidelines, such as environmental enrichment, may improve treatment compliance and patient outcomes.