Chronic Pain and Substance Use Disorders: A Brief Narrative Review of Genetic, Neurobiological, and Environmental Contributions to Comorbidity.

Background: Chronic pain (CP) and substance use disorders (SUDs) frequently co-occur. This brief review highlights environmental, neurobiological, and genetic sources of comorbidity of CP and SUDs, focused on alcohol, nicotine, cannabis, and opioids. Methods: A literature search on CP and SUDs was performed using Google Scholar and PubMed. Relevant literature was summarized in a narrative review. Results: Recent genomic studies reveal that SUDs and CP share a significant portion of genetic variance, and causal inference methods suggest that CP and SUDs have bidirectional effects on one another. CP and SUDs share multiple neurobiological pathways such as the reward and stress systems, with studies implicating important regions such as the insular and anterior cingulate cortex, the ventral tegmental area, and the nucleus accumbens. Environmental risk factors for CP and SUDs include socioeconomic background, education, and broader environmental factors such as neighborhood resources, air quality and greenspace. Social support is also a protective factor against CP and SUD diagnoses and crucial for their successful treatment and remission. Conclusions: Promising new areas of research underlying CP and SUD comorbidity include female-specific CP conditions and substance use patterns, the role of the immune system in both SUDs and CP, and the rise of large biobanks that will further precision medicine by allowing researchers to jointly model genetic, neurobiological, and socioenvironmental factors underlying their co-occurrence. In summary, CP and SUDs are debilitating conditions with far-ranging consequences for both individuals and communities; investigating their shared etiology will result in better treatments for both.