Comorbidity of Alcohol Use Disorder and Chronic Pain: Genetic Influences on Brain Reward and Stress Systems

Abstract

Alcohol use disorder (AUD) is highly comorbid with chronic pain (CP). Evidence has suggested that neuroadaptive processes characterized by reward deficit and stress surfeit are involved in the development of AUD and pain chronification. Neurological data suggest that shared genetic architecture associated with the reward and stress systems may contribute to the comorbidity of AUD and CP. This monograph first delineates the prevailing theories of the development of AUD and pain chronification focusing on the reward and stress systems. It then provides a brief summary of relevant neurological findings followed by an evaluation of evidence documented by molecular genetic studies. Candidate gene association studies have provided some initial support for the genetic overlap between AUD and CP; however, these results must be interpreted with caution until studies with sufficient statistical power are conducted and replications obtained. Genomewide association studies have suggested a number of genes (e.g., TBX19, HTR7, and ADRA1A) that are either directly or indirectly related to the reward and stress systems in the AUD and CP literature. Evidence reviewed in this monograph suggests that shared genetic liability underlying the comorbidity between AUD and CP, if present, is likely to be complex. As the advancement in molecular genetic methods continues, future studies may show broader central nervous system involvement in AUD-CP comorbidity.

Keywords: Alcohol Use Disorder; Candidate Association Gene Studies; Chronic Pain; Comorbidity; Genomewide Association Studies.

Figure 1. Unique and common genetic influences to AUD and CP

Three classes of genetic involvement should be considered: possible genes that influence (1) both AUD and CP (genes in tangerine ellipse are associated with the reward pathways & genes in turquoise ellipse are associated with the stress pathways), (2) AUD independent of CP (in purple ellipse), and (3) CP independent of AUD (in red ellipse). Furthermore, there are genes that mediate or modulate the reward and stress systems, or broadly affect the central nervous system (in blue ellipse). The gene groups and corresponding genes in each group in this figure serve as examples and do not represent an exhaustive list. Among them, some have been supported by existing empirical findings, whilst others await further investigations.