Theoretical review
The comorbidity of insomnia, chronic pain, and depression: Dopamine as a putative mechanism

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Summary

Epidemiological, cross-sectional, and prospective studies suggest that insomnia, chronic pain, and depression frequently co-occur and are mutually interacting conditions. However, the mechanisms underlying these comorbid disorders have yet to be elucidated. Overlapping mechanisms in the central nervous system suggest a common neurobiological substrate(s) may underlie the development and interplay of these disorders. We propose that the mesolimbic dopamine system is an underappreciated and attractive venue for the examination of neurobiological processes involved in the interactions, development, exacerbation, and maintenance of this symptom complex. In the present article, studies from multiple disciplines are reviewed to highlight the role of altered dopaminergic function in the promotion of arousal, pain sensitivity, and mood disturbance. We argue that studies aiming to elucidate common factors accounting for the comorbidity of insomnia, chronic pain, and depression should evaluate functioning within the mesolimbic dopaminergic system and its effect on common processes known to be dysregulated in all three disorders.

Section snippets

Summary of studies simultaneously investigating insomnia, pain, and depression

Although relatively fewer studies have examined the triad of insomnia, chronic pain, and depression – or their symptoms – together in one model, there is growing support for the hypothesis that the three disorders are linked through common mechanisms. Wilson et al.18 examined comorbidities in a sample of chronic musculoskeletal pain patients and found that those diagnosed with depression were significantly more likely to have insomnia. Further, patients with both comorbidities reported greater

Mesolimbic DA and arousal

DA is a neurotransmitter from the catecholamine family that is considered to be a key neurobiological substrate of reward, and has traditionally been the target of pharmaceutical therapies for movement disorders, psychotic disorders, and to a lesser extent depression. Evidence also indicates, however, that DA is integral to the promotion and maintenance of arousal states (for reviews, see*29, 30).

Mesolimbic DA neurons originate in the ventral tegmental area and the substantia nigra pars

Conflicts of interest

None declared.

Acknowledgments

The authors would like to acknowledge funding support from NINDS/NINR grant T32 NS070201 (PHF) and R01 AR05487, R01 AR059410, R01 DE019731(MTS).

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