ReviewPain and depression comorbidity: A preclinical perspective
Introduction
Pain is one of the most common reasons that patients seek medical treatment, representing a major clinical, social and economic problem. The estimated prevalence of various pain conditions ranges from 8% to as high as 60% [1], [2], [3]. In the United States alone, chronic pain is estimated to affect at least 116 million adults, reduces quality of life, and costs society at least $636 billion annually [4]. Similarly, depression is among the most common and costly of all psychiatric disorders, accounting for 4.4% of total disability-adjusted life years [5]. Up to 65% of individuals have recurrent episodes of depressive disorders in their lifetime [6], [7]. Even worse, a large proportion of patients with depressive disorders were not diagnosed or did not receive treatment, and for those who did receive treatment, approximately 50% of patients with depression did not experience a response to first-line antidepressant therapy and the proportion of patients achieving a response decreases to approximately 30% with second-line treatment [8], [9], [10]. Unsurprisingly, the highly prevalent and chronic nature of depression creates a substantial economic and societal burden to society. It was estimated that the total cost of depression in the United States in 2000 was $83.1 billion [11] and €118 billion in Europe in 2004 [12].
Clinical observations have long recognized the comorbidity of pain and depression. These observations have led to some authors to label the comorbidity as the pain-depression syndrome or pain-depression dyad. Both conditions often coexist, respond to similar treatments, exacerbate one another, and share overlapping biological mechanisms [13], [14]. The comorbid nature of depression and pain has been extensively reviewed [15], [16], [17], [18]; however, the exact neurobiological mechanisms remain unclear, and mechanism-based preclinical studies are rare [19]. The goal of this review was to briefly summarize the clinical findings of pain-depression comorbidity, analyze the limited preclinical studies, and propose to develop and use domain interplay concept to study pain-depression comorbidity in future investigations.
Section snippets
Clinical findings of pain and depression comorbidity
Although both pain (particularly various chronic pain conditions) and depression are highly prevalent conditions, a growing body of literature suggests that the prevalence of pain in depressed patients and the prevalence of depression in pain patients are higher than when these two conditions are separately evaluated [18]. The prevalence of pain is averaged 65% in depressed patients across a pooled analysis of multiple studies [18]. Compared to those patients without depressive symptoms, the
Animal studies of the pain-depression relationship
Given the well-recognized reciprocal interactions between pain and depression, emerging animal studies are beginning to address this issue [19]. Over the years, many animal models have been developed that are designed to model different aspects and/or origins of sensory pain and have good construct and face validity (e.g., inflammatory, nerve injury or cancer pain), although they are not without challenge [36], [37]. In addition, because pain is an integral subjective experience that is
Pain-depression dyad and domain interplay modeling
Pain and depression both have characteristic behavioral phenotypes. Besides the complaint of sensory pain, patients with chronic pain also have altered psychological status, such as depressed mood, anger, catastrophizing, anhedonia, sleep disturbance, fatigue, cognitive impairment and suicidal ideation [82]. Many of these symptoms are consistent with the clinical diagnostic criteria of depression, which usually utilizes a checklist of 9 symptoms (DSM-V). Although the preclinical studies
Concluding remarks
Pain and depression represent two highly prevalent and deleterious neuropsychiatric disorders. Both conditions often co-occur, share some similar symptoms, and exacerbate one another, suggesting overlapping neurobiological underpinnings. Both clinical observations and animal studies point to the reciprocal causative relationships between pain and depression. However, the neural mechanisms of this interaction are largely unknown and there are no well-validated animal models to recruit core
Acknowledgements
This work was supported in part by the National Institute on Drug Abuse of the National Institutes of Health under Award no. R01DA034806. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.
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