The Relationship of Older Adults ’ Physical Pain to Depression and Post-Traumatic Stress Disorder ( PTSD ) : A Review

Background: Physical pain is very common in older age and is often accompanied by depressive as well as PTSD symptomatology. Many conceptualizations of the comorbidity of pain with depression and with PTSD exist, but they need to be tested on older adult populations. Purpose: This article covers existing literature on the relation between depression and pain in older age, as well as between older adults’ PTSD and pain. Additionally, several physiological, cognitive, and behavioral conceptualizations of why depression and PTSD are often related to pain are presented. Methods: The PsychInfo, PubMed, and Google Scholar databases were searched for relevant articles by utilizing the following terms in combination with chronic pain (as well as with pain alone): aging, older adults, elderly, depression, depressive, post-traumatic stress, and PTSD. Additionally, Thomson Reuters Web of Science database searches were conducted using the terms “elderly (and older adults) pain depression PTSD.” This review includes various articles that conceptualize the pain-depression, pain-PTSD, and pain-depression-PTSD links, yet, due to space limitations, the review is not comprehensive. Several pertinent reviews are referenced throughout the paper for readers interested in obtaining additional information in this area. Results: Depression and PTSD are comorbidities for pain at any age, and are characterized by several and often complex mechanisms that can exacerbate pain. Conclusion: The comorbidity of pain and factors such as depression and PTSD in older age should be addressed in more research studies, as few investigations are available in this area on the general population of older individuals. This is particularly the case for non-Caucasian older adults living with chronic pain.

the experience of pain and health outcomes, yet, the specific nature of the pain-depression-PTSD link remains unclear.This is especially applicable to older adults, a population that has seldom been studied on this topic.As detailed later, these three variables appear to share several common physiological, neurological, and immunological mechanisms; this makes researching them in a simultaneous fashion a challenging yet important task.To shed some light in this area, the present article incorporates a discussion of older adults' depression and PTSD in relation to pain.It also includes possible explanations for the comorbidity of pain experienced at any age with these two important variables.Due to space limitations, this is not a comprehensive review of the literature published on the topic of depression and pain, or PTSD and pain.However, several review articles are referenced for readers interested in additional information in this area.
Pain in older age is a very critical subject due to its significant negative impact on the rapidly growing older adult population.Indeed, with the United States (U.S.) population of individuals over the age of 65 growing rapidly, this country is observing a decrease in fertility rates and an increase in life expectancy [2].The concurrent growth in the older adult population and decline in fertility rates contribute to the relatively rapid pace of growth in the aging population within the U.S., which, as predicted two decades ago, will observe a sharp increase from 7 percent to 14 percent in the older adult population within just 69 years [3].Astoundingly, this figure could be an underestimation of the size of the older population in the next few decades, especially in view of recent medical advances.

Introduction
In a high quality research study conducted earlier this year, Outcalt, Kroenke, Krebs, et al. [1] emphasized that depression and post-traumatic stress disorder are often present in individuals living with chronic pain and typically have negative consequences on both

The Comorbid Relationship of Depression and Pain Introduction
Major depressive disorder is one of the most widely depressive manifestations examined in the literature.The 12-month prevalence rate of a major depressive episode among people 50 years of age and older is about 5.5% [21].Furthermore, there exists a disparity between the prevalence of depression among older men and women that is consistent with the well-established finding that women experience major depression about twice as often as men [22].Thus, older women should be especially targeted in research in this area.
Pain may present itself in a variety of ways such as a pathological condition (as previously mentioned), an undiagnosed medical condition, a neurological condition such as multiple sclerosis, or a somatic condition such as cancer or rheumatoid arthritis [23].The comorbidity rate of depression and chronic pain typically ranges between 30% and 60% [24].Research indicates a higher incidence of reported somatic complaints such as pain among individuals diagnosed with depression [25,26].On the other hand, literature also supports a link between the physical as well as the psychological distress of conditions of chronic pain and a higher likelihood of developing depression [27,28].Specifically, it has been documented that more than 50% of individuals experiencing chronic pain report clinical symptoms of depression [29].
The above-mentioned significant rates of depression-pain comorbidity have created a platform from which researchers have explored the direction of influence between depression and pain.Despite speculations regarding the direction of influence between these two variables, the factor that remains constant is the negative effect that the comorbidity of depression and physical pain have on each other.Specific to the older adult population, depression treatment outcomes are often negatively affected by pain.An example of relevant research is a longitudinal study on the course of older patients' depression, in which the experience of pain significantly weakened the probability of recovery, as 47% of those with major depressive disorder recovered, while only 9% of older adults with comorbid major depressive disorder and pain did [30].Furthermore, pre-existing medical conditions that lead to symptoms of chronic pain can be exacerbated by the presence of major depressive disorder.For instance, conditions such as fibromyalgia, a musculoskeletal disorder that manifests through a long-term pervasive muscular pain, may be triggered or worsened by depression [31,32].
Most of the explanations listed in the following sections for both depression and PTSD have not been formally tested on older adults and include samples that contain both older and younger adults, thus not allowing for generalizations of the results to geriatric populations.

Potential Explanations of Comorbidity of Depression and Pain
This section contains a summary of some of the well-known conceptualizations of the relationship between depression and pain.As already mentioned, due to space limitations, this review is not meant to be comprehensive.For the interested reader, published reviews in this area include articles by Blackburn-Munro & Blackburn-Munro [23], Bair, Robinson, Katon, and Kroenke [33], as well as Brooks, Kominek, Pham, and Fudin [34].

The diathesis-stress model
The Diathesis-Stress Model [35] postulates that the source of depression in cases of chronic pain is traced to a predisposition toward depression that is developed at the onset of stressful stimuli, such as chronic pain.What makes this model unique is its integration of biological, cognitive, and behavioral elements in combination with or independently reacting to stressful stimuli.The sensitivity to these stimuli in inducing the onset of depression depends on individual variations and predispositions.The behavioral and cognitive aspects of the model depend on the source and onset of depression, and are significantly influenced by chronic pain.For example, from a behavioral perspective, chronic pain may lead to an inability to engage in activities and thus can decrease the experience of positive reinforcement, resulting in negative affect and depression.From a cognitive perspective, chronic pain may present the individual with situations within the medical system in which attention and responses by professionals within the medical system may be perceived as dismissing, serving as a stressor in the development of depression [35,36].

Brain abnormalities
The literature on physiological differences (detected through neuroimaging) in brain structure and function among individuals with depression, neuropathic pain, and fibromyalgia indicates the existence of vast similarities in recorded brain abnormalities.Specifically, brain areas such as the dorsolateral prefrontal cortex, medial prefrontal cortex, lateral orbital prefrontal cortex, insula, nucleus accumbens, amygdala, hippocampus, and thalamus have been associated with functional or structural abnormalities.The results of such brain abnormalities may lead to a bidirectional relationship between chronic pain and depression, as they influence the perpetuation and severity of one another [37].For instance, electrophysiological, biochemical, and imaging reports suggest that abnormalities in both the function and structure of the amygdala -in cases of chronic pain and symptoms of depression as well as anxiety, may increase the amygdala's sensitivity to experiences of pain [38].According to Rainville, Bao, & Chrétien [39], negative perceptions and feelings that are characteristic of major depressive disorder also serve to augment the sensation and recognition of pain.Similarly, abnormalities in the structure and function of the dorsolateral prefrontal cortex in major depressive disorder and chronic pain disturbs the top-down process of emotion regulation in depression and pain regulation, altering sensations of pain within pain pathways, cognition, and ability to cope [40][41][42][43].
Regarding individuals with major depressive disorder and chronic pain, research exists on the simultaneous over-activation of the limbic system and on the effects of the prefrontal structures on decreasing dopaminergic activity due to an increased distress alert [37].Alterations in the ventral striatum and nucleus accumbens are reported to serve an important role in the body's stress and pain response, as well as in the reward and pain sedation mechanisms ISSN: 2469-5858 Alamdari and Laganà.J Geriatr Med Gerontol 2015, 1:1 to symptoms associated with depression, including a heightened experience of pain, reduction in social interaction and in sexual activity, as well as increased sleep [66][67][68].Because many behavioral symptoms of the sickness response are similar to those of depressive symptomatology, researchers have examined the relationship between PICs and depression, establishing a theory that incorporates a patho-physiological approach.
In a study targeting the older adult population via sampling over 3,000 physically healthy older adults, an elevated level of PICs IL-6, TNF, and/or C-reactive protein was found to be correlated with a heightened risk of depression by over double [69].Along with the variety of behavioral symptoms associated with the sickness response and the characteristics of depression, a heightened experience of pain has been found.After all, the sickness response is an essential response in increasing an organism's chance of survival.Researchers have studied the central nervous system's immunity reaction through the stimulation of neuroglial cells such as astrocytes and microglial cells to respond to physical threats such as inflammation or injury [66].The specific function of astrocytes, limited to function within the brain and spinal cord, is to manage neural communication; however, the specific function of microglial cells parallels the role of a macrophage, as these cells remove dead neurons at the location of injury [70].Stimulated neuroglial cells appear to function to generate various molecules such as PICs within the central nervous system as a response to neural signals from peripheral PICs stimulated by an immune stressor [71].In a study on 81 individuals diagnosed with fibromyalgia against 32 healthy individuals, participants suffering from fibromyalgia had higher levels of the IL-8 and scored higher on the Hamilton Depression Rating Scale than the control group [72].These findings suggest the existence of a relationship between an increased presence of cytokine and depressive symptoms as well the exacerbation of pain.

The Comorbid Relationship between PTSD and Pain Introduction
Mental health conditions such as PTSD greatly affect the older adult population and, in particular, older women.The prevalence of PTSD in older age falls within the 1.5% to 4% range [73], with the subclinical manifestation of PTSD in older men falling within the 7% to 15% range [74].The likelihood of exhibiting symptoms characteristic of PTSD is twice as high for women than men [75,76], highlighting the need for research in this area.Some scholars have speculated that this disparity may be due to a woman's higher risk of exposure to trauma like sexual abuse or assault that could lead to PTSD [77,78].Whatever the reason, it is essential to study PTSD in relation to pain among older adults, because the prevalence and epidemiology of the comorbidity of PTSD and chronic pain have not yet been widely explored in older age groups.Researchers have found it particularly difficult to differentiate the source of pain and whether its onset was a result of the same event that prompted the traumatic experience; however, recently there has been a growing interest in recognizing and assessing the PTSD-pain relationship [79].According to the National Co-morbidity Replication Survey, 7.3% of the individuals experiencing chronic back pain also exhibit symptoms of PTSD [80].In another epidemiological study from the Canadian Community Health Survey, differences were found in the comorbidity rate of chronic pain and PTSD related to specific pain conditions, as these rates were 7.7% among individuals with fibromyalgia and 46% among individuals with back pain [81].

Potential Explanations of Comorbidity of PTSD and Pain
As was the case for the above coverage of the pain-depression link, this section comprises only a selection of the conceptualizations of the pain-PTSD link.For more information on this topic, the interested reader is referred to reviews by Sharp and Harvey [82], Beck and Clapp [79], as well as Brennstuhl, Tarquinio, and Montel [83].The pain-PTSD link has been verified mainly within populations that are [44][45][46].The nucleus accumbens communicates with the prefrontal cortex gathering signals regarding cognition, emotional information from the amygdala, and information regarding the context of stimuli from the hippocampus [46].Similarly, the nucleus accumbens regulates the ventral tegmental area's dopaminergic activity.The findings of neuroimaging reports on the relationship between the nucleus accumbens and the ventral tegmental area suggest that there may be a disruption in functioning between the nucleus accumbens and ventral tegmental area in individuals with major depressive disorder and chronic pain [47,48].Over-activation of the amygdala, subgenual anterior cingulate cortex, and ventral medial prefrontal cortex could disrupt dopaminergic activity within the ventral tegmental area, resulting in a skewed reward mechanism, cognitive impairments, reduced desire to experience novel stimuli, and impaired pain management [44,45,[47][48][49].Furthermore, regarding people's susceptibility to experiencing chronic pain related to major depressive disorder, Bär et al. [50] highlighted the significance of the location of pain in individuals with depression, while cerebral blood flow in brain structures has been found to affect the emotional regulation of pain [51].

Hypothalamic-pituitary-adrenal axis mechanism
The activation of the hypothalamic-pituitary-adrenal (HPA) axis associated with the limbic and autonomic systems comprises a conceptualization that could explain a potential mechanism contributing to the onset of fibromyalgia and neuropathic pain as well as depression [37].Richards & O'hara [36] reviewed various studies that suggest an overstimulation of the HPA axis in both depressed and chronic pain conditions, defined by a greater level of cortisol stimulation and a decrease in morning cortisol suppression [52][53][54][55].Indeed, diseases such as fibromyalgia and depression may be triggered by stressors that stimulate the negative feedback loop within the HPA axis and prompt the production of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) released by the hypothalamus, which signals the release of adrenocorticotropic hormone (ACTH) through the pituitary gland.As a result, the secretion of ACTH activates the adrenal release of cortisol [56,57].The hormone cortisol is a glucocorticoid, also known as the stress hormone [58], and typically functions by reducing CRH and ACTH production, constricting any form of action within the body, including immune function [56,59].Exposure to a stressor for a prolonged period of time may result in the disruption of the HPA axis and fluctuating cortisol levels, affecting experiences of pain, as well as lethargy and mood [60,61].

Inflammatory mechanism
It is plausible that an impaired HPA axis -resulting in fluctuating levels of cortisol shared in chronic pain and depression patients -is not the only biological mechanism aiding their comorbidity, as a disruption in monoamine transmission could also contribute to it, in combination with HPA axis disruption [62].An abundance of pro-inflammatory proteins such as cytokines may be involved in the comorbidity of pain and depression [62,63].Cytokines are known to relay information to cells regarding the intensity and duration of response to an infection or disease.Unlike hormones whose secretion is regulated by glands, cytokines are secreted by immune cells within and outside the central nervous system and are regulated by feedback loops [64].
Among the different variations of cytokines, the molecules TNF-α, IL-1, and IL-6, among others, are associated with pro-inflammatory functions and are known as pro-inflammatory cytokines (PICs) [65].PICs play an important role in the "sickness response" [66], which is a natural mechanism intended to enhance survival through an increased constraint of movement and conservation of energy for the body's defensive purposes.This response includes physiological symptoms similar to the flu, such as elevations in body temperature as well as alterations in the regulation of the HPA axis and sympathetic nervous system while affecting secretions of hormones such as serotonin.The end result involves changes in behavior similar ISSN: 2469-5858 Alamdari and Laganà.J Geriatr Med Gerontol 2015, 1:1 is a predisposing factor in the development of PTSD and chronic pain.Asumundson et al.'s model proposes that anxiety sensitivity functions as a foundation for an enhanced awareness of danger during traumatic experiences, affecting sensitivity to both mental and physical distress [94].This sensitivity contributes to the development of comorbid PTSD and pain conditions.Empirical evidence is lacking on this theory.

Avoidant coping
Avoidant coping has been explored in the literature regarding pain and PTSD independently.Foa, Steketee, and Rothbaum [95] proposed that the development of presenting symptoms associated with PTSD is explained by the cognitive structure of fear (by Lang [96]).Lang's classic conceptualization of fear includes three aspects: 1) the feared stimuli, 2) somatic reactions and physical movement, as well as 3) the perception of the feared stimuli.The trauma-related memories formed based on these three variables influence the development of an automatic motive for escape from the perceived threatening stimuli.Lang described the process of developing a constant motive for escape from specific stimuli as being "programmed" to escape, based on the formulated structure of fear regarding the traumatic stimuli.Foa et al. hypothesized that stimuli in the environment may arouse the cognitive structure of fear and provoke behaviors of escape or avoidance from the feared stimuli [95].As a result, the lack of exposure to the feared stimuli may result in an inability to extinguish the fear and develop more comfort and reassurance of safety in the presence of the stimuli, maintaining the symptoms of PTSD.Vlaeyen and Linton [97] conceptualized pain-related fear as prompting avoidant behaviors in regard to physical activity and as a core element in the development of chronic pain from a previously acute condition, leading to a pain-related disability.Avoidant coping behaviors contribute to both the maintenance and the development of PTSD and chronic pain conditions, and can potentially contribute to their comorbidity [98].

Attentional bias
Williams, Mathews, and MacLeod defined attentional bias as a reaction to a stimulus that may be deferred [99].The Stroop task is an example of the effect of attentional bias on activity, as the task examines the effect of interference on speed of reaction.Stroop originally assessed color as a variable of interference on an individual's reaction time.Specifically, the task requires the individual to name the color of the ink and not read the word.For instance, if the word "GREEN" is in blue ink, the individual must state the word "blue."Stroop found that reaction time was longer and included many more errors when words did not match the color in which they were written than when both word and color of the text matched [100].Support for the attentional bias is displayed in individuals who may have an increased delay in identifying the color of the word related to their pathology as opposed to neutral words [79].Scholars have extended this conceptualization to cover delays in recognizing words related to pain among individuals with chronic pain [101].
In a study pertinent to the chronic pain-PTSD link, researchers observed an attentional bias within individuals experiencing both conditions in a sample of motor vehicle accident survivors, who were categorized into groups of those who had comorbid PTSD and chronic pain, only chronic pain, and a control group without PTSD or chronic pain.Some stimulus words were related to trauma, some to pain, some were neutral words, and some were positive words.Responses made by individuals with comorbid PTSD and chronic pain were delayed for both trauma and pain words, while individuals with only pain experienced delays only when presented with words related to pain [102].These results are indicative of the critical role that attentional bias has in relation to comorbid pain and PTSD, given the interplay between PTSD and chronic pain in attentional processing [79].Research is needed to provide explanations of the possible relationship between pain and PTSD in the context of attentional bias.
particularly vulnerable to experiencing PTSD, such as war veterans [1] and individuals who lived through a major disaster such as a severe earthquake [84] or another often-traumatic life circumstance like becoming a refugee [85].The latter authors noted that chronic pain is extremely common in their target population and that it is likely to maintain the mental symptoms of trauma.More research is needed on the pain-PTSD link within the general population of older adults.

Anxiety and perception of pain
According to Sharp and Harvey [82], the relationship between anxiety and PTSD serves an important role in heightening the perception of pain among individuals with comorbid PTSD and pain.The aforementioned authors conceptualized pain perception as being enhanced by anxiety while maximizing the level of pain sensed, emotional discomfort, and physical impairments.Some studies have supported this claim, such as research on patients with accidentrelated chronic pain [86].
Upon using neuroimaging to capture neural structures associated with pain processing in individuals with PTSD within a sample of veterans who had experienced combat and veterans who had not, following the administration of a fixed-temperature assessment, it was discovered that perception of pain was reduced among individuals with PTSD [87].Neuroimaging reports also showed specific patterns of activity within neural structures, such as increased activity within the left hippocampal region and reduced activity within the bilateral ventrolateral prefrontal cortex and the right amygdala during the fixed-temperature assessment among individuals with PTSD.Neuroimaging conducted during the individual temperature assessment indicated an increase in activity within the right putamen and bilateral insula, as well as reduced activity within the right precentral gyrus and right amygdala.This study's authors hypothesized that the unique patterns of activity within these neural structures contribute to the difference in processing pain among individuals with PTSD [87].Some scholars have contended that anxiety is a potential determinant of comorbid pain and PTSD [79].Indeed, there is empirical support for a significant role of anxiety in both increased pain sensitivity and PTSD, based on research findings on a sample of burn victims studied over the course of one year following the traumatic injury.Variables including the anxiety and dissociation that developed within a year's span of the onset of the trauma, as well as female gender, were significant predictors of PTSD [88].The results of this investigation suggest that anxiety may play an essential role in the development of comorbid pain and PTSD.

Anxiety sensitivity
The conceptualization of anxiety sensitivity is based upon the mutual maintenance model of Sharp and Harvey [82].It includes elements that contribute to perpetuating the comorbidity of PTSD and chronic pain, recognizing that individuals with comorbid PTSD and pain share a discomfort with arousal-based sensations [89].The foundation of the anxiety sensitivity mechanism is the misperception of all anxious sensations as dangerous; thus, individuals with comorbid PTSD and pain may be more inclined to inaccurately perceive and unconsciously exaggerate physical sensations such as pain and arousal [90,91].In a male veteran sample, research findings confirmed the mediating role of anxiety sensitivity in the maintenance of comorbidity between PTSD and chronic pain [92].These results are similar to more recent empirical findings [93] on chronic musculoskeletal pain patients of an unspecified age residing in Spain.

Vulnerability model
Asmundson, Coons, Taylor, and Katz [94] used features of Sharp and Harvey's conceptualization of anxiety sensitivity [82] to develop the vulnerability model.They suggested that anxiety sensitivity is a variable present prior to the experience of trauma or pain and ISSN: 2469-5858 Alamdari and Laganà.J Geriatr Med Gerontol 2015, 1:1

A Potential Explanation of Comorbidity of Depression, PTSD, Pain and a Brief Review of Pertinent Research Depression and decreased behavioral activity
The depression and decreased behavioral activity is a straightforward conceptualization that incorporates both PTSD and depression in relation to pain.As postulated by Sharp and Harvey [82], it presupposes that both PTSD and chronic pain could be maintained by fatigue and lethargy and by the often-related reduction in activity levels.At the present time, few researchers have studied these three variables simultaneously, and even fewer have targeted older adults specifically.In this regard, a Web of Science database search using the terms "older adults pain depression PTSD" did not return any relevant publication.However, the search "elderly pain depression PTSD" did yield one pertinent cross-sectional study sampled from the general German population aged 60 to 85, 19% of whom reported widespread pain [103].Compared to control participants, older adults living with widespread pain had a higher prevalence of potential depressive disorder and PTSD.
Briefly, regarding non-geriatric research, studies focused on the pain-depression-PTSD link include cross-sectional research in which it was found that PTSD impacts reports of physical discomfort by male veterans via underlying depressive symptomatology and anxiety sensitivity [92].In another study on male veterans, researchers discovered that the pain-PTSD link was fully mediated by depression [104].Moreover, among individuals in chronic pain as a result of an Responses of medical practitioners to individuals' experience of chronic pain may be perceived as dismissing and serve as a stressor in the development of depression 2. a. Brain abnormalities may lead to a bidirectional relationship between chronic pain and depression b.Overstimulation of the HPA axis due to exposure to stressor(s) over a continuous period of time may impair HPA axis and influence cortisol levels, resulting in experience of pain and disruption of mood 3. An abundance of pro-inflammatory proteins may be involved in the comorbidity of pain and depression 1. a and b.Banks and Kerns [35] 2. a. Maletic and Riason [37] b1.Aguglia, Salvi, Maina, Rossetto, Aguglia [60] b2.Gracely, Ceko, Bushnell [61] 3. a. Hartman et al. [63] b.Penninx et al. [69] c.Gür accident, while PTSD was directly related to depression, depression was directly related to the magnitude of pain and indirectly related to pain intensity via its effect on disability [105].In baseline data on 250 Veterans Affairs primary care patients, depression and PTSD were independently and significantly related to higher pain reports, as well as to higher rates of disability and lower quality of life [1].As to relevant studies targeting women in particular, 2015 research showed that depressed women and women who screened positive for PTSD had a higher prevalence of having the pain disorder vulvodynia, which is indicative of the fact that 1) those two disorders can contribute to the probability of experiencing vulvodynia, or 2) as the study's authors pointed out, depression, PTSD, and vulvodynia share patho-physiological as well as risk profiles [106].Table 1 offers a concise summary of the review provided herein.

Conclusions
There are numerous conceptualizations linking pain to depression or to PTSD, yet not enough explanations have been provided for the pain-depression-PTSD link.According to some of the aforementioned researchers, pain, depression, and PTSD are likely to share some common foundations in terms of physiological, neurological, and/or immunological mechanisms.Their interrelation is complex and needs to be further studied.As recommended by Outcalt and colleagues [1], clinicians should assess and treat both depression and PTSD in patients living with chronic pain.Interested researchers should adopt longitudinal designs, as most of the published information in this area is cross-sectional evidence and some of it is still merely speculative.The causality of the chronic pain-psychopathology link typically differs depending on each mental disorder and is often mediated by biological and psychosocial factors [107].Scholars should investigate this topic with samples of older adults, also due to the fact that some of those factors could be age-dependent.
As already mentioned, despite the importance of investigating older adults' physical pain and its comorbidity with depression and PTSD symptomatology, most of the studies in this area are specific to war veterans who have a PTSD diagnosis.For instance, in 2015 research, chronic face, head, and neck pain were significantly related to depression among war veterans living with PTSD [108].It is critical to study these variables within war veteran populations, given that they are at high risk for chronic pain and related neurobehavioral problems [109].This is also the case for other vulnerable populations that are particularly at risk for PTSD such as traumatized refugees [85].Nevertheless, it is important to examine pain, PTSD, and depression in community-dwelling older adults who have not undergone such extreme experiences yet must deal with pain, depression, and PTSD on a regular basis.Moreover, as noted by Gureje [107], because the evolution of the pain-psychopathology comorbidity seems to differ for men and women, geriatric research is needed on this topic.Gender-specific pain-psychopathology models should be developed and tested, to provide accurate and, if needed, differential assessment and treatment options for men and women and reduce possible gender disparities in this geriatric research area.Furthermore, race/ethnicity-specific geriatric studies on pain and related psychopathology should be conducted, in view of research findings indicating racial/ethnic differences in experimental and clinical pain and function among older knee osteoarthritis patients [110].These results suggest possible racial/ethnic differences in the somatosensory system and in patho-physiological mechanisms.Indeed, compared to Caucasians, older racial/ethnic minority individuals are facing even higher health disparities than their younger counterpart in receiving needed medical care such as prostate cancer treatment [111].More efforts should be made to reduce race/ethnicity-related disparities in geriatric care.To this end, it is highly recommended that researchers pay particular attention to racial/ethnic diversity when gathering older adult samples for future research on the interplay of the variables discussed in the present article.This will allow scholars to begin filling cultural research gaps on the pain-depression-PTSD link while accounting for important yet under-studied potential risk factors for pain such as the aforementioned perceived racial discrimination.In particular, it is critical to innovatively examine whether the results of existing empirical studies conducted primarily on Caucasian samples can be generalized to non-Caucasian older individuals.In turn, the findings of future studies may serve as foundations on which to base tailored pain assessment and management (including coverage of pain's psychiatric comorbidities) to be implemented in a culturally appropriate manner to reduce inequalities in health.
, Karakoç, Nas, Denli, & Saraç [72] B. Potential Explanations of Comorbidity of PTSD and Pain 1. Patients with accident-related chronic pain 2. Veterans with PTSD who had experienced combat versus veterans who had not 3. a. Burn victims b.Veterans c. Chronic musculoskeletal pain patients 4. No population tested 5. a.Individuals with PTSD symptomatology b.Individuals with musculoskeletal pain c.Individuals with comorbid PTSD and chronic pain 6. a.Individuals with chronic pain b.Motor vehicle accident survivors with comorbid PTSD and chronic pain or with only chronic pain 1. Anxiety enhances the perception of pain 2. Pain is processed differently among individuals with PTSD 3. Sensitivity to anxious or arousal-based stimuli can contribute to the development and maintenance of comorbid PTSD and pain 4. Anxiety sensitivity for an enhanced awareness of danger during trauma may contribute to developing comorbid PTSD and chronic pain conditions 5. a.The use of avoidant coping to deal with fearful stimuli and consequent inability to extinguish the fear maintain symptoms of PTSD b.Acute pain may develop into a chronic painrelated disability as a result of pain-related fear and avoidant behaviors c.Avoidant coping behaviors can contribute to the maintenance and development of comorbid PTSD and pain 6. a. Delayed recognition of words related to pain b.Delayed recognition of words related to both pain and trauma among individuals with PTSD and chronic pain; delayed recognition of words related only to pain among those with only chronic pain 1. Geisser, Roth, Bachman, and Eckert [86] 2. Gueze et al. [87] 3. a. Van Loey, Maas, Faber, & Taal [88] b.Jakupcak et al. [92] c.López-Martínez, Ramírez-Maestre, and Esteve [93] 4. Asmundson, Coons, Taylor, & Katz [94] 5. a. Foa, Steketee, & Rothbaum [95] b.Vlaeyen and Linton [97] c.Bosco, Gallinati, & Clark [98] 6. a. Pincus & Morley [101] b.Beck, Freeman, Shipherd, Hamblen, & Lackner [102] C. Potential Explanation of Comorbidity of Depression, PTSD, and Pain 1. Older adults with widespread pain 2. a. and b.Male veterans c.Individuals with chronic pain as a result of an accident 3. Women with depression and women with PTSD 1.Evidence on the significance of the depression-PTSD-pain link 2. a. and b.Depression mediates the PTSDpain link c.PTSD is directly related to depression; depression is directly related to pain magnitude and indirectly to pain intensity via its effect on disability 3. Depression, PTSD, and vulvodynia may share patho-physiological patterns and risk factors 1. Häuser, Glaesmer, Schmutzer, & Brähler [103] 2. a. Jakupcak et al. [92] b.Poundja, Fikretoglu, & Brunet [104] c.Roth, Geisser, & Bates [105]3.Iglesias-Rios, Harlow, & Reed[106]

Table 1 :
Summary of Main Findings