Understanding Comorbid Posttraumatic Stress Disorder and Chronic Pain: Current Treatments and Future Directions

It is crucial for providers, researchers, and consumers to understand chronic pain through a comprehensive model that accounts for both the complexity of the pain experience and the complicated changes in the pain experience and phenotype with in the context of trauma. Early theories of pain, which are covered later in this chapter, failed to adequately account for pain complexity and are insufficient to guide diagnosis, understanding, and treatment of trauma-related pain (i.e., pain and comorbid posttraumatic stress disorder [PTSD]). The first part of this chapter will describe the evolution of understanding pain from unidimensional Cartesian models to more complex models that culminated in the predominant contemporary biopsychosocial model. The biopsychosocial model accurately acknowledges that the experience of pain cannot be explained solely through the physical experience and that the physical experience is affected by factors seemingly unrelated to one’s physical pain. Hence, any proposed explanatory models of chronic pain comorbidity must also acknowledge this fact. Finally, the chapter will explore existing treatments for comorbid pain and PTSD (both pharmacological and nonpharmacological) and will offer suggestions on future directions for research and clinical care that may guide ongoing efforts to effectively treat these complex patient populations.

Prevalence of Chronic Pain and Posttraumatic Stress Disorder

Up to 40% of adults in the United States experience chronic pain, defined as persistent pain lasting for at least 6 months, with costs estimated at $560 billion. Chronic pain may occur within several contexts, including musculoskeletal injury, cancer, and traumatic events. Indeed, pain is highly comorbid with PTSD, a disorder characterized by avoidance, hypervigilance, negative cognitions and affect, and intrusive symptoms (e.g., flashbacks). Moreover, those with chronic pain are more likely to endorse PTSD symptoms than their counterparts without chronic pain. ^, Military populations are particularly susceptible to this comorbidity and are more likely to be diagnosed with PTSD and/or chronic pain compared with the civilian population. ^, With advancements in battlefield technology, and medicine more generally, current military personnel have a better chance at surviving than those in the Vietnam era; nevertheless, physical and mental health conditions persist beyond their time of service. Similarly, civilians who have experienced a traumatic event are also more likely to survive due to advancements in medicine. Therefore it is pertinent to examine the current state of the science as it relates to how these two common health conditions (i.e., chronic pain and PTSD) are understood and treated, the historical context from which this thinking evolved, and the innovations that may lie ahead.

Historical and Modern Perspectives of Pain Treatment

In order to understand current pharmacologic treatments for pain, it is important to place these treatments within the context, evolution, and acquired knowledge of earlier biomedical models dating back to Descartes. Descartes viewed pain as one of the principal perceptual and physical bodily experiences that test the existence of the body. He believed that pain was a disturbance passed through nerve fibers throughout the body until it reached the brain and was evidence that the mind and body are dualistic mechanisms responding in tandem to specific stimuli such as temperature and pain. Not only did this promote thought from philosophers, it also subsequently led scientists to attempt to locate pain nerve fibers within the body that transferred pain sensations. Descartes’ theory, also now known as the specificity theory , was essential in promoting research related to specific functions of nerve pathways to the brain in response to pain. The two-step process consists of the (1) body integrating a pain signal into one bodily sensation and (2) traveling to the brain where it is mechanically perceived. This influenced the practice of medicinal usage, whereby practitioners pursued physical pain treatments, such as herb usage for analgesic effects or physicians severing specific pain nerve fibers to prevent pain signals from reaching the brain.

Descartes’ specificity theory was further developed by physician Charles Bell in his influential essay, the Idea of a New Anatomy of the Brain , which ultimately led to the discovery of the central nervous system (CNS). The CNS provides a direct relationship between a stimulus and the sensation of pain via sensory receptors known as “nociceptors.” Nociceptive pain reception occurs when noxious stimuli are sensed by pain receptors, or nociceptors, located in the skin and then transmitted via electric signals to higher brain centers for processing. ^{, , ,}

The relationship between nociception and pain is complex because the inputs involved are beyond biological nociception. Opposition of Descartes’ specificity theory of pain has led to other historical pain conceptualizations, including the intensity theory of pain and the pattern theory of pain . The intensity theory of pain hypothesizes that the experience of pain is the result of a significant intensity or threshold being reached. This led neurologists and physiologists in the 1800s to formulate the theory that the intensity of pain is directly related to the amount of associated tissue injury. After a certain threshold, an increased painful sensory input would summate and transmit in the spinal cord (i.e., CNS) and then to the brain. Researchers during this time theorized that this central summation generated impulse sensations that were interpreted as pain for the individual only when the number of intense responding fibers and their discharge frequency exceeded a certain threshold that then determined the perceptual response to the nociceptive (sensory) input. ^{, , ,}

Modern theories of pain foretold the most utilized theoretical perspective to date, the biopsychosocial model. The gate control theory sought to combine and support the main principles of the specificity, intensity, and pattern theories of pain. Melzack and Wall theorized that there is a mechanistic gate in the spinal cord, specifically in the dorsal horn, that controls the transmission of sensory information in the spinal cord and to the brain. This mechanism is controlled by the activity in the large and small fibers. Large fibers inhibit or close the gate, whereas small fibers enable or open the gate. When nociceptive pain, tissue injury, or pain information reaches a certain threshold that exceeds the inhibition of the gate, this opens the gate and activates the pathways that lead to the experience of pain and pain-related behaviors (e.g., taking hand away from fire). Therefore this theory provided a neural basis and reconciled the earlier biomedical models of pain (i.e., specificity, intensity, and pattern theories of pain). This also laid the foundation for pain research and pain mechanisms in the 20th century. However, Melzack and Wall (1965) acknowledged that a more comprehensive model was needed to consider the emotional and cognitive effects of pain and their effects on pain-related behavior when an individual is experiencing pain. ^{, ,}

The need for a more comprehensive pain model led Melzack to create the neuromatrix theory of pain, which attempted to explain the nature of pain, and is based on prominent pain biomedical models. Melzack (in 2001) proposed that pain is a complex experience that is shaped by unique neurosignatures within the brain’s neural network, which he coined as the body-self neuromatrix. ^, This network assimilates cognitive evaluation, sensory-discriminative, and motivational-affective networks and posits that the output patterns of the neuromatrix engage perceptual, behavioral, and homeostatic systems within the body and mind in response to an injury and/or chronic physical and cognitive stress. Melzack’s theory was formulated on pain syndromes that had no organic injury such as phantom limb pain and nonspecific low-back pain. Preceding biomedical models dating back to Descartes did not hold true to the assumption that there must be tissue damage in order for pain to occur. Similarly, according to Melzack’s neuromatrix model, pain could have no correlation with tissue damage and can be the product of multiple parts of the CNS working together to generate a painful experience (e.g., fibromyalgia). This theory provided a comprehensive explanation of pain by integrating tenets from the specificity theory with affective and pattern-response theories to formulate the neuromatrix theory of pain , with the experience of pain being the result of an interplay of these various neural networks. Melzack and Casey encouraged medical professionals to move away from a sensory-dominant approach (e.g., surgical, pharmacologic) and treat chronic pain with a more multidisciplinary/multimodal (including pharmacologic and nonpharmacologic approaches) biopsychosocial approach. ^{, ,} This multimodal theory contributed to a biopsychosocial model for evaluating and treating pain.

Recent movement toward a biopsychosocial approach for treating chronic pain views an individual as an integrated “whole person” whose mind and body are interconnected and manifest dynamic interactions between biological, psychologic, and social components of their painful experience. The biopsychosocial model of pain is well supported by research and has expanded upon the biological mediators of chronic pain, elucidating the role of maladaptive stress responses via the hypothalamic-pituitary-adrenal (HPA) axis. Chronic pain dysregulates the HPA axis activity, and thus cortisol levels, which in turn is associated with differences in pain intensity, pain thresholds, and anxiety levels.

Explaining the Chronic Pain and Posttraumatic Stress Disorder Comorbidity

As far back as 2001, researchers have attempted to coalesce the available research in order to explain the relationship between chronic pain and PTSD. During this time, the shared vulnerability and mutual maintenance models of comorbidity ^, began their ascent as prominent heuristics through which to view the co-occurring disorders. Both acknowledge the role of psychological and social variables, while not ignoring the biological contributions, through the biopsychosocial model. Nevertheless, there is a great deal that has yet to be determined about how these disorders are linked.

Shared Vulnerability: Anxiety Sensitivity

One of the earliest models of pain and PTSD comorbidity was based on observations of hypervigilance associated with both conditions that created a mutual vulnerability for the comorbidity. Viewing chronic pain and PTSD from a shared vulnerability perspective highlights a diathesis related to anxiety sensitivity (AS) and genetic predispositions. AS refers to how people think about their bodily sensations, as they relate to how manageable the thoughts are (e.g., “It is an impossibility to control my thoughts about my disorders.”), whether the sensations have potential social consequences (e.g., “I may be unwelcome if people see me limping.”), and whether the sensations have potential physical consequences (e.g., “If this pain continues, my leg will probably be amputated.”). ^, Separate lines of research show that individuals with chronic pain and PTSD symptoms have increased levels of AS. Within a chronic pain context, AS predicts increased opioid dependence, severity, and misuse, stress, and disordered eating. Within a PTSD context, AS is implicated in emotion dysregulation, symptoms of obsessive-compulsive disorder , and decreased distress tolerance. Sensations within the body prime mental representations of what may occur; when these mental representations occur within a comorbid context (such as chronic pain and PTSD), they may have compounding detrimental consequences. In other words, among those who have comorbid PTSD and chronic pain, any reminder of physical pain or trauma may be associated with increased levels of anxiety and attention to the symptoms compared with those who have one or none of the disorders.

Among a comorbid PTSD and chronic pain population, AS plays an important role in symptom manifestation and evidence supports its inclusion within a stress-diathesis model of chronic pain and PTSD. ^, Among those with musculoskeletal pain, AS was elevated if they had been through a traumatic experience and exhibited symptoms of PTSD, compared with those who did not exhibit these symptoms. Separately, AS and PTSD symptoms predict emotional distress and interact with each other, whereby emotional distress worsens among those with musculoskeletal pain. This suggests that heightened anxiety around physical symptoms may worsen the effect of PTSD on one’s physical pain-related distress. Among those with chronic pain, AS is a significant predictor of PTSD symptoms above and beyond one’s history of trauma, highlighting how thoughts related to the pain experience and bodily sensations may play a role in PTSD.

Hyperarousal symptoms of PTSD are often characterized via their physiologic manifestations, relating this symptom cluster to AS. Indeed, both hyperarousal and numbing symptoms are significantly related to AS among individuals diagnosed with chronic musculoskeletal back pain. Among prisoners of war, hyperarousal longitudinally mediates the relationship between captivity and AS and between captivity and pain catastrophizing. Nevertheless, the long-term implications of AS are unclear, as AS predicts initial, but not later, neuropathic pain among those who received treatment in a trauma center.

Shared Vulnerability: Genetic Cause

Within the shared vulnerability model, genetic vulnerabilities play a prominent role, highlighting the biological component of the biopsychosocial model. Decades of research on the stress-vulnerability model shows that genetic predispositions play a role in both physical and mental health. Approximately 30%–40% of the variance in PTSD is heritable. Much of the genetic architecture underlying the risk for PTSD appears to overlap with vulnerabilities for depression and anxiety. It is quite possible that there are multiple genetic architectures underlying PTSD, which may explain the difficulties in the replication of findings by genome-wide association studies.

At this time, there are few well-supported genetic markers of both PTSD and chronic pain. However, the current research of genetic markers of stress (HPA axis) and inflammation for PTSD and chronic pain supports overlap of these disorders. FK506 binding protein 5 (FKBP5) polymorphisms provide one of the most promising gene candidates for PTSD vulnerability. High expression of FKBP5 is linked to greater glucocorticoid receptor sensitivity and lower basal cortisol levels, and low basal cortisol levels are thought to be a vulnerability factor for developing PTSD after a traumatic event. In an epigenetic study, Blacker and colleagues found that FKBP5 methylation increased in nonresponders to PTSD treatment and decreased in responders to treatment. The direction of methylation related to PTSD appears to be allele-specific, with the methylation or demethylation associated with greater severity of PTSD dependent on the exact allele being modified.

There is even less known about genetic and epigenetic involvement in chronic pain. Variants of the FKBP5 gene are associated with chronic pain development after trauma exposure, and the stress response microRNA (miRNA) 320a is linked to the development of chronic pain after car accidents.

Both the HPA axis and the immune system are involved in PTSD and chronic pain, further substantiating a fundamental biological link between the two conditions. Expression of immune system genes is associated with the presence of PTSD and upregulation of immune system genes is associated with greater intrusion symptoms of PTSD. Polymorphisms of immune system genes have been implicated as vulnerabilities for PTSD. ^, Studies of stress hormones and inflammatory markers support genetic findings of altered immune and HPA axis regulation in PTSD. Interestingly, many of the miRNAs associated with PTSD are involved in the regulation of stress and proinflammatory responses implicated in chronic pain. Indeed, there are several miRNAs associated with pain sensitization, inflammation, and stress responses. ^, Further studies are still needed to conclusively elucidate specific shared markers for underlying vulnerability.

Mutual Maintenance Model

The mutual maintenance model of the chronic pain and PTSD comorbidity incorporates all three factors of the tripartite biopsychosocial model, weaving an intricate tale of biological predispositions, affective and cognitive components, and social aspects of the pain experience into one explanatory model. The model hypothesizes that the unique comorbidity associated with chronic pain and PTSD is due to each disorder influencing the other (i.e., mutually maintaining). The mutual maintenance model highlights seven different cognitive and emotional processes that form a shared mechanism of comorbidity: attentional biases, AS, reminders of traumatic experiences, avoidance, negative affect and decreased physical activity, negative perceptions of illness, and the inability to use effective coping strategies. Despite the considerable attention paid to the chronic pain and PTSD comorbidity, research has marginally progressed from its original formulation of nearly 20 years ago.

Common Pharmacologic Targets of Chronic Pain/Posttraumatic Stress Disorder Comorbidity

There is some overlap between the pharmacological interventions recommended for chronic pain and PTSD, further substantiating an underlying process that may mutually maintain both conditions. Common treatments for chronic pain include acetaminophen, nonsteroidal antiinflammatory drugs, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors (SNRIs), anticonvulsants, opioids, and muscle relaxants. A couple selective serotonin reuptake inhibitors (SSRIs) are approved by the US Food and Drug Administration (FDA) for PTSD, but research shows mixed effectiveness of SSRIs for PTSD symptoms. Research indicates that an SNRI, venlafaxine, may be more effective in reducing symptoms of PTSD compared with SSRIs. There is also evidence that noradrenaline, which is increased by SNRIs, has anti-inflammatory and neuroprotective roles in chronic pain.

Medications for PTSD may or may not be prescribed directly after a traumatic experience. There is some research indicating that glucocorticoids used immediately after a traumatic event reduce the risk of developing PTSD. Holbrook and colleagues found postinjury use of opioids was linked to lower rates of PTSD after severe injuries; however, the exact mechanisms for lower PTSD rates (whether biological or psychological) are unknown. Although benzodiazepines are frequently prescribed to individuals with PTSD, they may increase the risk of suppressed breathing when taken with opioids. Concurrent use of benzodiazepines and opioids predicts problematic opioid use. ^,

Although controversial, there is increasing interest in cannabinoid compounds (including cannabidiol [CBD] and Δ ⁹ -tetrahydrocannabinol [THC]), because these compounds have accumulated some support for benefit in separate studies of chronic pain and PTSD. Indeed, the endocannabinoid system is currently under investigation for both chronic pain and PTSD and the pain and PTSD comorbidity. In an observational study of self-administered cannabis, investigators identified a 3-point decrease in pain using a 0–10 visual analogue scale after cannabis use. Unfortunately, the outcomes of the study were limited (e.g., the duration of reduced pain was not reported) and more work is needed to substantiate a benefit of causal cannabis use for pain. The author did specify, however, that THC potency, not CBD potency, was the strongest predictor of pain reduction. Cannabinoids have been shown to enhance fear extinction, exhibit anxiolytic effects, and reduce inflammation, all of which are potentially relevant to both PTSD and chronic pain. Much more information is needed to endorse cannabinoids as the recommended treatment for either condition, and both CBD and THC derivatives are regulated by the FDA in the United States. Epidiolex (a form of CBD), Marinol (a form of THC), Syndros (a form of THC), and Cesamet (structurally similar to THC) have limited approved treatment uses. To date, there are no FDA-approved cannabinoids for the treatment of chronic pain, and there is still a lack of high-quality research regarding safety and effectiveness of cannabinoids.

Nonpharmacological Targets of Chronic Pain and Posttraumatic Stress Disorder Comorbidity

Nonpharmacological treatment approaches for addressing the chronic pain and PTSD comorbidity are still in their infancy, with only a handful of clinical trials providing a guideline for clinicians. Overall, treatment recommendations include the following: psychoeducation related to PTSD and chronic pain symptoms, treatments related to how these symptoms are associated with each other, decreasing avoidance, decreasing attentional biases and arousal, and increasing positive mood and acceptance.

The most common treatments for chronic pain and PTSD, separately, are built upon the foundations of CBT techniques and the biopsychosocial model. In PTSD treatment, avoidance and maladaptive thinking patterns are often targeted. Similarly, maladaptive coping strategies (e.g., pain nonacceptance and catastrophizing) are often targeted in chronic pain treatment using an integrated biopsychosocial model. Current treatments designed to decrease symptoms within the chronic pain and PTSD comorbidity often pull from these approaches. When treatments do not necessarily target the chronic pain and PTSD comorbidity but assess outcomes related to both disorders, moderate effects for PTSD and small effects for pain outcomes emerge, which shows psychological interventions can provide benefit for both of these comorbid conditions. ACT is a third-wave CBT intervention that focuses on valued actions, acceptance, and cognitive flexibility. A recent meta-analysis revealed that ACT for chronic pain results in small effect sizes for improvements in functioning, quality of life, and pain intensity. It found a moderate effect size for anxiety and large effect sizes for pain acceptance and comorbid depression. Another meta-analysis found similar results with a smaller effect size for depression when ACT was used for chronic pain. In veterans with chronic pain and PTSD, clinically significant reductions in PTSD symptoms and improved pain outcomes were observed after treatment with ACT.

Targeting the chronic pain and PTSD comorbidity, Otis et al. developed a treatment that included elements from cognitive processing therapy and CBT for pain, producing mixed results. The treatment included goal-setting, meaning-making, and exposure. Although the small trial (of six total individuals) resulted in three individuals dropping out of treatment, those who stayed in treatment endorsed a decrease in pain-related disability and PTSD symptoms. In a study focused on chronic PTSD symptoms, Beck et al. implemented a CBT group therapy protocol, wherein 80% of individuals endorsed chronic pain in the sample. Although the sample size was small, medium to large effect sizes were found after treatment for PTSD and pain-related disability. Nevertheless, one-third of the sample subjects dropped out, and only 29% of the treatment group endorsed what the authors called “high end-state functioning,” defined as minimal PTSD and depression scores. Finally, a trauma-focused CBT intervention, which included psychoeducation, exposure, cognitive restructuring, and relaxation techniques, resulted in significant decreases in both PTSD and pain-related disability in the treatment group compared with the waitlist control.

With such a complicated population, wherein treatments for even one of the two disorders remain to be completely understood, nontraditional approaches offer a compelling and holistic alternative that has been tested with some success. Somatic reexperiencing, which focuses on bodily sensations related to traumatic experiences, combined with exercise, was implemented in a RCT for comorbid chronic pain and PTSD. Although the treatment resulted in a decrease in PTSD symptoms, pain-related disability remained unchanged, indicating more was needed to address the symptoms of pain. Other treatments have been more successful in concurrently treating pain symptoms and PTSD, including eye movement desensitization and reprocessing (EMDR) therapy and accelerated response therapy, a therapy that utilizes eye movements, along with imaginal exposure and rescripting.

Modification of Pain Management Delivery Pathways

Chronic pain and PTSD are notably complex, and both clinicians and researchers confronting this problem understand that the strongest treatments are likely to include multiple modalities. Indeed, some of the strongest work in chronic pain management focuses on interdisciplinary models of care that include medical, physical, and psychological interventions meaningfully integrated into a unified conceptual model of care ( see Functional Restoration). Complex PTSD also responds well to intensive outpatient treatment that mimics interdisciplinary pain management through a strong focus on both functional and psychologic treatments (see Massed Prolonged Exposure). Although effective, these high-intensity treatments are notoriously difficult to implement, so large medical systems have begun to explore care systems designed to organize different treatments for pain and PTSD using existing but disconnected clinical resources. By organizing existing treatments and increasing communication between providers, health systems hope to better address the comorbid pain and PTSD complexity and obtain better outcomes. For example, the Department of Veterans’ Affairs has established a stepped care model of pain management that encourages routine assessment of PTSD and recommendations for referral to evidence-based care for pain-suffering veterans who screen positive for PTSD. The Defense Health Agency (DHA) has begun to implement a comprehensive pain management pathway that includes components for both pain and PTSD treatment organized under a comprehensive system of care. Research on pain and PTSD comorbidity has begun to shift toward pragmatic studies of these integrated systems, offering perhaps the strongest potential for effectively addressing this comorbidity. Future studies should capitalize on nascent health systems and clinical informatics resources to enhance this endeavor.

Future Directions

Research on interventions for either chronic pain or PTSD has grown for decades, and more needs to be done to strengthen and refine interventions for each of these conditions. Unfortunately, few studies have examined treatments designed to effectively address both conditions concordantly. This lack of research attention is particularly disturbing in light of the growing recognition of high comorbidity rates between these conditions and the well-demonstrated complexity of the pain-PTSD phenotype. Initial models explaining the chronic pain and PTSD comorbidity have provided invaluable insight toward better understanding how and why these disorders seem to be so difficult to treat. For one, treating PTSD or chronic pain alone comes with its own problems: attrition rates are high; individuals fail to respond to treatment; and, each disorder has a multifaceted symptom profile affecting many aspects of individuals’ lives (e.g., social and physical functioning). In one sense, the comorbidity is like any other, wherein common thoughts, emotions, and behaviors maintain the disorders. In a more complicated sense, each disorder challenges patients in finding alternative ways of being in the world. One’s assumptions about a fair and just world are disrupted; interpretations of bodily sensations that once seemed harmless are now terrifying; enjoyable and meaningful activities may no longer be possible; and the feedback received from others that imply acceptance and commonality may now be altered. If a more thorough understanding is to be attained and treatments are to be improved, methodological considerations and novel mechanisms will need to be addressed.

Conclusion

This chapter characterized the epidemiology, cause, maintaining factors, current treatments, and future directions of the unique comorbidity between chronic pain and PTSD. Within either a chronic pain or PTSD sample, rates of having the other disorder are high, particularly in military personnel and those who are more vulnerable at developing this comorbid condition. Various genetic, cognitive, and emotional components appear to play a role in how these disorders are developed and maintained. The shared vulnerability model posits that AS and genetic predispositions (particularly as they relate to the HPA axis and stress response) make it more likely that certain individuals will develop this comorbidity. Similarly, it appears these disorders are mutually maintained by individuals avoiding physical and psychological pain, being more attuned to their experiences as they relate to chronic pain and PTSD, having negative affective and cognitive responses to these experiences, being constantly reminded of the pain and/or traumatic event, and being unable to effectively cope with the pain and/or PTSD symptoms. Since these theoretical models have been introduced, little progress has been made in how to best understand and treat this comorbidity. Recent technological advances have allowed for the possibility to gain causal and moment-by-moment knowledge (e.g., EMA) of how these disorders interact. Finally, the role of identity within this comorbidity has yet to be fully explored and offers a promising novel target of change that encompasses many aspects of both the shared vulnerability and mutual maintenance models.