Ebook: Pain Syndromes – From Recruitment to Returning Troops

This Advanced Research Workshop (ARW), “Wounds of War IV: Pain Syndromes – From Recruitment to Returning Troops,” was convened to discuss the topic of increased pain syndromes in service men and women around the world. Research has shown that those who have served in both combat missions and peacekeeping operations are at an increased risk for pain syndromes. Research suggests that this may result from their “wounds of war.” Some wounds may be more “invisible,” such as suicide, depression, stress and traumatic brain injury, while others are more visibly apparent, such as physical disabilities.

During this workshop, we discussed many aspects of pain and how to effectively deal with this issue. Specifically, some of the questions addressed were:

1. The Vulnerability to Pain syndromes: Are certain types of people at a higher risk for pain syndromes (background, ethnicity, childhood trauma, etc.)?

2. The Diagnosis and Assessment Issues of Pain Syndromes: Which methods are used to diagnose and assess pain?

3. The Treatment of Pain Syndromes: What are the latest treatment and therapy opportunities for soldiers who experience pain syndromes?

4. Clinical Updates on Pain Syndromes: What can we learn from recent clinical updates on pain syndromes?

Through this workshop, we have come closer to understanding what programs are already in place in various countries for detection, assessment, prevention, and treatment. Through the presentation of these existing plans, practitioners can start to formulate a more common set of best practices and guidelines which can be implemented throughout organizations in countries worldwide with the common goal to always seek to serve our service members more effectively.

This ARW has given participants an opportunity to foster essential international collaborative research on pain syndromes, a common and disabling consequence of war, terrorism, and natural disasters. As a result, it represents an important landmark in efforts to help soldiers and civilians of NATO and partner nations become more resilient in the face of international conflict.

The full papers within this publication focus on the key presentations during the workshop, act as the permanent record of this event and provide tangible documentation of the ideas that formed the basis of discussion and collaboration at the workshop. This text is organized to mirror the program from the event so as to provide an overview of the ideas of presenters and participants in the ARW.

Financial support for the workshop was provided by several sponsors. We would like to acknowledge the generous contributions of the NATO Science for Peace and Security Programme, the Croatian Ministry of Health and Social Welfare, the Austrian Ministry of Defence (MOD), the University Hospital Dubrava, the Virtual Reality Medical Institute, the Interactive Media Institute and the Virtual Reality Medical Center.

The workshop was organized and this accompanying publication was compiled and edited jointly by the Interactive Media Institute, San Diego, California, USA and Virtual Reality Medical Institute, Brussels, Belgium. Professor Dr. Brenda K. Wiederhold and Professor Dr. Krešimir Ćosić, as conference co-chairs, selected and invited the majority of the speakers and participants. Conference coordinator Mr. James Cullen organized logistics including registration, travel, lodging and meals, assembling of workshop materials, and other arrangements for the ARW. Prof. Dr. Wiederhold chose the beautiful Austrian location where the event took place and Mr. Daniele Pizzioli helped with registration and on-site direction for attendees. Ms. Emily Butcher, Ms. Allison Ines and Ms. Christina Valenti reviewed the conference program and full manuscripts, helping with editing and assembly of this and other associated texts.

This paper examines drug use trends and patterns among U.S. military personnel with an emphasis on prescription drug misuse (i.e., nonmedical use) and prescription pain medication misuse. Data were drawn from the large-scale population-based U.S. Department of Defense Surveys of Health Related Behaviors among Active Duty Military Personnel. Assessment of trends showed large reductions in illicit drug use (including prescription drug misuse) from 1980 to 2002. From 2002 to 2008, prescription drug misuse increased. The key driver of the high rates of past-month prescription drug misuse in 2008 (11%) was past-month misuse of pain medications (10%). The strongest predictor of prescription pain medication misuse was having a prescription for pain medication. Holders of prescriptions for pain medications were nearly three times more likely to misuse prescription pain relievers than those who did not have a prescription. Being in the Army, meeting criteria for Posttraumatic Stress Disorder (PTSD), and engaging in heavy alcohol use were also strong predictors of pain medication misuse. Findings suggest that easy access to pain medications is a key factor in misuse and that better education about the dangers of misusing prescription pain relievers and closer monitoring of prescription drugs may be needed to decrease misuse. Further studies are needed to determine the nature and extent of pain medication misuse, the characteristics of misusers, and their motivations for misuse. Additional research is also needed to develop and implement targeted interventions that reduce misuse of pain medications.

Over the past decade, there have been more than 1,280 service members with amputations resulting from injuries sustained in Iraq and Afghanistan. Current research indicates that the majority of these amputees will suffer from phantom limb pain, defined as the perception of pain in a missing limb. However, despite the wealth of research on phantom limb pain the mechanisms behind the phenomenon remain obscure. Mirror therapy appears to be the most promising therapy to date. The current paper reviews the pivotal theories on phantom limb pain (peripheral, spinal, and psychological factors, the body schema, the neuromatrix, cortical reorganization, pain and proprioceptive memory, and movement) with the hopes of highlighting key gaps in our understanding of the disorder.

Childhood adversity is a common occurrence associated with poor physical and mental health outcomes in adulthood. Population-based studies have found exposure to childhood adversity increases the likelihood of adult chronic health conditions, mental disorders, and suicide behavior, with exposure to an increasing number of adversities resulting in a greater likelihood of these outcomes. Preliminary evidence indicates that military personnel may be at a higher likelihood of experiencing adversity, and as such, it is necessary to fully examine the effects of these events among these individuals. Initial research in this area has found an association between childhood adversity and poor physical and mental health outcomes. However, the extant literature is limited by only examining a few types of adversity, investigating a limited number of physical and mental health outcomes, and not examining males and females separately. Moreover, there is still debate over the combined effect of childhood adversity and combat exposure on adult physical and mental health outcomes. Future research will be needed to further investigate these relationships in this unique population.

With the increasing number of female military personnel and veterans, it is pivotal that appropriate resources are in place for their health needs. The National Epidemiologic Study on Alcohol and Related Conditions, a nationally representative sample of the civilian U.S. population (n=34,653, ages 20 years and older), was used to investigate whether women who reported combat exposure differed 1) from combat-exposed men and 2) from non-combat exposed civilian women in the prevalence of physical conditions and reported interference due to bodily pain. Respondents were asked whether they had been diagnosed with one or more of a number of past-year physical conditions by a physician or other mental health professional. Obesity (body mass index > 30) was also assessed through self-reported height and weight, while a subscale from the Medical Outcomes Study Short Form (SF-12) assessed past-month bodily pain. Logistic regression models adjusted for age and household income were used to understand differences between combat-exposed women and both control groups. Combat women were found to be approximately twice as likely as men who endorsed combat to report having any physical condition (adjusted odds ratio [AOR] 2.02, 95% confidence interval 1.04-3.94). Combat women were more likely than general population women to report arteriosclerosis/hypertension, obesity, and any physical condition (AOR range 2.27-2.72). No differences between combat women and either control group were noted for interference due to bodily pain. These findings are noteworthy for health professionals involved in the treatment of military women and for investigators of military women's health.

An extensive number of different studies, from animal models to clinical and family studies, support the important role of genetic background and epigenetic factors, besides the effects of environmental milieu, on the variability of pain response. So far, precise mechanisms of pain perception and transmission in the central nervous system have not been fully understood. However, comprehensive data imply that a disinhibition and imbalance of the neurotransmitters serotonin and norepinephrine might play key roles. Both neurotransmitters have complex pathways, comprised of numerous receptors, autoreceptors, transporters and enzymes. Recently, it has been shown that clinically relevant inter-individual differences in pain perception and regulation are influenced by a tri-allelic polymorphism in the serotonin transporter gene. In the central nervous system there is another important group of proteins, neurotrophins, which regulate cell growth and survival, differentiation, apoptosis, and cytoskeleton restructuring. The dysregulation of brain-derived neurotrophic factors has been found in individuals with Traumatic Brain Injury and Posttraumatic Stress Disorder, with chronic pain as one of the common clinical features. Genomics has a promising potential to contribute to advances in the elucidation of pain mechanisms and control. With modern laboratory techniques that enable the identification of candidate genes by linkage mapping, whole-genome association, and single gene association studies, genes responsible for different pain disorders could be isolated in the near future. Knowledge of these genetic factors could further support another important issue – personalized medicine – that could improve the efficacy of pain management and lower adverse event profiles.

Pain is a major health problem. It is estimated that over 100 million people in the U.S. suffer from chronic pain with a projected cost of $560-635 billion annually for medical costs and lost productivity. In response to the chronic pain epidemic, the prescribing of opioids has increased dramatically during the last 20 years. This increase has contributed to the creation of a new public health concern – the misuse of prescription opiates. At the fulcrum of these two health crises are healthcare providers including doctors, dentists, nurses and others who are involved in the diagnosis and treatment of pain. Yet the topics of pain diagnosis and treatment receive relatively little attention in the formal training of most healthcare professionals. The National Institute of Health (NIH) Pain Consortium is helping to address this issue by establishing Centers of Excellence for Pain Education (PCoEs.) These PCoEs will develop and implement curricula to help train healthcare professionals in the diagnosis and management of pain. The anticipated result is that these PCoEs will provide healthcare professionals with educational tools to help prepare them better to diagnose, treat, and manage pain and help them minimize the potential for opioid abuse and addiction.

Severe psychological or mental pain, on one hand, is defined as an experience of unbearable torment which can be associated with a psychiatric illness (e.g., Posttraumatic Stress Disorder) or a tragic loss such as the death of an important person. On the other hand, the dominant model in physical pain perception describes a “neuromatrix” which is activated in response to painful stimuli and is also regulated by psychological factors. It was reported that emotions interact with the somato-sensory-discriminant system and that this interaction can produce a sensitization or desensitization to painful stimuli. Further, hypnotically suggested pain seems to produce a pattern of brain region activation similar to that associated with an actual painful stimulus, indicating that mechanisms in the central nervous system may be sufficient to produce the experience of pain even in the absence of external stimulation of the peripheral nerves. It was also proposed by the interpersonal-psychological theory of suicide that exposure to painful and provocative experiences such as combat contribute to fearlessness concerning death and increased physical pain tolerance, which serve to enhance the individual's capability to adopt suicidal behavior. It was further reported that psychological pain is a useful and unique construct in patients with major depressive episodes that can be reliably assessed and may aid in the evaluation of suicidal risk. However, not only environmental factors but also genetic predisposition seem to play an important role in the pathogenesis of suicidal behavior. The interplay between genes and environmental factors involved in suicidal behavior will be discussed.

Pain syndromes are increasingly prevalent in the military and the causes, resulting complications, existing treatment and possibilities for improved care in the future are in need of attention. By constantly being exposed to combat and living in war zones, servicemen and women face increased risk of complicated injuries, including amputations, penetrating wounds, spinal cord injuries, and traumatic brain injuries (TBIs). In addition, many service members may undergo multiple surgical procedures as a result of serious injury. The incidence of pain syndromes is significantly higher when present with Posttraumatic Stress Disorder (PTSD) and other psychiatric disorders such as depression. The combination of these “poly-trauma” events makes the management of both acute and chronic pain in military populations challenging. A multifactorial approach is necessary, and the introduction of new approaches and technology can increase the numbers of tools available to combat this significant health issue in troops

Posttraumatic Stress Disorder (PTSD) is assumed to represent a marker of stress vulnerability rather than a reaction after exposure to a trauma. The underlying biology of PTSD consists of the pre-traumatic biological and physiological risk factors that affect the ability to cope with the traumatic event. Diagnoses involving pain are extremely common among war veterans. The prevalence of chronic pain occurs more frequently in subjects with PTSD (25-80%) than in control subjects, while chronic pain patients have more frequent PTSD than other groups. It is proposed that PTSD mediates chronic pain symptoms. The biological substrates of vulnerability to PTSD and pain include central neurotransmitters, neurotrophic factors, and neuroendocrine systems, while physiological factors include those related to attention, hyperarousal, avoidance, cognition, and anxiety. The severity of PTSD has been found to be correlated with the severity of chronic pain. The neurobiological mechanisms underlying altered pain perception in combat exposed veterans with PTSD are still unclear. Therefore, the aim of this preliminary study was to assess peripheral biomarkers (platelet serotonin [5-HT] concentration, platelet monoamine oxidase type B [MAO-B] activity) and to determine genetic polymorphisms of MAO-B, dopamine-beta-hydroxylase (DBH), catechol-o-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), serotonin transporter (5-HTT), and serotonin 5HT2A receptor, in male Croatian war veterans with current and chronic combat-related PTSD subdivided into those with or without pain syndrome. The objectives were to elucidate the distribution of the genotypes or alleles for MAO-B intron 13, - 1021C/T DBH, Val158/108Met COMT, Val66Met BDNF, 102T/C 5HT2A polymorphisms and 5-HTT gene-linked polymorphic region (5-HTTLPR), and to explore the relation between these variants and pain syndrome in combat-related PTSD. The hypothesis of this study was that these biomarkers would differ between veterans with or without pain syndrome. Since it has been shown that early treatment of pain would prevent the development of chronic pain syndrome, this study aimed to find biomarkers that would provide earlier treatment of pain syndrome, in order to reduce consequences of the pain-related conditions in veterans with PTSD. Participants (N=142) included in the study were unrelated, medication-free Caucasian male war veterans with combat-related PTSD. Veterans had current and chronic PTSD, diagnosed using the Structured Clinical Interview (SCID) based on DSM-IV Disorders. Veterans were categorized according to the presence of pain syndrome into those with or without pain syndrome. The biological and genetic markers were determined from the blood samples using biochemical and genetic analyses. The results, expressed as means ± standard deviations, were evaluated using one-way analysis of variance, and differences in the genotype and allele frequencies were evaluated using a χ² test. Although altered platelet 5-HT concentration was associated with particular symptoms in PTSD, platelet 5-HT concentration was not significantly different between veterans with or without pain syndrome. These results suggest that platelet 5-HT is not a biomarker of the pain syndrome in PTSD. Platelet MAO-B activity, controlled for the smoking status, did not differ significantly between veterans with or without pain syndrome. These data did not confirm the hypothesis that platelet MAO-B might be used as a peripheral marker of the pain syndrome in PTSD. The frequencies of the MAO-B intron 13, DBH-1021C/T, COMT Val158/108Met, BDNF Val66Met, 102T/C 5HT2A, 5HTTLPR variants did not differ significantly between groups of veterans with PTSD with or without pain syndrome, presumably due to the small number of included veterans. In conclusion, our preliminary findings suggest that although combat experience affects the circuits mediating stress response, as well as neural circuitry underlying pain processing, the selected biomarkers, which have been shown to be associated with particular psychopathological symptoms or altered behaviours in PTSD, were similar between groups of veterans with PTSD with or without pain syndrome. These data suggest that further additional studies with larger groups are warranted to shed further light on these associations.

Today, clinicians are more aware of the link between Posttraumatic Stress Disorder (PTSD) and physical pain syndromes, which can both be found in traumatized military troops after traumatic events are incurred during military operations. The current formulation of PTSD is based on the notion that dissociated memories of trauma can be expressed as intrusive thoughts, affective states, sensory perceptions and somatoform dissociations, sometimes represented as pain syndromes. It is well known that patients suffering from PTSD (i.e., war veterans) experience a triad of symptoms: intrusive symptoms; emotional numbness with avoidant strategies; and hyperarousal. However, these patients also have physical symptoms – the most common are chronic fatigue and pain syndromes (i.e., chronic headaches, noncardiac chest pain, and unexplained chronic pain in the pelvic region). In this study, we will present three clinical cases of participants in military and war operations and then analyze the various etiological sources of pain syndromes in PTSD, presenting the possibility that painful symptoms or syndromes can be an etiological intrusion or somatoform dissociation during an anniversary reaction. Therefore, these pain syndromes represent a part of the spectrum of posttraumatic reactions that affect military members long after returning from the “battlefield.”

This is a case report of a wounded soldier who suffered a multiple organ injury as a result of an Improvised Explosive Device (IED) explosion under his armored personnel carrier. His injuries were extreme. The soldier suffered an amputation of his right lower limb with enucleaction in the hip joint, amputation of his left lower limb in the middle of the thigh, a multi-level backbone injury with spinal cord damage resulting in the dysfunction of sphincters, disorders of peristalsis and a partial limitation of breathing activity, chest injuries resulting in a complete amputation of the left lung and a lower part of the right lung as well as distress to the middle part of the lung, an abdominal injury with damage to the fascia and muscles requiring a titanium wire mesh implant across the whole abdomen area, and an injury of the left elbow joint resulting in faulty functioning of this joint.

The injuries suffered by the soldier resulted in a continuous 18-month stay in the hospital. Every day of his hospitalization resulted in a fight with his physical and mental pain. This pain was exacerbated by a series of interventional orthopedic surgeries, e.g., removal of the backbone stabilization system due to penetration of the fixing screws through the skin because of emaciation. Pain treatment for this patient was greatly restricted due to his respiratory distress and the rehabilitation activities administered. The patient's death was caused by respiratory distress resulting from pneumonia. He was conscious until the very end.

This paper contains a case report describing a 44-year old career soldier, a veteran of six deployments outside of Poland (Lebanon, Kosovo, twice in Iraq and twice in Afghanistan). During his latest deployment he developed some lesions on his hands and feet in the form of skin cracks and exfoliation. Fluid was seeping from these areas and they were causing acute pain resulting in a complete inability to perform everyday activities. The patient was treated during his deployment and a slight improvement in symptoms occurred. After returning to Poland he was hospitalized twice in the Department of Dermatology of the Military Institute of Medicine because of worsened skin symptoms (seeping cracks, epidermis exfoliation, finger contractures, and acute pain preventing normal functioning). The diagnosis revealed contact dermatisis. The applied symptomatic treatment resulted in only temporary improvement followed by a recurrence of the symptoms. After a psychiatric consultation a possibility of a psychogenic basis of the lesions was identified. The patient was admitted to the Department of Psychiatry and Combat Stress of the Military Institute of Medicine (DP&CS), where the examination showed a comorbidity of PTSD symptoms and the lesions. An experiment using Virtual Reality (VR) has clearly displayed the occurrence of skin reactions while the patient was exposed to war scenes. The outcome of the medication and individual applied psychotherapy reduced the lesions to a level allowing for normal everyday functioning of the patient and the longest achieved remission of the lesions to-date.

The healthcare costs for treating pain for wounded military personnel, veterans, and their families have grown exponentially. To either mitigate or completely resolve these issues for both one's personal well-being and U.S. economic practicality and stability, new approaches outside the Western medical model of intervention are required. A number of complementary and alternative healing modalities are providing substantive results in both arenas, thus reducing pharmaceutical and long-term healthcare dependencies and, most importantly, addressing the much-needed physical and psychological challenges faced by military personnel, veterans, and their families.

Estimated costs of healthcare and lost work productivity are in excess of $100 billion per year. Nearly one-third of U.S. adults suffer from chronic pain (pain lasting more than three months). A recent study on this subject showed that low back pain alone has associated costs estimated to near $90 billion dollars. At the present time, most providers treat chronic pain patients with a combination of analgesics and non-drug approaches. That said, many of these professionals are also starting to incorporate the use of technology (e.g., Virtual Reality and biofeedback) into their practice. The purpose of this study was to compare standard chronic pain treatment (i.e., assisted relaxation with a clinician) with technology-assisted relaxation without a clinician. Results suggest that there was a greater reduction in self-rated pain when participating in the relaxation imagery session enhanced with technology.

Psychological health and resilience are indispensable requirements for military personnel serving in combat zones. Their importance is even greater because of their close relationship to the experience of pain. An example shows a German NCO with chronic dental pain for three years after deployment whose pain ceased after psychotrauma therapy.

Differentiated prevention programs are becoming more and more important to protect troops not only from Posttraumatic Stress Disorder, but also from depression, anxiety disorders, and pain syndromes.

Prevention programs in the German Armed Forces follow a “Framework Regulation for Coping with Psychological Stress of Servicemen.” The concept defines measures on a three phase and three level basis. The three phases include pre-deployment preparation, deployment itself, and post-deployment measures. Right now the Framework Regulation is being further developed. The focus has shifted from psychological stress to psychological fitness (PF). PF needs to be defined and operationalized by its components. The practical implementation includes a computer-based training program during pre-deployment training. Regular screening measures will monitor the PF of troops and regulate an individualized combination of post-deployment modules to strengthen personal resources. These components of primary and secondary prevention also include elements to reduce the basis for mental and physical pain.

The concepts and their relation to pain will be presented and discussed.

Recent research suggests that chronic Posttraumatic Stress Disorder (PTSD) and chronic low back pain (LBP) frequently co-occur and that similar mechanisms may exist for maintaining both conditions. On the basis of medical records, interviews and different self-reported questionnaires we analyzed the relationship between chronic LBP, chronic PTSD and quality of life in 406 Croatian war veterans. Our results have shown that chronic PTSD may be associated with greater pain perception in war veterans. There is a need for a multidisciplinary approach in the treatment of patients with chronic PTSD and comorbid chronic LBP in order to optimize treatment that would result in more cost-effective care. Today, in the treatment of chronic pain and chronic PTSD the focus is on so-called “rational polypharmacy.” The authors would like to present their clinical experience in the treatment of patients with chronic LBP and chronic PTSD.

Pain is among the most common medical complaints, and is associated with impaired quality of life of affected individuals and consequent large societal costs. Taking into account the multidimensional nature of pain, this paper describes the concept of the pain mental state vector, which integrates affective, cognitive, physiological, and motor representations. Bottom-up pain pathways and descending pain modulatory pathways are briefly reviewed, before discussing top-down multimodal cognitive regulation of pain. Due to empirical success of pain management that relies on attentional distraction facilitated by Virtual Reality (VR), as well as prior literature on the underlying neurobiological mechanisms, the paper also discusses some aspects of the neurobiology of multimodal cognitive regulation of pain.