Pain Comorbidities: Understanding and Treating the Complex Patient

Q: This book appears during IASP's Global Year Against Headache. How do headaches relate to comorbidity?
A: Headache disorders are estimated to affect nearly half the world's adult population. They represent a major source of disability and a large economic burden to society. Headache disorders have a tendency to coexist with a number of other conditions, many of which are painful, such as fibromyalgia, myofascial pain syndrome, dysmenorrhea, endometriosis, or irritable bowel syndrome. Epidemiological findings suggest that having comorbid pain conditions may influence the transition of episodic to chronic headache. Identification and early treatment of these conditions in the headache patient may influence the evolution of the disease.

Q: Which of the nonpainful comorbidities link with headache?
A: Evidence has also rapidly grown in recent years for a link between various expressions of cardiovascular disease (CVD) – a major health problem in the general population – and headache symptoms, especially migraine. In one instance, it can complicate diagnosis, as in the case of focal signs of migraine and stroke. In another, one disease can remind the clinician of another, such as migraine and coronary disease. Or, one prophylactic treatment can be effective for two diseases, such as ACE inhibitors or sartans for migraine patients with hypertension. At the same time, a concurrent CVD in migraine patients may preclude or limit the therapeutic use of symptomatic treatments, such as triptans, that affect the cardiovascular system. Other important headache comorbidities occur with psychiatric/mood disorders, whose presence may change the therapeutic approach to headache; for example, some prophylactic agents can worsen depression.

Q: Diabetes and obesity currently surge in developed countries. How do these conditions correlate with chronic pain?
A: On one hand, diabetes frequently has painful complications, such as painful diabetic neuropathy, which can be very difficult to treat; and on the other hand, similarly to hypertension, having diabetes can decrease or even abolish the perception of pain in a number of specific conditions that normally involve acute pain, such as myocardial infarction, thus delaying their identification and treatment. Obesity presents an important risk factor for the development of certain types of pain, especially osteoarthritis and low back pain, and the concurrence of pain and overweight/obesity will decrease the patient's quality of life. An important aspect of the obesity/pain link is that many pharmacological treatments of chronic pain cause weight gain as an important adverse effect, which may create a vicious cycle in these comorbid patients.

Q: For Maria Adele: You published a lot on visceral pain, and you include a chapter on this topic in Pain Comorbidities. What are some of the most important new research findings that may lead to better treatment?
A: Both experimental and clinical studies have contributed to a better understanding of visceral pain mechanisms, which is the fundamental step toward better strategies of treatment that are not merely symptomatic. Research on experimental models, using different approaches, including genetic interventions, have helped in identifying the potential molecular targets for new drugs, whose efficacy is now being tested in clinical trials, in some cases with encouraging results. Clinical research studies have highlighted the importance of comorbidities of different visceral pains in the same patient, showing how specific treatment of one visceral disease may significantly relieve pain arising from another organ with a related innervation. The fact that cholecystectomy may reduce angina pain in patients with comorbid coronary artery disease and biliary calculosis and the finding that urinary stone elimination after lithotripsy can relieve menstrual pain in women with concurrent urinary calculosis and dysmenorrhea are just two examples of how important it is to consider viscerovisceral interactions in the same patient for therapeutic purposes.

Q: For Troels: You authored a chapter on neuropathic pain. It is well known that diabetes may lead to peripheral neuropathy. What other conditions do you discuss? And what lines of research indicate the most promise in terms of understanding and treating neuropathy?
A: Diabetes is the prototypic disorder that may give rise to a neuropathic pain syndrome, which has certain characteristics, i.e., a cluster of symptoms and signs. This typical presentation has created the erroneous idea that neuropathic pain is one specific disorder. The term "neuropathic pain" includes a large number of conditions with different etiologies that require separate diagnostic approaches, and in most cases distinct therapies. There has been a tendency to treat the pain phenomena without attempting to address the underlying cause and the associated comorbidities. It is our hope that this book may help to address this issue. The book mentions various other metabolic and inflammatory conditions that may be accompanied by a neuropathic pain. These include Guillain-Barré syndrome, neuroborreliosis, vasculitic disorders such as Sjögren's disease, sarcoidosis, and HIV neuropathies, among other inflammatory conditions. Among metabolic causes, avitaminosis in particular may be a neglected area in the developing world. More research is clearly needed.

Q: Can you give some examples of the presentation of what you call a "complex patient?"
A: A "complex patient" may be someone with a headache who has concurrent cardiovascular disease/hypertension, obesity, diabetes, and depression. Eliminating the possibility that the headache is secondary to the patient's cardiovascular/dysmetabolic status would be the first, mandatory step, especially in the case of a recent-onset headache. Then, if a diagnosis of primary headache emerges, depending on the type of headache, one should choose symptomatic and prophylactic headache treatments, taking into account all the indications and contraindications linked to the comorbidities and their current treatment. Another group of complex patients includes those with type I and/or II complex regional pain syndrome (CRPS). These patients have many different comorbidities, and it can be difficult to separate the various components. Until recently, CRPS type I was considered to be a neuropathic pain condition, but with the new IASP definition of neuropathic pain, CRPS is no longer seen as part of this category. It is important to remember that a rational management plan for all patients depends on proper diagnosis.

Q: How are these patients typically managed in industrialized countries?
A: A multidisciplinary pain clinic might offer notable advantages in the management of the complex patient, but unfortunately this option is not available everywhere. In many circumstances, patients "migrate" from one specialist to another, and they are often treated with an "in sequence," rather than an integrated, paradigm for their medical problems.

Q: If a patient is seeing a specialist for a specific disorder and has multiple concurrent problems, is it possible that the patient may miss out on potentially helpful interventions?
A: It is unfortunately possible that some important information is being lost if there is not enough collaboration among the specialists of different disciplines consulted by the patient. In an era of super-specialization, where there is a trend of treating diseases specifically and separately, we must acknowledge the essential role of a unifying clinical figure who can sum up and coordinate all the specialistic interventions for a pain patient.

Q: Do older adults endure more comorbidities, and do they require different treatment options?
A: Yes, multimorbidity is estimated to affect from 55% to 98% of all older persons and is associated with a high degree of disability. This represents a major clinical challenge at present, given the progressive aging of the population. Diagnosis of pain comorbidities may be more difficult in the elderly, owing to different symptoms from those of younger adults, and pharmacological treatment may require particular prudence because of the reduced margin between effective and toxic doses for many drugs, especially analgesics. Also, programs of physical therapy and rehabilitation as well as psychological interventions need to be tailored to the specific needs of this fragile segment of the population.

Q: How would you summarize your findings?
A: Analysis is important, but synthesis is essential. The key message we would like to convey to clinicians – whatever their specialty – is never to forget that the patient with comorbidities is a whole person whose clinical picture represents a complex interaction of multiple factors and not merely the sum of symptoms of each separate condition.

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Preface
Introduction by Harold Merskey

Part I: General Aspects, Epidemiology, and Models

1. Epidemiology of Pain and Non-Pain Comorbidities
   Clare H. Dominick and Fiona M. Blyth
2. Experimental Animal Models of Pain and Non-Pain Comorbidities
   Anna P. Malykhina
3. Experimental Human Models and Assessment of Pain in Non-Pain Conditions
   Lars Arendt-Nielsen, Thomas Graven-Nielsen, and Laura Petrini
4. A Neurobiological Approach to Chronic Pain and Comorbidities: Evidence from Animal Models
   Gordon Munro
5. Genetic Factors in Comorbid Pain Disorders
   Dan Buskila and Antonio Collado Cruz
6. Hormonal Contributions to Comorbid Pain Conditions
   Roger B. Fillingim and Margareta Ribeiro-Dasilva
7. The Role of the Immune System in Chronic Pain Comorbidities
   Peter M. Grace, Linda R. Watkins, and Mark R. Hutchinson
8. The Influence of Psychosocial Environment in Pain Comorbidities
   Akiko Okifuji and Dennis C. Turk

Part II: Concurrent Pain and Non-Pain Conditions

9. Pain and Hypertension
   Stephen Bruehl
10. Neuropathic Pain in Diabetes: Diagnosis and Management
    Solomon Tesfaye
11. Obesity and Pain
    Peggy Mason
12. Headache and Cardiovascular Disease
    Paolo Martelletti and Andrea Negro
13. Neuropathic Pain in Metabolic and Inflammatory Diseases
    Troels Staehelin Jensen
14. Pain and Affective Disorders: Looking Beyond the "Chicken and Egg" Conundrum
    Ephrem Fernandez and Robert D. Kerns
15. Myofascial Pain Syndromes in Headache Patients
    César Fernández-de-las-Peñas, Ana Isabel de-la-Llave-Rincón, and Cristina Alonso-Blanco
16. Concurrent Visceral Pain Syndromes: The Concept of Viscerovisceral Hyperalgesia
    Maria Adele Giamberardino, Giannapia Affaitati, and Raffaele Costantini
17. Visceral Pain and Headache in Fibromyalgia
    Robert D. Gerwin
18. Muscular Pain Comorbidities in Joint Diseases
    Thomas Graven-Nielsen, Henning Bliddal, and Lars Arendt-Nielsen

Part III: Management Aspects

19. The Multidisciplinary Pain Center: Treating Comorbidities
    John D. Loeser
20. Pharmacological Approach to Pain and Its Comorbidities
    Lucy A. Bee, Leonor Gonçalves, and Anthony H. Dickenson
21. Antidepressants in Pain, Anxiety, and Depression
    Nicole Gellings Lowe and Stephen M. Stahl
22. Physical Training and Rehabilitation in Patients with Pain Comorbidities
    Harriet M. Wittink and Jeanine Verbunt
23. Psychological Management of Chronic Pain and Comorbidities
    Lance M. McCracken
24. Synopsis
    Maria Adele Giamberardino and Troels Staehelin Jensen

Index

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"This publication by IASP Press provides readers with a comprehensive update on chronic pain and its multiple interactions with medical comorbidities. The editors are leading experts in complex pain states, such as neuropathic pain, fibromyalgia, and headache, and the contributing authors have a range of expertise that spans from basic science research to clinical aspects of pain, including related physiotherapy and psychology considerations. … In summary, this is an excellent textbook that provides an in-depth review of complex pain states with a focus on patients with coexisting diseases. The information is novel and up-to-date and provides clinicians with a holistic approach to the management of pain patients with extensive comorbidities."
Akilan Velayudhan, MBBS, 2013, Can J Anesth.

"This book sets out to offer an in-depth analysis of complex clinical situations involving multiple concurrent diseases. As with most other clinical entities, pain rarely presents on its own, but is clouded by multiple other diagnoses. The first section of the book describes the epidemiological relation between pain and non-pain comorbidities and the possible genetic, hormonal, immunological and psychological links. The second section explores the interaction between pain and conditions such as hypertension, obesity, diabetes, and a range of other visceral disorders. The last section discusses implications for treatment and management. The importance of a multidisciplinary approach is emphasised, and includes pharmacological, physical and psychological therapies. This book will be of use and interest to those specialising in the management of chronic pain."
Roger Woodruff, March 2013, IAHPC Newsletter

"Attempts to reduce chronic pain to single parts of the body, to single genes, or single environmental factors, have failed. Pain is an emergent phenomenon: it emerges in a constellation of multiple factors. The book very successfully explores the relationships between many of these factors – genes, hormones, nerves, emotional states, mindframes. It makes an enormous effort to understand the difficulty of the individual patient addressing the B (‘biological’) and the P (‘psychological’) in the BPS (‘biopsychosocial’) model of pain."
Jens Foell, International Musculoskeletal Medicine, 2013.

"This expansive and well-illustrated book reviews the clinical presentation and management of interactions among diverse medical conditions, including myofascial pain, headache, fibromyalgia, visceral pain, hypertension, diabetes, osteoarthritis, low back pain, obesity, depression, and anxiety. The editors have carefully assembled a collection of evidence-based articles examining the nature, modalities of diagnosis, and treatment of complex clinical situations involving multiple concurrent diseases and their overall influence on the experience of pain."
Stewart B. Leavitt, February 2013, pain-topics.org

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