Updates & Features
Chronic Overlapping Pain Conditions
Christin Veasley, Co-Founder & Director, Chronic Pain Research Alliance
Impact vs Belief – a disconnect in chronic pain
The Institute of Medicine’s (IOM) historic 2011 report, Relieving Pain in America, documented the profound cumulative impact of chronic pain on our nation, finding that four in ten American adults live with chronic pain disorders, with annual costs exceeding $500 billion.1
In March 2013, the National Poll on Chronic Pain was conducted online by Zogby Analytics for Research!America. The survey had a sample size of 1,016 with a theoretical sampling error of +/- 3.1%.2 A major highlight of the survey was that most Americans (63%) reported knowing someone with pain so severe that s/he sought prescription medications to treat it. Further, the majority, 60%, reported thinking that chronic pain tends to be dismissed by doctors and the general public. However, when respondents were asked to select health conditions they considered to be major health problems in the US, only 18% listed chronic pain as a major health problem, demonstrating a major public disconnect.
One reason for this disconnect can be traced back to a longstanding underinvestment in pain research by the U.S. federal government. Chronic pain affects the same number of people as cancer, heart disease and diabetes combined (100 million), and in 2016, the National Institutes of Health (NIH) invested 95% less on pain research than it did on research for these three conditions ($483 million on pain research vs. $7.9 billion on cancer, diabetes and heart disease research).3 The disparity is even more glaring when one compares the research investment to financial burden – with a federal investment of less than 1% of the annual cost of chronic pain ($560-635 billion).
Current initiatives to improve chronic pain management in the US
Nevertheless, positive initiatives are in development. In March 2016, the Department of Health and Human Services released the first federal interagency plan to develop a new system of pain care in the United States, called the National Pain Strategy. Further, the development of the first federal interagency pain research strategy is underway. Also, for the first time, the Department of Health and Human Services has included pain in its plan to address the opioid epidemic, and the NIH, along with the U.S. Food and Drug Administration and pharmaceutical industry is developing the first public-private partnership to develop novel treatments for both chronic pain and opioid addiction.
Chronic Overlapping Pain Conditions – emergence, symptoms, mechanisms & unmet need
Coming back to the beginning of this article, the IOM report noted the increasing recognition and importance of a cluster of prevalent pain conditions that frequently co-occur, share common underlying disease mechanisms, and either solely or predominantly affect women.1 The concept of coexisting pain conditions was recognized by the National Institutes of Health and the US Congress as a set of disorders that co-aggregate and include, but are not limited to temporomandibular disorder (TMD), fibromyalgia (FM), irritable bowel syndrome (IBS), vulvodynia, myalgic encephalomyelichronic fatigue syndrome (ME/CFS), interstitial cystitis/painful bladder syndrome (IC/PBS), endometriosis, chronic tension-type headache, migraine headache, and chronic low back pain. Collectively, the state of clinical overlap of these conditions are increasingly referred to as Chronic Overlapping Pain Conditions (COPCs).4
Not everyone who develops one of these conditions will go on to develop more, however many do, particularly women. The complexity of overlap makes any combination and number of conditions possible. Some people develop multiple conditions around the same time, while others develop them in succession over many years.5
It’s common for COPCs patients to suffer from other chronic conditions, such as sleep or mood disorders. Also, chronic pain has a far-reaching impact, causing fatigue, difficulty with thinking and understanding, and varying degrees of physical, social and sexual dysfunction. These conditions can develop before chronic pain starts, at the same time, or afterwards.
Mounting publications further substantiate that these conditions share common underlying disease mechanisms, mainly in the immune, neural and endocrine systems. Cumulatively, evidence suggests that multiple genetic factors, when coupled with environmental exposures (eg, injury, infections, and physical and psychological stress), increase the susceptibility to highly prevalent COPCs by enhancing pain sensitivity and/or affecting psychological vulnerability.6
A delay in accurate diagnosis and effective treatment commonly experienced by individuals with COPCs can have serious consequences, including worsening of both site-specific and body-wide symptoms, which in turn, makes COPCs more difficult to effectively treat. A vicious cycle ensues, leading to poorer health outcomes, diminished quality of life and increased disability. The toll extends far beyond the affected and their families, substantially impacting the health, workforce and productivity of the nation as a whole.3
Given their widespread prevalence and financial toll, significant rates of overlap, similar symptom presentation, common disease mechanisms and appreciable unmet treatment demand, there is a tremendous opportunity for research and development of safe and effective treatments for COPCs. As a result of the meager federal, private and industry research investment in COPCs to date, evidence-based treatment options are woefully few and inadequate. Furthermore, only a handful of FDA-approved pharmaceutical treatments exist for half of these conditions, only two of which have been approved in the last five years. None are indicated for more than one COPC, although several are used off-label to treat a number of these conditions. The resultant situation is that COPCs sufferers and their clinicians must use trial‑and‑error methods selected from a myriad of treatments, most with unknown safety and efficacy data (especially when combined), until they identify a combination that brings some relief.4
Presently, there are four national multi-center studies in various stages of development, execution and publication: MAPP, OPPERA, Complex Persistent Pain Conditions: Unique & Shared Pathway of Vulnerability and Pain, and The Interoception Imaging Network (PAIN) Repository.
Although the mechanisms that underlie most of these conditions are still poorly understood, COPCs have been associated with a state of pain amplification resulting from either peripheral and/or central mechanisms manifested as widespread hyperalgesia on the basis of quantitative sensory testing, with sensory and also affective perturbation. Although assessing all of these domains is not practical clinically, screening methods are needed that permit the identification of patients requiring more intensive treatments. Computer adaptive testing approaches also can be implemented, which greatly reduce respondent burden.7,8
Despite our ability to assess multiple facets relevant to COPCs, treatment of COPCs and chronic pain more generally, remains challenging. Current interventions retain a focus on sensory aspects of pain despite the knowledge that chronic pain is heavily influenced by biopsychosocial factors. Regardless, some positive evidence for combination therapy for COPCs, clinical outcomes remain suboptimal and additional research and stratification methods are needed. This may be in part attributable to the failure to appropriately incorporate COPCs into the design and conduct of most clinical trials.9
Future research direction
Obviating how future trials will account for COPCs, an important step will be to collect more comprehensive biopsychosocial and molecular data, across multiple domains, to allow investigators to identify subgroups that reflect potentially distinct pathophysiologic mechanisms. Broad-based information regarding clinical features, pain amplification, and psychosocial functioning can be subjected to sophisticated statistical approaches (e.g., cluster analysis, latent class analysis) to permit identification of phenotypic profiles. These phenotypic data can then be combined with genetic and other biomarker data to characterize the biological mechanisms contributing to the empirically defined subgroups. Stratified analysis can then be performed to identify subgroups that are particularly responsive (or nonresponsive) to treatment.
- Institute of Medicine Report from the Committee on Advancing Pain Research, Care, and Education: Relieving Pain in America, A Blueprint for Transforming Prevention, Care, Education and Research. The National Academies Press, 2011 http://books.nap.edu/openbook.php?record_id=13172&page=1.
- A Research!America poll of U.S. adults conducted in partnership with Zogby Analytics in March 2013
- NIH-Wide Strategy Plan Fiscal years 2016-2020
- Veasley C, et al. Chronic Pain Research Alliance. http://www.chronicpainresearch.org/public/CPRA_WhitePaper_2015-FINAL-Digital.pdf. Published May 2015
- Chronic overlapping pain conditions. Patient guide. Chronic Pain Research Alliance. 2018. http://www.chronicpainresearch.org/public/CPRA_Patient_Guide.pdf
- Maixner W, et al. J Pain. 2016; 17(9 Suppl):T93-T107
- Sturgeon JA, et al. J Pain 2015; 16:291-298.e1
- Sturgeon JA, et al. Pain 2015; 156:2627-2633
- Clauw DJ. JAMA 2014; 311:1547-1555