Chronic Pain in Heart Failure

Chronic pain, defined as pain that persists 3 to 6 months beyond normal healing time,1 remains a challenging and complex problem. According to data tabulated by the Centers of Disease Control and Prevention, over 51 million people experience chronic pain, 17 million of whom report pain that notably restricts daily activities.2 Chronic pain is particularly burdensome in conjunction with chronic heart failure (HF) because of its relationship with other common symptoms including dyspnea, activity intolerance, cognitive dysfunction, depression, anxiety, and sleep disturbances.3–5 Pain when combined with these symptoms exacerbates already low activity intolerance4 and contributes to high symptom burden6–9 that increases patient suffering and decreases health-related quality of life.3 Prevalence rates of chronic pain among patients with HF can range upwards of 85% to 91% depending on the location of pain, age, gender, and comorbidity.3,8,10,11 Authors of previous studies have reported that pain is more common than other classic symptoms in HF, including dyspnea, fatigue, and low energy.4,8 In addition, an estimated 31% to 57% of patients with HF experience moderate to severe pain.11,12 Given the high prevalence and severity of pain in this population, novel and comprehensive treatments are needed. Evangelista and colleagues13 previously described chronic pain in HF as "unrecognized and untreated," and this sentiment remains relevant more than a decade later. There are few robust pharmacological and nonpharmacological treatment options for chronic pain detailed in national clinical practice guidelines for HF.14 Opioids are commonly prescribed for pain among patients with HF, but effectiveness remains suboptimal for many.6 In addition, opioid use has been linked to higher rates of coronary heart disease and cardiovascular death.15 There has been a subsequent shift toward nonopioid alternatives, such as nonsteroidal anti-inflammatory drugs, but commonly prescribed nonsteroidal anti-inflammatory drugs, including ibuprofen and diclofenac, are not recommended for patients with HF because of their adverse effects on fluid retention16 and kidney function.17 Potential nonpharmacological options for pain relief include physical therapy, stretching, walking, and heat/cold therapy, but these approaches remain understudied and generally underused among patients with HF.6,18 We conducted a literature search of PubMed and CINAHL on September 13, 2023, using the keywords "pain," "heart failure," and "non-pharmacologic" and found 2 published clinical trials in which the effectiveness of nonpharmacologic interventions was examined for reducing pain in HF.19,20 Bakitas and colleagues19 published a study of an early palliative care telehealth intervention and reported that pain intensity and pain interference with daily life improved in the intervention group, but the trial did not aim to directly manage pain. Groninger and colleagues20 published a study of a virtual reality intervention and reported that pain scores were improved in the intervention group. However, the authors reported an underpowered sample and was unable to examine long-term effects of the intervention.20 Ultimately, the current literature, although promising, is lacking in key areas, particularly the long-term efficacy and effects of interventions on underlying mechanisms of pain. Additional studies are needed to address the barriers that are slowing both the development and testing of novel interventions for pain in HF. One of these barriers is that chronic pain in HF remains poorly characterized beyond a location-based pain taxonomy. Seventy studies were published in the past 3 decades in which investigators characterized locations of chronic pain among patients with HF.3 The most common locations reported were chest (13%–47%), back and shoulders (14%–58%), lower extremities (22%–71.3%), neurologic pain/headaches (3%–26.6%), abdominal pain (4%–31.9%), and generalized pain (7%).3,6,13,21–24 Of these aforementioned studies, few examined other aspects of pain beyond prevalence and severity, such as limitations with activities or emotional distress.21 Pain is a broad multidimensional construct with several methods of classification beyond locations, including but not limited to subtypes, and functional limitations.25 Some types of pain, such as ischemic chest pain, are precipitated by impaired oxygenation to tissues.26 In contrast, chronic pain in locations other than chest pain (eg, musculoskeletal pain) can be connected to multiple etiologies including inflammation, edema, impaired circulation, visceral ischemia, and musculoskeletal fatigue.3 On the basis of available evidence, patients with HF frequently experience cardiac and noncardiac pain,21 meaning that pain is likely driven by both HF and other chronic conditions. This indicates that an intricate and comprehensive approach to pain characterization in this population is vital before tailored interventions can be developed and tested. One of the most important and vexing questions regarding characterization of chronic pain among patients with HF is what portion of pain is contributed by HF pathophysiology (eg, inflammation, volume and pressure overload, neurohormonal dysregulation)27 or by other comorbid conditions (eg, diabetes, arthritis). Etiology-based classification represents a promising avenue of pain characterization in this patient population that moves beyond a location-based taxonomy to more mechanistic and pathologic representations. One example is the delineation of pain subtypes as defined by the International Society for the Study of Pain, which consists of nociceptive, neuropathic, mixed, and nociplastic pain.28 Nociceptive pain occurs when there is real or potential harm to nonneural tissue, triggering the activation of nociceptors.28 In the case of HF, pain may be nociceptive because of inflammatory responses triggered by both the innate and adaptive immune systems after damage to the heart muscle.29 Neuropathic pain arises from damage or illness affecting the somatosensory nervous system.28 Although its occurrence is not well understood among patients with HF, it is possible that immune-mediated neuropathy plays a role in chronic pain presentation. Inflammatory processes can harm components of the peripheral nervous system and may contribute to neuropathic pain.30 In our previous pilot study conducted to determine genomic biomarkers underlying pain among 24 patients with HF, we found over 15 genes that overwhelmingly coded for proteins involved in immune and inflammatory processes, and were significantly upregulated in patients who reported pain compared with patients who did not report pain. However, the pain measures available were not robust enough to stratify patients by subtypes.31 Pain is not purely a biologic process but is influenced by multiple psychosocial factors.32 Theoretical frameworks have yet to be developed that fully describe the relationships between chronic pain and all contributing factors among patients with HF. We found only 1 previously published conceptual model that identified a constellation of factors influencing chronic pain in HF.33 Proposed factors included biological (ie, HF severity, cognitive processing, neurological), affective (ie, depression, anxiety), sociocultural (ie, cultural and religious beliefs, social support), and behavioral factors.13,33 Although an important first step, many factors were difficult to operationalize, and all were conceptually isolated, indicating a need for further revisions and testing. Another potential model is the biopsychosocial model of chronic pain,34,35 which has been previously adapted for older adult populations,32 but not for HF. New conceptual models grounded by empirical evidence are needed to better understand pain within the context of unique contributing factors, including neurohormonal imbalances, inadequate social support and relationships, affective disorders, HF severity, cognitive dysfunction, and central nervous system processing disorders, among others.3 Given the high prevalence of chronic pain in HF and the current state of the theoretical and empirical literature, there are at least 4 research priorities needed to improve characterization and treatment of pain. One research priority is to develop a comprehensive and holistic clinical pain questionnaire that is HF specific, reliable, valid, sensitive to change, and feasible to administer. A second research priority is to identify the pathways in which chronic pain arises or worsens in HF in the context of other symptoms and comorbid conditions. This constitutes an important gap in the literature, as authors of a previously conducted systematic review of symptom clusters in cardiovascular disease reported that patients with HF experience a high burden of symptom severity, but only 2 of these studies mentioned pain.36 A third research priority is to build understanding of the relationships between pain and age, gender, and self-reported race as well as social determinants of health. This is essential to construct theoretical frameworks that adequately capture all the salient components that impact chronic pain. A final research priority is to develop, administer, and evaluate targeted interventions that address underlying etiologies of pain. Future interventions for chronic pain in HF should integrate components of nurse-centric care, including self-care techniques, multidisciplinary collaboration, and pharmacologic and nonpharmacologic approaches.37 Chronic pain is a key nurse-sensitive outcome38 and is integral to patient-centered and holistic care. Nurses should recognize that patients with HF frequently experience both chest pain and pain in other locations and that it is often poorly managed even with medications.6 Nurses can reduce barriers to optimal pain management through patient education, support, and provision of resources.39 Regrettably, patients with HF are among the most frequently hospitalized40 yet are frequently not provided a concrete care plan to control pain after discharge.18,41 Patient education is especially important for safe administration of pain medications, particularly opioids, as well as mitigating associated risk factors. Monitoring and acting when pain worsens is also crucial to prevent adverse outcomes, as pain increases 30-day healthcare use42 and may be an indicator of serious adverse emergencies, such as acute coronary syndrome. The need for better characterization and interventions for pain has been previously recognized,13 but little progress has been made. Pain has been established as a common and debilitating problem for patients with HF, but treatment and management options remain insufficient. Deep phenotyping studies of pain and associated factors are only the first step before effective interventions can be developed. Given the complexity of pain in this patient population, it is likely that targeted interventions may need to be developed and compared to ascertain which provides the most benefit. Ultimately, proper management of pain among patients with HF is a crucial component to alleviate suffering and increase quality of life.