Pain Management in Lung Cancer Rehabilitation

Pain Definition

In June 2020, the International Association for the Study of Pain (IASP) revised the definition of pain for the first time since 1979, after 2 years of development. The revised pain definition from the IASP reads as “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.” Six additional notes were added to this revised definition, further describing pain as a personal experience with biopsychosocial factors, as a concept shaped by life experiences, and as distinct from pure nociception. It goes on to emphasize that a patient's pain narrative should be respected, and that verbal communication is not the only way to report pain. Although pain serves as a protective mechanism, it can also seriously impact functional, social, and psychological well-being. The IASP pain definition is widely accepted by international organizations, including the World Health Organization. Patients with lung cancer can have acute pain (<6 months), chronic pain (>6 months), or acute on chronic pain, that can range from mild to severe in intensity, and may be multifactorial in nature, including neuropathic, visceral, and somatic pain components. This will be discussed in depth later in this chapter.

Pain Theories as Related to Cancer

Biopsychosocial Model of Pain. The biopsychosocial model of pain succeeds the biomedical model of pain, which dates back hundreds of years to Descartes, as well as the gate control theory which dates to the 1960s as described by Melzack and Wall. ^, The biopsychosocial model described by Turk and Flor posits that biological factors modulate pathophysiological alarms, psychological factors influence the analysis of these internal signals, and that social factors determine the behavioral response to these bodily signs and symptoms. ^, This model applies to both acute and chronic pain, is widely accepted within the pain science community, and applies well to cancer pain. The biopsychosocial model focuses on illness instead of disease and proposes that patients can vary in their responses to somatic sensations, based on psychosocial factors. In the biopsychosocial model of pain, the biological, psychological, and social factors can vary in influence at different times within the same patient, as well as vary between patients with the same underlying diagnosis. Ultimately, our understanding of pain has changed throughout the course of human history from a unidimensional construct, to a multidimensional concept which requires an interdisciplinary approach.

Total Pain . Dame Cicely Saunders, founder of the modern hospice movement, with training in nursing, social work, and medicine, introduced the concept of “total pain” to include physical, psychological, social, and spiritual elements, as described in her early writings. Although emphasis is often placed on physical pain, a patient's pain experience may also include any or all components of pain related to their emotional state, loss or change in their societal and familial role, as well existential, religious, and/or spiritual distress. The framework of total pain emphasizes each patient's uniqueness and unique pain experience.

Symptom Clusters. It has been suggested that the symptoms experienced in lung cancer often occur in clusters throughout the course of the disease. In cancer, symptom clusters have been defined as multiple symptoms that exist simultaneously that are related to each other through a common mechanism, although they may not share the same etiology. Hamada and colleagues identified three symptom clusters that predominate in patients with advanced lung cancer: a fatigue/anorexia cluster, a pain cluster, and a numbness cluster. The pain cluster has the strongest influence on an individual's emotions, compounding symptoms of pain, anxiety, and sadness. There is evidence that pain has a positive correlation with fatigue, disrupted sleep, and distress in individuals with lung cancer, suggesting that these symptoms may exist concurrently and intensify overall symptom severity. Symptom clusters affect quality of life (QOL) and functional status to varying degrees. Pain clusters have been shown to interfere with physical, emotional, and social aspects of everyday life. Lin et al. found that the cooccurrence of pain, fatigue, disturbed sleep, and distress negatively correlated with functional status and QOL measures in patients with lung cancer who underwent surgical intervention. Managing pain without considering other cluster symptoms may result in inadequate treatment, persistent symptom burden, and poor QOL. To improve the overall well-being of patients with lung cancer, attention needs to focus on developing comprehensive pain management strategies that address symptom clusters to reduce pain and distress experienced in this population.

Pain in Lung Cancer—Types and Locations

Pain in lung cancer encompasses a broad spectrum of symptomatology and etiology and therefore is often poorly characterized and challenging to treat. One method of classification is by defining whether the patient's pain is directly related to the malignancy or due to the various antineoplastic treatment modalities that are utilized. Pain may also be categorized by location, duration, and/or by its nature.

Somatic or nociceptive pain is defined as “physiological pain due to stimulation of the sensory nociceptors located in tissues.” It may occur due to direct damage of local structures, or be referred from visceral organs. Neuropathic pain , also called “nerve pain,” is caused by an injury or insult to the central or peripheral nervous system, causing the pain centers in the brain, spinal cord, and peripheral nerves to produce abnormal nerve impulses. Acute pain usually occurs secondary to a defined injury or insult, with a short duration and predictable course. Chronic pain is defined more so by duration. The pain pattern is vaguer, with gradual or ill-defined onset, possibly waxing, and waning severity, and may last the majority of the day. Up to 75% of patients with lung cancer report chronic pain. Breakthrough pain is defined as a “transient exacerbation of pain that occurs spontaneously or in relation to a […] trigger, despite relatively stable […] background pain.”

Chest and back pain are the most common locations of pain in patients with advanced lung cancer. Direct effect of local tumor invasion most commonly causes somatic chest or back pain which is ipsilateral to the site of the malignancy. A Pancoast tumor, located at the apex of the lung, can cause pain in the upper chest and ipsilateral arm as it grows and compresses nearby anatomy causing both somatic and neuropathic pain. Costopleural syndrome, caused by tumor invasion of the pleura, is another direct consequence of the malignancy, most commonly mesothelioma. Metastases to the ribs may cause localized bony pain. If the intercostal nerves are damaged, there is associated neuropathic pain. The main cause of breakthrough pain in lung cancer patients is due to bony metastases. This complex pain pathway is associated with both inflammatory and neuropathic pain at the site of metastasis.

Epidemiology and Prevalence of Pain in Lung Cancer

The incidence of lung cancer continues to be on the rise, accounting for 11.4% of all new cancer cases worldwide. In the United States, there have been notable improvements in survival rates of individuals with lung cancer, owing to tobacco cessation initiatives, early detection, and advancements in treatments for both early and late-stage disease. Yet, lung cancer continues to have the highest mortality rate of all cancer types, accounting for 18% of cancer deaths world wide. Lung cancer has a high propensity to metastasize or recur locally. In fact, most patients with lung cancer present with advanced stage disease at the time of diagnosis. Recurrence of lung cancer is common within the first 2 years following treatment, with a majority of tumors recurring distally from the primary site. ^,

Pain continues to be the most common symptom associated with cancer and, in general, is more prevalent in those with metastatic or terminal disease (66%). As a result, pain is one of the most prevalent symptoms experienced by patients with lung cancer. Improvements in lung cancer survival have impacted the prevalence of pain in this population since more individuals are living with prolonged and persistent symptoms. Unfortunately, management of pain continues to be challenging due to the multifactorial nature of pain associated with lung cancer as well as the overall medical complexity of this patient population. Comprehensive and interdisciplinary assessment is imperative for management of pain in individuals with lung cancer.

Effect of Pain on Quality of Life and Function

Patients with lung cancer experience a variety of symptoms throughout their disease course due to the tumor burden and treatment-related side effects. The most common symptoms reported in this patient population include dyspnea, fatigue, and pain. Compared to other types of cancer, those with lung cancer have higher levels of distress, which can negatively impact overall function and health related QOL. ^, In the United States, 32% of patients with advanced stage lung cancer have reported moderate to severe pain. Pain interferes with psychological well-being in patients with lung cancer and has the potential to exacerbate and prolong symptoms of depression, especially if poorly controlled. Identifying and treating symptoms that negatively impact QOL is essential for improving outcomes and overall survival in lung cancer. ^, As a result, there has been a paradigm shift toward symptom-focused care in patients with lung cancer which include routine assessment of symptoms and early intervention of supportive services such as rehabilitation and palliative medicine.

The Pain Trajectory

Pain from lung cancer and its treatment is present throughout the disease trajectory from the time of diagnosis, through active treatment, and into survivorship or end-of-life care. Knowledge about pain generators throughout the disease continuum is important to improve the management of pain in lung cancer.

Pain at diagnosis. Pain is one of the most common complaints among individuals with lung cancer at the time of diagnosis. Patients diagnosed with primary lung cancer report pain at baseline prior to any treatment or intervention. One reason for this could be that a majority of patients with lung cancer present with late-stage disease at the time of diagnosis ^, and, generally, patients with more advanced disease are more likely to experience pain than those with early disease. Lung cancer diagnosed in its early stages (such as incidental pulmonary nodules) is not often associated with pain. It is speculated that a proportion of baseline pain in early-stage lung cancer represents exacerbation of comorbid musculoskeletal pain rather than direct effect of tumor. The leading causes of malignancy-related pain in advanced lung cancer are skeletal metastatic disease, apical Pancoast tumors, and chest wall disease. For individuals with advanced disease at diagnosis, pain can typically occur due to direct, local tumor invasion, malignant pleural effusions, bone metastases, and/or brachial plexopathy.

Thoracic/chest pain is one of the more commonly reported early symptoms at the time of diagnosis and continues to progress throughout the disease course. Chest pain in lung cancer can arise from localized neoplastic spread but also from secondary complications of the disease such as persistent cough, pulmonary embolism, and obstructive pneumonitis. Additionally, pain prior to surgery may be heightened as a result of the emotional and financial stress of being diagnosed with a life-threatening disease in addition to the physical symptoms endured. Studies have recognized that patients with higher preoperative pain are more likely to have persistent pain following surgery. Knowledge about premorbid pain and function can help anticipate complications following interventions and is essential for making informed management decisions.

Pain during treatment. Pain was found to be prevalent in patients with lung cancer at a rate of 39.3% after curative treatment and 55.0% during anticancer treatment. Treatment for lung carcinoma depends on type (nonsmall cell lung cancer vs. small cell lung cancer) and stage of disease (local vs. metastatic). Patients may undergo one or multiple treatment modalities such as surgery, chemotherapy, or radiation therapy. Surgical resection has been shown to improve overall survival in those with operable lung cancer; however, undergoing surgery can result in unexpected complications as well as the development of acute pain syndromes which can further progress to chronic pain if left untreated. Etiologies of pain during treatment are commonly attributed to surgical procedures, chemotherapy, immunotherapy, radiation therapy, or tumor related (see Fig. 13.1 ).

Acute pain after thoracotomy has been described as the most severe postprocedural pain. This surgery involves manipulation of intrathoracic structures and can result in rib fractures, muscle contusions, stretching of intercostal nerves, and pleural irritation. Management of postoperative pain presents a major challenge to providers due to the complexity of the patient's pain when even the act of taking deep breaths or early mobilization—all important in preventing postsurgical complications—can exacerbate pain. Proper management of postoperative pain is essential as lack of adequate pain control can delay discharge and preclude the patient's ability to participate in rehabilitation which leads to poor outcomes.

Systemic therapy used in lung cancer includes chemotherapy, immunotherapy, or targeted therapy. Patients may receive one or more types of systemic therapy alone or in combination with radiation or surgery. Pain experienced as a result from systemic treatments can be debilitating and negatively impact an individual's function. For example, chemotherapy can induce a painful polyneuropathy in the upper and lower extremities and may result in impairments in gait and activities of daily living. Immune-mediated arthralgias and myalgias have also been reported while taking immune checkpoint inhibitors such as pembrolizumab for nonsmall cell lung cancer.

Pain in survivorship. Many cancer survivors experience physical impairments which may progress to disability if gone undetected or undertreated. Most posttreatment pain syndromes are neuropathic in nature and commonly result from direct nerve injury from prior treatments (surgery, radiation, or chemotherapy) or complications from the cancer itself. Lung cancer patients can develop chronic pain following thoracotomy also referred to as post thoracotomy pain syndrome . It is defined as thoracic pain around the surgical site lasting longer than 2 months following surgery. The exact mechanism is unclear but is hypothesized to have neuropathic and myofascial pain characteristics. Neuropathic pain syndromes can extend into the survivorship stage due to the complexity of symptoms and challenge of mitigating pain related to nerve injury. Moreover, there is a lot of variability between patient symptoms as well as their response to treatment. For cancer survivors in general, it is important to exclude tumor recurrence when presenting with new pain or pain that is persistent and not amenable to treatments.

Team Members in Cancer Pain Management—Providers and Allied Health Professionals

It is not just one specialty's role to provide adequate pain management for patients with cancer. The best way to provide complex pain management is with an interdisciplinary, team approach. Pain is typically a key question on any patient intake form and should be followed up every time. Oncologists, primary care providers, physiatrists, and hospitalists are first-line responders providing primary palliative care, which includes pain relief. These providers, although not specialty trained in symptom management, can still provide medications, therapies, and interventions, within their scope, that contribute toward alleviating patients' pain. Palliative medicine specialists, who are subspecialty trained and board certified, are uniquely placed to provide secondary or tertiary palliative care, which often includes complex pain medication regimens, use of controlled substances, and/or referrals to radiation oncology or even anesthesiology for interventional pain management.

The nonphysician members of the patient care team play an equally integral role in pain management. Social workers and case managers often wear many hats, helping patients with cancer navigate their appointments, providing support for completing the myriad forms needed to ensure care coverage, and depending on their skillset, providing supportive talk therapy that can help patients address the psychosocial components of pain. Talk therapy, in its many forms, can also be provided by clinical psychologists, who are a tremendous asset to oncology programs. Nursing staff is primed to provide patient education about pain medication administration, ensure medication adherence, and answer questions as able. They are also involved in other forms of patient care, such as wound care, which can have a profound impact on pain and discomfort. Physical, occupational, and speech therapists address pain directly through rehabilitation and desensitization techniques, as well as addressing the functional impairments that arise from cancer pain, by means of assistive devices, durable medical equipment, compensatory strategies, and caregiver training. Healthcare chaplaincy can be a great support to both religious and nonaffiliated patients and their families, providing comfort and guidance to alleviate spiritual and existential distress.