H. Lee Moffitt Cancer Center & Research Institute

Introduction

In the cancer population, quality of life may be compromised by poorly controlled symptoms, impairments in physical and psychosocial functioning, and other problems. Pain is a highly prevalent symptom with a serious impact on both the patient and the family. The World Health Organization, international and national professional organizations, and governmental agencies of the United States and other countries have all acknowledged the importance of pain management as part of routine cancer care.

Cancer Pain Evaluation

Inadequate pain assessment represents a highly prevalent barrier to effective management. The management of cancer pain depends on a comprehensive assessment of phenomenology and pathogenesis, the relationship between the pain and the disease, and the impact of the pain and comorbid conditions that may influence quality of life. A standard nomenclature and a multidimensional approach are essential components of a comprehensive evaluation.

The description of the pain should characterize its temporal features, intensity, topography, quality, and exacerbating and relieving factors. The information gathered through a detailed history, physical examination, and review of laboratory and imaging studies, usually clarifies the relationship between the pain and the disease. This assessment determines the need for further evaluation and influences the selection of specific therapies.

Therapeutic decision making may be informed by inferences about the pathophysiology of pain. This pathophysiology can be divided into nociceptive, neuropathic, psychogenic, and idiopathic categories. The term nociceptive is applied to pains that are presumed to be maintained by ongoing tissue injury. Nociceptive pain is called somatic when the ongoing activation is related to primary afferent nerves in somatic tissues (eg, bone, joint, or muscle) and visceral when viscera afferents are activated by injury. Pains that are nociceptive, such as bone pain, are the most prevalent type associated with cancer.

Psychogenic pain, a generic term that refers to pain syndromes sustained mainly by psychological factors, is rarely diagnosed in the cancer population. Nonetheless, personality, mood, and comorbid psychiatric disorders can strongly influence the perception of pain, and psychological assessment is a fundamental goal of the pain evaluation.

Idiopathic pain is defined as pain that persists in the absence of an identifiable physical or psychological substrate. In medically ill populations, it is often the first sign of occult disease progression.

Pain Syndromes

Persistent somatic pain can be due to neoplastic invasion of bone, joint, muscle or connective tissue. Bone pain syndromes are the most prevalent. Bone metastases are often painless, and the factors that distinguish a painful lesion from a painless one are poorly understood. Multifocal bone pain is usually caused by widespread metastases.

The spine is the most common site of bone metastases, and back pain is an extremely common problem in the cancer population. Any neoplastic lesion of the vertebra has the potential to damage spinal cord or nerve roots and produce devastating neurological compromise. Specific pain patterns (eg, "crescendo" pain, pain flare with recumbency, or radicular pain), specific neurological findings (eg, radiculopathy), and specific radiological findings (eg, 50% collapse of a vertebral body) are suspicious of epidural compression. Magnetic resonance imaging (MRI) is the preferred method to evaluate the epidural space. Early diagnosis and treatment of the tumor will prevent neurological deficits. Epidural spinal cord compression is a compelling example of the value of syndrome recognition in cancer pain assessment.

Visceral nociceptive pain syndromes can result from obstruction, infiltration, or compression of visceral structures, including hollow viscus and supporting connective tissues (Table 2). Most of these syndromes are overt and easily diagnosed. A few can pose diagnostic challenges, particularly when preceding the diagnosis of the neoplasm.

Neuropathic pain syndromes may be caused by tumor infiltration or compression of nerve, plexus, or roots, or by the remote effects of malignancy on peripheral nerves (Table 2). These syndromes are highly variable. The character of the pain can be aching or dysesthetic (abnormal pain sensations, such as burning), the location can be anywhere in the dermatomal region innervated by the damaged neural structure, and the dysfunction may or may not be motor, sensory, or autonomic.

Most posttreatment pain syndromes are neuropathic. The predisposing factors for chronic neuropathic pain following nerve injury are unknown. Any surgical incision, even minor, can induce a neuropathic pain syndrome. For example, the postmastectomy syndrome, which may be precipitated by injury to the intercostobrachial nerve, causes a tight, burning sensation in the medial aspect of the upper arm, the axilla, and the upper aspect of the anterior chest wall. This pain is not associated with tumor recurrence. In contrast, persistent or recurrent pain after thoracotomy can be treatment related, but it is usually related to the neoplasm.

Radiation-induced fibrosis can cause peripheral nerve injury. The resultant chronic neuropathic pain usually appears months to years following treatment. Contrary to nerve injury related to neoplasm, the pain is generally less prominent and slowly progressive. It is often associated with weakness, sensory disturbances, radiation changes of the skin, and lymphedema.

Painful dysesthesias, paresthesias, cramps, and restless legs associated with mild weakness, sensory loss, or autonomic dysfunction may follow treatment with neurotoxic chemotherapy (eg, vincristine, cisplatin, paclitaxel). Although most patients report gradual improvement after therapy is discontinued, some develop a persistent, painful polyneuropathy.

Assessment of Related Constructs

The therapeutic model known as palliative care is appropriate for addressing the problem of cancer pain as one issue related to suffering. Palliative care is a model of care focused on patients with progressive, incurable illness and their families. It is a therapeutic approach that aims to enhance the quality of life of the patient and family throughout the course of the disease as well as help them face the prospect of death. Near the end of life, palliative care must intensify and ensure that comfort will be a priority, values and decisions will be respected, practical support will be available, and opportunities will exist for growth and resolution.

All clinicians who care for cancer patients should provide palliative care as a part of good medical practice. This care must be provided throughout the course of the disease. Effective treatment for pain is an essential aspect of this care. Referral to specialists in palliative care is appropriate whenever symptom distress cannot be managed, a high level of global suffering exists, or the need for a comprehensive team approach to care is needed. The hospice program in the United States represents a model of specialized programs for providing palliative care at the end of life.

Treatment of Cancer Pain

The successful treatment of cancer pain requires the use of therapies that are consistent with the etiology of pain, the patient’s medical status, and the goals of care. Although the principal approach for the management of cancer pain is opioid-based pharmacotherapy, each patient should be considered for a range of potential strategies, including disease-oriented interventions (eg, radiation and chemotherapy) and other analgesic techniques.

Pharmacologic Approaches

The size of the starting dose varies with the severity of the pain, previous exposure to opioid, and the medical condition of the patient. In patients with limited opioid exposure, the starting dose is usually equivalent to 5 to 10 mg of parenteral morphine every four hours. Based on clinical experience, the size of the rescue dose is typically in the range of 5% to 15% of the total daily dose. With oral dosing, the minimal interval between rescue doses usually should be 1.5 to 2 hours, which allows the maximal effect of the dose to occur before the next one is taken. With intravenous administration, the minimal interval can be as short as 10 to 15 minutes.

Individualization of the dose is the key principle in opioid therapy. The goal is to achieve a favorable balance between analgesia and side effects through a process of gradual dose adjustment. There is no "correct" or "maximal" dose. In response to poorly controlled pain, the dose should be increased unless precluded by treatment-limiting side effects. The size of each dose increment usually is either the total of the "rescue" doses consumed during the previous 24 hours or 30% to 50% of the current daily dose (sometimes higher in cases of severe pain).

For patients do not respond satisfactorily to opioid therapy, other strategies must be considered. These strategies may include other pharmacologic approaches or nonpharmacologic interventions such as nerve blocks, surgical procedures, or psychological therapies (Table 6).

The effective management of cancer pain may require the use of other classes of analgesic drugs. The non-opioid analgesics include acetaminophen and the nonsteroidal anti-inflammatory drugs (NSAIDs). Adjuvant analgesics are drugs that have a primary indication other than pain but are analgesic in certain circumstances.

Acetaminophen and the NSAIDs produce dose-dependent analgesic effects, and they have dose-response relationships characterized by a minimal effective dose and a ceiling dose for analgesia. There is large individual variation in the minimal effective dose, toxic dose, and ceiling dose. Given the variability in the minimum effective dose and ceiling dose, titration from a relatively low starting dose should be considered in the medically ill.

Adjuvant analgesics include numerous drugs in diverse classes (Table 7). In the cancer population, these drugs are usually administered after opioid therapy has been optimized.

Other Analgesic Techniques

For patients who do not respond adequately to drug therapy, alternative analgesic therapies must be considered. These therapies include a large number of anesthesiologic, surgical, neurostimulatory, physiatric, and psychological interventions (Table 6).

Neuraxial drug administration (intraspinal techniques) and neural blockade are the most commonly used anesthesiologic techniques. Continuous epidural or subarachnoid infusion of an opioid is now routinely tried in the management of patients with refractory focal or multifocal (nociceptive or neuropathic) cancer pains. The usual indication is pain in the lower half of the body that cannot be managed at opioid doses below those associated with intolerable and unmanageable somnolence or cognitive impairment. The addition of a local anesthetic or other drug to the opioid may provide significant analgesia when intraspinal opioids alone are insufficient.

Neural blockade with a local anesthetic may be undertaken for diagnostic, prognostic, or therapeutic purposes. Focal muscle or connective tissue pains associated with discrete trigger points sometimes improve with injection of local anesthetic into the affected area. Neurolysis using phenol or alcohol is considered when other nondestructive approaches are not possible or have failed, the pain is well localized, and the block will not compromise strength or sphincter function.

Neurosurgical techniques directed against specific peripheral or central nervous system structures can benefit a highly selected group with refractory cancer related pain. Cordotomy is most often used.

Neurostimulatory techniques can be relatively noninvasive (eg, transcutaneous electrical nerve stimulation [TENS] and acupuncture) or invasive (eg, dorsal column stimulation or deep brain stimulation). Support for the use of these interventions for cancer pain is anecdotal. TENS and acupuncture are often tried.

Physiatric therapies, including modalities (eg, medicinal diathermy and cryotherapy) and therapeutic exercises also have analgesic effects. In some cases, orthotics that reduce weight bearing or stabilize a painful limb can be helpful. The supporting literature for these approaches is anecdotal. Positive effects are commonly observed, however, and these approaches can be used to address both functional decline and pain.

Most patients will eventually adapt to emotional and psychological disturbances associated with cancer and will respond to reassurance, support, and adequate information. For others, referral to a mental health professional will be needed. Individual psychotherapy, group therapy, and family therapy are all useful. Psychological interventions can sometimes ameliorate pain or improve pain-related coping. Cognitive-behavioral and psycho-educational interventions are supported by extensive clinical experience and are particularly helpful in patients harboring misconceptions about pain, treatments, and other issues.

Alternative or complementary medicine approaches have a growing role in the search for pain relief, although no controlled studies have been conducted for any of these interventions. Physicians are generally well served by being open to these interventions, discussing the possible risks and benefits, and being supportive should patients choose to pursue an approach that is likely to be safe.

Conclusions

Cancer pain represents one of the multiple facets of a progressive illness that may undermine quality of life and profoundly burden the family. Pain management is essential in a broader perspective of palliative care, which aims to maintain quality of life throughout the course of disease and manage the complex problems that can occur as patients approach the end of life. Pain management in the medically ill depends on the ability to conduct a comprehensive assessment, competently provide analgesic drugs, and communicate with the patient and family.