Pain Management in Older Adults

Clinical Therapeutics/Volume ], Number ], 2013

Pain Management in Older Adults Bridget Tracy, MD; and R. Sean Morrison, MD Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, New York, New York ABSTRACT Background: Chronic pain is prevalent among older adults but is underrecognized and undertreated. The approach to pain assessment and management in older adults requires an understanding of the physiology of aging, validated assessment tools, and common pain presentations among older adults. Objective: To identify the overall principles of pain management in older adults with a specific focus on common painful conditions and approaches to pharmacologic treatment. Methods: We searched PubMed for common pain presentations in older adults with heart failure, endstage renal disease, dementia, frailty, and cancer. We also reviewed guidelines for pain management. Our review encompassed 2 guidelines, 10 original studies, and 22 review articles published from 2000 to the present. This review does not discuss nonpharmacologic treatments of pain. Results: Clinical guidelines support the use of opioids in persistent nonmalignant pain. Opioids should be used in patients with moderate or severe pain or pain not otherwise controlled but with careful attention to potential toxic effects and half-life. In addition, clinical practice guidelines recommend use of oral nonsteroidal anti-inflammatory drugs with extreme caution and for defined, limited periods. Conclusion: An understanding of the basics of pain pathophysiology, assessment, pharmacologic management, and a familiarity with common pain presentations will allow clinicians to effectively manage pain for older adults. (Clin Ther. 2013;]:]]]–]]]) & 2013 Elsevier HS Journals, Inc. All rights reserved. Key words: elderly patients, geriatrics, pain.

INTRODUCTION Pain is a subjective experience that can be challenging to assess and treat.1 This is particularly true for older adults, many of whom live with serious illness accompanied by significant pain and symptom

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burdens.2–4 The approach to pain assessment and management in older adults differs from that in younger adults. Older adults may underreport pain or may have difficulty communicating, and physicians may undertreat pain because of inherent biases and concerns about use of medications in older patients. Concurrent illness and comorbid conditions make pain evaluation and treatment more difficult and patients more likely to experience medication adverse effects.5,6 In this article, we review overall principles of pain management in older adults and then specifically focus on common painful conditions and approaches to treatment based on a review of literature and 2 major pain guidelines.5,7

PHYSIOLOGIC CHANGES ASSOCIATED WITH AGING The physiologic changes observed through aging are well described and are important when considering the pharmacologic management of pain. The body’s total water and lean mass decrease, whereas body fat increases, affecting volume of distribution, plasma concentration, and elimination of drugs. Bones and viscera shrink, and the basal metabolic rate decreases. These changes can be difficult to quantify and vary from person to person.8 Additional important changes in renal function, hepatic metabolism, and the central nervous system are described below.

Renal Function Renal function declines as a normal part of aging because of a loss of nephrons, decreased renal plasma flow, tubular secretion and reabsorption, hydrogen secretion, and decreased water absorption and excretion.8,9 Decreased clearance of drugs may lead to the buildup of metabolites. Increased susceptibility to Accepted for publication September 30, 2013. http://dx.doi.org/10.1016/j.clinthera.2013.09.026 0149-2918/$ - see front matter & 2013 Elsevier HS Journals, Inc. All rights reserved.

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Clinical Therapeutics volume depletion and decreased thirst may increase the risk of nephrotoxicity. Commonly used medications are more likely to damage older kidneys, in particular nonsteroidal anti-inflammatory drugs (NSAIDs).10

Gastrointestinal and Hepatic Function The gastrointestinal tract experiences some changes with aging that affect absorption and metabolism of medications. Transit through the esophagus and colon may be slowed. The stomach may atrophy and produce less acid. Pancreatic and liver function is usually well maintained, but the cytochrome P450 system may decline with age. In particular, the decline in demethylization, the process by which benzodiazepines are metabolized, may necessitate dose adjustments.10

Brain and Central Nervous System Changes Pain perception is often altered in older adults, and although this does not lead to decreases in pain, it often leads to changes in the expression of pain, particularly in patients with cognitive impairment.11–13

PAIN ASSESSMENT A comprehensive pain assessment is key to effective pain management. Self-report provides the most accurate and reliable information. In studies that examine patient reports of pain, both clinicians’ and family members’ perceptions underestimate pain severity as reported by patients.14–16 There are indeed challenges in assessing pain in older adults, but these can be circumvented. Visual scales and assistive hearing devices can be used in patients with hearing impairment, whereas larger print or use of verbal scales for reporting pain can be helpful for patients with visual impairment.7 Even cognitive impairment does not preclude a direct assessment of the patient because most patients with mild-to-moderate dementia are capable of reporting pain using any number of validated tools.11 For patients with severe cognitive impairment, the Pain Assessment Checklist for Seniors with Limited Ability to Communicate, the Pain Assessment in Advanced Dementia, and the Doloplus-2 scale have been created and validated to assess pain.13 Finally, clinicians can ask family members and caregivers to give their own impression to add to information gleaned from the patient and physical examination, but this should not serve as substitute. The use of validated instruments can improve the diagnosis and treatment of pain in older adults. The

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visual analog scale, for which patients place a mark on a horizontal or vertical line that represents a spectrum from no pain to severe pain, is helpful in patients who have difficulty speaking. The Faces Pain Scale, Numeric Rating Scale, and Verbal Descriptor Scale (VDS) have all been used in older adults. The Numeric Rating Scale asks a patient to rate pain on a scale of 0 to 10. The VDS has the patient describe their pain as mild, moderate, or severe. Both have been validated in patients with mild to moderate cognitive impairment, although the VDS is more reliable, preferred, and more easily completed by patients with cognitive impairment.12 An important component of pain assessment, particularly in older adults, is an evaluation of its effect on the patient’s quality of life and function. Depression can alter the perception of pain and lead to difficulty coping. Alternatively, pain and loss of function can lead to depression.17 There are several validated tools for functional assessment developed in older adults, including the Range of Motion scale, performance of activities of daily living, Timed Up and Go test, Katz Activities of Daily Living Scale, Lawton Instrumental Activities of Daily Living, and Functional Independence Measure. The Geriatric Depression Scale has been developed to screen for depression in older adults and is easily administered in a yes/no format. Depression often makes pain worse, and vice versa; therefore, screening and treating one without the other can lead to difficulty resolving both conditions.17 The Brief Pain Inventory and the Geriatric Pain Measure are both well-validated tools that assess the effect of pain on quality of life in older adults.12 There are other barriers to achieving effective pain assessment and management. Many older adults and health care practitioners have concerns about addiction to pain medications. Taking a history that includes questions about substance abuse can identify patients at increased risk of psychological dependence for the clinician, but educating patients on the tolerability of opioids in those at low risk for psychological dependence will allay their fears.5,7,18 Patients may have concerns about masking their disease, beliefs that pain is a “normal” part of aging, or lack of understanding of their diagnoses. They may have a lack of information about medications and nonpharmacologic pain control interventions, inadequate access to health care resources, or embarrassment about the use of adaptive devices that might reduce pain and emotional stress.7,19

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B. Tracy and R.S. Morrison

TRADITIONAL ANALGESICS The World Health Organization’s pain ladder is the most widely known model for pain management and provides a stepwise approach. The first step, for patients with mild pain, is the use of nonopioid medications, such as acetaminophen or NSAIDs with or without an adjuvant agent. The second step, for patients with moderate pain, involves adding a weak opioid medication alone or in combination with a nonopioid, with or without the use of an adjuvant agent. The third step, for patients with severe pain, advises the use of a strong opioid with or without an adjuvant.1 Medications can be written on a scheduled or on an as-needed basis. Pain that is episodic should be treated with medication as needed, whereas persistent pain or pain that is expected to last for several days should be treated with scheduled dosing and a back-up additional medication given as needed to relieve breakthrough pain. Too often, pain is undertreated because of failure to use as-needed medications or inappropriate use of as-needed medications where scheduled dosing would be appropriate. Older adults are the most vulnerable for undertreatment of pain, particularly those in nursing homes who cannot manage their own medications.2,3 Analgesics written on an asneeded basis should be made available at intervals that correspond with their duration and with mindfulness of combination medications (eg, oxycodone and acetaminophen).

Nonopioid Medications Acetaminophen is commonly used as an effective analgesic with moderate relief among older adults. However, acetaminophen toxicity is also the leading cause of acute liver failure in the United States, mostly because of unintentional overdose. Older adults should probably not exceed 3 g/d of acetaminophen. Monitoring total daily dosage can be difficult and is often complicated by combination medications and polypharmacy. Since 2011, the Food and Drug Administration (FDA) has limited the amount of acetaminophen in combination medications to 325 mg per pill to help address this problem. Still, acetaminophen remains the first-line choice for mild pain in older adults.20 Typically, NSAIDs provide more effective analgesia than acetaminophen but carry cardiovascular, renal, and gastrointestinal risks. Both nonselective NSAIDs and those selective for the cyclooxygenase-2 isoenzyme

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are associated with increased risk of hospitalization, renal toxicity, myocardial infarction, stroke, and death.20 The American Geriatrics Society’s clinical practice guidelines recommend use of oral NSAIDs with extreme caution and for defined, limited periods.5

Opioid Medications In properly screened and monitored patients, opioids provide a tolerable and effective means of analgesia for a variety of persistent pain syndromes, although most clinicians are comfortable with their use in cancer pain.5 These medications mimic the action of naturally occurring opioid peptides and bind to receptors in both the brain and spinal cord.7 Unlike acetaminophen and NSAIDs, opioids exhibit no ceiling effect and can produce profound analgesia by gradual dose escalation. Opioids can be administered in a variety of enteral and parenteral preparations. Morphine, for example, is available in pill, liquid, and suppository form and can be swallowed or absorbed through the buccal or rectal mucosa. Most of the strong opioids come in both short-acting, immediate-release and long-acting, sustained-release formulations. Opioids can also be administered intravenously, subcutaneously, intramuscularly, and absorbed transcutaneously. Rates of onset of analgesic effect differ among these various routes, however. Opioids given intravenously have an onset within minutes, whereas orally administered medication can take up to 1 hour for onset. Subcutaneous and intramuscular injections have a time to onset of approximately 30 minutes. The transdermal fentanyl patch may take 12 to 24 hours after first application before maximum effect is achieved. Patients should be reassessed frequently with initiation and adjustment of opioids to evaluate pain relief and any adverse effects. Although no data are available to establish appropriate doses for analgesia in older adults, a reasonable starting dose may be 30% to 50% of that recommended for a younger adult. Titration of an opioid should be performed by increasing the total daily dose by 25% to 50% every 24 hours until an effective analgesic dose is achieved. If pain is severe, more frequent titration with close observation may be needed. When selecting an opioid, it is important to account for the patient’s liver and renal function, current medications, and ability to consume the preparation. Hydromorphone, oxycodone, and methadone are

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Clinical Therapeutics metabolized by the liver, whereas morphine is metabolized by the kidney. Hydromorphone, methadone, and fentanyl are more tolerable choices in patients with renal impairment, whereas fentanyl is the preferred medication for liver impairment. Methadone is particularly difficult to dose because of its extremely long half-life, and its use should be reserved only for those clinicians familiar with its variable metabolism.7 Opioids cause adverse effects that, if anticipated, can be well managed. Constipation is the most common adverse effect of opioids but can occur in older adults from a variety of other causes as well. Increased physical activity, water intake, and dietary fiber should be encouraged when appropriate, but any patient taking opioids should be prophylactically placed on a bowel regimen that consists of a stimulant laxative, such as senna without a stool softener.21,22 There is little evidence indicating the best bowel regimen, but a small study found no benefit of the addition of a stool softener to senna when compared with senna alone.23 A recent Cochrane review of laxatives and methylnatrexone in the treatment of opioid-induced constipation found limited evidence to suggest that methylnatrexone was superior; however, the long-term adverse effects and tolerability are unknown.24 Constipation is also the most common reason for nausea related to fecal impaction. Nausea may be seen as an adverse effect of opioids relating to slowed gastric motility, increased activity at the chemotrigger zone, or vestibular sensitivity. Treatment of nausea should be tailored to the underlying cause. Specific causes of nausea and suggested treatments are summarized in Table I.25 Other common adverse effects include sweating, dry mouth, pruritis, and urinary retention. Many physicians worry about respiratory depression, but this is rarely observed when patients are prescribed low doses that are titrated slowly and gradually over time. Another worrisome adverse effect of opioids is myoclonus, but this is rare and may be managed by dose alteration, change in the route of administration, or change to another opioid formulation.

PAINFUL CONDITIONS AND THEIR TREATMENT Heart Failure Heart failure is primarily a disease of older adults. Its prevalence increases with age, and 80% of heart failure patients are age 465 years.26 Not surprisingly,

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an increasing number of patients with heart failure have multiple comorbidities and high symptom burden.26,27 Dyspnea and fatigue are the hallmarks of heart failure; however, data from the study to understand prognoses and preferences for outcomes and risks of treatments (SUPPORT) of 49000 seriously ill adults 15% of whom had a primary diagnosis of heart failure, revealed that 41% of patients with heart failure had severe pain “most of the time” in the last 3 days of life. The experience of pain in heart failure patients is complex and understudied. Pain severity is likely influenced by overall symptom burden, psychosocial distress, and functional status. Recent data from the Pain Assessment, Incidence & Nature in Heart Failure study, which looked at outpatient and hospice heart failure patients, found that 480% of patients had pain, 40% reported chest pain and 76% reported pain at other sites. Pain correlated with degenerative joint disease or other arthritis, shortness of breath, and angina. A significant number of patients reported use of NSAIDs despite their contraindication in heart failure, but without relief. Only opioid analgesics provided relief of pain.27 Clinical guidelines from the American Pain Society, American Academy of Pain Medicine, and the American Geriatrics Society support the use of opioids in persistent nonmalignant pain.5,19 Opioids appear to be the most tolerable and effective choice of analgesic in patients with heart failure, although more research is needed in this area.

End-Stage Renal Disease An increasing body of literature indicates that endstage renal disease (ESRD) patients are among the most symptomatic of any with chronic disease. Among patients undergoing hemodialysis, 37% to 50% experience chronic pain, and 82% of that group report moderate to severe pain. The number and severity of reported symptoms are on par with patients hospitalized in palliative care settings with cancer. These symptoms are undertreated even at the end of life.28 The origin of pain in ESRD patients is complex and likely multifactorial. Patients with diabetes and vascular disease may experience painful neuropathies or ischemic limbs. Arthritis and musculoskeletal pain are also common but often more severe than in patients without ESRD. A number of unique, painful syndromes are associated with ESRD, including calciphylaxis, nephrogenic sclerosing fibrosis, dialysis-related Volume ] Number ]

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Table I. Causes of and treatments for nausea.25 Cause

Clinical Features

Receptors

Treatments

Drug toxicity (eg, opioids and digoxin), ischemic bowel disease, infections, tumor products, renal failure, liver failure, hypercalcemia, ketoacidosis

Constant nausea, variable vomiting

Stimulation of chemotrigger zone via dopamine 2, 5-HT3 receptors

Antidopaminergic, promethazine, prochlorperazine, chlorpromazine, haloperidol, 5-HT3 antagonists, ondansetron

Cortical

Increased intracranial pressure, leptomeningeal carcinomatosis, anxiety, pain

Headache, visual changes, focal neurologic deficits, altered sensorium

Benzodiazepines, corticosteroid, treat reversible causes

Impaired gastric emptying

Drug adverse effects (opioids and TCAs), ascites, autonomic dysfunction, tumor infiltration

Epigastric fullness or pain, early satiety, reflux, hiccups

Visceral

Bowel obstruction, peritoneal carcinomatosis, constipation

Diffuse dull, aching, or crampy abdominal pain

Stimulation of vomiting center via 5-HT2, anticholinergic muscarinic, and histamine type 1 receptors Stimulation of vomiting center via vagal signals from gastric mechanoreceptors, anticholinergic muscarinic and histamine type1 receptors Stimulation of vomiting center via vagal afferents from serosal mechanoreceptors

Vestibular

Motion sickness, labyrinthine disorders, medications

Symptoms related to position, vertigo

GI ¼ gastrointestinal; TCA ¼ tricyclic antidepressant.

Stimulation of vestibular apparatus via anticholinergic muscarinic and histamine receptors

Prokinetics, metoclopramide

Bowel regimen, senna, corticosteroids, medical or surgical management of obstruction Antihistamines, scopolamine, remove offending medications

Sedation, orthostatic hypotension, extrapyramidal adverse effects, constipation, diarrhea, fatigue, headache, QTc prolongation Sedation, delirium, hypertension, gastritis, osteoporosis, delirium, hyperglycemia, immune suppression Avoid in complete GI obstruction

See above

Dizziness, blurred vision, sedation, malaise, urinary retention, constipation, avoid in older adults

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Chemical

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Clinical Therapeutics amyloidosis, and renal osteodystrophy. Dialysis itself causes pain in 13% of patients, presenting as headaches, cramping, or infections stemming from central venous catheters. As a result of this significant burden and undertreatment, quality of life for ESRD patients is low. Despite the increasing prevalence of pain among ESRD patients, analgesic use has decreased. The reasons for this are not dissimilar from undertreatment of pain in other disease entities, but lack of understanding of the pharmacokinetic properties and pharmacodynamics in ESRD presents a large challenge. The principles of a stepwise approach to prescribing analgesia, using the smallest effective dose of opioids, also apply to ESRD patients. For mild pain, acetaminophen is the analgesic of choice, and NSAIDs should be avoided in ESRD. Whenever possible, adjuvant medications should be used. A significant number of patients with ESRD have neuropathic pain from diabetes or vascular disease. Pregabalin or gabapentin are first-line medications for neuropathy in ESRD patients. Tricyclic antidepressants (TCAs) can be used but are second-line medications because of their anticholinergic, histaminergic, and adrenergic properties, of which older adults and ESRD patients are less tolerant. Opioids should be used in patients with moderate or severe pain or pain not otherwise controlled but with careful attention to potential toxic effects and half-life. Morphine has been reported to cause myoclonus, seizures, and prolonged respiratory depression in patients with renal failure due to the accumulation of its active metabolites morphine-6glucuronide and morphine-3-glucuronide. Alternative opioids that are better tolerated in ESRD are hydromorphone, fentanyl, and methadone. Extended-release formulations should be avoided in ESRD patients to minimize the risk of accumulation of toxic metabolites. Short-acting formulations are better tolerated.28

Dementia Worldwide, 24 million people are estimated to have dementia. Because there is no cure for dementia, care is focused on palliation of symptoms and preservation of dignity. Pain, dyspnea, and agitation are common symptoms in the dementia population. These patients commonly have osteoarthritis, and as their illness progresses and become bedbound, they are at risk for contractures and pressure ulcers that cause pain.29

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Too often, patients with dementia receive suboptimal palliative care because of the challenges in assessing symptoms and fears surrounding the use of opioids. Pain assessment in dementia should include all of the elements mentioned above but additionally combine patient reports with caregiver reports and direct patient observations. Even patients with moderate or severe dementia may be able to communicate the presence and severity of pain. In those who may have difficulty with verbal scales, alternatives, such as the Wong Baker Faces Pain Scales, can be used. Observation by caregivers or practitioners may reveal signs of distress, including changes in facial expression, vocalization, interaction, activity, and mental status. Delirium, agitation, and irritability may be signs of physical discomfort in the nonverbal patient. Additional validated tools in elderly patients with dementia include the Pain Assessment Checklist for Seniors with Limited Ability to Communicate, the Pain Assessment in Advanced Dementia, and the Doloplus-2 scale.13 Acetaminophen should be the first-line therapy for patients with mild pain, but opioids remain the cornerstone of pain management in this population. Special considerations are needed in dosing medications for patients with cognitive impairment who may not be able to communicate their needs. They are unlikely to ask for medications, making short-acting as-needed pain medications less effective. Whenever possible, scheduled dosing and long-acting medications should be used.

Frailty Frailty syndrome has become recognized as a distinct phenotype of vulnerable aging. It is marked by a decline in physical function and physiologic reserves. Xue30 and Fried et al31 described the most widely used definition of frailty as having Z3 of the following: (1) low grip strength, (2) slowed walking speed, (3) low physical activity, (4) self-reported exhaustion, and (5) unintentional weight loss. Frail, elderly individuals have poor tolerance to medical, social, and psychological stressors. They are at risk for falls, functional impairment, or loss of independence in activities of daily living, leading to higher rates of hospitalization and death. Other proposed characteristics of frailty include deficits in cognition, balance, motor processing and emotional status, low self-rated health, and poor social support. Pain is the most common symptom in this group.30–32

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B. Tracy and R.S. Morrison Recognizing frailty early is important. The implementation of interdisciplinary geriatric and palliative models of care, including comprehensive geriatric assessment and symptom management, can help identify these vulnerable patients. There is strong evidence to suggest that exercise interventions, including aerobic and progressive resistance training, can improve muscle strength, gait speed, endurance, balance, and mobility and reduce falls in frail older adults. Liberalizing diet and assistance in feeding may improve oral intake in frail patients, but more research on pharmacologic interventions for fatigue and weight loss is needed.32,33 Pain is common in frail patients, in part because of comorbid conditions such as arthritis, but the experience of pain may be influenced by concomitant depression as well as functional status. These patients are at high risk for osteopenia and osteoporosis, compression fractures of the vertebrae, traumatic fractures from falls, pressure ulcers, neuropathy, and painful contractures.32 Pain assessment may be challenging because of communication or cognitive barriers similar to those seen in dementia.13 Pain management may be affected by increased susceptibility to adverse effects of pain medications, interactions with medications for other comorbid conditions, and altered clearance of analgesic medications.

Cancer Two-thirds of patients with advanced cancer report pain. Often, cancer patients have multiple pain sites and causes.34 Persistent somatic pain is often caused by neoplastic invasion of bone, joint, muscle, or connective tissue. Visceral pain is commonly caused by direct infiltration, compression, obstruction of hollow organs, or stretching of the thoracic or abdominal viscera. The National Comprehensive Cancer Network issued guidelines in 2010 and updated those guidelines in 2013 for adult cancer pain management, integrating multidisciplinary pain management strategies and targeted coanalgesics.35 All pain management should include psychosocial support, patient and family education, and exploration of integrative interventions, as well as monitoring and anticipation of analgesic adverse effects. Patients who are opioid naive and experiencing mild pain should be offered acetaminophen, NSAIDs, coanalgesic or adjuvant therapies for specific pain syndromes (discussed below), and

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short-acting opioids. This may not be possible in older patients, in whom NSAIDs are often relatively contraindicated. If pain is rated at a moderate level, short-acting opioids should be titrated to analgesic effect. Patients in severe pain should have more frequent and rapid titration of opioids. Opioid-tolerant patients are defined as those who are long-term daily users of opioids for pain relief in an equivalent of Z60 mg/d of oral morphine. For opioidtolerant patients whose analgesic goals are not met or who rate their pain as moderate, the National Comprehensive Cancer Network recommends giving a breakthrough dose of medication calculated at 10% or the total opioids taken in the previous 24 hours and assessing for efficacy and adverse effects within 1 hour for oral medications and 15 minutes for intravenous medications. Older patients will have a more pronounced pharmacologic effect after any weightadjusted opioid dose than younger patients. The analgesia will be more intense and will cause more adverse effects. This enhanced effect is likely due to a lesser volume of distribution, decreased clearance, and diminished target organ reserve. When possible, agents targeted at specific cancer pain syndromes should be used in addition or sometimes in place of traditional analgesics. These agents have previously been referred to as adjuvant therapies, but coanalgesic is probably a more appropriate term.35 The use of multiple medications in older adults can often lead to problematic drug-drug interactions and an increased prevalence of adverse effects, and careful attention should be paid to the interactions and possible toxic effects of these agents because older adults are more vulnerable to both.5

Bone Pain Bone pain from metastatic disease is common in lung, breast, prostate cancer, and multiple myeloma. Bone pain may be multifocal or generalized. Multifocal pain is due to direct tumor invasion from metastases, whereas generalized pain is seen in replacement of the bone marrow by neoplasm in hematogenous malignant tumors and, less commonly, solid tumors.36 The mechanism by which a metastatic lesion becomes painful is poorly understood. Indeed, 425% of patients with bone metastases are pain free.37 The cause is likely the culmination of the release of inflammatory mediators, cytokines, and growth factors from tumor cells, upregulation of

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Mode of Action Drug

Antidepressants Selective serotonin reuptake Inhibition of serotonin and norepinephrine reuptake, Nausea, treatment of depression, sedation, with reuptake inhibitors, tricyclic inhibition of serotonin and norepinephrine reuptake, anticholinergic effects, cardiac inhibition antidepressants sodium channel blockade, anticholinergic arrhythmias, treatment of depression Anticonvulsants Gabapentin, pregabalin Decreased release of glutamate, norepinephrine, No major drug-drug interaction, sedation, with calcium substance P, affecting calcium channels dizziness modulation Opioids Morphine, hydromorphone m-Receptor agonists Sedation, nausea, constipation, dizziness, rapid onset analgesia Topical agents Lidocaine 5% patch Sodium channel blockade Rash, local erythema, no systemic effects Combination Gabapentin-morphine, See above; synergistic Sedation, nausea, constipation, dizziness, therapy gabapentin-oxycodone, synergistic pain relief, lower doses of gabapentin-nortriptyline each individual drug

Neuropathic pain can have several origins in the cancer patient. Tumor may cause compression, mechanical traction, or infiltration of nerve trunks and plexi. Alternatively, paraneoplastic syndromes associated with antineuronal nuclear antibodies type 1 (anti-Hu) or demyelinating polyneuropathies associated with lymphomas may cause pain. Finally,

Class

Neuropathic Pain

Table II. Treatments for neuropathic pain.41

peripheral and central neural processes, and changes in the interaction of osteoblast and osteoclast activity. Although opioids play a role in pain relief for bone pain, more targeted therapies can complement or even supplant their use. The mainstay of treatment for bone pain is bisphosphonate therapy. Bisphosphonates were approved for use in advanced cancer by the FDA in the 1990s and recently reviewed in a Cochrane meta-analysis.38,39 Data support the use of bisphosphonates in osteolytic bone metastases from breast cancer, solid tumors, and multiple myeloma for pain management when used as an adjuvant. There is also substantial evidence that bisphosphonates reduce the risk of pathologic fractures. There are 2 FDAapproved bisphosphonates for the treatment of pain from bone metastases and prevention of skeletalrelated events: pamidronate and zolendronate. There are no oral agents currently approved for bone metastases in the United States. Adverse effects of bisphosphonates include fever, flulike reactions, nausea, hypocalcemia, and osteonecrosis of the jaw. In addition to bisphosphonates, corticosteroids are often used in cancer pain–related bone metastases, as well as nerve compression, headache from increased intracranial pressure, and pain from bowel obstruction. Corticosteroids are integral in the management of spinal cord compression as well, although the benefits must be weighed against the many wellknown adverse effects and toxic effects. Radiation therapy is effective in the treatment of bone pain. Patients with localized pain may have radiation treatment to the affected area and obviate the need for systemic medications. Adverse effects from radiation are usually limited to the exposed structures. Patients with diffuse bone metastases and pain may be candidates for radionuclide therapy. Radionuclides, such as radioactive strontium and samarium, can provide sustained pain relief within days. The main adverse effect of these treatments is bone marrow suppression.40

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Clinical Therapeutics

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B. Tracy and R.S. Morrison antineoplastic agents themselves may result in neuropathy, notably cisplatinum, taxoids, and vincristine. There are 5 classes of medications that have been studied and found to be effective in treating neuropathic pain (Table II).41 Selection of a treatment modality should take into account the adverse effect profile of the drug and other concomitant symptoms present in the patient. For instance, a patient with neuropathic pain and depression would likely benefit from an antidepressant. In younger patients, TCAs are the first-line therapy for neuropathic pain; however, the anticholinergic effects make them a poor choice for older adults, with the exception of nortriptyline, which has been found to be more tolerable.42 Still, TCAs should be avoided in favor of a selective serotonin reuptake inhibitor or anticonvulsant. Neuropathic pain often requires a combination of therapies for adequate pain relief and may occasionally require more invasive therapy, such as local nerve blocks or radiation therapy.7,41

CONCLUSION Pain is difficult to treat and a task made all the more challenging in older adults with chronic illness. An understanding of the basics of pain pathophysiology, assessment, and pharmacologic management and familiarity with common pain presentations will allow clinicians to effectively manage pain for older adults.

ACKNOWLEDGMENTS This work was supported by the National Palliative Care Research Center. Dr. Morrison is the recipient of a Mid-Career Investigator Award in Patient Oriented Research from the National Institute on Aging (grant K24 AG022345). All authors contributed equally to the literature search, data interpretation, figure creation, and writing of the manuscript.

CONFLICTS OF INTEREST The authors have indicated that they have no conflicts of interest regarding the content of this article.

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Address correspondence to: Bridget Tracy, MD, Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1070, New York, NY 10029. E-mail: [email protected]

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