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32 Pain in Adults with Cancer

32 Pain in Adults with Cancer
The Massachusetts General Hospital Handbook of Pain Management

32
Pain in Adults with Cancer

Jeffrey A. Norton and Annabel D. Edwards

We must all die. But that I can save him from days of torture, that is what I feel as my great and ever new privilege. Pain is a more terrible lord of man than even death.
—Albert Schweitzer (1875–1965)

I. Defining cancer pain
II. Barriers to appropriate cancer pain management
III. Pain assessment

1. Pain descriptions

2. Specific elements of the history and physical examination

3. Helpful diagnostic studies
IV. Cancer pain management

1. Primary treatment of malignancy

2. Pharmacotherapy

3. Anesthetic techniques

4. Neurosurgical techniques
V. Conclusion
Selected Readings

The American Cancer Society estimates that in the year 2000, 1.2 million new cases of invasive cancer will be diagnosed in the United States alone. Of all the symptoms that a person experiences while living with cancer, pain is the most feared. At least one third of cancer patients have pain at the time of their diagnosis. Up to two thirds of patients with advanced cancer rate their pain level as moderate to severe. A large portion (about 90%) of all cancer patients with pain can be treated effectively with the multidisciplinary modes of treatment currently and readily available.
I. DEFINING CANCER PAIN
The term cancer pain does not have a specific definition. In fact, cancer patients as a group have some of the most diverse types of pain. Their pain can stem from any of the following:

Tumor invasion or compression of other tissues by tumor

Surgery and biopsies

Radiation damage to tissues

Neuropathies caused by chemotherapy or other treatments

Ischemia

Inflammation

Blocked or damaged organ structures (visceral pain)

Decreased mobility and arthropathies (musculoskeletal pain)

Pathologic fractures
Some pain occurs in direct temporal relationship to an event such as surgery. Other types of pain start days or months after an initiating event and get worse with time, as may happen with peripheral neuropathy induced by chemotherapy. It is common for many types of pain to coexist in patients with cancer. In addition, some pains are constant, whereas others are incidental to specific movements, and still others are intermittent and resulting from physiologic factors. Timing issues related to pain occurrence influence the therapeutic approach used.
Common words used to describe pain, such as chronic pain, often do not lead to an understanding of the basic mechanism of the pain. It is important to avoid using such phrases casually, as they can inhibit effective evaluation and treatment. The success of pharmacologic pain therapy lies primarily in the proper match between a specific pain mechanism and the pharmacologic effect of the chosen medication. The success of nonpharmacologic adjuvant pain therapies, such as relaxation or self-hypnosis, depends on the patient’s abilities and beliefs, practice (or use over time), the modality chosen, and sometimes the pain mechanism.
Another aspect of pain is related to the patient’s sense of wellness. Psychic pain, or suffering, can play a major role in a patient’s overall quality of life. Ignoring this type of “pain” is as harmful as ignoring somatic pain. Physical pain and psychic pain are so closely entwined that it makes no sense to treat one without the other. The abolition of physical pain means little when a patient is unable to derive pleasure from life.
II. BARRIERS TO APPROPRIATE CANCER PAIN MANAGEMENT
Unfortunately, many barriers still exist to the effective treatment of cancer pain, despite the fact that most cancer pain can be treated relatively easily with basic pain management techniques. These barriers are multifactorial and include the following:

Lack of knowledge about the various mechanisms behind cancer pain syndromes

Lack of knowledge about the variety of medications used to treat the various mechanisms of pain

Failure to properly assess the patient in pain

Fears (of the patient, the patient’s family, and healthcare providers) about addiction and the use of controlled substances

Fear of complications or side effects of opioid analgesics

Lack of respect for or knowledge of nonpharmacologic therapies

Fear that use of opioids may hasten death near the end of life
Patients may, in fact, create significant barriers to their own care, which is why a careful assessment of their attitudes and worries is necessary. Cancer patients have stated in a number of surveys that they see pain as inevitable and that they should be able to tolerate it. They worry that physicians will be distracted from treating the cancer if they mention the pain, or that they will be seen as complainers. Often, denial is a factor because many patients see worsening pain as a sign of worsening disease, so they do not want to think about it or admit to it. Some patients cannot afford the medications prescribed and instead of asking if there is an alternative that is less expensive, they simply do not fill their prescriptions. There are also patients who just do not want to take multiple pills.
Problems in the healthcare system can also impact on pain management efforts. Insurance coverage may make specific forms of therapy unattainable. The availability of medications may be restricted by insurance or pharmacy willingness to carry various products. Instruction about pain and its management is not common in medical schools and is barely mentioned in the majority of textbooks. In addition, practitioners who do provide pain management are often poorly reimbursed for their time.
Some problems that foster poor pain management may well be addressed over the next year or two as the new Joint Commission for the Accreditation of Hospital Organizations (JCAHO) regulations relating to pain management are put into place and graded. These regulations will impact all types of healthcare facilities examined by the JCAHO (for website, see Appendix III).
III. PAIN ASSESSMENT
Proper assessment of the nature of a patient’s pain or pains and the probable cause or causes is essential for effective treatment. Each pain needs to be evaluated separately, as the mechanisms may differ and require different treatments. Because new pain can develop and old pain can worsen or improve (e.g., with disease progression, new health problems, treatment of the disease), the pain situation should be reassessed regularly.
Pain is a combination of sensory and emotional reactions to intense stimuli. It is inherently a subjective experience. Thus a large part of a pain assessment comes from the information the patient provides. The diagnosis of cancer brings with it many emotional responses that may strongly overlay the patient’s report. Perhaps this plays a role in the tendency of providers to underestimate pain. Understanding how the cancer patient thinks of himself or herself and the disease can be important.
1. Pain descriptions
The two major pieces of information that the patient provides include the level of pain and the description of the pain (i.e., what it feels like). Pain level is measured on a scale, most commonly from 0 to 10 (where 0 is no pain and 10 is the worst pain imaginable). Scales can be verbal or written; they may use colors, numbers, lines, or faces; or they may rely on behavioral cues. The key is to find a scale that works for the individual patient and to use that scale consistently. Levels of pain cannot be compared between patients. The scale can only measure changes (e.g., evaluate the effect of interventions) in an individual patient.
A general goal is to try to get a patient below a 5/10 level of pain, but this is purely empirical. Some patients are content with a 5/10 level, whereas others are miserable. The ultimate goal is to achieve a reasonable level of comfort while minimizing side effects; patients and providers need to decide together when this goal has been reached.
Patients’ descriptions of pain help determine the mechanisms of pain. When pain is primarily from a recent injury (nociceptive), words like sharp and throbbing are often used and the patient can often point directly to a place that hurts. Pain that derives from damaged nerves may elicit descriptors like shooting, burning, electrical, painful numbness, or pins and needles. This type of pain tends to be more diffuse or to travel from one place to another. These verbal indicators are not precise but they are helpful. Clinical knowledge and experience inform treatment decisions as well.
2. Specific elements of the history and physical examination
All the usual features of the history and physical examination are relevant (Chapter 4). The following aspects of the history and physical are of particular importance in cancer patients.
Review of medications
Ask about herbal or home remedies (which are very popular and widely advertised to cancer patients) so that adverse interactions can be avoided and the treatment plan can be simplified. A careful determination of all pain medications that have been prescribed, whether in the past or recently, is also warranted, so that the patient is clear about which medications to take.
Treatment history
About 20% of cancer patients have pain secondary to treatment, so the history of treatments is crucial. Pain caused by treatments may confuse the clinical picture for the practitioner and make a patient less willing to continue with the therapeutic plan.
Pain secondary to radiation includes plexopathy, myelopathy, mucositis, and bone necrosis. Mechanisms include fibrosis, tissue ischemia, necrosis, and inflammation.
Pain secondary to chemotherapy may be caused by peripheral neuropathy, mucositis, bone necrosis, or herpes zoster. Vincristine, cisplatin, and paclitaxel (Taxol) commonly cause neuropathies. Methotrexate, 5-flurouracil deoxyribonucleoside, and many other drugs can cause mucositis, which usually starts 1 to 2 weeks into therapy. Mechanisms include inflammation and nerve damage.
Pain secondary to procedures or surgery includes acute pain, phantom pain, stump pain, postdural puncture headache, and nerve injury pain (particularly after nephrectomy and thoracotomy). Mechanisms are usually nociceptive or neuropathic.
History of concomitant disease
Concomitant diseases can be responsible for a cancer patient’s pain. For example, shingles: often affects cancer patients because of their immunocompromised state. Pain occurs during acute shingles and can become chronic (postherpetic neuralgia). This very debilitating and distressing pain state is extremely difficult to treat. Early and aggressive treatment of the shingles and associated acute pain is important (see Chapter 25, IV, 1, iii).
Pain history
Some pain syndromes are more likely to occur with specific cancers. For example, bone metastases occur commonly with neoplasms of the lung, bronchus, prostate, breast, rectum, and colon. Frequent sites of disease include the long bones, spine, pelvis, femur, and skull. The pain is usually well-localized somatic pain that is often aggravated by movement (incidental pain). The clinician should be aware of the possibility of completed or impending pathologic fracture, as well as the presence of potentially life-threatening hypercalcemia that can accompany widespread bony metastases.
Compression of the spinal cord by epidural or spinal metastases is a medical emergency. If treatment for cord compression is initiated when the patient is ambulatory, neurologic function is usually maintained. On the other hand, only 50% of patients who have paraparesis before treatment regain ambulatory function. Patients who are frankly paraplegic rarely if ever regain motor strength. The following points about the syndrome of spinal cord compression are important:

Approximately 5% to 10 % of cancer patients develop vertebral body metastases.

In up to 8% of patients, vertebral metastasis and back pain are the presenting symptoms of cancer.

Dull, aching, midline back pain presents first in 90% of patients with epidural metastases.

Symptoms may progress to sharp radicular pains, and neurologic deficits can appear approximately 6 to 7 weeks after initial symptoms.

Changes in bowel or bladder function, as well as sensory changes, may herald spinal cord compression.

Treatment includes immediate high-dose steroids, emergent radiation therapy, and occasionally surgical decompression or stabilization.

Patients exhibiting classic warning symptoms of impending or actual cord compression should be sent to the emergency room immediately.
Table 1 presents a summary of the characteristics of this and other pain syndromes.

Table 1. Characteristics of pain syndromes in patients with cancer

Psychological assessment
The diagnosis of cancer, regardless of type or prognosis, often brings with it a series of automatic assumptions and expectations, mostly negative. It is important to clarify these concerns and to help patients obtain help if necessary (e.g., support groups, counseling, family discussion).
Neurologic examination
A neurologic examination often reveals early or previously missed cancer or cancer treatment effects. Small changes in sensation or strength may be a clue to new or extended tumor involvement. One survey demonstrated that over 60% of the cancer patients sent to a pain management center had previously undetected lesions that were picked up in the assessment process.
3. Helpful diagnostic studies
(i) Radiologic
Imaging studies are helpful in filling out the details of the evaluation of a patient with cancer pain. These studies should be acquired and evaluated early in the course of treatment. They provide a baseline for measuring disease progression or regression, and they also provide essential information to the various specialists who become involved in the patient’s care. Examples include the following:
Conventional radiology, or plain films are excellent for diagnosis of fracture or other bony abnormalities. Some soft-tissue tumors and visceral pathology can be seen on plain films.
Computed tomography is excellent for bony abnormalities and metastatic lesions.
Magnetic resonance imaging is excellent for soft-tissue abnormalities, and very useful for analysis of spinal pathology and bony metastatic disease.
Bone scan, using radioactive compound to detect areas of increased bone growth or turnover, is extremely useful for detection of bony metastases.
(ii) Neurophysiologic
See Chapter 7 for a description of these studies.
Electromyography is used to examine muscle activity to detect an abnormality that may demonstrate nerve pathology.
Nerve conduction studies are useful for the detection of neuropathy or other disease of the nervous system. They can help clarify, for example, whether tumor is involved in the plexus.
Quantitative sensory testing includes a variety of noninvasive studies that explore the functioning of sensory nerve pathways. The results can often expose abnormal functioning in specific components of the pain pathway thus, helping to clarify possible mechanisms of pain.
IV. CANCER PAIN MANAGEMENT
1. Primary treatment of malignancy
Primary treatment of malignancies with surgical resection, radiation therapy, or systemic chemotherapy is often a successful treatment for cancer-related pain. However, analgesic medication or other pain treatment added during the primary treatment helps to improve a patient’s experience with the cancer treatment, and can be tapered when it is no longer needed. Pain treatment also helps patients to remain compliant with treatment protocols that are difficult. Early intervention helps prevent long-term pain problems such as postherpetic neuralgia and phantom limb pain.
2. Pharmacotherapy
To raise awareness of functional pain management treatment protocols for cancer pain, the World Health Organization (WHO) developed a stepwise treatment algorithm, which was widely disseminated around the world (Fig. 1). This WHO analgesic ladder is composed of three basic steps that can be outlined as follows:

Figure 1. WHO analgesic ladder.

Step 1: Start with nonopioid analgesics for mild pain.
Step 2: Begin using opioids such as hydrocodone or codeine for mild to moderate pain, with or without nonopioid analgesics.
Step 3: Use the more potent opioids such as morphine or hydromorphone (Dilaudid) for moderate to severe pain, with or without nonopioid analgesics.
Other adjuvant medications (see later) can be added at any step of the ladder. This logical guide to cancer pain treatment has proved extremely helpful throughout the world. It has provided a simple algorithm to direct cancer pain therapy using widely available and inexpensive medications.
However, in the United States and other advanced countries, there is now debate about whether the stepladder should be modified. For example, it has been suggested that the concept of “mild” opioids in the second step should be abandoned because these are really “strong” opioids in formulations that have dose limitations because of the addition of acetaminophen or aspirin. Would it actually be preferable to give opioids and nonopioids separately, especially since the advent of more potent and safer nonopioid analgesics? Also, because the safety and tolerability of long-acting opioids is well established, should the use of “mild” opioids in the second step be abandoned in favor of long-acting opioids?
Also, the stepladder concept has been extended by some to include two possible higher-level step interventions. Step 4 would be the use of devices as epidural catheters, implanted opioid pumps, and spinal cord stimulators. A fifth step might include cryotherapy, radio-frequency lesioning, and neurosurgical treatment techniques.
Some practitioners worry that the ladder concept may be misconstrued, resulting in the treatment of all patients with the same protocol despite differences in pain levels and mechanisms of pain. For example, some patients may present with severe pain and need to be treated at a higher step of the ladder rather than the first step. However, it should be clear that the WHO analgesic ladder is meant to act as a guide not a predetermined treatment plan.
The various classes of medications commonly used to treat cancer pain and related symptoms are summarized in Table 2 and discussed next.

Table 2. Drugs commonly used in the management of cancer pain

(i) Nonopioid analgesics
This group comprises the nonsteroidal anti-inflammatory agents (NSAIDs), acetaminophen, and tramadol. (Tramadol is difficult to classify because it does have mu opioid receptor activity, but this is not its sole analgesic activity, and the drug does not behave like the standard opioids.) Unlike the opioids, these medications do not cause physiologic dependence, but they all have ceiling effects (in contrast to the opioids). As they are synergistic with opioids, the two types of drugs can be used together in lower doses than either one alone, which may reduce the potential toxicity of each. They are widely prescribed and often provide real benefit.
It is common for liver or kidney function to be impaired in cancer patients, so caution must be used when prescribing these medications (see Chapter 8). This caution extends to the use of combination therapies such as Percocet, Percodan, Vicodin, and Vicoprofen, which contain NSAIDs or acetaminophen. Accidental overdoses of acetaminophen associated with the use of these combination therapies have occurred because of a lack of awareness of their constituents. As widely used as these medications are, they can cause harm.
There are two classes of NSAIDs on the market at this time, the nonselective COX inhibitors (e.g., aspirin, ibuprofen, naproxen sodium), and the cyclooxygenase-2 (COX-2) selective inhibitors (e.g., celecoxib and rofecoxib). The nonselective group causes a higher incidence of side effects related to gastric distress and platelet dysfunction. The COX-2 selective group causes a lower incidence of these problems, but it is not free of them. These newer agents have been available in United States only in the last few years, and they are still being assessed in cancer patients. It will be a few more years before we can evaluate their role, determine their risk, and decide if they should be emphasized in place of traditional therapies such as choline magnesium salicylate (Trilisate).
Ketorolac is the only NSAID that can be given parenterally for analgesia in the United States. This medication is rarely used for chronic pain, but it is useful for the short-term management of acute pain and is as efficacious as morphine for mild to moderate pain. It should be used for only 3 to 5 days. Gastric distress and bleeding are the major potential problems with its use.
Acetaminophen is a useful analgesic and antipyretic, but it should be avoided in patients with impaired liver function because it is potentially hepatotoxic.
Tramadol is useful for mild to moderate pain, especially for patients who do not wish to take opioids. It is occasionally useful for severe pain in combination with other nonopioid analgesics and/or adjuncts in patients who cannot tolerate opioids. It is known to lower seizure thresholds, so it must be used with caution in patients with seizure disorders or brain pathology. Tramadol competes for protein-binding sites and may potentiate the effects of Coumadin.
(ii) Opioids
Opioids are the mainstay of cancer pain treatment and their use can markedly improve the quality of life of these patients. Fears of addiction are unwarranted in cancer patients, and they (and their family and caregivers) should be reassured of this so that fear of addiction does not prevent appropriate opioid use. Another related fear is that death will be hastened at the end of life by using opioids. In fact, the contrary is true, and it has been demonstrated that the lives of terminally ill patients can be prolonged and the quality of their final days improved by opioid analgesia. Caregivers should not hesitate to use appropriate doses of opioids at the end of life, guided by the patient’s level of pain and distress.
a) Choice of opioid
The WHO has designated morphine the standard for the treatment of cancer-related pain on the basis of its efficacy, its ready availability throughout the world, widespread familiarity with its use, and its low cost. However, multiple opioids exist, both naturally occurring and synthetic, and each has advantages and disadvantages in the clinical care of cancer pain patients. Factors affecting the choice of an opioid agent may include drug potency, half-life, toxicity, and available routes of administration.
b) Short-acting versus long-acting
Another consideration in drug choice relates to the pattern and timing of the patient’s pain. For example, if a patient’s pain is primarily related to specific and infrequent activities, the use of an intermittent short-acting opioid preparation is preferred. Examples include MSIR (morphine sulfate, immediate release), oxycodone, and Dilaudid. If, on the other hand, a patient’s pain is constant throughout the day, then long-acting opioid preparations should be emphasized, reserving short-acting opioid medications for intermittent exacerbations of the pain (often referred to as breakthrough pain). Examples of long-acting opioids include MS Contin, OxyContin, and methadone. See Chapter 9 for a full description of these drugs.
Methadone is an excellent analgesic; it is very inexpensive, it has additional benefits in the dorsal horn, and it is completely legal to use for pain provided that the words For Pain appear on the prescription. It does, however, tend to accumulate (because of its affinity for protein-binding sites and its slow rate of metabolism), and it may require a downward dose adjustment 5 to 10 days after initiating its use or after a dose increase.
Breakthrough pain is defined as a transitory exacerbation of pain superimposed on a background of otherwise stable pain treated with analgesic. Reported by 50% to 66% of cancer patients, it can be related to movement (e.g., bony metastases), general activity, time of day, other physiologic changes, or possibly disease progression. Whenever possible, moments in which breakthrough pain are likely to occur should be anticipated and treated 30 to 45 minutes ahead of time (e.g., as before taking a shower each morning or changing a dressing).
c) Route of administration
Oral administration of opioids is always preferred and usually easily accomplished early in the treatment of cancer-related pain. However, as disease progresses or enters the terminal phase, it may become necessary to use other routes of administration. Patients with face and neck pathology may not be able to swallow, and those with gastrointestinal tract pathology may not be able to reliably absorb oral preparations.
Fentanyl in the form of the Duragesic patch provides a 3-day sustained-release opioid therapy that can be useful for patients with stable pain who have trouble using oral medications or who are active and find regular oral dosing inconvenient. As with any longacting preparation, breakthrough medication should be provided in addition. There may be problems with this treatment choice in cancer patients. First, doses are not readily titrated (up or down) because of the absorption characteristics of both the patch and the subcutaneous depot (see Chapter 9). Changes (up and down) may take up to 18 hours to be complete. Some patients are sensitive to the adhesives in the patch and develop skin irritations. Some cancer patients become cachectic, losing their subcutaneous body fat, which may alter the absorption rate of the fentanyl. There may be less constipation because the oral route is avoided.
Parenteral opioids can be delivered intramuscularly (IM), intravenously (IV), or subcutaneously (SC). The IM route is irritating, painful, and not needed. SC infusions of opiates are satisfactory if the IV route is not available, although serum levels are not as stable and depend on local perfusion and absorption. The use of the SC route limits the volume of medication that can be delivered (volumes over 10 mL/hr tend to cause local irritation and poor absorption), thereby limiting drug choice (e.g., methadone cannot be concentrated to more than 10 mg/mL; Dilaudid and morphine are available in highly concentrated forms). Many cancer patients have some form of intravenous access in place, and it can be utilized for pain medications.
Patients who are alert and wish to have control over their own analgesia often benefit from using a patient-controlled analgesia (PCA) device. This provides flexibility and can be used for continuous infusion, intermittent injection, or a combination of the two. The patient can carry the device around with in a fanny pack, a small backpack, or a pocket. The most commonly used PCA opioids are morphine and Dilaudid. Other opioids such as fentanyl, methadone, and, rarely, meperidine (Demerol) can be used.
More invasive opioid delivery systems include epidural and intrathecal catheter systems. These treatments often benefit cancer patients who require relatively large doses of systemic opioid, especially when side effects are intolerable, because neuraxial doses are much smaller. Approximately one-tenth the IV dose is needed for epidural delivery and one-hundredth for intrathecal delivery. The addition of a local anesthetic agent such as bupivacaine can provide supplementary analgesia and reduce the amount of opioid needed. Catheters can be used with an external injection port for intermittent injections, with an external infusion pump (PCA is also an option), or with a totally implanted delivery system. Unfortunately, catheter placement is contraindicated in patients with infection or coagulopathy. A backup plan should always be in place because most catheter problems, if they arise, cannot be fixed at home, requiring a trip to the hospital and a delay before treatment can be reinstated.
d) Side effects
The opioids have a number of well-recognized and often troublesome side effects including respiratory depression, nausea, slowing of bowel movements, sedation, euphoria, dysphoria, and pruritus. By slowly increasing opioid doses in cancer patients as pain levels increase, most side effects can be avoided, including respiratory depression, which is rarely a problem.
Two side effects of opioids, however, remain potentially significant for cancer patients despite dosing changes: constipation and sedation. Constipation can usually be avoided by placing the patient on a bowel regime consisting of stimulating laxatives [e.g., senna concentrate (Senokot), two tablets, twice daily]. Bulk-forming laxatives do not reverse the problem of slowing of bowel movements and may actually make matters worse.
However effective opioids are in controlling cancer pain, some patients are reluctant to use them because they would rather have pain than feel drowsy and confused. For these patients, feeling alert and interactive (especially with family members) is so important that they reject pain medication. The addition of a stimulant (e.g., dextroamphetamine, methylphenidate) can help relieve these symptoms without compromising analgesia. Alternatively, nonopioid and adjunctive treatments can be maximized to allow for lower opioid doses.
e) Tolerance
Some degree of tolerance to opioids is common in cancer patients because these drugs are often used over long periods of time (tolerance is not addiction–see Chapter 9). As tolerance increases, dosage escalations are necessary to achieve the same level of comfort. Very high opioid doses may be reached in an attempt to meet the analgesic requirement, and sometimes these high doses result in toxicity, in particular, myoclonus. It may be beneficial in such cases to try to reduce tolerance and, at the same time, the opioid dosage. This can be attempted in a number of ways:
Opioid rotation: Switching from one opioid to another may be helpful because of partial cross-tolerance between opioids. Switching to methadone may be the best choice because of methadone’s additional N-methyl-D-aspartate (NMDA) receptor antagonism (see Chapter 9). It is often possible to reduce the equivalent dose of the new opioid to half or one quarter, or, in the case of methadone, even to one tenth. This is our most common response to tolerance.
Resting period off opioids: In the case of mild to moderate cancer pain, it is sometimes possible to discontinue opioid medication altogether for a while, substituting nonopioid analgesics and/or adjuvants. A 1- to 2-week rest from opioids may allow the opioid receptors to reset, thereby reducing or eliminating tolerance.
NMDA antagonists: Tolerance is known to be dependent on NMDA receptor activity. Some clinical studies have shown that the coadministration of NMDA antagonists may reduce opioid tolerance. The NMDA antagonist most often used for this purpose is dextromethorphan, which is now available as an over-the counter medication.
(iii) Adjuvant analgesics
Whereas the nonopioid analgesics and the opioids just described are used for their primary analgesic effects, there are other drugs that have useful secondary analgesic effects. These are referred to as the adjuvant analgesics and they come from such drug classes as antidepressants, anticonvulsants, antispasmodics, local anesthetics, and corticosteroids. A full description of these drugs can be found in Chapter 10 and Chapter 11. In cancer pain patients, these drugs can be used particularly to treat a neuropathic pain component (e.g., gabapentin), to treat pain-associated depression or insomnia (e.g., tricyclic antidepressants), or to shrink a tumor mass that may be causing pain (steroids).
NOTE: Cancer patients are often on complex treatment protocols requiring that they take a number of medications. When possible, the treatment regimen should be kept simple or simplified. Try to choose medications that give more than one benefit at a time. For example, nortriptyline, a tricyclic antidepressant, has been shown to be beneficial in the treatment of neuropathic pain and it has the secondary benefit of augmenting sleep. In the upper dosage range, it can also treat depression.
(iv) Bisphosphonates and calcitonin
Severe bone pain frequently accompanies bone metastases. Although this pain does respond somewhat to opioids and NSAIDs, it is often useful to think in terms of treating the causative pathology. External beam radiation can be extremely helpful, as can systemic radioisotopes (see Chapter 20). Bone pain caused by osteoclast-induced bone resorption by tumor (typically breast metastases) may also be responsive to agents that inhibit bone resorption, such as the bisphosphonates (e.g., pamidronate) and calcitonin. These agents are also used to treat hypercalcemia of malignancy. Although these agents appear to be beneficial in some patients, other patients show no response. Study findings are mixed, and additional studies are warranted to define criteria that may predict clinical efficacy.
3. Anesthetic techniques
Research in pain management has shown that peripheral and central sensitization are involved in most types of clinical pain syndromes. In addition, certain forms of chronic cancer pain may be mediated by the sympathetic nervous system. Both somatic and sympathetic nerves can be blocked in the treatment of cancer pain. It is important when referring to nerve blockade to note whether it is an anesthetic (reversible) or a neurolytic/neurodestructive (more permanent) block. (For a full description of diagnostic and therapeutic procedures used in pain management see Chapter 12 and Chapter 13.)
Perhaps the most rewarding block for cancer patients is the celiac plexus block for the treatment of pain associated with pancreatic cancer and other intra-abdominal malignancies. This is usually a two-stage procedure. After needle placement, a local anesthetic is injected. If the pain is significantly abated, a lytic agent such as alcohol or phenol is injected. The local anesthetic usually wears off after a few hours. The lytic part of the block may not become effective for a couple of days. This block has a painrelieving efficacy rate of greater than 80% and can be repeated if necessary. Most patients with pancreatic pain get several months of pain relief from this procedure.
4. Neurosurgical techniques
With the advent of implantable devices for neuraxial analgesics, neurosurgical procedures for the management of pain are rarely used. These procedures are indicated in a few select patients and can be complicated by neurologic dysfunction. Examples of these procedures (see also Chapter 14) include the following:

Peripheral neurectomy

Anterolateral cordotomy, usually for contralateral somatic pain below the C5 dermatomal level

Dorsal rhizotomy

Hypophysectomy, best used for widespread hormonally mediated metastatic cancer (i.e., breast or prostate)
V. CONCLUSION
Cancer pain is almost always multifactorial and variable, making ongoing assessment critical to good care. Careful and regular assessment also helps to ensure the best quality of life for cancer patients. From the initial diagnosis of disease to the final stages of life, pain management techniques can relieve pain in the vast majority of cancer patients. It is often helpful to refer patients to a multidisciplinary pain treatment center when they present with a complex pain picture, preferably before the pain and associated symptoms are out of control.
SELECTED READINGS

1.
Ahmedzai S. Pain control in patients with cancer. Eur J Cancer 1997;33:555–562.

2.
Cutson TM. Management of cancer pain. Prim Care 1998;25:407–420.

3.
Du Pen SL, Kharasch ED, Williams A, et al. Chronic epidural bupivacaine-opioid infusion in intractable cancer pain. Pain 1992; 49:293–300.

4.
Fitzgibbon DR, Galer BS. The efficacy of opioids in cancer pain syndromes. Pain 1994;58:429–431.

5.
Grond S, Radbruch L, Meuser T, et al. Assessment and treatment of neuropathic cancer pain following WHO guidelines. Pain 1999;79:15–20.

6.
Levy M. Pharmacologic treatment of cancer pain. N Engl J Med 1996;335:1124–1130.

7.
Mercadante S. Opioid rotation for cancer pain: rationale and clinical aspects. Cancer 1999; 86:1856–1866.

8.
Patt RB, ed. Cancer pain. Philadelphia: JB Lippincott, 1993.

9.
Payne R. Mechanisms and management of bone pain. Cancer 1997;80(8 suppl):1608–1613.

10.
Portenoy R, et al. Breakthrough pain: Characteristics and impact in patients with cancer pain. Pain 1999; 81:129–134.

11.
Portenoy R, Portenoy RK, Hagen NA. Breakthrough pain: Definition, prevalence and characteristics. Pain 1990;41:273–281.

12.
World Health Organization Expert Committee. Cancer pain relief and palliative care. Geneva: World Health Organization, 1990.

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