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Acetaminophen or an NSAID may be used instead of an opioid for mild pain or as a co-analgesic to reduce opioid dosage. NSAIDs can also be added to the opioid for pain associated with inflammation.

NSAIDs should be given with caution to patients who are at increased renal, gastrointestinal (GI), or cardiac risk or who have bleeding disorders. If NSAIDs are prescribed over the long term, monitor blood pressure, blood urea nitrogen, creatinine, complete blood count, and fecal occult blood every 3 months. Concurrent proton pump inhibitor therapy may forestall GI problems. Switching to a different agent or a COX-2 inhibitor may make continuation of effective NSAID therapy possible when GI toxicity is troublesome but not serious.

Chronic acetaminophen therapy is not without risks. The safety of the 4-g maximum daily dose has not been definitively established over the long term, Dr Paice notes. Problems may arise with cachectic patients, she points out: “the metabolic breakdown of acetaminophen depends on enzymes that may not be released without eating. These people are at greater risk from toxic by-products of acetaminophen.”

With NSAIDs and particularly acetaminophen, the risk of overdose is raised by the cumulative impact of hidden sources. “It’s embedded in so many over-the-counter preparations—sinus medicines, sleep medicines. Most people don’t read the label that carefully,” she says.


Co-analgesics may be required for cancer pain of certain etiologies, alone or in combination with opioids.

For neuropathic pain, antidepressants and anticonvulsants are first-line drugs of choice. Tricyclics (imipramine, desipramine) are the best validated and most commonly prescribed among the antidepressants. A low initial dose with gradual titration will optimize tolerability. Anticholinergic adverse effects (dry mouth, sedation, urinary hesitancy) are common, however, particularly with the more effective tertiary amines imipramine and amitriptyline. Other antidepressants, including duloxetine, venlafaxine, and bupropion, may be better tolerated by some patients, but less evidence supports their efficacy for neuropathic pain.

Among anticonvulsants, gabapentin and pregabalin are most often used. Of the two, pregabalin is more efficiently absorbed and can be titrated more quickly. Topical agents, such as the lidocaine patch or diclofenac gel, can augment systemic pharmacotherapy.

Glucocorticoids are effective for acute pain related to inflammation or nerve compression and for bone pain, but their extended use carries the risk of significant adverse effects. Bone pain may also benefit from an NSAID; a trial of bisphosphonates, hormone therapy, or chemotherapy; or from physical therapy.


Diagnostic and therapeutic maneuvers common in cancer care (arterial or central lines, injections, bone marrow aspiration, lumbar puncture, skin biopsy) are sufficiently uncomfortable and anxiety-producing for many patients to merit preemptive analgesic treatment. The guidelines advocate a multimodal approach with an emphasis on local anesthetics such as lidocaine, prilocaine, or tetracaine, delivered via creams, iontophoretic devices, or subcutaneous injection (allow sufficient time for anesthetic onset). Sedation, systemic analgesia, even general anesthesia may be indicated. Nonpharmacologic approaches (such as massage, heat or ice, ultrasound, or relaxation training) frequently have a role as well.

“Patients usually tolerate procedures better when they know what to expect,” the authors say. Providing full explanations with ample time for patients to assimilate information and have questions answered can reduce anticipatory anxiety.


Patients and families need to be reassured that steps can and will be taken to manage pain and its accompanying distress and will most likely involve oral medication only. They will benefit emotionally from the simple acknowledgment that pain is a problem and that the clinician will work together with them and remain available until they gain relief.

Talking through the issues surrounding pain — its meaning to the patient and the fears that surround it — can be enormously helpful. In progressive disease, “it’s a wonderful opportunity to address advance care planning,” Dr Paice emphasizes.

Psychosocial support may include teaching coping skills that reduce the impact of pain and give the patient some measure of control. These include relaxation and distraction techniques, guided imagery, and cognitive strategies to maximize comfort and limit stress. CDs and other resources are widely available and can be quite helpful, says Dr Paice.

Relaxation and guided imagery may be particularly valuable for breakthrough pain, during the interval before rescue medication begins to work, she says. “It can keep muscle tension down and keep pain from escalating while waiting for the immediate-release medication to work.”

Depression is closely linked to pain and may become more evident as physical symptoms are brought under control. Refer patients to a mental health professional when indicated.

Patient and family education should include full explanation of why medications are prescribed, what they can be expected to do, and how best to use them. “Most patients require education about how to use rescue medication for breakthrough pain,” adds Dr Paice. Cautions surrounding controlled substances (safeguarding them in the home, for example) and the impact of sedating medication on driving and other activities are important to discuss.


Physical modalities are often valuable adjuncts to pharmacotherapy. Physical therapy might be indicated, for example, for disuse syndromes that accompany and compound chronic pain; a therapist’s guidance in gait, posture, and movement can help minimize pain after surgery. Application of heat, cold, ultrasound, and electrical stimulation often substantially reduce muscle pain. Massage can be extremely useful when there is significant muscle involvement and for general relaxation.

Alternative and complementary modalities, such as acupuncture and acupressure, are highly acceptable to some patients.

Medical interventions such as nerve block are worth considering for certain types of cancer pain, after surgery, or when adequate analgesia is not otherwise possible without intolerable side effects. These generally require consultation with a pain specialist or referral to a specialty clinic.

Among commonly used procedures are epidural, intrathecal, and regional plexus infusions of opioids, local anesthetics, or other medications using an external or implanted pump. Neurodestructive procedures can be very useful for well-localized pain syndromes. For example, celiac plexus block can relieve the pain of pancreatic cancer, and superior hypogastric plexus block can be used for midline pelvic pain. Neurostimulation may be indicated for neuropathy and radiofrequency ablation for painful bone lesions.


The full text of the National Comprehensive Cancer Network’s Clinical Practice Guidelines in Oncology: Adult Cancer Pain, is available online at: www.nccn.org/professionals/physician_gls/PDF/pain.pdf. Registration (which is free) is required for access. ONA

Carl Sherman is a medical writer in New York City.