Medical evaluation
Pain history
The medical evaluation should begin with a thorough history. As there are no objective means with which to verify the presence of pain, one must believe a patient’s complaint. The physiologic signs of acute pain—elevated blood pressure and pulse rate—are unreliable in subacute or chronic pain.
Most cancer patients report more than one site of pain. A detailed history of each type of pain should be elicited (Table 1). As the chief complaint resolves, what was initially a secondary problem may require attention.
Pain rating scales
Such scales should be used to establish a baseline against which the success of treatment may be judged (Figure 2). Behavioral observations may be used to assess patients who are unable to 
communicate. Although there are standardized tools for preverbal children, they are not available for impaired adults. Thus, it is sometimes necessary to treat pain presumptively.
Physical examination
This includes careful neurologic testing, especially if neuropathic pain is suspected. Pain in an area of reduced sensation, allodynia (ie, when normal stimuli are reported as painful), and hyperpathia or summation of painful stimuli indicate a neuropathic process. The assessment should evaluate the putative mechanisms that may underlie the pain.
Review of disease extent and current conditions
The extent of disease and current medical conditions must be determined.
Diagnostic tests
Diagnostics should be reviewed and supplemented as necessary.
Treatment and drug history
Cancer treatment and prior analgesic interventions, along with their outcomes, should be recorded. Psychological dependency on any drug, including alcohol(Drug information on alcohol), must be identified.
Psychosocial assessment
To establish trust, the evaluating clinician should explore with the patient the significance of the pain complaint. The impact of pain and other symptoms on functional status must be understood to establish treatment goals. Suffering may be attributable to many factors besides physical complaints. The clinician should ask about such psychological factors as financial worries, loss of independence, family problems, social isolation, and fear of death. Often, cancer patients meet diagnostic criteria for the psychiatric diagnosis of adjustment disorder with anxiety and/or depressed mood.
Subgrouping of patients
To help define therapeutic goals, the patient’s age and prognosis may be considered. Adjustments in drug doses are usually needed for elderly patients, who are more sensitive to analgesics and their side effects. Adolescents may require relatively larger doses of opioids. Pain in children is underreported and should be specifically elicited using age-appropriate assessment tools.
Pharmacologic treatment
The WHO has devised a three-step analgesic ladder outlining the use of non-opioid analgesics, opioid analgesics, and adjuvan
t medications for progressively severe pain. According to this schema, a nonopioid analgesic, with or without an adjuvant agent, should be tried first (step 1). If pain persists or increases on this regimen, the patient should be switched to an opioid plus a nonopioid agent, with or without an adjuvant medication (step 2). If pain continues or intensifies despite this change in therapy, a more potent dose of opioid analgesic should be prescribed, with or without a nonopioid and/or an adjuvant agent (step 3). This basic approach remains clinically useful.
Nonopioid analgesics
Nonopioid analgesics are associated with ceiling effects, and exceeding the maximum dose ranges can result in organ toxicity. Potential side effects, such as hematologic, renal, and gastrointestinal reactions, may be of clinical concern in cancer patients (Table 2). Cyclo-oxygenase (COX)-2 inhibitors are many times more potent against COX-2 than COX-1. Clinicians are advised to watch the emerging literature regarding the safety of these agents.
Opioid analgesics
General guidelines for opioid therapy are outlined in Table 3.
Dosage Opioid agonists do not exhibit ceiling effects. Dosing is guided by efficacy and limited by side effects (Table 4). Dosages of tablets combining a nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen and an opioid are limited according to the nonopioid component.
Routes of administration The oral route should be used when possible, although some patients may express a preference for
an alternative route. If so, or if the oral route is not feasible or systemic side effects are uncontrollable, alternative routes (eg, transdermal, transmucosal, rectal, and neuraxial infusion) are indicated. Such alternative routes of administration of certain opioid agonists (see Table 5) may improve patients’ quality of life and may be particularly useful for treating certain types of cancer pain.
Side effects of opioids can usually be anticipated and treated. In particular, with regular opioid dosing, laxatives should be prescribed for constipation.
Physical dependence and tolerance to some effects develop with chronic opioid use. Tolerance to respiratory depression, sedation, and nausea is likely. Tolerance to analgesia is not a major clinical problem and can usually be managed by changing the dose or substituting another agent.
Most current definitions of addiction imply a behavioral syndrome of compulsive, harmful use but do not require the existence of physical dependence or tolerance. Aberrant drug-taking is not likely to occur in patients without a history of substance abuse. However, compliance should always be monitored.
Precautions during chronic therapy During chronic opioid therapy, certain precautions should be observed:
• Normeperidine is a toxic metabolite of meperidine that accumulates with repetitive dosing; thus, use of meperidine for chronic pain should be limited. Propoxyphene is also relatively contraindicated due to accumulation of norpropoxyphene.
• Placebo use is discouraged, as it does not help distinguish the pathophysiology of pain.
• Physical withdrawal symptoms can be avoided by tapering doses.
• A change in mental status should not be attributed to opioid therapy until medical and neurologic factors have been fully evaluated.
• Mixed agonist-antagonist drugs and partial agonist drugs are not recommended for cancer pain.
• Methadone(Drug information on methadone) has unique pharmacokinetics. Inexperienced practitioners should consult a pain medicine expert before prescribing methadone. See FDA warnings.
