(From Qiu Y, Noguchi Y, Honda M, et al. Brain processing of the signals ascending through unmyelinated C-fibers in humans: An event-related functional magnetic resonance imaging study. Cereb Cortex. 2006;16:1289-1295. Used with permission.)

Signals transmitted to the cerebral cortex variably emerge into conscious perception. Coordinated actions among subcortical and cortical areas create the subjective, affective, and cognitive responses that determine an individual’s reaction to the pain. The insula is the most frequently activated structure in fMRI pain studies and serves as a center for the integration of neural impulses.¹⁴ Damage to the insula can lead to pain asymbolia.¹⁵ The significance of pain is conveyed through connections between the insula and the striatum to parietal association cortices and the lateral prefrontal cortices.¹⁶ Supratentorial influences can dampen the pain, as in the case of an injured person who continues activities because the circumstances require self-preservation. In these cases, central neurons downregulate the perception of pain at the level of the spinal cord and dorsal horn by releasing endogenous opioid neuropeptides (endorphins, enkephalins, dynorphins), norepinephrine, GABA, and serotonin.

Treatment of Pain

Pharmacologic Agents

Nineteenth century physicians relied on an armamentarium of medications for pain control that included opium, morphine, codeine, and cocaine. The development of aspirin in 1897, the first compounded analgesic, revolutionized the treatment of pain. In the following century, numerous other agents were developed, with varying efficacy for a spectrum of pain conditions. Agents that are considered first line in the treatment of acute pain include opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), but these agents are less effective for neuropathic pain. Recommended first-line treatment of chronic neuropathic pain includes tricyclic antidepressants (TCAs), serotonin reuptake inhibitors, calcium channel α2δ ligands, and topical lidocaine. Second- and third-line therapies such as opioid analgesics, anticonvulsants, and antidepressants are more variable in their effectiveness and have broader side effect profiles, which limits their use (Table 157-1 and Fig. 157-2).

TABLE 157-1 Therapeutic Options by Pain Etiology

PAIN SOURCE	POTENTIAL AGENTS
Trauma/surgery/procedures	NSAIDs, opioids, acetaminophen, epidural analgesia
Acute sickle cell or cancer pain exacerbations	Opioids, NSAIDs, acetaminophen, steroids
Chronic low back pain	NSAIDs, opioids, muscle relaxants
Diabetic peripheral neuropathy	Antidepressants, anticonvulsants, capsaicin
Trigeminal neuralgia	Carbamazepine, baclofen, phenytoin
Postherpetic neuralgia	Antidepressants
Phantom limb pain	Carbamazepine, mexiletine, epidural analgesia
Cancer/HIV disease	Multiple combinations

HIV, human immunodeficiency virus; NSAIDs, nonsteroidal anti-inflammatory drugs.

FIGURE 157-2 Medications intervene in the transmission of pain signals at multiple sites along the pathway from the periphery to perception. NSAIDs, nonsteroidal anti-inflammatory drugs.

(Adapted from Gottschalk A, Smith D. New concepts in acute pain therapy: preemptive analgesia. Am Fam Physician. 2001;63:1979-1984.)

Nonsteroidal Anti-inflammatory Drugs

NSAIDs are inhibitors of prostaglandin synthesis that block cyclooxygenase (COX), the catalyst for the formation of prostaglandins from arachidonic acid. COX inhibition in the spinal cord and periphery results in downregulation of prostaglandin and thromboxane synthesis, both peripherally and centrally, thereby leading to antipyretic, analgesic, and anti-inflammatory effects. The most well known members of this class are aspirin, ibuprofen, and naproxen, which are nonselective COX-1 and COX-2 inhibitors. Selective COX-2 inhibitors include diclofenac and ketorolac. These medications are generally well tolerated, with gastrointestinal side effects being the most common. The gastrointestinal adverse effects are reduced with a selective COX-2 agent. Risk for dependency is very low. Special consideration of the preoperative use of these medications should be given because COX inhibition affects platelet aggregation as a result of inhibition of thromboxane A, which leads to difficulty with hemostasis. Because of possible interactions resulting in bradycardia, risk for gastrointestinal ulceration, and increased risk for bleeding, additional consideration should be given to prescribing NSAIDs for patients taking angiotensin-converting enzyme inhibitors, corticosteroids, warfarin, sulfonylureas, and methotrexate.

Acetaminophen

Although acetaminophen is often grouped with the NSAIDs because of its mild side effect profile and its effectiveness in analgesia and antipyresis, it does not produce an anti-inflammatory effect. The medication’s mechanism of action is still poorly understood but is believed to be related to a decrease in prostaglandin production through reduction of the oxidized form of COX and selective inhibition of prostaglandin H₂ synthase.¹⁷^–¹⁹ Additional research suggests that an acetaminophen metabolite may block the uptake of anandamide and consequently inhibit vanilloid receptor activation in nociceptors. There also appears to be a central effect on COX-3 inhibition leading to decreased PGE₂ concentrations within the brain.²⁰ Adverse effects include hepatotoxicity, most often associated with intentional overdose and patients with a history of alcohol abuse. Acetaminophen is only a weak inhibitor of platelet COX-1, and therefore the platelet inhibition effect is more limited than that with NSAIDs.

Anticonvulsants

Anticonvulsants have been used for the management of neuropathic pain since the 1960s. The mechanisms by which these agents act remain unclear, but hypotheses include their role in enhanced GABA inhibition (valproate, clonazepam), neuronal membrane stabilization (ion channel blockade agents such as carbamazepine, lamotrigine, oxcarbazepine), and binding at GABA (gabapentin, pregabalin) and N-methyl-D-aspartate (NMDA) receptor sites. Mechanisms of action are discussed further in the following sections.

Opioids

Opioids are one of the most effective classes of medications available to treat both acute and chronic pain and are therefore a mainstay for both types of pain. In one study examining the treatment of chronic central pain, patients’ pain intensity scores were significantly lower after the administration of opioids than after placebo.²¹ Opioids act to suppress pain through mu-receptor activation on primary afferent nerve fibers, dorsal horn neurons, and supraspinal pain center neurons. Presynaptic activation by bound opioids reduces neurotransmitter release, whereas postsynaptic activation causes hyperpolarization through increased conductance of potassium.²² Opioids were originally thought to be ineffective for neuropathic pain,²³ but more recent trials have demonstrated that pain intensity scores were significantly lower after opioid administration than after placebo for neuropathic pain.²⁴

The most common reasons that patients discontinue opioid therapy are inadequate analgesia and intolerable side effects.²⁵ In one prospective study, 17% of patients withdrew because of adverse events and 8% because of lack of efficacy (Table 157-2).²⁶ In general, side effects can be addressed by decreasing the dose or changing the route of administration. Opioid rotation, in which the opioid is combined with other medications in a complementary strategy, or using a second medication targeting the side effect can also alleviate side effects.²⁷ The most commonly prescribed opioid medications are morphine, codeine, oxycodone, hydrocodone, fentanyl, alfentanil, meperidine, propoxyphene, and methadone. Each varies in side effect profile, drug-drug interactions, and therapeutic effects. All members of the opioid class cross the placenta, although no teratogenic effects have been observed. If used during labor, the medications can cause neonatal depression. Interestingly, in Japan, opioids are rarely prescribed because other medications appear to provide satisfactory levels of relief.²⁸

TABLE 157-2 Adverse Effects of Opioids

SIDE EFFECT	MECHANISM
Neurological	Delirium, hallucination, euphoria, sedation/drowsiness, dizziness, diminished psychomotor performance, seizures, headaches, muscle rigidity, hyperalgesia, paradoxical pain
Cardiopulmonary	Cardiac dysrhythmias (bradycardia/long QTc, torsades de pointes), hypotension, decreased systemic vascular resistance, noncardiogenic pulmonary edema, respiratory depression
Gastrointestinal	Nausea and vomiting, constipation, gastroesophageal reflux disease, xerostomia, biliary duct obstruction
Genitourinary	Altered kidney function, urinary retention, peripheral edema
Endocrinologic	Hypogonadism, sexual dysfunction, osteoporosis

Tramadol is an atypical opioid related to codeine. It exerts some of the pain-relieving properties of opioids while having a more tolerable side effect profile by acting as a norepinephrine and serotonin reuptake inhibitor. Its primary metabolite, O-desmethyltramadol, has mu-opioid agonist activity, which provides tramadol a potency about 10% of morphine. Tramadol has been shown to cut pain levels by more than 50% in the treatment of neuropathic pain.²⁹ Adverse effects include nausea, sweating, vomiting, dry mouth, constipation, dizziness, sedation, and incoordination. There are also smaller risks of a reduced seizure threshold, respiratory depression, withdrawal symptoms, and serotonin syndrome. Caution should be exercised in prescribing tramadol to elderly patients because it can cause cognitive impairment. It has been demonstrated to have a much lower risk for abuse than other opioid drugs,³⁰ and it does not have the gastrointestinal side effects associated with NSAIDs (Table 157-3).

TABLE 157-3 Parenteral-Oral Opioid Equianalgesic Conversion

Ion Channel Blockers

Medications that block voltage-gated sodium channels, including lidocaine, amitriptyline, lamotrigine, and carbamazepine, raise the threshold for generating an action potential in peripheral nociceptors. Although these medications appear to have effects on some categories of chronic pain, this relief is not across the board for all types of pain. Lamotrigine has been shown to be most effective for trigeminal neuralgia ³¹ and less effective for human immunodeficiency virus (HIV) neuropathy, intractable neuropathic pain,³² and spinal cord injury–related pain. A meta-analysis demonstrated that there was no statistically significant benefit of treatment with lamotrigine for central poststroke pain or diabetic neuropathy, but anecdotal improvements are reported.³³ Similarly, carbamazepine was shown to be ineffective for acute herpes zoster but was effective in treating trigeminal neuralgia,³⁴ diabetic neuropathy, postherpetic neuralgia, and other neuropathic pain.³⁵ The adverse effects of ion channel blockers include drowsiness, dizziness, constipation, nausea, ataxia, rash, and headaches. Several medications, including carbamazepine, require surveillance monitoring of serum drug levels. Because of the less convincing results in trials with these medications, they are best used in patients who have failed first- and second-line medications.

Local anesthetics, such as topical lidocaine formulations, also inhibit action potential firing in nociceptors. Topical preparations include timed-release patches, gels, and creams. Careful titration allows a high degree of selectivity in the blockage of sensory neurons, whereas higher concentrations will also affect other modalities of neuronal signaling. These topical preparations are generally well tolerated, with local rash and erythema being the most common side effects. An alternating schedule in which the duration of patch use does not exceed 12 hours at a time can prevent skin effects and also avoid the theoretical risk for cardiac dysrhythmia.

Tricyclic Antidepressants

TCAs were the first medications approved by the U.S. Food and Drug Administration (FDA) for the treatment of neuropathic pain. Notably, their analgesic effect appears to be separate from their antidepressant action in that it is evoked at a lower dosage. Numerous studies have demonstrated the effectiveness of TCAs for postherpetic neuralgia and painful diabetic peripheral neuropathy. TCAs were no more effective than placebo in trials for HIV neuropathy, spinal cord injury, cisplatin neuropathy, neuropathic cancer pain, phantom limb pain, and chronic lumbar root pain. Patient response to TCAs is highly variable, and no more than 40% to 60% of patients achieve partial relief of pain with these agents.³⁶ Adverse effects include sedation, dry mouth, blurred vision, weight gain, and urinary retention. Major adverse effects of TCAs include cardiac toxicity, overdose risk, and potentiation of cytochrome P-450. Nortriptyline was associated with sinus tachycardia and increased ventricular ectopy in one trial of patients with depression and ischemic heart disease. Before administration, a patient’s cardiac history should be reviewed, and in some cases, cardiac function studies should be performed. Monitoring of drug levels is not usually indicated if the dosage is less than 150 mg/day.

Calcium Channel α2δ Ligands

GABAergic agents were introduced in the mid-1970s, with gabapentin first synthesized in 1977 and approved initially by the FDA for the treatment of complex partial seizures. Pregabalin was developed in 1989 and approved by the FDA in 2004. Their mechanism of action involves calcium channel α2δ subunit binding within the central nervous system. This results in a stabilizing effect on cell membranes, glutamate suppression, suppression of substance P transmission, influence on NMDA receptor sites, modulation of GABA receptors, and increased GABA inhibition.³⁷^–⁴⁰ Studies show little benefit of gabapentin in the treatment of acute pain, but GABAergic agents are highly effective in the treatment of chronic neuropathic pain. In one study, 42% of participants improved versus 19% with placebo.⁴¹ Pregabalin was the first medication approved by the FDA for the treatment of fibromyalgia syndrome. Adverse effects associated with GABAergic agents include dizziness, somnolence, headache, diarrhea, confusion, and nausea. The main dose-limiting effects are sedation and dizziness.

Acute Pain

Treatment of acute pain is geared toward disruption of the inflammatory mediators that contribute to peripheral nociceptive excitability and to the interruption of signal conduction and transmission from the periphery to the central nervous system. To this end, a combination of NSAIDs, opioids, and local anesthetics can be used. NSAIDs downregulate prostaglandin synthesis peripherally and centrally to decrease inflammatory mediators. Local anesthetics decrease or prevent nerve excitability by blocking voltage-gated ion channel activation. Epidural, intrathecal, and systemic opioids act at the site of interneurons to inhibit synaptic transmission of peripheral signals. Patient-controlled analgesia has been demonstrated to result in improved outcomes when compared with nurse-administered parenteral opioids.⁴² A strategy of multimodal therapy is recommended to address the pain cascade at several sites; this approach has been shown to convey improved postoperative pain control and reduced analgesia-related adverse effects. In both children and adults, postoperative acute pain prevention should begin in the preoperative period with an emphasis on educating patients about the procedure and shaping their expectations (Table 157-4).

TABLE 157-4 Acute Pain Management, Selected Medications

MEDICATION	DOSING	MAXIMUM DOSE
Acetaminophen	325-1000 mg PO q4-6h	1 g/dose, 4 g/24h
Parenteral NSAID
Ketorolac	30-60 mg IM or 15-30 mg IV q6h	120 mg/day
Oral NSAIDs
Ketorolac	10 mg PO q4-6h	40 mg/day; <5 days total
Celecoxib	200 mg PO bid	400 mg/day
Ibuprofen	400-600 mg PO q4-6h	2400 mg/day
Naproxen	250-500 mg PO bid	1250 mg/day
Parenteral Opioids
Fentanyl	50-100 µg IV q1-2h prn or 0.5-1.5 µg/kg/hr by IV infusion
Morphine	2.5-10 mg SC/IM/IV q2-6h prn or 0.8-10 mg/hr IV
Hydromorphone	1-4 mg SC/IM/IV q4-6h
Meperidine	50-150 mg SC/IM q3-4h
Methadone	2.5-5 mg SC/IM/IV q8-12h prn
Oral Opioids
Morphine	10-30 mg PO/SL q3-4h prn or 15-30 mg ER PO q8-12h
Hydromorphone	2-8 mg PO q3-4h prn
Methadone	2.5-10 mg PO q8-12h prn
Codeine	15-60 mg PO q4-6h	60 mg/dose
Hydrocodone	5-20 mg PO q4-6h	8 tablets in 24 hr
Oxycodone	5-30 mg PO q4h prn or 10-160 mg ER PO q12h
Tramadol	50-100 mg PO q4-6h prn	Maximum: 400 mg/day; 300 mg/day if >75 years old
Benzodiazepines
Diazepam	2-10 mg PO divided bid-qid	30 mg/8 hr
Lorazepam	2-3 mg/day PO/IM/IV divided bid-tid	10 mg/day

ER, extended release; NSAID, nonsteroidal anti-inflammatory drug; prn, as needed; SL, sublingual.

Acute Pain in Children

Pain in children has historically been underestimated, and it was not until the 1980s that studies quantified the prevalence of postoperative pain in pediatric patients and demonstrated that infants have a nearly equivalent distribution of nociceptors as adults.⁴³^–⁴⁵ Because infants and children cannot report their pain clearly, clinicians and parents must be observant of signs—including irritability, apathy, muscle rigidity, guarding, crying—that a child is experiencing pain. Scheduling doses of medications so that pain levels do not escalate and the use of nonmedical pain control measures (see later) facilitate a child’s comfort. Use of long-acting local anesthetics such as bupivacaine and providing analgesics on a dosing schedule help prevent pain beyond the child’s control. Topical local agents can make peripheral procedures more tolerable. Eutectic mixture of local anesthetics (EMLA) cream contains lidocaine and prilocaine, and onset of anesthesia is achieved within 60 minutes. Oral and intravenous NSAIDs and acetaminophen are the mainstays of treatment of mild to moderate pain in children and have both anti-inflammatory and analgesic effects. Mild to moderate pain can usually be treated with acetaminophen and NSAIDs, whereas severe pain may require opioid agents. Opioid use remains controversial in children, in part because of risk for respiratory depression and side effects, including sedation, nausea, and vomiting. However, opioids remain the drug of choice for severe pain and mechanically ventilated patients. Studies demonstrate successful control of acute pain with patient- or nurse-controlled analgesia in children as young as 6 years.⁴⁶^,⁴⁷ Anxiolytic medications such as midazolam can complement analgesics. In neonates, the clinician must take differences in blood-brain permeability and metabolism into account when selecting pain control regimens. Furthermore, children with pulmonary or neurological abnormalities may have altered thresholds for sedation and respiratory depression (Table 157-5).⁴⁸

TABLE 157-5 Acute Pain Management in Children, Selected Medications

Nonmedical interventions offer significant pain relief in children as well. Successful techniques include distraction through playing games, touch, playing music, muscular relaxation, and guided imagination.⁴⁹ Minimizing the duration of the procedures and any delays can also reduce a child’s pain and anxiety, as can controlling the level of noise and light in patient care areas.⁵⁰ The majority of American pediatric anesthesia centers offer modalities of complementary and alternative pain treatments, including biofeedback, guided imagery, hypnosis, massage, relaxation therapy, acupuncture, art therapy, meditation, therapeutic touch, music therapy, self-help groups, herbal medicine, yoga, Tai Chi, and chiropractic care.⁵¹ Some studies show a link to shorter postoperative hospital stays⁵² and reduced pain and anxiety⁵³ related to these nonmedical interventions.

Chronic Pain

In chronic pain, afferent function is altered in a persistent way as a result of peripheral and central nerve sensitization, and different management strategies are required. Although several of the medication classes used for acute pain are effective for chronic pain, other classes are far more optimal. Common agents used include NSAIDs, TCAs, ion channel blockers, and opioids. A meta-analysis evaluating the efficacy of several classes of medications identified the number needed to treat for beneficial response (Table 157-6).⁵⁴ It should be noted that none of these agents were completely effective, so a strategy of sequential trials of medication should be applied to identify each patient’s most effective pharmacologic regimen (Table 157-7).⁵⁵^,⁵⁶

TABLE 157-6 Treatment Effectiveness for Neuropathic Pain

MEDICATION CLASS	NUMBER NEEDED TO TREAT*
Tricyclic antidepressants	2.4
Carbamazepine	2.5
Tramadol	3.5
Gabapentin	3.7
Selective serotonin reuptake inhibitor	6.7
Dextromethorphan	1.9
Levodopa	3.4
Capsaicin	5.9
Mexiletine	38

* Number needed to treat is an epidemiologic calculation of treatment effectiveness and is defined as the number of patients who need to be treated to see benefit from the treatment in one patient.

TABLE 157-7 First-Line Medications for Neuropathic Pain

Management of chronic pain is best accomplished through a multimodal approach that addresses a patient’s behavior and lifestyle in addition to providing medical management. A multidisciplinary pain team model views pharmacotherapy not as a cure but as an integral component of a more comprehensive approach that involves physical therapy, psychiatry, invasive procedures, and complementary and alternative medicine interventions. A Japanese example of multidisciplinary treatment involves targeting identified pain behavior through patient education about their diagnosis, treatment strategies, influence of disuse, role of medications, incorporation of therapeutic exercise, long- and short-term goal setting, and cognitive and behavioral techniques, including relaxation techniques, reframing, breathing techniques, and positive imaging with the aim of reducing fears related to pain.⁵⁷ Furthermore, the addition of antidepressants, anxiolytics, and physical therapy can improve quality of life, especially physical and emotional function. Pharmacotherapy alone has an effect on reducing pain intensity without a demonstrable improvement in quality of life and degree of patient activity.⁵⁵

Tolerance, Addiction, and Withdrawal

Over time, many patients will need an increased dosage of a drug to produce the same level of analgesia that existed previously. Tolerance is suspected when a reduced physiologic effect is observed with constant dosing. Analgesic tolerance is not always evident during opioid treatment and is not to be confused with addiction, which is a dysfunctional craving for a drug action driven by physiologic and psychological factors.⁵⁸ Tolerance occurs in a minority of patients, and dose escalation can be required to continue to address patients’ pain needs.⁵⁹ This can be signaled by the decreased duration of analgesia that each dose provides a patient. Physical dependence on a substance is a state of adaptation in which a withdrawal syndrome can be provoked if the substance is decreased or discontinued or an antagonist is administered. Physical dependence is a normal adaptation to the drug, reinforced by continued use. Chronic pain patients may exhibit end-of-dose failure in which the pain worsens between doses of the opioid medications. Those taking medications on an as-needed basis may also experience intermittent withdrawal symptoms. The most important symptoms of opioid withdrawal are increased preexisting pain, deep bone pain, and diffuse muscles aches.

Addiction is the compulsive use of a substance despite physical harm. Many addicts become tolerant of their chosen drug with habitual use, but addiction is characterized by dysfunctional use behavior that includes impaired control over drug use, compulsive use, and continued use despite harm and craving. Pseudoaddiction results when pain is treated with an underpotent agent. This state leads patients to manifest signs of drug seeking that can be misinterpreted as signs of addiction.⁶⁰^,⁶¹

Addiction and diversion of opioid medications are a concern for clinicians prescribing chronic opioid therapy. However, of 2042 patients in a 17-study meta-analysis, in only 1 patient did signs of opioid addiction (“drug-seeking behavior”) develop, which translates to an addiction rate of 0.05% (Fig. 157-3).⁶² Misuse and abuse of medications used for the treatment of chronic pain have increased in the past decade. Thirty percent of illicit drug users report nonmedical prescription drug use; nearly half occur in young people aged 12 to 25.⁶³ The National Household Survey on Drug Abuse indicated a statistically significant increase in nonmedical use of opioids between 2000 and 2001,⁶⁴ but only a small proportion of this increase appears to involve patients with no previous abuse history who are receiving new opioid prescriptions. Several studies have revealed that patients without a history of substance abuse problems do not abuse the opioids prescribed to them for relief of chronic pain, and in some cases, patients’ fear of addiction developing leads to self-discontinuation of opioids.⁶⁵ In one study, more than 97% of patients who abuse opioids had a previous history of abusing opiates, alcohol, or other drugs.⁶⁶ The most commonly abused opioids are oxycodone, hydrocodone, hydromorphone, morphine, and methadone.

FIGURE 157-3 Patients with addiction behavior represent only a minority of patients treated with opioids for chronic pain conditions. NSAIDs, nonsteroidal anti-inflammatory drugs.

(Data from Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Pain Med. 2005;6:432-442.)

Despite these studies, clinicians are hesitant to prescribe opioids for numerous reasons: they are unfamiliar with dosing or with monitoring urine drug tests, have concerns about side effects, have concerns about illegal diversion and about causing addiction, or are apprehensive about regulatory scrutiny or about relying on patients to gauge their own pain intensity.⁶⁷ Enacting a set policy for opioid treatment can alleviate many of these concerns:

• Accurate and thorough documentation, including explicit statements of conditions of compliance

• Using tools that evaluate pain with measures beyond patient reporting alone because patients may misestimate the amount of opioids used or may misrepresent their use

• Drug screening—urine or blood—to monitor adherence by demonstrating expected drugs and their metabolites in samples

• Random pill counts: fewer pills predict diversion or pseudoaddiction, whereas more pills reflect undertaking

• Open and frank discussions between the prescribing clinician and patient about adverse effects, doses required, and adherence to prescribed doses

• Use of a “pain contract”—a written agreement that clearly defines the rules related to opioid prescribing, including the following: (1) patients should receive medications only from one practice, preferably from a single pharmacy; (2) stipulations for lost medications, toxicology screenings, early refill requests, and diversion of medications; and (3) articulated clear repercussions for violations of the agreement

Meticulous patient selection can help in preventing opioid abuse by identifying patients who are at high risk for the development of addictions. Pretreatment screening for the potential for drug abuse should include several assessments:

• Psychopathology

• CAGE questionnaire and other instruments to reflect addiction history ⁶⁸

• Opioid Risk Tool ⁶⁹: in the low-risk group, 94% did not display aberrant behavior, whereas in the high-risk group 91% did; high sensitivity and specificity

• Screener and Opioid Assessment for Patients with Pain (SOAPP)—a risk-benefit analysis consisting of 14 questions ⁷⁰

A history of opioid abuse alone should not rule out prescribing these medications to a patient. Rather, the clinician may choose to proceed with very close monitoring.⁶⁸ A survey of clinicians identified a belief that high daily opioid doses predispose to addiction,⁷¹ but this has not been demonstrated in studies. In general, younger patients and males have greater potential for problems.⁷² Other risks for potential abuse include a low functional level, excessive opioid needs, exaggeration of pain, deception or lying, doctor shopping, prescription forgery, frequent telephone calls or patient visits, and multiple medication allergies/intolerances.⁵⁸