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Chronic Musculoskeletal Pain: Rational Use of Opioid Analgesics, Part 2


How to determine whether opioids are appropriate, what to do about breakthrough pain, and how frequently to monitor.

ABSTRACT: Opioid analgesics are used routinely in managing acute musculoskeletal pain. However, physicians often hesitate to use them for chronic pain, such as that seen in rheumatoid arthritis, osteoarthritis, osteoporosis, and low back pain. Opioid analgesics are not firstline therapy for chronic pain; they should be used with other medications, such as nonopioid analgesics, anti-inflammatory drugs, muscle relaxants, antidepressants, anticonvulsants, topical preparations, and sleeping pills. A comprehensive patient assessment and an addiction history are essential. Consultation with a specialist in pain management often is helpful.

Key words: chronic musculoskeletal pain, opioid, analgesic

In many cases, the use of opioid analgesics for patients with chronic musculoskeletal pain is a legitimate treatment approach, and it is gaining acceptance in the medical community. Although some reports question the efficacy of long-term use of opioid analgesics in improving function,1 several randomized controlled trials of these agents showed at least a 30% reduction in pain.2 Although these medications are effective, physicians tend to underuse them because they lack knowledge about them and about addiction. They also fear regulatory scrutiny.

In part 2 of this 2-part article, I discuss how to assess patients who have chronic pain, determine the safety and appropriateness of treating them with opioid analgesics, and monitor them on a regular basis. In part 1 ("Chronic Musculoskeletal Pain: Rational Use of Opioid Analgesics, Part 1 "), I reviewed the properties and adverse effects of opioid analgesics and described the differences between physical dependency and addiction.


Opioid analgesics are not firstline therapy for chronic pain and are not recommended as the only treatment. They should be used as part of a comprehensive treatment plan that involves other medications and other modalities. Other medications to consider may include the following:

Nonopioid analgesics, such as acetaminophen.
Aspirin and other anti-inflammatory drugs.
Muscle relaxants.
Antidepressants (because patients with chronic pain often are depressed). (Low-dose tricyclic agents may have some utility in managing some chronic pain conditions, such as fibromyalgia syndrome [FMS] and neuropathic pain.) The dual selective serotonin-norepinephrine reuptake inhibitors (SSNRIs) duloxetine (Cymbalta) and milnacipran (Savella) also alleviate neuropathic pain; both are now FDA-approved for FMS.
Anticonvulsants for neuropathic pain, including gabapentin (Neurontin), pregabalin (Lyrica), and divalproex sodium (Depakote).
Topical preparations (eg, a lidocaine patch).
Drugs that are used to counteract residual opioid sedation, including modafinil (Provigil) and methylphenidate (Ritalin).
Sleeping pills (because patients who have chronic pain often have insomnia).

Optimal management of chronic pain involves a team effort. In addition to the primary care physician, possible team members include a rheumatologist, orthopedic surgeon, physiatrist, physical therapist, anesthesiologist, pain specialist (who can perform invasive procedures, such as epidural corticosteroid injections or nerve ablation, or insert a spinal cord stimulator or intrathecal pump), biofeedback specialist, hypnotist, acupuncturist, neurologist, neurosurgeon, addictionist, and psychologist. Psychotherapy, especially that involving cognitive-behavioral and spiritual therapies, may help some patients by teaching them how to be more accepting of their condition.


Before a patient starts taking opioid analgesics for chronic pain, a comprehensive assessment is indicated. The first step is to assess the goal of treatment-is it to make a diagnosis of pain and eliminate it by removing the source or to allow the patient to live more comfortably with the pain?

Next, has the patient had a workup to determine the cause of the pain and the treatment options? For example, a patient with severe hip pain resulting from osteoarthritis might be best served by undergoing a hip replacement, which might result in no pain and improved function. Of course, this requires obtaining an adequate history of the pain problem, its onset and cause, and what treatments and medications have been used. If the pain problem is not new, obtaining old records from other treating physicians (including imaging studies, procedures, and consultations) is important.

A detailed description of the pain may help direct treatment. For example, neuropathic pain-pain related to direct nerve damage or injury-may benefit from treatment with anticonvulsants or the SSNRI antidepressants duloxetine and milnacipran that alleviate both depression and some types of neuropathic pain. Examples of this type of pain are peripheral neuropathy, postherpetic neuralgia, and reflex sympathetic dystrophy (now called chronic regional pain syndrome).

Note that musculoskeletal pain, such as low back pain, often has a neuropathic component (eg, sciatica). Therefore, a trial of an anticonvulsant or an SSNRI (eg, venlafaxine [Effexor] or duloxetine) may be worthwhile.

Taking an addiction history is essential to determine the appropriateness of considering opioid therapy. This history should include questions about the patient's present and past use of alcohol, cigarettes, or illegal drugs, as well as any family history of addiction problems. Administration of the Opioid Risk Tool3 or Screener and Opioid Assessment for Patients with Pain4 also is helpful. Old medical records should be examined for indications of previous problems with prescribed opioid analgesics. A physical examination in which particular attention is paid to the painful areas is needed to obtain additional information about the pain problem.

If the patient has not seen a physiatrist or an anesthesiologist who specializes in pain management, such a consultation may be extremely helpful. Both specialists can evaluate the role of local injections, physical therapy, transcutaneous electric nerve stimulation units, and other physical modalities in relieving pain. The physiatrist may recommend an assistive device, such as a wheelchair or braces. The anesthesiologist might consider placement of a spinal cord stimulator for some types of pain. If the patient has an addiction history or there are emotional or psychological issues, consultation with an addictionist or psychiatrist can be very informative.


If the decision to prescribe an opioid analgesic is made, an understanding of the role of sustained-release versus short-acting opioids is helpful. Long-acting medications generally are recommended for roundthe- clock pain; short-acting preparations are best for intermittent pain or breakthrough pain (a combination of underlying pain with exacerbations that are related to increased activity, the weather, or mood changes or that have no apparent explanation).

Most long-acting formulations now available actually are opioid analgesics with a short half-life that have been formulated into a sustained-release preparation. These include the following:

Sustained-release morphine: generic MSER (lasts 8 to 12 hours), MSContin (lasts 8 to 12 hours), Avinza (a true 24-hour formulation), and Kadian (lasts 12 to 24 hours).
Sustained-release oxycodone: generic oxycodone ER, OxyContin (OxyContin lasts 8 to 12 hours [about 25% of patients require every-8-hour dosing]; the generic version often lasts a shorter time).
Sustained-release fentanyl patch: generic patch, Duragesic. The 12-μg patch is available only as Duragesic; higher doses are also available as generic. Duragesic patches last 3 days in most persons, although about 25% of patients require every-2-day dosing.
Extended-release oxymorphone (Opana).

The most commonly used truly long-acting opioid analgesic is methadone, which has a variable serum half-life averaging 24 hours (range, 8 to 59 hours). Once-a-day dosing prevents withdrawal symptoms, but for pain relief, 3 or 4 doses per day are usually necessary. Any provider who has a DEA license can prescribe methadone for pain, just like any other opioid.

The cost of methadone is much lower than that of other opioid analgesics. However, because it has a long serum half-life, methadone needs to be titrated upward more slowly than other opioid analgesics, with increases only every few days. In November 2006, after multiple methadone overdose cases were reported in patients who had recently started methadone therapy and whose dose was increased too quickly, the FDA issued a warning about the need for caution when increasing methadone doses (http://www.flsipp.org/BolenNotice.pdf).

Methadone also must be tapered more slowly. If it is stopped suddenly, withdrawal symptoms can be prolonged.

An additional problem is that conversion between methadone and other opioids is not linear; that is, the higher the dose of morphine (or other opioid) the patient receives, the relatively greater is the equianalgesic ratio of morphine to methadone. For example, a patient who has been receiving 10 mg/d of morphine can be switched to 10 mg/d of methadone, but the equianalgesic daily dose of methadone for a patient who previously received 100 mg/d of morphine may be only 20 mg.

In addition, methadone metabolism is affected significantly by commonly used drugs. For example, some anticonvulsants (eg, carbamazepine [Tegretol]) increase its metabolism so that patients who receive these drugs at the same time may require very large doses of methadone. When you are starting to prescribe methadone, consultation with a knowledgeable physician is advised.

The short-acting opioid analgesics on the market usually are combinations with acetaminophen (eg, Tylenol with Codeine, Lorcet, Percocet, Vicodin, and Norco) or with aspirin (Lortab and Percodan). They have a faster onset of action than the long-acting opioid analgesics, but they also have a shorter duration of action. Morphine, oxycodone, hydromorphone (Dilaudid), oxymorphone, codeine, and others are available in immediate-release formulations without added acetaminophen or aspirin. They may be preferable if the risk of high doses of aspirin or acetaminophen is a concern. In addition, for pain that is intense at onset, ultrarapid-release formulations of fentanyl (Actiq and Fentora) are available.

For ongoing pain, the sustainedrelease or long-acting opioid analgesics are preferable to the short-acting combinations for 2 reasons: a long-acting formulation requires less frequent dosing and provides a smoother blood level, resulting in more consistent pain relief and less euphoric effect, and although there is no upper limit to the quantity of opioid analgesic that can be prescribed safely, taking more than 4 g/d of acetaminophen (equivalent to 12 regular Tylenol tablets) increases the risk of liver toxicity. Similarly, excessive aspirin use may have adverse effects on the GI tract. It is best to separate the opioid analgesic from the aspirin or acetaminophen and then titrate each individually.

Managing breakthrough pain. Many patients with chronic pain have breakthrough pain. Therefore, many pain specialists provide these patients with a combination of a long-acting or sustained-release opioid analgesic for round-the-clock dosing and some quantity of a short-acting opioid analgesic for breakthrough pain. If a patient consistently requires multiple doses of the short-acting drug, increasing his or her long-acting daily dose is preferable so that you can decrease the quantity of breakthrough medication.

For example, a physician may have prescribed MS-Contin, 60 mg twice a day, for chronic pain plus MSIR (immediate-release morphine), 15 mg up to 4 times a day, for breakthrough pain. If the patient ends up consistently taking 4 of the breakthrough doses daily, it would make sense to increase his MS-Contin to three 60-mg doses per day so that his MSIR can be decreased to one or two 15-mg doses per day for breakthrough pain. Typically, the average daily breakthrough dose prescribed is recommended to constitute no more than 15% to 25% of the sustained- release daily dose.



When first prescribing an opioid analgesic for chronic pain, scheduling the patient for another visit after a week or two is a good idea. Once the patient's pain stabilizes, monthly or bimonthly visits often suffice. An easy way of remembering the key elements of assessment at each follow-up visit, described by Passik and Weinreb5 as the "4 A's," is the following:

Analgesia: Ask the patient, "On a scale of 1 to 10, how much pain are you having?"
Adverse effects: Impaired thinking, somnolence, constipation, nausea, etc.
Activities of daily living: Can the patient do more when taking the drug than when not? Document specific activities that the patient can perform (eg, walking, shopping for food, traveling to visit family, working in the garden, attending movies, and resuming employment).
"Aberrant drug-related behaviors": Whenever there is such behavior, its cause should be assessed and a decision should be made whether to discontinue the medication. If the patient appears to have an addiction problem, referral to an addiction medicine specialist for further evaluation is appropriate.

Many clinicians have now added a fifth "A" for Affect, that is, the patient's mood. The answer to each question should be documented in the chart.

The increased activity that opioid analgesic use permits the patient often results initially in a need for a larger dose. Therefore, when the patient requests an increased dose, the physician should carefully assess the reason why rather than jump to the conclusion that this is drug-seeking behavior or tolerance.

At each visit, every prescription should be documented on a data sheet and every deviation from the expected date or amount should be explained fully in the chart. For example, if a prescription is dated 2 days early because of a holiday, I document this on the data sheet.


Patients taking opioid analgesics long-term who experience trauma or have surgery still need pain medication for their acute pain problem, usually larger amounts. They should be maintained on their usual dose of opioid analgesic plus medication for acute pain. Because general surgeons and other physicians may be uncomfortable prescribing the relatively high doses of opioid analgesics that are required, you may need to talk with these specialists before the surgery.




Cicero TJ, Inciardi JA, Muñoz A. Trends in abuse of Oxycontin and other opioid analgesics in the United States: 2002-2004.

J Pain

. 2005;6:662-672.


Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: systematic review of efficacy and safety.


. 2004;112:372-380.


Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool.

Pain Med

. 2005; 6:432-442.


Butler SF, Budman SH, Fernandez K, Jamison RN. Validation of a screener and opioid assessment measure for patients with chronic pain.


. 2004; 112:65-75.


Passik SD, Weinreb HJ. Managing chronic nonmalignant pain: overcoming obstacles to the use of opioids.

Adv Ther

. 2000;17:70-83.

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