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Chronic Musculoskeletal Pain: Rational Use of Opioid Analgesics, Part 1

Chronic Musculoskeletal Pain: Rational Use of Opioid Analgesics, Part 1

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. Starting the patient at a low dose and progressively titrating upward for pain relief minimizes the adverse effects. The fear that prescribing opioid analgesics for chronic pain will engender addiction is not supported by experience.


Key words: chronic musculoskeletal pain, opioid, morphine, analgesic

Throughout history, various forms of morphine have been the most effective medications in relieving pain. Opioid analgesics—the natural, semisynthetic, and synthetic derivatives of morphine—are used routinely in the management of acute musculoskeletal pain. However, myths and misunderstandings about these drugs often prevent primary care physicians from prescribing them for chronic pain, such as that seen in common musculoskeletal conditions (eg, rheumatoid arthritis, osteoarthritis, osteoporosis, and low back pain). Although pain is one of the most common symptoms that bring patients to the physician's office, those with chronic musculoskeletal or other noncancer pain all too often are undertreated.

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 1 of this 2-part article, I review the properties and adverse effects of opioid analgesics and describe the differences between physical dependency and addiction. In part 2 in a coming issue, I will discuss how to assess patients who have chronic pain, determine the safety and appropriateness of treating them with these agents, and monitor them on a regular basis.

EFFECTS AND ADVERSE EFFECTS

Opioid analgesics exert their effects by binding to μ, κ, and δ receptors in the CNS (brain and spinal cord), the GI tract and, to a lesser extent, the peripheral tissues. They counteract pain signals ascending to the brain. Pain relief is their desired effect, but they also have adverse effects (eg, nausea, sedation, and constipation).

Starting treatment at a low dose and progressively titrating upward for pain relief minimizes the adverse effects while permitting development of tolerance (the need for an increased dose to achieve the same adverse effect or a diminished effect with the same dose) to the nauseating and sedating effects. Tolerance to nausea and sedation (and its extreme, respiratory depression) is desirable, but there is no tolerance to the constipating effect of opioid analgesics. Therefore, it is important for the patient to maintain a bowel regimen (stool softener, bowel stimulant, fluids, and activity) for as long as an opioid analgesic is being taken.

Tolerance to the pain-relieving effects of opioid analgesics is uncommon. Once titrated to an effective pain-relieving dose, most patients continue taking the same or a similar dose for long periods.3-5 Pain specialist Russell Portenoy, MD,6 wrote, "Contrary to conventional thinking, the development of analgesic tolerance appears to be a rare cause of failure of long-term opioid therapy."

Although there is some evidence to indicate that long-term exposure to high doses of opioid analgesics results in hyperalgesia (increased pain sensitivity),7 this is rarely of clinical significance. Most often, a request for an increased dose reflects increased physical activity, a worsening physical problem, or deterioration in the patient's psychological status (eg, depression).

An often unappreciated adverse effect of long-term opioid analgesic use is lowered sex hormone levels in men. In those who are taking significant doses of opioid analgesics long-term, subnormal testosterone levels are the rule rather than the exception.8

Plan on checking total and free testosterone levels in all men who are taking moderate to high doses of opioid analgesics. Many will need testosterone replacement, preferably with patches or transdermal preparations. It is wise to also monitor their prostate-specific antigen levels.

I recommend checking testosterone levels even in asymptomatic patients. Untreated hypotestosteronism can lead to osteoporosis in men, as well as decreased muscle strength.

Some patients taking morphine experience itching. Morphine is more likely than other opioid analgesics to cause histamine release and pruritus. If antihistamines do not provide enough relief, switching to another opioid analgesic may be the answer.

There is no accepted upper limit of safety for opioid analgesics. Because of genetic differences and varying pathology, there are enormous differences in patients in the amount of opioid analgesics they need for adequate pain relief. Historically, some patients with cancer have required grams of morphine. For many patients, however, 5 mg of hydrocodone (in Vicodin or Lorcet) provides adequate pain relief.

As long as the dose is started low and increased gradually, large doses may be taken and are limited only by adverse effects. Unlike acetaminophen, aspirin, and many other drugs, opioid analgesics do not have any specific organ toxicity. Thus, the right dose is the one that provides adequate pain relief without unacceptable adverse effects.

Typically, it takes 3 to 7 days for the body to overcome sedation produced by opioid analgesics. Thus, it is wise for patients to avoid driving when they begin to take these drugs and when they increase the dose. Once patients are taking a stable dose and feel alert, generally it is safe for them to drive because they have adequate psychomotor functioning.9-11 Of course, it is wise to avoid using alcohol and benzodiazepines before driving, because they are likely to increase any sedative effects of opioid analgesics.

Opioid analgesics are significantly safer than NSAIDs; they are not associated with upper GI bleeding or renal toxicity. This may be particularly important in older patients who are at risk for the GI and renal toxicity of NSAIDs.

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