Opioids merit consideration for treating chronic pain

Rational use of opioid analgesics for patients with chronic musculoskeletal pain can be an effective treatment option

By Jennifer P. Schneider, MD, PhD

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 practitioners from prescribing them for chronic pain, such as that seen in common musculoskeletal conditions (e.g., low back pain, osteoarthritis, rheumatoid arthritis, and osteoporosis).

Although pain is one of the most common symptoms that bring patients to a clini­cian’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 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, practitioners tend to underuse them because they lack knowledge about them, are concerned about possible addiction, and also fear regulatory scrutiny.

Adverse effects

Opioid analgesics exert their effects by binding to µ, κ, and δ receptors in the central nervous system (brain and spinal cord), the GI tract and, to a lesser extent, the peripheral tissues. They counteract pain signals ascending to the brain. Although pain relief is the desired effect, opioid analgesics also have adverse effects (e.g., nausea, sedation, and constipation).

Starting the patient 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 not 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 opioids is uncommon. Once titrated to an effective pain-relieving dose, most patients continue taking the same or a similar dose for long periods.³ Pain specialist Russell Portenoy, MD,⁴ wrote, “Contrary to conventional thinking, the development of analgesic tolerance appears to be a rare cause of failure of long-term opioid therapy.”

Although some evidence indicates that long-term exposure to high doses of opioid analgesics results in hyperalgesia (increased pain sensitivity), this is rarely of clinical significance.⁵ Most often, a request for an increased dose reflects increased physical activity, a worsening physical problem, or deterioration in the patient’s psychological status, such as 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, long-term, subnormal testosterone levels are the rule rather than the exception.⁶

Men who are taking moderate to high doses of opioids should have their total and free testosterone levels checked. Many will need testosterone replacement, preferably with patches or transdermal preparations. It is wise to also monitor their prostate-specific antigen levels. 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 agents. Because of genetic differences and varying pathology, there are enormous differences among 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 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. Therefore, the right dose is the one that provides adequate pain relief without unacceptable adverse effects.

Typically, it takes three to seven days for the body to overcome sedation produced by opioid agents. Thus, it is wise for patients to avoid driving when they begin to take these drugs and when the dose is increased. Once patients are taking a stable dose and feel alert, it is generally safe to drive because they have adequate psychomotor functioning.^7-9 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 nonsteroidal anti-inflammatory drugs; they are not associated with upper gastrointestinal bleeding or renal toxicity. This may be particularly important in older patients who are put at risk by the GI and renal toxi­city of NSAIDs.

Many practitioners believe that anyone who is taking opioid analgesics long-term becomes addicted. This misunderstanding results when the concepts of physical dependency and addiction are confused.

Physical dependency

This is a form of physiologic adaptation to the continuous presence of certain drugs in the body. Abrupt discontinuation of the drug after the body has become accustomed to it results in a predictable withdrawal syndrome. For opioid analgesics, this may include anxiety, irritability, goose bumps, salivation, lacrimation, rhinorrhea, dia­phoresis, nausea and vomiting, abdominal cramps, and insomnia.

Withdrawal from morphine begins at six to 12 hours after last use and peaks at one to three days. The symptoms associated with longer-acting opioids, such as methadone, have a slower onset and are less severe than those with shorter-acting drugs, such as morphine and hydromorphone. Withdraw­al symptoms may be avoided by tapering the drug over days.

Patients who take opioid analgesics for more than a few days should be considered physically dependent. The patient should be cautioned to avoid stopping the opioid suddenly because withdrawal symptoms may appear. Even if pain stops totally, the medication should be tapered. Opioid withdrawal is not dangerous, but it can be very uncomfortable.

A patient’s physical dependence on an opioid agent is a physiologic state in which abrupt cessation of it or administration of an opioid antagonist results in a withdrawal syndrome, according to the American Society of Addiction Medicine.¹⁰ It is expected in all persons in the presence of continuous use of opioids for therapeutic or nontherapeutic purposes and does not, in and of itself, imply addiction.

Corticosteroids are another class of drugs that produce physical dependency. The corollary, known by all physicians, is that when corticosteroids are stopped after ongoing use, they should be tapered rather than stopped abruptly. The same is true of opioid analgesics.

Addiction

This is a psychological and behavioral disorder characterized by the presence of all three of the following: loss of control (compulsive use); continuation despite adverse consequences; and obsession or preoccupation with obtaining and using the drug or other substance.As an addiction advances, the person’s life becomes progressively more constricted. The addiction becomes the top priority and relationships with family and friends suffer. The addict’s mental state grows preoccupied with the drug. Life revolves around obtaining and using the drug. This constriction distinguishes use of a drug by an addict from its appropriate use by a patient who has chronic pain.
Clinicians who are uncomfortable prescribing opioid analgesics probably have patients who keep requesting more me­­­di­cation and seem preoccupied with the quantity being prescribed. These patients often are stigmatized with the label of “drug seeker.” The real problem may be that the pain management is inadequate. Once a sufficient dose of an opioid agent is prescribed, this pseudoaddiction vani­shes.

Does prescribing opioid analgesics for pain lead to addiction? The fear that prescribing them for chronic pain will engender iatrogenic addiction is not supported by experience. Addiction to opioid analgesics from long-term treatment for pain rarely occurs in patients who do not have a history of addiction.^3,11

Even patients who have a previous history of addiction need not automatically be excluded from opioid analgesic treatment for chronic pain. Known addicts may benefit from the carefully supervised, judicious use of opioid analgesics for pain resulting from cancer, surgery, or recurrent painful illnesses.¹² When contemplating a prescription for opioid analgesics for a patient with an addiction history, however, practitioners are advised to consult with a pain or addiction medicine specialist.

For such patients, careful supervision is the key. This includes a contract outlining the practitioner’s expectations of the patient, provisions made for random urine screens, and increased attendance at 12-step self-help meetings.

Recovering alcoholics are less likely to relapse than patients who once were addicted to opioid analgesics.¹³ Prescribing them to former addicts should be considered only as a last resort—if every other approach has failed—and with the participation of an addiction medicine specialist. Patients who are current drug addicts cannot be trusted to manage their opioid pain medications reliably. These patients are not candidates for opioid therapy unless they are in a supervised setting with someone else dispensing the medication.

Comprehensive treatment plan

Opioid analgesics are not first-line 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 modali­ties. Other medications to consider may include the following:

• Nonopioid analgesics (for example, acetaminophen);• Aspirin and other NSAIDs;
• 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 and neuropathic pain;
• Anticonvulsants for neuropathic pain, including gabapentin, pregabalin, and di­valproex sodium;• Topical preparations (e.g., a lidocaine patch);
• Drugs used to counteract residual opioid sedation, including modafinil and methylphenidate; and• 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), biofeedback specialist, hypnotist, acupuncturist, neurologist, neurosurgeon, addictionist, and psychologist.

Jennifer P. Schneider, MD, PhD, is a physician certified in internal medicine, addiction medicine, and pain management. She is the author of eight books and numerous articles in professional journals. She has been a member of speakers bureaus for pharmaceutical companies that have an interest in the topic covered in this article.

This is part I of a two-part article. Next month, part II will discuss patient assessment and management of opioid use. A version of this article originally appeared in our sister publication, the Journal of Musculoskeletal Medicine, in March 2006.

References

1. Chou R, Clark E, Helfand M. Com­parative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: a systematic review. J Pain Symptom Manage 2003;26(5):1026-1048.2. Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain 2004;112(3):372-380.
3. Zenz MK, Strump M, Tryba M. Long-term oral opioid therapy in patients with chronic nonmalignant pain. J Pain Symp­tom Manage 1992;7:69-77.4. Portenoy RK. Using opioids for chronic nonmalignant pain: current thinking. Intern Med 1996;17(suppl):S25-S31.
5. Mercadante S, Ferrera P, Villari P. Hyper­algesia: an emerging iatrogenic syndrome. J Pain Symptom Manage 2003;26(2):769-775.    6. Rajagopal A, Vassilopoulou-Sellin R, Palmer JL, et al. Hypogonadism and sexual dysfunction in male cancer survivors receiving chronic opioid therapy. J Pain Symptom Manage 2003;26(5):1055-1061.
7. Jamison RN, Schein JR, Vallow S, et al. Neuropsychological effects of long-term opioid use in chronic pain patients. J Pain Symptom Manage 2003;26(4):913-921.8. Sabatowski R, Schwalen S, Rettig K, et al. Driving ability under long-term treatment with transdermal fentanyl. J Pain Symptom Manage 2003;25(1):38-47.
9. Fishbain DA, Cutler RG, Rosomoff HL, Rosomoff RJ. Are opioid-dependent/tolerant patients impaired in driving-related skills? A structured evidence-based interview. J Pain Palliat Care Pharmacother 2002;16(1):9-28.10. American Society of Addiction Medi­cine. Public policy statement on definitions related to the use of opioids in pain management/public policy statement on the rights and responsibilities of physicians in the use of opioids for the treatment of pain. J Addict Dis 1998;17:129-133.
11. Portenoy RK. Opioid therapy for chronic nonmalignant pain: current status. In: Fields HL, Liebeskind JC, eds. Pharma­cologic approaches to the treatment of chronic pain: new concepts and critical issues. Seattle: IASP Publications, 1994:247-287.12. American Academy of Pain Medicine and American Pain Society. The use of opioids for the treatment of chronic pain. Chicago; 1994. Position paper.
13. Dunbar SA, Katz NP. Chronic opioid therapy for nonmalignant pain in patients with a history of substance abuse: report of 20 cases. J Pain Symptom Manage 1996;11:163-171.