Knuckling Down on Arthritis Pain

NOVEMBER 01, 2006
Claire Saadeh, PharmD

Arthritis is a generic term that describes disorders of the joint(s). The 2 most common forms of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA), respectively affecting 20 million and 2.5 million Americans annually.1,2

OA, also known as degenerative joint disease or degenerative arthritis, is characterized by the breakdown and abrasion of joint cartilage, leading to joint pain and stiffness. Typically OA does not cause inflammation, deformity, or crippling. RA, on the other hand, is destructive and is commonly a debilitating systemic inflammatory disease.1

One of the major factors affecting the quality of life (QOL) for those with arthritis is pain. Undertreatment of pain in patients with either OA or RA may have serious physiologic effects (decreased immune function, impaired wound healing) and psychological effects (anxiety, depression, suffering). The overall goals of treatment for those suffering from OA or RA include slowing or correcting the underlying disorder and identifying pain as an issue to be addressed as soon as the disease is diagnosed.2

Characteristics of Arthritis Pain

Symptoms associated with OA typically include aching, stiffness, and limited range of motion of the affected joint(s). Pain associated with OA often is described as a deep, aching pain, and it may become more severe as the disease progresses. The onset of pain may be gradual, affecting only a few joints initially, and it may be aggravated by exercise.1

For those suffering with RA, joints that are affected are extremely painful, stiff, swollen, red, and warm to the touch. Initially, pain results from inflammation causing tenderness and swelling. As the disease progresses, erosion of the cartilage and bone contributes to the pain, and the pain may occur at rest and/or with activity. Pain frequently is described as aching or burning, moderately severe in nature, and occurring with exacerbations and remissions.1

Pharmacologic Management

For all types of arthritis pain, the primary management of pain includes pharmacologic therapy, as well as a comprehensive education process (emphasizing the importance of treatment compliance, rest, and exercise) and nonpharmacologic treatment (emphasizing rehabilitation therapy and support and/or possible surgical intervention if applicable).1,2 Pharmacologic treatment decisions often are based on clinical efficacy, adverse-effect profile, dosing and frequency, patient preference, and/or cost.


The primary goals of treatment for OA include decreasing joint pain, stiffness, and inflammation, improving and maintaining joint function and mobility, and maintaining or improving QOL.1-3 Pharmacologic options for the management of OA pain include acetaminophen (APAP), nonsteroidal anti-inflammatory drugs (NSAIDs), capsaicin, glucosamine, chondroitin, intra-articular injections (glucocorticoids or hyaluronic acid), tramadol, and opioid analgesics.3 The Table provides an overview of these options.

The American College of Rheumatology and the American Pain Society recommend APAP as first-line therapy for pain management for OA.2,4 APAP is relatively safe and, compared with NSAIDs, is as effective, better tolerated, and cheaper.2-5 Caution is needed with those patients who consume alcohol or who are at high risk for hepatotoxicity. An adequate trial of APAP should be conducted (ie, 2-3 g per day for several weeks) before APAP is considered ineffective.2

Subsequently, if inflammation is present or patients have failed therapy with APAP, NSAIDs are recommended. Although the nonselective NSAIDs (cyclooxygenase [COX]-1 inhibitors) and the selective COX-2 inhibitors exhibit different mechanisms of activity and differing toxicity profiles, their clinical efficacy in OA is similar.2,3 In general, the onset of analgesic activity may be experienced within hours; however, several weeks are necessary before the anti-inflammatory effects may be appreciated. For any given patient, the choice of NSAID often is based on personal experience (on the part of the patient and/or the prescriber), toxicity risk, allergies, compliance issues, and cost.

If an inadequate response is obtained with one NSAID, a trial with other NSAIDs is warranted, allowing a sufficient trial (several weeks) for each agent for optimal clinical benefit.2,3 Although the COX-2 selective agents have a decreased risk of gastrointestinal (GI) and bleeding complications, recent cardiovascular events associated with the COX-2 inhibitors require an individualized and thorough risk-to-benefit assessment.6-9

Capsaicin, an enzyme found in hot peppers, has shown clinical efficacy when used alone or in combination with oral analgesics. Capsaicin is a topical product that must be applied to the affected joint(s) consistently 4 times a day prior to symptom occurrence, allowing several weeks for sufficient pain relief. Local irritation and burning are common at the initiation of therapy, and proper hand washing is necessary after application.2,3

Two dietary supplements, glucosamine and chondroitin, have shown beneficial effects in reducing pain, improving mobility, and reducing joint-space narrowing in OA patients.2,10 Glucosamine, a product derived from chitin, has relatively low bioavailability and minimal side effects (mainly GI). The onset of clinical benefits usually is reported within weeks after initiating therapy. The American Pain Society recommends that all OA patients take 1500 mg of oral glucosamine sulfate daily.2

Chondroitin is a glycosaminoglycan demonstrating improvement in pain and function in a small number of clinical trials. Efficacy may be seen within months after initiating treatment. Long-term effectiveness and side effects need further evaluation.2

Intra-articular glucocorticoid injections are used in patients with intense flareups (evidence of severe joint inflammation and effusion). Limitations of this therapy include the potential for systemic effects of steroids, local infection risk, and a limit to the number of injections allowed per year (maximum of 3 or 4).

Hyaluronic acid is another intra-articular treatment option for those patients who are unresponsive to other therapies. It is a constituent of normal cartilage, providing lubrication and shock absorbency to the affected joint. Injections are administered once weekly for 3 or 5 weeks. Local side effects include acute joint swelling and skin reactions.2,3

Tramadol is a weak mu opioid agonist that inhibits the reuptake of serotonin and norepinephrine. This agent may be used alone or in combination with APAP or an NSAID, generally when an NSAID is considered ineffective. Caution is required in elderly patients, in cases of renal insufficiency or alcohol consumption, and in patients with seizure history. Slow titration is recommended. Drug interactions also exist (especially in patients taking monoamine oxidase inhibitors).2

Opioid analgesics are useful for those patients who do not experience relief with APAP, NSAIDs, intra-articular injections, or topical therapy and/or when the patient's QOL is affected by pain.2,3 Lowdose opioid products combined with APAP are initiated first, followed by pure opioid agonists (sustained-release morphine or oxymorphone, for example) for those who need better pain control. Propoxyphene, codeine, meperidine, or mixed agonist/antagonists are not optimal opioid analgesics. They have potentially serious adverse central nervous system side effects. Thus they should be avoided for long-term chronic use and should be avoided in elderly patients.11,12

Rheumatoid Arthritis

For patients with RA, 3 main classes of drugs are commonly used: disease-modifying antirheumatic drugs (DMARDs), such as hydroxychloroquine, etanercept, infliximab; NSAIDs; and corticosteroids. DMARDs may delay disease progression, may alter the natural history of the disease, and indirectly are effective in decreasing chronic pain. Responses usually are slow (taking weeks to months), and the toxicity profile may be severe.13-16

RA is primarily an inflammatory disease process; therefore, patients will benefit from the addition of an antiinflammatory agent. NSAIDs have been highly effective in reducing stiffness and pain associated with RA. As discussed previously, the clinical efficacy of all NSAIDs is considered equivalent. An adequate trial should be allowed prior to switching a patient to another NSAID or alternative therapy.2,14

Oral corticosteroids may be used in low doses for symptomatic relief until the benefits of DMARDs take effect, or they may be used in patients with difficult-to-control disease symptoms. Patients who experience disease flare-ups also may be candidates for high-dose steroid bursts. Long-term complications associated with steroids (infection risks, osteoporosis, hyperglycemia) often limit their use.14,15 Calcium and vitamin D supplementation are recommended in patients receiving long-term systemic corticosteroid therapy.16 Intermittent intra-articular corticosteroids may be utilized for intense flare-ups associated with severe inflammation and effusion.2

APAP has a limited role in RA but may warrant a trial if NSAIDs are ineffective. As with OA, topical capsaicin may be used as an adjunct for localized pain relief. In addition, tramadol and opioid analgesics are treatment options for those patients who are unresponsive to all other pain therapies and/or whose QOL is affected by pain.2,13

Dr. Saadeh is an associate professor of pharmacy practice at Ferris State University Sparrow Health System, Department of Pharmacy, Lansing, Mich.

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