Knuckling Down on Arthritis Pain

Pharmacy Times, Volume 0, 0

Arthritis is a generic term thatdescribes disorders of thejoint(s). The 2 most commonforms of arthritis are osteoarthritis (OA)and rheumatoid arthritis (RA), respectivelyaffecting 20 million and 2.5 millionAmericans annually.1,2

OA, also known as degenerative jointdisease or degenerative arthritis, is characterizedby the breakdown and abrasionof joint cartilage, leading to joint painand stiffness. Typically OA does notcause inflammation, deformity, or crippling.RA, on the other hand, is destructiveand is commonly a debilitating systemicinflammatory disease.1

One of the major factors affecting thequality of life (QOL) for those with arthritisis pain. Undertreatment of pain inpatients with either OA or RA may haveserious physiologic effects (decreasedimmune function, impaired wound healing)and psychological effects (anxiety,depression, suffering). The overall goalsof treatment for those suffering from OAor RA include slowing or correcting theunderlying disorder and identifying painas an issue to be addressed as soon asthe disease is diagnosed.2

Characteristics of Arthritis Pain

Symptoms associated with OA typicallyinclude aching, stiffness, and limitedrange of motion of the affected joint(s).Pain associated with OA often is describedas a deep, aching pain, and it maybecome 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 thatare affected are extremely painful, stiff,swollen, red, and warm to the touch.Initially, pain results from inflammationcausing tenderness and swelling. As thedisease progresses, erosion of the cartilageand bone contributes to the pain,and the pain may occur at rest and/orwith activity. Pain frequently is describedas aching or burning, moderately severein nature, and occurring with exacerbationsand remissions.1

Pharmacologic Management

For all types of arthritis pain, the primarymanagement of pain includes pharmacologictherapy, as well as a comprehensiveeducation process (emphasizingthe importance of treatment compliance,rest, and exercise) and nonpharmacologictreatment (emphasizing rehabilitationtherapy and support and/or possible surgicalintervention if applicable).1,2 Pharmacologictreatment decisions often arebased on clinical efficacy, adverse-effectprofile, dosing and frequency, patientpreference, and/or cost.


The primary goals of treatment for OAinclude decreasing joint pain, stiffness,and inflammation, improving and maintainingjoint function and mobility, andmaintaining or improving QOL.1-3 Pharmacologicoptions for the managementof OA pain include acetaminophen(APAP), nonsteroidal anti-inflammatorydrugs (NSAIDs), capsaicin, glucosamine,chondroitin, intra-articular injections (glucocorticoidsor hyaluronic acid), tramadol,and opioid analgesics.3 The Tableprovides an overview of these options.

The American College of Rheumatologyand the American Pain Society recommendAPAP as first-line therapy forpain management for OA.2,4 APAP is relativelysafe and, compared with NSAIDs, isas effective, better tolerated, and cheaper.2-5 Caution is needed with thosepatients who consume alcohol or whoare at high risk for hepatotoxicity. An adequatetrial of APAP should be conducted(ie, 2-3 g per day for several weeks)before APAP is considered ineffective.2

Subsequently, if inflammation is presentor patients have failed therapy withAPAP, NSAIDs are recommended. Althoughthe nonselective NSAIDs (cyclooxygenase[COX]-1 inhibitors) and the selective COX-2 inhibitors exhibit differentmechanisms of activity and differing toxicityprofiles, their clinical efficacy in OA issimilar.2,3 In general, the onset of analgesicactivity may be experienced withinhours; however, several weeks are necessarybefore the anti-inflammatoryeffects may be appreciated. For anygiven patient, the choice of NSAID oftenis based on personal experience (on thepart of the patient and/or the prescriber),toxicity risk, allergies, compliance issues,and cost.

If an inadequate response is obtainedwith one NSAID, a trial with other NSAIDsis warranted, allowing a sufficient trial(several weeks) for each agent for optimalclinical benefit.2,3 Although the COX-2selective agents have a decreased risk ofgastrointestinal (GI) and bleeding complications,recent cardiovascular eventsassociated with the COX-2 inhibitorsrequire an individualized and thoroughrisk-to-benefit assessment.6-9

Capsaicin, an enzyme found in hotpeppers, has shown clinical efficacywhen used alone or in combination withoral analgesics. Capsaicin is a topicalproduct that must be applied to theaffected joint(s) consistently 4 times aday prior to symptom occurrence, allowingseveral weeks for sufficient painrelief. Local irritation and burning arecommon at the initiation of therapy, andproper hand washing is necessary afterapplication.2,3

Two dietary supplements, glucosamineand chondroitin, have shown beneficialeffects in reducing pain, improvingmobility, and reducing joint-space narrowingin OA patients.2,10 Glucosamine, aproduct derived from chitin, has relativelylow bioavailability and minimal sideeffects (mainly GI). The onset of clinicalbenefits usually is reported within weeksafter initiating therapy. The AmericanPain Society recommends that all OApatients take 1500 mg of oral glucosaminesulfate daily.2

Chondroitin is a glycosaminoglycandemonstrating improvement in pain andfunction in a small number of clinicaltrials. Efficacy may be seen withinmonths after initiating treatment. Long-termeffectiveness and side effects needfurther evaluation.2

Intra-articular glucocorticoid injectionsare used in patients with intense flareups(evidence of severe joint inflammationand effusion). Limitations of this therapyinclude the potential for systemiceffects of steroids, local infection risk, anda limit to the number of injections allowedper year (maximum of 3 or 4).

Hyaluronic acid is another intra-articulartreatment option for those patientswho are unresponsive to other therapies.It is a constituent of normal cartilage, providinglubrication and shock absorbencyto the affected joint. Injections are administeredonce weekly for 3 or 5 weeks.Local side effects include acute jointswelling and skin reactions.2,3

Tramadol is a weak mu opioid agonistthat inhibits the reuptake of serotonin andnorepinephrine. This agent may be usedalone or in combination with APAP or anNSAID, generally when an NSAID is consideredineffective. Caution is required inelderly patients, in cases of renal insufficiencyor alcohol consumption, and inpatients with seizure history. Slow titrationis recommended. Drug interactions alsoexist (especially in patients takingmonoamine oxidase inhibitors).2

Opioid analgesics are useful for thosepatients who do not experience reliefwith APAP, NSAIDs, intra-articular injections,or topical therapy and/or when thepatient's QOL is affected by pain.2,3 Lowdoseopioid products combined withAPAP are initiated first, followed by pureopioid agonists (sustained-release morphineor oxymorphone, for example) forthose who need better pain control.Propoxyphene, codeine, meperidine, ormixed agonist/antagonists are not optimalopioid analgesics. They have potentiallyserious adverse central nervoussystem side effects. Thus they should beavoided for long-term chronic use andshould be avoided in elderly patients.11,12

Rheumatoid Arthritis

For patients with RA, 3 main classes ofdrugs are commonly used: disease-modifyingantirheumatic 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 indecreasing chronic pain. Responses usuallyare slow (taking weeks to months),and the toxicity profile may be severe.13-16

RA is primarily an inflammatory diseaseprocess; therefore, patients willbenefit from the addition of an antiinflammatoryagent. NSAIDs have beenhighly effective in reducing stiffness andpain associated with RA. As discussedpreviously, the clinical efficacy of allNSAIDs is considered equivalent. An adequatetrial should be allowed prior toswitching a patient to another NSAID oralternative therapy.2,14

Oral corticosteroids may be used inlow doses for symptomatic relief untilthe benefits of DMARDs take effect, orthey may be used in patients with difficult-to-control disease symptoms. Patientswho experience disease flare-upsalso may be candidates for high-dosesteroid bursts. Long-term complicationsassociated with steroids (infection risks,osteoporosis, hyperglycemia) often limittheir use.14,15 Calcium and vitamin D supplementationare recommended inpatients receiving long-term systemiccorticosteroid therapy.16 Intermittentintra-articular corticosteroids may be utilizedfor intense flare-ups associatedwith severe inflammation and effusion.2

APAP has a limited role in RA but maywarrant a trial if NSAIDs are ineffective.As with OA, topical capsaicin may beused as an adjunct for localized painrelief. In addition, tramadol and opioidanalgesics are treatment options forthose patients who are unresponsive toall other pain therapies and/or whoseQOL is affected by pain.2,13

Dr. Saadeh is an associate professor ofpharmacy practice at Ferris StateUniversity Sparrow Health System,Department of Pharmacy, Lansing,Mich.

For a list of references, send a stamped,self-addressed envelope to: ReferencesDepartment, Attn. A. Rybovic, PharmacyTimes, Ascend Media Healthcare,103 College Road East, Princeton, NJ 08540;or send an e-mail request