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12 Articles in Volume 11, Issue #1
Simultaneous Use of Stimulants 
and Opioids
Therapy for Management of Childbirth Perineal Tears and Post-Partum Pain
Measuring Clinical Outcomes of Chronic Pain Patients
Real-Time Functional Magnetic Resonance Imaging in Pain Management
A Non-Surgical Treatment for Carpal Tunnel Syndrome
Fibromyalgia, Chronic Widespread Pain, and the Fallacy of Pain from Nowhere
Sonoanatomy and Injection Technique of the Iliolumbar Ligament
Back Surgery That Does Not Relieve Pain
The Immune System and Headache
Diversity in Pharmacologic Treatment of Pain
Memantine for Migraine and Tension-Type Headache Prophylaxis
Pain Management in Inflammatory Arthritis

Pain Management in Inflammatory Arthritis

The optimal treatment course is patient specific and likely involves a multi-disciplinary team including a rheumatologist, primary care physician, physical therapists and allied health practitioners.

Arthritis or joint inflammation afflicts over 70 million Americans and makes the prevalence of this condition one of the highest for all medical health problems. The debate continues as to whether general arthritis is a medical condition (pathology) or whether this commonly made diagnosis has become a catchall term used to appease patient complaints but does little to validate those complaints. Is what we typically see on radiography in an aged spine representative of a disease process or are these merely a series of age-related and/or adaptive changes consistent with Wolffs law—namely, that bone tissue characteristics (appearance) will be determined by the forces/stresses imposed on this tissue. The corollary to Wolff’s law is Davis’s law, which addresses re-modeling of collagen-based tissue and espouses a similar premise: soft tissue also remodels according to the stresses imposed on it. We know that both bone and soft tissue will adapt accordingly to the forces that are encountered. Our environment plays a key role in how our tissues are shaped and sometimes these shapes take on uncharacteristic (abnormal) appearances—yet are functional nonetheless. It appears that there are a number of important factors that eventually determine whether a person manifests with chronic joint inflammation including both environment and genetics. 
For the purposes of this report, we will not address the garden variety joint aches that most people experience to some degree as part of injury or the aging process and typically referred to as common osteoarthritis (OA). Rather, we will address the more serious and debilitating inflammatory arthritides that are diagnosed using blood chemistry and/or lab-based biomarkers, radiology, biopsies/aspiration and via examination/observation. This is not to say that the more severe form of degenerative osteoarthritis cannot have an inflammatory component leading to arthralgia. We will, however, examine the arguably more serious and difficult to treat arthritis subgroup involving progressive bouts of inflammation and joint erosion which includes rheumatoid (RA) and gouty arthritis. 

Rheumatoid Arthritis

Figure 1. Comparative differences between a normal, osteoarthritic and rheumatoid joint. (Adapted from arthritic joints illustration by Medicine Net, Inc.)As seen in Figure 1, comparative differences between a normal, osteoarthritic and rheumatoid joint are illustrated with the key difference being that the swollen synovial membrane is both visible and palpable in an RA-afflicted joint. Inflammation is a hallmark sign and a distinguishing feature of RA with the distribution of the inflammation (symmetrical or asymmetrical) also being important. Generally in RA, the patient has symmetrical, small joint swelling such as in the feet, hands, wrists and knees. Another hallmark feature of RA is the presence of small nodules (rheumatoid nodules) around the fingers and elbows as illustrated in Figure 2. These nodules also help in the identification of RA and are used in the examination phase of the diagnostic process, along with blood tests that screen for C-reactive protein, sedimentation rate and specific antibodies such as the rheumatoid factor (RF), antinuclear antibodies (ANA), and the cyclic citrullinated peptide (CCP) antibodies—all of which are frequently found in persons with RA. 1 


Figure 2. A hallmark feature of rheumatoid arthritis (RA) is the presence of small nodules (rheumatoid nodules) around the fingers. The clinical manifestations of RA are due, in large part, to the histological changes that occur in this disease. RA is a systemic inflammatory disease and as such has multiple organ system manifestations but we will focus on those processes that affect the joints. We have mentioned that the synovium in RA can become inflamed and hypertrophied causing the joint to become swollen and hot (synovitis). The synovial membrane acts as an important source of nutrition for both hyaline and fibro-cartilage since each have an inherently poor vascularity and ability to self-nourish. In addition to a central nutrition function, synovial membranes manufacture synovial fluid and natural lubricants such as hyaluronic acid. In RA, the synovial membrane, which is usually a few cells thick, can be as much as 8 to10 cells thick. The composition of this matrix consists of inflammatory cells such as T and B lymphocytes, macrophages and mast cells along with new blood vessels (angiogenesis) and all acting to choke the function out of the synovium. Hypertrophied synovium is referred to as pannus and it is this destructive mix of cell types that is thought to eventually lead to bone and cartilage erosion. 2 When this inflammatory substance collects in a stagnant manner for prolonged periods at a time, the surrounding tissue is adversely affected as well and includes the stimulation and release of proteolytic enzymes from both chondrocytes and synovial cells. These protein-destroying enzymes will eventually cause proteoglycan lysis that leads to cartilage breakdown. Invading synovial tissue cause Figure 3. RA-afflicted joint on examination and on x-ray.a similar destruction in bone tissue by stimulating the release of prostaglandins and proteases—by both synovial cells and osteoclasts. The synovial fluid contained in the synovial space becomes infiltrated with neutrophils. The synovial space in a healthy joint is more of a potential space with very little fluid in the cavity itself. In RA, the fluid amount can be much greater thus forming synovial effusions that consist primarily of plasma filtrates having high protein content.

Radiologic Features

On plain film radiography, the RA joint is seen as having bony erosions and the hyaline cartilage is seen as being symmetrically reduced in height. This is consistent with cartilage degradation mediated either by chondrocytic action or from the neutrophil-infested synovial fluid previously mentioned. Figure 3 illustrates what an RA-afflicted joint might look like on x-ray. The greater the bony and cartilage damage within the joint, the greater the expected disability in a patient since the process of joint erosion is more often than not a painful one. In the later stages of RA, it is not unusual to find that painful, weak and unstable joints eventually succumb to biomechanical forces acting to cause joint deformity thus perpetuating the cycle of disability. The primary radiologic tool of choice to monitor RA continues to be radiography since it is cost effective and so allows accurate serial assessments to be performed on patients. This, in turn, allows for detection of disease progression using comparative studies. Conventional MRI has limited utility at this time partly due to the challenge of MRI application on small joints such as the MCP, PIP, DIP and IP joints of the hand. 
With regards to MRI, what is of interest and holds great promise is the use of sodium MRI studies—especially as it pertains to cartilage assessment. Initially developed to assess cartilage status in osteoarthritis, sodium MRI will inevitably find a wider array of clinical applications as research continues. The actual physical differences between conventional and sodium MRI equipment have to do with the magnet size, field strength and frequency. Since the coil in an MRI determines the frequency, sodium MRI requires a different coil since sodium resonates at a different frequency than hydrogen. Both hydrogen (as in conventional MRI) and sodium both exhibit an MR effect but at different frequencies. What sodium MRI looks for is the sodium content in the most abundant molecular chain that makes up cartilage, namely, glycosaminoglycans (GAG). These GAG molecules form proteoglycan which are important in the formation of hyaline cartilage. These Figure 4b. Similar inflammatory process of gout in the small joints of the hand.GAG molecules are also important in water retention and provide the cartilage “cushioning effect” in a healthy joint. Researchers feel that a reduction in the GAG content in cartilage is a precursor to arthritis. 3 Since sodium MRI reveals more information about cartilage than conventional MRI (by virtue of superior image resolution) this diagnostic test may have applications in detecting sub-clinical disease—in other words, underlying asymptomatic disease. Having a test that can predict the risk of disease in susceptible individuals could prove extremely valuable in conditions such as RA.

Clinical Manifestations/Treatment

Patients with more severe forms of RA will, in many cases, manifest not only with joint pain stemming from synovial effusions, bony erosions and cartilage degradation but also will have soft tissue involvement such as teno-synovitis of the flexor tendons in the hand, ankylosis of the carpal bones and nodular hyperplasia in the tendon sheath causing a “triggering” effect. These events can result in significant impairment in areas such as the hand and can lead to joint subluxation, dislocations and eventual auto-fusion. When the knees are involved, patients have an entirely new set of challenges relating to gait, dynamic balance and general weight-bearing limitations. Chronic swelling in joints leads to joint weakness through reflex muscle inhibition brought about by joint fluid. This weakness in the joints, especially the lower extremity, can represent safety issues for patients as they perform their ADLs that may include using stairs or lifting and carrying objects. The joint erosions and soft tissue swelling combine to make muscle/tendon strengthening very challenging for patients having such joint fragility. 
Treatment for inflammatory arthritis such as RA consists of a multimodal approach and includes pharmaceuticals such as salicylates and NSAIDs to reduce the production of prostaglandins which can trigger pain and inflammation. NSAIDs have largely replaced salicylate therapy and act to inhibit cox-1 and cox-2 (cyclo-oxygenase enzymes) since these help produce prostaglandins. Another class of drugs, known as disease modifying anti-rheumatic drugs (DMARDS), all act to interfere with the immune process that promotes inflammation. Biologic agents act to inhibit key factors responsible for the inflammatory responses in the immune system such as T-cell activation, TNF antagonists and IL-1 antagonists. Finally, the corticosteroid drugs are often used to suppress the total immune response thereby decreasing swelling and inflammation in tissue. Clearly the focus for pharmacotherapy is inflammation reduction or suppression. This is a laudable goal since the inflammatory response (small or large) is the prime factor in patients that eventually drives impairment. A large magnitude inflammatory response equates to more joint damage and disability. The restoration of function is usually carried out by both physical and occupational therapists who spend many hours training RA patients in the proper exercise type and dosage, efficient posture, proper shoe wear, joint conservation techniques and ADL re-training when necessary. These interventions are typically directed by a rheumatologist who is a specialist in arthritis management.

Gouty Arthritis

There are literally hundreds of arthritides but not all have a significantly debilitating inflammatory component to them. Gouty arthritis is unique and has been deliberately chosen to contrast with RA because of the unique underlying cause of inflammation in this particular condition. Inflammation or joint swelling can have many causes, with some etiologies having more serious implications than others and also may be more responsive to treatment in general. Gout is a result of abnormal purine metabolism that initially leads to an accumulation of uric acid in the blood (hyperuricemia) and, in susceptible persons, to the eventual deposition of urate crystals in joints—specifically the synovial lining and fluid. 4 As the immune system responds to the crystal deposition, the result is an influx of white blood cells and inflammatory chemical messengers causing a localized engorgement. The pressure build up and noxious stimulation by these inflammatory elements all lead to swelling, pain and extreme rubor and tenderness in the affected area. 5 There is a large male to female attack disparity, with males being afflicted more than twice as much as females. There are almost 5 million people having gouty arthritis disease in the US. 6 Figure 4a illustrates this gout phenotype with the classic shiny, swollen, red and inflamed (hot) toe. The great toe is a common area that is affected in those who have this disease. Figure 4b illustrates a similar inflammatory process in the small joints of the hand.

Clinical Manifestations

Gout can be suspected when a patient has painful attacks of arthritis at the base of the toes with ankles and knees being the next most common areas. Unlike RA, which shows a symmetrical distribution in joint affliction, gouty arthritis tends to manifest asymmetrically and attacks one joint at a time. Arthrocentesis, or joint aspiration, is particularly useful in diagnosing gout since uric acid crystals and infectious agents can be identified. In chronic gout, the formation of tophi or crystal deposits is not uncommon and these can appear virtually anywhere in the body including vocal cords and spinal cord areas, but are most often found around the fingers, elbows and great toe (see Figure 5a). In the more acute phases of gout, the bursal tissue is often a site of crystal deposition and often leads to a bursitis. Patients manifesting with gouty arthritis can have a very difficult time exercising and/or moving in general. When a joint contains sharp needle-like crystal depositions, motion can cause the crystalline particles to irritate and damage intra-articular surfaces. This is analogous to having a sac filled with glass shards that scrapes the inside of the joint at each twist and turn. In severe gout, these large crystalline deposits can become extremely painful and destructive to a joint making any type of joint motion difficult and leads to irreversible articular damage.
Acute attacks of gout can be brought on by overconsumption of purine-rich foods, alcohol (beer and liquor) and medications that might elevate the levels of uric acid. Like the RA patient, those who have gout are at higher risk for other diseases such as renal insufficiency. Many patients with gout often have pre-existing risk factors for renal disease such as hypertension and diabetes. The likelihood of a person with gout to develop renal stones is several times that of a healthy person. 7 Renal stones may precede the onset of gout in approximately 40% of patients since elevated uric acid levels could exist for many years prior to manifesting with gout. The increased uric acid load could conceivably affect other organ systems before manifesting as crystalline accumulation in a specific joint.

Diagnostic Tests

The definitive test for gouty arthritis is joint aspiration and subsequent lab analysis that confirms the presence of monosodium urate crystals in the joint. It is not enough to demonstrate high elevation of uric acid levels in the blood or hyper-uricemia. In fact, as many as 10% of patients manifesting with gout symptoms will have normal blood uric acid levels. 8 The sensitivity for synovial fluid analysis for crystals is 84% and specificity 100%. This form of analysis has a better probability of ruling in–versus ruling out—the condition of interest. Having said this, a high specificity might also be due to a preponderance of false negatives so corroborative testing is recommended. In later stages of gouty arthritis, radiography may be of benefit since crystalline depositions are identifiable on both ultrasonography—as a hyperechoic area often with acoustic shadowing consistent with imaging solid objects embedded in tissue—as well as x-ray findings of calcified tophi combined with erosions not typical of RA (see Figure 5b). Erosions that are more characteristic of gout include extra-capsular erosions often with overhanging edges. Oftentimes, the joint spaces continue to be well-maintained despite erosions and calcifications—unlike the RA afflicted joint whose space can be compromised. 9 

Gout Treatment

Figure 5a. Cronic gout of the elbow with formation of tophi or crystal deposits.Figure 5b. Xray showing manifestation of gout: calcified tophi combined with erosions not typical of RA.

Gouty arthritis is treated according to the phase of disease progression. For a patient in the acute phase, pain management is the key. The first line medications appear to be NSAIDs, steroidal agents (prednisone)—with medications like colchicine, probenecid and allopurinol used mostly in the more chronic stages of gout. Colchicine has been monitored closely in the US due to it’s inherent toxicity (narrow therapeutic window) and guidelines for the use of colchicine in gout have been made available for rheumatologists. 10 In general, for acute gout the goal is to reduce inflammation and pain. In the later stages of gout, the clinical goals progress to prevention of uric acid deposition in the joint. As in every patient situation, the various drug combinations need to be selected based on the patient profile including age, co-morbidities, drug interactions and sensitivities to medications (allergies).
In extreme cases of longstanding and untreated gout, orthopedic surgery might become necessary, although this scenario is not common. Joint debridement and possible replacement is always a possibility when joint destruction has occurred and the ability of a patient to compensate for these losses is poor. The role of conservative treatment such as physical therapy should be considered but not in the acute phase. We have, on occasion, provided transdermal iontophoresis, using dexamethasone as the active agent, and applied it locally and directly over the painful area. In cases where gouty arthritis has interfered with a person’s ability to work or recreate on a regular basis, deconditioning and weakness set in and provide a logical target for physical therapy. A therapeutic exercise program in the non-acute phase of gout can make good sense since these patients tend to have associated morbidities that also can be addressed or positively influenced by an exercise program—i.e., diabetes, hypertension, elevated trigycerides and excess weight. 


 Inflammatory arthritides exist in many forms and their causes are just as numerous. In many cases, precise mechanisms have not yet been identified. What is known is that they can be directly debilitating and associated with overall increases in all cause mortality since arthritides usually do not exist in isolation. The optimal treatment course is patient specific and likely involves a multi-disciplinary team consisting of rheumatologist, primary care physician and allied health practitioners to name a few. The pathogenesis of inflammatory arthritis is not always clear but those pathways that have been identified can often be modified and improved with appropriate pharmacotherapy including injections. To prevent further joint destruction and improve current joint and muscle capabilities, physicians can refer patients for physical and occupational therapy. Pool physical therapy has been very beneficial in rehabilitation of inflammatory joint conditions since it allows unrestricted motion and vigorous muscle contractions with minimal stress on the joints. Strong muscle contraction is a pre-requisite for joint stability which, in turn, is a pre-requisite for safe and efficient movement. When underlying inflammation can be controlled and managed, patients can have a good chance of living a full and active life. Not discussed in this report are the potential important roles of neutraceuticals and supplements, adequate rest/sleep and proper nutrition—all of which can impact the severity and progression of inflammatory arthritis.

Last updated on: December 28, 2012
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