Pain Management in Inflammatory Arthritis
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.
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
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 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.