We searched MEDLINE and Embase, combining the term “osteoarthritis” with “pain”, “genetics”, “genes”, “management”, or “treatment”.
SeminarPathogenesis and management of pain in osteoarthritis
Introduction
Osteoarthritis is a common disorder of synovial joints. It is characterised pathologically by focal areas of damage to the articular cartilage, centred on load-bearing areas, associated with new bone formation at the joint margins (osteophytosis), changes in the subchondral bone, variable degrees of mild synovitis, and thickening of the joint capsule (figure 1).1 When this disease is advanced it is visible on plain radiographs, which show narrowing of joint space (due to cartilage loss), osteophytes, and sometimes changes in the subchondral bone (figure 2).2 Osteoarthritis can arise in any synovial joint in the body, but is most common in the hands, knees, hips, and spine. A single joint could be involved, but more commonly several joints are affected. This condition is strongly age-related, being less common before 40 years, but rising in frequency with age, such that most people older than 70 years have radiological evidence of osteoarthritis in some joints.3
The clinical problems associated with these pathological and radiographic changes include joint pain related to use, short-lasting inactivity stiffness of joints, pain on movement with a restricted range, and cracking of joints (crepitus). Pain is particularly important, and osteoarthritis is thought to be the biggest cause of the high rate of regional joint pain in older people.4, 5 However, the correlation between radiographic evidence of osteoarthritis and the symptomatic disease is rather weak. This raises issues relating to the definition of the so-called disease and to the extent to which we should be studying the cause of joint damage, or the causes of pain and physical disability in older people.
Section snippets
Scope
The purpose of this Seminar is to focus on three topical, important, inter-related, and controversial aspects of the disorder. First, we consider the relations between joint damage and joint pain, before reviewing some data about the risk factors and pathogenesis for each of these factors, concentrating on progression of joint damage and persistence of pain. We then consider the genetics of osteoarthritis, and the inter-related issue of the phenotypic expression of the disease. Finally, we
Joint damage and joint pain
Radiography has been the main method used to define osteoarthritis for epidemiological purposes. Community-based radiography studies show that this condition is extremely common in older people.3, 6, 7 But frequency data vary, partly because of population differences, perhaps also because of the use of different cut-off points to define the presence or absence of osteoarthritis, and because problems exist with the sensitivity of the radiograph.8, 9 The use of MRI and arthroscopy make it clear
Risk factors associated with joint damage and its progression
Problems with the definition of osteoarthritis, and the populations used to study it, affect the data available about risk factors. Many data about the risk factors for joint damage are available from community studies that have generally used the Kellgren and Lawrence X-ray grading system to define osteoarthritis.8 In addition to age, the other main risk factors for radiographic changes include family history, some inherited and developmental conditions that affect bone or joint growth or
The pathogenesis of joint damage
The tissue that has attracted most attention in relation to the pathogenesis of this disease is articular cartilage, largely because of the striking changes in this tissue in advanced osteoarthritis (figure 1). The surfaces of joints are covered by a thin layer of articular cartilage resting on subchondral bone. Cartilage does not have nerves or blood vessels, whereas both are plentiful in bone. Healthy joint cartilage distributes static and dynamic joint loading and decreases friction.
Risk factors for joint pain
Surprisingly few data are available about the risk factors for joint pain. Most published investigations assume that joint pathology is the main cause, and are then concerned with the search for factors other than radiographic changes that might explain the variance in pain in populations. But, as Hadler48 and others have pointed out, investigations into the epidemiology of pain, without assuming a disease cause, are probably worthwhile.
One review5 divided musculoskeletal pain in the community
The pathogenesis of joint pain
Cartilage is aneural, so whatever its role in the pathogenesis of joint damage, it cannot be the tissue that directly generates pain. By contrast, subchondral bone, periosteum, synovium, ligaments, and the joint capsule are all richly innervated and contain nerve endings that could be the source of nociceptive stimuli in osteoarthritis.55 Imaging studies at the knee joint have shown a correlation between pain and both synovitis and subchondral bone changes, suggesting that these two tissues
Phenotypes, genotypes, and classification
The spectrum of joint problems and symptoms experienced by people with so-called osteoarthritis is very wide. Many have suggested that this condition is a group of disorders with a similar pathological endpoint rather than a single disease entity, and many attempts have been made to subdivide osteoarthritis by the number and distribution of joints affected (generalised or localised osteoarthritis) or the presence or absence of any obvious cause (primary or secondary osteoarthritis).
Debate has
Diagnosis and assessment
The main clinical features of the disease make it, in general, an easily recognised clinical entity (panel).
In practice, the most common clinical problem is differentiation of painful osteoarthritis from three other common causes of regional or generalised joint pain in older people: referred pain, periarticular (soft-tissue) conditions, and somatisation (regional pain in the absence of any local pathological cause). Pain in lower limb joints can be referred from the spine, or from the joint
Principles of management
Several reviews and guidelines on the management of osteoarthritis exist, based on evidence from trials about the effectiveness of the various interventions available.47, 93, 94, 95 We do not intend to review these data, but rather outline some general principles that we believe are important for good management of people with this condition.
Although symptomatic osteoarthritis is very common in the community, much of it is mild, and progression to severe disease is fairly uncommon. Moreover, it
Conclusions
Osteoarthritis is an increasingly important public-health problem.99, 100 Over recent years good progress has been made in our understanding of many of the associations and pathogenic pathways responsible for both the pain and joint damage. As a result, we can develop theoretical strategies for primary prevention of joint damage, through reduction of obesity and joint trauma in particular, but these strategies seem unlikely to decrease osteoarthritis in the short term.47 Therefore, more
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