Elsevier

The Lancet

Volume 365, Issue 9463, 12–18 March 2005, Pages 965-973
The Lancet

Seminar
Pathogenesis and management of pain in osteoarthritis

https://doi.org/10.1016/S0140-6736(05)71086-2Get rights and content

Summary

The term osteoarthritis describes a common, age-related, heterogeneous group of disorders characterised pathologically by focal areas of loss of articular cartilage in synovial joints, associated with varying degrees of osteophyte formation, subchondral bone change, and synovitis. Joint damage is caused by a mixture of systemic factors that predispose to the disease, and local mechanical factors that dictate its distribution and severity. Various genetic abnormalities have been described, but most sporadic osteoarthritis probably depends on minor contributions from several genetic loci. Osteoarthritic joint damage may be associated with clinical problems, but the severity of joint disease is only weakly related to that of the clinical problem. For this reason the associations and pathogenesis of pain are in as much need of investigation as joint damage. Subchondral bone and synovium may be responsible for nociceptive stimuli, and peripheral neuronal sensitisation is an important feature, and can result in normal activities (such as walking) causing pain. Central pain sensitisation can also occur, and psychosocial factors are important determinants of pain severity. We present a stepwise approach to the management of 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

Search strategy and selection criteria

We searched MEDLINE and Embase, combining the term “osteoarthritis” with “pain”, “genetics”, “genes”, “management”, or “treatment”.

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