Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Current Osteoporosis Reports
Published in: Current Osteoporosis Reports 5/2018

Open Access 01-10-2018 | Bone and Joint Pain (T King and S Amin, Section Editors)

Mechanisms of Osteoarthritis (OA) Pain

Authors: Terence W. O’Neill, David T. Felson

Published in: Current Osteoporosis Reports | Issue 5/2018

Login to get access

Abstract

Purpose of Review

Osteoarthritis (OA) is a major cause of pain and disability worldwide. There is, however, a relatively poor correlation between the severity of OA based on plain radiograph changes and symptoms. In this review, we consider the mechanisms of pain in OA.

Recent Findings

It is now widely recognised that OA is a disease of the whole joint. Data from large observational studies which have used magnetic resonance imaging (MRI) suggest that pain in OA is associated with a number of structural factors including the presence of bone marrow lesions (BMLs) and also synovitis. There is evidence also of alterations in nerve processing and that both peripheral and central nerve sensitisation may contribute to pain in OA.

Summary

Identification of the causes of pain in an individual patient may be of benefit in helping to better target with appropriate therapy to help reduce their symptoms and improve function.
Literature
1.
Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 1998;41:778–99.CrossRefPubMed
2.
3.
Guccione AA, Felson DT, Anderson JJ, Anthony JM, Zhang Y, Wilson PW, et al. The effects of specific medical conditions on the functional limitations of elders in the Framingham study. Am J Public Health. 1994;84:351–8.CrossRefPubMedPubMedCentral
4.
Hunter DJ, Schofield D, Callander E. The individual and socioeconomic impact of osteoarthritis. Nat Rev Rheumatol. 2014;10:437–41.CrossRefPubMed
5.
Lawrence JS, Bremner JM, Bier F. Osteoarthrosis; prevalence in the population and relationship between symptoms and x-ray changes. Ann Rheum Dis. 1966;25:1–24.CrossRefPubMedPubMedCentral
6.
Dieppe PA. Relationship between symptoms and structural change in osteoarthritis. What are the important targets for osteoarthritis therapy? J Rheumatol (Suppl). 2004;70:50–3.
7.
Doherty M, Bijlsma J, Arden N, Hunter DJ, Dalbeth N. Introduction : what is osteoarthritis? In: Doherty M, Bijlsma J, Arden N, Hunter DJ, Dalbeth N, editors. Oxford textbook of osteoarthritis and crystal Arthropathy. 3rd ed. Oxford: OUP; 2016. p. 3–12.CrossRef
8.
Hannan MT, Felson DT, Pincus T. Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee. J Rheumatol. 2000;27:1513–7.PubMed
9.
10.
Hunter DJ, Roemer FW. Imaging: magnetic resonance imaging. In: Doherty M, Bijlsma J, Arden N, Hunter DJ, Dalbeth N, editors. Oxford textbook of osteoarthritis and crystal Arthropathy. 3rd ed. Oxford: OUP; 2016. p. 177–89.
11.
Grönblad M, Liesi P, Korkala O, Karaharju E, Polak J. Innervation of human bone periosteum by peptidergic nerves. Anat Rec. 1984;209:297–9.CrossRefPubMed
12.
Reimann I, Christensen SB. A histological demonstration of nerves in subchondral bone. Acta Orthop Scand. 1977;48:345–52.CrossRefPubMed
13.
Hirasawa Y, Okajima S, Ohta M, Tokioka T. Nerve distribution to the human knee joint: anatomical and immunohistochemical study. Int Orthop. 2000;24:1–4.CrossRefPubMedPubMedCentral
14.
Hukkanen M, Konttinen YT, Rees RG, Santavirta S, Terenghi G, Polak JM. Distribution of nerve endings and sensory neuropeptides in rat synovium, meniscus and bone. Int J Tissue React. 1992;14:1–10.PubMed
15.
Ashraf S, Wibberley H, Mapp PI, Hill R, Wilson D, Walsh DA. Increased vascular penetration and nerve growth in the meniscus: a potential source of pain in osteoarthritis. Ann Rheum Dis. 2011;70:523–9.CrossRefPubMed
16.
17.
Dye SF, Vaupel GL, Dye CC. Conscious neurosensory mapping of the internal structures of the human knee without intra-articular anaesthesia. Am J Sports Med. 1998;26:773–7.CrossRefPubMed
18.
Suri S, Gill SE, Massena de Camin S, Wilson D, McWilliams DF, Walsh DA. Neurovascular invasion at the osteochondral junction and in osteophytes in osteoarthritis. Ann Rheum Dis. 2007;66:1423–8.CrossRefPubMedPubMedCentral
19.
20.
Felson DT, Chaisson CE, Hill CL, Totterman SM, Gale ME, Skinner KM, et al. The association of bone marrow lesions with pain in knee osteoarthritis. Ann Intern Med. 2001;134:541–9.CrossRefPubMed
21.
Hill CL, Gale DG, Chaisson CE, Skinner K, Kazis L, Gale ME, et al. Knee effusions, popliteal cysts, and synovial thickening: association with knee pain in osteoarthritis. J Rheumatol. 2001;28:1330–7.PubMed
22.
Hill CL, Gale DR, Chaisson CE, Skinner K, Kazis L, Gale ME, et al. Periarticular lesions detected on magnetic resonance imaging: prevalence in knees with and without symptoms. Arthritis Rheum. 2003;48:2836–44.CrossRefPubMed
23.
• Barr AJ, Campbell TM, Hopkinson D, Kingsbury SR, Bowes MA, Conaghan PG. A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis. Arthritis Res Ther. 2015;17:228–64. In this comprehensive review, the authors looked at published data concerning the relationship between subchondral bone features in peripheral OA, symptoms and structural progression of disease. The data suggest that there are independent associations between imaging assessed bone pathology, structural progression and pain in the knee, hip and hand . CrossRefPubMedPubMedCentral
24.
Zanetti M, Bruder E, Romero J, Hodler J. Bone marrow edema pattern in osteoarthritic knees: correlation between MR imaging and histologic findings. Radiology. 2000;215:835–40.CrossRefPubMed
25.
Taljanovic MS, Graham AR, Benjamin JB, Gmitro AF, Krupinski EA, Schwartz SA, et al. Bone marrow edema pattern in advanced hip osteoarthritis: quantitative assessment with magnetic resonance imaging and correlation with clinical examination, radiographic findings, and histopathology. Skelet Radiol. 2008;37:423–31.CrossRef
26.
Felson DT, Niu J, Guermazi A, Roemer F, Aliabadi P, Clancy M, et al. Correlation of the development of knee pain with enlarging bone marrow lesions on magnetic resonance imaging. Arthritis Rheum. 2007;56:2986–92.CrossRefPubMed
27.
Davies-Tuck ML, Wluka AE, Wang Y, English DR, Giles GG, Cicuttini F. The natural history of bone marrow lesions in community based adults with no clinical osteoarthritis. Ann Rheum Dis. 2009;68:904–8.CrossRefPubMed
28.
Zhang Y, Nevitt M, Niu J, Lewis C, Torner J, Guermazi A, et al. Fluctuation of knee pain and changes in bone marrow lesions, effusions, and synovitis on magnetic resonance imaging. Arthritis Rheum. 2011;63:691–9.CrossRefPubMed
29.
Callaghan MJ, Parkes MJ, Hutchinson CE, Gait AD, Forsythe LM, Marjanovic EJ, et al. A randomised trial of a brace for patellofemoral osteoarthritis targeting knee pain and bone marrow lesions. Ann Rheum Dis. 2015;74:1164–70.CrossRefPubMed
30.
Ayral X, Pickering EH, Woodworth TG, Mackillop N, Dougados M. Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis -- results of a 1 year longitudinal arthroscopic study in 422 patients. Osteoarthr Cartil. 2005;13:361–7.CrossRef
31.
Roemer FW, Javaid KM, Guermazi A, Thomas M, Kiran A, Keen R, et al. Anatomical distribution of synovitis in knee osteoarthritis and its association with joint effusion assessed on non-enhanced and contrast-enhanced MRI. Osteoarthr Cartil. 2010;18:1269–74.CrossRef
32.
Loeuille D, Chary-Valckenaere I, Champigneulle J, Rat AC, Toussaint F, Pinzano-Watrin A, et al. Macroscopic and microscopic features of synovial membrane inflammation in the osteoarthritic knee: correlating magnetic resonance imaging findings with disease severity. Arthritis Rheum. 2005;52:3492–501.CrossRefPubMed
33.
Hill CL, Hunter DJ, Niu J, Clancy M, Guermazi A, Genant H, et al. Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis. Ann Rheum Dis. 2007;66:1599–603.CrossRefPubMedPubMedCentral
34.
Baker K, Grainger A, Niu J, Clancy M, Guermazi A, Crema M, et al. Relation of synovitis to knee pain using contrast enhanced MRIs. Ann Rheum Dis. 2010;69:1779–83.CrossRefPubMed
35.
• O'Neill TW, Parkes MJ, Maricar N, Marjanovic EJ, Hodgson R, Gait AD, et al. Synovial tissue volume: a treatment target in knee osteoarthritis (OA). Ann Rheum Dis. 2016;75:84–90. In this open-label study in men and women with symptomatic knee OA, intra-articular steroid therapy was associated with a significant improvement in knee pain and a reduction in synovial tissue volume (an indicator of synovitis) with a significant correlation between change in knee pain and change in synovial tissue volume (STV). Among those whose pain subsequently recurred, STV also increased. The correlation between change in pain and change in STV was relatively small, however, suggesting the importance of other structural/non-structural factors in explaining pain in OA. CrossRefPubMed
36.
Phan CM, Link TM, Blumenkrantz G, Dunn TC, Ries MD, Steinbach LS, et al. MR imaging findings in the follow-up of patients with different stages of knee osteoarthritis and the correlation with clinical symptoms. Eur Radiol. 2006;16:608–18.CrossRefPubMed
37.
Moisio K, Eckstein F, Chmiel JS, Guermazi A, Prasad P, Almagor O, et al. Denuded subchondral bone and knee pain in persons with knee osteoarthritis. Arthritis Rheum. 2009;60:3703–10.CrossRefPubMedPubMedCentral
38.
Torres L, Dunlop DD, Peterfy C, Guermazi A, Prasad P, Hayes KW, et al. The relationship between specific tissue lesions and pain severity in persons with knee osteoarthritis. Osteoarthr Cartil. 2006;14:1033–40.CrossRef
39.
Hernández-Molina G, Neogi T, Hunter DJ, Niu J, Guermazi A, Reichenbach S, et al. The association of bone attrition with knee pain and other MRI features of osteoarthritis. Ann Rheum Dis. 2008;67:43–7.CrossRefPubMed
40.
Englund M, Niu J, Guermazi A, Roemer FW, Hunter DJ, Lynch JA, et al. Effect of meniscal damage on the development of frequent knee pain, aching, or stiffness. Arthritis Rheum. 2007;56:4048–54.CrossRefPubMed
41.
Amin S, Guermazi A, Lavalley MP, Niu J, Clancy M, Hunter DJ, et al. Complete anterior cruciate ligament tear and the risk for cartilage loss and progression of symptoms in men and women with knee osteoarthritis. Osteoarthr Cartil. 2008;16:897–902.CrossRef
42.
43.
So A, Patel J, Jones A. Pain: mechanisms and management. In: Bijlsma JWJ, Hachulla E, editors. EULAR textbook of rheumatic diseases. 2nd ed. London: BMJ Publishing Group; 2015. p. 1332–53.
44.
45.
Woolf CJ, Safieh-Garabedian B, Ma QP, Crilly P, Winter J. Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity. Neuroscience. 1994;62:327–31.CrossRefPubMed
46.
Halliday DA, Zettler C, Rush RA, Scicchitano R, McNeil JD. Elevated nerve growth factor levels in the synovial fluid of patients with inflammatory joint disease. Neurochem Res. 1998;23:919–22.CrossRefPubMed
47.
Nicol GD, Vasko MR. Unravelling the story of NGF-mediated sensitization of nociceptive sensory neurons: ON or OFF the Trks? Mol Interv. 2007;7:26–41.CrossRefPubMed
48.
Ghilardi JR, Freeman KT, Jimenez-Andrade JM, Coughlin K, Kaczmarska MJ, Castaneda-Corral G, et al. Neuroplasticity of sensory and sympathetic nerve fibers in the painful arthritic joint. Arthritis Rheum. 2012;64:2223–32.CrossRefPubMedPubMedCentral
49.
Lane NE, Schnitzer TJ, Birbara CA, Mokhtarani M, Shelton DL, Smith MD, et al. Tanezumab for the treatment of pain from osteoarthritis of the knee. N Engl J Med. 2010;363:1521–31.CrossRefPubMedPubMedCentral
50.
• Brown MT, Murphy FT, Radin DM, Davignon I, Smith MD, West CR. Tanezumab reduces osteoarthritic knee pain: results of a randomized, double-blind, placebo-controlled phase III trial. J Pain. 2012;13:790–8. Tanezumab is a monoclonal antibody directed against nerve growth factor (NGF) that blocks the interaction of NGF with its receptors. This phase III double-blind RCT showed that NGF blockade by tanezumab had superior analgesic efficacy in OA of the knee compared with placebo. CrossRefPubMed
51.
Brown MT, Murphy FT, Radin DM, Davignon I, Smith MD, West CR. Tanezumab reduces osteoarthritic hip pain. Results of a randomised, double-blind, placebo-controlled phase III trial. Arthritis Rheum. 2013;65:1795–803.CrossRefPubMed
52.
Lluch E, Torres R, Nijs J, Van Oosterwijck J. Evidence for central sensitization in patients with osteoarthritis pain: a systematic literature review. Eur J Pain. 2014;18:1367–75.CrossRefPubMed
53.
Rahman W, Dickenson AH. Osteoarthritis-dependent changes in anti-nociceptive action of Nav1.7 and Nav1.8 sodium channel blockers: an in vivo electrophysiological study in the rat. Neuroscience. 2015;295:103–16.CrossRefPubMed
54.
Neogi T, Guermazi A, Roemer F, Nevitt MC, Scholz J, Arendt-Nielsen L, et al. Association of joint inflammation with pain sensitisation in knee osteoarthritis: the multicentre osteoarthritis study. Arthritis Rheumatol. 2016;68:654–61.CrossRefPubMedPubMedCentral
55.
Arendt-Nielsen L. Pain sensitisation in osteoarthritis. Clin Exp Rheumatol. 2017;35(Suppl 107):S68–74.
56.
Hochberg MC, Wohlreich M, Gaynor P, Hanna S, Risser R. Clinically relevant outcomes based on analysis of pooled data from 2 trials of duloxetine in patients with knee osteoarthritis. J Rheumatol. 2012;39:352–8.CrossRefPubMed
Metadata
Title
Mechanisms of Osteoarthritis (OA) Pain
Authors
Terence W. O’Neill
David T. Felson
Publication date
01-10-2018
Publisher
Springer US
Published in
Current Osteoporosis Reports / Issue 5/2018
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-018-0477-1

Other articles of this Issue 5/2018

Current Osteoporosis Reports 5/2018 Go to the issue

Epidemiology and Pathophysiology (F Cosman and D Shoback, Section Editors)

Vertebral Fracture Identification as Part of a Comprehensive Risk Assessment in Patients with Osteoporosis

Regenerative Biology and Medicine in Osteoporosis (T Webster, Section Editor)

Carbon Nanomaterials for Treating Osteoporotic Vertebral Fractures

Epidemiology and Pathophysiology (F Cosman and D Shoback, Section Editors)

The Influence of Cortical Porosity on the Strength of Bone During Growth and Advancing Age

Epidemiology and Pathophysiology (F Cosman and D Shoback, Section Editors)

Current Understanding of the Pathophysiology of Osteonecrosis of the Jaw

Muscle and Bone (L Bonewald and M Hamrick, Section Editors)

Targeting the Muscle-Bone Unit: Filling Two Needs with One Deed in the Treatment of Duchenne Muscular Dystrophy

Bone and Joint Pain (T King and S Amin, Section Editors)

Mechanisms for Joint Pain in Rheumatoid Arthritis (RA): from Cytokines to Central Sensitization