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Current Rheumatology Reports
Published in: Current Rheumatology Reports 6/2012

01-12-2012 | RHEUMATIC MANIFESTATIONS OF OTHER DISEASES (R STAUD, SECTION EDITOR)

Mechanisms of Chronic Pain in Osteoarthritis

Author: Hans-Georg Schaible

Published in: Current Rheumatology Reports | Issue 6/2012

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Abstract

Pain is a major clinical problem of osteoarthritis (OA). Recently, OA has been thought to be a disease of the whole joint with both destruction of cartilage and inflammatory components such as synovitis and bone marrow lesions. Clinical studies have documented a significant inflammatory soft tissue contribution to the severity and frequency of OA pain. Both clinical and experimental studies have provided evidence for the sensitization of pain pathways during OA, involving pronounced changes in joint nociceptors and changes of the nociceptive processing in the spinal cord, brainstem, and thalamocortical system. Additionally, evidence has been provided for neuropathic pain components in OA models. Concerning molecular mechanisms of OA pain and potential options for pain therapy, studies on nerve growth factor, cytokines, sodium channel blockers, hyaluronic acid preparations, and others are addressed in this review.
Literature
1.
Breivik H, Collett B, Ventafridda V, et al. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006;10:287–333.PubMedCrossRef
2.
Felson DT. Developments in the clinical understanding of osteoarthritis. Arthritis Res Ther. 2009;11:203.PubMedCrossRef
3.
Konttinen YT, Sillat T, Barreto G, et al. Osteoarthritis as an autoinflammatory disease caused by chondrocyte-mediated inflammatory responses. Arthritis Rheum. 2012;64:613–6.PubMedCrossRef
4.
5.
Bondeson J, Blom AB, Wainwright S. The role of synovial macrophages and macrophage-produced mediators in driving inflammatory and destructive responses in osteoarthritis. Arthritis Rheum. 2010;62:647–57.PubMedCrossRef
6.
• Zhang Y, Nevitt M, Niu J, 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. This paper reports important data on the sources of pain in patients with knee OA.PubMedCrossRef
7.
Ordeberg G. Evidence of sensitization to pain in human osteoarthritis. In: Felson DT, Schaible H-G, editors. Pain in osteoarthritis. Hoboken: Wiley Blackwell; 2009. p. 199–209.
8.
Hochman JR, Gagliese L, Davis AM, Hawker GA. Neuropathic pain symptoms in a community knee OA cohort. Osteoarthritis Cartilage. 2011;19:647–54.PubMedCrossRef
9.
Eckstein F, Cotofana S, Wirth W, et al. Greater rates of cartilage loss in painful knees than in pain-free knees after adjustment for radiographic disease stage. Arthritis Rheum. 2011;63:2257–67.PubMedCrossRef
10.
Wittoek R, Cruyssen BV, Verbruggen G. Predictors of functional impairment and pain in erosive osteoarthritis of the interphalangeal joints. Arthritis Rheum. 2012;64:1430–6.PubMedCrossRef
11.
Schaible H-G. Joint pain – Basic mechanisms. In: McMahon SB, Koltzenburg M, editors. Wall and Melzack´s textbook of pain. 6th ed. Oxford: Elsevier; 2012. in press.
12.
Im H-J, Kim J-S, Li X, et al. Alteration of sensory neurons and spinal response to an experimental osteoarthritis pain model. Arthritis Rheum. 2010;62:2995–3005.PubMedCrossRef
13.
Ivanavicius SP, Ball AD, Heapy CG, et al. Structural pathology in a rodent model of osteoarthritis is associated with neuropathic pain: increased expression of ATF-3 and pharmacological characterisation. Pain. 2007;128:272–82.PubMedCrossRef
14.
Orita S, Ishikawa T, Miyagi M, et al. Pain-related sensory innervation in monoiodoacetate-induced osteoarthritis in rat knees that gradually develops neuronal injury in addition to inflammatory pain. BMC Musculoskelet Disord. 2011;12:134.PubMedCrossRef
15.
Liu P, Okun A, Guo R-C, et al. Ongoing pain in the MIA model of osteoarthritis. Neurosci Lett. 2011;493:72–5.PubMedCrossRef
16.
Ferland CE, Levrty S, Beaudry F, Vachon P. Gait analysis and pain response of two rodent models of osteoarthritis. Pharmacol Biochem Behav. 2011;97:603–10.PubMedCrossRef
17.
Malfait AM, Ritchie J, Gil AS, et al. ADAMTS-5 deficient mice do not develop mechanical allodynia associated with osteoarthritis following medial meniscal destabilization. Osteoarthritis Cartilage. 2010;18:572–80.PubMedCrossRef
18.
19.
Schuelert N, McDougall JJ. Grading of monosodium iodoacetate-induced osteoarthritis reveals a concentration-dependent sensitization of nociception in the knee joint of the rat. Neurosci Lett. 2009;465:184–8.PubMedCrossRef
20.
McDougall JJ, Andruski B, Schuelert N, et al. Unravelling the relationship between age, nociception and joint destruction in naturally occurring osteoarthritis of Dunkin Hartley guinea pigs. Pain. 2009;141:222–32.PubMedCrossRef
21.
Schaible H-G, Ebersberger A, Natura G. Update on peripheral mechanisms of pain: beyond prostaglandins and cytokines. Arthritis Res Ther. 2011;13:210.PubMedCrossRef
22.
•• Lane NE, Schnitzer TJ, Birbara CA, et al. Tanezumab for the treatment of pain from osteoarthritis of the knee. N Engl J Med. 2010;363:1521–31. This study shows for the first time the use of a monoclonal antibody to NGF in pain treatment in patients with moderate to severe OA pain.PubMedCrossRef
23.
Nagashima H, Suzuki M, Araki S, et al. Preliminary assessment of the safety and efficacy of tenazumab in Japanese patients with moderate to severe osteoarthritis of the knee: a randomized, double-blind, dose-escalation, placebo-controlled study. Osteoarthritis Cartilage. 2011;19:1405–12.PubMedCrossRef
24.
Schnitzer TJ, Lane NE, Birbara C, et al. Long-term open-label study of tanezumab for moderate to severe osteoarthritis. Osteoarthritis Cartilage. 2011;19:639–46.PubMedCrossRef
25.
Bennett D. NGF, sensitization of nociceptors. In: Schmidt RF, Willis WD, editors. Encyclopedia of pain, volume 2. Berlin, Heidelberg New York, Tokyo: Springer; 2007. p. 1338–42.CrossRef
26.
McNamee KE, Burleigh A, Gompels LL, et al. Treatment of murine osteoarthritis with TrkAd5 reveals a pivotal role for nerve growth factor in non-inflammatory joint pain. Pain. 2010;149:386–92.PubMedCrossRef
27.
Richter F, Natura G, Loeser S, et al. Tumor necrosis factor-α (TNF-α) causes persistent sensitization of joint nociceptors for mechanical stimuli. Arthritis Rheum. 2010;62:3806–14.PubMedCrossRef
28.
Schaible H-G, Segond von Banchet G, Boettger MK, et al. The role of proinflammatory cytokines in the generation and maintenance of joint pain. Ann N Y Acad Sci. 2010;1193:60–9.PubMedCrossRef
29.
Boettger MK, Leuchtweis J, Kümmel D, et al. Differential effects of locally and systemically administered soluble glycoprotein 130 on pain and inflammation in experimental arthritis. Arthritis Res Ther. 2010;12:R140.PubMedCrossRef
30.
Attur M, Belitskaya-Lévy I, Oh C, et al. Increased interleukin-1ß gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheum. 2011;63:1908–17.PubMedCrossRef
31.
Schuelert N, McDougall JJ. Involvement of Nav1.8 sodium channels in the transduction of mechanical pain in a rodent model of osteoarthritis. Arthritis Res Ther. 2012;14:R5.PubMedCrossRef
32.
Schuelert N, Zhang C, Mogg AJ, et al. Paradoxical effects of the cannabinoid CB(2) receptor agonist GW405833 on rat osteoarthritic knee joint pain. Osteoarthritis Cartilage. 2010;18:1536–43.PubMedCrossRef
33.
Zhang W, Robertson J, Jones AC, Dieppe PA, Doherty M. The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis. 2008;67:1716–23.PubMedCrossRef
34.
Boettger MK, Kümmel D, Harrison A, Schaible H-G. Evaluation of long-term antinociceptive properties of of stabilized hyaluronic acid preparation (NASHA) in an animal model of repetitive joint pain. Arthritis Res Ther. 2011;13:R110.PubMedCrossRef
35.
Jorgensen A, Stengaard-Pedersen K, Simonsen O, et al. Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double blind study of 337 patients followed for 1 year. Ann Rheum Dis. 2010;69:1097–102.PubMedCrossRef
36.
Chevalier X, Jerosch J, Goupille P, et al. Single, intraarticular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo controlled trial. Ann Rheum Dis. 2010;69:113–9.PubMedCrossRef
37.
Berenbaum F, Grifka J, Cazzaniga J, et al. A randomised, double-blind, controlled trial comparing two intra-articular hyaluronic acid preparations differing by their molecular weight in symptomatic knee osteoarthritis. Ann Rheum Dis. doi:10.​1136/​annrheumdis-2011-200972.
38.
Gomis A, Miralles A, Schmidt RF, Belmonte C. Intra-articular injections of hyaluronan solutions of different elastoviscosity reduce nociceptive nerve activity in a model of osteoarthritic knee joint of the guinea pig. Osteoarthritis Cartilage. 2009;17:798–804.PubMedCrossRef
39.
Ashraf S, Mapp PI, Walsh DA. Contributions of angiogenesis to inflammation, joint damage, and pain in a rat model of osteoarthritis. Arthritis Rheum. 2011;63:2700–10.PubMedCrossRef
40.
Arendt-Nielsen L, Nie H, Laursen MB, et al. Sensitization in patients with painful knee osteoarthritis. Pain. 2010;149:573–81.PubMedCrossRef
41.
Rahman W, Bauer CS, Bannister K, et al. Descending serotoninergic facilitation and the antinociceptive effects of pregabalin in a rat model of osteoarthitic pain. Mol Pain. 2009;5:45.PubMedCrossRef
42.
Sagar DR, Staniaszek LE, Okine BN, et al. Tonic modulation of spinal hyperexcitability by the endocannabinoid receptor system in a rat model of osteoarthritis pain. Arthritis Rheum. 2010;62:3666–76.PubMedCrossRef
43.
Telleria-Diaz A, Schmidt M, Kreusch S, et al. Spinal antinociceptive effects of cyclooxygenase inhibition during inflammation: involvement of prostaglandins and endocannabinoids. Pain. 2010;148:26–35.PubMedCrossRef
44.
Kosek E, Ordeberg G. Lack of pressure pain modulation by heterotopic noxious conditioning stimulation in patients with painful osteoarthritis before, but not following surgical pain relief. Pain. 2000;88:69–78.PubMedCrossRef
45.
Gwilym SE, Keltner JR, Warnaby CE, et al. Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients. Arthritis Rheum. 2009;61:1226–34.PubMedCrossRef
46.
Kulkarni B, Bentley DE, Elliott R, et al. Arthritic pain is processed in brain areas concerned with emotions and fear. Arthritis Rheum. 2007;56:1345–54.PubMedCrossRef
47.
Gwilym SE, Filippini N, Douaud G, et al. Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty. Arthritis Rheum. 2010;62:2930–40.PubMedCrossRef
48.
Rodriguez-Raecke R, Niemeier A, Ihle K, et al. Brain gray matter decrease in chronic pain is the consequence and not the cause of pain. J Neurosci. 2009;29:13746–50.PubMedCrossRef
49.
Hess A, Axmann R, Rech J, et al. Blockade of TNF-α rapidly inhibits pain responses in the central nervous system. PNAS. 2011;108:3731–36.PubMedCrossRef
Metadata
Title
Mechanisms of Chronic Pain in Osteoarthritis
Author
Hans-Georg Schaible
Publication date
01-12-2012
Publisher
Current Science Inc.
Published in
Current Rheumatology Reports / Issue 6/2012
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-012-0279-x

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