骨关节炎疼痛的机制

秦夕茹; 张立智

doi:10.16766/j.cnki.issn.1674-4152.001971

骨关节炎疼痛的机制

doi: 10.16766/j.cnki.issn.1674-4152.001971

秦夕茹¹,
张立智^2, ,

1.
同济大学附属杨浦医院全科，上海 200090
2.
同济大学附属杨浦医院骨科，上海 200090

基金项目:

国家自然科学基金面上项目 81572218

上海市自然科学基金 13ZR1439100

上海市卫生局局级课题面上项目科研基金 20124303

详细信息

通讯作者:
张立智，E-mail：drzhanglizhi001@163.com

中图分类号: R684.3 R441.1
计量
- 文章访问数: 202
- HTML全文浏览量: 155
- PDF下载量: 21
- 被引次数: 0
出版历程
- 收稿日期: 2020-09-05
- 网络出版日期: 2022-02-16

Mechanisms of Osteoarthritis Pain

QIN Xi-ru¹,
ZHANG Li-zhi^{2
, ,}

1.
Department of General Practice, Yangpu Hospital Affiliated to Tongji University, Shanghai 200090, China

摘要

摘要: 骨关节炎(osteoarthritis，OA)是最常见的关节疾病，其发病率逐年增加，目前尚无有效的治愈方法，是导致老年人功能残疾的常见原因之一。对膝OA的认识不足、预防及治疗延迟是导致其发病率逐年升高的重要原因。疼痛是OA的早期警示信号，也是OA的主要症状，还是临床最重要的诊断依据。由于目前对早期疼痛重视不足，对患者疼痛的原因和机制认识不足，常会导致OA疼痛的治疗效果不佳，患者对治疗效果不满意，病变持续进展，甚至导致患者关节残疾，最终需要进行关节置换。因此，很有必要了解疼痛产生的原因，疼痛的特点，疼痛的传导与感知，疼痛与骨关节炎病变发生、发展之间的关系，以及疼痛的病理生理学机制。研究显示，OA疼痛具有复杂的病理生理学机制，它不仅是异常应力和生物学作用下关节的伤害性疼痛，还和局部炎症、外周和中枢神经病变紧密相关，也受多种因素调节(如患者的精神、遗传因素和气候影响等)。而且，临床研究强调OA疼痛并不是单一的和固定不变的。疼痛的发生是可以独立于结构改变而存在的，而且在不同患者和不同的特定时间发生程度也不同。本文对OA疼痛机制的研究进展进行综述，以期有利于辅助医师在临床工作中探寻治疗效果不佳的原因，改善治疗效果，对疼痛进行从基础到临床科学地转化研究，有利于将来对OA疼痛患者进行最佳管理。
- 骨关节炎 /
- 疼痛 /
- 损伤 /
- 神经 /
- 调控因子
Abstract: Osteoarthritis (OA) is the most common joint disease, and its incidence is increasing by years. Currently, there is no effective cure, yet OA is one of the most common causes of functional disability in the elderly. The insufficient knowledge of knee OA and subsequent delayed prevention and treatment of knee OA are the important reasons leading to the increasing morbidity. In clinic, pain is one of the earliest signs in the early stages of OA. Pain is also the main symptom of OA and is one of the most important criteria for diagnosis. Owing to the frequent neglect of early OA pain and insufficient understanding of the cause and mechanism of OA pain, getting satisfactory treatment effect is often difficult. As a result, the incidence of complaints of patients is increasing. Subsequently, progress of the lesions is continuing, which are closely related to the joint disability of patients and eventually joint replacement. Therefore, the causes, characteristics, conduction and perception of pain; the relationship between pain occurrence and development of osteoarthritis and the pathophysiological mechanism of OA pain must be identified. Studies show that OA-related pain has a complex pathophysiologic mechanism, and it is not only a kind of joint injurious pain depending on abnormal stress and biological interplay but also closely related to local inflammation, peripheral and central neuropathy and regulated by a variety of factors (e.g. spirit, gene, weather, etc). Furthermore, clinical findings emphasize that OA is not a stable and linear condition. Pain experience is independent of structural modifications, and it occurs to varying degrees in a patient- and time-specific manner. Therefore, this review covers studies on the mechanisms of OA pain. The review is expected to be helpful for physicians to find the cause of poor curative effect and improve them, for researchers to make transformation from basic study to clinical work, for patients to acquire an optimal management relieving OA-related pain in the future.
- Osteoarthritis /
- Pain /
- Damage /
- Nervous /
- Regulatory factors

HTML全文

参考文献(42)

[1]	VAN DER HEIJDEN R A, OEI E H, BRON E E, et al. No difference on quantitative magnetic resonance imaging in patellofemoral cartilage composition between patients with patellofemoral pain and healthy controls[J]. Am J Sports Med, 2016, 44(5): 1172-1178. doi: 10.1177/0363546516632507
[2]	OKWERA A, MAY S. Views of general practitioners toward physiotherapy management of osteoarthritis-a qualitative study[J]. Physiother Theory Pract, 2019, 35(10): 940-946. doi: 10.1080/09593985.2018.1459987
[3]	MACKOWIAK J, JONES J T, DASA V. A comparison of 4-year total medical care costs, adverse outcomes, and opioid/prescription analgesic use for 3 knee osteoarthritis pain treatments: Intra-articular hyaluronic acid, intra-articular corticosteroids, and knee arthroplasty[J]. Semin Arthritis Rheum, 2020, 50(6): 1525-1534. doi: 10.1016/j.semarthrit.2020.01.003
[4]	KULKARNI K, KARSSIENS T, KUMAR V, et al. Obesity and osteoarthritis[J]. Maturitas, 2016, 89: 22-28. doi: 10.1016/j.maturitas.2016.04.006
[5]	TEIRLINCK C H, SONNEVELD D S, BIERMA-ZEINSTRA S M A, et al. Daily pain measurements and retrospective pain measurements in hip osteoarthritis patients with intermittent pain[J]. Arthritis Care Res (Hoboken), 2019, 71(6): 768-776. doi: 10.1002/acr.23711
[6]	FU K, ROBBINS S R, MCDOUGALL J J. Osteoarthritis: the genesis of pain[J]. Rheumatology (Oxford), 2018, 57(suppl_4): iv43-iv50. doi: 10.1093/rheumatology/kex419
[7]	DE LOGU F, GEPPETTI P. Ion channel pharmacology for pain modulation[J]. Handb Exp Pharmacol, 2019, 260: 161-186. doi: 10.1007/164_2019_336
[8]	O'NEILL T W, FELSON D T Mechanisms of osteoarthritis (OA) pain[J]. Curr Osteoporos Rep, 2018, 16(5): 611-616. doi: 10.1007/s11914-018-0477-1
[9]	HE B H, CHRISTIN M, MOUCHBAHANI-CONSTANCE S, et al. Mechanosensitive ion channels in articular nociceptors drive mechanical allodynia in osteoarthritis[J]. Osteoarthritis Cartilage, 2017, 25(12): 2091-2099. doi: 10.1016/j.joca.2017.08.012
[10]	KAWARAI Y, ORITA S, NAKAMURA J, et al. Analgesic effect of duloxetine on an animal model of monosodium iodoacetate-induced hip osteoarthritis[J]. J Orthop Res, 2020, 38(2): 422-430. doi: 10.1002/jor.24480
[11]	LACAGNINA M J, WATKINS L R, GRACE P M. Toll-like receptors and their role in persistent pain[J]. Pharmacol Ther, 2018, 184: 145-158. doi: 10.1016/j.pharmthera.2017.10.006
[12]	KALAITZOGLOU E, GRIFFIN T M, HUMPHREY M B. Innate immune responses and osteoarthritis[J]. Curr Rheumatol Rep, 2017, 19(8): 45. doi: 10.1007/s11926-017-0672-6
[13]	ROSENBERG J H, RAI V, DILISIO M F, et al. Damage-associated molecular patterns in the pathogenesis of osteoarthritis: Potentially novel therapeutic targets[J]. Mol Cell Biochem, 2017, 434(1-2): 171-179. doi: 10.1007/s11010-017-3047-4
[14]	NEFLA M, HOLZINGER D, BERENBAUM F, et al. The danger from within: alarmins in arthritis[J]. Nat Rev Rheumatol, 2016, 12(11): 669-683. doi: 10.1038/nrrheum.2016.162
[15]	DENK F, BENNETT D L, MCMAHON S B. Nerve growth factor and pain mechanisms[J]. Annu Rev Neurosci, 2017, 40: 307-325. doi: 10.1146/annurev-neuro-072116-031121
[16]	NEES T A, ROSSHIRT N, REINER T, et al. Inflammation and osteoarthritis-related pain[J]. Schmerz, 2019, 33(1): 4-12. doi: 10.1007/s00482-018-0346-y
[17]	SCHAIBLE H G. Osteoarthritis pain. Recent advances and controversies[J]. Curr Opin Support Palliat Care, 2018, 12(2): 148-153. doi: 10.1097/SPC.0000000000000334
[18]	MILLER R E, KIM Y S, TRAN P B, et al. Visualization of peripheral neuron sensitization in a surgical mouse model of osteoarthritis by in vivo calcium imaging[J]. Arthritis Rheumatol, 2018, 70(1): 88-97. doi: 10.1002/art.40342
[19]	ZHANG F, LIU Y, ZHANG D, et al. Suppression of KCNQ/M potassium channel in dorsal root ganglia neurons contributes to the development of osteoarthritic pain[J]. Pharmacology, 2019, 103(5-6): 257-262. doi: 10.1159/000496422
[20]	TROUVIN A P, PERROT S. Pain in osteoarthritis. Implications for optimal management[J]. Joint Bone Spine, 2018, 85(4): 429-434. doi: 10.1016/j.jbspin.2017.08.002
[21]	BARTLEY E J, KING C D, SIBILLE K T, et al. Enhanced pain sensitivity among individuals with symptomatic knee osteoarthritis: Potential sex differences in central sensitization[J]. Arthritis Care Res (Hoboken), 2016, 68(4): 472-480. doi: 10.1002/acr.22712
[22]	VINCENT T L. Mechanoflammation in osteoarthritis pathogenesis[J]. Semin Arthritis Rheum, 2019, 49(3S): S36-S38. http://www.sciencedirect.com/science/article/pii/S0049017219306535
[23]	CHANG S H, MORI D, KOBAYASHI H, et al. Excessive mechanical loading promotes osteoarthritis through the gremlin-1-NF-κB pathway[J]. Nat Commun, 2019, 10(1): 1442. doi: 10.1038/s41467-019-09491-5
[24]	CHOI W S, LEE G, SONG W H, et al. The CH25H-CYP7B1-RORα axis of cholesterol metabolism regulates osteoarthritis[J]. Nature, 2019, 566(7743): 254-258. doi: 10.1038/s41586-019-0920-1
[25]	WU J, WANG K, XU J, et al. Associations between serum ghrelin and knee symptoms, joint structures and cartilage or bone biomarkers in patients with knee osteoarthritis[J]. Osteoarthritis Cartilage, 2017, 25(9): 1428-1435. doi: 10.1016/j.joca.2017.05.015
[26]	LEE S H, KWON J Y, JHUN J, et al. Lactobacillus acidophilus ameliorates pain and cartilage degradation in experimental osteoarthritis[J]. Immunol Lett, 2018, 203: 6-14. doi: 10.1016/j.imlet.2018.07.003
[27]	KLEIN-WIERINGA I R, DE LANGE-BROKAAR B J, YUSUF E, et al. Inflammatory cells in patients with endstage knee osteoarthritis: A comparison between the synovium and the infrapatellar fat pad[J]. J Rheumatol, 2016, 43(4): 771-778. doi: 10.3899/jrheum.151068
[28]	LI Y S, LUO W, ZHU S A, et al. T cells in osteoarthritis: Alterations and beyond[J]. Front Immunol, 2017, 8: 356. doi: 10.3389/fimmu.2017.00356/pdf
[29]	EYMARD F, CHEVALIER X. Inflammation of the infrapatellar fat pad[J]. Joint Bone Spine, 2016, 83(4): 389-393. doi: 10.1016/j.jbspin.2016.02.016
[30]	WANG Q, LEPUS C M, RAGHU H, et al. Ige-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis[J]. Elife, 2019, 8: e39905. http://www.researchgate.net/publication/333090533_IgE-mediated_mast_cell_activation_promotes_inflammation_and_cartilage_destruction_in_osteoarthritis/download
[31]	BORBÉLY É, SÁNDOR K, MARKOVICS A, et al. Role of capsaicin-sensitive nerves and tachykinins in mast cell tryptase-induced inflammation of murine knees[J]. Inflamm Res, 2016, 65(9): 725-736. doi: 10.1007/s00011-016-0954-x
[32]	MULEY M M, REID A R, BOTZ B, et al. Neutrophil elastase induces inflammation and pain in mouse knee joints via activation of proteinase-activated receptor-2[J]. Br J Pharmacol, 2016, 173(4): 766-777. doi: 10.1111/bph.13237
[33]	曾允富, 卞阳阳, 王溶, 等. 梓醇抑制骨关节炎发病机制的研究[J]. 中华全科医学, 2019, 17(10): 1626-1630, 1651. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY201910004.htm
[34]	陈亮, 杨晓凌. 骨关节炎患者血清中炎性因子IL-1β、IL-6和COX-2的表达[J]. 中国临床医学, 2016, 23(1): 61-62. https://www.cnki.com.cn/Article/CJFDTOTAL-LCYX201601017.htm
[35]	WALSH D A. Editorial: Synovitis and pain sensitization[J]. Arthritis Rheumatol, 2016, 68(3): 561-562. doi: 10.1002/art.39487
[36]	LEUNG Y Y, HUEBNER J L, HAALAND B, et al. Synovial fluid pro-inflammatory profile differs according to the characteristics of knee pain[J]. Osteoarthritis Cartilage, 2017, 25(9): 1420-1427. doi: 10.1016/j.joca.2017.04.001
[37]	MILLER R E, TRAN P B, ISHIHARA S, et al. Microarray analyses of the dorsal root ganglia support a role for innate neuro-immune pathways in persistent pain in experimental osteoarthritis[J]. Osteoarthritis Cartilage, 2020, 28(5): 581-592. doi: 10.1016/j.joca.2020.01.008
[38]	施利华, 李恒, 郭潘, 等. miRNA-27a和miRNA-146a在骨性关节炎患者中的诊断意义[J]. 中华全科医学, 2020, 18(3): 412-414, 418. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY202003020.htm
[39]	李坤, 张育民, 王亚康, 等. 上调microRNA-543表达对大鼠骨关节炎软骨细胞的保护作用[J]. 中国临床医学, 2018, 25(2): 239-243. https://www.cnki.com.cn/Article/CJFDTOTAL-LCYX201802015.htm
[40]	EDWARDS R R, DWORKIN R H, SULLIVAN M D, et al. The role of psychosocial processes in the development and maintenance of chronic pain[J]. J Pain, 2016, 17(9 Suppl): T70-92.
[41]	TURK D C, FILLINGIM R B, OHRBACH R, et al. Assessment of psychosocial and functional impact of chronic pain[J]. J Pain, 2016, 17(9 Suppl): T21-49.
[42]	HELMINEN E E, SINIKALLIO S H, VALJAKKA A L, et al. Determinants of pain and functioning in knee osteoarthritis: A one-year prospective study[J]. Clin Rehabil, 2016, 30(9): 890-900. doi: 10.1177/0269215515619660