THE BACK PAGE RESEARCH REVIEW Investigating the science on joint diseases REVIEWED BY SHAWN THISTLE STUDY TITLE: Degenerative Joint Disease and Neuroinflammation AUTHORS: Fusco M, Skaper SD, Coaccioli S, et al. PUBLICATION INFORMATION: Pain Practice 2017; 17: 522-532. I t has long been thought that rheu-matic and musculoskeletal diseases were centered in the joint cartilage. However, recent research suggested that subchondral bone also plays a significant role. Studies using MRI have shown that changes in subchon-dral bone, including thickening, re-duced flexibility, and reduced trabecu-lar density, may be significant in osteoarthritis and microcrystalline ar-thropathy development. In some cases, there is evidence that these types of subchondral bone changes may precede cartilage injury. Recently, a systematic review con-firmed an association between bone lesions, osteophytes, and changes in bone morphology, independently from one another with structural osteoar-thritis progression and joint replace-ments. An association was also found between bone lesions and changes in bone morphology and pain related to osteoarthritis in the knees, hands, and hips. Together, this points to robust cross-talk between the articular carti-lage and subchondral bone in cases of joint disease. During periods of elevated subchon-dral bone turnover, cytokines and trophic factors are released and interact with articular cartilage, creating a pos-itive feedback loop between cartilage damage and the bone healing process. When stimuli such as inappropriate loads or the presence of subchondral bone catabolic factors affect chondro-cytes, they undergo a change in pheno-type and begin to produce cytokines and chemokines. These then act in a paracrine fashion (exerting its effect in the immediate vicinity), initiating a vicious cycle leading to cartilage deg-radation. This tissue damage then triggers an inflammatory reaction in-volving the synovia and rapidly acti-vates articular mast cells. Finally, oste-oblasts in patients with osteoarthritis show a change in chondrocyte pheno-type in favour of hypertrophic differen-tiation and matrix mineralization. New targets for treatment Mast cells and microglia at the cellular level can be modulated to attack both peripheral and central neuroinflamma-tion, reducing pain and promoting restoration of tissue homeostasis, lim-iting disease progression. This makes them very attractive targets for medical intervention. Synovial fluid shows dras-tically reduced levels of N-palmitoy-lethanolamine (PEA) in patients with osteoarthritis or rheumatoid arthritis, which suggests that PEA might have a protective role in joints. Therefore, PEA supplementation may be benefi-cial to individuals with those condi-tions. PEA supplementation also shows anti-inflammatory and analgesic effects in conditions with chronic inflamma-tion, modulates mast cell degranula-tion, reduces activation of spinal cord microglia, reduces chronic and neuro-pathic pain associated with a variety of pathologies, and reduces pain and improves function in patients with temporomandibular disorders. Cannabinoid receptor CB1 and CB2 agonists have a protective role in joint diseases. CB1 intervenes in bone re-modelling and age-dependant bone loss, while CB2 protects against bone loss, and endows immune cells with immunomodulatory and anti-inflam-matory activities. Substances such as PEA activate CB2 receptors, making them good options for the treatment of rheumatic diseases. Peroxisome proliferator-activated receptors alpha and gamma have also been proposed as potential targets for joint diseases, with studies suggesting that their agonists reduce synthesis of inflammatory and catabolic agents, preventing cartilage lesions. Application, conclusions DR. SHAWN THISTLE is the founder and CEO of RRS Education, providing weekly research reviews, online courses and seminars to help busy clinicians integrate current research evidence rationally into practice. For more information, visit: www.rrseducation.com. Shawn can be reached by email at [email protected] 26 Canadian Chiropractor October 2017 Pain resulting from joint disease comes from both inflammatory and neuro-pathic components. There is still no clear pathogenesis of joint disease, however, the prevailing consensus sup-ports underlying cross-talk between cartilage and subchondral bone. Disease-modifying drugs, specifically those capable of counteracting disease progression, should be the future focus of research. These include molecules targeting cannabinoid receptors (such as PEA) and PPARs. This research could change the focus of osteoarthritis and rheumatoid arthritis treatment from symptomatic relief to maintaining or even reversing joint damage. www.canadianchiropractor.ca
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