The degeneration-pain relationship in the temporomandibular joint: Current understandings and rodent models

Abstract

Temporomandibular disorders (TMD) represent a group of musculoskeletal conditions involving the temporomandibular joints (TMJ), the masticatory muscles and associated structures. Painful TMD are highly prevalent and conditions afflict 4% of US adults annually. TMD include heterogenous musculoskeletal pain conditions, such as myalgia, arthralgia, and myofascial pain. A subpopulations of TMD patients show structural changes in TMJ, including disc displacement or degenerative joint diseases (DJD). DJD is a slowly progressing, degenerative disease of the TMJ characterized by cartilage degradation and subchondral bone remodeling. Patients with DJD often develop pain (TMJ osteoarthritis; TMJ OA), but do not always have pain (TMJ osteoarthrosis). Therefore, pain symptoms are not always associated with altered TMJ structures, which suggests that a causal relationship between TMJ degeneration and pain is unclear. Multiple animal models have been developed for determining altered joint structure and pain phenotypes in response to various TMJ injuries. Rodent models of TMJOA and pain include injections to induce inflammation or cartilage destruction, sustained opening of the oral cavity, surgical resection of the articular disc, transgenic approaches to knockout or overexpress key genes, and an integrative approach with superimposed emotional stress or comorbidities. In rodents, TMJ pain and degeneration occur during partially overlapping time periods in these models, which suggests that common biological factors may mediate TMJ pain and degeneration over different time courses. While substances such as intra-articular pro-inflammatory cytokines commonly cause pain and joint degeneration, it remains unclear whether pain or nociceptive activities are causally associated with structural degeneration of TMJ and whether structural degeneration of TMJ is necessary for producing persistent pain. A thorough understanding of the determining factors of pain-structure relationships of TMJ during the onset, progression, and chronification by adopting novel approaches and models should improve the ability to simultaneously treat TMJ pain and TMJ degeneration.

Elucidation of neuronal activity in mouse models of TMJ injury byin vivoGCaMP Ca2+imaging of intact trigeminal ganglion neurons

“…Animal models mimicking the high levels of inflammation observed in the TMJ of TMD patients have been developed using direct injection of chemical agents, including complete Freund’s adjuvant (CFA), zymosan, carrageenan, mustard oil, monoiodoacetate, albumin, and formalin, into the TMJ to cause inflammation. It has been confirmed that intra-TMJ injections of CFA cause mechanical hyperalgesia within the TMJ in rodents[9]. Consistent with this, we confirmed hypersensitivity lasting up to 7 days in the V3 region of CFA-injected mice by the von Frey test (Fig.…”

“…While CFA can induce acute inflammatory reactions and histological modifications in the TMJ, including extracellular matrix accumulation and soft tissue alterations, CFA does not cause cartilage and bone degradation. Furthermore, this model is not fully representative of the underlying causes driving the sustained pain and degeneration experienced by human patients, as it does not encompass the unidentified foundational elements contributing to the persistence of these conditions [9]. Because excessive TMJ activity and prolonged mouth opening are risk factors in development of TMD [6], the FMO model of TMD-related pain is attractive [15,33].…”

“…TMD is the second most common musculoskeletal disorder, affecting 5-12% of the US population (NIH). It consists of myalgia, arthralgia, and myofascial pain, resulting in headaches, limited jaw motion, and pain-related disability [9]. Existing treatments for TMD are not always effective in all patients, underscoring the need for more advanced, mechanism-based therapies.…”

Effect of manual therapy on tinnitus in patients with TMJ

“…TMD can affect up to 70% of the population with most of them being young patients. 12 Classic subpopulations of TMD are known as myofascial, disc displacement with or without reduction, and degenerative joint disease 13 . TMD can be caused by trauma, bruxism, malocclusion, and TMJ disk dislocation 11 .…”

Temporomandibular Disorder Treated With Chiropractic Therapy

“…TMD is primarily characterized by musculoskeletal pain syndromes which comprise myofascial pain, myalgia, and arthralgia. [ 2 ]. The etiology of TMD is not fully understood; however, it is believed to involve a combination of biological, environmental, social, emotional, and cognitive factors.…”