Development of a Rat Model of Mechanically Induced Tunable Pain and Associated Temporomandibular Joint Responses

• Published in: Journal of oral and maxillofacial surgery Vol. 74; no. 1; pp. 54.e1 - 54.e10
• Main Authors: Kartha, Sonia, BS, Zhou, Timothy, Granquist, Eric J., DMD, MD, Winkelstein, Beth A., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2016
• Subjects: Animals; Biomechanical Phenomena; Cartilage, Articular - chemistry; Cartilage, Articular - pathology; Chondrocytes - chemistry; Chondrocytes - pathology; Chronic Pain - etiology; Chronic Pain - metabolism; Dentistry; Disease Models, Animal; Facial Pain - etiology; Facial Pain - metabolism; Female; Hypoxia-Inducible Factor 1, alpha Subunit - analysis; Mandibular Condyle - chemistry; Mandibular Condyle - pathology; Matrix Metalloproteinase 13 - analysis; Osteoarthritis - etiology; Osteoarthritis - metabolism; Random Allocation; Range of Motion, Articular - physiology; Rats; Rats, Sprague-Dawley; Sensation - physiology; Stress, Mechanical; Surgery; Temporomandibular Joint Disorders - etiology; Temporomandibular Joint Disorders - metabolism; Time Factors; Tumor Necrosis Factor-alpha - analysis
• ISSN: 0278-2391; 1531-5053
• DOI: 10.1016/j.joms.2015.09.005

Purpose Although mechanical overloading of the temporomandibular joint (TMJ) is implicated in TMJ osteoarthritis (OA) and orofacial pain, most experimental models of TMJ-OA induce only acute and resolving pain, which do not meaningfully simulate the pathomechanisms of TMJ-OA in patients with chronic pain. The aim of this study was to adapt an existing rat model of mechanically induced TMJ-OA, to induce persistent orofacial pain by altering only the jaw-opening force, and to measure the expression of common proxies of TMJ-OA, including degradation and inflammatory proteins, in the joint. Materials and Methods TMJ-OA was mechanically induced in a randomized, prospective study using 2 magnitudes of opening loads in separate groups (ie, 2-N, 3.5-N and sham control [no load]). Steady mouth opening was imposed daily (60 minutes/day for 7 days) in female Holtzman rats, followed by 7 days of rest, and orofacial sensitivity was measured throughout the loading and rest periods. Joint structure and extent of degeneration were assessed at day 14 and expression of matrix metalloproteinase-13 (MMP-13), hypoxia-inducible factor-1α (HIF-1α), and tumor necrosis factor-α (TNF-α) in articular cartilage was evaluated by immunohistochemistry and quantitative densitometry methods at day 7 between the 2 loading and control groups. Statistical differences of orofacial sensitivity and chondrocyte expression between loading groups were computed and significance was set at a P  value less than .05. Results Head-withdrawal thresholds for the 2 loading groups were significantly decreased during loading ( P < .0001), but that decrease remained through day 14 only for the 3.5-N group ( P < .00001). At day 14, TMJs from the 2-N and 3.5-N groups exhibited truncation of the condylar cartilage, typical of TMJ-OA. In addition, a 3.5-N loading force significantly upregulated MMP-13 ( P < .0074), with nearly a 2-fold increase in HIF-1α ( P < .001) and TNF-α ( P < .0001) at day 7, in 3.5-N loaded joints over those loaded by 2 N. Conclusion Unlike a 2-N loading force, mechanical overloading of the TMJ using a 3.5-N loading force induced constant and nonresolving pain and the upregulation of inflammatory markers only in the 3.5-N group, suggesting that these markers could predict the maintenance of persistent orofacial pain. As such, the development of a tunable experimental TMJ-OA model that can separately induce acute or persistent orofacial pain using similar approaches provides a platform to better understand the pathomechanisms involved and possibly to evaluate potential treatment strategies for patients with painful TMJ-OA.