Abstract
Although pre-clinical models of pain are useful for defining relationships between biological mechanisms and pain, common methods testing peripheral sensitivity do not translate to the human pain experience. Facial grimace scales evaluate affective pain levels in rodent models by capturing and scoring spontaneous facial expression. But, the Rat Grimace Scale (RGS) has not assessed the common disorder of temporomandibular joint (TMJ) pain. A rat model of TMJ pain induced by jaw loading (1 hr/day for 7 days) was used to investigate the time course of RGS scores and compare them between different loading magnitudes with distinct peripheral sensitivity profiles (0N–no sensitivity, 2N–acute sensitivity, 3.5N–persistent sensitivity). In the 3.5N group, RGS is elevated over baseline during the loading period and one day after loading and is correlated with peripheral sensitivity (ρ = −0.48, p = 0.002). However, RGS is not elevated later when that group exhibits peripheral sensitivity and moderate TMJ condylar cartilage degeneration. Acutely, RGS is elevated in the 3.5N loading group over the other loading groups (p < 0.001). These findings suggest that RGS is an effective tool for detecting spontaneous TMJ pain and that spontaneous pain is detectable in rats that develop persistent TMJ sensitivity, but not in rats with acute resolving sensitivity.
Highlights
Pre-clinical rodent studies commonly assess pain by measuring hypersensitivity in the relevant dermatome for the pathology or etiology being studied[1]
Facial grimace scales have been used to characterize visceral, inflammatory, and neuropathic pain in rodent models of skin and joint inflammation, cervical radiculopathy, peripheral neuropathy, bladder infection, and abdominal constriction[16,18,19,41], this is the first report of facial grimace for temporomandibular joint (TMJ) pain and in the context of repeated joint over-loading, which is a major cause of joint degeneration and pain[42,43,44,45]
Since Rat Grimace Scale (RGS) is elevated over baseline during the TMJ loading period and one day after its cessation (Fig. 3), affective components of pain appear to be detectable both acutely after a single joint loading and throughout repeated loading sessions
Summary
Pre-clinical rodent studies commonly assess pain by measuring hypersensitivity in the relevant dermatome for the pathology or etiology being studied[1]. Peripheral sensitivity is measured using mechanical stimuli to illicit a withdrawal response, defining a threshold for sensitivity[5,6,7,8,9,10] This method is useful for investigating some forms of sensitivity, it assesses only the evoked component of pain[3] and nociceptive pain pathways[11]. RGS scores were compared across separate groups of rats receiving different degrees of TMJ loading (0N, 2N, 3.5N) (Fig. 2), known to induce different reflex responses. Exposure to repeated TMJ loading at different magnitudes produces distinct TMJ sensitivity profiles evoked in response to von Frey filament stimuli[5,7]. Despite the widespread use of Mankin scoring to evaluate cartilage degeneration in animal models of TMJ osteoarthritis[37,38,39], the temporal relationship between TMJ pain and structural changes of the joint remains poorly understood
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