Nociceptive behavioural assessments in mouse models of temporomandibular joint disorders

Abstract

Orofacial pain or tenderness is a primary symptom associated with temporomandibular joint (TMJ) disorders (TMDs). To understand the pathological mechanisms underlying TMDs, several mouse models have been developed, including mechanical stimulus-induced TMD and genetic mouse models. However, a lack of feasible approaches for assessing TMD-related nociceptive behaviours in the orofacial region of mice has hindered the in-depth study of TMD-associated mechanisms. This study aimed to explore modifications of three existing methods to analyse nociceptive behaviours using two TMD mouse models: (1) mechanical allodynia was tested using von Frey filaments in the mouse TMJ region by placing mice in specially designed chambers; (2) bite force was measured using the Economical Load and Force (ELF) system; and (3) spontaneous feeding behaviour tests, including eating duration and frequency, were analysed using the Laboratory Animal Behaviour Observation Registration and Analysis System (LABORAS). We successfully assessed changes in nociceptive behaviours in two TMD mouse models, a unilateral anterior crossbite (UAC)-induced TMD mouse model and a β-catenin conditional activation mouse model. We found that the UAC model and β-catenin conditional activation mouse model were significantly associated with signs of increased mechanical allodynia, lower bite force, and decreased spontaneous feeding behaviour, indicating manifestations of TMD. These behavioural changes were consistent with the cartilage degradation phenotype observed in these mouse models. Our studies have shown reliable methods to analyse nociceptive behaviours in mice and may indicate that these methods are valid to assess signs of TMD in mice.

Preclinical models of deep craniofacial nociception and temporomandibular disorder pain

“…Specific functions of the orofacial areas such as bite force could determine the nociception in the deep craniofacial tissues of the animals [ 151 , 206 ]. The validity for usage of bite force in the animals could be explained by the evidence of a reduction of bite force in painful TMD patients [ 207 , 208 ].…”

Antisense Oligonucleotide-Based Therapy on miR-181a-5p Alleviates Cartilage Degradation of Temporomandibular Joint Osteoarthritis via Promoting SIRT1

“…According to previous research, TMJOA manifestations can be observed 3 weeks post-UAC surgery in mice ( Li et al, 2020 ). Therefore, we started bilateral miR-181a-5p ASO injections in the TMJ cavity at the 4th week after UAC, and they were administered twice a week for 6 consecutive weeks.…”

“…In the current study unilateral anterior crossbite surgery was performed to simulate malocclusion, which successfully established a stable TMJOA mouse model. In a series of previous studies a sustained abnormal occlusal relationship changed incisal guidance during mastication, resulting in TMJ degenerative and pathological changes, which can mimic TMJOA caused by an abnormal occlusal relationship and excessive joint loading in humans ( Li et al, 2020 ; Liu et al, 2021 ).…”

The neurobiology of pain and facial movements in rodents: Clinical applications and current research

“…Restoring the normal meal duration can serve as an indicator of the pharmacologic efficacy of anti-inflammatory drugs such as dexamethasone ( 115 ), or capsaicin, a compound known to eliminate C-fibers that participate in the nociceptive pathway ( 114 ). Similarly, mice with temporomandibular joint pain had decreased eating duration and frequency, an effect that was consistent with cartilage degradation, making it a reliable method for pain recognition ( 116 ). Adequate dosage of multimodal analgesic treatments with opioids and non-steroidal anti-inflammatory drugs after a surgical procedure has been shown to preserve food intake in rats undergoing implantation of epidural electrodes ( 117 ).…”