Impact of stress on pain sensitization and emotional responses in a rat model of persistent TMJ inflammation.

Abstract

OBJECTIVE: Temporomandibular disorders (TMDs) are frequently associated with psychological distress, including anxiety and depression, which can modulate pain perception and sensitivity. This study investigated the impact of acute and chronic stress on the progression of temporomandibular joint (TMJ) pain, secondary hyperalgesia, and stress-induced affective disturbances. DESIGN: Using a well-established preclinical model, Wistar-Hannover rats underwent persistent TMJ inflammation via intra-articular administration of Freund's complete adjuvant (CFA). Orofacial mechanical allodynia and secondary hyperalgesia were assessed using von Frey test in the orofacial region and hot plate test in the hind paw. To evaluate the influence of stress on affective behaviors, Acute stress (AS), chronic restraint stress (CRS) and Unpredictable chronic stress (UCS) paradigms were implemented, followed by behavioral assessments using the elevated plus maze (EPM), open field (OF), and sucrose preference tests. RESULTS: Results demonstrated that chronic stress exacerbated CFA-induced orofacial allodynia. TMJ inflammation induced secondary hyperalgesia, with AS partially restoring baseline nociception, while UCS amplified central sensitization. Notably, CRS did not influence hind paw nociception in CFA-injected rats. Behavioral analyses revealed that CFA injection heightened anxiety-like behavior by decreased open-arm exploration. Acute stress further intensified anxiety and impaired exploratory activity, whereas chronic stresses significantly worsened both anxiety- and depression-like behaviors. CONCLUSION: These findings underscore the complex interplay between stress and pain processing in TMDs, highlighting the detrimental role of chronic stress in exacerbating pain sensitivity and emotional dysregulation. Understanding these mechanisms could lead to more effective, targeted treatments, improving patient outcomes.