The involvement of orexin-1 receptors in modulation of feeding and anxiety-like behavior in rats with complete Freund’s adjuvant-induced temporomandibular joint disorder

Orexin-A (OXA), a neuropeptide produced in the hypothalamus, is recognized for its role in modulating orofacial nociception and regulating feeding behaviors, as well as its impact on psychophysiological responses. This study investigated the role of orexin-1 receptors (OX1R) in modulating nociceptive behaviors induced by noxious stimulation of the temporomandibular joint (TMJ) and the associated changes in mood and feeding behaviors in rats with complete Freund's adjuvant (CFA)-induced temporomandibular disorders (TMDs). Bilateral cannulation of the lateral ventricles was performed in rats. To induce nociception, CFA was injected unilaterally into the left TMJ of the rats. Nociceptive behaviors were assessed using the hot plate and tail flick tests, while anxiety-like behavior and food intake were evaluated using an elevated plus maze (EPM) and a food preference device, respectively. The results demonstrated a significant increase in nociceptive scores and anxiety-like behaviors, along with reductions in water and food consumption following CFA injection. However, post-treatment with OXA at concentrations of 50 and 100 pM/rat significantly decreased thermal nociceptive scores, alleviated anxiety-like behavior, and increased water and food intake. These beneficial effects were reversed when OXA was co-administered with SB-334867 (40 nM/rat), an OX1R antagonist. Collectively, our findings suggest that OX1R signaling plays a role in the modulation of anxiety-like behavior and abnormalities in food intake in CFA-treated rats. Understanding the involvement of OXA and its receptors in CFA-induced TMJ nociception and behavioral changes may pave the way for potential therapeutic interventions targeting OX1R signaling in the management of TMD-associated symptoms.