Alpha-pinene modulates feeding behavior and hypothalamic orexin-A expression in a rat model of painful temporomandibular disorder.

Abstract

BACKGROUND: Temporomandibular disorders (TMDs) are common conditions involving the temporomandibular joint (TMJ) and masticatory muscles, often presenting with pain and impaired orofacial function. Painful TMD can disrupt jaw motor activities, including chewing and feeding behavior, reflecting alteration in muscle performance and central neuroregulation. The hypothalamic neuropeptide orexin A integrates pain, arousal, and energy balance and may be involved in these disturbances. This study examined whether intracerebroventricular (ICV) administration of alpha-pinene, an anti-inflammatory monoterpene, could modulate pain-related impairments in feeding behavior and orexin A expression in a rat model of inflammatory TMD. METHODS: TMJ inflammation was induced in male Wistar rats via Complete Freund's Adjuvant (CFA) injection. Rats received ICV alpha-pinene (0.1, 0.2, or 0.4 μg/rat). Feeding behavior parameters-including meal frequency, duration, and total intake-were recorded with an automated monitoring system as functional readouts of masticatory muscle activity during food processing. Anxiety-like behavior was evaluated using the elevated plus maze, and hypothalamic orexin A expression was assessed by immunohistochemistry. RESULTS: CFA-treated rats showed reduced pain thresholds, anxiety-like behavior, and impaired feeding behavior, including fewer meals, shorter feeding duration, and reduced intake. Alpha-pinene, particularly at 0.4 μg/rat, significantly improved these behavioral outcomes and restored hypothalamic orexin A expression compared with untreated CFA rats. CONCLUSIONS: Alpha-pinene mitigated pain-related disruptions in feeding behavior and restored hypothalamic orexin A expression in a rat model of TMJ inflammation. These findings highlight the interplay between orofacial pain, altered oral motor function, and central neuroregulation. The observed behavioral improvements suggest that alpha-pinene may offer therapeutic benefits for managing functional impairments associated with both muscular and joint-related TMD pain, supporting its potential as a candidate for integrative TMD management.