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

**Authors:** Hanieh Eghbali, Mehdi Abbasnejad, Maryam Raoof, Mahnaz Zamyad, Saeed Esmaeili-Mahani, Razieh Kooshki, Mojdeh Mansoori, Frank Lobbezoo

PMC · DOI: 10.22514/jofph.2026.019 · 2026-03-12

## TL;DR

Alpha-pinene reduces pain and improves feeding behavior in rats with temporomandibular joint inflammation.

## Contribution

Alpha-pinene's effect on feeding behavior and hypothalamic orexin-A in a TMD rat model is newly demonstrated.

## Key findings

- Alpha-pinene at 0.4 μg/rat improved pain thresholds and feeding behavior in CFA-treated rats.
- Alpha-pinene restored hypothalamic orexin A expression in rats with TMJ inflammation.
- CFA-treated rats showed anxiety-like behavior and impaired feeding patterns.

## 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.

## Linked entities

- **Chemicals:** alpha-pinene (PubChem CID 6654)

## Full-text entities

- **Genes:** Nos3 (nitric oxide synthase 3) [NCBI Gene 24600] {aka eNos}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Hcrt (hypocretin neuropeptide precursor) [NCBI Gene 25723] {aka orexin-A}, Slc2a4 (solute carrier family 2 member 4) [NCBI Gene 25139] {aka Glut4}
- **Diseases:** TMJ (MESH:D013706), orofacial (MESH:D020820), muscle tension (MESH:D018781), TMD (MESH:D049310), hyperalgesia (MESH:D006930), impairments in muscle coordination (MESH:D001259), orofacial pain (MESH:D005157), hemorrhage (MESH:D006470), Anxiety (MESH:D001007), edema (MESH:D004487), functional deficits (MESH:D001289), hypersensitivity (MESH:D004342), Inflammation (MESH:D007249), muscle (MESH:D019042), Pain (MESH:D010146), orofacial dysfunction (MESH:C564676), impaired feeding behavior (MESH:D001068), TMDs (MESH:D013705), fatigue (MESH:D005221), chronic pain (MESH:D059350), neuroinflammation (MESH:D000090862)
- **Chemicals:** ethanol (MESH:D000431), 3,3'-diaminobenzidine (MESH:D015100), formalin (MESH:D005557), monoterpene (MESH:D039821), xylazine (MESH:D014991), Flcm7415 (-), Paraffin (MESH:D010232), NO (MESH:D009569), water (MESH:D014867), essential oils (MESH:D009822), glucose (MESH:D005947), Saline (MESH:D012965), xylene (MESH:D014992), Alpha-pinene (MESH:C005451), eosin (MESH:D004801), alcohol (MESH:D000438), Hematoxylin (MESH:D006416)
- **Species:** Salvia rosmarinus (rosemary, species) [taxon 39367], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13036620/full.md

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Source: https://tomesphere.com/paper/PMC13036620