POSSIBILITIES AND LIMITATIONS OF PRECLINICAL ANIMAL MODELS BASED ON ACTIVATION OF THE TRIGEMINAL SYSTEM

Inflammatory pathways may play a role in orofacial pain and headache disorders, sensitising trigeminal nociceptors and thereby causing hyperalgesia and allodynia. Although head and facial pain cannot be perfectly modelled in animals, orofacial allodynia or hyperalgesia can be reliably assessed following various inflammatory or nerve-injury–related stimuli. We aimed to characterise multiple models to establish robust and reproducible preclinical systems. Functional assessments were performed across four models. Mechanical pain thresholds were assessed using von Frey filaments. After complete Freund’s adjuvant was injected into the right whisker pad, 76% of animals developed orofacial allodynia, with mean thresholds decreasing from 18.30 g to 5.4 g. Following cranial drilling, an inflammatory mixture was applied to the dura mater, resulting in periorbital allodynia in 45% of rats, with thresholds decreasing to 10.40 g. Partial ligation of the right infraorbital nerve produced allodynia restricted to the right side of the face: 53% of animals developed allodynia (mean threshold 9.50 g). In the nitroglycerin-induced model, allodynia developed in 67% of animals, with thresholds decreasing to 12.22 g. Trigeminal activation-induced allodynia can be evaluated across all models; therefore, each model is suitable for investigating different pathophysiological mechanisms. However, the magnitude, stability, and incidence of the induced allodynia vary across models. Consequently, when testing novel drug candidates, the specific limitations and distinct pathophysiological backgrounds of each model must be carefully considered when interpreting the data. Funding: NAP-3; Chronic Pain Research Group, NKFIH K 138046, TKP2021-EGA-16, RRF-2.3.1-21-2022-00015, PTE ÁOK-KA-2025-28, and ÚNKP-23-4-II