Experimental animal models of orofacial pain have been instrumental in elucidating biological pathways underlying the antinociceptive effect of botulinum neurotoxin type A (BoNT/A). Although several mechanisms have been proposed to explain how BoNT/A relieves pain, the precise modes of action, particularly in the oral and maxillofacial areas, remain elusive. The purpose of this review was to synthesize and assess the latest proposed mechanisms of action through which BoNT/A attenuates orofacial pain in established animal models. A comprehensive search was conducted using the terms “botulinum neurotoxin,” “mechanism,” and “orofacial pain” or “trigeminal neuralgia.” Only animal studies involving the establishment of an orofacial pain model were selected. Additional relevant studies were identified through manual screening of cited references. Over the past five years, several animal pain models have been established to decipher the mechanisms underlying the BoNT/A-mediated antinociception in orofacial pain. The proposed mechanisms include retrograde transport, neuronal excitability regulation, neuropeptide inhibition, inflammatory modulation, and opioid system stimulation in both the peripheral and central nervous systems. Despite the insubstantial number of investigations and findings, BoNT/A exhibits multidimensional modulation of nociceptive responses and, therefore, remains a promising therapeutic agent for managing orofacial pain conditions, with animal studies consistently providing insights into the mechanism of its antinociceptive action.

Trigeminal neuralgia (TN) is a debilitating neuropathic facial pain disorder characterized by sudden, severe paroxysmal pain that markedly impairs quality of life. Although current pharmacological treatments provide pain relief, their adverse effects highlight the need for safer alternative therapies. Curcumin, a natural polyphenol, exhibits anti-inflammatory and neuroprotective properties with minimal side effects. In this study, we examined the impact of intraperitoneal curcumin administration on the trigeminal ganglia in a TN rat model induced by unilateral infraorbital nerve constriction (IONC). Behavioral tests revealed that curcumin significantly reduced mechanical hypersensitivity compared with vehicle-treated controls. Immunohistochemical analysis showed decreased expression of glial fibrillary acidic protein (GFAP) and activating transcription factor 3 (ATF3), established markers of satellite glial cell (SGC) activation and neuronal stress in the trigeminal ganglia. Furthermore, curcumin administration reduced tumor necrosis factor-α (TNF-α) expression and modulated phosphorylated signal transducer and activator of transcription 3 (pSTAT3) activity. These findings suggest that curcumin alleviates neuropathic pain by suppressing glial activation and pSTAT3-related pro-inflammatory signaling. Curcumin may therefore represent a promising potential therapeutic candidate for TN, warranting further investigation into its clinical applicability and underlying mechanisms.

Background: While whole‐body postural control requires integration of the sensorimotor system, the involvement of jaw muscle activity in this control remains unclear. Objective: This study aimed to clarify the relationship between jaw muscle activity and whole‐body postural stability by measuring jaw‐opening and closing muscle activities, as well as whole‐body postural sway during postural perturbations with two different levels of predictability. Methods: Twelve healthy adults (7 males, 5 females; median age 21.0 years) underwent vertical perturbations by holding a bar at shoulder height. In the cued condition (C‐cond), the participants were given a 3‐s countdown before the bar was loaded with 3% of their body weight, whereas in the uncued condition (U‐cond), the load was applied without prior cueing. Jaw‐closing (masseter) and jaw‐opening (anterior suprahyoid) muscle activities were measured using surface electromyography (EMG). Bar dynamics and center‐of‐foot‐pressure (COP) were assessed with motion capture and a force plate. Bar‐drop distances, EMG activity, and the proportion of trials with muscle activity exceeding baseline were compared between conditions using the Wilcoxon signed‐rank test, Friedman, Mann–Whitney U and chi‐square tests, as appropriate, with Bonferroni corrections. Results: Vertical bar displacement was greater in the U‐cond compared with the C‐cond (−46.0 mm vs. −27.4 mm, the Wilcoxon signed‐rank test, p < 0.05). Left anterior suprahyoid activity exceeded baseline in 91.7% of uncued trials versus 58.3% in cued trials (the chi‐square test with the Bonferroni correction applied, adjusted p < 0.05). COP displacement increased when masseter and anterior suprahyoid muscle activity exceeded baseline in the U‐cond (the Mann–Whitney U test with Bonferroni correction, adjusted p < 0.05). Conclusion: Increased activation of jaw‐opening muscles during uncued perturbations compared with cued perturbations suggests that anterior suprahyoid muscles are recruited for postural control, supporting their involvement in maintaining stability.