115: ENDOCANNABINOID SYSTEM ATTENUATES EMOTIONAL STRESS-INDUCED OROFACIAL MUSCULOSKELETAL PAIN IN RATS

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic primary orofacial pain, , , , Pharmacological interventions, Assessment and Measurement of Pain/Nociception, Neurocircuit modulation (could include opto, DREADDs), , , , ,

Background and Aims: Orofacial musculoskeletal pain (OMP) affects individuals with temporomandibular disorders (TMD), a group of conditions affecting temporomandibular joint, chewing muscles and associated structures. A biopsychosocial model of pain is now recognized in the etiology of muscular TMD, highlighting the complexity related to OMP. Painful TMD is typically chronic, bilateral, diffuse, and associated with jaw movement, aligning with the criterion for nociplastic pain addressed by Kosek et al. (2021). In this sense, the objective is to study the OMP induced by psychological/emotional stress (ES) in rats, regarding the role of the endocannabinoid system (ECS) through CB1 and CB2 receptors.

Methods: Male Wistar rats were divided into OMP was induced by psychological/emotional stress using the communication box model and evaluated through the mechanical threshold in masticatory muscles by Von Frey method. To assess anxiety-like behavior, the elevated plus-maze test was performed. Histological analysis was performed in samples of adrenal glands. c-Fos, CB1 and CB2 immunostaining were evaluated in the trigeminal ganglion (TG) and in the trigeminal nucleus caudalis (Sp5C). The selective CB1 or CB2 antagonist (AM251 or AM630, respectively) or the cannabinoid receptor non-selective agonist (WIN55,212-2) were administered in both groups and the OMP was evaluated.

Results: The results show an increase in the mechanical sensitivity of the masticatory muscles in the ES group, accompanied by increased c-Fos expression in the TG and Sp5C. ES groups presented a decrease in open arms entries and in the % of time spent in the open arms in the plus maze test. ES group showed a higher concentration of cytoplasmic vacuoles, AM251 and AM630 increased mechanical sensitivity, while WIN55,212-2 decreased the ongoing OMP. Furthermore, ES increased CB1 density in the TG and elevated both CB1 and CB2 in the Sp5C. Additionally, CB2 was also increased in the masseter muscle.

Conclusions: In conclusion, the data suggest that emotional stress causes mechanical sensitivity in the temporalis and masseter muscles, mimicking what happens in patients with painful muscular TMD, and also increases the expression of cannabinoid receptors in the trigeminal pain pathway and in masseter muscle. The blockade or activation of these receptors, mainly CB1, modifies the sensitivity in the evaluated muscles, indicating that cannabinoid drugs or the modulation of the ECS may be a way of interest for the treatment of OMP associated with stress, frequently observed in patients with TMD.

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Presenting Author: Mariana Lima Vale
Submitting Author: Bruno Freitas-Alves

Senior Author: Mariana Lima Vale

IASP 2026 Global Year theme of Neuropathic Pain: No

• Bruno Wesley de Freitas Alves: PhD Student - Federal University of Ceará
• Sarah Sanders Silveira: PhD - Federal University of Ceará
• Mario Roberto Pontes Lisboa: PhD - Federal University of Ceará
• Jéssica Jamile Ribeiro Nogueira - Federal University of Ceará
• Karoline Luanne Santos de Menezes - Federal University of Ceará
• Anamaria Falcão Pereira: PhD - Federal University of Ceará
• Ricardo de Freitas Lima: PhD - Federal University of Ceará
• Delane Viana Gondim: PhD - Federal University of Ceará
• Mariana Lima Vale: PhD - Federal University of Ceará