35: Time-Dependent Characterization of Orofacial Pain in STZ-Induced Diabetic Rats via Operant Assay

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic neuropathic pain, , , , , , , , , , Assessment and Measurement of Pain/Nociception, Behavioral studies

Background and Aims: Diabetic neuropathy is a prevalent and disabling complication of type 1 diabetes, causing chronic pain and diminished quality of life despite glycemic control. It can impair trigeminal nerve function, disrupting orofacial sensory processing and pain perception. Rodent models of streptozotocin (STZ)-induced diabetes demonstrate hyperalgesia across multiple regions, including the orofacial area, yet the mechanisms underlying trigeminal dysfunction remain unclear. This study investigated time-dependent patterns of diabetic neuropathic pain in male Wistar Hannover rats, focusing on orofacial outcomes. The trigeminal inflammatory profile was assessed to provide mechanistic insight and support the development of more effective clinical strategies for managing diabetic neuropathy.

Methods: Experimental diabetes was induced by a single intraperitoneal injection of streptozotocin (60 mg/kg) in male Wistar Hannover rats. Nociceptive responses were assessed using the orofacial operant assay (Hugo Basile) at baseline and at weeks 1, 3, and 5 following diabetes induction. At week 5, von Frey and acetone tests were performed on both the face and hind paws for comparative analysis. Trigeminal ganglia were collected for quantification of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) using ELISA.

Results: Thermal nociception (operant test) showed a significant reduction in contacts in diabetic rats versus controls at week 3 (p = 0.0255). Cold stimulation also reduced contacts at weeks 1 and 5, while the acetone test indicated increased orofacial grooming at week 5, suggesting heightened cold sensitivity (p = 0.0814). Mechanical nociception revealed fewer contacts at week 5 (p < 0.05). Von Frey testing confirmed decreased nociceptive thresholds in both hind paws (p = 0.00059) and the orofacial region (p = 0.0040). Trigeminal TNF-α levels were elevated in diabetic animals (4623 ± 97 pg/mL) compared to controls (2753 ± 121 pg/mL).

Conclusions: Together, these findings demonstrate that diabetic orofacial neuropathy exhibits distinct time-dependent modulation across sensory modalities, with progressive mechanical hypersensitivity and altered thermal responsiveness emerging throughout disease progression. The concomitant increase in trigeminal TNF-α suggests that neuroinflammatory mechanisms contribute to the development of orofacial pain in diabetes. These results advance the understanding of trigeminal involvement in diabetic neuropathy and highlight the importance of temporally targeted therapeutic strategies aimed at controlling neuroinflammation and preventing the chronification of orofacial pain.

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Presenting Author: Milena Barbosa Costa
Submitting Author: Milena Barbosa Costa

Senior Author: Milena Barbosa Costa

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Daniela Maria Escobar Espinal - University of São Paulo
• Elaine Aparecida del Bel Belluz Guimarães - University of São Paulo
• Glauce Crivelaro do Nascimento Marangoni - University of São Paulo