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Updated: May 15, 2026

Chronic Constriction Injury of the Distal Infraorbital Nerve (DIoN-CCI) in Mice to Study Trigeminal Neuropathic Pain
Published on: March 8, 2024
Orofacial neuropathic pain mouse model induced by Trigeminal Inflammatory Compression (TIC) of the infraorbital nerve
Fei Ma1, Liping Zhang, Danielle Lyons
1Department of Physiology MS-508, College of Medicine, University of Kentucky, Lexington, KY 40536-0298, USA.
Background:
Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC) model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity.
Results:
The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild nerve trauma. Nerve edema is observed in the contacting infraorbital nerve bundle as well as macrophage infiltration in the trigeminal ganglia. Centrally in the spinal trigeminal nucleus, increased immunoreactivity for an activated microglial marker is evident (OX42, postoperative day 70). Mechanical thresholds of the affected whisker pad are significantly decreased on day 3 after chromic gut suture placement, persisting at least 10 weeks. The mechanical allodynia is reversed by suppression of microglial activation. Cold allodynia was detected at 4 weeks.
Conclusions:
A simple, effective, and reproducible chronic mouse model mimicking clinical orofacial neuropathic pain (Type 2) is induced by placing chromic gut suture between the infraorbital nerve and the maxillary bone. The method produces mild inflammatory compression with significant continuous mechanical allodynia persisting at least 10 weeks and cold allodynia measureable at 4 weeks.
Insights
A new mouse model for trigeminal neuropathic pain was developed using mild nerve compression. This model reliably causes mechanical allodynia for at least 10 weeks, aiding orofacial pain research.
Area of Science:
- Neuroscience
- Pain Research
- Animal Models
Background:
- Trigeminal neuropathic pain causes severe orofacial pain, often triggered by light touch.
- Existing rodent models for orofacial pain have limitations, especially in mice.
- A novel mouse trigeminal inflammatory compression (TIC) model is presented to study orofacial pain.
Purpose of the Study:
- To introduce and validate a new chronic mouse model for orofacial neuropathic pain.
- To establish a reliable method for inducing trigeminal nerve inflammation and hypersensitivity in mice.
Main Methods:
- Surgical placement of chromic gut suture near the infraorbital nerve in mice.
- Induction of mild nerve compression and inflammation.
- Assessment of mechanical and cold allodynia, nerve edema, and microglial activation.
Main Results:
- The trigeminal inflammatory compression (TIC) model reliably induced mechanical allodynia, persisting for over 10 weeks.
- Nerve edema and macrophage infiltration were observed in the infraorbital nerve and trigeminal ganglia.
- Suppression of microglial activation reversed mechanical allodynia; cold allodynia was detected at 4 weeks.
Conclusions:
- A simple, reproducible mouse model for chronic orofacial neuropathic pain (Type 2) was successfully developed.
- The model mimics clinical pain by inducing sustained mechanical and cold allodynia.
- This model provides a valuable tool for investigating orofacial pain mechanisms and potential therapies.

