Characterization of electrophysiological properties of trigeminal ganglion neurons that innervate the maxillary sinus in mice

The 2024 MSC Emerging Science Contest for Early-Career Investigators took place on December 9, 2024. Below is a written summary of one of the presentations from the contest. (A recording of the event is available here).

Category: Pain

Runner up: Saurav Gupta, University of Alabama at Birmingham

Title: Characterization of electrophysiological properties of trigeminal ganglion neurons that innervate the maxillary sinus in mice

Hypothesis, methodology, findings and conclusions
Our research aimed to understand the nerve cells responsible for transmitting pain signals from the maxillary sinus (a sinus in the cheek area) to the brain. We hypothesized that these neurons, located in the trigeminal ganglion (TG), play a crucial role in generating noxious pressure and persistent pain during migraine or sinus pain. To test this, we injected a fluorescent dye into the sinus of mice, which allowed us to track and study the electrical activity of these specific neurons using a method called patch-clamp recording. We compared these neurons in normal mice and genetically modified mice to explore differences in their electrical properties.

We found that the sinus-related neurons had unique characteristics: they were small, had broader electrical signals (action potentials), and fired persistently when stimulated, which may explain their role in ongoing pain. These neurons were distinct from other known pain neurons (Nav1.8-positive) because they had a larger size, different firing properties, and showed features commonly seen in pain-sensing neurons (nociceptors).

This study adds new understanding by showing that sinus-related pain might be caused by a specific subset of neurons with unique properties, which could help explain why sinus pain can become chronic and hard to treat. For clinicians, this suggests that new treatments targeting these specific neurons could improve care for patients suffering from chronic sinus pain, particularly those who do not respond well to current therapies like antibiotics or sinus surgeries.

Implications for understanding migraine disease and/or its comorbidities, or how the research holds promise as a new avenue of future migraine study.
Our research on the nerve cells that transmit pain signals from the maxillary sinus may have important implications for understanding migraine disease. Migraines often present with symptoms that mimic sinus infections, such as facial pressure and pain. By identifying a distinct subset of neurons responsible for sinus pain, we open up the possibility that these same neurons might play a role in migraine-related sinus-like symptoms. This could help clarify why migraines are sometimes misdiagnosed as sinus issues and offer new insights into the connection between the trigeminal system and migraine-related pain.

Additionally, chronic pain from the sinuses might be a comorbidity for some migraine patients. Since our study highlights the unique properties of sinus-innervating neurons, understanding how these neurons interact with migraine pathways could shed light on why some patients experience both sinus and migraine pain. If sinus TG neurons contribute to the overactivation of pain pathways during a migraine, targeting these neurons may offer a novel approach to alleviating certain migraine symptoms.

Future migraine studies could focus on how these sinus TG neurons behave in migraine models and whether they are activated or altered during migraine attacks. This research holds promise for developing new migraine treatments that specifically target sinus-related pain pathways, providing relief for patients who experience both sinus pain and migraine.

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