Highlights

  • Automated Pain Measurement: Dr. Basbaum’s lab developed an automated, machine-learning-based system (DeepLabCut) to objectively track and quantify pain-related behaviors in mice, enhancing the accuracy and reproducibility of results.
  • Model Relevance: The FRICT-ION mouse model shows carbamazepine (a standard TN treatment) reverses pain symptoms, validating the model’s relevance to human TN.
  • Novel Drug Findings:
    • Alpha-2A receptor agonists (like PS75) proved highly effective without causing sedation or low blood pressure, an improvement over related drugs.
    • Compound X also demonstrated strong efficacy, but its identity remains confidential due to intellectual property.
    • NSAIDs and CGRP antagonists (migraine drugs) were ineffective, suggesting the model specifically captures TN pain mechanisms, not just general facial pain.
  • Advanced Neuronal Imaging: The team worked on establishing a method to monitor individual trigeminal ganglion neurons in awake animals—groundbreaking for understanding where TN drugs exert their effects.
  • Therapeutic Implications: Early data suggest PS75 acts locally at the trigeminal ganglion, paving the way for TN treatments that target the problem area while avoiding central nervous system side effects.
Allan Basbaum, PhD – Topic Speaker

Co-Chair SAB, University of California San Francisco

Dr. Allan Basbaum began pain research with Ronald Melzack at McGill University, received his Ph.D. from University of Pennsylvania, and did postdoctoral research with Patrick Wall. Presently, he is a professor and chair of the Department of Anatomy at UCSF. His research focuses on peripheral and central nervous system mechanisms that process pain and itch messages, including molecular mechanisms that contribute to chronic pain after tissue or nerve injury. He served as Editor-in-Chief of PAIN, is a member of the National Academy of Medicine, and the National Academy of Sciences, and is a fellow of the UK Royal Society.

PRESENTATION SUMMARY
Dr. Allan Basbaum, Co-Chair of the Facial Pain Research Foundation’s Scientific Advisory Board and Professor at UCSF, presented his laboratory’s work on developing and testing new pain medications for trigeminal neuralgia (TN). His group is using a refined version of Dr. Karin Westlund’s “FRICT-ION” mouse model — the same mouse model many of the day’s other speakers have been using — to identify medications that work and to understand exactly where in the body they are acting.

A challenge in pain research is that mouse pain experiments often rely on someone watching a mouse and counting how many times the mouse rubs its face or wipes its cheek. This is slow, can be biased, and is hard to reproduce. Dr. Basbaum’s lab has built an automated system using cameras and machine-learning software (called DeepLabCut) that tracks paw movement and head movement automatically — turning subjective observations into clean, quantitative measurements that any computer can verify. Head movement turned out to be the most sensitive readout, lasting up to five months after the initial nerve injury.

Using this system, the team tested several drug classes. Carbamazepine — the standard TN treatment in patients — reversed the mouse pain measures, confirming the model is clinically relevant. A new class of medications called alpha-2A receptor agonists (specifically a compound called PS75) worked very well and, importantly, did not produce the sedation or low blood pressure that limits a related drug (dexmedetomidine) currently used in intensive care units. A separate experimental compound — referred to as “Compound X” — was very effective but the lab cannot disclose its identity yet because of intellectual property considerations.

Notably, the team showed that some drug classes do NOT work in this model: NSAIDs (like ibuprofen) and a CGRP antagonist (a class used for migraine) had no effect. This is important because it confirms the model is specifically capturing TN-like nerve pain — not just generic facial pain.

The most novel part of the work is a method, submitted for publication, allows the team to record activity of individual neurons inside the trigeminal ganglion (the nerve cluster supplying the face) for a full year in awake animals. This is unprecedented technology that could finally answer the fundamental question of where TN pain medications are actually acting — in the brain, in the spinal cord, or directly at the trigeminal ganglion. Early data suggest PS75 acts directly on the ganglion. Future work will compare this to where other drugs act, with the goal of designing better TN treatments that work locally and avoid the side effects of medications that affect the whole brain.