These are the details from the FPRF Symposium presentation regarding a potential rescue medication for trigeminal neuralgia (TN) breakthrough pain.
Lightning Talk Overview: Dr. Stephen Bart (Vanderbilt Health) discussed a novel approach: combining guanfacine (usually used for high blood pressure and ADHD) and lidocaine (nerve block) as a nasal spray to help TN patients quickly manage severe pain episodes at home.
Why these medications? – Vanderbilt’s BioVU database research indicated that guanfacine targets the ADRA2B gene, which is strongly associated with trigeminal nerve disorders. – This led them to try guanfacine as a potential adjunct for TN.
Clinical Trial: – 38 participants: Compared lidocaine-alone with lidocaine plus guanfacine in a crossover study. – The combination provided significantly better pain relief (for the first 8 hours) than lidocaine alone, with no serious adverse effects. – Guanfacine’s effect is short-lived (fading within a day), matching its breakdown time in the body.
Next Steps: – Development of a nasal spray combining lidocaine and guanfacine for at-home use as a rescue therapy. – Preliminary tests with a 3D-printed nasal model showed promising targeting and minimal risk to the lungs. – Plans include FDA discussions, manufacturing, and larger multi-center trials, with ongoing support from the Facial Pain Research Foundation.
Details:
Dr. Stephen Bart, a researcher on the drug repurposing team at Vanderbilt Health, gave a brief lightning talk at the Facial Pain Research Symposium about a new treatment approach for trigeminal neuralgia (TN) breakthrough pain. The idea is to combine two existing medications — both already FDA-approved for other conditions — and reformulate them as a nasal spray that patients could keep at home as a “rescue” medication for moments of severe pain.
How the medications were chosen: Vanderbilt has a large database (called BioVU) that links thousands of patients’ genetic information with their de-identified medical records. The drug repurposing team searched for signals in BioVU starting from genes that drugs are known to target and looking for medical conditions that are more common in people with specific genetic variations. They found that people with a particular variation in a gene called ADRA2B (which makes a receptor that the medication guanfacine binds to) are about 4.6 times more likely to have a trigeminal nerve disorder. That suggested that guanfacine — already approved decades ago for high blood pressure and ADHD — might help with TN.
The clinical trial: The team tested this idea in a 38-patient randomized trial. Patients received either a lidocaine nerve block alone or lidocaine plus a small dose of guanfacine, then later crossed over to receive the other treatment. The combination produced significantly more pain relief in the first 8 hours than lidocaine alone, with no serious side effects. The added benefit from guanfacine faded within a day, which is consistent with how long it takes the body to break down guanfacine.
What’s next: Many TN patients can’t easily get a nerve-block injection — they must schedule an appointment, wait, and deal with insurance, which doesn’t work for those who need something right now! The team is now developing an intranasal spray that combines lidocaine and guanfacine that patients could use at home for breakthrough pain. They’ve already tested the spray’s aim using a 3D-printed model of the human nasal cavity, with most of the drug reaching the right area where the trigeminal nerve runs, and very little ending up in the lungs. The next steps are FDA discussions, manufacturing scale-up, and a multi-center trial as a rescue medication, which the Facial Pain Research Foundation is supporting.