Optimizing Kv7 Channel Openers for Treatment of GWI Pain

Our laboratory developed an animal model that replicates some of the symptoms of the chronic pain of GWI. Through this animal model we identified molecular targets in pain sensing neurons, which appear to have been chronically altered following exposure to insecticides and repellants that were present in the GW theater. Kv7 openers (KVOs) have known analgesic/palliative capacities that could serve as treatments for the chronic pain associated with GWI. We have previously shown that Retigabine (aKVO) can temporarily reverse signs of GWI pain. In an effort to improve upon these findings, we tested the capacity of a combination KVO treatment strategy to reverse pain-signs in our GWI pain model. Experiments completed in year 1 confirm that certain combinations of KVOs can significantly improve outcomes on molecular targets relative to the performance of individual KVOs. Experiments have further shown that these KVO combinations can greatly retard action potential discharges that occur following an acetylcholine challenge. In year 2 we will move toward behavioral testing in our rat model.