# Cell Danger Response Theory A theory put forth by Robert Naviaux, MD, PhD. He proposes that cells signal distress via release of extracellular ATP (eATP). When cells are damaged, under attack, metabolically stressed, or even just under threat, they will "bleed" ATP to alert surrounding cells to their distress. The amount of eATP they leak is proportional to the danger. This signal is spread through neighboring cells to the rest of the body, including to the brain through the vagus nerve. The eATP activates purinergic receptors which signal the cell to switch from daily maintenance functions to a state of self defense. The Cell Danger Response must be completed before the healing cycle can begin. Once the eATP signals go down, the cells become more receptive to parasympathetic "top down" signals of safety. Therefore, a person with cells chronically stuck in the cell danger response will experience illness signals and behavior (eg. fatigue, pain). Furthermore, the cell danger response is very metabolically expensive. It is, after all, utilizing energy currency as its signaling molecule. Therefore, when the danger signaling volume needs to be turned up (eg. illness signals are not leading to the desired illness behaviors) or when the cell danger response is being activated frequently (eg. because the cell danger response is being triggered over and over again) the cell handles this by increasing sensitivity so that a less expensive signal (less ATP) is needed to produce the same response. Acquired hypersensitivity to eATP signaling causes hypersensitivity to many environmental changes across several sensory domains: infections, environmental chemicals, exercise, social stress, etc. Dr. Naviaux has studied subjects with ME/CFS and ADHD. Both populations have symptomatic improvement with antipurinergic therapy (blocking eATP receptors or increasing breakdown rate of eATP). # Antipurinergic Therapy Suramin blocks ATP loss but is not yet available for use in humans. Plavix, a prescription antiplatelet medication, is also a purinergic (ADP) receptor blocker. Promising herbs: berberine containing herbs or extracts (Coptis chinensis, goldenseal, oregon grape, barberry), ginsenasides or ginseng (synapsin intranasal may be better for brain inflammation), andragrafis, Chinese skullcap - combining all of these may be helpful. # Sources and Links 1. [Naviaux Lab](https://naviauxlab.ucsd.edu/publications/) 2. [Robert Naviaux, MD, PhD | ME/CFS Cell Danger Response, Metabolic Features, Low-energy in Nature - YouTube](https://www.youtube.com/watch?v=u028TAyB9S4)