The precise mechanisms by which electrical stimulation affects pain intensity are not known. However, it is postulated that Cranial Electro Stimulator treatment reduce pain and symptoms by two main mechanisms of action, "gate control" and "modulation of brain and body neurochemicals".

Cranial electrical stimulation, and stimulation at selected points of the peripheral nervous system, have been shown to modulate brain neurochemicals, such as endorphins, serotonin, ACTH, epinephrine and norepinephrine. Some of these neurochemicals act as natural morphine-like agents to inhibit pain, while others raise the pain threshold in a natural manner. Studies have shown that serotonin, beta-endorphins and ACTH levels have continued to change up to four hours following treatment. However, the positive effect of the neurochemical changes on patient pain level has been reported to last up to 48 hours after treatment.

A recent neurochemical study indicates that beta-endorphin, serotonin and melatonin increase in plasma and cerebrospinal fluid after a 20-minute cranial stimulation treatment. (J Neurol OrthopMed Surg (1998) 18:94-97)