Endogenous opioids in the etiology and treatment of multiple sclerosis

Endogenous opioids are enkephalins and endorphins that are primarily produced in the brain and have multiple actions throughout the body. Enkephalins and endorphins act at opioid receptors and their activity can be blocked by opioid antagonists. A small pentapeptide termed opioid growth factor (OGF), and chemically termed [Met5]-enkephalin, has been shown to have causative and therapeutic roles in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). Enkephalin levels are reduced in animals and humans during MS relapses, and may play a role in etiology. Exogenous therapy with OGF or endogenous stimulation of OGF by low dosages of naltrexone (LDN) reverse the course of progressive EAE and limit the number of relapses in relapsing- remitting EAE. Individuals prescribed LDN report less fatigue and a better quality of life while using LDN. This chapter summarizes the information from studies using two different animal models of EAE, as well as two different treatment regimens of two different compounds-OGF or LDN. In all investigations, the presence of enkephalins resulted in beneficial effects.