Release of intracellular potassium as the physiological stimulus for pain

¹ Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Evidence is presented that various types of pain-producing stimuli also release intracellular potassium, and that potassium is a pain-producing stimulus. If the potassium releasing process is inhibited or neutralized by calcium, or reversed by increasing cellular uptake of potassium by means of a glucose-insulin combination, the response to painful stimuli is decreased. Calcium appears to have a more immediate effect on pain, while the effects of the glucose-insulin combination become more apparent at a later stage. When the two agents are combined there is no summation of the effect produced by each one individually. Itch is not affected by this glucose-insulin combination. It is suggested that the role of histamine in pain production is via the potassium releasing process. Evidence is considered to indicate that the major effect of a noxious stimulus is not the direct effect on the pain receptor but indirect due to the tissue reaction.