Effects of prostaglandin E(2) on the intensity of bradykinin-evoked pain from skin and veins of humans

Prostaglandin E(2) increases bradykinin-induced spike activity from polymodal nociceptors of the skin and deep tissues in animals, suggesting sensitization of these receptors. To see whether these neurophysiological observations in animals correspond with increased pain intensity in humans, and whether also vascular nociceptors are sensitized, we studied in humans the effects of prostaglandin E(2) on the intensity of pain evoked by bradykinin via the nociceptive systems of skin and veins. In seven healthy subjects, bradykinin was injected into the skin and into a vascularly isolated hand vein segment, prior to and after local application of prostaglandin E(2). Subsequent pain intensity was recorded continuously with an electronically controlled visual analogue scale. Prostaglandin E(2) alone never elicited pain, but without exception increased the intensity of bradykinin-induced pain in a concentration-related manner at concentrations from 10(-9) to 10(-6) M, both in skin and veins. Thus, bradykinin is more painful after pretreatment with prostaglandin E(2), suggesting sensitization of nociceptors of the skin, but also of hand veins in humans.