ATP, P2X receptors and pain pathways

A role for ATP in nociception and pain induction was proposed on the basis of human psychophysical experiments shortly after the formulation of the pu rinergic hypothesis. Following the pharmacological definition of distinct P 2X and P2Y purinergic receptor subtypes by Burnstock and his collaborators, molecular cloning studies have identified the gene products that underlie the effects of ATP on peripheral sensory neurons. One particular receptor, P2X,, is of particular interest in the context of pain pathways, because it is relatively selectively expressed at high levels by nociceptive sensory neurons. Evidence that this receptor may play a role in the excitation of s ensory neurons has recently been complemented by studies that suggest an ad ditional presynaptic role in the regulation of glutamate release from prima ry afferent neurons in the dorsal horn of the spinal cord. In this brief re view, we discuss the present state of knowledge of the role of ATP in pain induction through its action on peripheral P2X receptors. (C) 2000 Elsevier Science B.V. All rights reserved.