Role of P2X3 Purinoreceptors of Nociceptive Afferent Neurons in the Formation of an Inflammation-Related Pain Syndrome

Abstract

Ionotropic purine P2X receptors play important roles in the processes of generation and transmission of nociceptive signals. The relative roles of certain subtypes of these receptors in the above processes have not, however, been finally elucidated. To a significant extent, this is explained by the absence of selective modulators of their functioning. In this study, we examined the effects of a nonhydrolyzable analog of diadenosine polyphosphates (ADPs), diadenosine 5’,5’’’-P1,P4-(β,γ-methylene) tetraphosphate (AppCH 2 ppA), on purinoreceptors of segmental sensory neurons in vitro and also effects of this agent in vivo on nociception in rats under conditions of induction of different pain syndromes. As was found, this ADP selectively modulates functioning of purinoreceptors of the P2X 3 subtype, and high-affinity desensitization is the mechanism of this effect. It was observed that ADP significantly influences the mechanisms of peripheral, but not central, sensitization under inflammation conditions. The results obtained allow us to conclude that receptors of the P2X 3 subtype can be considered the main receptor group responsible for transmission of nociceptive information under the above-mentioned conditions. It was also demonstrated that P2X 3 receptors are practically not involved in the processes of generation of pain syndromes of neuropathic nature.