The role of adenosine and P2Y receptors expressed by multiple cell types in pain transmission

Abstract

The role of extracellular nucleotides and nucleosides as signaling molecules in cell-to-cell communication has now been clearly established. This is particularly true in the central and peripheral nervous system, where purines and pyrimidines are involved in both physiological and pathological interactions between neurons and surrounding glial cells. It can be thus foreseen that the purinergic system could represent a new potential target for the development of effective analgesics, also through the normalization of neuronal functions and the inhibition of glial cell activation. Research in the last 15 years has progressively confirmed this hypothesis, but no purinergic-based analgesics have reach the market so far; in the present review we have collected the more recent discoveries on the role of G protein-coupled P2Y nucleotide and of adenosine receptors expressed by both neurons and glial cells under painful conditions, and we have highlighted some of the challenges that must be faced to translate basic and preclinical studies to clinics.

Electroacupuncture Inhibits the Activity of Astrocytes in Spinal Cord in Rats with Visceral Hypersensitivity by Inhibiting P2Y1 Receptor‐Mediated MAPK/ERK Signaling Pathway

“…EA stimulation can significantly inhibit the PKC membrane translocation level thereby inhibiting the pain signal transmission process and thus playing an analgesic role in the visceral hypersensitivity [32]. Upon P2Y 1 receptor activation, the endogenous glutamate released by astrocytes has an excitatory regulatory effect on neurons [33]. In this study, we tested the hypothesis that EA may inhibit the activity of glial cells by jointly inhibiting the P2Y 1 receptor-mediated activation of PKC and MAPK/ ERK pathway to relieve visceral hypersensitivity.…”

Purinergic Signaling in Endometriosis-Associated Pain

“…In recent years, many articles concerning endometriosis-associated pain and treatments for pain-relief have been published (reviewed in [ 10 , 11 , 49 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ]); independently, the purinergic mechanisms involved in pain (reviewed in [ 18 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]) are also being studied. However, purinergic signaling in relation to endometriosis-associated pain has yet to be fully explored.…”

Cell Communications among Microorganisms, Plants, and Animals: Origin, Evolution and Interplays

“…A particular intercellular connection is the synapse either between neurons or between a neuron and a muscle cell [96]. which they are ligands of the P2X receptor (ATP-gated receptor channel) and of the P2Y receptor (seven-transmembrane spanning receptor) that are both involved in pain sensitivity [101,102]. In contrast, adenosine acts through P1 receptors [103].…”