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P2X3 Receptor Involvement in Pain States

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Abstract

The understanding of how pain is processed at each stage in the peripheral and central nervous system is the precondition to develop new therapies for the selective treatment of pain. In the periphery, ATP can be released from various cells as a consequence of tissue injury or visceral distension and may stimulate the local nociceptors. The highly selective distribution of P2X3 and P2X2/3 receptors within the nociceptive system has inspired a variety of approaches to elucidate the potential role of ATP as a pain mediator. Depolarization by ATP of neurons in pain–relevant neuronal structures such as trigeminal ganglion, dorsal root ganglion, and spinal cord dorsal horn neurons are well investigated. P2X receptor-mediated afferent activation appears to have been implicated in visceral and neuropathic pain and even in migraine and cancer pain. This article reviews recently published research describing the role that ATP and P2X receptors may play in pain perception, highlighting the importance of the P2X3 receptor in different states of pain.

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Fig. 1

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Abbreviations

BBG:

Brilliant blue G

BzATP:

2′- and 3′-O-(4-benzoyl-benzoyl)-ATP

CFA:

complete Freund’s adjuvant

CGRP:

calcitonin gene related peptide

DRG:

dorsal root ganglion

ERK:

extracellular signal-regulated protein kinase

Ip5I:

di-inosine pentaphosphate

IBS:

irritable bowel syndrome

α,β-meATP:

α,β-methylene ATP

2-MeSATP:

2-methylthio ATP

NK-1:

neurokinin-1

PAR:

proteinase-activated receptors

PPADS:

pyridoxal-phosphate-6-azophenyl-2′, 4′-disulfonic acid

RB2:

reactive blue 2

TG:

trigeminal ganglion

TNP-ATP:

trinitrophenyl-substituted ATP

TRPV1:

transient receptor potential vanilloid 1

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  1. Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Haertelstrasse 16-18, 04107, Leipzig, Germany

    Kerstin Wirkner & Peter Illes

  2. Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1450, Budapest, Hungary

    Beata Sperlagh

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  1. Kerstin Wirkner
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Wirkner, K., Sperlagh, B. & Illes, P. P2X3 Receptor Involvement in Pain States. Mol Neurobiol 36, 165–183 (2007). https://doi.org/10.1007/s12035-007-0033-y

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