The neural-glial purinergic receptor ensemble in chronic pain states.
Chronic pain is characterized by enhanced sensory neurotransmission that underlies increased sensitivity to noxious stimuli and the perception of non-noxious stimuli as painful. Evidence from neurophysiological and pharmacological studies demonstrates that ATP produces pain by directly enhancing neuronal excitability via the activation of specific ligand-gated ion channels, the P2X3 and P2X2/3 receptors. In addition, ATP activates CNS glial cells (e.g. microglia) in response to persistent nociceptive stimulation. This latter effect involves several distinct receptor-mediated signaling pathways linked to the P2X4, P2X7 and P2Y(12) receptors. This review summarizes new data that places these purinergic signaling events in a mechanistic context that illustrates the ability of ATP to initiate and maintain states of heightened sensory neuron excitability associated with persistent pain.
Jarvis
Michael F
MF
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6123, USA. michael.jarvis@abbott.com
D000818:Animals; D002908:Chronic Disease; D006801:Humans; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D018048:Receptors, Purinergic P2