Targeting the cholinergic system as a therapeutic strategy for the treatment of pain.
Acetylcholine mediates its effects through both the nicotinic acetylcholine receptors (ligand-gated ion channels) and the G protein-coupled muscarinic receptors. It plays pivotal roles in a diverse array of physiological processes and its activity is controlled through enzymatic degradation by acetylcholinesterase. The effects of receptor agonists and enzyme inhibitors, collectively termed cholinomimetics, in antinociception/analgesia are well established. These compounds successfully inhibit pain signaling in both humans and animals and are efficacious in a number of different preclinical and clinical pain models, suggesting a broad therapeutic potential. In this review we examine and discuss the evidence for the therapeutic exploitation of the cholinergic system as an approach to treat pain.
Jones
Philip G
PG
Neuroscience Discovery Research, Wyeth Research, CN8000, Princeton, NJ 08543, USA. philip.jones@sepracor.com
Dunlop
John
J
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D006801:Humans; D010146:Pain / Q000378:metabolism; D059408:Pain Management; D011950:Receptors, Cholinergic / Q000502:physiology*
D011950:Receptors, Cholinergic; D000110:Acetylcholinesterase; D000109:Acetylcholine