title: HCN2 ion channels: an emerging role as the pacemakers of pain.
abstract: Acute nociceptive pain is caused by the direct action of a noxious stimulus on pain-sensitive nerve endings, whereas inflammatory pain (both acute and chronic) arises from the actions of a wide range of inflammatory mediators released following tissue injury. Neuropathic pain, which is triggered by nerve damage, is often considered to be very different in its origins, and is particularly difficult to treat effectively. Here we review recent evidence showing that members of the hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channel family - better known for their role in the pacemaker potential of the heart - play important roles in both inflammatory and neuropathic pain. Deletion of the HCN2 isoform from nociceptive neurons abolishes heat-evoked inflammatory pain and all aspects of neuropathic pain, but acute pain sensation is unaffected. This work shows that inflammatory and neuropathic pain have much in common, and suggests that selective blockers of HCN2 may have value as analgesics in the treatment of pain.
authors.affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Emery
authors.forename: Gareth T
authors.initials: GT
authors.lastname: Young
authors.forename: Peter A
authors.initials: PA
authors.lastname: McNaughton
mesh_terms: D000200:Action Potentials; D059787:Acute Pain / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007249:Inflammation / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism*; D059226:Nociceptive Pain / Q000209:etiology / Q000378:metabolism*; D015221:Potassium Channels; D011458:Prostaglandins E / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism
chemical_list: C578710:HCN2 protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D011458:Prostaglandins E; D043562:Receptors, G-Protein-Coupled; D000242:Cyclic AMP