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Hyperpolarisation-activated cyclic nucleotide (HCN)-modulated ion channels are best known for their fundamental pacemaker role in the heart; here, we review data demonstrating that the HCN2 isoform acts in an analogous way as a \u2018pacemaker for pain\u2019, in that its activity in nociceptive neurons is critical for the maintenance of electrical activity and for the sensation of chronic pain in pathological pain states. Pharmacological block or genetic deletion of HCN2 in sensory neurons provides robust pain relief in a variety of animal models of inflammatory and neuropathic pain, without any effect on normal sensation of acute pain. We discuss the implications of these findings for our understanding of neuropathic pain pathogenesis, and we outline possible future opportunities for the development of efficacious and safe pharmacotherapies in a range of chronic pain syndromes.<\/jats:p>","DOI":"10.1042\/bcj20160287","type":"journal-article","created":{"date-parts":[[2016,9,12]],"date-time":"2016-09-12T10:47:33Z","timestamp":1473677253000},"page":"2717-2736","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["HCN2 ion channels: basic science opens up possibilities for therapeutic intervention in neuropathic pain"],"prefix":"10.1042","volume":"473","author":[{"given":"Christoforos","family":"Tsantoulas","sequence":"first","affiliation":[{"name":"Wolfson Centre for Age-Related Research, King's College London, Guy's Campus, London Bridge, London, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R.","family":"Mooney","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Cambridge, Cambridge, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"McNaughton","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age-Related Research, King's College London, Guy's Campus, London Bridge, London, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2016,9,12]]},"reference":[{"key":"2021112216314742600_BCJ-2016-0287C1","unstructured":"Sherrington, C.S\n          . 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