{"title":"HCN channels: novel therapeutic targets for peripheral neuropathic pain.","authors":"Paul Howard","doi":"10.1136/spcare-2025-005509","DOIUrl":null,"url":null,"abstract":"<p><p>Hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels control neuronal firing thresholds. Together with sodium channels, they accumulate at sites of nerve injury, creating ectopic foci of action potential generation (EFAPG) that result in neuropathic pain.Their presence may explain why EFAPG do not always respond to sodium channel blockers (eg, lacosamide). Further, several current analgesics (clonidine, dexmedetomidine, ketamine and systemic lidocaine) block HCN channels in addition to their better-known actions. Future research could explore the use of ivabradine (an HCN blocker) and multichannel blockade for refractory EFAPG and develop tools to distinguish EFAPG from secondary 'upstream' pain mechanisms (eg, central sensitisation).</p>","PeriodicalId":9136,"journal":{"name":"BMJ Supportive & Palliative Care","volume":" ","pages":"469-472"},"PeriodicalIF":2.0000,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMJ Supportive & Palliative Care","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/spcare-2025-005509","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEALTH CARE SCIENCES & SERVICES","Score":null,"Total":0}
引用次数: 0
Abstract
Hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels control neuronal firing thresholds. Together with sodium channels, they accumulate at sites of nerve injury, creating ectopic foci of action potential generation (EFAPG) that result in neuropathic pain.Their presence may explain why EFAPG do not always respond to sodium channel blockers (eg, lacosamide). Further, several current analgesics (clonidine, dexmedetomidine, ketamine and systemic lidocaine) block HCN channels in addition to their better-known actions. Future research could explore the use of ivabradine (an HCN blocker) and multichannel blockade for refractory EFAPG and develop tools to distinguish EFAPG from secondary 'upstream' pain mechanisms (eg, central sensitisation).
期刊介绍：
Published quarterly in print and continuously online, BMJ Supportive & Palliative Care aims to connect many disciplines and specialties throughout the world by providing high quality, clinically relevant research, reviews, comment, information and news of international importance.
We hold an inclusive view of supportive and palliative care research and we are able to call on expertise to critique the whole range of methodologies within the subject, including those working in transitional research, clinical trials, epidemiology, behavioural sciences, ethics and health service research. Articles with relevance to clinical practice and clinical service development will be considered for publication.
In an international context, many different categories of clinician and healthcare workers do clinical work associated with palliative medicine, specialist or generalist palliative care, supportive care, psychosocial-oncology and end of life care. We wish to engage many specialties, not only those traditionally associated with supportive and palliative care. We hope to extend the readership to doctors, nurses, other healthcare workers and researchers in medical and surgical specialties, including but not limited to cardiology, gastroenterology, geriatrics, neurology, oncology, paediatrics, primary care, psychiatry, psychology, renal medicine, respiratory medicine.
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