Gareth R Tibbs, Rajendra Uprety, J David Warren, Nicole P Beyer, Rebecca L Joyce, Matthew A Ferrer, Wilfredo Mellado, Victor S C Wong, David C Goldberg, Melanie W Cohen, Christopher J Costa, Zhucui Li, Guoan Zhang, Noah E Dephoure, Dipti N Barman, Delin Sun, Helgi I Ingólfsson, Anthony A Sauve, Dianna E Willis, Peter A Goldstein
BACKGROUND: Neuropathic pain impairs quality of life, is widely prevalent, and incurs significant costs. Current pharmacological therapies have poor/no efficacy and significant adverse effects; safe and effective alternatives are needed. Hyperpolarisation-activated cyclic nucleotide-regulated (HCN) channels are causally implicated in some forms of peripherally mediated neuropathic pain. Whilst 2,6-substituted phenols, such as 2,6-di-tert-butylphenol (26DTB-P), selectively inhibit HCN1 gating and are antihyperalgesic, the development of therapeutically tolerable, HCN-selective antihyperalgesics based on their inverse agonist activity requires that such drugs spare the cardiac isoforms and do not cross the blood-brain barrier...
August 9, 2023: British Journal of Anaesthesia