I am a
Home I AM A Search Login

Papers of the Week

Papers: 12 Aug 2023 - 18 Aug 2023

Basic Science

Animal Studies, Molecular/Cellular, Neurobiology, Pharmacology/Drug Development

Neuropathic Pain

2023 Aug 09

Br J Anaesth


An anchor-tether ‘hindered’ HCN1 inhibitor is antihyperalgesic in a rat spared nerve injury neuropathic pain model.


Tibbs GR, Uprety R, Warren JD, Beyer NP, Joyce RL, Ferrer MA, Mellado W, Wong VSC, Goldberg DC, Cohen MW, Costa CJ, Li Z, Zhang G, Dephoure NE, Barman DN, Sun D, Ingólfsson HI, Sauve AA, Willis DE, Goldstein PA


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.