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Papers of the Week
An anchor-tether ‘hindered’ HCN1 inhibitor is antihyperalgesic in a rat spared nerve injury neuropathic pain model.
Authors
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 PAAbstract
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.