title: Hyperpolarization-activated cyclic nucleotide-gated channels may contribute to regional anesthetic effects of lidocaine.
abstract: BACKGROUND
  Local anesthetics (e.g., lidocaine) have been found to inhibit hyperpolarization-activated cyclic nucleotide-gated (HCN) channels besides sodium channels. However, the exact role of HCN channels in regional anesthesia in vivo is still elusive.
  
  
  METHODS
  Sciatic nerve block and intrathecal anesthesia were performed using lidocaine in wild-type and HCN1 channel knockout (HCN1) mice. EC50 of lidocaine and durations of 1% lidocaine were determined. In electrophysiologic recordings, effects of lidocaine on HCN channel currents, voltage-gated sodium channel currents, and neural membrane properties were recorded on dorsal root ganglia neurons.
  
  
  RESULTS
  In both sciatic nerve block and intrathecal anesthesia, EC50 of lidocaine for tactile sensory blockade (2 g von Frey fiber) was significantly increased in HCN1 mice, whereas EC50 of lidocaine for pinprick blockade was unaffected. Durations of 1% lidocaine were significantly shorter in HCN1 mice for both sciatic nerve block and intrathecal anesthesia (n = 10). ZD7288 (HCN blocker) could significantly prolong durations of 1% lidocaine including pinprick blockade in sciatic nerve block (n = 10). Forskolin (raising cyclic adenosine monophosphate to enhance HCN2) could significantly shorten duration of pinprick blockade of 1% lidocaine in sciatic nerve block (n = 10). In electrophysiologic recordings, lidocaine could nonselectively inhibit HCN channel and sodium channel currents both in large and in small dorsal root ganglia neurons (n = 5 to 6). Meanwhile, lidocaine caused neural membrane hyperpolarization and increased input resistance of dorsal root ganglia neurons but not in large dorsal root ganglia neurons from HCN1 mice (n = 5-7).
  
  
  CONCLUSIONS
  These data indicate that HCN channels may contribute to regional anesthetic effects of lidocaine. By inhibiting HCN channels, lidocaine could alter membrane properties of neurons.
authors.affiliation: From the Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu, China (C.Z., B.K., D.L., T.L., J.L., X.C.); Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China (Y.Z., P.L., J.L.); and Department of Anesthesiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.C.).
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhou
authors.forename: Bowen
authors.initials: B
authors.lastname: Ke
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Peng
authors.initials: P
authors.lastname: Liang
authors.forename: Daqing
authors.initials: D
authors.lastname: Liao
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Chen
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000037:antagonists & inhibitors* / Q000502:physiology*; D007278:Injections, Spinal; D008012:Lidocaine / Q000008:administration & dosage*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D016896:Treatment Outcome
chemical_list: D000779:Anesthetics, Local; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008012:Lidocaine