title: Minocycline inhibits hyperpolarization-activated currents in rat substantia gelatinosa neurons.
abstract: Minocycline is a widely used glial activation inhibitor that could suppress pain-related behaviors in a number of different pain animal models, yet, its analgesic mechanisms are not fully understood. Hyperpolarization-activated cation channel-induced Ih current plays an important role in neuronal excitability and pathological pain. In this study, we investigated the possible effect of minocycline on Ih of substantia gelatinosa neuron in superficial spinal dorsal horn by using whole-cell patch-clamp recording. We found that extracellular minocycline rapidly decreases Ih amplitude in a reversible and concentration-dependent manner (IC50 = 41 μM). By contrast, intracellular minocycline had no effect. Minocycline-induced inhibition of Ih was not affected by Na(+) channel blocker tetrodotoxin, glutamate-receptor antagonists (CNQX and D-APV), GABAA receptor antagonist (bicuculine methiodide), or glycine receptor antagonist (strychnine). Minocycline also caused a negative shift in the activation curve of Ih, but did not alter the reversal potential. Moreover, minocycline slowed down the inter-spike depolarizing slope and produced a robust decrease in the rate of action potential firing. Together, these results illustrate a novel cellular mechanism underlying minocycline's analgesic effect by inhibiting Ih currents of spinal dorsal horn neurons.
authors.affiliation: Department of Pediatrics, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Pain Clinic, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Daying
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pain Clinic, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Mengye
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Center for Laboratory Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Pediatrics, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China; Center for Laboratory Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China. Electronic address: liutaomm@hotmail.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000378:metabolism*; D008161:Lumbosacral Region; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D008911:Minocycline / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D017207:Rats, Sprague-Dawley; D013331:Strychnine / Q000502:physiology; D013376:Substantia Gelatinosa / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D046509:Tissue Culture Techniques
chemical_list: D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D049990:Membrane Transport Modulators; C017069:bicuculline methiodide; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D008911:Minocycline; D013331:Strychnine; D001640:Bicuculline
keywords: Ih current; Minocycline; Substantia gelatinosa neuron; Whole-cell patch-clamp recording