title: Effects of minocycline on Na+ currents in rat dorsal root ganglion neurons.
abstract: Minocycline is an inhibitor of microglial activation and proliferation. Minocycline suppresses pain-related behaviors in many different pain states, which correlates closely with its inhibition of microglial activation and subsequent release of pro-inflammatory mediators in the spinal cord. Na(+) channels in dorsal root ganglion (DRG) neurons are implicated in the generation of inflammatory and neuropathic pain. To elucidate a possible peripheral mechanism of minocycline analgesia, effects of minocycline on tetrodotoxin-sensitive and tetrodotoxin-resistant Na(+) currents in rat DRG neurons were investigated. Minocycline potently inhibited both types of Na(+) currents with IC(50) values of 350 nM and 410 nM, respectively. The inhibition was accompanied by a depolarizing shift of the activation voltage. However, minocycline slowed the inactivation and speeded up the recovery from inactivation. These results suggest minocycline may exert analgesia peripherally thorough Na(+) channel inhibition in the primary afferent neurons as well as centrally through microglial inhibition in the spinal cord.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: Hong Im
authors.initials: HI
authors.lastname: Kim
authors.forename: Jungho
authors.initials: J
authors.lastname: Kim
authors.forename: Mijung
authors.initials: M
authors.lastname: Park
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Song
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008911:Minocycline / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000700:Analgesics; D000900:Anti-Bacterial Agents; D015222:Sodium Channels; D013779:Tetrodotoxin; D008911:Minocycline