title: Minocycline enhances inhibitory transmission to substantia gelatinosa neurons of the rat spinal dorsal horn.
abstract: Minocycline, a second-generation tetracycline, is well known for its antibiotic, anti-inflammatory, and antinociceptive effects. Modulation of synaptic transmission is one of the analgesic mechanisms of minocycline. Although it has been reported that minocycline may suppress excitatory glutamatergic synaptic transmission, it remains unclear whether it could affect inhibitory synaptic transmission, which also plays a key role in modulating pain signaling. To examine the effect of minocycline on synaptic transmission in rat spinal substantia gelatinosa (SG) neurons, we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) using whole-cell patch-clamp recording at a holding potential of 0 mV. Bath application of minocycline significantly increased the frequency but not the amplitude of sIPSCs in a reversible and concentration-dependent manner with an EC50 of 85. The enhancement of inhibitory synaptic transmission produced by minocycline was not affected by the glutamate receptor antagonists CNQX and D-APV or by the voltage-gated sodium channel blocker tetrodotoxin (TTX). Moreover, the potency of minocycline for facilitating sIPSC frequency was the same in both glycinergic and GABAergic sIPSCs without changing their decay phases. However, the facilitatory effect of minocycline on sIPSCs was eliminated in a Ca(2+)-free Krebs solution or by co-administration with calcium channel blockers. In summary, our data demonstrate that baseline inhibitory synaptic transmission in SG neurons is markedly enhanced by minocycline. This may function to decrease the excitability of SG neurons, thus leading to a modulation of nociceptive transmission.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: H-Z
authors.initials: HZ
authors.lastname: Peng
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: L-X
authors.initials: LX
authors.lastname: Ma
authors.affiliation: Center for Laboratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: M-H
authors.initials: MH
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: T
authors.initials: T
authors.lastname: Hu
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: T
authors.initials: T
authors.lastname: Liu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013376:Substantia Gelatinosa / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D008911:Minocycline
keywords: inhibitory postsynaptic currents; minocycline; nociception; substantia gelatinosa; whole-cell patch clamp