Minocycline Enhances Inhibitory Transmission To Substantia Gelatinosa Neurons Of The Rat Spinal Dorsal Horn

Objective: Minocycline, a second-generation of 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 has remained unclear whether it could affect inhibitory synaptic transmission which also plays a key role in modulating pain signalling. To investigate the analgesic mechanisms of minocycline, we examined the effect of minocycline on inhibitory synaptic transmission in rat spinal substantia gelatinosa(SG) neurons by using whole-cell patch clamp recording.Methods: After spinal slice was prepared, we recorded the spontaneous inhibitory postsynaptic currents(s IPSCs) in different groups at a holding potential(HP) of 0 m V.Results: Bath application of minocycline significantly increased the frequency but not the amplitude of s IPSCs in a reversible and concentration-dependent manner with EC50 of 85 μM. The enhancement of inhibitory synaptic transmission produced by minocycline was not affected by glutamate receptor antagonists CNQX and APV or voltage-gated sodium channel blocker tetrodotoxin(TTX). Moreover, the potency of minocycline for facilitating s IPSC frequency was the same in both glycinergic and GABAergic s IPSCs without changing their decay phases. However, the facilitatory effect of minocycline on s IPSCs was eliminated in a Ca2+-free Krebs solution or co-administration with calcium channel blockers.Conclusions: In summary, our data demonstrate that inhibitory synaptic transmission in substantia gelatinosa neurons is markedly enhanced by minocycline. This may function to decrease excitability of substantia gelatinosa neuron, thus leading to a modulation of nociceptive transmission.