[ ABSTRACT] Rebound depolarization is a special phenomenon of the neurons which generates action potential fol-lowed by a hyperpolarization stimulation.It can be recorded in many kinds of neurons and is the intrinsic membrane charac-teristic of them.Rebound depolarization plays an important role in regulating the firing pattern, rhythmic activity and sy-naptic plasticity of neurons.This review focuses on the basic characteristics, the function and mechanism of the rebound depolarization in physiological and pathological conditions, which provides reference for the clinical treatment of rebound depolarization-related diseases.

OBJECTIVETo investigate the effect of minocycline on hyperpolarization-activated current (Ih) in the substantia gelatinosa (SG) neurons in rat spinal dorsal horn.

METHODSIn vitro spinal cord transverse slices were prepared from 3-5-week-old male Sprague-Dawley rats. Using whole-cell patch clamp technique, Ih currents were recorded before and after bath application of minocycline (1-300 µmol/L) to the SG neurons.

RESULTSIh currents were observed in nearly 50% of the recorded neurons, and were blocked by Ih blocker CsCl and ZD7288. Minocycline rapidly and reversibly reduced the amplitude of Ih and decreased the current density in a concentration-dependent manner with an IC50 of 34 µmol/L.

CONCLUSIONMinocycline suppresses the excitability of SG neurons through inhibiting the amplitude and current density of Ih and thereby contributes to pain modulation.

Animals ; Male ; Minocycline ; pharmacology ; Neurons ; drug effects ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Substantia Gelatinosa ; cytology

The thalamocortical (TC) circuit is closely associated with pain processing. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 channel is predominantly expressed in the ventral posterolateral thalamus (VPL) that has been shown to mediate neuropathic pain. However, the role of VPL HCN2 in modulating TC circuit activity is largely unknown. Here, by using optogenetics, neuronal tracing, electrophysiological recordings, and virus knockdown strategies, we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex (S1HL) as well as mechanical hypersensitivity following spared nerve injury (SNI)-induced neuropathic pain in mice. Either pharmacological blockade or virus knockdown of HCN2 (shRNA-Hcn2) in the VPL was sufficient to alleviate SNI-induced hyperalgesia. Moreover, shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL-S1HL circuit. Together, our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.
Animals ; Mice ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics* ; Neuralgia ; RNA, Small Interfering ; Thalamus/metabolism* ; Up-Regulation