말초신경 손상에 의한 배근신경절 세포의 전기생리적 특성 변화

Abstract

Background: The neuropathic pain induced by peripheral nerve injury has been shown to be spontaneous, hyperalgesia and allodynia. If the neuropathic pain is related to the sympathetic system, it is classified as a sympathetically maintained pain (SMP). SMP is aggravated by sympathetic activation, and sympathetic block is used as a clinical treatment. Until now, it has been unclear what mechanism is involved in the aggravation of the pain due to sympathetic activation. Many investigations relating to this topic, using experimental animal models, have confirmed that the sensory nerve is activated due to sympathetic activation, and is mediated by the alpha adrenergic receptor. However, the detailed mechanism for the involvement of the alpha adrenergic receptor on the sympathetic-sensory coupling is controversial, as many previous experiments have been performed using in vivo preparations that could not exclude many complicating factors. Therefore, injured dorsal root ganglion cells were isolated, and the effects of norepinephrine, which is known to be involved in membrane excitability, investigated on several ionic channels. Methods: The neuropathic animal models were made by ligation of the L5 and L6 spinal nerves of rats. The dorsal root ganglion cells were immediately isolated, and the electrophysiologic properties studied using a patch clamp technique.

Results: In the current clamp mode, the membrane excitability was confirmed to be increased by the norepinephrine, and in the voltage clamp mode, the inward Ca2⁢ and outward K⁢ currents were decreased by the norepinephrine, in the DRG neuron of the neuropathic model rat. Yohimbine, an α2 antagonist, suppressed the inhibitory effect of the norepinephrine on the inward Ca2⁢ and outward K⁢ currents of the neuropathic DRG neuron. Cadmium, a calcium channel blocker, suppressed the inhibitory effect of the norepinephrine on the outward K⁢ current, and iberiotoxin, a calcium activated potassium channel (KCa) blocker, suppressed the inhibitory effect of the norepinephrine on the outward K⁢ current of the neuropathic DRG neuron.

Conclusions: These results suggest the direct actions of norepinephrine on DRG neuron at least contribute to the sympathetic-sensory coupling, and that suppression of the KCa channel activity may be an important mechanism in this process.