Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Biochem Biophys Res Commun. 2019 Apr 30;512(2):352-359. doi: 10.1016/j.bbrc.2019.03.051. Epub 2019 Mar 17.
The ability to detect noxious stimulation is essential to an organism's survival and wellbeing. Chronic pain is characterized by abnormal sensitivity to normal stimulation coupled with a feeling of unpleasantness. This condition afflicts people worldwide and severely impacts their quality of life and has become an escalating health problem. The spinal cord dorsal horn is critically involved in nociception and chronic pain. Especially, the substantia gelatinosa (SG) neurons of lamina II, which receives nociceptive inputs from primary afferents. Two major models are used to study chronic pain in animals, including nerve injury and the injection of a complete Freund's adjuvant (CFA) into the hind paw. However, how these models induce glutamatergic synaptic plasticity in the spinal cord is not fully understood. Here, we studied synaptic plasticity on excitatory transmissions in the adult rat SG neurons. Using in vitro and in vivo whole-cell patch-clamp recording methods, we analyzed spontaneous excitatory postsynaptic currents (sEPSCs) 2 weeks following nerve injury and 1 week following CFA injection. In the spinal slice preparation, these models increased both the frequency and amplitude of sEPSCs in SG neurons. The frequency and amplitude of sEPSCs in the nerve injury and the CFA group were reduced by the presence of tetrodotoxin (TTX). By contrast, TTX did not reduce the sEPSCs compared with miniature EPSCs in naïve rats. Next, we analyzed the active electrophysiological properties of neurons, which included; resting membrane potentials (RMPs) and the generation of action potentials (APs) in vitro. Interestingly, about 20% of recorded SG neurons in this group elicited spontaneous APs (sAPs) without changing the RMPs. Furthermore, we performed in vivo whole-cell patch-clamp recording in SG neurons to analyze active electrophysiological properties under physiological conditions. Importantly, in vivo SG neurons generated sAPs without affecting RMP in the nerve injury and the CFA group. Our study describes how animal models of chronic pain influence both passive and active electrophysiological properties of spinal SG neurons.
检测有害刺激的能力对生物体的生存和健康至关重要。慢性疼痛的特征是对正常刺激异常敏感，并伴有不愉快的感觉。这种情况在全球范围内都有发生，严重影响了人们的生活质量，已经成为一个不断加剧的健康问题。脊髓背角在伤害感受和慢性疼痛中起着关键作用。特别是，I 层的胶状质（SG）神经元，它接收来自初级传入的伤害性输入。有两种主要的动物模型用于研究慢性疼痛，包括神经损伤和向后爪注射完全弗氏佐剂（CFA）。然而，这些模型如何在脊髓中诱导谷氨酸能突触可塑性还不完全清楚。在这里，我们研究了成年大鼠 SG 神经元兴奋性传递中的突触可塑性。使用离体和体内全细胞膜片钳记录方法，我们分析了神经损伤后 2 周和 CFA 注射后 1 周的自发兴奋性突触后电流（sEPSC）。在脊髓切片制备中，这些模型增加了 SG 神经元中 sEPSC 的频率和幅度。神经损伤和 CFA 组中 sEPSC 的频率和幅度可被河豚毒素（TTX）降低。相比之下，与未处理的大鼠相比，TTX 并没有降低 sEPSC 与微电泳 EPSC 的比值。接下来，我们分析了神经元的主动电生理特性，包括：静息膜电位（RMP）和动作电位（AP）的产生。有趣的是，该组约 20%的记录的 SG 神经元在不改变 RMP 的情况下自发产生 AP（sAP）。此外，我们在 SG 神经元中进行了体内全细胞膜片钳记录，以分析生理条件下的主动电生理特性。重要的是，在神经损伤和 CFA 组中，体内 SG 神经元产生 sAP 而不影响 RMP。我们的研究描述了慢性疼痛动物模型如何影响脊髓 SG 神经元的被动和主动电生理特性。
