Brigham Young University, Department of Psychology/Neuroscience, Provo, Utah, 84602, USA.
College of Korean Medicine, Daegu Haany University, Daegu, 42158, South Korea.
Brain Stimul. 2020 Mar-Apr;13(2):403-411. doi: 10.1016/j.brs.2019.11.012. Epub 2019 Dec 4.
Growing evidence suggests that mechanical stimulation modulates substrates in the supraspinal central nervous system (CNS) outside the canonical somatosensory circuits.
OBJECTIVE/METHODS: We evaluate mechanical stimulation applied to the cervical spine at the C7-T1 level (termed "MStim") on neurons and neurotransmitter release in the mesolimbic dopamine (DA) system, an area implicated in reward and motivation, utilizing electrophysiological, pharmacological, neurochemical and immunohistochemical techniques in Wistar rats.
Low frequency (45-80 Hz), but not higher frequency (115 Hz), MStim inhibited the firing rate of ventral tegmental area (VTA) GABA neurons (52.8% baseline; 450 s) while increasing the firing rate of VTA DA neurons (248% baseline; 500 s). Inactivation of the nucleus accumbens (NAc), or systemic or in situ antagonism of delta opioid receptors (DORs), blocked MStim inhibition of VTA GABA neuron firing rate. MStim enhanced both basal (178.4% peak increase at 60 min) and evoked DA release in NAc (135.0% peak increase at 40 min), which was blocked by antagonism of DORs or acetylcholine release in the NAc. MStim enhanced c-FOS expression in the NAc, but inhibited total expression in the VTA, and induced translocation of DORs to neuronal membranes in the NAc.
These findings demonstrate that MStim modulates neuron firing and DA release in the mesolimbic DA system through endogenous opioids and acetylcholine in the NAc. These findings demonstrate the need to explore more broadly the extra-somatosensory effects of peripheral mechanoreceptor activation and the specific role for mechanoreceptor-based therapies in the treatment of substance abuse.
越来越多的证据表明，机械刺激会调节脊髓上中枢神经系统（CNS）中感觉以外的基质。
目的/方法：我们评估了应用于 C7-T1 水平颈椎的机械刺激（称为“MStim”）对中脑边缘多巴胺（DA）系统神经元和神经递质释放的影响，该系统与奖励和动机有关，使用电生理学、药理学、神经化学和免疫组织化学技术在 Wistar 大鼠中进行。
低频（45-80 Hz）而非高频（115 Hz）MStim 抑制腹侧被盖区（VTA）GABA 神经元的放电率（基线的 52.8%；450 s），同时增加 VTA DA 神经元的放电率（基线的 248%；500 s）。伏隔核（NAc）失活或全身或原位拮抗δ阿片受体（DORs），阻断 MStim 抑制 VTA GABA 神经元放电率。MStim 增强了 NAc 中的基础（60 分钟时峰值增加 178.4%）和诱发的 DA 释放（40 分钟时峰值增加 135.0%），这被 NAc 中的 DOR 拮抗剂或乙酰胆碱释放所阻断。MStim 增强了 NAc 中的 c-FOS 表达，但抑制了 VTA 中的总表达，并诱导了 DORs 在 NAc 神经元膜中的易位。
这些发现表明，MStim 通过 NAc 中的内源性阿片类物质和乙酰胆碱调节中脑边缘 DA 系统中的神经元放电和 DA 释放。这些发现表明需要更广泛地探索外周机械感受器激活的非感觉作用，以及基于机械感受器的治疗在治疗药物滥用中的特定作用。
