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青少年身体虐待的伤害性应激模型可引起情境性恐惧和扣带回伤害性神经可塑性变化。

A nociceptive stress model of adolescent physical abuse induces contextual fear and cingulate nociceptive neuroplasticities.

机构信息

Cingulum Neurosciences Institute, Manlius, NY, USA.

Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA.

出版信息

Brain Struct Funct. 2018 Jan;223(1):429-448. doi: 10.1007/s00429-017-1502-3. Epub 2017 Aug 31.

DOI:10.1007/s00429-017-1502-3
PMID:28861709
Abstract

Adolescent physical abuse impairs emotional development and evokes cingulate pathologies, but its neuronal and circuit substrates are unknown. Conditioning adolescent rabbits with noxious colorectal distension for only 2 h over 3 weeks simulated the human child abuse in amplitude, frequency, and duration. Thermal withdrawal thresholds were unchanged suggesting that sensitized spinal mechanisms may not be operable. Unchanged weight, stools, colorectal histology, and no evidence of abdominal pain argue against tissue injury or irritable bowel syndrome. Contextual fear was amplified as they avoided the site of their abuse. Conditioning impacted anterior cingulate and anterior midcingulate (ACC, aMCC) neuron excitability: (1) more neurons responded to cutaneous and visceral (VNox) noxious stimuli than controls engaging latent nociception (present but not manifest in controls). (2) Rear paw stimulation increased responses over forepaws with shorter onsets and longer durations, while forepaw responses were of higher amplitude. (3) There were more VNox responses with two excitatory phases and longer durations. (4) Some had unique three-phase excitatory responses. (5) Long-duration VNox stimuli did not inhibit neurons as in controls, suggesting the release of an inhibitory circuit. (6) aMCC changes in cutaneous but not visceral nociception confirmed its role in cutaneous nociception. For the first time, we report neuroplasticities that may be evoked by adolescent physical abuse and reflect psychogenic pain: i.e., no ongoing peripheral pain and altered ACC nociception. These limbic responses may be a cognitive trace of abuse and may shed light on impaired human emotional development and sexual function.

摘要

青少年躯体虐待会损害情绪发展并引发扣带病变,但其神经元和回路基础尚不清楚。仅用 2 小时,对青少年兔子进行 3 周的有害结直肠扩张条件反射,模拟了人类儿童虐待的幅度、频率和持续时间。热退缩阈值没有变化,这表明敏感的脊髓机制可能不起作用。体重、粪便、结直肠组织学均无变化,且无腹痛证据,这表明不存在组织损伤或肠易激综合征。由于它们避免了受虐待的地方,因此情境性恐惧加剧。条件反射会影响前扣带和前中扣带(ACC,aMCC)神经元的兴奋性:(1)与对照组相比,更多的神经元对皮肤和内脏(VNox)有害刺激有反应,从而激活了潜在的伤害感受(在对照组中存在但未表现出)。(2)后爪刺激引起的反应超过前爪,其潜伏期更短,持续时间更长,而前爪反应的幅度更高。(3)有更多具有两个兴奋相和更长持续时间的 VNox 反应。(4)有些神经元具有独特的三相兴奋反应。(5)与对照组相比,长时 VNox 刺激不会抑制神经元,这表明抑制性回路被释放。(6)aMCC 在皮肤而非内脏痛觉中的变化证实了其在皮肤痛觉中的作用。我们首次报告了青少年躯体虐待可能引发的神经可塑性变化,并反映了心理性疼痛:即,没有持续的外周疼痛和 ACC 伤害感受改变。这些边缘系统的反应可能是虐待的认知痕迹,并可能为受损的人类情绪发展和性功能提供线索。

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