关键词: anterior cingulate cortex in vivo calcium imaging neuropathic pain nociception sensory representation

Mesh : Humans Mice Animals Gyrus Cinguli / diagnostic imaging Nociception / physiology Neuralgia Brain Nociceptors

来  源:   DOI:10.1073/pnas.2212394120   PDF(Pubmed)

Abstract:
The perception of pain is a multidimensional sensory and emotional/affective experience arising from distributed brain activity. However, the involved brain regions are not specific for pain. Thus, how the cortex distinguishes nociception from other aversive and salient sensory stimuli remains elusive. Additionally, the resulting consequences of chronic neuropathic pain on sensory processing have not been characterized. Using in vivo miniscope calcium imaging with cellular resolution in freely moving mice, we elucidated the principles of nociceptive and sensory coding in the anterior cingulate cortex, a region essential for pain processing. We found that population activity, not single-cell responses, allowed discriminating noxious from other sensory stimuli, ruling out the existence of nociception-specific neurons. Additionally, single-cell stimulus selectivity was highly dynamic over time, but stimulus representation at the population level remained stable. Peripheral nerve injury-induced chronic neuropathic pain led to dysfunctional encoding of sensory events by exacerbation of responses to innocuous stimuli and impairment of pattern separation and stimulus classification, which were restored by analgesic treatment. These findings provide a novel interpretation for altered cortical sensory processing in chronic neuropathic pain and give insights into the effects of systemic analgesic treatment in the cortex.
摘要:
疼痛的感知是由分布式大脑活动引起的多维感觉和情绪/情感体验。然而,受累的大脑区域对疼痛并不特异。因此,大脑皮层如何区分伤害性和其他令人厌恶和显著的感觉刺激仍然难以捉摸。此外,慢性神经性疼痛对感觉过程的影响尚未得到表征。在自由移动的小鼠中使用具有细胞分辨率的体内微镜钙成像,我们阐明了前扣带皮质的伤害性和感觉编码的原理,疼痛处理所必需的区域。我们发现人口活动,不是单细胞反应,允许区分有害和其他感官刺激,排除了伤害性感受特异性神经元的存在。此外,随着时间的推移,单细胞刺激选择性是高度动态的,但人口层面的刺激代表性保持稳定。周围神经损伤引起的慢性神经性疼痛通过加重对无害刺激的反应以及模式分离和刺激分类的损害而导致感觉事件的功能失调。通过镇痛治疗恢复了。这些发现为慢性神经性疼痛中皮质感觉过程的改变提供了新的解释,并提供了对皮质中全身镇痛治疗效果的见解。
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