Department of Physiology, University of Bern, Bern 3012, Switzerland.
Grupo de Neurociencia de Sistemas, Instituto de Fisiología y Biofísica "Bernardo Houssay", Universidad de Buenos Aires y Consejo Nacional de Investigaciones Científicas y Técnicas, Grupo de Neurociencia de Sistemas, Buenos Aires C1121ABG, Argentina.
Proc Natl Acad Sci U S A. 2023 Jun 6;120(23):e2212394120. doi: 10.1073/pnas.2212394120. Epub 2023 May 30.
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.
疼痛的感知是一种源自分布式大脑活动的多维感觉和情感/情感体验。然而，涉及的大脑区域并非专门用于疼痛。因此，皮层如何将伤害性感受与其他厌恶和显著的感觉刺激区分开来仍然难以捉摸。此外，慢性神经病理性疼痛对感觉处理的后果尚未得到描述。使用在体微型显微镜钙成像技术，对自由活动的小鼠进行细胞分辨率的成像，我们阐明了前扣带皮层（疼痛处理所必需的区域）中伤害性和感觉编码的原理。我们发现，群体活动而不是单细胞反应允许区分有害与其他感觉刺激，排除了存在伤害感受特异性神经元的可能性。此外，单细胞刺激选择性随时间具有高度动态性，但群体水平的刺激表示保持稳定。外周神经损伤引起的慢性神经病理性疼痛导致感觉事件的编码功能障碍，表现为对无害刺激的反应加剧以及模式分离和刺激分类受损，这些可通过镇痛治疗得到恢复。这些发现为慢性神经病理性疼痛中皮层感觉处理的改变提供了新的解释，并深入了解了系统镇痛治疗在皮层中的作用。
