Principles of nociceptive coding in the anterior cingulate cortex

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.

Claustrum projections to the anterior cingulate modulate nociceptive and pain-associated behaviour

“…The ACC plays many functions in the sensory and emotional processing of pain 2,3,40,41 . Distinct circuits within the ACC likely modulate these diverse functions through connections to varied subcortical and cortical connections 42,43 .…”

An amygdala-to-cingulate cortex circuit for conflicting choices in chronic pain

“…Finally, it would be important to follow the activity patterns of ACC-projecting BLA neurons during the different stages of the task in order to establish their exact contribution to the avoidance behavior. 57 All these points could represent potential new avenues for exploration.…”

Dysregulated neuromodulation in the anterior cingulate cortex in chronic pain

“…Chronic pain-induced increase in the likelihood of pyramidal activation with any given stimulus leads to disruptions in what we pay attention to. Recent endoscopic imaging studies conclude that the proportion of nociception-sensitive neurons in the ACC is increased in neuropathic conditions (Li Anna et al, 2021;Acuña et al, 2023). Behaviorally, a disruption in the filtering process required for sensory discrimination might explain why a noxious stimulus specifically receives our attention in normal conditions and why an innocuous stimulus can be perceived as painful in neuropathic conditions (Vander Weele et al, 2018).…”

“…Lastly, although ACC activity is positively correlated with pain sensitization, this is not always the case. Recent reports indicate that gabapentin and nitrous oxide can in fact induce an increase in ACC activity alongside analgesia (Acuña et al, 2023;Weinrich et al, 2023). Given this, the role of the ACC in modulating attention and pain perception is more nuanced than it appears and it may be possible to reinstate proper somatosensory filtering by increasing the activity of specific ACC circuits.…”