A cellular mechanism contributing to pain-induced analgesia.

Franciosa, Federica; Acuña, Mario A; Nevian, Natalie E; Nevian, Thomas (2024). A cellular mechanism contributing to pain-induced analgesia. (In Press). Pain Wolters Kluwer 10.1097/j.pain.0000000000003315

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The anterior cingulate cortex (ACC) plays a crucial role in the perception of pain. It is consistently activated by noxious stimuli and its hyperactivity in chronic pain indicates plasticity in the local neuronal network. However, the way persistent pain effects and modifies different neuronal cell types in the ACC and how this contributes to sensory sensitization is not completely understood. This study confirms the existence of 2 primary subtypes of pyramidal neurons in layer 5 of the rostral, agranular ACC, which we could classify as intratelencephalic (IT) and cortico-subcortical (SC) projecting neurons, similar to other cortical brain areas. Through retrograde labeling, whole-cell patch-clamp recording, and morphological analysis, we thoroughly characterized their different electrophysiological and morphological properties. When examining the effects of peripheral inflammatory pain on these neuronal subtypes, we observed time-dependent plastic changes in excitability. During the acute phase, both subtypes exhibited reduced excitability, which normalized to pre-inflammatory levels after day 7. Daily conditioning with nociceptive stimuli during this period induced an increase in excitability specifically in SC neurons, which was correlated with a decrease in mechanical sensitization. Subsequent inhibition of the activity of SC neurons projecting to the periaqueductal gray with in vivo chemogenetics, resulted in reinstatement of the hypersensitivity. Accordingly, it was sufficient to enhance the excitability of these neurons chemogenetically in the inflammatory pain condition to induce hypoalgesia. These findings suggest a cell type-specific effect on the descending control of nociception and a cellular mechanism for pain-induced analgesia. Furthermore, increased excitability in this neuronal population is hypoalgesic rather than hyperalgesic.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology
UniBE Contributor:	Franciosa, Federica Angela, Acuña Miranda, Mario Andrés, Nevian, Natalie, Nevian, Thomas
Subjects:	600 Technology > 610 Medicine & health
ISSN:	1872-6623
Publisher:	Wolters Kluwer
Language:	English
Submitter:	Pubmed Import
Date Deposited:	08 Jul 2024 11:35
Last Modified:	08 Jul 2024 11:35
Publisher DOI:	10.1097/j.pain.0000000000003315
PubMed ID:	38968393
URI:	https://boris.unibe.ch/id/eprint/198593