The central amygdala to periaqueductal gray pathway comprises intrinsically distinct neurons differentially affected in a model of inflammatory pain

Abstract

Key points The central nucleus of the amygdala (CeA) encompasses the main output pathways of the amygdala, a temporal lobe structure essential in affective and cognitive dimensions of pain. A major population of neurons in the CeA send projections to the periaqueductal gray (PAG), a key midbrain structure that mediates coping strategies in response to threat or stress. CeA‐PAG neurons are topographically organized based on their targeted subregion within the PAG. PAG‐projecting neurons in the central medial (CeM) and central lateral (CeL) regions of CeA are intrinsically distinct. CeL‐PAG neurons are a homogeneous population of intrinsically distinct neurons while CeM‐PAG neurons are intrinsically heterogeneous. Membrane properties of distinct CeM‐PAG subtypes are altered in the complete Freund's adjuvant model of inflammatory pain. Abstract A major population of neurons in the central nucleus of amygdala (CeA) send projections to the periaqueductal gray (PAG), a key midbrain structure that mediates coping strategies in response to threat or stress. While the CeA‐PAG pathway has proved to be a component of descending anti‐nociceptive circuitry, the functional organization of CeA‐PAG neurons remains unclear. We identified CeA‐PAG neurons in C57BL/6 mice of both sexes using intracranial injection of a fluorescent retrograde tracer into the PAG. In acute brain slices, we investigated the topographical and intrinsic characteristics of retrogradely labelled CeA‐PAG neurons using epifluorescence and whole‐cell electrophysiology. We also measured changes to CeA‐PAG neurons in the complete Freund's adjuvant (CFA) model of inflammatory pain. Neurons in the central lateral (CeL) and central medial (CeM) amygdala project primarily to different regions of the PAG. CeL‐PAG neurons consist of a relatively homogeneous population of intrinsically distinct neurons while CeM‐PAG neurons are intrinsically heterogeneous. Membrane properties of distinct CeM‐PAG subtypes are altered 1 day after induction of the CFA inflammatory pain model. Collectively, our results provide insight into pain‐induced changes to a specific population of CeA neurons that probably play a key role in the integration of noxious input with endogenous analgesia and behavioural coping response.

Cell-type specificity of neuronal excitability and morphology in the central amygdala

“…Together, our results 32 identify fundamentally important distinguishing features of PKCδ + and Som + cells that support cell-33 type-specific function in the CeA. 34 35 Keywords: central amygdala, Somatostatin, protein kinase C delta, intrinsic excitability, 36 morphology, neuropathic pain 37 2002, Chieng et al, 2006, Schiess et al, 1999, Li and Sheets, 2018. Recent studies have further 64 shown that CeLC neurons with different firing properties are topographically organized based on 65 their projection targets (Li and Sheets, 2018), suggesting that heterogeneity of function within the 66 CeLC might also be anatomically defined.…”

Inhibitory Effects of Columbianadin on Nociceptive Behaviors in a Neuropathic Pain Model, and on Voltage-Gated Calcium Currents in Dorsal Root Ganglion Neurons in Mice

“…To acclimatize mice to the test procedure, they were placed in the containers for 45 min prior to each test session. A set of eight calibrated von Frey filaments ranging from 0.008 to 6 g (North Coast Medical, Morgan Hill, CA, USA) were applied alternately to the plantar surface of each hind paw until they bent (Li and Sheets, 2018). The duration of each stimulus was approximately 1 s and nociceptive behaviors were considered to be retraction/lifting, rapid shaking, and/or licking of the hind paw.…”

Stress-induced analgesia: The role of the HPA axis hormones

“…Особую роль для развития СВА играет взаимодействие между амигдалой и ЦСВСМ (Kim et al 2013;Li, Sheets 2018). Основой для этого взаимодействия выступают КРФ сигнальные пути, вовлекающиеся в регуляцию болевой чувствительности.…”