Mar 29, 2020

An Amygdalo-Parabrachial Pathway Regulates Pain Perception and Chronic Pain

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Charles RaverAsaf Keller

Abstract

The parabrachial (PB) complex mediates both ascending nociceptive signaling and descending pain modulatory information in the affective/emotional pain pathway. We have recently reported that chronic pain is associated with amplified activity of PB neurons in a rat model of neuropathic pain. Here we demonstrate that similar activity amplification occurs in mice, and that this is related to suppressed inhibition to lateral parabrachial (LPB) neurons from the CeA in animals of either sex. Animals with pain after chronic constriction injury of the infraorbital nerve (CCI-Pain) displayed higher spontaneous and evoked activity in PB neurons, and a dramatic increase in after-discharges, responses that far outlast the stimulus, compared with controls. LPB neurons in CCI-Pain animals showed a reduction in inhibitory, GABAergic inputs. We show that, in both rats and mice, LPB contains few GABAergic neurons, and that most of its GABAergic inputs arise from CeA. These CeA GABA neurons express dynorphin, somatostatin, and/or corticotropin releasing hormone. We find that the efficacy of this CeA-LPB pathway is suppressed in chronic pain. Further, optogenetically stimulating this pathway suppresses acute pain, and inhibiting it, in naive anim...Continue Reading

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Mentioned in this Paper

Negative Regulation of Glutamate Receptor Signaling Pathway
DNA Amplification
Corticotropin-Releasing Hormone
Dynorphins
Optogenetics
Protein Expression
GABAergic Neurons
Pain
Amygdaloid Structure
Acute Onset Pain

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