Electrophysiological Properties of Neuronal Subpopulations Within the Spinopontoamygdaloid Pathway in Relation to A Mouse Model of Time-Dependent Neuropathic Pain

In this study we evaluated neurons within both the parabrachial nucleus (PBN) and central amygdala (CeA). These two regions are part of the spinopontoamygdaloid pathway, responsible for relaying nociceptive information from medullary dorsal horns to the PBN which projects to the CeA. In rodent models, synaptic pain plasticity within this pathway has been characterized previously. Our goal was to understand the intrinsic and firing properties of PBN neurons projecting to the CeA, as well as the distinct genetic subtypes of CeA neurons and how these might vary depending on sex and timepoint following neuropathic injury. To this end, we used patch-clamp electrophysiology to target neurons of interest labeled by fluorescent retrograde tracers or cre-dependent tdTomato fluorescence expressed in transgenic mice. Firing type heterogeneity was observed in both the general and CeA projecting populations of the PBN, and pain plasticity only within the general population. Within the CeA, cells expressing calcitonin gene-related peptide receptor (CGRPR+) display an excitability gradient along rostro-caudal levels, and only neurons patched from caudal slices exhibited pain plasticity. In protein kinase delta expressing CeA neurons (PKCδ+), female mice showed injury-induced increases in excitability in both firing types, while this was only observed in late firing neurons in experiments using male mice. At a four-week timepoint following injury, we see no significant injury-induced change in excitability in CGRPR+ or PKCδ+, however somatostatin expressing neurons do show increases in excitability. This demonstrates the relevance of sex, chronicity and anatomical position to the CeA’s capacity to modulate pain.