This is my newest paper, in which, by means of in vivo single unit spinal cord electrophysiology in rats, I optogenetically activated coeruleospinal circuit and investigated its effect on the expression status of Diffuse Noxious Inhibitory Controls (DNIC).
Coerulean noradrenergic system yet again proofs to be heterogeneous, and here we show that it also stands true for its role in the modulation of spinal WDR neurons' excitability. My work on this started in 2016 by finding an unexpected action of spinal alpha2-adrenoceptor antagonist (atipamezole) in a disease model I was studying in that time. Searching for answers took off, and led to pretty cool basic system neuroscience. Yet again a disease teaches us something about basics of the system functioning (spoiler alert - the disease paper is yet to come).
Abstract: Brainstem to spinal cord noradrenergic pathways include a locus coeruleus origin projection and diffuse noxious inhibitory controls. While both pathways are traditionally viewed as exerting an inhibitory effect on spinal neuronal activity, the locus coeruleus was previously shown to have a facilitatory influence on thermal nociception according to the subpopulation of coerulean neurons activated. Coupled with knowledge of its functional modular organisation and the fact that diffuse noxious inhibitory controls are not expressed in varied animal models of chronicity, we hypothesised a regulatory role for the locus coeruleus on non-coerulean, discrete noradrenergic cell group(s).
We implemented locus coeruleus targeting strategies by microinjecting canine adenovirus encoding for channelrhodopsin-2 under a noradrenaline-specific promoter in the spinal cord (retrogradely labelling a coeruleospinal module) or the locus coeruleus itself (labelling the entire coerulean module). Coeruleospinal module optoactivation abolished diffuse noxious inhibitory controls (Two-Way ANOVA, P < 0.0001), which were still expressed following locus coeruleus neuronal ablation.
We propose that the cerulean system interacts with, but does not directly govern, diffuse noxious inhibitory controls. This mechanism may underlie the role of the locus coeruleus as a ‘chronic pain generator’. Pinpointing the functionality of discrete top-down pathways is crucial for understanding sensorimotor modulation in health and disease.