The flow of somatosensory information through the spinal dorsal horn is regulated by synaptic inhibition, which acts upon excitatory and inhibitory interneurons, but the former are especially prone to disinhibition.
In models of chronic migraine, neuronal complexity is diminished in head-pain processing regions but restored through HDAC6 inhibition, which increases tubulin acetylation and cytoskeletal flexibility, and CGRP receptor blockade.
Alterations to brain network communication leading to a progressive loss in descending inhibitory modulation of the spinal cord is a key determinate of pain state development following peripheral nerve injury.
Although primary sensory neuron-derived calcitonin gene-related peptide (CGRP) contributes to the processing of pain messages, an understudied population of dorsal horn CGRP-expressing interneurons also contributes to the processing of mechanical sensitivity.
A signal amplifier network that transmits mechanical pain is delineated through characterising an excitatory interneuron population in the spinal cord dorsal horn and defining the postsynaptic populations they regulate.
An interdisciplinary approach uncovers a new antinociceptive molecular mechanism and shows that the adhesion GPCR CIRL adjusts the sensation of gentle touch and noxious mechanical insult in opposite directions.
Development of a fully automated pain scale using machine learning tools in computational neuroethology and creation of new software, reveals a robust circuit-dissection compatible platform for objective pain measurement.