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Calvo-Enrique, L.

Publications and source records attributed to Calvo-Enrique, L..

2 recordsLinked to original sources

Neural ensembles that encode affective mechanical and heat pain in mouse spinal cord

Acute pain is an unpleasant experience caused by noxious stimuli. How the spinal neural circuits attribute differences in quality of noxious information remains unknown. By means of genetic capturing, activity manipulation and single cell RNA sequencing, we identified distinct neural ensembles in mouse spinal cord encoding mechanical and heat pain. Re-activation or silencing of these ensembles potentiated or stopped, respectively, affective but not reflex behaviour without altering pain behaviour to cross stimuli modality. Within ensembles, polymodal Gal+ inhibitory neurons with monosynaptic contacts to A-fiber sensory neurons gated affective pain independent of modality. Peripheral nerve injury led to microglia driven inflammation and an ensemble transition with decreased recruitment of Gal+ inhibitory neurons and increased excitatory drive. However, activating Gal+ neurons reversed hypersensitivity associated with neuropathy. Our results reveal the existence of a spinal representation which forms the neural basis of the discriminative and affective qualities of acute pain and that these neurons are under the control of a shared feed-forward inhibition.

neuroscience↗

Sensory Schwann cells are required for mechanical nociception and touch perception

That sensory neurons alone transduce mechanical stimuli was challenged by the discovery of nociceptive Schwann cells that can initiate pain. Consistent with the existence of inherently mechanosensitive sensory Schwann cells, we found that the mechanosensory function of almost all nociceptors, including those signaling fast pain, were critically dependent on sensory Schwann cells. Furthermore, in polymodal nociceptors, sensory Schwann cells signal mechanical, but not cold or heat pain. Terminal Schwann cells also surround mechanoreceptor nerve-endings within the Meissners corpuscle and in at hair follicle lanceolate endings that both signal vibrotactile touch. Within Meissners corpuscles, two molecularly and functionally distinct sensory Schwann cells positive for Sox10 and Sox2 differentially modulate rapidly adapting mechanoreceptor function. Using optogenetics we show that Meissners corpuscle Schwann cells are necessary for the perception of low threshold vibrotactile stimuli. These results show that sensory Schwann cells within diverse glio-neural mechanosensory end-organs are sensors for mechanical pain as well as necessary for touch perception. Thus, specialized sensory Schwann are central to the transduction of mechanical forces that underpin somatic sensation.

neuroscience↗