TAFA4 Reverses Mechanical Allodynia through Activation of GABAergic Transmission and Microglial Process Retraction
Articolo
Data di Pubblicazione:
2018
Abstract:
C-low-threshold mechanoreceptors (C-LTMRs) are sensory neurons that, beyond conveying pleasant touch, modulate nociceptive transmission within the spinal cord. However, pain alleviation by C-LTMRs remains poorly understood. Here, we show that the C-LTMR-derived TAFA4 chemokine induces a reinforcement of inhibitory synaptic transmission within spinal networks, which consequently depresses local excitatory synapses and impairs synaptic transmission from high-threshold C-fibers. In animals with inflammation induced by Freund's complete adjuvant, TAFA4 decreases the noxious stimulus-induced neuronal responses recorded in vivo and alleviates mechanical pain. Both effects are blocked by antagonists of GABAergic transmission. Furthermore, TAFA4 promotes microglial retraction in inflammation and increases the number of inhibitory synapses on lamina IIi somata. Altogether, these results demonstrate GABAergic interneurons to be the first integration relay for C-LTMRs and highlight a tight interplay between sensory neurons, microglial cells, and spinal interneurons, which fine-tunes inhibitory activity and nociceptive transmission in pathological conditions.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
SUPERFICIAL DORSAL-HORN; FORMYL PEPTIDE RECEPTORS; RAT SPINAL-CORD; CENTRAL SENSITIZATION; LAMINA-II; PERIPHERAL INFLAMMATION; PAIN HYPERSENSITIVITY; GLIAL ACTIVATION; NEUROPATHIC PAIN; NEURONS
Elenco autori:
Kambrun Charline, Roca-Lapirot Olivier, Salio Chiara, Landry Marc, Moqrich Aziz, Le Feuvre Yves
Link alla scheda completa:
Link al Full Text:
Pubblicato in: