GABAAergic inhibition or dopamine denervation of the A11 hypothalamic nucleus induces trigeminal analgesia

Pain
Khaled AbdallahRadhouane Dallel

Abstract

Descending pain-modulatory systems, either inhibitory or facilitatory, play a critical role in both acute and chronic pain. Compared with serotonin and norepinephrine, little is known about the function of dopamine (DA). We characterized the anatomical organization of descending DA pathways from hypothalamic A11 nuclei to the medullary dorsal horn (MDH) and investigated their role in trigeminal pain. Immunochemistry analysis reveals that A11 is a heterogeneous nucleus that contains at least 3 neuronal phenotypes, DA, GABA, and alpha-calcitonin gene-related peptide (α-CGRP) neurons, exhibiting different distribution patterns, with a large proportion of GABA relative to DA neurons. Using fluorogold, we show that descending pathways from A11 nuclei to MDH originate mainly from DA neurons and are bilateral. Facial nociceptive stimulation elevates Fos immunoreactivity in both ipsilateral and contralateral A11 nuclei. Fos immunoreactivity is not detected in DA or projecting neurons but, interestingly, in GABA neurons. Finally, inactivating A11, using muscimol, or partially lesioning A11 DA neurons, using the neurotoxin 6-hydroxydopamine, inhibits trigeminal pain behavior. These results show that A11 nuclei are involved in pain proces...Continue Reading

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Citations

Oct 17, 2015·European Journal of Pain : EJP·X MoissetD Bouhassira
Mar 18, 2020·International Journal of Molecular Sciences·Hiroharu MaegawaHitoshi Niwa
Sep 28, 2017·Clinical and Experimental Pharmacology & Physiology·Parisa MoazenMitra Norozpor
Oct 27, 2018·Frontiers in Neural Circuits·Kathrin KoblingerPatrick J Whelan
Jun 12, 2019·Current Neuropharmacology·Changsheng LiFeng Tao
Aug 29, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Hiroyuki NakamoriYasutake Shimizu
Mar 18, 2017·Neurochemical Research·Hidechika OzawaShuichi Ueda

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