• Khaled Abdallah, Lénaic Monconduit, Alain Artola, Philippe Luccarini, and Radhouane Dallel.
• aClermont Université, Université d'Auvergne, Neuro-Dol, Clermont-Ferrand & Inserm U1107, F-63100, Clermont-Ferrand, France bCHU Clermont-Ferrand, Service d'Odontologie, Clermont-Ferrand, France.
• Pain. 2015 Apr 1;156(4):644-55.

AbstractDescending 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 processing. Interestingly, however, pain seems to activate GABAergic neurons within A11 nuclei, which suggests that pain inhibits rather than activates descending DA controls. We show that such inhibition produces an antinociceptive effect. Pain-induced inhibition of descending DA controls and the resulting reduced DA concentration within the dorsal horn may inhibit the transfer of nociceptive information to higher brain centers through preferential activation of dorsal horn D2-like receptors.

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