title: GABAAergic inhibition or dopamine denervation of the A11 hypothalamic nucleus induces trigeminal analgesia.
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 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.
authors: Clermont Université, Université d'Auvergne, Neuro-Dol, Clermont-Ferrand & Inserm U1107, F-63100, Clermont-Ferrand, France CHU Clermont-Ferrand, Service d'Odontologie, Clermont-Ferrand, France.
authors: Khaled
authors: K
authors: Abdallah
authors: Lénaic
authors: L
authors: Monconduit
authors: Alain
authors: A
authors: Artola
authors: Philippe
authors: P
authors: Luccarini
authors: Radhouane
authors: R
authors: Dallel
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003714:Denervation; D004298:Dopamine / Q000378:metabolism*; D004302:Dorsomedial Hypothalamic Nucleus / Q000166:cytology* / Q000502:physiology*; D007839:Functional Laterality; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D008297:Male; D009043:Motor Activity; D009118:Muscimol / Q000494:pharmacology; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D010147:Pain Measurement; D051381:Rats; D013565:Sympatholytics / Q000633:toxicity; D014277:Trigeminal Neuralgia / Q000503:physiopathology / Q000628:therapy*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D058785:GABA-A Receptor Agonists; D013565:Sympatholytics; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; D015740:Calcitonin Gene-Related Peptide; D004298:Dopamine