title: Tonic and phasic descending dopaminergic controls of nociceptive transmission in the medullary dorsal horn.
abstract: The transfer of nociceptive information at the level of dorsal horn is subject to extensive processing by both local segmental and supraspinal mechanisms, including descending dopaminergic controls, originating from the hypothalamic A11 nucleus. The inhibitory role of dopamine on evoked pain via activation of D2-like receptors at the level of the dorsal horn is well established. Here, by use of behavioral, electrophysiological, and anatomical techniques, we examined within the trigeminal sensory complex, first, whether descending dopaminergic controls also modulate pain behavior after an inflammatory insult, and second, under which physiological conditions these descending dopaminergic controls are actually recruited. We show that D2 receptors are mostly located within superficial medullary dorsal horn where trigeminal nociceptive fibers abut. Activating these D2-like receptors inhibits, whereas blocking them enhances, both formalin- and capsaicin-evoked pain behavior and C-fiber-evoked action potential firing of trigeminal wide dynamic range (WDR) neurons. Moreover, windup and diffuse noxious inhibitory controls (DNIC), 2 dynamic properties of C-fiber-evoked firing of WDR neurons, are inhibited by activating and blocking, respectively, these D2-like receptors. Altogether, our results are consistent with a tonic inhibition of the trigeminal nociceptive input by descending dopaminergic controls via activation of D2-like receptors at the level of superficial medullary dorsal horn. Such dopamine-dependent tonic inhibition of nociceptive information can be dynamically modulated by pain. This suggests that dysregulation of descending dopaminergic controls should translate in patients into diffuse, cephalic, and extracephalic pain symptoms--spontaneous pain, decreased pain thresholds, deficient DNIC, or some combination of these.
authors.affiliation: Clermont Université, Université d'Auvergne, Neurobiologie de la douleur trigéminale, BP 10448, F-63000 Clermont-Ferrand, France Inserm, U929, F-63000 Clermont-Ferrand, France CHU Clermont-Ferrand, Service d'Odontologie, F-63003 Clermont-Ferrand, France IUT Génie Biologique, 63172 Aubière, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lapirot
authors.forename: Céline
authors.initials: C
authors.lastname: Melin
authors.forename: Alice
authors.initials: A
authors.lastname: Modolo
authors.forename: Charline
authors.initials: C
authors.lastname: Nicolas
authors.forename: Yassine
authors.initials: Y
authors.lastname: Messaoudi
authors.forename: Lénaic
authors.initials: L
authors.lastname: Monconduit
authors.forename: Alain
authors.initials: A
authors.lastname: Artola
authors.forename: Philippe
authors.initials: P
authors.lastname: Luccarini
authors.forename: Radhouane
authors.initials: R
authors.lastname: Dallel
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000344:Afferent Pathways / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D002211:Capsaicin / Q000009:adverse effects; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D008297:Male; D008526:Medulla Oblongata / Q000473:pathology*; D008845:Microinjections; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D010146:Pain / Q000139:chemically induced / Q000473:pathology*; D010147:Pain Measurement; D020671:Posterior Horn Cells / Q000503:physiopathology*; D011493:Protein Kinase C / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D013469:Sulpiride; C087857:protein kinase C gamma; D011493:Protein Kinase C; D002211:Capsaicin; D004298:Dopamine