title: NK1 receptor-expressing spinoparabrachial neurons trigger diffuse noxious inhibitory controls through lateral parabrachial activation in the male rat.
abstract: Diffuse noxious inhibitory controls (DNIC) are very powerful long-lasting descending inhibitory controls, which are pivotal in modulating the activity of spinal and trigeminal nociceptive neurons. The principal feature of DNIC is that they are subserved by a loop that involves supraspinal structures that have not yet been identified. Using behavioral, in vivo extracellular electrophysiological and anatomical approaches, we studied the neuronal network underlying DNIC. Using a new behavioral model of DNIC, in which facial grooming produced by formalin injection into the vibrissa pad is inhibited by a conditioning noxious stimulation, formalin injection into the hindpaw, we show that blockade of NK1 receptors in the lumbar spinal cord - by intrathecal administration of the NK1 receptor antagonist, RP67580 - largely attenuates DNIC-induced facial analgesia. In a second series of experiments, WDR neurons were recorded from the trigeminal subnucleus oralis and inhibited their C-fiber-evoked responses by the conditioning noxious heat stimulation of the hindpaw. We show that inactivating the lateral parabrachial area - by microinjecting the GABA(A) agonist, muscimol - strongly attenuates DNIC-induced inhibition of C-fiber-evoked responses. Finally, our neuroanatomical tracing study demonstrates that the descending pathway for DNIC does not involve direct descending projections from the PB area. We conclude that (1) lamina I/III spinoparabrachial neurons that express the NK1 receptor and (2) parabrachial neurons are involved in the ascending part of the loop underlying DNIC and that the descending pathway for DNIC might include indirect projections to the spinal or medullary dorsal horn.
authors.affiliation: Inserm U929, Neurobiologie de la douleur trigéminale, Faculté de Chirurgie Dentaire, 11 boulevard Charles de Gaulle, F-63000 Clermont-Ferrand, France Univ Clermont1, Clermont-Ferrand F-63000, France CHU Clermont-Ferrand, Clermont-Ferrand F-63000, France Faculté médecine dentaire, Monastir, Tunisia.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lapirot
authors.forename: Raja
authors.initials: R
authors.lastname: Chebbi
authors.forename: Lénaic
authors.initials: L
authors.lastname: Monconduit
authors.forename: Alain
authors.initials: A
authors.lastname: Artola
authors.forename: Radhouane
authors.initials: R
authors.lastname: Dallel
authors.forename: Philippe
authors.initials: P
authors.lastname: Luccarini
mesh_terms: D000344:Afferent Pathways / Q000503:physiopathology*; D000818:Animals; D005246:Feedback; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D009433:Neural Inhibition; D010146:Pain / Q000503:physiopathology*; D011149:Pons / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D011984:Sensory Receptor Cells; D013116:Spinal Cord / Q000503:physiopathology*
chemical_list: D018040:Receptors, Neurokinin-1