title: Galanin-Mediated Behavioural Hyperalgesia from the Dorsomedial Nucleus of the Hypothalamus Involves Two Independent Descending Pronociceptive Pathways.
abstract: Activation of the dorsomedial nucleus of the hypothalamus (DMH) by galanin (GAL) induces behavioural hyperalgesia. Since DMH neurones do not project directly to the spinal cord, we hypothesized that the medullary dorsal reticular nucleus (DRt), a pronociceptive region projecting to the spinal dorsal horn (SDH) and/or the serotoninergic raphe-spinal pathway acting on the spinal 5-HT3 receptor (5HT3R) could relay descending nociceptive facilitation induced by GAL in the DMH. Heat-evoked paw-withdrawal latency (PWL) and activity of SDH neurones were assessed in monoarthritic (ARTH) and control (SHAM) animals after pharmacological manipulations of the DMH, DRt and spinal cord. The results showed that GAL in the DMH and glutamate in the DRt lead to behavioural hyperalgesia in both SHAM and ARTH animals, which is accompanied particularly by an increase in heat-evoked responses of wide-dynamic range neurons, a group of nociceptive SDH neurones. Facilitation of pain behaviour induced by GAL in the DMH was reversed by lidocaine in the DRt and by ondansetron, a 5HT3R antagonist, in the spinal cord. However, the hyperalgesia induced by glutamate in the DRt was not blocked by spinal ondansetron. In addition, in ARTH but not SHAM animals PWL was increased after lidocaine in the DRt and ondansetron in the spinal cord. Our data demonstrate that GAL in the DMH activates two independent descending facilitatory pathways: (i) one relays in the DRt and (ii) the other one involves 5-HT neurones acting on spinal 5HT3Rs. In experimental ARTH, the tonic pain-facilitatory action is increased in both of these descending pathways.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.|Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland.
authors.forename: Diana
authors.initials: D
authors.lastname: Amorim
authors.affiliation: Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Viisanen
authors.affiliation: Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.affiliation: Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Armando
authors.initials: A
authors.lastname: Almeida
authors.affiliation: Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Pertovaara
authors.affiliation: Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Filipa
authors.initials: F
authors.lastname: Pinto-Ribeiro
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004594:Electrophysiology; D019004:Galanin / Q000737:chemistry*; D018698:Glutamic Acid / Q000737:chemistry; D006930:Hyperalgesia / Q000139:chemically induced*; D007031:Hypothalamus / Q000378:metabolism*; D008012:Lidocaine / Q000737:chemistry; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D059225:Nociception; D017294:Ondansetron / Q000737:chemistry; D010146:Pain; D011312:Pressure; D011498:Protein Precursors / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D012701:Serotonin / Q000737:chemistry; D013116:Spinal Cord / Q000378:metabolism
chemical_list: C489169:Gal protein, rat; D011498:Protein Precursors; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; D018698:Glutamic Acid; D017294:Ondansetron; D019004:Galanin; D008012:Lidocaine