title: A role of supraspinal galanin in behavioural hyperalgesia in the rat.
abstract: BACKGROUND
  In chronic pain disorders, galanin (GAL) is able to either facilitate or inhibit nociception in the spinal cord but the contribution of supraspinal galanin to pain signalling is mostly unknown. The dorsomedial nucleus of the hypothalamus (DMH) is rich in galanin receptors (GALR) and is involved in behavioural hyperalgesia. In this study, we evaluated the contribution of supraspinal GAL to behavioural hyperalgesia in experimental monoarthritis.
  
  
  METHODS
  In Wistar-Han males with a four week kaolin/carrageenan-induced monoarthritis (ARTH), paw-withdrawal latency (PWL) was assessed before and after DMH administration of exogenous GAL, a non-specific GALR antagonist (M40), a specific GALR1 agonist (M617) and a specific GALR2 antagonist (M871). Additionally, the analysis of c-Fos expression after GAL injection in the DMH was used to investigate the potential involvement of brainstem pain control centres. Finally, electrophysiological recordings were performed to evaluate whether pronociceptive On- or antinociceptive Off-like cells in the rostral ventromedial medulla (RVM) relay the effect of GAL.
  
  
  RESULTS
  Exogenous GAL in the DMH decreased PWL in ARTH and SHAM animals, an effect that was mimicked by a GALR1 agonist (M617). In SHAM animals, an unselective GALR antagonist (M40) increased PWL, while a GALR2 antagonist (M871) decreased PWL. M40 or M871 failed to influence PWL in ARTH animals. Exogenous GAL increased c-Fos expression in the RVM and dorsal raphe nucleus (DRN), with effects being more prominent in SHAM than ARTH animals. Exogenous GAL failed to influence activity of RVM On- or Off-like cells of SHAM and ARTH animals.
  
  
  CONCLUSIONS
  Overall, exogenous GAL in the DMH had a pronociceptive effect that is mediated by GALR1 in healthy and arthritic animals and is associated with alterations of c-Fos expression in RVM and DRN that are serotonergic brainstem nuclei known to be involved in the regulation of pain.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences (ECS), University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Amorim
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences (ECS), University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: David-Pereira
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences (ECS), University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Marques
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences (ECS), University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Sónia
authors.initials: S
authors.lastname: Puga
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences (ECS), University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Rebelo
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences (ECS), University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Patrício
authors.initials: P
authors.lastname: Costa
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), School of Health Sciences (ECS), 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: Life and Health Sciences Research Institute (ICVS), School of Health Sciences (ECS), 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: D000704:Analysis of Variance; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000150:complications*; D002351:Carrageenan / Q000009:adverse effects; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D019004:Galanin / Q000494:pharmacology*; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D007616:Kaolin / Q000009:adverse effects; D008297:Male; D016760:Proto-Oncogene Proteins c-fos; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D007616:Kaolin; D019004:Galanin; D002351:Carrageenan