title: Pronociception from the dorsomedial nucleus of the hypothalamus is mediated by the rostral ventromedial medulla in healthy controls but is absent in arthritic animals.
abstract: The dorsomedial nucleus of the hypothalamus (DMH) has been proposed to participate in stress-induced hyperalgesia through facilitation of pronociceptive cells in the rostroventromedial medulla (RVM). We hypothesized that the DMH participates in hyperalgesia induced by arthritis. The DMH was pharmacologically manipulated while assessing heat-evoked nociceptive behavior or the discharge rates of pronociceptive RVM ON- and antinociceptive RVM OFF-like cells in NAIVE, SHAM and monoarthritic (ARTH) animals. In NAIVE and SHAM animals, the changes in nociceptive behavior induced by activation of the DMH by glutamate and inhibition by lidocaine were in line with earlier evidence indicating that the DMH has a nociceptive facilitating role. However, in ARTH animals, neither activation nor inhibition of the DMH influenced pain-like behavior evoked by stimulation of an uninflamed skin region (paw and tail). In accordance with these behavioral results, activation or inhibition of the DMH induced pronociceptive changes in the discharge rates of RVM cells in NAIVE and SHAM animals, which suggests that the DMH has a pronociceptive role mediated by the RVM in normal animals. However, in ARTH animals, both glutamate and lidocaine in the DMH failed to influence either pain-like behavior or noxious stimulation-evoked responses of RVM cells, while blocking the DMH increased spontaneous activity in the pronociceptive RVM ON cells. Our data indicate that the DMH participates in descending facilitation of cutaneous nociception in healthy controls, but it is not engaged in the regulation of cutaneous nociception in monoarthritic animals, while a minor role in tonic suppression of nociception in arthritis cannot be discarded.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences (ECS), Campus of Gualtar, University of Minho, 4750-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Filipa
authors.initials: F
authors.lastname: Pinto-Ribeiro
authors.forename: Diana
authors.initials: D
authors.lastname: Amorim
authors.forename: Ana
authors.initials: A
authors.lastname: David-Pereira
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Monteiro
authors.forename: Patricio
authors.initials: P
authors.lastname: Costa
authors.forename: Antti
authors.initials: A
authors.lastname: Pertovaara
authors.forename: Armando
authors.initials: A
authors.lastname: Almeida
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000150:complications; D001640:Bicuculline / Q000494:pharmacology; D002351:Carrageenan / Q000633:toxicity; D004195:Disease Models, Animal; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D004347:Drug Interactions; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000209:etiology / Q000473:pathology*; D008297:Male; D008526:Medulla Oblongata; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects
chemical_list: D058787:GABA-A Receptor Antagonists; D002351:Carrageenan; D001640:Bicuculline
keywords: ARTH; Arthritic pain; CTRL; DMH; Descending pain modulation; Dorsomedial hypothalamic nucleus (DMH); GLU; H; HPA; LIDO; MS; NPS; ON-like cells; P; PAG; PW; Pronociception; RVM; Rostral ventromedial medulla (RVM); SAL; TF; TS; arthritic animals/arthritis; control animals/controls; dorsomedial nucleus of the hypothalamus; glutamate; hypothalamus–pituitary–adrenal axis; lidocaine; mechanical stimulation; noxious peripheral stimulation; paw-withdrawal; periaqueductal gray matter; peripheral noxious heat stimulation; peripheral noxious mechanical stimulation; rostral ventromedial medulla; saline solution; tail-flick; thermal stimulation