title: Amitriptyline reverses hyperalgesia and improves associated mood-like disorders in a model of experimental monoarthritis.
abstract: Affective disorders are common comorbidities of chronic inflammatory pain that are often overlooked in primary care. As the impact of inflammatory pain upon mood-like disorders in animal models is not well known, our objective was to assess whether prolonged experimental monoarthritis (ARTH) induced the development of anxiety and depressive-like behaviours in rodents and if amitriptyline, an antidepressant commonly used in the treatment of chronic pain, could reverse both nociceptive and mood-like impairments. Experimental ARTH was induced through an injection of kaolin/carrageenan into the right knee joint with control (SHAM) animals injected with saline. Four weeks after induction, ARTH animals displayed mechanical hyperalgesia and a depressive-like phenotype as they showed a significant increase in immobility and a decrease in the latency to immobility in the forced-swimming test at the expense of the time spent climbing/swimming. ARTH animals also displayed a decreased sucrose preference, an index of anhedonia and anxiety-like behaviour as time spent exploring the open arms of the elevated-plus-maze was decreased when compared to controls. The anxiety-like phenotype was also supported by an increase in the number of fecal boli left in the open field. In ARTH animals, the administration of amitriptyline decreased mechanical hyperalgesia and increased sucrose preference and the time spent climbing, although it had a deleterious effect in the performance of control animals. Our data show that this model of ARTH can be useful for the study of chronic pain-mood disorders comorbidities and that amitriptyline is able to partly reverse the associated nociceptive and emotional impairments.
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences (ECS), Campus of Gualtar, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: dianaamorim@ecsaude.uminho.pt.
authors: D
authors: D
authors: Amorim
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences (ECS), Campus of Gualtar, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: anapereira@ecsaude.uminho.pt.
authors: A
authors: A
authors: David-Pereira
authors: Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland. Electronic address: antti.pertovaara@helsinki.fi.
authors: A
authors: A
authors: Pertovaara
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences (ECS), Campus of Gualtar, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: aalmeida@ecsaude.uminho.pt.
authors: A
authors: A
authors: Almeida
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences (ECS), Campus of Gualtar, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: filiparibeiro@ecsaude.uminho.pt.
authors: F
authors: F
authors: Pinto-Ribeiro
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology* / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000150:complications*; D002351:Carrageenan / Q000494:pharmacology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D007616:Kaolin / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D019964:Mood Disorders / Q000188:drug therapy* / Q000209:etiology*; D009043:Motor Activity / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming / Q000523:psychology
chemical_list: D018712:Analgesics, Non-Narcotic; D000639:Amitriptyline; D007616:Kaolin; D002351:Carrageenan
keywords: Amitriptyline; Experimental monoarthritis; Mechanical hyperalgesia; Pain-mood disorders comorbidity