title: Minocycline reduces mechanical allodynia and depressive-like behaviour in type-1 diabetes mellitus in the rat.
abstract: A common and devastating complication of diabetes mellitus is painful diabetic neuropathy (PDN) that can be accompanied by emotional disorders such as depression. A few studies have suggested that minocycline that inhibits microglia may attenuate pain hypersensitivity in PDN. Moreover, a recent study reported that minocycline has an acute antidepressive-like effect in diabetic animals. Here we studied whether (i) prolonged minocycline treatment suppresses pain behaviour in PDN, (ii) the minocycline effect varies with submodality of pain, and (iii) the suppression of pain behaviour by prolonged minocycline treatment is associated with antidepressive-like effect. The experiments were performed in streptozotocin-induced rat model of type-1 diabetes. Pain behaviour was evoked by innocuous (monofilaments) and noxious (paw pressure) mechanical stimulation, innocuous cold (acetone drops) and noxious heat (radiant heat). Depression-like behaviour was assessed using forced swimming test. Minocycline treatment (daily 80mg/kg per os) of three-week duration started four weeks after induction of diabetes. Diabetes induced mechanical allodynia and hyperalgesia, cold allodynia, heat hypoalgesia, and depression-like behaviour. Minocycline treatment significantly attenuated mechanical allodynia and depression-like behaviour, while it failed to produce significant changes in mechanical hyperalgesia, cold allodynia or heat hypoalgesia. The results indicate that prolonged per oral treatment with minocycline has a sustained mechanical antiallodynic and antidepressive-like effect in PDN. These results support the proposal that minocycline might provide a treatment option for attenuating sensory and comorbid emotional symptoms in chronic PDN.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine (EM), Campus of Gualtar, University of Minho, 4750-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: dianaamorim@med.uminho.pt.
authors.forename: Diana
authors.initials: D
authors.lastname: Amorim
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine (EM), Campus of Gualtar, University of Minho, 4750-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: soniapuga@med.uminho.pt.
authors.forename: Sónia
authors.initials: S
authors.lastname: Puga
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine (EM), Campus of Gualtar, University of Minho, 4750-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: braganca_91@hotmail.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Bragança
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine (EM), Campus of Gualtar, University of Minho, 4750-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: a59212@alunos.uminho.pt.
authors.forename: António
authors.initials: A
authors.lastname: Braga
authors.affiliation: Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland. Electronic address: antti.pertovaara@helsinki.fi.
authors.forename: Antti
authors.initials: A
authors.lastname: Pertovaara
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine (EM), Campus of Gualtar, University of Minho, 4750-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: aalmeida@med.uminho.pt.
authors.forename: Armando
authors.initials: A
authors.lastname: Almeida
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine (EM), Campus of Gualtar, University of Minho, 4750-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: filiparibeiro@med.uminho.pt.
authors.forename: Filipa
authors.initials: F
authors.lastname: Pinto-Ribeiro
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D003080:Cold Temperature; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D011897:Random Allocation; D017208:Rats, Wistar; D014110:Touch
chemical_list: D000700:Analgesics; D000928:Antidepressive Agents; D007004:Hypoglycemic Agents; D008911:Minocycline
keywords: Depressive-like behaviour; Mechanical allodynia; Minocycline; Type-1 diabetes animal model