title: Minocycline modulates neuropathic pain behaviour and cortical M1-M2 microglial gene expression in a rat model of depression.
abstract: There is a paucity of data on the role of microglia and neuroinflammatory processes in the association between chronic pain and depression. The current study examined the effect of the microglial inhibitor minocycline on depressive-like behaviour, spinal nerve ligation (SNL)-induced mechanical and cold allodynia and associated changes in the expression of genes encoding microglial markers (M1 vs. M2 polarisation) and inflammatory mediators in the prefrontal cortex in the olfactory bulbectomised (OB) rat model of depression. Acute minocycline administration did not alter OB-induced depressive-like behaviour but prevented SNL-induced mechanical allodynia in both OB and sham rats. In comparison, chronic minocycline attenuated OB-induced depressive-like behaviour and prevented the development of SNL-induced mechanical allodynia in OB, but not sham, rats. Further analysis revealed that SNL-induced mechanical allodynia in OB rats was attenuated by chronic minocycline at almost all time-points over a 2week testing period, an effect observed only from day 10 post-SNL in sham rats. Chronic administration of minocycline reduced the expression of CD11b, a marker of microglial activation, and the M1 pro-inflammatory cytokine IL-1β, in the prefrontal cortex of sham-SNL animals. In comparison, the expression of the M2 microglia marker (MRC2) and anti-inflammatory cytokine IL-10 was increased, as were IL-1β, IL-6 and SOCS3, in the prefrontal cortex of OB-SNL animals following chronic minocycline. Thus, chronic minocycline attenuates neuropathic pain behaviour and modulates microglial activation and the central expression of inflammatory mediators in a manner dependent on the presence or absence of a depressive-like phenotype.
authors.affiliation: Physiology, School of Medicine, National University of Ireland Galway, University Road, Galway, Ireland; Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, University Road, Galway, Ireland.
authors.forename: Nikita N
authors.initials: NN
authors.lastname: Burke
authors.affiliation: Physiology, School of Medicine, National University of Ireland Galway, University Road, Galway, Ireland; Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, University Road, Galway, Ireland; NCBES Centre for Pain Research and Galway Neuroscience Centre, National University of Ireland Galway, University Road, Galway, Ireland.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Kerr
authors.affiliation: Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, University Road, Galway, Ireland; NCBES Centre for Pain Research and Galway Neuroscience Centre, National University of Ireland Galway, University Road, Galway, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: Moriarty
authors.affiliation: Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, University Road, Galway, Ireland; NCBES Centre for Pain Research and Galway Neuroscience Centre, National University of Ireland Galway, University Road, Galway, Ireland.
authors.forename: David P
authors.initials: DP
authors.lastname: Finn
authors.affiliation: Physiology, School of Medicine, National University of Ireland Galway, University Road, Galway, Ireland; NCBES Centre for Pain Research and Galway Neuroscience Centre, National University of Ireland Galway, University Road, Galway, Ireland. Electronic address: michelle.roche@nuigalway.ie.
authors.forename: Michelle
authors.initials: M
authors.lastname: Roche
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects*; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D008911:Minocycline
keywords: Allodynia; Antidepressant; Cytokine; Microglia; Neuroinflammation; Olfactory bulbectomy; Prefrontal cortex; Spinal nerve ligation; von Frey