title: The influence of microglia activation on the efficacy of amitriptyline, doxepin, milnacipran, venlafaxine and fluoxetine in a rat model of neuropathic pain.
abstract: The analgesic properties of antidepressants are often used in the treatment of neuropathy; however their influence on glial cells in maintaining neuropathic pain is unknown. Our studies examined the neuropathic pain-relieving properties after intraperitoneal injection of amitriptyline, doxepin, milnacipran, venlafaxine and fluoxetine 7 days after sciatic nerve injury (CCI) in rats and its influence on microglia/macrophages (IBA-1) and astroglia (GFAP) activation in the spinal cord and dorsal root ganglia (DRG) using Western blot. All tested antidepressants significantly reduced CCI-induced allodynia but hyperalgesia was only antagonised by fluoxetine, doxepine and venlafaxine. The strongest analgesia was observed after fluoxetine administration. Western blot analysis showed the upregulation of the IBA-1 in the lumbar spinal cord and DRG after amitriptyline or milnacipran administration in CCI-exposed rats, whereas after fluoxetine the downregulation was observed. The administration of doxepin did not change the IBA-1 protein level in both studied structures; however venlafaxine decreased the IBA-1 only in the DRG. No changes in the GFAP level in both structures were observed after any of listed above antidepressants administration. Chronic minocycline treatment enhanced amitriptyline and milnacipran, but did not fluoxetine analgesia under neuropathic pain in rats. Our results suggest that nerve injury-induced pain is related with the activation of microglia, which is diminished by fluoxetine treatment in the neuropathic pain model.
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zychowska
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Krakow, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Rojewska
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Krakow, Poland.
authors.forename: Wioletta
authors.initials: W
authors.lastname: Makuch
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Krakow, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Przewlocka
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Krakow, Poland. Electronic address: joamika@if-pan.krakow.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Mika
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003511:Cyclohexanols / Q000494:pharmacology / Q000627:therapeutic use; D003521:Cyclopropanes / Q000494:pharmacology / Q000627:therapeutic use; D004316:Doxepin / Q000494:pharmacology / Q000627:therapeutic use; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects*; D000078764:Milnacipran; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
chemical_list: C100745:Aif1 protein, rat; D000928:Antidepressive Agents; D002135:Calcium-Binding Proteins; D003511:Cyclohexanols; D003521:Cyclopropanes; D008840:Microfilament Proteins; D005473:Fluoxetine; D004316:Doxepin; D000639:Amitriptyline; D000069470:Venlafaxine Hydrochloride; D000078764:Milnacipran
keywords: Antidepressants; Astroglia; Microglia; Neuropathic pain