title: Aromatase inhibition exacerbates pain and reactive gliosis in the dorsal horn of the spinal cord of female rats caused by spinothalamic tract injury.
abstract: Central pain syndrome is characterized by severe and excruciating pain resulting from a lesion in the central nervous system. Previous studies have shown that estradiol decreases pain and that inhibitors of the enzyme aromatase, which synthesizes estradiol from aromatizable androgens, increases pain sensitivity. In this study we have assessed whether aromatase expression in the dorsal horns of the spinal cord is altered in a rat model of central pain syndrome, induced by the unilateral electrolytic lesion of the spinothalamic tract. Protein and mRNA levels of aromatase, as well as the protein and mRNA levels of estrogen receptors α and β, were increased in the dorsal horn of female rats after spinothalamic tract injury, suggesting that the injury increased estradiol synthesis and signaling in the dorsal horn. To determine whether the increased aromatase expression in this pain model may participate in the control of pain, mechanical allodynia thresholds were determined in both hind paws after the intrathecal administration of letrozole, an aromatase inhibitor. Aromatase inhibition enhanced mechanical allodynia in both hind paws. Because estradiol is known to regulate gliosis we assessed whether the spinothalamic tract injury and aromatase inhibition regulated gliosis in the dorsal horn. The proportion of microglia with a reactive phenotype and the number of glial fibrillary acidic protein-immunoreactive astrocytes were increased by the injury in the dorsal horn. Aromatase inhibition enhanced the effect of the injury on gliosis. Furthermore, a significant a positive correlation of mechanical allodynia and gliosis in the dorsal horn was detected. These findings suggest that aromatase is up-regulated in the dorsal horn in a model of central pain syndrome and that aromatase activity in the spinal cord reduces mechanical allodynia by controlling reactive gliosis in the dorsal horn.
authors.affiliation: Department of Cell and Molecular Biology (S.G.), Department of Animal Biology (A.H.-R.), School of Biology, College of Science (S.G.), University of Tehran, Tehran, Iran; Consejo Superior de Investigaciones Científicas (L.M.G.-S.), Instituto Cajal, E-28002 Madrid, Spain; Neurobiology Research Center (F.K., M.J.), Shahid Beheshti University of Medical Sciences, Tehran, Iran; and Department of Pharmacology, Faculty of Medicine (M.J.), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Samar
authors.initials: S
authors.lastname: Ghorbanpoor
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: Ali
authors.initials: A
authors.lastname: Haeri-Rohani
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Jorjani
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000009:adverse effects*; D018450:Disease Progression; D005260:Female; D005911:Gliosis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D006930:Hyperalgesia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010146:Pain / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D017288:Pain Threshold; D051381:Rats; D017207:Rats, Sprague-Dawley; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000235:genetics / Q000473:pathology; D013133:Spinothalamic Tracts / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology
chemical_list: D047072:Aromatase Inhibitors; D001141:Aromatase