title: The antinociceptive effects of estradiol on adjuvant-induced hyperalgesia in rats involve activation of adrenergic and serotonergic systems.
abstract: OBJECTIVE
  Estradiol is a female hormone required for maintaining pregnancy and developing follicles in the ovary. Estradiol has been shown to perform a variety of physiological activities, including pain reduction. In this study, we tested the hypothesis that estradiol exerts antinociceptive effects in a rat model of inflammatory hyperalgesia.
  
  
  METHODS
  We established a subacute hyperalgesia model using plantar injection of Freund's complete adjuvant (FCA) in Sprague-Dawley rats. We administered estradiol every 24 h, beginning 12 h after FCA administration, and used the plantar test to determine its effect on hyperalgesia. To determine the mechanism of action of estradiol, we evaluated the role of the opioid antinociceptive system using naloxone and the role of the descending pain inhibitory system using the α-2-receptor antagonist yohimbine and the serotonin receptor antagonist methysergide.
  
  
  RESULTS
  Administration of FCA induced hyperalgesia, which was significantly reduced by estradiol treatment compared to controls. Moreover, this effect was not antagonized by naloxone, but was attenuated by α-2-receptor and serotonin-receptor antagonists.
  
  
  CONCLUSIONS
  Estradiol is known to perform a variety of physiological functions. Our findings suggest that one such function is antinociception via an interaction with α-2 receptors and serotonin receptors.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka-Hasamamachi, Yufu, Oita, 879-5593, Japan. kent024@oita-u.ac.jp
authors.forename: Kentaro
authors.initials: K
authors.lastname: Okuda
authors.forename: Hideo
authors.initials: H
authors.lastname: Iwasaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Naozumi
authors.initials: N
authors.lastname: Takeshima
authors.forename: Junji
authors.initials: J
authors.lastname: Takatani
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Uchino
authors.forename: Takayuki
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000700:Analgesics; D000818:Animals; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy*; D007278:Injections, Spinal; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000700:Analgesics; D009292:Narcotic Antagonists; D018341:Receptors, Adrenergic, alpha-2; D012702:Serotonin Antagonists; D015016:Yohimbine; D012701:Serotonin; D009270:Naloxone; D004958:Estradiol; D005620:Freund's Adjuvant; D008784:Methysergide