title: Differential effects of general anesthetics on anxiety-like behavior in formalin-induced pain: involvement of ERK activation in the anterior cingulate cortex.
abstract: BACKGROUND
  Pain-related anxiety and depression are well known to be comorbid with chronic pain and adversely affect patient quality of life. Recent studies have shown that anxiety-like behaviors also develop with acute surgical pain, but the effects of general anesthetics on acute pain-related anxiety are unknown.
  
  
  OBJECTIVE
  The present study aimed to compare the effects of different general anesthetics on anxiety-like behaviors that follow formalin-induced acute pain in a rat model.
  
  
  METHODS
  Formalin-induced acute inflammatory pain was established by intraplantar injection of 1% formalin without anesthesia or with anesthesia using the clinical anesthetics sevoflurane, propofol, or pentobarbital sodium. Anxiety-like behaviors were studied using the open-field test and elevated plus maze. Phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 expression in the anterior cingulate cortex (ACC) and spinal cord was examined using immunohistochemistry.
  
  
  RESULTS
  Anxiety-like behaviors were observed at 24 and 72 h post-formalin injection. Concomitantly, p-ERK 1/2 expression was upregulated in the ACC at 1 and 24 h post-formalin injection. While all three general anesthetics effectively blocked nociceptive responses and activation of ERK in the rat ACC following formalin injection during anesthesia, only sevoflurane inhibited ERK activation in the spinal cord and ACC at 24 h post-injection.
  
  
  CONCLUSIONS
  This study suggests that sevoflurane, but not intravenous anesthetics, inhibits pain-related anxiety, along with ERK activation in the ACC, probably through inhibition of spinal nociceptive transmission. Intraoperative application of inhaled anesthetics may be a better choice to reduce postoperative anxiety.
authors.affiliation: Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Ren-Min Road 86, Changsha, Hunan, 410011, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Ren-Min Road 86, Changsha, Hunan, 410011, China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Ren-Min Road 86, Changsha, Hunan, 410011, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.affiliation: School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia.
authors.forename: Fiona H
authors.initials: FH
authors.lastname: Zhou
authors.affiliation: Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Chang-Qi
authors.initials: CQ
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Ren-Min Road 86, Changsha, Hunan, 410011, China. 13975148864@139.com.
authors.forename: Jun-Mei
authors.initials: JM
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Ren-Min Road 86, Changsha, Hunan, 410011, China. xyeyyrupingdai@gmail.com.
authors.forename: Ru-Ping
authors.initials: RP
authors.lastname: Dai
mesh_terms: D018685:Anesthetics, Inhalation; D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005557:Formaldehyde; D006179:Gyrus Cinguli / Q000378:metabolism*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D010147:Pain Measurement; D010424:Pentobarbital / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D005557:Formaldehyde; D000077149:Sevoflurane; D048049:Extracellular Signal-Regulated MAP Kinases; D010424:Pentobarbital; D015742:Propofol
keywords: Anesthetics; Anterior cingulate cortex; Anxiety; Extracellular signal-regulated kinase; Propofol; Sevoflurane