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Psychopharmacology

, Volume 232, Issue 24, pp 4433–4444 | Cite as

Differential effects of general anesthetics on anxiety-like behavior in formalin-induced pain: involvement of ERK activation in the anterior cingulate cortex

  • Cong Luo
  • Yan-Ling Zhang
  • Wei Luo
  • Fiona H Zhou
  • Chang-Qi Li
  • Jun-Mei XuEmail author
  • Ru-Ping DaiEmail author
Original Investigation

Abstract

Rationale

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.

Keywords

Anxiety Anesthetics Sevoflurane Propofol Extracellular signal-regulated kinase Anterior cingulate cortex 

Notes

Conflict of Interest

The authors declare that they have no competing interests.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of AnesthesiologyThe Second Xiangya Hospital of Central South UniversityChangshaChina
  2. 2.Department of Anatomy and Neurobiology, Xiangya School of MedicineCentral South UniversityChangshaChina
  3. 3.School of Pharmacy and Medical Sciences, Division of Health SciencesUniversity of South AustraliaAdelaideAustralia

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