Moderate hypercapnia-induced anesthetic effects and endogenous opioids

Neurosci Lett. 2006 Jul 31;403(1-2):20-3. doi: 10.1016/j.neulet.2006.04.026. Epub 2006 May 15.


The purpose of this report is to explore the mechanisms of hypercapnia-induced antinociception. We carried out three experiments, the first to confirm whether moderate hypercapnia induces anesthetic effects, the second to determine whether naloxone reverses the anesthetic effects, and the third to evaluate whether beta-endorphin is related to the anesthetic effects. In a pre-test, we determined the optimal CO(2) concentration in a chamber which would cause moderate hypercapnia in rats. Eighteen rats were divided into control, hypercapnia, and hypercapnia plus naloxone groups in experiment 1. The naloxone group rats were injected with naloxone (10 mg/kg) intraperitoneally before gas inhalation. After 60 min gas inhalation, 10% formalin was injected into the left rear paw of all rats, and nociceptive behaviors were observed for 1 h. In experiment 2, 11 rats were divided into control and hypercapnia groups. The brain was removed and fixed under pentobarbital anesthesia. Sections were immunostained for c-Fos and beta-endorphin (ACTH) with the ABC method. All neurons double-labeled for c-Fos and beta-endorphin (ACTH) in the arcuate nucleus were counted by blinded investigators. Moderate hypercapnia (PaCO(2) 83+/-7 mmHg) reduced nociceptive behavior in the formalin test and naloxone pre-treatment attenuated this phenomenon. However, beta-endorphin-producing neurons were not activated by CO(2) inhalation. Endogenous opioids are related to moderate, hypercapnia-induced anesthetic effects, but, beta-endorphin-producing neurons in the hypothalamus were not activated by the CO(2) inhalation stress.

MeSH terms

  • Anesthetics, Inhalation / pharmacology*
  • Animals
  • Carbon Dioxide / pharmacology*
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Male
  • Naloxone / pharmacology
  • Narcotic Antagonists
  • Neurons / drug effects
  • Neurons / metabolism
  • Pain / metabolism
  • Pain / physiopathology*
  • Pain Measurement
  • Pain Threshold
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid / physiology*
  • beta-Endorphin / biosynthesis*


  • Anesthetics, Inhalation
  • Narcotic Antagonists
  • Proto-Oncogene Proteins c-fos
  • Receptors, Opioid
  • Carbon Dioxide
  • Naloxone
  • beta-Endorphin