General anesthetics inhibit the nitrous-oxide-induced activation of corticotropin releasing factor containing neurons in rats.
The activation of intracerebral corticotropin releasing factor (CRF) system is involved in nitrous oxide analgesia. We evaluated the effect of general anesthetics on nitrous-oxide-induced CRF activation and antinociception. Male Sprague-Dawley rats inhaled isoflurane (0%, 0.6%, 1.0% and 1.5%) or were administered with intravenous propofol (0, 0.1 and 0.2 mg/kg/min), with or without 75% nitrous oxide inhalation, for 90 min. The brain was fixed with fixative, and brain sections, including the paraventricular nucleus of the hypothalamus, were double immunostained with c-Fos and CRF antibodies to assess the activation of CRF-containing neurons. In other groups of rats, the effect of propofol on nitrous oxide antinociception was evaluated with tail flick latency tests. Both inhaled isoflurane and intravenous propofol inhibited nitrous-oxide-induced activation of CRF neurons, suggesting that these general anesthetics may inhibit one of the analgesic mechanisms of nitrous oxide. Indeed, propofol inhibited the antinociceptive action of nitrous oxide, as evaluated with tail flick latencies (TFL).
Sawamura
Shigehito
S
Department of Anesthesia, Showa General Hospital, 2-450, Tenjin-cho, Kodaira, Tokyo 187-8510, Japan. sawamura-tky@umin.ac.jp
Obara-Nawata
Mizuki
M
Takeda
Kenji
K
Hanaoka
Kazuo
K
D018681:Anesthetics, General / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers; D001923:Brain Chemistry / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D007150:Immunohistochemistry; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009609:Nitrous Oxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
D018681:Anesthetics, General; D018685:Anesthetics, Inhalation; D015415:Biomarkers; D016760:Proto-Oncogene Proteins c-fos; D003346:Corticotropin-Releasing Hormone; D007530:Isoflurane; D009609:Nitrous Oxide; D015742:Propofol