Laughing Gas Relieves Pain by Selectively Releasing Specific Enkephalins in the Brain
Nitrous oxide selectively increased met-enkephalin and met-enkephalin-Arg-Phe in brain CSF without affecting beta-endorphin, leu-enkephalin, or dynorphin.
Quick Facts
What This Study Found
Nitrous oxide selectively increased met-enkephalin and met-enkephalin-Arg-Phe in third ventricular CSF without affecting beta-endorphin, leu-enkephalin, or dynorphin.
Key Numbers
How They Did This
Eight acclimated dogs with chronically implanted third ventricle cannulae. CSF samples collected before and during nitrous oxide exposure. Five opioid peptides measured by radioimmunoassay.
Why This Research Matters
The mechanism of nitrous oxide analgesia has been debated for decades. This study provides the most direct evidence that it works through selective enkephalin release, resolving a long-standing controversy.
The Bigger Picture
Nitrous oxide is one of the most widely used anesthetics. Finally understanding its mechanism — selective enkephalin release — could help develop better versions or alternatives.
What This Study Doesn't Tell Us
Animal study in dogs. CSF collection from the third ventricle may not reflect peptide changes in all brain regions. Only acute exposure was tested.
Questions This Raises
- ?Could the selective enkephalin release be enhanced for better analgesia?
- ?Do other anesthetic gases work through similar opioid mechanisms?
Trust & Context
- Key Stat:
- Selective release Only met-enkephalin and met-ENK-Arg-Phe increased — the other three opioid peptides were completely unaffected
- Evidence Grade:
- Moderate — animal study with direct CSF measurement. Provides the most direct evidence to date for nitrous oxide's opioid mechanism.
- Study Age:
- Published in 1995 (31 years ago). This finding is now widely accepted as part of nitrous oxide's analgesic mechanism.
- Original Title:
- Nitrous oxide selectively releases Met5-enkephalin and Met5-enkephalin-Arg6-Phe7 into canine third ventricular cerebrospinal fluid.
- Published In:
- Anesthesia and analgesia, 80(4), 664-70 (1995)
- Authors:
- Finck, A D, Samaniego, E, Ngai, S H
- Database ID:
- RPEP-00320
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
How does laughing gas stop pain?
This study shows nitrous oxide selectively triggers the release of specific natural painkillers (met-enkephalin) in the brain. It doesn't broadly activate the opioid system — just these particular peptides.
Is this why naloxone can reverse nitrous oxide effects?
Yes — since nitrous oxide works by releasing enkephalins (which act on opioid receptors), blocking those receptors with naloxone partially reverses the pain relief, confirming the opioid mechanism.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-00320APA
Finck, A D; Samaniego, E; Ngai, S H. (1995). Nitrous oxide selectively releases Met5-enkephalin and Met5-enkephalin-Arg6-Phe7 into canine third ventricular cerebrospinal fluid.. Anesthesia and analgesia, 80(4), 664-70.
MLA
Finck, A D, et al. "Nitrous oxide selectively releases Met5-enkephalin and Met5-enkephalin-Arg6-Phe7 into canine third ventricular cerebrospinal fluid.." Anesthesia and analgesia, 1995.
RethinkPeptides
RethinkPeptides Research Database. "Nitrous oxide selectively releases Met5-enkephalin and Met5-..." RPEP-00320. Retrieved from https://rethinkpeptides.com/research/finck-1995-nitrous-oxide-selectively-releases
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.