Enkephalin Peptides From the Adrenal Glands May Explain Why Stress Blocks Pain
Researchers showed that enkephalin-like peptides released from the adrenal glands mediate the opioid form of stress-induced pain relief in rats, while a separate non-opioid mechanism operates independently.
Quick Facts
What This Study Found
Different patterns of foot shock in rats activated two distinct pain-suppression mechanisms: opioid and non-opioid stress analgesia. Adrenal demedullation (removing the adrenal medulla) and adrenal denervation reduced opioid stress analgesia but did not affect non-opioid stress analgesia. Reserpine, which is known to increase concentrations of adrenal medullary enkephalin-like peptides, potentiated the opioid form of stress analgesia.
These findings established that adrenal enkephalins — endogenous opioid peptides produced outside the brain — are key mediators of opioid stress-induced pain relief.
Key Numbers
How They Did This
Rats were subjected to different patterns of foot shock to induce stress analgesia. Some rats underwent adrenal demedullation (surgical removal of the adrenal medulla) or adrenal denervation to eliminate adrenal enkephalin release. Others were treated with reserpine to increase adrenal enkephalin levels. Pain sensitivity was then measured to determine whether opioid or non-opioid analgesia was affected.
Why This Research Matters
This study helped establish that the body has multiple built-in pain-control systems, and that enkephalin peptides from the adrenal glands play a specific role in one of them. Understanding how endogenous opioid peptides mediate stress analgesia has been fundamental to pain research and has informed our understanding of how the body manages pain without external drugs.
The Bigger Picture
Published in Science in 1982, this study is a foundational paper in the field of endogenous opioid peptides. It helped establish the concept that the body produces its own painkillers and that the adrenal glands are a significant peripheral source. This work influenced decades of research on pain management, stress physiology, and the development of opioid pharmacology.
What This Study Doesn't Tell Us
The study used foot shock in rats, which is an artificial stressor that may not fully represent human stress experiences. The abstract does not report specific sample sizes or statistical details. As a 1982 study, the techniques available were more limited than modern approaches to measuring peptide release and receptor activity.
Questions This Raises
- ?Do adrenal enkephalins play a similar role in human stress-induced analgesia, or do central brain mechanisms dominate?
- ?Could enhancing adrenal enkephalin release offer a non-addictive approach to pain management?
- ?How do the opioid and non-opioid stress analgesia systems interact under different types of real-world stress?
Trust & Context
- Key Stat:
- Two distinct pain-suppression systems Stress activates both opioid (enkephalin-mediated) and non-opioid analgesia — removing the adrenal medulla eliminated only the opioid type
- Evidence Grade:
- This is an animal experimental study published in Science, one of the most prestigious scientific journals. It provides strong mechanistic evidence in rats but was not designed to test clinical applications in humans.
- Study Age:
- Published in 1982, this is a classic foundational paper. Its core finding — that adrenal enkephalins mediate opioid stress analgesia — has been widely cited and built upon in subsequent decades of pain and neuropeptide research.
- Original Title:
- Adrenal medullary enkephalin-like peptides may mediate opioid stress analgesia.
- Published In:
- Science (New York, N.Y.), 217(4559), 557-9 (1982)
- Authors:
- Lewis, J W, Tordoff, M G, Sherman, J E, Liebeskind, J C
- Database ID:
- RPEP-00014
Evidence Hierarchy
Frequently Asked Questions
What are enkephalins?
Enkephalins are small peptides (5 amino acids long) that your body naturally produces. They bind to opioid receptors — the same receptors that morphine and other opioid drugs target — and help suppress pain. They're essentially your body's built-in painkillers.
Why does stress sometimes make people not feel pain?
Under extreme stress, your body releases enkephalins and other opioid peptides (plus non-opioid mechanisms) that suppress pain signals. This evolutionary adaptation likely helped our ancestors survive injuries during dangerous situations by allowing them to keep functioning despite being hurt.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-00014APA
Lewis, J W; Tordoff, M G; Sherman, J E; Liebeskind, J C. (1982). Adrenal medullary enkephalin-like peptides may mediate opioid stress analgesia.. Science (New York, N.Y.), 217(4559), 557-9.
MLA
Lewis, J W, et al. "Adrenal medullary enkephalin-like peptides may mediate opioid stress analgesia.." Science (New York, 1982.
RethinkPeptides
RethinkPeptides Research Database. "Adrenal medullary enkephalin-like peptides may mediate opioi..." RPEP-00014. Retrieved from https://rethinkpeptides.com/research/lewis-1982-adrenal-medullary-enkephalinlike-peptides
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.