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.
Two distinct pain-suppression systemsStress activates both opioid (enkephalin-mediated) and non-opioid analgesia — removing the adrenal medulla eliminated only the opioid type
What the researchers 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.
Why it 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.
How the study worked
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.
What this study cannot 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.
How to read the evidence
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.
When this study was published
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.
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.
Questions still open
- 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?
Common questions
What are enkephalins?
Why does stress sometimes make people not feel pain?
Read the original research
Adrenal medullary enkephalin-like peptides may mediate opioid stress analgesia.
Science (New York, N.Y.), 217(4559), 557-9
Citation
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.