Enkephalins inhibit relaxation nerve signals in human colon muscle through delta-opioid receptors, directly explaining one mechanism behind opioid-induced constipation.
Delta receptors: 100x more potent than muDelta-selective opioid agonists were 100-fold more effective than mu agonists at inhibiting colon relaxation nerve signals
What the researchers found
Enkephalins inhibit non-adrenergic, non-cholinergic inhibitory neurotransmission in human colon through prejunctional delta-opioid receptors with high selectivity.
Why it matters
This explains one mechanism by which opioids cause constipation. By blocking the nerve signals that normally relax the colon, opioid peptides reduce colon movement.
How the study worked
Sucrose-gap technique measured electrical responses in human colon circular muscle. Multiple opioid agonists and antagonists were tested to determine receptor selectivity.
What this study cannot tell us
In-vitro study using human tissue. The isolated tissue preparation removes normal neural network activity. Only one region of the colon was studied.
How to read the evidence
Moderate in-vitro study using human colon tissue with thorough pharmacological characterization. Directly relevant to human physiology.
When this study was published
Published in 1990. The delta-opioid mechanism of gut dysmotility has been validated and informs current approaches to managing opioid-induced constipation.
The bigger picture
This study identified the specific receptor mechanism behind opioid constipation in human tissue. By blocking the nerve signals that relax the colon, enkephalins effectively slow gut transit. This understanding has informed the development of peripherally-acting opioid antagonists (like methylnaltrexone) that treat opioid-induced constipation without affecting pain relief.
Questions still open
- Could delta-selective opioid antagonists specifically treat constipation without affecting pain relief?
- Are delta receptor levels altered in irritable bowel syndrome?
Common questions
How does this relate to opioid-induced constipation?
Can this mechanism be blocked without affecting pain relief?
Read the original research
Enkephalins modulate inhibitory neuromuscular transmission in circular muscle of human colon via delta-opioid receptors.
The Journal of physiology, 431, 465-78
Citation
Hoyle, C H; Kamm, M A; Burnstock, G; Lennard-Jones, J E. (1990). Enkephalins modulate inhibitory neuromuscular transmission in circular muscle of human colon via delta-opioid receptors.. The Journal of physiology, 431, 465-78.