Blocking Enzymes That Destroy Natural Painkillers Boosts Pain Relief From Acupuncture and Opioid Peptides | Research

The takeaway

A peptidase inhibitor cocktail enhanced pain relief from met-enkephalin, beta-endorphin, and electroacupuncture, but not from dynorphin — revealing peptide-specific enzyme vulnerabilities.

Acupuncture enhanced too
The enzyme inhibitors boosted electroacupuncture analgesia, proving acupuncture works partly through endogenous opioid peptides

What the researchers found

Peptidase inhibitor mixture enhanced antinociception from met-enkephalin, beta-endorphin, and electroacupuncture, but not dynorphin-(1-13).

Why it matters

The body makes its own painkillers (opioid peptides) but enzymes break them down quickly. This study shows that blocking those enzymes can dramatically improve natural pain relief, pointing toward a drug strategy that works with the body rather than replacing its signals.

How the study worked

Rats received intrathecal injections of the peptidase inhibitor mixture (amastatin, captopril, phosphoramidon) followed by opioid peptides or electroacupuncture at the Hoku point. Pain threshold was measured by hind paw pressure test.

What this study cannot tell us

Animal study in rats using spinal injection. The enzyme inhibitors were given directly into the spinal canal, not by mouth. The combination approach has not been tested in humans.

How to read the evidence

Moderate — animal study with multiple comparisons and a revealing dissociation between peptide types.

When this study was published

Published in 1994 (32 years ago). Dual enkephalinase inhibitors have since been developed and tested in humans.

The bigger picture

Instead of giving people opioid drugs, we could boost their own natural painkillers by blocking the enzymes that destroy them. This is potentially a non-addictive approach to pain management.

Questions still open

Could peptidase inhibitors be developed as non-addictive pain medications?
Why is dynorphin resistant to this enzyme inhibitor combination?

Common questions

How does blocking enzymes help with pain?

Your body constantly produces natural painkillers (opioid peptides), but enzymes rapidly break them down. Blocking those enzymes lets your natural painkillers last longer and work better — enhancing your own pain relief system.

Is this related to how acupuncture works?

Yes — the enzyme inhibitors also enhanced acupuncture's pain-relieving effect, confirming that acupuncture triggers the release of endogenous opioid peptides. Protecting those peptides from breakdown makes acupuncture more effective.

Read the original research

Effects of a mixture of peptidase inhibitors (amastatin, captopril and phosphoramidon) on Met-enkephalin-, beta-endorphin-, dynorphin-(1-13)- and electroacupuncture-induced antinociception in rats.

Japanese journal of pharmacology, 66(3), 337-45

View on PubMed ↗

Citation

Kishioka, S; Miyamoto, Y; Fukunaga, Y; Nishida, S; Yamamoto, H. (1994). Effects of a mixture of peptidase inhibitors (amastatin, captopril and phosphoramidon) on Met-enkephalin-, beta-endorphin-, dynorphin-(1-13)- and electroacupuncture-induced antinociception in rats.. Japanese journal of pharmacology, 66(3), 337-45.