Blocking the Enzyme That Destroys Natural Painkillers Enhances the Body's Own Pain Relief | Research

The takeaway

Inhibiting endopeptidase 24.15 (which degrades longer opioid peptides like dynorphin) enhanced natural stress-induced pain relief — a strategy to boost endogenous painkillers without adding external opioids.

Enhanced endogenous pain relief
Endopeptidase 24.15 inhibitor boosted the body's own opioid-mediated pain relief during stress, reversed by naloxone

What the researchers found

Central administration of an endopeptidase 24.15 inhibitor enhanced opioid-mediated swim stress antinociception. The effect was reversed by naloxone.

Why it matters

Instead of adding external opioids (which carry addiction risk), this approach boosts the body's own pain-relief peptides by preventing their breakdown. This could inspire new pain treatments.

How the study worked

Rats received intracerebroventricular injections of the enzyme inhibitor cFP-AAF-pAB before swim stress testing. Pain thresholds were measured before and after. Naloxone was used to confirm opioid involvement.

What this study cannot tell us

Animal study in rats using brain injections. The enzyme inhibitor was given centrally, not orally. Acute stress model may not represent chronic pain. Early-stage research.

How to read the evidence

Preliminary animal study with brain injection. Proof of concept for enzyme inhibition strategy but far from clinical application.

When this study was published

Published in 1991. This concept has evolved into dual enkephalinase inhibitors now in clinical development.

The bigger picture

This represents a fundamentally different approach to pain management: instead of adding opioid drugs (with their addiction and side effect risks), boost the body's own opioid peptides by preventing their breakdown. This concept has inspired development of dual enkephalinase inhibitors now in clinical trials.

Questions still open

Could oral endopeptidase inhibitors provide practical pain relief?
Would this approach have lower addiction risk than external opioids?

Common questions

How is this different from taking a painkiller?

Instead of adding an external opioid drug, this approach protects the body's own natural painkillers from being destroyed. It's like increasing your natural pain relief capacity rather than replacing it with a drug.

Could this be less addictive than opioid drugs?

Theoretically yes. By working through the body's own opioid system rather than flooding receptors with external drugs, the response may be more balanced and physiological — though this needs clinical validation.

Read the original research

Increases in opioid-mediated swim antinociception following endopeptidase 24.15 inhibition.

Physiology & behavior, 50(4), 843-5

View on PubMed ↗

Citation

Kest, B; Orlowski, M; Bodnar, R J. (1991). Increases in opioid-mediated swim antinociception following endopeptidase 24.15 inhibition.. Physiology & behavior, 50(4), 843-5.