Your Body's Built-In Pain Relief System: Endogenous Peptides and the Opioid Crisis

Your body produces its own pain-relieving peptides — enkephalins, endorphins, and dynorphins — that work through the same pathways as opioid drugs but without the addiction risk.

Bán, E Gy et al.·Brain research bulletin·2020·Moderate EvidenceReview
RPEP-04686ReviewModerate Evidence2020RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Review
Evidence
Moderate Evidence
Sample
Review article — no direct study population; discusses mechanisms relevant to patients with neuropathic pain and opioid use disorders
Participants
Review article — no direct study population; discusses mechanisms relevant to patients with neuropathic pain and opioid use disorders

What This Study Found

The human body has a sophisticated built-in pain relief system that uses endogenous peptides and neurotransmitters — including enkephalins (met- and leu-enkephalin), β-endorphin, dynorphins, endocannabinoids, noradrenaline, dopamine, serotonin, and ATP — working through multiple receptor types (α2-adrenergic, μ-opioid, and others) to modulate pain signaling.

The review maps how these natural pain-relieving molecules interact within the descending pain modulation pathways, with particular focus on neuropathic pain caused by nerve injury, diabetes, or chemotherapy. It also examines why excessive exogenous opioid use creates problems through the sympathetic nervous system, contributing to the opioid crisis.

Notably, while the US and Canada experienced a severe opioid crisis, most European countries did not — despite also increasing pain medication use — suggesting that prescribing practices and regulatory frameworks, not just pain prevalence, drive opioid misuse.

Key Numbers

Endogenous pain modulators reviewed: enkephalins, β-endorphin, dynorphins, cannabinoids, noradrenaline, dopamine, serotonin, ATP · Key receptors: α2-adrenergic, μ-opioid · Context: US/Canada opioid crisis vs Europe

How They Did This

Narrative review synthesizing published research on endogenous neurotransmitters and neuropeptides involved in pain modulation, with emphasis on their roles in neuropathic pain and the mechanisms by which exogenous opioid overuse leads to adverse effects through sympathetic nervous system activation.

Why This Research Matters

Understanding the body's natural pain-relieving peptides is essential for developing alternatives to addictive opioids. By mapping how endogenous opioid peptides like enkephalins and endorphins work alongside other neurotransmitters, this review identifies pathways that could be therapeutically enhanced without the addiction risk of exogenous opioids — a critical need given the ongoing opioid crisis.

The Bigger Picture

The opioid crisis has intensified the search for non-addictive pain treatments. This review highlights that the body already possesses a sophisticated peptide-based pain relief system. Research into enhancing these natural pathways — rather than overwhelming them with synthetic opioids — represents one of the most promising directions in pain medicine, with implications for neuropathic pain, cancer pain, and chronic pain management.

What This Study Doesn't Tell Us

This is a narrative review, not a systematic review or meta-analysis. It synthesizes existing literature without new experimental data. The comparison between the US/Canada and European opioid situations is high-level and does not control for the many socioeconomic and regulatory variables that differ between regions.

Questions This Raises

  • ?Can therapies that boost endogenous opioid peptide levels provide effective pain relief without addiction risk?
  • ?Why did the opioid crisis develop differently in Europe versus North America, and what role did prescribing practices play?
  • ?Could combination approaches targeting multiple endogenous pain pathways simultaneously offer better neuropathic pain control?

Trust & Context

Key Stat:
8+ natural pain relievers Your body produces multiple endogenous peptides and neurotransmitters that modulate pain through the same pathways targeted by prescription opioids
Evidence Grade:
This is a narrative review consolidating established knowledge about endogenous pain modulation pathways. The underlying evidence spans decades of neuroscience research, though this paper presents no new experimental data.
Study Age:
Published in 2020, this review was written in the context of the ongoing opioid crisis and remains highly relevant as the search for non-addictive pain treatments continues to intensify.
Original Title:
The role of the endogenous neurotransmitters associated with neuropathic pain and in the opioid crisis: The innate pain-relieving system.
Published In:
Brain research bulletin, 155, 129-136 (2020)
Database ID:
RPEP-04686

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study

Summarizes existing research on a topic.

What do these levels mean? →

Frequently Asked Questions

What are endogenous opioid peptides?

Endogenous opioid peptides are natural pain-relieving molecules your body produces, including endorphins, enkephalins, and dynorphins. They bind to the same receptors as drugs like morphine and fentanyl, but are produced in controlled amounts and don't cause the dependency and withdrawal that prescription opioids do.

Can understanding these natural painkillers help solve the opioid crisis?

Potentially, yes. By understanding how the body naturally controls pain through these peptides and neurotransmitters, researchers can develop drugs that enhance the body's own pain-relief system rather than flooding it with synthetic opioids. This approach could provide effective pain management with lower addiction risk.

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Cite This Study

RPEP-04686·https://rethinkpeptides.com/research/RPEP-04686

APA

Bán, E Gy; Brassai, A; Vizi, E S. (2020). The role of the endogenous neurotransmitters associated with neuropathic pain and in the opioid crisis: The innate pain-relieving system.. Brain research bulletin, 155, 129-136. https://doi.org/10.1016/j.brainresbull.2019.12.001

MLA

Bán, E Gy, et al. "The role of the endogenous neurotransmitters associated with neuropathic pain and in the opioid crisis: The innate pain-relieving system.." Brain research bulletin, 2020. https://doi.org/10.1016/j.brainresbull.2019.12.001

RethinkPeptides

RethinkPeptides Research Database. "The role of the endogenous neurotransmitters associated with..." RPEP-04686. Retrieved from https://rethinkpeptides.com/research/ban-2020-the-role-of-the

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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.