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.
8+ natural pain relieversYour body produces multiple endogenous peptides and neurotransmitters that modulate pain through the same pathways targeted by prescription opioids
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
Who was studied
Review article — no direct study population; discusses mechanisms relevant to patients with neuropathic pain and opioid use disorders
What this study cannot 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.
How to read the evidence
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.
When this study was published
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.
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.
Questions still open
- 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?
Common questions
What are endogenous opioid peptides?
Can understanding these natural painkillers help solve the opioid crisis?
Read the original research
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
Citation
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