Fibromyalgia Patients Have Normal Opioid Peptide Levels — No Endorphin Deficiency | Research

The takeaway

CSF dynorphin A and met-enkephalin levels were normal in fibromyalgia patients — no evidence of endorphin deficiency — explaining why opioid medications often don't help this condition.

Normal opioid levels in fibromyalgia
CSF dynorphin A and met-enkephalin were at normal levels, directly contradicting the endorphin deficiency theory

What the researchers found

CSF dynorphin A (14.3 fmol/ml) and met-enkephalin-Arg-Phe (35.1 fmol/ml) were normal in fibromyalgia. No evidence of endorphin deficiency.

Why it matters

If fibromyalgia is not caused by an opioid peptide deficiency, this explains why opioid painkillers often do not work well for fibromyalgia. Treatment needs to target other mechanisms.

How the study worked

Cerebrospinal fluid was collected from fibromyalgia patients via lumbar puncture. Dynorphin A and met-enkephalin-Arg-Phe were measured by radioimmunoassay and correlated with previously measured beta-endorphin levels.

What this study cannot tell us

Cross-sectional study. CSF levels may not reflect activity at pain-processing sites. Normal total levels do not rule out local deficiencies or functional problems with the opioid system.

How to read the evidence

Moderate cross-sectional study with quantitative CSF measurements. Cannot rule out local or functional opioid system problems.

When this study was published

Published in 1991. The finding that fibromyalgia is not an opioid deficiency disorder has been reinforced by subsequent research.

The bigger picture

This finding redirected fibromyalgia research away from opioid deficiency toward other mechanisms like central sensitization, supporting the current clinical practice of avoiding opioids for fibromyalgia.

Questions still open

If opioid levels are normal, what drives fibromyalgia pain?
Could opioid receptor sensitivity (not levels) be altered?

Common questions

If endorphins are normal, why does fibromyalgia hurt?

Fibromyalgia appears to involve central sensitization — the nervous system's volume is turned up, amplifying normal signals into pain. The problem is signal processing, not a lack of natural painkillers.

Why don't opioids work for fibromyalgia?

Since there's no opioid deficiency to correct, adding opioid drugs doesn't address the underlying problem. The pain comes from oversensitive pain processing, which requires different treatments like anticonvulsants or serotonin-norepinephrine drugs.

Read the original research

No evidence for endorphin deficiency in fibromyalgia following investigation of cerebrospinal fluid (CSF) dynorphin A and Met-enkephalin-Arg6-Phe7.

Pain, 46(2), 139-143

View on PubMed ↗Publisher’s paper ↗

Citation

Vaerøy, Henning; Nyberg, Fred; Terenius, Lars. (1991). No evidence for endorphin deficiency in fibromyalgia following investigation of cerebrospinal fluid (CSF) dynorphin A and Met-enkephalin-Arg6-Phe7.. Pain, 46(2), 139-143. https://doi.org/10.1016/0304-3959(91)90068-9