Dynorphin A(1-17) in the spinal cord actively opposes pain relief from most analgesics, functioning as an endogenous anti-painkiller that limits how effective pain drugs can be.
Femtomole doses oppose pain reliefExtremely small amounts of spinal dynorphin A(1-17) are sufficient to activate the antianalgesic system that limits pain drug effectiveness
What the researchers found
Dynorphin A(1-17) mediates an antianalgesic (pain-relief-opposing) system in the spinal cord. Most analgesics activate both pain relief and this dynorphin-mediated opposition simultaneously.
Why it matters
This challenges the view that all opioid peptides are painkillers. Dynorphin A can oppose pain relief, which means the body has a built-in system that limits how much pain relief any drug can provide.
How the study worked
Mice received intrathecal dynorphin antibodies followed by intracerebroventricular analgesic drugs. Pain was measured by tail-flick response. Multiple analgesic types were tested.
What this study cannot tell us
Animal study in mice using spinal and brain injections. The very small doses active in the antianalgesic effect are unusual and the mechanism is not fully understood.
How to read the evidence
Preliminary animal study in mice using spinal and brain injections. The anti-analgesic concept is compelling but uses non-physiological drug delivery.
When this study was published
Published in 1990. The dynorphin anti-analgesic system has been further characterized and is now recognized as a factor in opioid tolerance and chronic pain.
The bigger picture
This finding has profound implications for pain management. If the body automatically activates a dynorphin-mediated opposition to pain relief, then blocking this system could make existing painkillers more effective — potentially allowing lower doses. It also helps explain why chronic pain patients may develop tolerance: the anti-analgesic system may become hyperactive.
Questions still open
- Could blocking spinal dynorphin make pain medications more effective at lower doses?
- Is the dynorphin anti-analgesic system overactive in chronic pain patients?
Common questions
How can an opioid peptide oppose pain relief?
Could this help develop better pain medications?
Read the original research
Spinal dynorphin A (1-17): possible mediator of antianalgesic action.
Neuropharmacology, 29(7), 609-17
Citation
Fujimoto, J M; Arts, K S; Rady, J J; Tseng, L F. (1990). Spinal dynorphin A (1-17): possible mediator of antianalgesic action.. Neuropharmacology, 29(7), 609-17.