Hind paw inflammation increased spinal dynorphin on the injured side within 24 hours and caused opposite changes in pressure vs heat pain sensitivity.
Side-specific dynorphin increaseIn the spinal cord dorsal horn on the same side as inflammation
What the researchers found
Within 24 hours of inflammation, dynorphin increased specifically in the ipsilateral (same-side) dorsal horn of the spinal cord. Met-enkephalin, leu-enkephalin, and opioid receptor densities did not change.
The inflamed paw showed pronounced supersensitivity to morphine's painkilling effect against pressure pain, starting at 24 hours and increasing at 1 week.
Opioid antagonists (naloxone and the kappa-preferring MR 2266) made the pain worse, suggesting endogenous opioids were already partially controlling the pain.
By 3-5 weeks, inflammation had spread to the opposite paw. Dynorphin was now elevated bilaterally and in the cervico-thoracic cord. Met-enkephalin and leu-enkephalin also rose bilaterally. Adrenal glands were enlarged and plasma beta-endorphin was elevated, signs of chronic stress.
No changes in mu, delta, or kappa receptor density were found at any time point.
Why it matters
This study mapped the complete trajectory of how local inflammation reshapes the spinal cord's opioid system. The early selective dynorphin response, morphine supersensitivity, and eventual spread to the whole opioid system provide a detailed model of how chronic pain develops and why it becomes harder to treat over time.
How the study worked
Rats received Mycobacterium butyricum in one hind paw. Pain was measured with pressure and heat tests over 5 weeks. Opioid peptides measured by immunoassay in spinal cord segments. Opioid receptor binding measured by autoradiography. Morphine sensitivity and opioid antagonist effects tested.
What this study cannot tell us
Tested in rats with an artificial inflammation model. The 5-week timeline may not match human chronic pain development. Opioid peptide measurements were limited to a few time points. Did not test whether the opioid changes were beneficial or detrimental.
How to read the evidence
Moderate animal study with 5-week follow-up and multiple opioid peptide measurements.
When this study was published
Published in 1988 — established the concept of inflammation-driven spinal opioid remodeling.
The bigger picture
Different pain types (pressure vs heat) are regulated by different opioid systems. Understanding this could lead to more targeted pain treatments for inflammatory conditions.
Questions still open
- Could selective kappa agonists treat inflammatory pressure pain?
- Why does inflammation decrease heat sensitivity while increasing pressure sensitivity?
Common questions
Why did pressure and heat pain change in opposite directions?
What is the dorsal horn?
Read the original research
Inflammation of the hind limb as a model of unilateral, localized pain: influence on multiple opioid systems in the spinal cord of the rat.
Pain, 35(3), 299-312
Citation
Millan, M J; Członkowski, A; Morris, B; Stein, C; Arendt, R; Huber, A; Höllt, V; Herz, A. (1988). Inflammation of the hind limb as a model of unilateral, localized pain: influence on multiple opioid systems in the spinal cord of the rat.. Pain, 35(3), 299-312. https://doi.org/10.1016/0304-3959(88)90140-6