Conflict of Interest: The authors declare that there are no conflicts of interest.
Chronic Morphine Increases Fos-Positive Neurons After Concurrent Cornea and Tail Stimulation
Article first published online: 19 SEP 2011
© 2011 American Headache Society
Headache: The Journal of Head and Face Pain
Volume 52, Issue 2, pages 262–273, February 2012
How to Cite
Robbins, A., Schmitt, D., Winterson, B. J. and Meng, I. D. (2012), Chronic Morphine Increases Fos-Positive Neurons After Concurrent Cornea and Tail Stimulation. Headache: The Journal of Head and Face Pain, 52: 262–273. doi: 10.1111/j.1526-4610.2011.01999.x
- Issue published online: 6 FEB 2012
- Article first published online: 19 SEP 2011
- Accepted for publication June 30, 2011.
- medication overuse headache;
- trigeminal nucleus;
- chronic morphine;
Objective.— The aim of the present study was to examine the effect of chronic morphine exposure on diffuse noxious inhibitory controls in a large population of neurons throughout the medullary dorsal horn, as assessed using immunocytochemistry for c-Fos protein.
Background.— Overuse of medications, including the opioids, to treat migraine headache can lead to progressively more frequent headaches. In addition, chronic daily headache sufferers and chronic opioid users both lack the inhibition of pain produced by noxious stimulation of a distal body region, often referred to as diffuse noxious inhibitory controls.
Methods.— In urethane anesthetized rats, Fos-positive neurons were quantified in chronic morphine and vehicle-treated animals following 52°C noxious thermal stimulation of the cornea with and without the application of a spatially remote noxious stimulus (placement of the tail in 55°C water).
Results.— When compared to chronic morphine-treated animals that did not receive the spatially remote noxious stimulus, chronic morphine-treated animals given corneal stimulation along with the spatially remote noxious stimulus demonstrated a 163% increase (P < .05) in the number of Fos-positive neurons in the superficial laminae of the medullary dorsal horn and a 682% increase (P < .01) in deep laminae that was restricted to the side ipsilateral to the applied stimulus. In contrast, no significant difference was found in Fos-like immunoreactivity in vehicle-treated animals given concurrent cornea and tail stimulation or only cornea stimulation in either superficial or deep laminae.
Conclusions.— It is proposed that an increase in descending facilitation and subsequent loss of diffuse noxious inhibitory controls contributes to the development of medication overuse headache.