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Eur J Pain. 2011 Aug;15(7):716-23. doi: 10.1016/j.ejpain.2010.12.002. Epub 2011 Jan 28.

Differential central pain processing following repetitive intramuscular proton/prostaglandin E₂ injections in female fibromyalgia patients and healthy controls.

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  • 1Department of Clinical and Cognitive Neuroscience, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.



While the etiology of fibromyalgia syndrome (FMS) remains unclear, it is assumed that both peripheral and central components are involved.


To investigate central activation patterns following chemically-induced muscle pain we repetitively injected protons (low pH) and prostaglandin E(2) (PGE(2)) in isotonic solution into the left extensor carpi radialis brevis muscle of female FMS patients and female healthy control subjects (HC). The injection of protons/PGE(2) has the advantage that it is not prone to tachyphylaxis compared to capsaicin and hypotonic saline solution. During the repetitive injections continuous pain ratings were recorded and functional magnetic resonance imaging measurements were conducted.


Injection of protons/PGE(2) led to activation of the anterior and medial cingulate cortices, contralateral primary sensory cortex, bilateral insula and thalamus, left basal ganglia, left orbitofrontal cortex and the cerebellum in FMS patients. In HC, activations were found only in the anterior, medial, and posterior cingulate cortices, and the primary somatosensory cortex. The contrast between the groups revealed significantly stronger activation for FMS patients in the left anterior insula. Peak pain ratings were comparable between HC and FMS patients, but pain duration (sustained pain) was prolonged in FM.


Repetitive proton/PGE(2)-induced excitation of muscle tissue led to a more prolonged perception of pain and more wide-spread activation in pain-related brain areas in FMS, especially in the left (ipsilateral) insula, whereas acute protons/PGE(2)-induced pain processing was similar in the two groups. These data provide further evidence for enhanced central pain processing in FMS patients.

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