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From the Department of Nuclear Medicine (Drs. Schreckenberger, Siessmeier, Landvogt, and Bartenstein, and A. Viertmann and H.-G. Buchholz), Institute of Physiology and Pathophysiology (Drs. Rolke and Treede), Department of Neurology (Drs. Rolke and Birklein), Johannes Gutenberg-University Mainz, Germany.
Address correspondence and reprint requests to Dr. Mathias Schreckenberger, Department of Nuclear Medicine, Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany; e-mail: schreckenberger{at}nuklear.klinik.uni-mainz.de
Objective: Muscle pain differs from skin pain with respect to quality, accuracy of localization, and unpleasantness. This study was conducted to identify the brain regions associated with the affective-motivational component of tonic skin and muscle pain.
Methods: Forty healthy volunteers were investigated in three groups with different F-18 fluorodeoxyglucose PET activation scans. A verbal rating scale (VRS) was used to quantify pain intensity and unpleasantness. One group was investigated during painful infusion of an acidified phosphate buffer (pH 5.2) into either muscle or skin for 30 minutes. Muscle and skin infusions were adjusted to achieve pain intensity rating of VRS = 40. The second group received sham stimulation of muscle and skin by infusion of non-acidified phosphate buffer (pH 7.3 to 7.4, pain intensity = 0). The third group underwent only one PET scan without sensory stimulation.
Results: Unpleasantness ratings were higher (VRS 38.3 vs 25.5) during IM compared to intracutaneous stimulation, despite the same pain intensity (VRS = 40). Sham stimulation revealed no pain or unpleasantness. Regional cerebral glucose metabolism during sham stimulation showed similar findings for intracutaneous and IM infusions with significant activations of the bilateral anterior cingulate, bilateral frontal (premotor) cortex, and the ipsilateral parietal operculum. The comparison of pain vs sham stimulation revealed activations of the bilateral insula for IM but not intracutaneous stimulation. The unpleasantness perception in skin and muscle stimulation was positively correlated to the bilateral insular metabolism.
Conclusion: The data suggest that the insula represents one main structure where the unpleasantness of tonic pain perception is encoded.
Supported by the Deutsche Forschungsgemeinschaft (Bi 579/1–1 and Tr 236/13–3), the Bundesministerium für Bildung und Forschung (German Research Network on Neuropathic Pain), and the MAIFOR program of the University of Mainz.
Received June 7, 2004. Accepted in final form December 10, 2004.
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