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The Journal of Neuroscience, May 17, 2006, 26(20):5492-5499; doi:10.1523/JNEUROSCI.2059-05.2006

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Behavioral/Systems/Cognitive
Brain Activation during Input from Mechanoinsensitive versus Polymodal C-Nociceptors

Belinda Susanne Ruehle, Hermann Otto Handwerker, Jochen Klaus Maria Lennerz, Ralf Ringler, and Clemens Forster

Institute of Physiology and Pathophysiology, University of Erlangen/Nuernberg, D-91054 Erlangen, Germany

Correspondence should be addressed to Dr. Clemens Forster, Institute of Physiology and Pathophysiology, University of Erlangen/Nuernberg, Universitaetsstrasse 17, D-91054 Erlangen, Germany. Email: forster{at}physiologie1.uni-erlangen.de

C-nociceptors mediating cutaneous pain in humans can be distinguished in mechano-heat-responsive units (CMH) and mechano-insensitive units (CM_i). However, if sensitized in damaged tissue, CM_i play an important role in inflammatory pain. CM_i differ from CMH by higher electrical thresholds and by mediating the axon reflex. Using these properties, we established two stimulation paradigms: (1) transcutaneous stimulation (TCS) of low current density below the CM_i threshold and (2) intracutaneous stimulation (ICS) of high current density that excites CM_i. This was proven by the quantification of the axon-reflex flare. Applying these stimulation paradigms during functional magnetic resonance imaging, we investigated whether nociceptor stimulation that recruits CM_i leads to different cerebral activation than stimuli that do not recruit CM_i. Brain activation by CM_i was inferred by subtraction. Both stimuli recruited multiple afferents other than CM_i, and we expected a common network of regions involved in different aspects of pain perception and motor nocifensive reactions in both stimuli. ICS that additionally recruited CM_i should activate regions with low acuity that are involved in pain memory and emotional attribution. Besides a common network of pain in both stimuli, TCS activated the supplementary motor area, motor thalamic nuclei, the ipsilateral insula, and the medial cingulate cortex. These regions contribute to a pain processing loop that coordinates the nocifensive motor reaction. CM_i nociceptor activation did not cause relevant activation in this loop and does not seem to play a role in withdrawal. The posterior cingulate cortex was selectively activated by ICS and is apparently important for the processing of inflammatory pain.

Key words: pain; nociception; electric stimulation; fMRI; imaging; cortical; brain

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Received May 21, 2005; revised April 10, 2006; accepted April 10, 2006.

Correspondence should be addressed to Dr. Clemens Forster, Institute of Physiology and Pathophysiology, University of Erlangen/Nuernberg, Universitaetsstrasse 17, D-91054 Erlangen, Germany. Email: forster{at}physiologie1.uni-erlangen.de

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				I. Morrison, M. V. Peelen, and P. E. Downing The Sight of Others' Pain Modulates Motor Processing in Human Cingulate Cortex Cereb Cortex, September 1, 2007; 17(9): 2214 - 2222. [Abstract] [Full Text] [PDF]

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