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Peripheral and central components of habituation of heat pain perception and evoked potentials in humans

Greffrath, Wolfganga,*,1; Baumgärtner, Ulfb,1; Treede, Rolf-Detlefb

doi: 10.1016/j.pain.2007.04.026
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For the neurophysiological examination of nociceptive pathways, contact-heat evoked potentials (contact-heat EPs) are elicited by repetitive brief noxious heat stimuli. Suppression of heat responses in primary nociceptive neurons during repetitive stimulation has been shown in animal models in vivo and in vitro. We now investigated whether heat pain and contact-heat EPs in humans display equivalent signs of habituation. Heat pain and EPs were elicited in 16 volunteers with a contact thermode (30 °C s−1). Heat pulses at three intensities (pain threshold, moderate noxious and maximum available) were applied to the right forearm either by moving the thermode after each pulse to variable locations or when fixed to one location (inter-stimulus intervals 8–10 s). Contact-heat EPs consisted of an early negativity in temporal leads (N1), followed by a biphasic response at the vertex (N2-P2). Pain ratings and contact-heat EPs (N1 and N2-P2 components) displayed significant temperature dependence. N2-P2 correlated positively with ratings. With stimulation at variable locations, both measures slowly decreased with time constants τ of 2 min (ratings) and 12 min (EPs). With stimulation at a fixed location, habituation was much faster for both, ratings (τ = 10 s) and EPs (τ = 33 s). As a consequence, both measures were significantly reduced (p < 0.005) leading to a rightward shift of the stimulus–response function by 5 °C. In conclusion, human heat pain perception and contact-heat EPs display signs of rapid habituation when stimulation is restricted to a fixed location and thus, reflect fatigue of peripheral nociceptive neurons. Habituation within the central nervous system is slower and less pronounced.

aDivision of Neurophysiology, Center of Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Ludolf-Krehl-Str. 13-17, D-68167 Mannheim, Germany

bInstitute of Physiology and Pathophysiology, Johanes Gutenberg-University, Saarstr. 21, D-55099 Mainz, Germany

*Corresponding author. Tel.: +49 (0) 621 383 9933; fax: +49 (0) 621 383 9921.

E-mail: wolfgang.greffrath@medma.uni-heidelberg.de

1These two authors contributed equally to this work.

E-mail: wolfgang.greffrath@medma.uni-heidelberg.de

Submitted July 3, 2006; received in revised form April 12, 2007; accepted April 20, 2007.

© 2007 Lippincott Williams & Wilkins, Inc.
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