Habituation to painful stimulation involves the antinociceptive system
Abstract
The perception of pain results from an interaction between nociceptive and antinociceptive mechanisms. A better understanding of the neural circuitry underlying these physiological interactions provides an important opportunity to develop better treatment strategies for and ultimately even prevent pain. Here, we investigated how repeated painful stimulation over several days is processed, perceived and finally modulated in the healthy human brain. Twenty healthy subjects were stimulated daily with a 20min pain paradigm for 8 consecutive days, and functional MRI performed on days 1, 8 and 22. Repeated painful stimulation over several days resulted in substantially decreased pain ratings to identical painful stimuli. The decreased perception of pain over time is reflected in decreased BOLD responses to nociceptive stimuli in classical pain areas, including thalamus, insula, SII and the putamen. In contrast to this finding, we found that pain-related responses in the rACC, specifically the subgenual anterior cingulate cortex (sgACC), significantly increased over time. Given this area's predominant role in endogenous pain control, this response pattern suggests that habituation to pain is at least in part mediated by increased antinociceptive activity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Responses to a cue could change over the course of the experimental session due to factors such as fatigue, habituation or learning.
“However, it is important to note that responses to a cue could change over the course of the experimental session due to factors such as fatigue, habituation or learning23–28.”
From Boundary effects of expectation in human pain perception (2019) · cites this paper as [28]
Sensitivity to painful stimulation can vary over time.
“Our interest in how perception changes across the experimental session was motivated by the observation that sensitivity to painful stimulation can vary over time15,16,28,29.”
From Boundary effects of expectation in human pain perception (2019) · cites this paper as [28]
Cites
Statistical parametric maps in functional imaging: A general linear approach
Friston, K. J., Holmes, A. P., Worsley, K. J., Poline, J. ‐., Frith, C. D., & Frackowiak, R. S. J. (1994) · Human Brain Mapping · doi:10.1002/hbm.460020402 · Cited by 9,688 · see citing works
Pain Affect Encoded in Human Anterior Cingulate But Not Somatosensory Cortex
Rainville, P., Duncan, G. H., Price, D. D., Carrier, B., & Bushnell, M. C. (1997) · Science · doi:10.1126/science.277.5328.968 · Cited by 2,629 · see citing works
Bonica, J. J., Melzack, R., & Wall, P. D. (1999) · Cited by 2,537 · see citing works
Functional imaging of brain responses to pain. A review and meta-analysis (2000)
Peyron, R., Laurent, B., & García-Larrea, L. (2000) · Neurophysiologie Clinique/Clinical Neurophysiology · doi:10.1016/s0987-7053(00)00227-6 · Cited by 2,171 · see citing works
Pain and emotion interactions in subregions of the cingulate gyrus
Vogt, B. A. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1704 · Cited by 1,810 · see citing works
Pain demands attention: A cognitive–affective model of the interruptive function of pain.
Eccleston, C., & Crombez, G. (1999) · Psychological Bulletin · doi:10.1037/0033-2909.125.3.356 · Cited by 1,718 · see citing works
Quantitative sensory testing: a comprehensive protocol for clinical trials
Rolke, R., Magerl, W., Andrews, K., Schalber, C., Caspari, S. S., Birklein, F., & Treede, R. (2005) · European Journal of Pain · doi:10.1016/j.ejpain.2005.02.003 · Cited by 1,521 · see citing works
Placebo and Opioid Analgesia-- Imaging a Shared Neuronal Network
Petrovic, P., Kalso, E., Petersson, K. M., & Ingvar, M. (2002) · Science · doi:10.1126/science.1067176 · Cited by 1,488 · see citing works
3D statistical neuroanatomical models from 305 MRI volumes
Evans, A. C., Collins, D. L., Mills, S., Brown, E. D., Kelly, R. L., & Peters, T. M. (2005) · IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC) · doi:10.1109/nssmic.1993.373602 · Cited by 1,487 · see citing works
Dissociating pain from its anticipation in the human brain
Ploghaus, A., Tracey, I., Gati, J. S., Clare, S., Menon, R. S., Matthews, P. M., & Rawlins, J. N. P. (1999) · Science · doi:10.1126/science.284.5422.1979 · Cited by 1,151 · see citing works
THE MECHANISM OF PLACEBO ANALGESIA
Levine, J., Gordon, N., & Fields, H. (1978) · The Lancet · doi:10.1016/s0140-6736(78)92762-9 · Cited by 1,094 · see citing works
Neural organization of the defensive behavior system responsible for fear
Fanselow, M. S. (1994) · Psychonomic Bulletin & Review · doi:10.3758/bf03210947 · Cited by 1,000 · see citing works
Imaging how attention modulates pain in humans using functional MRI
Bantick, S. J., Wise, R. G., Ploghaus, A., Clare, S., Smith, S. M., & Tracey, I. (2002) · Brain · doi:10.1093/brain/awf022 · Cited by 888 · see citing works
How Many Subjects Constitute a Study?
Friston, K. J., Holmes, A. P., & Worsley, K. J. (1999) · NeuroImage · doi:10.1006/nimg.1999.0439 · Cited by 814 · cited 1× · see citing works
“At the group level, a random effects approach (Friston et al., 1999) treating individual subjects as a random factor and including non-sphericity correction was applied.”
MethodMethod for quantitative estimation of thermal thresholds in patients.
Fruhstorfer, H., Lindblom, U., & Schmidt, W. C. (1976) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.39.11.1071 · Cited by 785 · see citing works
Placebo Effects Mediated by Endogenous Opioid Activity on μ-Opioid Receptors
Zubieta, J.-K., Bueller, J. A., Jackson, L. R., Scott, D. J., Xu, Y., Koeppe, R. A., Nichols, T. E., & Stohler, C. S. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.0439-05.2005 · Cited by 779 · see citing works
Valet, M., Sprenger, T., Boecker, H., Willoch, F., Rummeny, E., Conrad, B., Erhard, P., & Tolle, T. R. (2004) · Pain · doi:10.1016/j.pain.2004.02.033 · Cited by 708 · see citing works
Bornhövd, K., Quante, M., Glauche, V., Bromm, B., Weiller, C., & Büchel, C. (2002) · Brain · doi:10.1093/brain/awf137 · Cited by 584 · see citing works
Self-citationMechanisms of placebo analgesia: rACC recruitment of a subcortical antinociceptive network
Bingel, U., Lorenz, J., Schoell, E., Weiller, C., & Büchel, C. (2006) · Pain · doi:10.1016/j.pain.2005.08.027 · Cited by 567 · see citing works
Self-citationTREATMENT OF EXCESSIVE AXILLARY SWEATING
Gibbs, J. R. (1974) · The Lancet · doi:10.1016/s0140-6736(74)91979-5 · Cited by 560 · see citing works
Price, D. D., Milling, L. S., Kirsch, I., Duff, A., Montgomery, G. H., & Nicholls, S. S. (1999) · Pain · doi:10.1016/s0304-3959(99)00081-0 · Cited by 559 · see citing works
An MRI-Based Probabilistic Atlas of Neuroanatomy
Evans, A. C., Kamber, M., Collins, D. L., & MacDonald, D. J. (1994) · Springer eBooks · doi:10.1007/978-1-4615-2546-2_48 · Cited by 449 · see citing works
Pain-related cerebral activation is altered by a distracting cognitive task
Petrović, P., Petersson, K. M., Ghatan, P. H., Stone‐Elander, S., & Ingvar, M. (2000) · Pain · doi:10.1016/s0304-3959(99)00232-8 · Cited by 419 · see citing works
Kong, J., Gollub, R. L., Rosman, I. S., Webb, J. M., Vangel, M. G., Kirsch, I., & Kaptchuk, T. J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.3556-05.2006 · Cited by 395 · see citing works
Büchel, C., Bornhövd, K., Quante, M., Glauche, V., Bromm, B., & Weiller, C. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-03-00970.2002 · Cited by 380 · see citing works
Self-citationNeural Mechanisms of Antinociceptive Effects of Hypnosis
Faymonville, M. E., Laureys, S., Degueldre, C., DelFiore, G., Luxen, A., Franck, G., Lamy, M., & Maquet, P. (2000) · Anesthesiology · doi:10.1097/00000542-200005000-00013 · Cited by 370 · see citing works
Somatotopic Activation of Opioid Systems by Target-Directed Expectations of Analgesia
Benedetti, F., Arduino, C., & Amanzio, M. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-09-03639.1999 · Cited by 350 · see citing works
Thermal testing: normative data and repeatability for various test algorithms
Yarnitsky, D., & Sprecher, E. (1994) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(94)90239-9 · Cited by 303 · see citing works
Subcortical structures involved in pain processing: evidence from single-trial fMRI
Bingel, U., Quante, M., Knab, R., Bromm, B., Weiller, C., & Büchel, C. (2002) · Pain · doi:10.1016/s0304-3959(02)00157-4 · Cited by 265 · see citing works
Self-citationPerceived Controllability Modulates the Neural Response to Pain
Salomons, T. V., Johnstone, T., Backonja, M.-M., & Davidson, R. J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1315-04.2004 · Cited by 253 · see citing works
FANSELOW, M. S. (1986) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1986.tb14617.x · Cited by 238 · see citing works
Reduced habituation to experimental pain in migraine patients: a CO2 laser evoked potential study
Valeriani, M., de Tommaso, M., Restuccia, D., Pera, D. L., Guido, M., Iannetti, G. D., Libro, G., Truini, A., Trapani, G. D., Puca, F., et al. (2003) · Pain · doi:10.1016/s0304-3959(03)00137-4 · Cited by 238 · see citing works
Magnetic Resonance Scanning and Epilepsy
Shorvon, S. D., Fish, D. R., Andermann, F., Bydder, G. M., & Stefan, H. (1994) · Springer eBooks · doi:10.1007/978-1-4615-2546-2 · Cited by 232 · see citing works
Yarnitsky, D., & Ochoa, J. L. (1990) · Pain · doi:10.1016/0304-3959(90)91055-n · Cited by 204 · see citing works
Adler, L. J., Gyulai, F. E., Diehl, D. J., Mintun, M. A., Winter, P. M., & Firestone, L. L. (1997) · Anesthesia & Analgesia · doi:10.1097/00000539-199701000-00023 · Cited by 174 · see citing works
Adler, L. J., Gyulai, F. E., Diehl, D. J., Mintun, M. A., Winter, P. M., & Firestone, L. L. (1997) · Anesthesia & Analgesia · doi:10.1213/00000539-199701000-00023 · Cited by 174 · see citing works
Mechanisms of pain modulation in chronic syndromes
Bolay, H., & Moskowitz, M. A. (2002) · Neurology · doi:10.1212/wnl.59.5_suppl_2.s2 · Cited by 160 · see citing works
Functional activity mapping of the mesial hemispheric wall during anticipation of pain
Porro, C. A., Cettolo, V., Francescato, M. P., & Baraldi, P. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00184-8 · Cited by 150 · see citing works
Human Brain Activity Response to Fentanyl Imaged by Positron Emission Tomography
Firestone, L. L., Gyulai, F. E., Mintun, M. A., Adler, L. J., Urso, K., & WINTER, P. M. (1996) · Anesthesia & Analgesia · doi:10.1097/00000539-199606000-00025 · Cited by 147 · see citing works
Somatotopic Representation of Nociceptive Information in the Putamen: An Event-related fMRI Study
Bingel, U., Gläscher, J. P., Weiller, C., & Büchel, C. (2004) · Cerebral Cortex · doi:10.1093/cercor/bhh094 · Cited by 127 · see citing works
Self-citationDavis, K. D., Taub, E., Duffner, F., Lozano, A. M., Tasker, R. R., Houle, S., & Dostrovsky, J. O. (2000) · Journal of neurosurgery · doi:10.3171/jns.2000.92.1.0064 · Cited by 109 · see citing works
The cognitive modulation of pain: hypnosis- and placebo-induced analgesia
Kupers, R. C., Faymonville, M.-É., & Laureys, S. (2005) · Progress in brain research · doi:10.1016/s0079-6123(05)50019-0 · Cited by 104 · see citing works
Flor, H., Diers, M., & Birbaumer, N. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2003.12.064 · Cited by 101 · see citing works
Markenson, J. A. (1996) · The American Journal of Medicine · doi:10.1016/s0002-9343(96)00133-7 · Cited by 94 · see citing works
Chronic low back pain and the reaction to repeated acute pain stimulation
Peters, M. L., Schmidt, A. J. M., & den Hout, M. A. V. (1989) · Pain · doi:10.1016/0304-3959(89)90176-0 · Cited by 89 · see citing works
Body Site Variation of Heat Pain Sensitivity
Taylor, D. J., McGillis, S. L. B., & Greenspan, J. D. (1993) · Somatosensory & Motor Research · doi:10.3109/08990229309028850 · Cited by 82 · see citing works
Pain perception decrement produced through repeated stimulation
Monique Ernst, D., Lee, M. H. M., Dworkin, B. R., & Zaretsky, H. H. (1986) · Pain · doi:10.1016/0304-3959(86)90077-1 · Cited by 80 · see citing works
Greenspan, J. D., & McGillis, S. L. B. (1994) · Somatosensory & Motor Research · doi:10.3109/08990229409028875 · Cited by 79 · see citing works
Habituation to bearable experimental pain elicited by tooth pulp electrical stimulation
Condes-Lara, M., Calvo, J. M., & Fernandez-Guardiola, A. (1981) · Pain · doi:10.1016/0304-3959(81)90004-x · Cited by 74 · see citing works
Milne, R. J., Kay, N., & IRWIN, R. J. (1991) · Experimental Brain Research · doi:10.1007/bf00231861 · Cited by 68 · see citing works
Willoch, F., Gamringer, U. J., Medele, R. J., Steude, U., & Tölle, T. R. (2003) · Pain · doi:10.1016/s0304-3959(02)00423-2 · Cited by 62 · see citing works
STUDIES ON HABITUATION TO COLD PAIN
LEBLANC, J., & Potvin, P. (1966) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y66-033 · Cited by 55 · see citing works
Woestenburg, J. C., Verbaten, M. N., & Slangen, J. L. (1983) · Biological Psychology · doi:10.1016/0301-0511(83)90026-1 · Cited by 54 · see citing works
Has basic research contributed to chronic pain treatment?
Jensen, T. S., Gottrup, H., Kasch, H., Nikolajsen, L., Terkelsen, A. J., & Witting, N. (2001) · Acta Anaesthesiologica Scandinavica · doi:10.1034/j.1399-6576.2001.450913.x · Cited by 44 · see citing works
The auditory event related potentials in episodic and chronic pain sufferers
Demirci, S., & Savaş, S. (2002) · European Journal of Pain · doi:10.1053/eujp.2001.0342 · Cited by 37 · see citing works
Temperature thresholds for cutaneous pain
Neisser, U. (1959) · Journal of Applied Physiology · doi:10.1152/jappl.1959.14.3.368 · Cited by 36 · see citing works
Trigeminofacial Reflexes in Primary Headaches
Cecchini, A., Sandrini, G., Fokin, I. V., Moglia, A., & Nappi, G. (2003) · Cephalalgia · doi:10.1046/j.1468-2982.2003.00572.x · Cited by 32 · see citing works
Evidence for a non-specific mechanism of habituation.
GLASER, E. M., & Gc, W. (1953) · PubMed · Cited by 31 · see citing works
Evoked potential decrements in auditory cortex. II. Critical test for habituation
Westenberg, I. S., & Weinberger, N. M. (1976) · Electroencephalography and Clinical Neurophysiology · doi:10.1016/0013-4694(76)90187-5 · Cited by 30 · see citing works
Habituation in a simple repetitive motor task: a study with movement-related cortical potentials
Dirnberger, G., Duregger, C., Lindinger, G., & Lang, W. (2003) · Clinical Neurophysiology · doi:10.1016/s1388-2457(03)00328-6 · Cited by 29 · see citing works
Dimitrijevic, M. R., & Nathan, P. W. (1973) · Brain · doi:10.1093/brain/96.2.337 · Cited by 28 · see citing works
Adaptive Modifikationen des K�lteschmerzes
Strempel, H. (1976) · European Journal of Applied Physiology · doi:10.1007/bf00421630 · Cited by 28 · see citing works
Dowman, R., & Rosenfeld, J. P. (1985) · Experimental Neurology · doi:10.1016/0014-4886(85)90261-4 · Cited by 22 · see citing works
Duranti, R., Galletti, R., & Pantaleo, T. (1983) · Electroencephalography and Clinical Neurophysiology · doi:10.1016/0013-4694(83)90273-0 · Cited by 22 · see citing works
Neuronale Mechanismen der Schmerzchronifizierung
Zimmermann, M. (2004) · Der Orthopäde · doi:10.1007/s00132-004-0646-z · Cited by 12 · see citing works
Adaptive Modifikationen des KÄlteschmerzes III. Mitteilung: Kurzzeitversuche mit 1-Min-Intervallen
Strempel, H. (1978) · European Journal of Applied Physiology · doi:10.1007/bf00429680 · Cited by 10 · see citing works
Lack of habituation of pain evoked potentials after naloxone.
Janicki, P. K., Libich, J., & Gumulka, W. S. (1980) · PubMed · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Legrain, V., Iannetti, G. D., Plaghki, L., & Mouraux, A. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.10.005 · Cited by 854 · see citing works
Activation of the Opioidergic Descending Pain Control System Underlies Placebo Analgesia
Eippert, F., Bingel, U., Schoell, E. D., Yacubian, J., Klinger, R., Lorenz, J., & Büchel, C. (2009) · Neuron · doi:10.1016/j.neuron.2009.07.014 · Cited by 839 · see citing works
Self-citationChronic pain may change the structure of the brain
May, A. (2008) · Pain · doi:10.1016/j.pain.2008.02.034 · Cited by 649 · see citing works
Self-citationNeuroimaging of the periaqueductal gray: State of the field
Linnman, C., Moulton, E. A., Barmettler, G., Becerra, L. R., & Borsook, D. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.11.095 · Cited by 402 · see citing works
Central mechanisms of pain revealed through functional and structural MRI
Davis, K. D., & Moayedi, M. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-012-9386-8 · Cited by 376 · see citing works
Neurobiology of depression, fibromyalgia and neuropathic pain
Maletic, V. (2009) · Frontiers in bioscience · doi:10.2741/3598 · Cited by 369 · see citing works
Localization of pain-related brain activation: A meta-analysis of neuroimaging data
Duerden, E. G., & Albanese, M. (2013) · Human Brain Mapping · doi:10.1002/hbm.21416 · Cited by 342 · see citing works
Imaging CNS Modulation of Pain in Humans
Bingel, U., & Tracey, I. (2008) · Physiology · doi:10.1152/physiol.00024.2008 · Cited by 308 · see citing works
Self-citationPrestimulus functional connectivity determines pain perception in humans
Ploner, M., Lee, M., Wiech, K., Bingel, U., & Tracey, I. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906186106 · Cited by 297 · see citing works
Self-citationBerna, C., Leknes, S., Holmes, E. A., Edwards, R. R., Goodwin, G. M., & Tracey, I. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.01.014 · Cited by 287 · see citing works
Hsu, D. T., Kirouac, G. J., Zubieta, J.-K., & Bhatnagar, S. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00073 · Cited by 228 · see citing works
Rütgen, M., Seidel, E.-M., Silani, G., Riečanský, I., Hummer, A., Windischberger, C., Petrovic, P., & Lamm, C. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1511269112 · Cited by 208 · see citing works
Brain imaging of pain: state of the art
Morton, D. L., Jones, A. K. P., & Sandhu, J. (2016) · Journal of Pain Research · doi:10.2147/jpr.s60433 · Cited by 211 · see citing works
Changes in brain gray matter due to repetitive painful stimulation
Teutsch, S., Herken, W., Bingel, U., Schoell, E. D., & May, A. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.05.044 · Cited by 200 · see citing works
Self-citationYounger, J., Shen, Y. F., Goddard, G., & Mackey, S. (2010) · Pain · doi:10.1016/j.pain.2010.01.006 · Cited by 193 · see citing works
Redgrave, P., Vautrelle, N., & Reynolds, J. N. J. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.07.060 · Cited by 183 · see citing works
Moayedi, M., Weissman‐Fogel, I., Crawley, A. P., Goldberg, M. B., Freeman, B. V., Tenenbaum, H. C., & Davis, K. D. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.12.013 · Cited by 176 · see citing works
Pain: A Precision Signal for Reinforcement Learning and Control
Seymour, B. (2019) · Neuron · doi:10.1016/j.neuron.2019.01.055 · Cited by 164 · see citing works
Functional connectivity of the human insular cortex during noxious and innocuous thermal stimulation
Peltz, E., Seifert, F., DeCol, R., Dörfler, A., Schwab, S., & Maihöfner, C. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2010.09.012 · Cited by 175 · see citing works
Brodmann area 10: Collating, integrating and high level processing of nociception and pain
Peng, K., Steele, S. C., Becerra, L. R., & Borsook, D. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.11.004 · Cited by 159 · see citing works
Chronic exposure to insufficient sleep alters processes of pain habituation and sensitization
Simpson, N. S., Scott‐Sutherland, J., Gautam, S., Sethna, N. F., & Haack, M. (2017) · Pain · doi:10.1097/j.pain.0000000000001053 · Cited by 152 · see citing works
Habituation and sensitization to heat and cold pain in women with fibromyalgia and healthy controls
Smith, B. W., Tooley, E. M., Montague, E. Q., Robinson, A. E. R., Cosper, C. J., & Mullins, P. G. (2008) · Pain · doi:10.1016/j.pain.2008.09.018 · Cited by 145 · see citing works
White matter brain and trigeminal nerve abnormalities in temporomandibular disorder
Moayedi, M., Weissman-Fogel, I., Salomons, T. V., Crawley, A. P., Goldberg, M. B., Freeman, B. V., Tenenbaum, H. C., & Davis, K. D. (2012) · Pain · doi:10.1016/j.pain.2012.04.003 · Cited by 144 · see citing works
Yücel, M. A., Aasted, C. M., Petkov, M. P., Borsook, D., Boas, D. A., & Becerra, L. R. (2015) · Scientific Reports · doi:10.1038/srep09469 · Cited by 135 · see citing works
Cortical and subcortical responses to high and low effective placebo treatments
Geuter, S., Eippert, F., Attar, C. H., & Büchel, C. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.11.029 · Cited by 130 · see citing works
Self-citationNeurobiology of Value Integration: When Value Impacts Valuation
Park, S. Q., Kahnt, T., Rieskamp, J., & Heekeren, H. R. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4973-10.2011 · Cited by 125 · see citing works
Strigo, I. A., Simmons, A. N., Matthews, S. C., Grimes, E. M., Allard, C. B., Reinhardt, L. E., Paulus, M. P., & Stein, M. B. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.03.034 · Cited by 124 · see citing works
Resting state connectivity correlates with drug and placebo response in fibromyalgia patients
Schmidt-Wilcke, T., Ichesco, E., Hampson, J. P., Kairys, A., Peltier, S., Harte, S., Clauw, D. J., & Harris, R. E. (2014) · NeuroImage: Clinical · doi:10.1016/j.nicl.2014.09.007 · Cited by 122 · see citing works
Lack of endogenous modulation and reduced decay of prolonged heat pain in older adults
Riley, J. L., King, C. D., Wong, F., Fillingim, R. B., & Mauderli, A. P. (2010) · Pain · doi:10.1016/j.pain.2010.04.020 · Cited by 122 · see citing works
Dynamic thermal perception: A review and agenda for future experimental research
Vellei, M., de Dear, R., Inard, C., & Jay, O. (2021) · Building and Environment · doi:10.1016/j.buildenv.2021.108269 · Cited by 117 · see citing works
Down-Regulation of Insular Cortex Responses to Dyspnea and Pain in Asthma
von Leupoldt, A., Sommer, T., Kegat, S., Eippert, F., Baumann, H. J., Klose, H. F. E., Dahme, B., & Büchel, C. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200902-0300oc · Cited by 116 · see citing works
Self-citationBrain mediators of the effects of noxious heat on pain
Atlas, L. Y., Lindquist, M. A., Bolger, N. P., & Wager, T. D. (2014) · Pain · doi:10.1016/j.pain.2014.05.015 · Cited by 112 · see citing works
The Role of Resilience and Purpose in Life in Habituation to Heat and Cold Pain
Smith, B. W., Tooley, E. M., Montague, E. Q., Robinson, A. E. R., Cosper, C. J., & Mullins, P. G. (2009) · Journal of Pain · doi:10.1016/j.jpain.2008.11.007 · Cited by 112 · see citing works
Menstrual pain is associated with rapid structural alterations in the brain
Tu, C., Niddam, D. M., Yeh, T., Lirng, J.-F., Cheng, C.-M., Chou, C.-C., Chao, H., & Hsieh, J. (2013) · Pain · doi:10.1016/j.pain.2013.05.022 · Cited by 111 · see citing works
Tabor, A., Thacker, M. A., Moseley, G. L., & Körding, K. P. (2017) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1005142 · Cited by 111 · see citing works
Harper, D., Ichesco, E., Schrepf, A., Hampson, J. P., Clauw, D. J., Schmidt‐Wilcke, T., Harris, R. E., & Harte, S. E. (2018) · Journal of Pain · doi:10.1016/j.jpain.2018.01.001 · Cited by 110 · see citing works
Cortical and white matter alterations in patients with neuropathic pain after spinal cord injury
Yoon, E. J., Kim, Y. K., Shin, H., Lee, Y., & Kim, S. E. (2013) · Brain Research · doi:10.1016/j.brainres.2013.10.007 · Cited by 106 · see citing works
Habituation to pain: Further support for a central component
Rennefeld, C., Wiech, K., Schoell, E. D., Lorenz, J., & Bingel, U. (2010) · Pain · doi:10.1016/j.pain.2009.12.014 · Cited by 104 · see citing works
Self-citationBlockade of Endogenous Opioid Neurotransmission Enhances Acquisition of Conditioned Fear in Humans
Eippert, F., Bingel, U., Schoell, E. D., Yacubian, J., & Büchel, C. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5336-07.2008 · Cited by 100 · see citing works
Self-citationAn fMRI study on the acute effects of exercise on pain processing in trained athletes
Scheef, L., Jankowski, J., Daamen, M., Weyer, G., Klingenberg, M., Renner, J., Mueckter, S., Schürmann, B., Mußhoff, F., Wagner, M., et al. (2012) · Pain · doi:10.1016/j.pain.2012.05.008 · Cited by 105 · see citing works
Ichesco, E., Quintero, A., Clauw, D. J., Peltier, S., Sundgren, P. C., Gerstner, G. E., & Schmidt‐Wilcke, T. (2011) · Headache The Journal of Head and Face Pain · doi:10.1111/j.1526-4610.2011.01998.x · Cited by 101 · see citing works
Sex differences in endogenous pain modulation by distracting and painful conditioning stimulation
Quiton, R. L., & Greenspan, J. D. (2007) · Pain · doi:10.1016/j.pain.2007.09.001 · Cited by 98 · see citing works
Mobascher, A., Brinkmeyer, J., Warbrick, T., Musso, F., Wittsack, H. J., Stoermer, R., Saleh, A., Schnitzler, A., & Winterer, G. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.09.004 · Cited by 97 · see citing works
Structural basis of empathy and the domain general region in the anterior insular cortex
Mutschler, I., Reinbold, C., Wankerl, J., Seifritz, E., & Ball, T. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00177 · Cited by 92 · see citing works
Rodriguez‐Raecke, R., Doganci, B., Breimhorst, M., Stankewitz, A., Büchel, C., Birklein, F., & May, A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2197-10.2010 · Cited by 89 · see citing works
Self-citationMorphing voxels: the hype around structural imaging of headache patients
May, A. (2009) · Brain · doi:10.1093/brain/awp116 · Cited by 89 · see citing works
Self-citationWilcox, C. E., Mayer, A. R., Teshiba, T. M., Ling, J. M., Smith, B. W., Wilcox, G. L., & Mullins, P. G. (2015) · Pain Medicine · doi:10.1111/pme.12785 · Cited by 83 · see citing works
Sex differences in connectivity of the subgenual anterior cingulate cortex
Wang, G., Erpelding, N., & Davis, K. D. (2014) · Pain · doi:10.1016/j.pain.2014.01.005 · Cited by 82 · see citing works
Bogdanov, V. B., Viganò, A., Noirhomme, Q., Bogdanova, O. V., Guy, N., Laureys, S., Renshaw, P. F., Dallel, R., Phillips, C. L. M., & Schoenen, J. E. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.11.028 · Cited by 76 · see citing works
Neuronal mechanisms during repetitive trigemino-nociceptive stimulation in migraine patients
Aderjan, D., Stankewitz, A., & May, A. (2010) · Pain · doi:10.1016/j.pain.2010.06.024 · Cited by 76 · see citing works
Self-citationAcupuncture modulates cortical thickness and functional connectivity in knee osteoarthritis patients
Chen, X., Spaeth, R. B., Retzepi, K., Ott, D., & Kong, J. (2014) · Scientific Reports · doi:10.1038/srep06482 · Cited by 75 · see citing works
Koenen, L. R., Icenhour, A., Forkmann, K., Pasler, A., Theysohn, N., Forsting, M., Bingel, U., & Elsenbruch, S. (2017) · Pain · doi:10.1097/j.pain.0000000000000924 · Cited by 76 · see citing works
Self-citationStructural Brain Alterations in Patients with Lumbar Disc Herniation: A Preliminary Study
Luchtmann, M., Steinecke, Y., Baecke, S., Lützkendorf, R., Bernarding, J., Kohl, J., Jöllenbeck, B., Tempelmann, C., Ragert, P., & Firsching, R. P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090816 · Cited by 72 · see citing works
Koo, T. K. K., Guo, J., & Brown, C. M. (2013) · Journal of Manipulative and Physiological Therapeutics · doi:10.1016/j.jmpt.2013.01.001 · Cited by 72 · see citing works
Schmidt‐Wilcke, T. (2015) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2015.04.030 · Cited by 71 · see citing works
Treister, R., Pud, D., Ebstein, R. P., Laiba, E., Raz, Y., Gershon, E., Haddad, M., & Eisenberg, E. (2011) · Journal of Pain · doi:10.1016/j.jpain.2011.02.348 · Cited by 70 · see citing works
Sleep Fragmentation Hypersensitizes Healthy Young Women to Deep and Superficial Experimental Pain
Iacovides, S., George, K., Kamerman, P. R., & Baker, F. C. (2017) · Journal of Pain · doi:10.1016/j.jpain.2017.02.436 · Cited by 71 · see citing works
The relationship between pain-induced autonomic arousal and perceived duration.
Piovesan, A., Mirams, L., Poole, H. M., Moore, D., & Ogden, R. (2018) · Emotion · doi:10.1037/emo0000512 · Cited by 72 · see citing works
Brain activity associated with pain, hyperalgesia and allodynia: an ALE meta-analysis
Lanz, S., Seifert, F. C., & Maihöfner, C. (2011) · Journal of Neural Transmission · doi:10.1007/s00702-011-0606-9 · Cited by 69 · see citing works
Bingel, U., Herken, W., Teutsch, S., & May, A. (2008) · Pain · doi:10.1016/j.pain.2008.09.030 · Cited by 69 · see citing works
Self-citationCerebral Representation of the Relief of Itch by Scratching
Vierow, V., Fukuoka, M., Ikoma, A., Dörfler, A., Handwerker, H. O., & Forster, C. (2009) · Journal of Neurophysiology · doi:10.1152/jn.00207.2009 · Cited by 68 · see citing works
Abnormal Brain Functional Connectivity of the Hypothalamus in Cluster Headaches
Qiu, E., Wang, Y., Ma, L., Tian, L., Liu, R., Dong, Z., Xu, X. Z., Zou, Z., & Yu, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057896 · Cited by 68 · see citing works
Buckalew, N. A., Haut, M. W., Aizenstein, H. J., Morrow, L. A., Perera, S., Kuwabara, H., & Weiner, D. K. (2010) · Pain Medicine · doi:10.1111/j.1526-4637.2010.00899.x · Cited by 66 · see citing works
Boundary effects of expectation in human pain perception
Hird, E. J., Charalambous, C., El-Deredy, W., Jones, A. K. P., & Talmi, D. (2019) · Scientific Reports · doi:10.1038/s41598-019-45811-x · Cited by 68 · see citing works
Mobascher, A., Brinkmeyer, J., Warbrick, T., Musso, F., Wittsack, H., Saleh, A., Schnitzler, A., & Winterer, G. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2008.12.051 · Cited by 64 · see citing works
Grey matter changes of the pain matrix in patients with burning mouth syndrome
Sinding, C., Gransjøen, A. M., Schlumberger, G., Grushka, M., Frasnelli, J., & Singh, P. B. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13156 · Cited by 64 · see citing works
Across- and within-session variability of ratings of painful contact heat stimuli
Quiton, R. L., & Greenspan, J. D. (2007) · Pain · doi:10.1016/j.pain.2007.08.034 · Cited by 63 · see citing works
Cortical pain processing in migraine
Coppola, G., Parisi, V., Renzo, A. D., & Pierelli, F. (2019) · Journal of Neural Transmission · doi:10.1007/s00702-019-02089-7 · Cited by 61 · see citing works
Lerman, I. R., Davis, B. A., Huang, M., Huang, C. W., Sorkin, L. S., Proudfoot, J. A., Zhong, E., Kimball, D. F., Rao, R., Simon, B. J., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0201212 · Cited by 62 · see citing works
Treister, R., Eisenberg, E., Gershon, E., Haddad, M., & Pud, D. (2009) · European Journal of Pain · doi:10.1016/j.ejpain.2009.10.005 · Cited by 60 · see citing works
Li, K., Liu, L., Yin, Q., Dun, W., Xu, X., Liu, J., & Zhang, M. (2016) · Brain Imaging and Behavior · doi:10.1007/s11682-016-9533-6 · Cited by 62 · see citing works
Wagner, G., Koschke, M., Leuf, T., Schlösser, R. G. M., & Bär, K. (2008) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2008.10.021 · Cited by 59 · see citing works
Altered Regional Brain Morphology in Patients With Chronic Facial Pain
Schmidt‐Wilcke, T., Hierlmeier, S., & Leinisch, E. (2010) · Headache The Journal of Head and Face Pain · doi:10.1111/j.1526-4610.2010.01637.x · Cited by 56 · see citing works
Influence of Interoceptive Fear Learning on Visceral Perception
Zaman, J., Weltens, N., Ly, H. G., Struyf, D., Vlaeyen, J. W. S., den Bergh, O. V., Wiech, K., Oudenhove, L. V., & Diest, I. V. (2015) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000257 · Cited by 53 · see citing works
Riedl, V., Valet, M., Wöller, A. A., Sorg, C., Vogel, D., Sprenger, T., Boecker, H., Wohlschläger, A. M., & Tölle, T. R. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.04.011 · Cited by 54 · see citing works
May, A., Rodriguez‐Raecke, R., Schulte, A., Ihle, K., Breimhorst, M., Birklein, F., & Jürgens, T. P. (2012) · European Journal of Pain · doi:10.1002/j.1532-2149.2011.00023.x · Cited by 51 · see citing works
Self-citationRodriguez‐Raecke, R., Ihle, K., Ritter, C., Muhtz, C., Otte, C., & May, A. (2013) · European Journal of Pain · doi:10.1002/j.1532-2149.2013.00407.x · Cited by 49 · see citing works
Self-citationGodinho, F. L. F., Faillenot, I., Perchet, C., Frot, M., Magnin, M., & Garcı́a-Larrea, L. (2011) · European Journal of Pain · doi:10.1002/j.1532-2149.2011.00039.x · Cited by 53 · see citing works
Neuroimaging of pain: what does it tell us?
Davis, K. D. (2011) · Current Opinion in Supportive and Palliative Care · doi:10.1097/spc.0b013e3283458f96 · Cited by 51 · see citing works
Body awareness and pain habituation: the role of orientation towards somatic signals
Ginzburg, K., Tsur, N., Karmin, C., Speizman, T., Tourgeman, R., & Defrin, R. (2015) · Journal of Behavioral Medicine · doi:10.1007/s10865-015-9676-8 · Cited by 50 · see citing works
Jürgens, T. P., Schulte, A., Klein, T., & May, A. (2012) · European Journal of Pain · doi:10.1002/j.1532-2149.2012.00135.x · Cited by 50 · see citing works
Self-citationBrain activation patterns underlying fast habituation to painful laser stimuli
Mobascher, A., Brinkmeyer, J., Warbrick, T., Musso, F., Schlemper, V., Wittsack, H. J., Saleh, A., Schnitzler, A., & Winterer, G. (2010) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2009.10.008 · Cited by 48 · see citing works
tDCS modulates cortical nociceptive processing but has little to no impact on pain perception
Ihle, K., Rodriguez‐Raecke, R., Luedtke, K., & May, A. (2014) · Pain · doi:10.1016/j.pain.2014.07.018 · Cited by 47 · see citing works
Self-citationHaloperidol blocks dorsal striatum activity but not analgesia in a placebo paradigm
Wrobel, N., Wiech, K., Forkmann, K., Ritter, C., & Bingel, U. (2014) · Cortex · doi:10.1016/j.cortex.2014.02.023 · Cited by 45 · see citing works
Self-citationMildly negative social encounters reduce physical pain sensitivity
Borsook, T. K., & MacDonald, G. (2010) · Pain · doi:10.1016/j.pain.2010.07.022 · Cited by 45 · see citing works
Habituation to Pain in “Medication Overuse Headache”: A CO 2 Laser‐Evoked Potential Study
Ferraro, D., Vollono, C., Miliucci, R., Virdis, D., Armas, L. D., Pazzaglia, C., Pera, D. L., Tarantino, S., Balestri, M., Trapani, G. D., et al. (2012) · Headache The Journal of Head and Face Pain · doi:10.1111/j.1526-4610.2012.02151.x · Cited by 45 · see citing works
Magerl, W., Burkart, D., Fernandez, A., Schmidt, L., & Treede, R. (2011) · Pain · doi:10.1016/j.pain.2011.11.021 · Cited by 43 · see citing works
Opposite Effects of Stress on Pain Modulation Depend on the Magnitude of Individual Stress Response
Geva, N., & Defrin, R. (2017) · Journal of Pain · doi:10.1016/j.jpain.2017.11.011 · Cited by 43 · see citing works
Stankewitz, A., Valet, M., Schulz, E., Wöller, A. A., Sprenger, T., Vogel, D., Zimmer, C., Mühlau, M., & Tölle, T. R. (2013) · Pain · doi:10.1016/j.pain.2013.05.019 · Cited by 41 · see citing works
Monroe, T. B., Fillingim, R. B., Bruehl, S. P., Rogers, B. P., Dietrich, M. S., Gore, J. C., Atalla, S., & Cowan, R. L. (2017) · Pain Medicine · doi:10.1093/pm/pnx084 · Cited by 42 · see citing works
Sensory and sympathetic correlates of heat pain sensitization and habituation in men and women
Breimhorst, M., Hondrich, M., Rebhorn, C., May, A., & Birklein, F. (2012) · European Journal of Pain · doi:10.1002/j.1532-2149.2012.00133.x · Cited by 41 · see citing works
Self-citationWeissman‐Fogel, I., Dror, A. A., & Defrin, R. (2014) · European Journal of Pain · doi:10.1002/ejp.562 · Cited by 41 · see citing works
Orbitofrontal disinhibition of pain in migraine with aura: An interictal EEG-mapping study
Lev, R., Granovsky, Y., & Yarnitsky, D. (2010) · Cephalalgia · doi:10.1177/0333102409357249 · Cited by 41 · see citing works
Luedtke, K., May, A., & Jürgens, T. P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048857 · Cited by 41 · see citing works
Self-citationMigraine pain: reflections against vasodilatation
Panconesi, A., Bartolozzi, M. L., & Guidi, L. (2009) · The Journal of Headache and Pain · doi:10.1007/s10194-009-0130-6 · Cited by 41 · see citing works
Enhanced Pain Expectation in Migraine: EEG ‐Based Evidence for Impaired Prefrontal Function
Lev, R., Granovsky, Y., & Yarnitsky, D. (2012) · Headache The Journal of Head and Face Pain · doi:10.1111/j.1526-4610.2012.02297.x · Cited by 41 · see citing works
Multiple chemical sensitivity: It's time to catch up to the science
Molot, J., Sears, M., & Anisman, H. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105227 · Cited by 40 · see citing works
Enhanced Short-Term Sensitization of Facial Compared With Limb Heat Pain
Schmidt, K., Schunke, O., Forkmann, K., & Bingel, U. (2015) · Journal of Pain · doi:10.1016/j.jpain.2015.05.003 · Cited by 40 · see citing works
Self-citationJürgens, T. P., Sawatzki, A., Henrich, F., Magerl, W., & May, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0099507 · Cited by 40 · see citing works
Self-citationGabis, L. V., Shklar, B., Baruch, Y. K., Raz, R., Gabis, E., & Geva, D. (2009) · Journal of Rehabilitation Medicine · doi:10.2340/16501977-0315 · Cited by 39 · see citing works
- Authors
- Bingel, U., Schoell, E., Herken, W., Büchel, C., & May, A.
- Affiliations
- Universität Hamburg (DE)
- Corresponding author
- Bingel, U.
- Venue
- Pain
- Published
- 2007-09
- Volume
- 131
- Issue
- 1
- Pages
- 21-30
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W2003102568
- Cited by
- 298
- References
- 66
- Citations by year
- 2026: 4 · 2025: 18 · 2024: 9 · 2023: 12 · 2022: 21 · 2021: 19 · 2020: 11 · 2019: 12 · 2018: 17 · 2017: 18 · 2016: 7 · 2015: 21 · 2014: 20 · 2013: 14 · 2012: 20
- FWCI
- 12.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Volkswagen Foundation
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- pain habituation, antinociception, endogenous pain control, subgenual anterior cingulate cortex, nociceptive processing, pain perception, thalamus, insula, somatosensory cortex, putamen
- MeSH terms
- Adult, Brain, Evoked Potentials, Somatosensory, Habituation, Psychophysiologic, Humans, Male, Pain, Physical Stimulation, Pain Threshold
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review