Distinct and shared cerebral activations in processing innocuous versus noxious contact heat revealed by functional magnetic resonance imaging

Whether innocuous heat (IH)‐exclusive brain regions exist and whether patterns of cerebral responses to IH and noxious heat (NH) stimulations are similar remain elusive. We hypothesized that distinct and shared cerebral networks were evoked by each type of stimulus. Twelve normal subjects participated in a functional MRI study with rapidly ramped IH (38°C) and NH (44°C) applied to the foot. Group activation maps demonstrated three patterns of cerebral activation: (1) IH‐responsive only in the inferior parietal lobule (IPL); (2) NH‐responsive only in the primary somatosensory cortex (S1), secondary somatosensory cortex (S2), posterior insular cortex (IC), and premotor area (PMA); and (3) both IH‐ and NH‐responsive in the middle frontal gyrus, inferior frontal gyrus (IFG), anterior IC, cerebellum, superior frontal gyrus, supplementary motor area, thalamus, anterior cingulate cortex (ACC), lentiform nucleus (LN), and midbrain. According to the temporal analysis of regions of interest, the IPL exclusively responded to IH, and the S2, posterior IC, and PMA were exclusively activated by NH throughout the entire period of stimulation. The IFG, thalamus, ACC, and LN responded differently during different phases of IH versus NH stimulation, and the NH‐responsive‐only S1 responded transiently during the early phase of IH stimulation. BOLD signals in bilateral IPLs were specifically correlated with the ratings of IH sensation, while responses in the contralateral S1 and S2 were correlated with pain intensity. These results suggest that distinct and shared spatial and temporal patterns of cerebral networks are responsible for the perception of IH and NH. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.

[1]  Volkmar Glauche,et al.  Somatotopic organization of human somatosensory cortices for pain: a single trial fMRI study , 2004, NeuroImage.

[2]  M. Honda,et al.  Expectation of Pain Enhances Responses to Nonpainful Somatosensory Stimulation in the Anterior Cingulate Cortex and Parietal Operculum/Posterior Insula: an Event-Related Functional Magnetic Resonance Imaging Study , 2000, The Journal of Neuroscience.

[3]  J D Greenspan,et al.  Regional intensive and temporal patterns of functional MRI activation distinguishing noxious and innocuous contact heat. , 2005, Journal of neurophysiology.

[4]  Krish D. Singh,et al.  fMRI of Thermal Pain: Effects of Stimulus Laterality and Attention , 2002, NeuroImage.

[5]  R. Turner,et al.  Characterizing Evoked Hemodynamics with fMRI , 1995, NeuroImage.

[6]  D. Kenshalo,et al.  Response characteristics of cutaneous warm receptors in the monkey. , 1977, Journal of neurophysiology.

[7]  C Büchel,et al.  Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study. , 2002, Brain : a journal of neurology.

[8]  P. Goldman-Rakic,et al.  Infrequent events transiently activate human prefrontal and parietal cortex as measured by functional MRI. , 1997, Journal of neurophysiology.

[9]  J. Greenspan,et al.  Reversible pain and tactile deficits associated with a cerebral tumor compressing the posterior insula and parietal operculum , 1992, Pain.

[10]  T. Rasmussen,et al.  Tumoural parietal lobe epilepsy. Clinical manifestations and outcome in 34 patients treated between 1934 and 1988. , 1995, Brain : a journal of neurology.

[11]  Christian Maihöfner,et al.  Differential coding of hyperalgesia in the human brain: A functional MRI study , 2005, NeuroImage.

[12]  H. Breiter,et al.  Human brain activation under controlled thermal stimulation and habituation to noxious heat: An fMRI study , 1999, Magnetic resonance in medicine.

[13]  W T Blume,et al.  Seizures involving secondary sensory and related areas. , 1992, Brain : a journal of neurology.

[14]  H. Breiter,et al.  Reward Circuitry Activation by Noxious Thermal Stimuli , 2001, Neuron.

[15]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[16]  James N. Campbell,et al.  Peripheral mechanisms of cutaneous nociception , 2006 .

[17]  H. Burton,et al.  Somatic submodality distribution within the second somatosensory (SII), 7b, retroinsular, postauditory, and granular insular cortical areas of M. fascicularis , 1980, The Journal of comparative neurology.

[18]  D. Gitelman,et al.  Neuroanatomic Overlap of Working Memory and Spatial Attention Networks: A Functional MRI Comparison within Subjects , 1999, NeuroImage.

[19]  M. Tseng,et al.  Effects of aging on contact heat‐evoked potentials: The physiological assessment of thermal perception , 2007, Muscle & nerve.

[20]  E. Chudler,et al.  Behavioral outcome of posterior parietal cortex injury in the monkey , 1996, Pain.

[21]  Jonathan C. W. Brooks,et al.  Somatotopic organisation of the human insula to painful heat studied with high resolution functional imaging , 2005, NeuroImage.

[22]  R. Peyron,et al.  Functional imaging of brain responses to pain. A review and meta-analysis (2000) , 2000, Neurophysiologie Clinique/Clinical Neurophysiology.

[23]  C. Maihöfner,et al.  Secondary somatosensory cortex is important for the sensory discriminative dimension of pain: A functional MRI-study , 2006, Clinical Neurophysiology.

[24]  J. Hyvärinen,et al.  Function of the parietal associative area 7 as revealed from cellular discharges in alert monkeys. , 1974, Brain : a journal of neurology.

[25]  Bruce Pike,et al.  Differentiating noxious- and innocuous-related activation of human somatosensory cortices using temporal analysis of fMRI. , 2002, Journal of neurophysiology.

[26]  R. LaMotte,et al.  Comparison of responses of warm and nociceptive C-fiber afferents in monkey with human judgments of thermal pain. , 1978, Journal of neurophysiology.

[27]  E. Reiman,et al.  Thermosensory activation of insular cortex , 2000, Nature Neuroscience.

[28]  T. Rasmussen,et al.  Parietal lobe epilepsy. Clinical manifestations and outcome in 82 patients treated surgically between 1929 and 1988. , 1995, Brain : a journal of neurology.

[29]  H. E. Torebjörk,et al.  Limitation of sensitization to injured parts of receptive fields in human skin C-nociceptors , 1996, Experimental Brain Research.

[30]  D. Kenshalo,et al.  Response characteristics of cutaneous cold receptors in the monkey. , 1977, Journal of neurophysiology.

[31]  R. Koeppe,et al.  Comparison of human cerebral activation pattern during cutaneous warmth, heat pain, and deep cold pain. , 1996, Journal of neurophysiology.

[32]  R. Meyer,et al.  Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: correlation with pain threshold in humans. , 1995, The Journal of physiology.

[33]  Hyun Wook Park,et al.  BRAIN ACTIVATION RELATED TO AFFECTIVE DIMENSION DURING THERMAL STIMULATION IN HUMANS: A FUNCTIONAL MAGNETIC RESONANCE IMAGING STUDY , 2007, The International journal of neuroscience.

[34]  B. Green,et al.  "Warmth-insensitive fields": evidence of sparse and irregular innervation of human skin by the warmth sense. , 1998, Somatosensory & motor research.

[35]  David Yarnitsky,et al.  Studies of heat pain sensation in man: perception thresholds, rate of stimulus rise and reaction time , 1990, Pain.

[36]  D. Collins,et al.  Automatic 3D Intersubject Registration of MR Volumetric Data in Standardized Talairach Space , 1994, Journal of computer assisted tomography.

[37]  J. Maisog,et al.  Pain intensity processing within the human brain: a bilateral, distributed mechanism. , 1999, Journal of neurophysiology.

[38]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[39]  C. L. Kwan,et al.  Functional MRI study of thalamic and cortical activations evoked by cutaneous heat, cold, and tactile stimuli. , 1998, Journal of neurophysiology.

[40]  Ronald Melzack,et al.  The short-form McGill pain questionnaire , 1987, Pain.

[41]  S. Jacobson,et al.  The thalamic afferents to the inferior parietal lobule of the rhesus monkey , 1978, The Journal of comparative neurology.

[42]  R. Meyer,et al.  Comparison of heat and mechanical receptive fields of cutaneous C-fiber nociceptors in monkey. , 1990, Journal of neurophysiology.

[43]  C. Robinson,et al.  Organization of somatosensory receptive fields in cortical areas 7b, retroinsula, postauditory and granular insula of M. fascicularis , 1980, The Journal of comparative neurology.

[44]  R. Meyer,et al.  Evidence for two different heat transduction mechanisms in nociceptive primary afferents innervating monkey skin. , 1995, The Journal of physiology.

[45]  Jean-Luc Anton,et al.  Region of interest analysis using an SPM toolbox , 2010 .

[46]  A. Pertovaara The influence of stimulus temperature rise rate, adapting temperature, and stimulus duration on suprathreshold responses evoked by noxious heat in the glabrous skin of the limb Comparison of neuronal discharge in the rat spinal dorsal horn with human sensations , 1999, Experimental Brain Research.

[47]  S Minoshima,et al.  Temporal and spatial dynamics of human forebrain activity during heat pain: analysis by positron emission tomography. , 2001, Journal of neurophysiology.

[48]  Gregory A. Miller,et al.  A parietal–frontal network studied by somatosensory oddball MEG responses, and its cross-modal consistency , 2005, NeuroImage.

[49]  D. Yeomans,et al.  Nociceptive responses to high and low rates of noxious cutaneous heating are mediated by different nociceptors in the rat: electrophysiological evidence , 1996, Pain.

[50]  H. Shibasaki,et al.  Seizures arising from the inferior parietal lobule can show ictal semiology of the second sensory seizure (SII seizure) , 2003, Journal of neurology, neurosurgery, and psychiatry.

[51]  Karen D Davis,et al.  Neurophysiological and anatomical considerations in functional imaging of pain , 2003, Pain.

[52]  D. Kenshalo,et al.  Spatial summation on the forehead, forearm, and back produced by radiant and conducted heat. , 1967, Journal of comparative and physiological psychology.

[53]  L. Krubitzer,et al.  Somatotopic organization of cortical fields in the lateral sulcus of Homo sapiens: Evidence for SII and PV , 2000, The Journal of comparative neurology.

[54]  Katsuyuki Sakai,et al.  The prefrontal cortex and working memory: physiology and brain imaging , 2004, Current Opinion in Neurobiology.

[55]  Jürgen Lorenz,et al.  Thermoreceptive innervation of human glabrous and hairy skin: a contact heat evoked potential analysis , 2005, Pain.

[56]  R. M. Siegel,et al.  Corticocortical connections of anatomically and physiologically defined subdivisions within the inferior parietal lobule , 1990, The Journal of comparative neurology.

[57]  Karl J. Friston,et al.  Cortical and subcortical localization of response to pain in man using positron emission tomography , 1991, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[58]  Jong S. Kim Patterns of sensory abnormality in cortical stroke , 2007, Neurology.

[59]  J. Downar,et al.  A multimodal cortical network for the detection of changes in the sensory environment , 2000, Nature Neuroscience.

[60]  James N. Campbell,et al.  Latency to detection of first pain , 1983, Brain Research.

[61]  D. Yarnitsky,et al.  Single C nociceptor responses and psychophysical parameters of evoked pain: effect of rate of rise of heat stimuli in humans. , 1992, The Journal of physiology.

[62]  Karl J. Friston,et al.  Generalisability, Random Effects & Population Inference , 1998, NeuroImage.

[63]  Edmund T. Rolls,et al.  Warm pleasant feelings in the brain , 2008, NeuroImage.

[64]  Lars Arendt-Nielsen,et al.  Contact Heat Evoked Potentials to Painful and Non-Painful Stimuli: Effect of Attention Towards Stimulus Properties , 2004, Brain Topography.

[65]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .