Parametric trial-by-trial prediction of pain by easily available physiological measures

Summary Skin conductance and pupil dilation responses to painful stimuli accurately predict behavioral pain ratings across subjects on the individual trial level. ABSTRACT Pain is commonly assessed by subjective reports on rating scales. However, in many experimental and clinical settings, an additional, objective indicator of pain is desirable. In order to identify an objective, parametric signature of pain intensity that is predictive at the individual stimulus level across subjects, we recorded skin conductance and pupil diameter responses to heat pain stimuli of different durations and temperatures in 34 healthy subjects. The temporal profiles of trial‐wise physiological responses were characterized by component scores obtained from principal component analysis. These component scores were then used as predictors in a linear regression analysis, resulting in accurate pain predictions for individual trials. Using the temporal information encoded in the principal component scores explained the data better than prediction by a single summary statistic (ie, maximum amplitude). These results indicate that perceived pain is best reflected by the temporal dynamics of autonomic responses. Application of the regression model to an independent data set of 20 subjects resulted in a very good prediction of the pain ratings demonstrating the generalizability of the identified temporal pattern. Utilizing the readily available temporal information from skin conductance and pupil diameter responses thus allows parametric prediction of pain in human subjects.

[1]  S. Nieuwenhuis,et al.  The anatomical and functional relationship between the P3 and autonomic components of the orienting response. , 2011, Psychophysiology.

[2]  Joachim M. Buhmann,et al.  Decoding the perception of pain from fMRI using multivariate pattern analysis , 2012, NeuroImage.

[3]  Franco Lepore,et al.  Brain activity associated with the electrodermal reactivity to acute heat pain , 2009, NeuroImage.

[4]  T. Ledowski,et al.  Monitoring of sympathetic tone to assess postoperative pain: skin conductance vs surgical stress index , 2009, Anaesthesia.

[5]  D. Price,et al.  The validation of visual analogue scales as ratio scale measures for chronic and experimental pain , 1983, Pain.

[6]  T. Ledowski,et al.  Monitoring Electrical Skin Conductance: A Tool for the Assessment of Postoperative Pain in Children? , 2009, Anesthesiology.

[7]  F. Benedetti,et al.  Repeatability of autonomic responses to pain anticipation and pain stimulation , 2006, European journal of pain.

[8]  Peter König,et al.  Independent encoding of grating motion across stationary feature maps in primary visual cortex visualized with voltage-sensitive dye imaging , 2011, NeuroImage.

[9]  C. Chapman,et al.  Sensory and affective dimensions of phasic pain are indistinguishable in the self-report and psychophysiology of normal laboratory subjects. , 2001, The journal of pain : official journal of the American Pain Society.

[10]  Elena Peltz,et al.  Brain activity during sympathetic response in anticipation and experience of pain , 2013, Human brain mapping.

[11]  I Korhonen,et al.  Novel multiparameter approach for measurement of nociception at skin incision during general anaesthesia. , 2006, British journal of anaesthesia.

[12]  Peter König,et al.  Overt Visual Attention as a Causal Factor of Perceptual Awareness , 2011, PloS one.

[13]  Pupil dilation response to noxious stimulation: Effect of varying nitrous oxide concentration , 2007, Clinical Neurophysiology.

[14]  Gian Domenico Iannetti,et al.  A novel approach to predict subjective pain perception from single-trial laser-evoked potentials , 2013, NeuroImage.

[15]  Claudia Plant,et al.  Decoding an individual's sensitivity to pain from the multivariate analysis of EEG data. , 2012, Cerebral cortex.

[16]  M. Lindquist,et al.  An fMRI-based neurologic signature of physical pain. , 2013, The New England journal of medicine.

[17]  M. Bushnell,et al.  Autonomic responses to heat pain: Heart rate, skin conductance, and their relation to verbal ratings and stimulus intensity , 2011, PAIN®.

[18]  C. Chapman,et al.  Phasic pupil dilation response to noxious stimulation in normal volunteers: relationship to brain evoked potentials and pain report. , 1999, Psychophysiology.

[19]  C. Koch,et al.  Pupil dilation reflects perceptual selection and predicts subsequent stability in perceptual rivalry , 2008, Proceedings of the National Academy of Sciences.

[20]  C. Chapman,et al.  Investigating dose-dependent effects of placebo analgesia: A psychophysiological approach , 2012, PAIN.

[21]  Ashutosh Kumar Singh,et al.  The Elements of Statistical Learning: Data Mining, Inference, and Prediction , 2010 .

[22]  Tor D Wager,et al.  Predicting Individual Differences in Placebo Analgesia: Contributions of Brain Activity during Anticipation and Pain Experience , 2011, The Journal of Neuroscience.

[23]  R. Høifødt,et al.  The effect of experimenter gender on autonomic and subjective responses to pain stimuli , 2007, PAIN.

[24]  G. Schwarz Estimating the Dimension of a Model , 1978 .

[25]  Paul Pauli,et al.  You can see pain in the eye: pupillometry as an index of pain intensity under different luminance conditions. , 2008, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[26]  Berrin Maraşligil,et al.  İnsanlarda Yenilik N2 Yanıtı Hedef Uyaranların Zamansal Sınıflamasını Yansıtır , 2011 .

[27]  W. Willis Central nervous system mechanisms for pain modulation. , 1985, Applied neurophysiology.

[28]  Robert Tibshirani,et al.  The Elements of Statistical Learning: Data Mining, Inference, and Prediction, 2nd Edition , 2001, Springer Series in Statistics.

[29]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[30]  C. Chapman,et al.  Pain and the defense response: structural equation modeling reveals a coordinated psychophysiological response to increasing painful stimulation , 2003, Pain.

[31]  Wolfgang Ellermeier,et al.  Gender differences in pain ratings and pupil reactions to painful pressure stimuli , 1995, Pain.

[32]  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.

[33]  R. Treede,et al.  Human brain mechanisms of pain perception and regulation in health and disease , 2005, European journal of pain.

[34]  R. Treister,et al.  Differentiating between heat pain intensities: The combined effect of multiple autonomic parameters , 2012, PAIN®.

[35]  J. Lagopoulos Electrodermal activity , 2007, Acta Neuropsychiatrica.

[36]  Clifford M. Hurvich,et al.  The impact of model selection on inference in linear regression , 1990 .

[37]  C. Büchel,et al.  Dissociable Neural Responses Related to Pain Intensity, Stimulus Intensity, and Stimulus Awareness within the Anterior Cingulate Cortex: A Parametric Single-Trial Laser Functional Magnetic Resonance Imaging Study , 2002, The Journal of Neuroscience.

[38]  Xiao-Li Meng,et al.  Comparing correlated correlation coefficients , 1992 .

[39]  H. Storm,et al.  The assessment of postoperative pain by monitoring skin conductance: results of a prospective study * , 2007, Anaesthesia.