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      Novel Characterization Of Thermal Temporal Summation Response By Analysis Of Continuous Pain Vs Time Curves And Exploratory Modeling

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          Abstract

          Background

          Temporal summation (TS) refers to the increased perception of pain with repetitive noxious stimuli. While thermal TS is generally considered a behavioral correlate of spinal windup, noxious heat pulses also trigger additional sensory processes which were modeled in this study.

          Methods

          Nineteen healthy volunteers (9 females, mean age 29.2, SD 10.5) underwent two identical TS experiments, spaced a week apart. The TS paradigm consisted of 10 identical heat pulses with individualized temperatures at the thenar eminence (0.5Hz). We extracted 3 features from continuous TS response curves: Lag, time to first feel pain; Slope, the rate of pain increase between the first and most painful heat pulse; and Delta, the maximum drop in pain after peak pain is reached. We then examined the within-individual stability of these features, followed by the Pearson’s correlations among these features and between the features and negative affect.

          Results

          All 3 features were stable over 1 week. Lag and Delta were negatively correlated ( r = −0.5, p = 0.042). Slope did not correlate with Lag or Delta, but strongly correlated with a traditional TS measure, first pulse pain and peak pain difference ( r = 0.91, p < 0.0001). Negative affects such as trait and state anxiety were negatively correlated with baseline ( r = −0.49, p = 0.031) and peak stimulating temperature ( r = −0.48, p = 0.039), respectively, suggesting an association between anxiety and greater pain sensitivity.

          Conclusion

          We were able to decouple spinal windup from other perceptual processes generated by phasic thermal TS paradigms and demonstrate temporal stability of these curve features. These curve features may help better characterize the complex sensory response to noxious heat pulses and serve as biomarkers to profile patients with chronic pain.

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          Most cited references 41

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          State-dependent opioid control of pain.

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            Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera.

            Quantification of the human painful sensory experience is an essential step in the translation of knowledge from animal nociception to human pain. Translational models for assessment of pain are very important, as such models can be used in: 1) basic mechanistic studies in healthy volunteers; 2) clinical studies for diagnostic and monitoring purposes; 3) pharmacological studies to evaluate analgesic efficacy of new and existing compounds. Quantitative pain assessment, or quantitative sensory testing (QST), provides psychophysical methods that systematically document alterations and reorganization in nervous system function and, in particular, the nociceptive system. QST is defined as the determination of thresholds or stimulus response curves for sensory processing under normal and pathophysiological conditions. The modern concept of advanced QST for experimental pain assessment is a multimodality, multitissue approach where different pain modalities (thermal, mechanical, electrical, and chemical) are applied to different tissues (skin, muscles, and viscera) and the responses are assessed by psychophysical methods (thresholds and stimulus-response functions). Many new and advanced technologies have been developed to help relieve evoked, standardized, and painful reactions. Assessing pain has become a question of solving a multi-input, multi-output problem, with the solution providing the possibility of teasing out which pain pathways and mechanisms are involved, impaired, or affected. Many methodologies have been developed for quantitative assessment of pain perception and involved mechanisms. This paper describes the background for the different methods, the use in basic pain experiments on healthy volunteers, how they can be applied in drug profiling, and the applications in clinical practice.
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              Development of the Fear of Pain Questionnaire--III.

              Fear and/or anxiety about pain is a useful construct, in both theoretical and clinical terms. This article describes the development and refinement of the Fear of Pain Questionnaire (FPQ), which exists in its most current form as the FPQ-III. Factor analytic refinement resulted in a 30-item FPQ-III which consists of Severe Pain, Minor Pain, and Medical Pain subscales. Internal consistency and test-retest reliability of the FPQ-III were found to be good. Four studies are presented, including normative data for samples of inpatient chronic pain patients, general medical outpatients, and unselected undergraduates. High fear of pain individuals had greater avoidance/escape from a pain-relevant Behavioral Avoidance Test with Video, relative to their low fear counterparts, suggesting predictive validity. Chronic pain patients reported the greatest fear of severe pain. Directions for future research with the FPQ-III are discussed, along with general comments about the relation of fear and anxiety to pain.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                JPR
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                02 December 2019
                2019
                : 12
                : 3231-3244
                Affiliations
                [1 ]Department Of Anesthesiology, Perioperative And Pain Medicine, Stanford University School of Medicine , Stanford, CA, USA
                [2 ]Brain And Mind Research Center, Nagoya University , Nagoya, Japan
                [3 ]Department of Biomedical Data Science, School of Medicine, Stanford University , Stanford, CA, USA
                Author notes
                Correspondence: Jiang-Ti Kong Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School Of Medicine , 1070 Arastradero Road, Suite 200, Palo Alto, CA94304, USATel +1 650-723-1235Fax +1 650-725-9642 Email jtkong@stanford.edu
                Article
                212137
                10.2147/JPR.S212137
                6898991
                © 2019 Kong et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 4, Tables: 6, References: 53, Pages: 14
                Funding
                We acknowledge funding support by NIH K24 DA029262 (S.M.), NIH T32 GM89626 (J.K.), NIH K23 AT008477 (J.K.) NIH K23 DA031808 (K.J.), NIH KL2 TR001083 (R.O.), and Chris Redlich Endowment (S.M.)
                Categories
                Original Research

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