Stress-induced analgesia (SIA) is an adaptive response of reduced nociception following demanding acute internal and external stressors. Although a psychobiological understanding of this phenomenon is of importance for stress-related psychiatric and pain conditions, comparably little is known about the psychobiological mechanisms of SIA in humans. The aim of this study was to investigate the effects of acute psychosocial stress on heat pain perception and its possible neuroendocrine mediation by salivary cortisol levels and α-amylase activity in healthy men. Employing an intra-individual assessment of heat pain parameters, acute psychosocial stress did not influence heat pain threshold but significantly, albeit slightly, increased heat pain tolerance. Using linear mixed-model analysis, this effect of psychosocial stress on heat pain tolerance was not mediated by increases of salivary cortisol and state anxiety levels or by the activity of α-amylase. These results show that while psychosocial stress is selectively analgesic for heat pain tolerance, this observed effect is not mediated by stress-induced increases of salivary cortisol and α-amylase activity, as proxies of both the hypothalamus-pituitary-adrenal axis and the autonomic nervous system activation.

Amit Z, Galina ZH: Stress-induced analgesia: adaptive pain suppression. Physiol Rev 1986;66:1091-1120.
Parikh D, Hamid A, Friedman TC, Nguyen K, Tseng A, Marquez P, Lutfy K: Stress-induced analgesia and endogenous opioid peptides: the importance of stress duration. Eur J Pharmacol 2011;650:563-567.
Willer JC, Dehen H, Cambier J: Stress-induced analgesia in humans: endogenous opioids and naloxone-reversible depression of pain reflexes. Science 1981;212:689-691.
Flor H, Grüsser SM: Conditioned stress-induced analgesia in humans. Eur J Pain 1999;3:317-324.
Flor H, Birbaumer N, Schulz R, Grüsser SM, Mucha RF: Pavlovian conditioning of opioid and nonopioid pain inhibitory mechanisms in humans. Eur J Pain 2002;6:395-402.
al'Absi M, Petersen KL: Blood pressure but not cortisol mediates stress effects on subsequent pain perception in healthy men and women. Pain 2003;106:285-295.
Yilmaz P, Diers M, Diener S, Rance M, Wessa M, Flor H: Brain correlates of stress-induced analgesia. Pain 2010;151:522-529.
al'Absi M, Nakajima M, Grabowski J: Stress response dysregulation and stress-induced analgesia in nicotine dependent men and women. Biol Psychol 2013;93:1-8.
Vachon-Presseau E, Martel MO, Roy M, Caron E, Albouy G, Marin MF, Plante I, Sullivan MJ, Lupien SJ, Rainville P: Acute stress contributes to individual differences in pain and pain-related brain activity in healthy and chronic pain patients. J Neurosci 2013;33:6826-6833.
Janal MN, Colt EW, Clark WC, Glusman M: Pain sensitivity, mood and plasma endocrine levels in man following long-distance running: effects of naloxone. Pain 1984;19:13-25.
Lautenschläger G, Habig K, Best C, Kaps M, Elam M, Birklein F, Krämer HH: The impact of baroreflex function on endogenous pain control: a microneurography study. Eur J Neurosci 2015;42:2996-3003.
Rhudy JL, Meagher MW: Fear and anxiety: divergent effects on human pain thresholds. Pain 2000;84:65-75.
de Wied M, Verbaten MN: Affective pictures processing, attention, and pain tolerance. Pain 2001;90:163-172.
Rhudy JL, Meagher MW: Negative affect: effects on an evaluative measure of human pain. Pain 2003;104:617-626.
Ford GK, Finn DP: Clinical correlates of stress-induced analgesia: evidence from pharmacological studies. Pain 2008;140:3-7.
Rhudy JL, Williams AE, McCabe KM, Russell JL, Maynard LJ: Emotional control of nociceptive reactions (ECON): do affective valence and arousal play a role? Pain 2008;136:250-261.
Wiech K, Tracey I: The influence of negative emotions on pain: behavioral effects and neural mechanisms. Neuroimage 2009;47:987-994.
Schedlowski M, Enck P, Rief W, Bingel U: Neuro-bio-behavioral mechanisms of placebo and nocebo responses: implications for clinical trials and clinical practice. Pharmacol Rev 2015;67:697-730.
Quelhas Martins A, McIntyre D, Ring C: Aversive event unpredictability causes stress-induced hypoalgesia. Psychophysiology 2015;52:1066-1070.
Fechir M, Breimhorst M, Kritzmann S, Geber C, Schlereth T, Baier B, Birklein, F: Naloxone inhibits not only stress-induced analgesia but also sympathetic activation and baroreceptor-reflex sensitivity. Eur J Pain 2012;16:82-92.
Millan MJ: Descending control of pain. Prog Neurobiol 2002;66:355-474.
Schlereth T, Birklein F: The sympathetic nervous system and pain. Neuromolecular Med 2008;10:141-147.
Butler RK, Finn DP: Stress-induced analgesia. Prog Neurobiol 2009;88:184-202.
Terman GW, Lewis JW, Liebeskind JC: The effects of corticosterone on opioid stress analgesia. Proc West Pharmacol Soc 1984;27:447-450.
Song ZH, Takemori AE: Involvement of spinal kappa opioid receptors in the antinociception produced by intrathecally administered corticotropin-releasing factor in mice. J Pharmacol Exp Ther 1990;254:363-368.
Sutton LC, Fleshner M, Mazzeo R, Maier SF, Watkins LR: A permissive role of corticosterone in an opioid form of stress-induced analgesia: blockade of opiate analgesia is not due to stress-induced hormone release. Brain Res 1994;663;19-29.
Filaretov AA, Bogdanov AI, Yarushkina NI: Stress-induced analgesia. The role of hormones produced by the hypophyseal-adrenocortical system. Neurosci Behav Physiol 1996;26:572-578.
Lariviere WR, Melzack R: The role of corticotropin-releasing factor in pain and analgesia. Pain 2000;84:1-12.
Finn DP, Jhaveri MD, Beckett SRG, Madjd A, Kendall DA, Marsden CA, Chapman V: Behavioral, central monoaminergic and hypothalamo-pituitary-adrenal axis correlates of fear-conditioned analgesia in rats. Neuroscience 2006;138:1309-1317.
al'Absi M, Petersen KL, Wittmers LE: Adrenocortical and hemodynamic predictors of pain perception in men and women. Pain 2002;96:197-204.
Benarroch EE: Pain-autonomic interactions. Neurol Sci 2006;27(suppl 2):S130-S133.
Bantel C, Trapp S: The role of the autonomic nervous system in acute surgical pain processing - what do we know? Anaesthesia 2011;66:541-544.
Maixner W, Touw KB, Brody MJ, Gebhart GF, Long JP: Factors influencing the altered pain perception in the spontaneously hypertensive rat. Brain Res 1982;237:137-145.
al'Absi M, Buchanan T, Lovallo WR: Pain perception and cardiovascular responses in men with positive parental history for hypertension. Psychophysiology 1996;33:655-661.
Fillingim RB, Maixner W: The influence of resting blood pressure and gender on pain responses. Psychosom Med 1996;58:326-332.
van Stegeren AH, Wolf OT, Kindt M: Salivary alpha amylase and cortisol responses to different stress tasks: impact of sex. Int J Psychophysiol 2008;69:33-40.
Wittwer A, Krummenacher P, La Marca R, Ehlert U, Folkers G: Salivary alpha-amylase correlates with subjective heat pain perception. Pain Med 2016;17:1131-1136.
Kirschbaum C, Pirke KM, Hellhammer DH: The ‘Trier Social Stress Test' - a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 1993;28:76-81.
Krummenacher P, Candia V, Folkers G, Schedlowski M, Schönbächler G: Prefrontal cortex modulates placebo analgesia. Pain 2010;148:368-374.
Pud D, Golan Y, Pesta R: Hand dominancy - a feature affecting sensitivity to pain. Neurosci Lett 2009;467:237-240.
Kirschbaum C, Kudielka BM, Gaab J, Schommer NC, Hellhammer DH: Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. Psychosom Med 1999;61:154-162.
Kirschbaum C, Wüst S, Strasburger CJ: ‘Normal' cigarette smoking increases free cortisol in habitual smokers. Life Sci 1992;50:435-442.
Badrick E, Bobak M, Britton A, Kirschbaum C, Marmot M, Kumari M: The relationship between alcohol consumption and cortisol secretion in an aging cohort. J Clin Endocrinol Metab 2008;93:750-757.
Laakmann G, Wittmann M, Gugath M, Mueller OA, Treusch J, Wahlster U, Stalla GK: Effects of psychotropic drugs (desimipramine, chlorimipramine, sulpiride and diazepam) on the human HPA axis. Psychopharmacology (Berl) 1984;84:66-70.
Ludäscher P, Valerius G, Stiglmayr C, Mauchnik J, Lanius RA, Bohus M, Schmahl C: Pain sensitivity and neural processing during dissociative states in patients with borderline personality disorder with and without comorbid posttraumatic stress disorder: a pilot study. J Psychiatry Neurosci 2010;35:177-184.
Stanley B, Sher L, Wilson S, Ekman R, Huang YY, Mann JJ: Non-suicidal self-injurious behavior, endogenous opioids and monoamine neurotransmitters. J Affect Disord 2010;124:134-140.
Allen AP, Kennedy PJ, Cryan JF, Dinan TG, Clarke G: Biological and psychological markers of stress in humans: focus on the Trier Social Stress Test. Neurosci Biobehav Rev 2014;38:94-124.
Gaab J, Rohleder N, Nater UM, Ehlert U: Psychological determinants of the cortisol stress response: the role of anticipatory cognitive appraisal. Psychoneuroendocrinology 2005;30:599-610.
Perogamvros I, Owen LJ, Newell-Price J, Ray DW, Trainer PJ, Keevil BG: Simultaneous measurement of cortisol and cortisone in human saliva using liquid chromatography-tandem mass spectrometry: application in basal and stimulated conditions. J Chromatogr B Analyt Technol Biomed Life Sci 2009;877:3771-3775.
Faul F, Erdfelder E, Buchner A, Lang A-G: Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 2009;41:1149-1160.
Pruessner JC, Kirschbaum C, Meinlschmid G, Hellhammer DH: Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology 2003;28:916-931.
Pinheiro JC, Bates DM: Mixed-Effects Models in S and S-PLUS. New York, Springer, 2002.
Singer JD, Willett JB: Applied Longitudinal Data Analysis: Modeling Change and Event Occurrence. New York, Oxford University Press, 2003.
Kenny DA, Korchmaros JD, Bolger N: Lower level mediation in multilevel models. Psychol Methods 2003;8:115-128.
Baron RM, Kenny DA: The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 1986;51:1173-1182.
MacKinnon DP: Introduction to Statistical Mediation Analysis. New York, Erlbaum, 2008.
MacKinnon DP, Fairchild AJ, Fritz MS: Mediation analysis. Annu Rev Psychol 2007;58:593-614.
MacKinnon DP, Krull JL, Lockwood CM: Equivalence of the mediation, confounding and suppression effect. Prev Sci 2000;1:173-181.
Harris G, Rollman GB: The validity of experimental pain measures. Pain 1983;17:369-376.
Merskey H, Spear FG: Pain - Psychological and Psychiatric Aspects. London, Baillière, Tindall & Cassell, 1967.
Hartwig AC: Peripheral beta-endorphin and pain modulation. Anesth Prog 1991;38:75-78.
Yarushkina NI: The role of hypothalamo-hypophyseal-adrenocortical system hormones in controlling pain sensitivity. Neurosci Behav Physiol 2008;38:759-766.
Yarushkina NI, Bagaeva TR, Filaretova LP: Central corticotropin-releasing factor (CRF) may attenuate somatic pain sensitivity through involvement of glucocorticoids. J Physiol Pharmacol 2011;62:541-548.
al'Absi M, Rokke PD: Can anxiety help us tolerate pain? Pain 1991;46:43-51.
Benedetti F, Amanzio M, Vighetti S, Asteggiano G: The biochemical and neuroendocrine bases of the hyperalgesic nocebo effect. J Neurosci 2006;26:12014-12022.
Peyron R, García-Larrea L, Grégoire MC, Costes N, Convers P, Lavenne F, Mauguière F, Michel D, Laurent B: Haemodynamic brain responses to acute pain in humans: sensory and attentional networks. Brain 1999;122:1765-1780.
Geuze E, Westenberg HG, Jochims A, de Kloet CS, Bohus M, Vermetten E, Schmahl C: Altered pain processing in veterans with posttraumatic stress disorder. Arch Gen Psychiatry 2007;64:76-85.
Blackburn-Munro G, Blackburn-Munro RE: Chronic pain, chronic stress and depression: coincidence or consequence? J Neuroendocrinol 2001;13:1009-1023.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.