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Scandinavian Journal of Pain

Official Journal of the Scandinavian Association for the Study of Pain

Editor-in-Chief: Breivik, Harald

CiteScore 2017: 0.84

SCImago Journal Rank (SJR) 2017: 0.401
Source Normalized Impact per Paper (SNIP) 2017: 0.452

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Volume 18, Issue 3


The influence of isometric exercise on endogenous pain modulation: comparing exercise-induced hypoalgesia and offset analgesia in young, active adults

Samuel Harris / Michele Sterling
  • RECOVER Injury Research Centre, NHMRC Centre for Research Excellence in Recovery Following Road Traffic Injuries, The University of Queensland, Brisbane, Australia
  • Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia
  • Other articles by this author:
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/ Scott F. Farrell
  • RECOVER Injury Research Centre, NHMRC Centre for Research Excellence in Recovery Following Road Traffic Injuries, The University of Queensland, Brisbane, Australia
  • Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ashley Pedler
  • RECOVER Injury Research Centre, NHMRC Centre for Research Excellence in Recovery Following Road Traffic Injuries, The University of Queensland, Brisbane, Australia
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/ Ashley D. Smith
  • Corresponding author
  • School of Allied Health Sciences, Griffith University, 58 Parklands Dr, Southport, Gold Coast, QLD 4215, Australia, Phone: +1 403 281 7264
  • Email
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Published Online: 2018-03-30 | DOI: https://doi.org/10.1515/sjpain-2017-0177


Background and aims

Impairment of endogenous analgesia has been associated with the development, maintenance and persistence of pain. Endogenous analgesia can be evaluated using exercise-induced hypoalgesia (EIH) and offset analgesia (OffA) paradigms, which measure temporal filtering of sensory information. It is not clear if these paradigms are underpinned by common mechanisms, as EIH and OffA have not previously been directly compared. A further understanding of the processes responsible for these clinically relevant phenomena may have future diagnostic and therapeutic utility in management of individuals with persistent pain conditions. The primary aim of this study was to investigate if there is a correlation between the magnitudes of EIH and OffA. The secondary aim of the study was to examine whether exercise influences OffA.


Thirty-six healthy, pain-free participants were recruited. EIH was evaluated using pressure pain thresholds (PPT) and pain ratings to suprathreshold pressure stimuli over tibialis anterior and the cervical spine. OffA evaluation utilised a three-step protocol, whereby individualised heat pain thermal stimuli [Numerical Rating Scale (NRS)=50/100] were applied (T1), before increasing 1 °C (T2), followed by 1 °C reduction (T3). The magnitude of OffA was calculated as the percentage reduction in the NRS from T2 to T3. PPT/suprathreshold pain ratings and OffA measures were recorded, before and after 5 min of isometric quadriceps exercise performed at 20–25% maximum voluntary contraction (MVC); and following a 15 min rest period. Data were analysed using repeated measures (RM) ANCOVA and correlational analyses.


There was no correlation between EIH measures (PPTs or pain ratings to suprathreshold pressure stimuli over tibialis anterior or the cervical spine) and OffA (p>0.11 for all). OffA was induced and not modulated by exercise (p=0.28).


Five minutes of 20–25% MVC lower limb isometric exercise provided non-pharmacological pain modulation in young, active adults. Magnitude of EIH was not correlated with that of OffA, and exercise did not influence magnitude of OffA.


These results suggest that in young, pain-free individuals, separate testing of these two paradigms is required to comprehensively evaluate efficacy of endogenous analgesia. If these results are replicated in patient populations, alternative or complementary methods to exercise interventions may be required to modulate impaired OffA.

Keywords: exercise-induced hypoalgesia; offset analgesia; isometric exercise; endogenous analgesia; temporal filtering; pain sensitivity


  • [1]

    Nahman-Averbuch H, Martucci KT, Granovsky Y, Weissman-Fogel I, Yarnitsky D, Coghill RC. Distinct brain mechanisms support spatial vs. temporal filtering of nociceptive information. Pain 2014;155:2491–501.PubMedCrossrefGoogle Scholar

  • [2]

    Staud R, Cannon RC, Mauderli AP, Robinson ME, Price DD, Vierck CJ. Temporal summation of pain from mechanical stimulation of muscle tissue in normal controls and subjects with fibromyalgia syndrome. Pain 2003;102:87–95.CrossrefPubMedGoogle Scholar

  • [3]

    King CD, Wong F, Currie T, Mauderli AP, Fillingim RB, Riley JL. Deficiency in endogenous modulation of prolonged heat pain in patients with irritable bowel syndrome and temporomandibular disorder. Pain 2009;143:172–8.CrossrefPubMedGoogle Scholar

  • [4]

    Seifert F, Kiefer G, DeCol R, Schmelz M, Maihöfner C. Differential endogenous pain modulation in complex-regional pain syndrome. Brain 2009;132:788–800.CrossrefPubMedGoogle Scholar

  • [5]

    Daenen L, Nijs J, Roussel N, Wouters K, Van Loo M, Cras P. Dysfunctional pain inhibition in patients with chronic whiplash-associated disorders: an experimental study. Clin Rheumatol 2013;32:23–31.PubMedCrossrefGoogle Scholar

  • [6]

    Meeus M, Nijs J, Huybrechts S, Truijen S. Evidence for generalized hyperalgesia in chronic fatigue syndrome: a case control study. Clin Rheumatol 2010;29:393–8.PubMedCrossrefGoogle Scholar

  • [7]

    Niesters M, Hoitsma E, Sarton E, Aarts L, Dahan A. Offset analgesia in neuropathic pain patients and effect of treatment with morphine and ketamine. Anesthesiology 2011;115:1063–71.PubMedCrossrefGoogle Scholar

  • [8]

    Niesters M, Proto PL, Aarts L, Sarton EY, Drewes AM, Dahan A. Tapentadol potentiates descending pain inhibition in chronic pain patients with diabetic polyneuropathy. Br J Anaesth 2014;113:148–56.CrossrefPubMedGoogle Scholar

  • [9]

    Suzan E, Treister R, Pud D, Haddad M, Eisenberg E. The effect of hydromorphone therapy on psychophysical measurements of the descending inhibitory pain systems in patients with chronic radicular pain. Pain Med 2015;16:168–75.PubMedCrossrefGoogle Scholar

  • [10]

    Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain 2011;152:S2–15.CrossrefPubMedGoogle Scholar

  • [11]

    Woolf CJ, Bennett GJ, Doherty M, Dubner R, Kidd B, Koltzenburg M, Lipton R, Loeser JD, Payne R, Torebjork E. Towards a mechanism-based classification of pain? Pain 1998;77:227–9.PubMedCrossrefGoogle Scholar

  • [12]

    Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol 2012;9:807–19.Google Scholar

  • [13]

    Dworkin RH. Mechanism-based treatment of pain. Pain 2012;153:2300.CrossrefPubMedGoogle Scholar

  • [14]

    Lannersten L, Kosek E. Dysfunction of endogenous pain inhibition during exercise with painful muscles in patients with shoulder myalgia and fibromyalgia. Pain 2010;151:77–86.CrossrefPubMedGoogle Scholar

  • [15]

    Grill JD, Coghill RC. Transient analgesia evoked by noxious stimulus offset. J Neurophysiol 2002;87:2205–8.PubMedCrossrefGoogle Scholar

  • [16]

    Koltyn KF. Analgesia following exercise: a review. Sports Med 2000;29:85–98.PubMedCrossrefGoogle Scholar

  • [17]

    Naugle KM, Fillingim RB, Riley JL 3rd. A meta-analytic review of the hypoalgesic effects of exercise. J Pain 2012;13:1139–50.PubMedCrossrefGoogle Scholar

  • [18]

    Niesters M, Dahan A, Swartjes M, Noppers I, Fillingim RB, Aarts L, Sarton EY. Effect of ketamine on endogenous pain modulation in healthy volunteers. Pain 2011;152:656–63.PubMedCrossrefGoogle Scholar

  • [19]

    Koltyn KF, Brellenthin AG, Cook DB, Sehgal N, Hillard C. Mechanisms of exercise-induced hypoalgesia. J Pain 2014;15:1294–304.CrossrefPubMedGoogle Scholar

  • [20]

    Martucci KT, Eisenach JC, Tong C, Coghill RC. Opioid-independent mechanisms supporting offset analgesia and temporal sharpening of nociceptive information. Pain 2012;153:1232–43.CrossrefPubMedGoogle Scholar

  • [21]

    Yelle MD, Rogers JM, Coghill RC. Offset analgesia: a temporal contrast mechanism for nociceptive information. Pain 2008;134:174–86.PubMedCrossrefGoogle Scholar

  • [22]

    Crombie KM, Brellenthin AG, Hillard CJ, Koltyn KF. Endocannabinoid and opioid system interactions in exercise-induced hypoalgesia. Pain Med 2018;19:118–23.CrossrefPubMedGoogle Scholar

  • [23]

    Koltyn KF, Trine MR, Stegner AJ, Tobar DA. Effect of isometric exercise on pain perception and blood pressure in men and women. Med Sci Sports Exerc 2001;33:282–90.PubMedGoogle Scholar

  • [24]

    Sternberg WF, Bokat C, Kass L, Alboyadjian A, Gracely RH. Sex-dependent components of the analgesia produced by athletic competition. J Pain 2001;2:65–74.PubMedCrossrefGoogle Scholar

  • [25]

    Honigman L, Yarnitsky D, Sprecher E, Weissman-Fogel I. Psychophysical testing of spatial and temporal dimensions of endogenous analgesia: conditioned pain modulation and offset analgesia. Exp Brain Res 2013;228:493–501.PubMedCrossrefGoogle Scholar

  • [26]

    Naugle KM, Cruz-Almeida Y, Fillingim RB, Riley JL 3rd. Offset analgesia is reduced in older adults. Pain 2013;154:2381–7.CrossrefPubMedGoogle Scholar

  • [27]

    Hoffman MD, Shepanski MA, Ruble SB, Valic Z, Buckwalter JB, Clifford PS. Intensity and duration threshold for aerobic exercise-induced analgesia to pressure pain. Arch Phys Med Rehabil 2004;85:1183–7.PubMedGoogle Scholar

  • [28]

    Umeda M, Newcomb LW, Ellingson LD, Koltyn KF. Examination of the dose-response relationship between pain perception and blood pressure elevations induced by isometric exercise in men and women. Biol Psychol 2010;85:90–6.PubMedCrossrefGoogle Scholar

  • [29]

    Fernandez M, Hartvigsen J, Ferreira ML, Refshauge KM, Machado AF, Lemes IR, Maher CG, Ferreira PH. Advice to stay active or structured exercise in the management of sciatica: a systematic review and meta-analysis. Spine 2015;40:1457–66.CrossrefPubMedGoogle Scholar

  • [30]

    Kobinata H, Ikeda E, Zhang S, Li T, Makita K, Kurata J. Disrupted offset analgesia distinguishes patients with chronic pain from healthy controls. Pain 2017;158:1951–9.PubMedCrossrefGoogle Scholar

  • [31]

    Vierck CJ Jr, Staud R, Price DD, Cannon RL, Mauderli AP, Martin AD. The effect of maximal exercise on temporal summation of second pain (windup) in patients with fibromyalgia syndrome. J Pain 2001;2:334–44.CrossrefPubMedGoogle Scholar

  • [32]

    Ruble SB, Hoffman MD, Shepanski MA, Valic Z, Buckwalter JB, Clifford PS. Thermal pain perception after aerobic exercise. Arch Phys Med Rehabil 2005;86:1019–23.CrossrefPubMedGoogle Scholar

  • [33]

    Magerl W, Krumova EK, Baron R, Tolle T, Treede RD, Maier C. Reference data for quantitative sensory testing (QST): refined stratification for age and a novel method for statistical comparison of group data. Pain 2010;151:598–605.CrossrefGoogle Scholar

  • [34]

    Thomas S, Reading J, Shephard RJ. Revision of the Physical Activity Readiness Questionnaire (PAR-Q). Can J Sport Sci 1992;17:338–45.PubMedGoogle Scholar

  • [35]

    Naugle KM, Naugle KE, Fillingim RB, Riley JL 3rd. Isometric exercise as a test of pain modulation: effects of experimental pain test, psychological variables, and sex. Pain Med 2014;15:692–701.CrossrefPubMedGoogle Scholar

  • [36]

    Smith AD, Jull G, Schneider G, Frizzell B, Hooper RA, Sterling M. Cervical radiofrequency neurotomy reduces central hyperexcitability and improves neck movement in individuals with chronic whiplash. Pain Med 2014;15:128–41.PubMedCrossrefGoogle Scholar

  • [37]

    Yarnitsky D, Sprecher E, Zaslansky R, Hemli JA. Heat pain thresholds: normative data and repeatability. Pain 1995;60:329–32.CrossrefPubMedGoogle Scholar

  • [38]

    Fruhstorfer H, Lindblom U, Schmidt WC. Method for quantitative estimation of thermal thresholds in patients. J Neurol Neurosurg Psychiatry 1976;39:1071–5.CrossrefPubMedGoogle Scholar

  • [39]

    Derbyshire SW, Osborn J. Enhancement of offset analgesia during sequential testing. Eur J Pain 2008;12:980–9.CrossrefPubMedGoogle Scholar

  • [40]

    Naugle KM, Riley JL 3rd. Self-reported physical activity predicts pain inhibitory and facilitatory function. Med Sci Sports Exerc 2014;46:622–9.CrossrefPubMedGoogle Scholar

  • [41]

    Hoeger Bement MK, Dicapo J, Rasiarmos R, Hunter SK. Dose response of isometric contractions on pain perception in healthy adults. Med Sci Sports Exerc 2008;40:1880–9.PubMedCrossrefGoogle Scholar

  • [42]

    Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc 1982;14:377–81.PubMedGoogle Scholar

  • [43]

    Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 2003;35:1381–95.PubMedCrossrefGoogle Scholar

  • [44]

    Neziri AY, Curatolo M, Nüesch E, Scaramozzino P, Andersen OK, Arendt-Nielsen L, Jüni P. Factor analysis of responses to thermal, electrical, and mechanical painful stimuli supports the importance of multi-modal pain assessment. Pain 2011;152:1146–55.CrossrefPubMedGoogle Scholar

  • [45]

    Braz JM, Nassar MA, Wood JN, Basbaum AI. Parallel “pain” pathways arise from subpopulations of primary afferent nociceptor. Neuron 2005;47:787–93.CrossrefPubMedGoogle Scholar

  • [46]

    Yeomans DC, Pirec V, Proudfit HK. Nociceptive responses to high and low rates of noxious cutaneous heating are mediated by different nociceptors in the rat: behavioral evidence. Pain 1996;68:133–40.PubMedCrossrefGoogle Scholar

  • [47]

    Yelle MD, Oshiro Y, Kraft RA, Coghill RC. Temporal filtering of nociceptive information by dynamic activation of endogenous pain modulatory systems. J Neurosci 2009;29:10264–71.CrossrefPubMedGoogle Scholar

  • [48]

    Derbyshire SW, Osborn J. Offset analgesia is mediated by activation in the region of the periaqueductal grey and rostral ventromedial medulla. NeuroImage 2009;47:1002–6.CrossrefPubMedGoogle Scholar

  • [49]

    Scheef L, Jankowski J, Daamen M, Weyer G, Klingenberg M, Renner J, Mueckter S, Schurmann B, Musshoff F, Wagner M, Schild HH, Zimmer A, Boecker H. An fMRI study on the acute effects of exercise on pain processing in trained athletes. Pain 2012;153:1702–14.PubMedCrossrefGoogle Scholar

  • [50]

    Hermans L, Calders P, Van Oosterwijck J, Verschelde E, Bertel E, Meeus M. An overview of offset analgesia and the comparison with conditioned pain modulation: a systematic literature review. Pain Physician 2016;19:307–26.PubMedGoogle Scholar

  • [51]

    Flodin P, Martinsen S, Mannerkorpi K, Löfgren M, Bileviciute-Ljungar I, Kosek E, Fransson P. Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three month physical exercise therapy. Neuroimage Clin 2015;9:134–9.CrossrefPubMedGoogle Scholar

  • [52]

    Vaegter HB, Handberg G, Graven-Nielsen T. Isometric exercises reduce temporal summation of pressure pain in humans. Eur J Pain 2015;19:973–83.PubMedCrossrefGoogle Scholar

  • [53]

    Martucci KT, Yelle MD, Coghill RC. Differential effects of experimental central sensitization on the time-course and magnitude of offset analgesia. Pain 2012;153:463–72.CrossrefPubMedGoogle Scholar

  • [54]

    Smith A, Ritchie C, Pedler A, McCamley K, Roberts K, Sterling M. Exercise induced hypoalgesia is elicited by isometric, but not aerobic exercise in individuals with chronic whiplash associated disorders. Scand J Pain 2017;15:14–21.PubMedCrossrefGoogle Scholar

  • [55]

    Lemming D, Borsbo B, Sjors A, Lind EB, Arendt-Nielsen L, Graven-Nielsen T, Gerdle B. Single-point but not tonic cuff pressure pain sensitivity is associated with level of physical fitness – a study of non-athletic healthy subjects. PLoS One 2015;10:e0125432.PubMedCrossrefGoogle Scholar

  • [56]

    Gurevich M, Kohn PM, Davis C. Exercise-induced analgesia and the role of reactivity in pain sensitivity. J Sports Sci 1994;12:549–59.PubMedCrossrefGoogle Scholar

  • [57]

    Koltyn KF, Garvin AW, Gardiner RL, Nelson TF. Perception of pain following aerobic exercise. Med Sci Sports Exerc 1996;28:1418–21.PubMedCrossrefGoogle Scholar

  • [58]

    Focht BC, Koltyn KF. Alterations in pain perception after resistance exercise performed in the morning and evening. J Strength Cond Res 2009;23:891–7.PubMedCrossrefGoogle Scholar

  • [59]

    Koltyn KF, Arbogast RW. Perception of pain after resistance exercise. Br J Sports Med 1998;32:20–4.PubMedCrossrefGoogle Scholar

About the article

Received: 2017-12-04

Revised: 2018-03-05

Accepted: 2018-03-06

Published Online: 2018-03-30

Published in Print: 2018-07-26

Authors’ statements

Research funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest: The authors do not have any conflicts of interest to declare.

Informed consent: All participants provided informed written consent prior to completing baseline questionnaires and resting physical measures.

Ethical approval: Ethical clearance for this study was granted by Griffith University Human Research Ethics Committee (#: 2016/307).

Citation Information: Scandinavian Journal of Pain, Volume 18, Issue 3, Pages 513–523, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1515/sjpain-2017-0177.

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