Endogenous Pain Modulation Induced by Extrinsic and Intrinsic Psychological Threat in Healthy Individuals

Published:November 27, 2017DOI:


      • Observing pain in another induces endogenous analgesia.
      • Threat of pain to oneself also initiates endogenous analgesia.
      • Endogenous analgesia was observed in the absence of any somatosensory afferent input.
      • Threat cues may significantly influence test paradigms for endogenous analgesia.


      Many factors interact to influence threat perception and the subsequent experience of pain. This study investigated the effect of observing pain (extrinsic threat) and intrinsic threat of pain to oneself on pressure pain threshold (PPT). Forty socially connected pairs of healthy volunteers were threat-primed and randomly allocated to experimental or control roles. An experimental pain modulation paradigm was applied, with non-nociceptive threat cues used as conditioning stimuli. In substudy 1, the extrinsic threat to the experimental participant was observation of the control partner in pain. The control participant underwent hand immersion in noxious and non-noxious water baths in randomized order. Change in the observing participant's PPT from baseline to mid- and postimmersion was calculated. A significant interaction was found for PPT between conditions and test time (F2,78 = 24.9, P < .005). PPT increased by 23.6% ± 19.3% between baseline and during hand immersion (F1,39 = 43.7, P < .005). Substudy 2 investigated threat of imminent pain to self. After a 15-minute break, the experimental participant's PPT was retested (“baseline 2”). Threat was primed by suggestion of whole arm immersion in an icier, larger water bath. PPT was tested immediately before anticipated arm immersion, after which the experiment ended. A significant increase in PPT between “baseline 2” and “pre-immersion” was seen (t = −7.6, P = .005), a pain modulatory effect of 25.8 ± 20.7%. Extrinsic and intrinsic threat of pain, in the absence of any afferent input therefore influences pain modulation. This may need to be considered in studies that use noxious afferent input with populations who show dysfunctional pain modulation.


      The effect on endogenous analgesia of observing another's pain and of threat of pain to oneself was investigated. Extrinsic as well as intrinsic threat cues, in the absence of any afferent input, increased pain thresholds, suggesting that mere threat of pain may initiate analgesic effects in traditional noxious experimental paradigms.

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        • Abrams M.P.
        • Carleton R.N.
        • Asmundson G.J.
        An exploration of the psychometric properties of the PASS-20 with a nonclinical sample.
        J Pain. 2007; 8: 879-886
        • Bernaba M.
        • Johnson K.A.
        • Kong J.T.
        • Mackey S.
        Conditioned pain modulation is minimally influenced by cognitive evaluation or imagery of the conditioning stimulus.
        J Pain Res. 2014; 7: 689-697
        • Bjorkedal E.
        • Flatten M.A.
        Expectations of increased and decreased pain explain the effect of conditioned pain modulation in females.
        J Pain Res. 2012; 5: 289-300
        • Burke A.L.
        • Mathias J.L.
        • Denson L.A.
        Psychological functioning of people living with chronic pain: A meta-analytic review.
        Br J Clin Psychol. 2015; 54: 345-360
        • Butler R.K.
        • Finn D.P.
        Stress-induced analgesia.
        Prog Neurobiol. 2009; 88: 184-202
        • Chesterton L.S.
        • Sim J.
        • Wright C.C.
        • Foster N.E.
        Interrater reliability of algometry in measuring pressure pain thresholds in healthy humans, using multiple raters.
        Clin J Pain. 2007; 23: 760-766
        • Colloca L.
        • Grillon C.
        Understanding placebo and nocebo responses for pain management.
        Curr Pain Headache Rep. 2014; 18: 419
        • Fallon N.
        • Li X.
        • Chiu Y.
        • Nurmikko T.
        • Stancak A.
        Altered cortical processing of observed pain in patients with fibromyalgia syndrome.
        J Pain. 2015; 16: 717-726
        • Ge H.Y.
        • Nie H.
        • Graven-Nielsen T.
        • Danneskiold-Samsøe B.
        • Arendt-Nielsen L.
        Descending pain modulation and its interaction with peripheral sensitization following sustained isometric muscle contraction in fibromyalgia.
        Eur J Pain. 2012; 16: 196-203
        • Geva N.
        • Defrin R.
        Enhanced pain modulation among triathletes: A possible explanation for their exceptional capabilities.
        Pain. 2013; 154: 2317-2323
        • Goffaux P.
        • Redmond W.J.
        • Rainville P.
        • Marchand S.
        Descending analgesia–when the spine echoes what the brain expects.
        Pain. 2007; 130: 137-143
        • Gougeon V.
        • Gaumond I.
        • Goffaux P.
        • Potvin S.
        • Marchand S.
        Triggering descending pain inhibition by observing ourselves or a loved-one in pain.
        Clin J Pain. 2016; 32: 238-245
        • Honigman L.
        • Bar-Bachar O.
        • Yarnitsky D.
        • Sprecher E.
        • Granovsky Y.
        Non-painful wide-area compression inhibits experimental pain.
        Pain. 2016; 157: 2000-2011
        • Jackson P.L.
        • Rainville P.
        • Decety J.
        To what extent do we share the pain of others? Insight from the neural bases of pain empathy.
        Pain. 2006; 125: 5-9
        • Klyne D.M.
        • Schmid A.B.
        • Moseley G.L.
        • Sterling M.
        • Hodges P.W.
        Effect of types and anatomic arrangement of painful stimuli on conditioned pain modulation.
        J Pain. 2015; 16: 176-185
        • Kosek E.
        • Ordeberg G.
        Lack of pressure pain modulation by heterotopic noxious conditioning stimulation in patients with painful osteoarthritis before, but not following, surgical pain relief.
        Pain. 2000; 88: 69-78
        • Le Bars D.
        • Dickenson A.H.
        • Besson J.M.
        Diffuse noxious inhibitory controls (DNIC). Effects on dorsal horn convergent neurones in the rat.
        Pain. 1979; 6: 283-304
        • Lewis G.N.
        • Rice D.A.
        • McNair P.J.
        Conditioned pain modulation in populations with chronic pain: A systematic review and meta-analysis.
        J Pain. 2012; 13: 936-944
        • Liebano R.E.
        • Rakel B.
        • Vance C.G.
        • Walsh D.M.
        • Sluka K.A.
        An investigation of the development of analgesic tolerance to TENS in humans.
        Pain. 2011; 152: 335-342
        • Lluch E.
        • Torres R.
        • Nijs J.
        • Van Oosterwijck J.
        Evidence for central sensitization in patients with osteoarthritis pain: A systematic literature review.
        Eur J Pain. 2014; 18: 1367-1375
        • Locke D.
        • Gibson W.
        • Moss P.
        • Munyard K.
        • Mamotte C.
        • Wright A.
        Analysis of meaningful conditioned pain modulation effect in a pain-free adult population.
        J Pain. 2014; 15: 1190-1198
      1. Merskey H. Bogduk N. Classification of Chronic Pain: Part III: Pain Terms, A Current List with Definitions and Notes on Usage. 2nd ed. IASP Task Force on Taxonomy. IASP Press, Seattle2011: 209-214
        • Moseley G.L.
        • Butler D.S.
        Fifteen years of explaining pain: The past, present, and future.
        J Pain. 2015; 16: 807-813
        • Nahman-Averbuch H.
        • Nir R.R.
        • Sprecher E.
        • Yarnitsky D.
        Psychological factors and conditioned pain modulation: A meta-analysis.
        Clin J Pain. 2016; 32: 541-554
        • Naugle K.M.
        • Fillingim R.B.
        • Riley J.L.
        A meta-analytic review of the hypoalgesic effects of exercise.
        J Pain. 2012; 13: 1139-1150
        • Nir R.
        • Yarnitsky D.
        • Honigman L.
        • Granot M.
        Cognitive manipulation targeted at decreasing the conditioning pain perception reduces the efficacy of conditioned pain modulation.
        Pain. 2012; 153: 170-176
        • Nir R.R.
        • Granovsky Y.
        • Yarnitsky D.
        • Sprecher E.
        • Granot M.
        A psychophysical study of endogenous analgesia: The role of the conditioning pain in the induction and magnitude of conditioned pain modulation.
        Eur J Pain. 2011; 15: 491-497
        • Osborne J.
        • Derbyshire S.W.
        Pain sensation evoked by observing injury in others.
        Pain. 2010; 148: 268-274
        • Ossipov M.H.
        • Morimura K.
        • Porreca F.
        Descending pain modulation and chronification of pain.
        Curr Opin Support Palliat Care. 2014; 8: 143-151
        • Pud D.
        • Granovsky Y.
        • Yarnitsky D.
        The methodology of experimentally induced diffuse noxious inhibitory control (DNIC)-like effect in humans.
        Pain. 2009; 144: 16-19
        • Rutgen M.
        • Seidel E.M.
        • Riecansky I.
        • Lamm C.
        Reduction of empathy for pain by placebo analgesia suggests functional equivalence of empathy and first-hand emotion experience.
        J Neurosci. 2015; 35: 8938-8947
        • Scheuren R.
        • Anton F.
        • Erpelding N.
        • Michaux G.
        Beep tones attenuate pain following Pavlovian conditioning of an endogenous pain control mechanism.
        PLoS One. 2014; 9 (e88710)
        • Sullivan M.J.
        • Bishop S.R.
        • Pivik J.
        The Pain Catastrophizing Scale: Development and validation.
        Psychol Assess. 1995; 7: 524-532
        • Wiech K.
        • Tracey I.
        The influence of negative emotions on pain: Behavioral effects and neural mechanisms.
        Neuroimage. 2009; 47: 987-994
        • Yarnitsky D.
        Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): Its relevance for acute and chronic pain states.
        Curr Opin Anaesthesiol. 2010; 23: 611-615