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Preserved Capacity for Placebo Analgesia in the Elderly

Published:September 08, 2016DOI:https://doi.org/10.1016/j.jpain.2016.08.012

      Highlights

      • Prevalence of chronic pain rises with age.
      • Age-related changes in the descending modulatory pathways could be a possible mechanism.
      • We experimentally explored endogenous pain modulation in younger compared with older adults.
      • Older adults show preserved capacity for endogenous pain modulation.
      • In the future, nonpharmacological analgesic treatment strategies could be enhanced in the elderly.

      Abstract

      The prevalence of chronic pain rises with increasing age. It has been suggested that the mechanisms responsible for the development of chronic pain overlap with mechanisms involved in aging, potentially implicating age-related changes in descending modulatory pathways. This observation raises the question whether other forms of endogenous pain modulation, in particular placebo analgesia, become compromised with age. Because of the known contribution of placebo effects to analgesic treatment outcomes this question is of important clinical relevance. In this study, we compared the response to thermal painful stimuli and the capacity for endogenous pain modulation between younger and older adults using a well established placebo analgesia paradigm involving expectancy and conditioning components. We recruited 30 younger (age 23–40 years, mean = 27.04, standard error of the mean ± .61) and 24 older adults (60–80 years, mean = 69.3, standard error of the mean ± .89). We observed increased heat pain thresholds and higher pain intensity ratings (in response to physically identical heat stimulation) in the older compared with the younger group. However, the placebo analgesic response was comparable between both age groups of healthy participants. The preserved capacity for placebo analgesia in our sample of older participants highlights the potential to use nonpharmacological analgesic treatment strategies in this age group and to exploit placebo mechanisms as an add-on to existing analgesic (pharmacological) treatment strategies.

      Perspective

      In contrast to the commonly shared view that endogenous pain modulation declines with age we found a comparable capacity for placebo analgesia in a group of healthy older and younger adults.

      Key words

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      References

        • Amanzio M.
        • Benedetti F.
        Neuropharmacological dissection of placebo analgesia: Expectation-activated opioid systems versus conditioning-activated specific subsystems.
        J Neurosci. 1999; 19: 484-494
        • Benedetti F.
        • Arduino C.
        • Costa S.
        • Vighetti S.
        • Tarenzi L.
        • Rainero I.
        • Asteggiano G.
        Loss of expectation-related mechanisms in Alzheimer’s disease makes analgesic therapies less effective.
        Pain. 2006; 121: 133-144
        • Bingel U.
        • Colloca L.
        • Vase L.
        Mechanisms and clinical implications of the placebo effect: Is there a potential for the elderly? A mini-review.
        Gerontology. 2011; 57: 354-363
        • Brassen S.
        • Gamer M.
        • Büchel C.
        Anterior cingulate activation is related to a positivity bias and emotional stability in successful aging.
        Biol Psychiatry. 2011; 70: 131-137
        • Brassen S.
        • Gamer M.
        • Peters J.
        • Gluth S.
        • Büchel C.
        Don’t look back in anger! Responsiveness to missed chances in successful and nonsuccessful aging.
        Science. 2012; 336: 612-614
        • Cherniack E.P.
        Would the elderly be better off if they were given more placebos?.
        Geriatr Gerontol Int. 2010; 10: 131-137
        • Colloca L.
        • Benedetti F.
        How prior experience shapes placebo analgesia.
        Pain. 2006; 124: 126-133
        • Eippert F.
        • Bingel U.
        • Schoell E.D.
        • Yacubian J.
        • Klinger R.
        • Lorenz J.
        • Buchel C.
        Activation of the opioidergic descending pain control system underlies placebo analgesia.
        Neuron. 2009; 63: 533-543
        • Elliott A.M.
        • Smith B.H.
        • Penny K.I.
        • Smith W.C.
        • Chambers W.A.
        The epidemiology of chronic pain in the community.
        Lancet. 1999; 354: 1248-1252
        • Enck P.
        • Bingel U.
        • Schedlowski M.
        • Rief W.
        The placebo response in medicine: Minimize, maximize or personalize?.
        Nat Rev Drug Discov. 2013; 12: 191-204
        • Fjell A.M.
        • Westlye L.T.
        • Amlien I.
        • Espeseth T.
        • Reinvang I.
        • Raz N.
        • Agartz I.
        • Salat D.H.
        • Greve D.N.
        • Fischl B.
        • Dale A.M.
        • Walhovd K.B.
        High consistency of regional cortical thinning in aging across multiple samples.
        Cereb Cortex. 2009; 19: 2001-2012
        • Fruhstorfer H.
        • Lindblom U.
        • Schmidt W.C.
        Method for quantitative estimation of thermal thresholds in patients.
        J Neurol Neurosurg Psychiatry. 1976; 39: 1071-1075
        • Fulton M.M.
        • Allen E.R.
        Polypharmacy in the elderly: A literature review.
        J Am Acad Nurse Pract. 2005; 17: 123-132
        • Good C.D.
        • Johnsrude I.S.
        • Ashburner J.
        • Henson R.N.
        • Friston K.J.
        • Frackowiak R.S.
        A voxel-based morphometric study of ageing in 465 normal adult human brains.
        NeuroImage. 2001; 14: 21-36
        • Grashorn W.
        • Sprenger C.
        • Forkmann K.
        • Wrobel N.
        • Bingel U.
        Age-dependent decline of endogenous pain control: Exploring the effect of expectation and depression.
        PLoS One. 2013; 8: e75629
        • Harkins S.W.
        • Price D.D.
        • Martelli M.
        Effects of age on pain perception: Thermonociception.
        J Gerontol. 1986; 41: 58-63
      1. Hautzinger M, Bailer M: Allgemeine Depressionsskala (ADS). Göttingen, Beltz Test GmbH, 1993

        • Helme R.D.
        • Gibson S.J.
        The epidemiology of pain in elderly people.
        Clin Geriatr Med. 2001; 17 (v): 417-431
        • Kaufman D.W.
        • Kelly J.P.
        • Rosenberg L.
        • Anderson T.E.
        • Mitchell A.A.
        Recent patterns of medication use in the ambulatory adult population of the United States: The Slone survey.
        JAMA. 2002; 287: 337-344
        • Krummenacher P.
        • Candia V.
        • Folkers G.
        • Schedlowski M.
        • Schonbachler G.
        Prefrontal cortex modulates placebo analgesia.
        Pain. 2010; 148: 368-374
        • Lariviere M.
        • Goffaux P.
        • Marchand S.
        • Julien N.
        Changes in pain perception and descending inhibitory controls start at middle age in healthy adults.
        Clin J Pain. 2007; 23: 506-510
        • Lautenbacher S.
        Experimental approaches in the study of pain in the elderly.
        Pain Med. 2012; 13: S44-S50
        • Lautenbacher S.
        • Huber C.
        • Kunz M.
        • Parthum A.
        • Weber P.G.
        • Griessinger N.
        • Sittl R.
        Hypervigilance as predictor of postoperative acute pain: Its predictive potency compared with experimental pain sensitivity, cortisol reactivity, and affective state.
        Clin J Pain. 2009; 25: 92-100
        • Maher R.L.
        • Hanlon J.T.
        • Hajjar E.R.
        Clinical consequences of polypharmacy in elderly.
        Exp Opin Drug Saf. 2014; 13: 57-65
        • Mather M.
        The affective neuroscience of aging.
        Annu Rev Psychol. 2016; 67: 213-238
        • Montgomery G.H.
        • Kirsch I.
        Classical conditioning and the placebo effect.
        Pain. 1997; 72: 107-113
        • Rolke R.
        • Magerl W.
        • Campbell K.A.
        • Schalber C.
        • Caspari S.
        • Birklein F.
        • Treede R.D.
        Quantitative sensory testing: A comprehensive protocol for clinical trials.
        Eur J Pain. 2006; 10: 77-88
        • Schretlen D.
        • Pearlson G.D.
        • Anthony J.C.
        • Aylward E.H.
        • Augustine A.M.
        • Davis A.
        • Barta P.
        Elucidating the contributions of processing speed, executive ability, and frontal lobe volume to normal age-related differences in fluid intelligence.
        J Int Neuropsychol Soc. 2000; 6: 52-61
        • Sittl R.
        • Griessinger N.
        • Likar R.
        Analgesic efficacy and tolerability of transdermal buprenorphine in patients with inadequately controlled chronic pain related to cancer and other disorders: A multicenter, randomized, double-blind, placebo-controlled trial.
        Clin Ther. 2003; 25: 150-168
        • Sullivan M.J.
        • Bishop S.R.
        • Pivik J.
        The pain catastrophizing scale: Development and validation.
        Psychol Assess. 1995; 7: 524
        • Voudouris N.J.
        • Peck C.L.
        • Coleman G.
        The role of conditioning and verbal expectancy in the placebo response.
        Pain. 1990; 43: 121-128
        • Wager T.D.
        • Atlas L.Y.
        • Leotti L.A.
        • Rilling J.K.
        Predicting individual differences in placebo analgesia: Contributions of brain activity during anticipation and pain experience.
        J Neurosci. 2011; 31: 439-452
        • Wager T.D.
        • Rilling J.K.
        • Smith E.E.
        • Sokolik A.
        • Casey K.L.
        • Davidson R.J.
        • Kosslyn S.M.
        • Rose R.M.
        • Cohen J.D.
        Placebo-induced changes in FMRI in the anticipation and experience of pain.
        Science. 2004; 303: 1162-1167
        • Walhovd K.B.
        • Fjell A.M.
        • Reinvang I.
        • Lundervold A.
        • Dale A.M.
        • Eilertsen D.E.
        • Quinn B.T.
        • Salat D.
        • Makris N.
        • Fischl B.
        Effects of age on volumes of cortex, white matter and subcortical structures.
        Neurobiol Aging. 2005; 26: 1261-1270
        • Welsh K.
        • Butters N.
        • Hughes J.
        • Mohs R.
        • Heyman A.
        Detection of abnormal memory decline in mild cases of Alzheimer’s disease using CERAD neuropsychological measures.
        Arch Neurol. 1991; 48: 278-281
        • Wiech K.
        • Ploner M.
        • Tracey I.
        Neurocognitive aspects of pain perception.
        Trends Cogn Sci. 2008; 12: 306-313
        • Woo C.W.
        • Roy M.
        • Buhle J.T.
        • Wager T.D.
        Distinct brain systems mediate the effects of nociceptive input and self-regulation on pain.
        PLoS Biol. 2015; 13: e1002036
        • Wrobel N.
        • Fadai T.
        • Sprenger C.
        • Hebebrand J.
        • Wiech K.
        • Bingel U.
        Are children the better placebo analgesia responders? An experimental approach.
        J Pain. 2015; 16: 1005-1011
        • Yezierski R.P.
        The effects of age on pain sensitivity: Preclinical studies.
        Pain Med. 2012; 13: S27-S36
        • Zhou S.
        • Després O.
        • Pebayle T.
        • Dufour A.
        Age-related decline in cognitive pain modulation induced by distraction: Evidence from event-related potentials.
        J Pain. 2015; 16: 862-872