Association of nocebo hyperalgesia and basic somatosensory characteristics in a large cohort.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
    • Abstract:
      Medical outcomes are strongly affected by placebo and nocebo effects. Prediction of who responds to such expectation effects has proven to be challenging. Most recent approaches to prediction have focused on placebo effects in the context of previous treatment experiences and expectancies, or personality traits. However, a recent model has suggested that basic somatosensory characteristics play an important role in expectation responses. Consequently, this study investigated not only the role of psychological variables, but also of basic somatosensory characteristics. In this study, 624 participants underwent a placebo and nocebo heat pain paradigm. Additionally, individual psychological and somatosensory characteristics were assessed. While no associations were identified for placebo responses, nocebo responses were associated with personality traits (e.g. neuroticism) and somatosensory characteristics (e.g. thermal pain threshold). Importantly, the associations between somatosensory characteristics and nocebo responses were among the strongest. This study shows that apart from personality traits, basic somatosensory characteristics play an important role in individual nocebo responses, in agreement with the novel idea that nocebo responses result from the integration of top-down expectation and bottom-up sensory information.
    • References:
      Vos, T. et al. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 386, 743–800 (2015). (PMID: 10.1016/S0140-6736(15)60692-4)
      Manchikanti, L., Singh, V., Kaye, A. D. & Hirsch, J. A. Lessons for better pain management in the future: learning from the past. Pain Ther. https://doi.org/10.1007/s40122-020-00170-8 (2020). (PMID: 10.1007/s40122-020-00170-8324100707203307)
      Wolters, F., Peerdeman, K. J. & Evers, A. W. M. Placebo and Nocebo effects across symptoms: from pain to fatigue, dyspnea, nausea, and itch. Front. Psychiatry 10, 470 (2019). (PMID: 31312148661450910.3389/fpsyt.2019.00470)
      Kaptchuk, T. J. & Miller, F. G. Placebo effects in medicine. N. Engl. J. Med. 373, 8–9 (2015). (PMID: 2613293810.1056/NEJMp1504023)
      Amanzio, M., Vase, L. & Mitsikostas, D. D. Editorial: Nocebo effects and their influence on clinical trials and practice: modulating factors in healthy and pathological conditions. Front. Pharmacol. 11, 100 (2020). (PMID: 32140109704238610.3389/fphar.2020.00100)
      Peerdeman, K. J. et al. Relieving patientsʼ pain with expectation interventions: a meta-analysis. Pain 157, 1179–1191 (2016). (PMID: 2694523510.1097/j.pain.0000000000000540)
      Colloca, L. & Barsky, A. J. Placebo and Nocebo effects. N. Engl. J. Med. 382, 554–561 (2020). (PMID: 3202337510.1056/NEJMra1907805)
      Evers, A. W. M. et al. Implications of placebo and nocebo effects for clinical practice: expert consensus. Psychother. Psychosom. 87, 204–210 (2018). (PMID: 29895014619188210.1159/000490354)
      Eippert, F. et al. Activation of the opioidergic descending pain control system underlies placebo analgesia. Neuron 63, 533–543 (2009). (PMID: 1970963410.1016/j.neuron.2009.07.014)
      Tinnermann, A., Geuter, S., Sprenger, C., Finsterbusch, J. & Büchel, C. Interactions between brain and spinal cord mediate value effects in nocebo hyperalgesia. Science 358, 105–108 (2017). (PMID: 2898305110.1126/science.aan1221)
      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. 67, 697–730 (2015). (PMID: 2612664910.1124/pr.114.009423)
      Bingel, U. et al. The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. Sci. Transl. Med. 3, 70ra14 (2011).
      Enck, P., Bingel, U., Schedlowski, M. & Rief, W. The placebo response in medicine: minimize, maximize or personalize?. Nat. Rev. Drug Discov. 12, 191–204 (2013). (PMID: 2344930610.1038/nrd3923)
      Kristensen, L. E. et al. Non-pharmacological effects in switching medication: the Nocebo effect in switching from originator to biosimilar agent. BioDrugs 32, 397–404 (2018). (PMID: 30269270618244810.1007/s40259-018-0306-1)
      Klinger, R., Blasini, M., Schmitz, J. & Colloca, L. Nocebo effects in clinical studies: hints for pain therapy. PAIN Rep. 2, e586 (2017). (PMID: 29034363563971710.1097/PR9.0000000000000586)
      Flaten, M. A., Simonsen, T. & Olsen, H. Drug-related information generates placebo and nocebo responses that modify the drug response. Psychosom. Med. 61, 250–255 (1999). (PMID: 1020497910.1097/00006842-199903000-00018)
      Howick, J. Unethical informed consent caused by overlooking poorly measured nocebo effects. J. Med. Ethics medethics-2019-–105903 (2020) https://doi.org/10.1136/medethics-2019-105903 .
      Greville-Harris, M. & Dieppe, P. Bad is more powerful than good: the Nocebo response in medical consultations. Am. J. Med. 128, 126–129 (2015). (PMID: 2523271610.1016/j.amjmed.2014.08.031)
      Engel, G. L. The need for a new medical model: a challenge for biomedicine. Science 196, 129–136 (1977). (PMID: 84746010.1126/science.847460)
      Blasi, Z. D., Harkness, E., Ernst, E., Georgiou, A. & Kleijnen, J. Influence of context effects on health outcomes: a systematic review. Lancet 357, 757–762 (2001). (PMID: 1125397010.1016/S0140-6736(00)04169-6)
      Fava, G. A., Guidi, J., Rafanelli, C. & Rickels, K. The clinical inadequacy of the placebo model and the development of an alternative conceptual framework. Psychother. Psychosom. 86, 332–340 (2017). (PMID: 2913105010.1159/000480038)
      Geers, A. L., Kosbab, K., Helfer, S. G., Weiland, P. E. & Wellman, J. A. Further evidence for individual differences in placebo responding: an interactionist perspective. J. Psychosom. Res. 62, 563–570 (2007). (PMID: 1746741110.1016/j.jpsychores.2006.12.005)
      Morton, D. L., Watson, A., El-Deredy, W. & Jones, A. K. P. Reproducibility of placebo analgesia: effect of dispositional optimism. Pain 146, 194–198 (2009). (PMID: 1969217810.1016/j.pain.2009.07.026)
      Vachon-Presseau, E. et al. Brain and psychological determinants of placebo pill response in chronic pain patients. Nat. Commun. 9, 3397 (2018). (PMID: 30209286613581510.1038/s41467-018-05859-1)
      Schweinhardt, P., Seminowicz, D. A., Jaeger, E., Duncan, G. H. & Bushnell, M. C. The anatomy of the mesolimbic reward system: a link between personality and the placebo analgesic response. J. Neurosci. 29, 4882–4887 (2009). (PMID: 19369556666532110.1523/JNEUROSCI.5634-08.2009)
      Davis, C., Ralevski, E., Kennedy, S. H. & Neitzert, C. The role of personality factors in the reporting of side effect complaints to moclobemide and placebo: a study of healthy male and female volunteers. J. Clin. Psychopharmacol. 15, 347–352 (1995). (PMID: 883006610.1097/00004714-199510000-00007)
      Colloca, L. et al. Prior therapeutic experiences, not expectation ratings, predict placebo effects: an experimental study in chronic pain and healthy participants. Psychother. Psychosom. https://doi.org/10.1159/000507400 (2020). (PMID: 10.1159/00050740033075796)
      Wang, Y. et al. Modeling learning patterns to predict placebo analgesic effects in healthy and chronic orofacial pain participants. Front. Psychiatry 11, 39 (2020). (PMID: 32116854702935510.3389/fpsyt.2020.00039)
      Pouillon, L. et al. The nocebo effect: a clinical challenge in the era of biosimilars. Expert Rev. Clin. Immunol. 14, 739–749 (2018). (PMID: 3011833810.1080/1744666X.2018.1512406)
      Buhle, J. T., Stevens, B. L., Friedman, J. J. & Wager, T. D. Distraction and placebo: two separate routes to pain control. Psychol. Sci. 23, 246–253 (2012). (PMID: 2226156810.1177/0956797611427919)
      Sprenger, C. et al. Attention modulates spinal cord responses to pain. Curr. Biol. 22, 1019–1022 (2012). (PMID: 2260850710.1016/j.cub.2012.04.006)
      Büchel, C., Geuter, S., Sprenger, C. & Eippert, F. Placebo analgesia: a predictive coding perspective. Neuron 81, 1223–1239 (2014). (PMID: 2465624710.1016/j.neuron.2014.02.042)
      Ongaro, G. & Kaptchuk, T. J. Symptom perception, placebo effects, and the Bayesian brain. Pain 160, 1–4 (2019). (PMID: 3008611410.1097/j.pain.0000000000001367)
      Grahl, A., Onat, S. & Büchel, C. The periaqueductal gray and Bayesian integration in placebo analgesia. eLife 7, e32930 (2018).
      Kelley, J. M. et al. Patient and practitioner influences on the placebo effect in irritable bowel syndrome. Psychosom. Med. 71, 789 (2009). (PMID: 19661195281814110.1097/PSY.0b013e3181acee12)
      Webster, R. K., Weinman, J. & Rubin, G. J. A systematic review of factors that contribute to nocebo effects. Health Psychol. 35, 1334–1355 (2016). (PMID: 2765780110.1037/hea0000416)
      Shapiro, A. K. Factors contributing to the placebo effect. Am. J. Psychother. 18, 73–88 (1964). (PMID: 10.1176/appi.psychotherapy.1964.18.s1.73)
      Koban, L., Rozic, L. & Wager, T. D. Brain predictors of individual differences in placebo responding. in Placebo and Pain 89–102 (Academic Press, London, 2013).
      Williams, D. G. Dispositional optimism, neuroticism, and extraversion. Personal. Individ. Differ. 13, 475–477 (1992). (PMID: 10.1016/0191-8869(92)90076-2)
      Schutte, J. W. & Hosch, H. M. Optimism, religiosity, and neuroticism: a cross-cultural study. Personal. Individ. Differ. 20, 239–244 (1996). (PMID: 10.1016/0191-8869(95)00147-6)
      Vambheim, S. M. & Flaten, M. A. A systematic review of sex differences in the placebo and the nocebo effect. J. Pain Res. 10, 1831–1839 (2017). (PMID: 28831271554826810.2147/JPR.S134745)
      Kállai, I., Barke, A. & Voss, U. The effects of experimenter characteristics on pain reports in women and men. Pain 112, 142–147 (2004). (PMID: 1549419410.1016/j.pain.2004.08.008)
      Mazzoni, G., Foan, L., Hyland, M. E. & Kirsch, I. The effects of observation and gender on psychogenic symptoms. Health Psychol. 29, 181–185 (2010). (PMID: 2023009110.1037/a0017860)
      Geuter, S. & Büchel, C. Facilitation of pain in the human spinal cord by nocebo treatment. J. Neurosci. 33, 13784–13790 (2013). (PMID: 23966699661865710.1523/JNEUROSCI.2191-13.2013)
      Geers, A. L., Briñol, P. & Petty, R. E. An analysis of the basic processes of formation and change of placebo expectations. Rev. Gen. Psychol. 23, 211–229 (2019). (PMID: 10.1037/gpr0000171)
      Rhudy, J. L., Güereca, Y. M., Kuhn, B. L., Palit, S. & Flaten, M. A. The influence of placebo analgesia manipulations on pain report, the nociceptive flexion reflex, and autonomic responses to pain. J. Pain 19, 1257–1274 (2018). (PMID: 2975835610.1016/j.jpain.2018.04.012)
      Horing, B., Weimer, K., Muth, E. R. & Enck, P. Prediction of placebo responses: a systematic review of the literature. Front. Psychol. 5, (2014).
      Manaï, M., van Middendorp, H., Veldhuijzen, D. S., Huizinga, T. W. J. & Evers, A. W. M. How to prevent, minimize, or extinguish nocebo effects in pain: a narrative review on mechanisms, predictors, and interventions. PAIN Rep. 4, e699 (2019). (PMID: 31583340674990710.1097/PR9.0000000000000699)
      Rolke, R. et al. Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur. J. Pain 10, 77–88 (2006). (PMID: 1629130110.1016/j.ejpain.2005.02.003)
      Meade, A. W. & Craig, S. B. Identifying careless responses in survey data. Psychol. Methods 17, 437 (2012). (PMID: 2250658410.1037/a0028085)
      Colloca, L., Sigaudo, M. & Benedetti, F. The role of learning in nocebo and placebo effects. Pain 136, 211–218 (2008). (PMID: 1837211310.1016/j.pain.2008.02.006)
      Klinger, R., Soost, S., Flor, H. & Worm, M. Classical conditioning and expectancy in placebo hypoalgesia: a randomized controlled study in patients with atopic dermatitis and persons with healthy skin. Pain 128, 31–39 (2007). (PMID: 1703009510.1016/j.pain.2006.08.025)
      Kirsch, I. et al. Expectancy and conditioning in placebo analgesia: Separate or connected processes?. Psychol. Conscious. Theory Res. Pract. 1, 51–59 (2014).
      Tibshirani, R. Regression shrinkage and selection via the LASSO. J. R. Stat. Soc. Ser. B Methodol. 58, 267–288 (1996).
    • Publication Date:
      Date Created: 20210113 Date Completed: 20210825 Latest Revision: 20230127
    • Publication Date:
      20240829
    • Accession Number:
      PMC7804006
    • Accession Number:
      10.1038/s41598-020-80386-y
    • Accession Number:
      33436821