Most people have heard of the placebo effect, while relatively few have heard of nocebo, even within the circles of medical staff. Placebo effect means positive results by treatment via pharmacological inert substances. In contrast to placebo, by nocebo effect, due to negative beliefs and expectations, opposite results are achieved. Said in a more formal manner, what a sick person expects, unfortunately, he/she most often gets.
It is a fact that a high number of medical staff is still uninterested in placebo and nocebo effects, although they would benefit from them. Maybe this is because the treatment would not seem “scientific enough”. However, the newest scientific evidence undoubtedly shows that placebo and nocebo effects arise out of very active neurobiological processes intervened by psychological mechanisms such as expectations and conditions. Regardless of whether or not the doctor or the patient are aware of this, placebo and nocebo effects are extremely powerful and represent a significant part of the treatment process, in treatment by methods of ancient cultures, as well as in modern medicine. Of course medicines hold their role, but understanding how the human mind processes information is also very important.
Drici MD, Raybaud F, Lunardo C, Iacono P, Gustovic P. Influence of the behaviour pattern on the nocebo response of healthy volunteers. Vol. 39, Br J Clin Pharmacol. 1995. p. 204–6.
2.
Hróbjartsson A, Gøtzsche PC. Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. Vol. 344, N Engl J Med. 2001. p. 1594–602.
3.
Enck P, Benedetti F, Schedlowski M. New insights into the placebo and nocebo responses. Vol. 59, Neuron. 2008. p. 195–206.
4.
Fuente-Fernández R, TJ R, V S, M S, DB C, AJ S. Expectation and dopamine release: mechanism of the placebo effect in Parkinson’s disease. Vol. 293, Science. 2001. p. 1164–6.
5.
Meissner M. The placebo effect and the autonomic nervous system: evidence for an intimate relationship. Vol. 366, Philos Trans R Soc Lond B Biol Sci. 2011. p. 1808–17.
6.
Colloca L, Miller FG. The nocebo effect and its relevance for clinical practice. Vol. 73, Psychosom Med. 2011. p. 598–603.
7.
Fuente-Fernández R, AJ S. The placebo effect in Parkinson’s disease. Vol. 25, Trends Neurosci. 2002. p. 302–6.
8.
Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, Zubieta JK. Individual differences in reward responding explain placebo-induced expectations and effects. Vol. 55, Neuron. 2007. p. 325–36.
9.
Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, Zubieta JK. Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. Vol. 65, Arch Gen Psychiatry. 2008. p. 220–31.
10.
Fuente-Fernández R. Uncovering the hidden placebo effect in deep-brain stimulation for Parkinson’s disease. Vol. 10, Parkinsonism Relat Disord. 2004. p. 125–7.
11.
Fuente-Fernández R, AG P, M Z, V S, DB C, TJ R, et al. Dopamine release in human ventral striatum and expectation of reward. Vol. 136, Behav Brain Res. 2002. p. 359–63.
12.
Fuente-Fernández R, M S, AJ S. The placebo effect in neurological disorders. Vol. 1, Lancet Neurol. 2002. p. 85–91.
13.
Schultz W. Predictive reward signal of dopamine neurons. Vol. 80, J Neurophysiol. 1998. p. 1–27.
14.
Hahn RA. A sociocultural model of illness and healing. 1985.
15.
Hahn RA. The nocebo phenomenon: concept, evidence, and implications for public health. Vol. 26, Prev Med. 1997. p. 607–11.
16.
Mazzoni G, Foan L, Hyland ME, Kirsch I. The effects of observation and gender on psychogenic symptoms. Vol. 29, Health Psychol. 2010. p. 181–5.
17.
Tracey I. Getting the pain you expect: mechanisms of placebo, nocebo and reappraisal effects in humans. Vol. 16, Nat Med. 2010. p. 1277–83.
18.
Schweiger A, Parducci A. Nocebo: the psychologic induction of pain. Vol. 16, Pavlov J Biol Sci. 1981. p. 140–3.
19.
Dworkin SF, Chen AC, LeResche L, Clark DW. Cognitive reversal of expected nitrous oxide analgesia for acute pain. Vol. 62, Anesth Analg. 1983. p. 1073–7.
20.
Benedetti F, Amanzio M, Vighetti S, Asteggiano G. The biochemical and neuroendocrine bases of the hyperalgesic nocebo effect. Vol. 26, J Neurosci. 2006. p. 12014–22.
21.
Rodriguez-Raecke R, Doganci B, Breimhorst M, Stankewitz A, Buchel C, Birklein F, et al. Insular cortex activity is associated with effects of negative expectation on nociceptive long-term habituation. Vol. 30, J Neurosci. 2010. p. 11363–8.
22.
Bingel U, Wanigasekera V, Wiech K, Ni Mhuircheartaigh R, Lee MC, Ploner M, et al. The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. Vol. 3, Sci Transl Med. 2011.
23.
Keltner F, A F, C R, R I, B F, H.L. Isolating the modulatory effect of expectation on pain transmission: a functional magnetic resonance imaging study. Vol. 26, J Neurosci. 2006. p. 4437–43.
24.
Koyama T, Tanaka YZ, Mikami A. Nociceptive neurons in the macaque anterior cingulated activate during anticipation of pain. Vol. 9, Neuroreport. 1998. p. 2663–7.
25.
Lorenz J, Hauck M, Paur RC, Nakamura Y, Zimmermann R, Bromm B, et al. Cortical correlates of false expectations during pain intensity judgments-a possible manifestation of placebo/nocebo cognitions. Vol. 19, Brain Behav Immun. 2005. p. 283–95.
26.
Porro CA, Baraldi P, Pagnoni G, Serafini M, Facchin P, Maieron M, et al. Does anticipation of pain affect cortical nociceptive systems? Vol. 22, J Neurosci. 2002. p. 3206–14.
27.
Manchikanti L, Giordano J, Fellows B, Hirsch JA. Placebo and nocebo in interventional pain management: a friend or a foe-or simply foes? Vol. 14:E157-75, Pain Physician. 2011.
28.
Goffaux P, Léonard G, Marchand S, Rainville P. Placebo analgesia. In: Pharmacology of Pain. 2010.
29.
Hróbjartsson A, Gøtzsche PC. Placebo interventions for all clinical conditions. Cochrane Database Syst Rev. 2010. p. 1 003974.
30.
Pollo A, Amanzio M, Arslanian A, Casadio C, Maggi G, Benedetti F. Response expectancies in placebo analgesia and their clinical relevance. Vol. 93, Pain. 2001. p. 77–84.
31.
Buckalew LW, Coffield KE. An investigation of drug expectancy as a function of capsule color and size and preparation form. Vol. 2, J Clin Psychopharmacol. 1982. p. 245–8.
32.
Moerman DE, Jonas WB. Deconstructing the placebo effect and finding the meaning response. Vol. 136, Ann Intern Med. 2002. p. 471–6.
33.
Branthwaite A, Cooper P. Analgesic effects of branding in treatment of headaches. Vol. 282, Br Med J. 1981. p. 1576–8.
34.
Moerman DE. Cultural variations in the placebo effect: Ulcers, anxiety, and blood pressure. Vol. 14, Med Anthropol Q. 2000. p. 51–72.
35.
Barsky AJ, Saintfort R, Rogers MP, Borus JF. Nonspecific medication side effects and the nocebo phenomenon. Vol. 287, JAMA. 2002. p. 622–7.
36.
Miller FG, Kaptchuk TJ. The power of context: reconceptualizing the placebo effect. Vol. 101, J R Soc Med. 2008. p. 222–5.
37.
Lamont EB, Christakis NA. Complexities in prognostication in advanced cancer: “to help them live their lives the way they want to.” Vol. 290, JAMA. 2003. p. 98–104.
38.
Sakala C. Letter from North America: understanding and minimizing nocebo effects in childbearing women. Vol. 34, Birth. 2007. p. 348–50.
39.
Amanzio M, Corazzini LL, Vase L, Benedetti F. A systematic review of adverse events in placebo groups of anti-migraine clinical trials. Vol. 146, Pain. 2009. p. 261–9.
40.
Rief W, Nestoriuc Y, Lilienfeld-Toal A, Dogan I, Schreiber F, Hofmann SG, et al. Differences in adverse effect reporting in placebo groups in SSRI and tricyclic antidepressant trials: a systematic review and meta-analysis. Vol. 32, Drug Saf. 2009. p. 1041–56.
41.
Mondaini N, Gontero P, Giubilei G, Lombardi G, Cai T, Gavazzi A, et al. Finasteride 5 mg and sexual side effects: how many of these are related to a nocebo phenomenon? Vol. 4, J Sex Med. 2007. p. 1708–12.
42.
Varelmann D, Pancaro C, Cappiello EC, Camann WR. Nocebo-induced hyperalgesia during local anesthetic injection. Vol. 110, Anesth Analg. 2010. p. 868–70.
43.
Taddio A, Shah V, Gilbert-MacLeod C, Katz J. Conditioning and hyperalgesia in newborns exposed to repeated heel lances. Vol. 288, JAMA. 2002. p. 857–61.
44.
Lombardi C, Gargioni S, Canonica GW, Passalacqua G. The nocebo effect during oral challenge in subjects with adverse drug reactions. Vol. 40, Eur Ann Allergy Clin Immunol. 2008. p. 138–41.
45.
Colagiuri B, Zachariae R. Patient Expectancy and Post-chemotherapy Nausea: a meta-analysis. Vol. 40, Ann Behav Med. 2010. p. 3–14.
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