The relation of emotions to placebo responses

The hypothesis put forth is that expectations of treatment effects reduce negative emotions and thereby reduce symptoms, e.g. pain. Negative emotions increase pain, and it is hypothesized that placebos reduce pain by reducing negative emotions, i.e. feelings of nervousness, fear and anxiety. Placebo analgesia has been shown to be mediated via opioid activity, and relaxation increases opioid activity. The placebo acquires its relaxing effect due to verbal information that pain will be reduced, or due to associations between the placebo and the reduction in pain after effective treatment. Thus, the placebo signals that unpleasantness will be less after administration of the placebo. This involves negative reinforcement which is due to activation of a dopaminergic system that has been found to be activated during placebo analgesia and is involved in positive emotions. The nocebo effect of increased pain is, consistent with this model, because of increased fear and anxiety. The new aspect of the presented model is the hypothesis that expectations reduce negative emotions, and that negative reinforcement that involves the dopaminergic reinforcement system should be a contributor to placebo responses.

[1]  V. Pravin Disorder , 2013 .

[2]  Irene Tracey,et al.  Corrigendum to “Investigation into the neural correlates of emotional augmentation of clinical pain” [Neuroimage 40/2 (2008) 759–766] , 2011, NeuroImage.

[3]  S. M. Vambheim,et al.  Gender Differences in Placebo Analgesia: Event-Related Potentials and Emotional Modulation , 2011, Psychosomatic medicine.

[4]  F. Benedetti,et al.  Disruption of opioid-induced placebo responses by activation of cholecystokinin type-2 receptors , 2011, Psychopharmacology.

[5]  Edzard Ernst,et al.  Placebo Effects: Understanding the Mechanisms in Health and Disease , 2010 .

[6]  Wael El-Deredy,et al.  Cognitive changes as a result of a single exposure to placebo , 2010, Neuropsychologia.

[7]  M. Flaten,et al.  Is fear of pain related to placebo analgesia? , 2010, Journal of psychosomatic research.

[8]  Nora D Volkow,et al.  Neurocircuitry of Addiction , 2010, Neuropsychopharmacology.

[9]  M. Flaten Drug effects: agonistic and antagonistic processes. , 2009, Scandinavian journal of psychology.

[10]  Christian Büchel,et al.  Direct Evidence for Spinal Cord Involvement in Placebo Analgesia , 2009, Science.

[11]  C. Büchel,et al.  Activation of the Opioidergic Descending Pain Control System Underlies Placebo Analgesia , 2009, Neuron.

[12]  K. Meissner Effects of placebo interventions on gastric motility and general autonomic activity. , 2009, Journal of psychosomatic research.

[13]  A. Hammers,et al.  Evidence for endogenous opioid release in the amygdala during positive emotion , 2009, NeuroImage.

[14]  Kenneth Hugdahl,et al.  Separating the effects of alcohol and expectancy on brain activation: An fMRI working memory study , 2008, NeuroImage.

[15]  M. Flaten,et al.  The Roles of Physiological and Subjective Stress in the Effectiveness of a Placebo on Experimentally Induced Pain , 2008, Psychosomatic medicine.

[16]  S. Siegel Learning and the wisdom of the body , 2008, Learning & behavior.

[17]  Fabrizio Benedetti,et al.  New Insights into the Placebo and Nocebo Responses , 2008, Neuron.

[18]  C. Sorg,et al.  Altered cerebral response to noxious heat stimulation in patients with somatoform pain disorder , 2008, PAIN®.

[19]  J. Rhudy,et al.  Emotional control of nociceptive reactions (ECON): Do affective valence and arousal play a role? , 2008, PAIN.

[20]  Irene Tracey,et al.  Investigation into the neural correlates of emotional augmentation of clinical pain , 2008, NeuroImage.

[21]  Robert A Koeppe,et al.  Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. , 2008, Archives of general psychiatry.

[22]  B. Oken,et al.  Expectancy effect: Impact of pill administration on cognitive performance in healthy seniors , 2008, Journal of clinical and experimental neuropsychology.

[23]  Brian Knutson,et al.  Valence and salience contribute to nucleus accumbens activation , 2008, NeuroImage.

[24]  Robert A. Koeppe,et al.  Individual Differences in Reward Responding Explain Placebo-Induced Expectations and Effects , 2007, Neuron.

[25]  R. Høifødt,et al.  The effect of experimenter gender on autonomic and subjective responses to pain stimuli , 2007, PAIN.

[26]  M. Boly,et al.  Naloxone-insensitive epidural placebo analgesia in a chronic pain patient. , 2007, Anesthesiology.

[27]  B. Vogt,et al.  Categories of placebo response in the absence of site-specific expectation of analgesia , 2006, Pain.

[28]  Fabrizio Benedetti,et al.  The Biochemical and Neuroendocrine Bases of the Hyperalgesic Nocebo Effect , 2006, The Journal of Neuroscience.

[29]  A. Finset,et al.  Cognitive and emotional factors in placebo analgesia. , 2006, Journal of psychosomatic research.

[30]  Kevin N. Ochsner,et al.  Neural correlates of individual differences in pain-related fear and anxiety , 2006, Pain.

[31]  R. Treede,et al.  Human brain mechanisms of pain perception and regulation in health and disease , 2005, European journal of pain.

[32]  B. Vogt Pain and emotion interactions in subregions of the cingulate gyrus , 2005, Nature Reviews Neuroscience.

[33]  T. Dietrich,et al.  Placebo in Emotional Processing— Induced Expectations of Anxiety Relief Activate a Generalized Modulatory Network , 2005, Neuron.

[34]  Donald D. Price,et al.  Increased placebo analgesia over time in irritable bowel syndrome (IBS) patients is associated with desire and expectation but not endogenous opioid mechanisms , 2005, Pain.

[35]  H. Fields,et al.  Pain and the Placebo: What We Have Learned , 2005, Perspectives in biology and medicine.

[36]  A. Parrott,et al.  Stress and arousal in sedative and stimulant cigarette smokers , 2005, Psychopharmacology.

[37]  Edward E. Smith,et al.  Placebo-Induced Changes in fMRI in the Anticipation and Experience of Pain , 2004, Science.

[38]  D. W. Brodeur The effects of stimulant and tranquilizer placebos on healthy subjects in a real-life situation , 1965, Psychopharmacologia.

[39]  M. Flaten,et al.  Placebo and Nocebo Responses, Cortisol, and Circulating Beta-Endorphin , 2003, Psychosomatic medicine.

[40]  D. Price,et al.  The contributions of suggestion, desire, and expectation to placebo effects in irritable bowel syndrome patients An empirical investigation , 2003, Pain.

[41]  F. Benedetti,et al.  Placebo analgesia and the heart , 2003, Pain.

[42]  L. Allan,et al.  A Signal Detection Theory Analysis of the Placebo Effect , 2002, Evaluation & the health professions.

[43]  P. Rainville Brain mechanisms of pain affect and pain modulation , 2002, Current Opinion in Neurobiology.

[44]  P. Matthews,et al.  Exacerbation of Pain by Anxiety Is Associated with Activity in a Hippocampal Network , 2001, The Journal of Neuroscience.

[45]  Brian Knutson,et al.  Anticipation of Increasing Monetary Reward Selectively Recruits Nucleus Accumbens , 2001, The Journal of Neuroscience.

[46]  T. Lynch,et al.  Pain and emotion: new research directions. , 2001, Journal of clinical psychology.

[47]  L. F. Barrett,et al.  Handbook of emotions, 2nd ed. , 2000 .

[48]  Herta Flor,et al.  Conditioned stress‐induced analgesia in humans , 1999, European journal of pain.

[49]  D. Price,et al.  An analysis of factors that contribute to the magnitude of placebo analgesia in an experimental paradigm , 1999, PAIN.

[50]  F. Vaccarino,et al.  Effects of CCK-4 infusion on the acoustic eye-blink startle and psychophysiological measures in healthy volunteers , 1999, Journal of psychopharmacology.

[51]  Terry D. Blumenthal,et al.  Caffeine-associated stimuli elicit conditioned responses: an experimental model of the placebo effect , 1999, Psychopharmacology.

[52]  F. Benedetti,et al.  Somatotopic Activation of Opioid Systems by Target-Directed Expectations of Analgesia , 1999, The Journal of Neuroscience.

[53]  M. Flaten,et al.  Drug-related information generates placebo and nocebo responses that modify the drug response. , 1999, Psychosomatic medicine.

[54]  Anthony K. P. Jones,et al.  The cortical representation of pain , 1999, PAIN.

[55]  F. Benedetti,et al.  Neuropharmacological Dissection of Placebo Analgesia: Expectation-Activated Opioid Systems versus Conditioning-Activated Specific Subsystems , 1999, The Journal of Neuroscience.

[56]  M. Flaten Information about drug effects modify arousal: An investigation of the placebo response , 1998 .

[57]  K. Waterloo,et al.  Pharmacological classical conditioning in humans , 1997 .

[58]  D. Ramsay,et al.  Biological consequences of drug administration: implications for acute and chronic tolerance. , 1997, Psychological review.

[59]  G. Koob,et al.  The neurobiology of drug addiction. , 1997, The Journal of neuropsychiatry and clinical neurosciences.

[60]  S. Bruehl,et al.  Relaxation training and opioid inhibition of blood pressure response to stress. , 1996, Journal of consulting and clinical psychology.

[61]  I. Kirsch,et al.  Mechanisms of Placebo Pain Reduction: An Empirical Investigation , 1996 .

[62]  F. Benedetti The opposite effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia , 1996, Pain.

[63]  L. F. Barrett,et al.  Handbook of Emotions , 1993 .

[64]  M. Bradley,et al.  Looking at pictures: affective, facial, visceral, and behavioral reactions. , 1993, Psychophysiology.

[65]  J. Salamone,et al.  A neurochemical and behavioral investigation of the involvement of nucleus accumbens dopamine in instrumental avoidance , 1993, Neuroscience.

[66]  Mark P. Jensen,et al.  Motivation and expectancy factors in symptom perception: a laboratory study of the placebo effect. , 1991, Psychosomatic medicine.

[67]  A. Ågmo,et al.  Reinforcing properties of ejaculation in the male rat: role of opioids and dopamine. , 1990, Behavioral neuroscience.

[68]  J. Laberg Alcohol and expectancy: subjective, psychophysiological and behavioral responses to alcohol stimuli in severely, moderately and non-dependent drinkers. , 1986, British journal of addiction.

[69]  J. Levine,et al.  Influence of the method of drug administration on analgesic response , 1984, Nature.

[70]  A. Goldstein,et al.  Partial antagonism of placebo analgesia by naloxone , 1983, Pain.

[71]  R. Eikelboom,et al.  Conditioning of drug-induced physiological responses. , 1982, Psychological review.

[72]  A. Schweiger,et al.  Nocebo: The psychologic induction of pain , 1981, The Pavlovian journal of biological science.

[73]  S. Siegel Morphine analgesic tolerance: its situation specificity supports a Pavlovian conditioning model. , 1976, Science.

[74]  S. Siegel,et al.  Evidence from rats that morphine tolerance is a learned response. , 1975, Journal of comparative and physiological psychology.

[75]  Clark Wc Sensory-decision theory analysis of the placebo effect on the criterion for pain and thermal sensitivity. , 1969 .

[76]  John C. Hancock,et al.  Signal Detection Theory , 1966 .

[77]  B. Skinner,et al.  Science and human behavior , 1953 .

[78]  Smith Ge,et al.  The Cortical Representation of the Macula. , 1930 .