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P.2.008 Duration over time of learned placebo analgesic responses
Behavioural pharmacology Conclusions: Taken together, our data suggest that pergolide (0.3 mg/kg/day) may counteract both behavioral and biochemical changes induced by 6-OHDA in a rat model of PD. Our study also suggests that these positive behavioral responses could be correlated with some antioxidant actions of pergolide. This could be useful for future investigations and clinical applications of dopaminergic drugs. Reference(s) [1] Hefco V., Yamada K., Hefco A., Hritcu L., Tiron A., Nabeshima T., 2003 Role of the mesotelencephalic dopamine system in learning and memory processes in the rat. Eur. J. Pharmacol. 475, 55−60. [2] Hritcu L, Ciobica A, Artenie V., 2008 Effects of right-unilateral 6-hydroxydopamine infusion-induced memory impairment and oxidative stress: relevance for Parkinson’s disease. Central European Journal of Biology 3, 250–257. [3] Micale V, Incognito T, Ignoto A, Rampello L, Spart`a M, Drago F., 2006 Dopaminergic drugs may counteract behavioral and biochemical changes induced by models of brain injury. Eur Neuropsychopharmacol. 16 195–203. Disclosure statement: This research was supported by the National Council of Scientific Research and University Education (Grant TD CNCSIS no. 464), Romania. P.2.008 Duration over time of learned placebo analgesic responses L. Colloca1 ° , F. Benedetti1 . 1 University of Turin, Department of Neuroscience, Turin, Italy In the last few years, there has been an increased emphasis on learning as modulator factor of placebo effects. The main reason for this is the awareness that a previous direct experience of benefit via pharmacological or biologically-significant cue exposure powerfully change behavior and clinical outcomes [1−3]. In fact, conditioning approaches used in many placebo studies, have provided strong evidence that placebo responses that are obtained via conditioning are more robust than those induced by verbal suggestions alone. A direction for future research is to determine the number of conditioning trials that is necessary to obtain placebo responses and to ensure their resistance to extinction. Here we test the effects of two sessions of conditioning (72 trials) on placebo modulation of repetitive painful stimuli (144 trials) delivered on the dorsum of the foot. Placebo procedure consisted in a simulation of a painkiller and was obtained by pairing green light to a series
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of stimuli that were made analgesic by lowering the intensity of stimulation surprisingly. Subjects were told that the activation of ankle’s electrodes (actually sham electrodes) respectively, induced analgesia. A red light was associated with a series of control painful stimuli. Eighteen subjects (5M; age 36±13 years) received two sessions of conditioning and 4 sessions of testing, whereby all the stimuli were delivered at the same intensity. Before the experimental session started, subjects were asked to rate in percentage, how much they expected that the treatment would work. In all the experimental conditions, at the end of each stimulation, pain intensity was assessed by means of Numerical Rating Scale (NRS), ranging from 0=no pain to 10=maximum imaginable pain. Within-subjects repeated ANOVAs were used to assess the effects of treatment (levels 2) and time (18 trials). The main effects of treatment were tested for each session (conditioning 1, 2 and testing sessions 1−4). The F-tests were followed by simple contrasts and the Bonferroni post-hoc tests for multiple comparisons. Spearman correlations were calculated between size of placebo responses and level of expectancy. After two sessions of conditioning, we observed strong placebo analgesic responses to painful stimulation (session 1, p < 0.001; session 2, p < 0.001; session 3, p < 0.01; session 4, p < 0.001). Interestingly, these effects did extinct over time. No significant correlations were found between the magnitude of placebo responses and subject’s expectations, thus suggesting that direct experience of effectiveness (via conditioning) is able to change and to “drive” subjects expectations. These findings contribute to increase our knowledge about the role of learning in creating placebo responses. Overall, from this research emerges that learning, via classical conditioning, powerfully shapes clinical and behavior outcomes. From a clinical perspective, it is plausible thinking that learning via prior exposure to effective treatments and repetitive reinforcements, may represent one of the most promising strategy to harness placebo responses in the clinical routine. Thus, understanding how to enhance placebo responses could have an important positive impact on scientific knowledge and health care. Reference(s) [1] Colloca, L., Benedetti, F., 2005 Placebo and painkillers: is mind as real as matter? Nature Rev Neurosci, 6(7): 245−52. [2] Colloca, L., Benedetti, F., 2006 How prior experience shapes placebo analgesia. Pain, 124(1−2):126−33. [3] Colloca, L., Tinazzi, M., Recchia, S., Le Pera, D., Fiaschi, A., Benedetti, F., Valeriani, M., 2008 Learning potentiates neurophysiological and behavioral placebo analgesic responses. Pain, 139(2):306−14.
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of stimuli that were made analgesic by lowering the intensity of stimulation surprisingly. Subjects were told that the activation of ankle’s electrodes (actually sham electrodes) respectively, induced analgesia. A red light was associated with a series of control painful stimuli. Eighteen subjects (5M; age 36±13 years) received two sessions of conditioning and 4 sessions of testing, whereby all the stimuli were delivered at the same intensity. Before the experimental session started, subjects were asked to rate in percentage, how much they expected that the treatment would work. In all the experimental conditions, at the end of each stimulation, pain intensity was assessed by means of Numerical Rating Scale (NRS), ranging from 0=no pain to 10=maximum imaginable pain. Within-subjects repeated ANOVAs were used to assess the effects of treatment (levels 2) and time (18 trials). The main effects of treatment were tested for each session (conditioning 1, 2 and testing sessions 1−4). The F-tests were followed by simple contrasts and the Bonferroni post-hoc tests for multiple comparisons. Spearman correlations were calculated between size of placebo responses and level of expectancy. After two sessions of conditioning, we observed strong placebo analgesic responses to painful stimulation (session 1, p < 0.001; session 2, p < 0.001; session 3, p < 0.01; session 4, p < 0.001). Interestingly, these effects did extinct over time. No significant correlations were found between the magnitude of placebo responses and subject’s expectations, thus suggesting that direct experience of effectiveness (via conditioning) is able to change and to “drive” subjects expectations. These findings contribute to increase our knowledge about the role of learning in creating placebo responses. Overall, from this research emerges that learning, via classical conditioning, powerfully shapes clinical and behavior outcomes. From a clinical perspective, it is plausible thinking that learning via prior exposure to effective treatments and repetitive reinforcements, may represent one of the most promising strategy to harness placebo responses in the clinical routine. Thus, understanding how to enhance placebo responses could have an important positive impact on scientific knowledge and health care. Reference(s) [1] Colloca, L., Benedetti, F., 2005 Placebo and painkillers: is mind as real as matter? Nature Rev Neurosci, 6(7): 245−52. [2] Colloca, L., Benedetti, F., 2006 How prior experience shapes placebo analgesia. Pain, 124(1−2):126−33. [3] Colloca, L., Tinazzi, M., Recchia, S., Le Pera, D., Fiaschi, A., Benedetti, F., Valeriani, M., 2008 Learning potentiates neurophysiological and behavioral placebo analgesic responses. Pain, 139(2):306−14.