Biomedical subjects

Fabrizio Benedetti

Publications and source records attributed to Fabrizio Benedetti.

25 records · Page 2Linked to original sources

PubMed2003

New insights into placebo analgesia.

PURPOSE OF REVIEW: The placebo effect is a widespread phenomenon in medicine, both in clinical trials and in routine medical practice. Most of our knowledge about the underlying psychological and physiological mechanisms comes from the study of placebo analgesia. RECENT FINDINGS: When the correct methodological approach is used, striking placebo effects can be detected and these can be mediated by conscious anticipatory processes or unconscious conditioning mechanisms. However, it should be stressed that many improvements observed after the administration of a placebo are not real placebo effects, but different phenomena such as spontaneous remission, regression to the mean and symptom detection ambiguity. Both neuropharmacological studies and brain imaging investigations show that placebo analgesia is mediated by endogenous opioids. Moreover, we also know that during placebo analgesia other systems change their functions, like the respiratory centres and the cardiovascular system. The placebo effect has also been approached from a different perspective by administering analgesics covertly. The results show that hidden medical treatments are less effective than open ones. SUMMARY: The understanding of the placebo effect may lead to better design of clinical trials and better medical practice. For example, it can be used in therapeutic protocols aimed at reducing drug intake.

Journal Article↗

PubMed2003

Temporal changes in movement time during the switch of the stimulators in Parkinson's disease patients treated by subthalamic nucleus stimulation.

OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a very effective therapy for the advanced phase of Parkinson's disease (PD). The functional inhibition of this nucleus is responsible for a significant improvement of cardinal motor symptoms of PD. The aim of the study was the assessment of the effectiveness of STN DBS on bradykinesia by the analysis of movement time (MT) in 2 conditions: with the stimulators turned on ('stim-on') or off ('stim-off'). METHODS: After pharmacological wash-out, 10 patients submitted to bilateral STN DBS were studied with an MT analyser in 3 phases: stim-on, stim-off and stim-on again, in order to establish the time course of MT lengthening, the posteffect duration and the latency of the effect of STN DBS. MT data were then compared with the UPDRS motor scores. RESULTS: After turning off the stimulators, MT progressively increases, reaching a plateau after about 30 min, which then lasts for the subsequent observation time (2 h). A significant elongation is achieved after the first 5 min. Upon pulse generator activation, MT shows a dramatic shortening, already significant after 2 min. Moreover, we observed a significant correlation between MT and the severity of PD, higher with bradykinesia than with rigidity or tremor. CONCLUSION: Our findings show a relevant effect of STN DBS on MT, a parameter strongly related to bradykinesia. This study confirms the effectiveness of STN inhibition on the whole parkinsonian triad, suggesting that this target can be considered a proper choice for the surgical treatment of advanced PD.

Aged↗

PubMed2002

Expectation modulates the response to subthalamic nucleus stimulation in Parkinsonian patients.

Expectations about future events are known to trigger neural mechanisms that affect both perception and action. Here we report that different and opposite expectations of bad and good motor performance modulate the therapeutic effects of subthalamic nucleus stimulation in Parkinsonian patients who had undergone chronic implantation of electrodes for deep brain stimulation. By analyzing the effects of subthalamic stimulation on the velocity of movement of the right hand, we found hand movement to be faster when the patients expected a good motor performance. The expectation of good performance was induced through a placebo-like procedure, thus indicating that placebo-induced expectations have influence on the treatment outcome. All these effects occurred within minutes, suggesting that expectations induce neural changes very quickly.

Aged↗

PubMed2002

How the doctor's words affect the patient's brain.

Clinicians have long known that context is important in any medical treatment and that the words and attitudes of doctors and nurses can have great impact on the patient. There is now experimental evidence indicating that the medical context influences specific neural systems. The importance of the context is shown by the lesser effectiveness of hidden administrations of analgesics compared with open ones. Because the placebo effect is a context effect, its study has been useful in clarifying this complex issue. There are now several lines of evidence that placebo analgesia is mediated by endogenous opioids and placebo motor improvement by endogenous dopamine. Moreover, a placebo treatment is capable of affecting many brain regions in depressed patients. All these studies, taken together, lead to a neurobiological understanding of the events occurring in the brain during the interaction between the therapist and his or her patient.

Analgesics, Opioid↗

PubMed2001

Response variability to analgesics: a role for non-specific activation of endogenous opioids.

Individual differences in pharmacokinetics and pharmacodynamics, the type of pain and the method of drug administration can account for the response variability to analgesics. By integrating a clinical and an experimental approach, we report here that another important source of variability is represented by individual differences in non-specific (placebo) activation of endogenous opioid systems. In the first part of this study, we analyzed the effectiveness of buprenorphine, tramadol, ketorolac and metamizol in the clinical setting, where the placebo effect was completely eliminated by means of hidden infusions. We found that the hidden injections were significantly less effective and less variable compared with open injections (in full view of the subject), suggesting that part of the response variability was due to non-specific factors (placebo). Since we could not administer the opioid antagonist, naloxone, to these patients, in the second part of this study, we induced experimental ischemic arm pain in healthy volunteers and found that, as occurred in clinical pain, the analgesic response to a hidden injection of the non-opioid ketorolac was less effective and less variable than an open injection. Most importantly, we obtained the same effects by adding naloxone to an open injection of ketorolac, thus blocking the opioid-mediated placebo component of analgesia. These findings indicate that both the psychological (hidden injection) and pharmacological (naloxone) blockade of the placebo response reduce the effectiveness of, and the response variability to, analgesic drugs. Therefore, an important source of response variability to analgesics appears to be due to differences in non-specific activation of endogenous opioid systems.

Adult↗

PubMed2001

Response expectancies in placebo analgesia and their clinical relevance.

Response expectancies have been proposed as the major determinant of placebo effects. Here we report that different expectations produce different analgesic effects which in turn can be harnessed in clinical practice. Thoracotomized patients were treated with buprenorphine on request for 3 consecutive days, together with a basal intravenous infusion of saline solution. However, the symbolic meaning of this basal infusion was changed in three different groups of patients. The first group was told nothing about any analgesic effect (natural history). The second group was told that the basal infusion was either a powerful painkiller or a placebo (classic double-blind administration). The third group was told that the basal infusion was a potent painkiller (deceptive administration). Therefore, whereas the analgesic treatment was exactly the same in the three groups, the verbal instructions about the basal infusion differed. The placebo effect of the saline basal infusion was measured by recording the doses of buprenorphine requested over the three-days treatment. We found that the double-blind group showed a reduction of buprenorphine requests compared to the natural history group. However, this reduction was even larger in the deceptive administration group. Overall, after 3 days of placebo infusion, the first group received 11.55 mg of buprenorphine, the second group 9.15 mg, and the third group 7.65 mg. Despite these dose differences, analgesia was the same in the three groups. These results indicate that different verbal instructions about certain and uncertain expectations of analgesia produce different placebo analgesic effects, which in turn trigger a dramatic change of behaviour leading to a significant reduction of opioid intake.

Aged↗

PubMed1996

The opposite effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia.

Discovery of the involvement of endogenous opiates in placebo analgesia represents an important step in understanding the mechanisms underlying placebo response. In the present study, we investigated the effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia in a human model of experimentally induced ischemic pain. First, we found that part of the placebo response was reversed by naloxone, confirming previous studies on the role of opioids in the placebo phenomenon. Second, since it was demonstrated that the action of exogenous and endogenous opiates is potentiated by proglumide, we analysed the effects of this cholecystokinin antagonist on placebo response and found that it enhanced placebo analgesia. The placebo effect can thus be modulated in two opposite directions: it can be partially abolished by naloxone and potentiated by proglumide. The fact that placebo potentiation by proglumide occurred only in placebo responders, but not in non-responders, suggests that activation of an endogenous opiate system is a necessary condition for the action of proglumide. These results suggest an inhibitory role for cholecystokinin in placebo response, although the low affinity of proglumide for cholecystokinin receptors does not rule out the possibility of other mechanisms.

Adult↗