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Fabrizio Benedetti - One of the best experts on this subject based on the ideXlab platform.

  • Treatment journey in rheumatoid arthritis with biosimilars: from better access to good disease control through cost savings and prevention of Nocebo Effects
    'BMJ', 2021
    Co-Authors: Fabrizio Benedetti, Roberto Caporali, Thomas Doerner, Burkhard Pieper, Minjun Jang
    Abstract:

    Early diagnosis and treatment of rheumatoid arthritis (RA) are of critical importance to halt the progression of the disease. Optimal use of advanced imaging techniques or biomarkers may facilitate early diagnosis of RA. Even though many disease-modifying anti-rheumatic drugs (DMARDs) are available for RA treatment, biological DMARDs (bDMARDs) offer expanding therapeutic options and good outcomes in patients with RA who do not have a sufficient response to conventional synthetic DMARDs. However, high costs of bDMARDs have limited patient access to optimised disease management and increased the cost burden for healthcare systems. The advent of biosimilars led to significant cost savings driven by price competition among the reference products, which could be beneficial for healthcare systems. Healthcare provider (HCP)–patient communication and informed shared decision-making are crucial to prevent the occurrence of a Nocebo Effect, which results from negative perceptions that patients may have and could lead to less Effective outcomes. Research has demonstrated that Effective communication between HCPs and patients utilising positive framing can improve acceptance by patients to be initiated on or switched to a biosimilar and can help to integrate biosimilars into routine clinical practice to maximise benefits for patients with RA

  • Nocebo and placebo modulation of hypobaric hypoxia headache involves the cyclooxygenase prostaglandins pathway
    Pain, 2014
    Co-Authors: Fabrizio Benedetti, Jennifer Durando, Sergio Vighetti
    Abstract:

    Nocebo and placebo Effects have been found to modulate several neurochemical systems, such as cholecystokinin, endogenous opioids, and endocannabinoids. Here we show that also the cyclooxygenase-prostaglandins pathway can be modulated by both Nocebos and placebos. In fact, we found that negative expectation, the crucial element of the Nocebo Effect, about headache pain led to the enhancement of the cyclooxygenase-prostaglandins pathway, which, in turn, induced pain worsening. As an experimental model, we studied hypobaric hypoxia headache at high altitude in 2 populations of subjects. Whereas the experimental Nocebo group received negative information by a single individual who was informed about the risk of headache, the control group did not know about the possible occurrence of headache. We found a significant increase in headache and salivary prostaglandins and thromboxane in the Nocebo group compared to the control group, suggesting that negative expectations enhance cyclooxygenase activity. In addition, placebo administration to headache sufferers at high altitude inhibited the Nocebo-related component of pain and prostaglandins synthesis, which indicates that the cyclooxygenase pathway can be modulated by both Nocebos and placebos. Our results show for the first time how Nocebos and placebos affect the synthesis of prostaglandins, which represent an important target of analgesic drugs, thus emphasizing once again the notion that placebos and drugs may use common biochemical pathways.

  • the role of learning in Nocebo and placebo Effects
    Acute Pain, 2008
    Co-Authors: Luana Colloca, Monica Sigaudo, Fabrizio Benedetti
    Abstract:

    The Nocebo Effect consists in delivering verbal suggestions of negative outcomes so that the subject expects clinical worsening. Here we show that Nocebo suggestions, in which expectation of pain increase is induced, are capable of producing both hyperalgesic and allodynic responses. By extending previous findings on the placebo Effect, we investigated the role of learning in the Nocebo Effect by means of a conditioning procedure. To do this, verbal suggestions of pain increase were given to healthy volunteers before administration of either tactile or low-intensity painful electrical stimuli. This Nocebo procedure was also carried out after a pre-conditioning session in which two different conditioned visual stimuli were associated to either pain or no-pain. Pain perception was assessed by means of a Numerical Rating Scale raging from 0 = tactile to 10 = maximum imaginable pain. We found that verbal suggestions alone, without prior conditioning, turned tactile stimuli into pain as well as low-intensity painful stimuli into high-intensity pain. A conditioning procedure produced similar Effects, without significant differences. Therefore, in contrast to placebo analgesia, whereby a conditioning procedure elicits larger Effects compared to verbal suggestions alone, learning seems to be less important in Nocebo hyperalgesia. Overall, these findings indicate that, by defining hyperalgesia as an increase in pain sensitivity and allodynia as the perception of pain in response to innocuous stimulation, Nocebos can indeed produce both hyperalgesic and allodynic Effects. These results also suggest that learning is not important in Nocebo hyperalgesia compared to placebo analgesia. 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  • the role of learning in Nocebo and placebo Effects
    Pain, 2008
    Co-Authors: Luana Colloca, Monica Sigaudo, Fabrizio Benedetti
    Abstract:

    The Nocebo Effect consists in delivering verbal suggestions of negative outcomes so that the subject expects clinical worsening. Here we show that Nocebo suggestions, in which expectation of pain increase is induced, are capable of producing both hyperalgesic and allodynic responses. By extending previous findings on the placebo Effect, we investigated the role of learning in the Nocebo Effect by means of a conditioning procedure. To do this, verbal suggestions of pain increase were given to healthy volunteers before administration of either tactile or low-intensity painful electrical stimuli. This Nocebo procedure was also carried out after a pre-conditioning session in which two different conditioned visual stimuli were associated to either pain or no-pain. Pain perception was assessed by means of a Numerical Rating Scale raging from 0 = tactile to 10 = maximum imaginable pain. We found that verbal suggestions alone, without prior conditioning, turned tactile stimuli into pain as well as low-intensity painful stimuli into high-intensity pain. A conditioning procedure produced similar Effects, without significant differences. Therefore, in contrast to placebo analgesia, whereby a conditioning procedure elicits larger Effects compared to verbal suggestions alone, learning seems to be less important in Nocebo hyperalgesia. Overall, these findings indicate that, by defining hyperalgesia as an increase in pain sensitivity and allodynia as the perception of pain in response to innocuous stimulation, Nocebos can indeed produce both hyperalgesic and allodynic Effects. These results also suggest that learning is not important in Nocebo hyperalgesia compared to placebo analgesia.

  • Nocebo hyperalgesia how anxiety is turned into pain
    Current Opinion in Anesthesiology, 2007
    Co-Authors: Luana Colloca, Fabrizio Benedetti
    Abstract:

    Purpose of reviewNocebo hyperalgesia is a phenomenon that is opposite to placebo analgesia and whereby expectation of pain increase plays a crucial role. In recent times, both the neuroanatomical and the neurochemical bases of the Nocebo Effect and of Nocebo-related Effects have begun to be explored

Sara Palermo - One of the best experts on this subject based on the ideXlab platform.

  • pain anticipation and Nocebo related responses a descriptive mini review of functional neuroimaging studies in normal subjects and precious hints on pain processing in the context of neurodegenerative disorders
    Frontiers in Pharmacology, 2019
    Co-Authors: Martina Amanzio, Sara Palermo
    Abstract:

    The exacerbation of a clinical condition or the occurrence of negative symptoms after an inert substance dispensation or a sham treatment is known as "Nocebo Effect." Nocebo is the psychobiological Effect due to the negative psychosocial context that accompanies a therapy, and it is a direct consequence of negative expectations by the patients and their own personal characteristics. Although the clinical relevance of the phenomenon is now recognized, a small number of studies have tried to ascertain its neural underpinnings (that it means Nocebo responses). Moreover, there is no consensus on the brain networks involved in Nocebo processes in humans. In particular, Nocebo hyperalgesia has attracted almost no research attention. We conducted a mini-review on the few experimental pain functional magnetic resonance imaging (fMRI) studies of Nocebo responses to discuss how negative expectancies and conditioning Effects engage brain networks to modulate pain experiences. Moreover, we present possible clinical implications considering Alzheimer's disease and behavioral frontotemporal dementia, in which the existence of a hypothetically disrupted neurocognitive anticipatory network-secondary to an endogenous pain modulatory system damage-may be responsible for pain processing alterations.

  • Analgesia da placebo, anticipazione dolorifica e i possibili correlati neurali dell'effetto Nocebo
    Mimesis Edizioni Milano, 2018
    Co-Authors: Sara Palermo
    Abstract:

    The Nocebo Effect is a psychobiological Effect that occurs when a negative psychosocial context that accompanies a therapy. Since the study of pain anticipation takes into account the temporal phase of the “expectation of hyperalgesia”, and considering that it is possible to stimulate such anticipatory processes merely through the use of negative verbalizations, this model is appropriate for studying the Nocebo response. To date, there are no univocal data about the brain areas involved in these processes or their cognitive roles. We conducted a meta-analysis on pain anticipation fMRI studies. We then applied a meta-analytic connectivity model to activations in the anterior cingulate cortex and the anterior insula, which correlate with the behavioral domains of action, emotion and perception. Our results support the hypothesis that there is a highly-distributed supramodal system, activated by pain anticipation, for processing information that enhances the self-regulation of adaptive responses to the environment

Luana Colloca - One of the best experts on this subject based on the ideXlab platform.

  • Comprehensive review The magnitude of Nocebo Effects in pain: A meta-analysis
    2020
    Co-Authors: Gitte Laue Petersen, Luana Colloca, Martina Amanzio, Nanna Brix Finnerup, Donald D Price, Staehelin Troels, Lene Vase
    Abstract:

    a b s t r a c t The investigation of Nocebo Effects is evolving, and a few literature reviews have emerged, although so far without quantifying such Effects. This meta-analysis investigated Nocebo Effects in pain. We searched the databases PubMed, EMBASE, Scopus, and the Cochrane Controlled Trial Register with the term ''Nocebo.'' Only studies that investigated Nocebo Effects as the Effects that followed the administration of an inert treatment along with verbal suggestions of symptom worsening and that included a no-treatment control condition were eligible. Ten studies fulfilled the selection criteria. The Effect sizes were calculated using Cohen's d and Hedges' g. The overall magnitude of the Nocebo Effect was moderate to large (lowest g = 0.62 [0.24-1.01] and highest g = 1.03 [0.63-1.43]) and highly variable (range of g = À0.43 to 4.05). The magnitudes and range of Effect sizes was similar to those of placebo Effects (d = 0.81) in mechanistic studies. In studies in which Nocebo Effects were induced by a combination of verbal suggestions and conditioning, the Effect size was larger (lowest g = 0.76 [0.39-1.14] and highest g = 1.17 [0.52-1.81]) than in studies in which Nocebo Effects were induced by verbal suggestions alone (lowest g = 0.64 [À0.25 to 1.53] and highest g = 0.87 [0.40-1.34]). These findings are similar to those in the placebo literature. As the magnitude of the Nocebo Effect is variable and sometimes large, this meta-analysis demonstrates the importance of minimizing Nocebo Effects in clinical practice.

  • the role of learning in Nocebo and placebo Effects
    Acute Pain, 2008
    Co-Authors: Luana Colloca, Monica Sigaudo, Fabrizio Benedetti
    Abstract:

    The Nocebo Effect consists in delivering verbal suggestions of negative outcomes so that the subject expects clinical worsening. Here we show that Nocebo suggestions, in which expectation of pain increase is induced, are capable of producing both hyperalgesic and allodynic responses. By extending previous findings on the placebo Effect, we investigated the role of learning in the Nocebo Effect by means of a conditioning procedure. To do this, verbal suggestions of pain increase were given to healthy volunteers before administration of either tactile or low-intensity painful electrical stimuli. This Nocebo procedure was also carried out after a pre-conditioning session in which two different conditioned visual stimuli were associated to either pain or no-pain. Pain perception was assessed by means of a Numerical Rating Scale raging from 0 = tactile to 10 = maximum imaginable pain. We found that verbal suggestions alone, without prior conditioning, turned tactile stimuli into pain as well as low-intensity painful stimuli into high-intensity pain. A conditioning procedure produced similar Effects, without significant differences. Therefore, in contrast to placebo analgesia, whereby a conditioning procedure elicits larger Effects compared to verbal suggestions alone, learning seems to be less important in Nocebo hyperalgesia. Overall, these findings indicate that, by defining hyperalgesia as an increase in pain sensitivity and allodynia as the perception of pain in response to innocuous stimulation, Nocebos can indeed produce both hyperalgesic and allodynic Effects. These results also suggest that learning is not important in Nocebo hyperalgesia compared to placebo analgesia. 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  • the role of learning in Nocebo and placebo Effects
    Pain, 2008
    Co-Authors: Luana Colloca, Monica Sigaudo, Fabrizio Benedetti
    Abstract:

    The Nocebo Effect consists in delivering verbal suggestions of negative outcomes so that the subject expects clinical worsening. Here we show that Nocebo suggestions, in which expectation of pain increase is induced, are capable of producing both hyperalgesic and allodynic responses. By extending previous findings on the placebo Effect, we investigated the role of learning in the Nocebo Effect by means of a conditioning procedure. To do this, verbal suggestions of pain increase were given to healthy volunteers before administration of either tactile or low-intensity painful electrical stimuli. This Nocebo procedure was also carried out after a pre-conditioning session in which two different conditioned visual stimuli were associated to either pain or no-pain. Pain perception was assessed by means of a Numerical Rating Scale raging from 0 = tactile to 10 = maximum imaginable pain. We found that verbal suggestions alone, without prior conditioning, turned tactile stimuli into pain as well as low-intensity painful stimuli into high-intensity pain. A conditioning procedure produced similar Effects, without significant differences. Therefore, in contrast to placebo analgesia, whereby a conditioning procedure elicits larger Effects compared to verbal suggestions alone, learning seems to be less important in Nocebo hyperalgesia. Overall, these findings indicate that, by defining hyperalgesia as an increase in pain sensitivity and allodynia as the perception of pain in response to innocuous stimulation, Nocebos can indeed produce both hyperalgesic and allodynic Effects. These results also suggest that learning is not important in Nocebo hyperalgesia compared to placebo analgesia.

  • Nocebo hyperalgesia how anxiety is turned into pain
    Current Opinion in Anesthesiology, 2007
    Co-Authors: Luana Colloca, Fabrizio Benedetti
    Abstract:

    Purpose of reviewNocebo hyperalgesia is a phenomenon that is opposite to placebo analgesia and whereby expectation of pain increase plays a crucial role. In recent times, both the neuroanatomical and the neurochemical bases of the Nocebo Effect and of Nocebo-related Effects have begun to be explored

Andrea W M Evers - One of the best experts on this subject based on the ideXlab platform.

  • Nocebo Effects on cowhage evoked itch a randomized controlled trial of classical conditioning and observational learning
    Acta Dermato-venereologica, 2021
    Co-Authors: Joseph S Blythe, Kaya J Peerdeman, Dieuwke S Veldhuijzen, Myrthe M E Van Schothorst, Mia A Thomaidou, Antoinette I M Van Laarhoven, Andrea W M Evers
    Abstract:

    To investigate learning processes underlying Nocebo Effects on itch, this study measured the efficacy of classical conditioning and observational learning for inducing Nocebo Effects on cowhage-evoked itch and scratching behaviour. A total of 58 healthy female participants were assigned to classical conditioning, observational learning, or sham conditioning groups. In the classical conditioning group, experimenters associated the application of an inert gel with increased itch intensity first-hand. In the observational learning group, a video of the conditioning paradigm was shown. Nocebo Effects were measured as the difference in itch or scratching between control and Nocebo test phase trials, compared between learning and control groups. Compared with sham conditioning, classical conditioning induced a significant Nocebo Effect on itch, while observational learning did not. No Nocebo Effect on scratching was detected. These results highlight the role that learning through direct experiences plays in pruritic symptoms. Future research should investigate how a patient's history of unsuccessful treatments shapes treatment outcomes.

Palermo Sara - One of the best experts on this subject based on the ideXlab platform.

  • Analgesia da placebo, anticipazione dolorifica e i possibili correlati neurali dell’effetto Nocebo
    Mimesis Edizioni, 2018
    Co-Authors: Palermo Sara
    Abstract:

    Riassunto: L’effetto Nocebo è l’effetto psicobiologico dovuto al contesto psicosociale negativo che accompagna una terapia. Dal momento che lo studio dell’anticipazione dolorifica prende in considerazione la fase temporale della “attesa dell’iperalgesia”, e considerando che – proprio come il Nocebo – è possibile elicitarla con il solo uso di verbalizzazioni negative, questo modello può permettere di studiare la risposta Nocebo. Ad oggi infatti non si dispone di dati univoci circa le aree coinvolte in questi processi e circa il ruolo cognitivo da queste ricoperto. Abbiamo condotto una meta-analisi su studi fMRI di anticipazione dolorifica su cui applicare un modello di connettività meta-analitica su due regioni di interesse: la corteccia cingolata e l’insula anteriori, le cui attivazioni sembrerebbero correlano ai domini comportamentali dell’azione, dell’emozione e della percezione. I risultati avvalorano l’ipotesi dell’esistenza di un sistema supramodale altamente distribuito, attivato dall’anticipazione del dolore, e, infine, volto all’elaborazione delle informazioni e all’auto-regolazione delle risposte adattive all’ambiente.Parole chiave: Placebo; Nocebo; Dolore; Correlati neurali; Comportamento umano Placebo Analgesia, Pain Anticipation, and the Possible Neural Correlates of Nocebo EffectAbstract: The Nocebo Effect is a psychobiological Effect that occurs when a negative psychosocial context that accompanies a therapy. Since the study of pain anticipation takes into account the temporal phase of the “expectation of hyperalgesia”, and considering that it is possible to stimulate such anticipatory processes merely through the use of negative verbalizations, this model is appropriate for studying the Nocebo response. To date, there are no univocal data about the brain areas involved in these processes or their cognitive roles. We conducted a meta-analysis on pain anticipation fMRI studies. We then applied a meta-analytic connectivity model to activations in the anterior cingulate cortex and the anterior insula, which correlate with the behavioral domains of action, emotion and perception. Our results support the hypothesis that there is a highly-distributed supramodal system, activated by pain anticipation, for processing information that enhances the self-regulation of adaptive responses to the environment.Keywords: Placebo; Nocebo; Pain; Neural Correlates; Human Behaviou