Blockade of nocebo hyperalgesia by the cholecystokinin antagonist proglumide.

Dipartimento di Neuroscienze, Università di Torino, Corso Raffaello, Italy.
Pain (Impact Factor: 5.84). 07/1997; 71(2):135-40. DOI: 10.1016/S0304-3959(97)03346-0
Source: PubMed

ABSTRACT In patients who reported mild postoperative pain, we evoked a nocebo response, a phenomenon equal but opposite to placebo. Patients who gave informed consent to increase their pain for 30 min received a substance known to be non-hyperalgesic (saline solution) and were told that it produced a pain increase. A nocebo effect was observed when saline was administered. However, if a dose of 0.5 or 5 mg of the cholecystokinin antagonist proglumide was added to the saline solution, the nocebo effect was abolished. A dose of 0.05 mg of proglumide was ineffective. The blockade of the nocebo hyperalgesic response was not reversed by 10 mg of naloxone. These results suggest that cholecystokinin mediates pain increase in the nocebo response and that proglumide blocks nocebo through mechanisms not involving opioids. Since the nocebo procedure represents an anxiogenic stimulus and previous studies showed a role for cholecystokinin in anxiety, we suggest that nocebo hyperalgesia may be due to a cholecystokinin-dependent increase of anxiety.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Placebo and nocebo effects are often regarded by clinicians as either a quaint reminiscence from the pre-therapeutic era, or simply as a technique for establishing the efficacy of therapeutic interventions within the locus of evidence-based practice. However, neither of these explanations sufficiently account for their complexity or their persistence and impact in clinical medicine. Placebo and nocebo effects are embedded in the very fabric of therapeutic relationships and are both a manifestation and outcome of the rituals that characterise clinical practice. They are also a stark reminder of the many personal and environmental factors, including the attitudes, beliefs and expectations of both doctor and patient, that shape the outcomes of health professional-patient interactions. We describe how recent biological and neuropsychiatric data have clarified the operation of placebo and nocebo effects in clinical practice - demonstrating the ability of the therapeutic context to modulate endogenous biological processes in a targeted manner. This, in turn, illustrates the potent philosophical and sociocultural aspects of medical praxis.
    Internal Medicine Journal 04/2014; 44(4):398-405. · 1.70 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: As research expands our understanding of underlying placebo mechanisms, interest turns to the clinical application of placebos. Whether placebos are appropriate and effective in the management of chronic pain in older people deserves considerable attention. The evidence suggests that adults of any age are responsive to placebos, and that placebo treatments can be effective for many conditions prevalent in older people. Though placebos in general already seem to be used with some regularity in medical practice, the use of placebos alone for chronic pain is probably unjustified unless other treatments are inadvisable or have been exhausted. However maximising the mechanisms that underpin placebo analgesia such as expectancy or the psychosocial context should be encouraged and would be considered a feature of good clinical practice. It would also be anticipated that older people may see an additional benefit with placebo treatments when such treatments reduce existing or planned medication regimes, as older people typically experience more comorbidities, increased susceptibility to adverse drug reactions, and altered pharmacological responses to drugs. Further research is still needed in placebo related treatment paradigms for the management of chronic pain in older people.
    Maturitas 12/2014; · 2.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The investigation of nocebo effects is evolving and a few literature reviews have emerged, however, so far without quantifying such effects. This quantitative systematic review 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 follow 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 = -0.43-4.05). The magnitudes and range of effect sizes was similar to those of placebo effects (d = 0.81) in mechanistic studies. In studies where 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 where nocebo effects were induced by verbal suggestions alone (lowest g = 0.64 (-0.25-1.53) and highest g = 0.87 (0.40-1.34)). These findings are similar to those in the placebo literature. Since the magnitude of the nocebo effect is variable and sometimes large, this systematic review demonstrates the importance of minimizing nocebo effects in clinical practice.
    Pain 04/2014; · 5.64 Impact Factor


Available from
Jun 3, 2014