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Conditioned placebo analgesia persists when subjects know they are receiving a placebo.

ABSTRACT: Belief in the effectiveness of a placebo treatment is widely thought to be critical for placebo analgesia. Many types of placebo responses--even those that depend on conditioning--appear to be mediated by expectations that are strengthened as treatment cues are reinforced with positive outcomes. However, placebo effects may occur even when participants are aware they are receiving a placebo. To address the question of whether conditioned placebo analgesia can persist in the absence of expectations, we studied the effects of long (4 days) versus short (1 day) conditioning to a placebo treatment. After an initial placebo test, a "reveal" manipulation convincingly demonstrated to participants that they had never received an active drug. Placebo analgesia persisted after the reveal in the long conditioning group only. These findings suggest that reinforcing treatment cues with positive outcomes can create placebo effects that are independent of reported expectations for pain relief.This article demonstrates a form of placebo analgesia that relies on prior conditioning rather than current expected pain relief. This highlights the importance of prior experience on pain relief and offers insight into the variability of placebo effects across individuals.

SUBMITTER: Schafer SM

PROVIDER: S-EPMC4424173 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Conditioned placebo analgesia persists when subjects know they are receiving a placebo.

Schafer Scott M SM Colloca Luana L Wager Tor D TD

The journal of pain 20150122 5

<h4>Unlabelled</h4>Belief in the effectiveness of a placebo treatment is widely thought to be critical for placebo analgesia. Many types of placebo responses--even those that depend on conditioning--appear to be mediated by expectations that are strengthened as treatment cues are reinforced with positive outcomes. However, placebo effects may occur even when participants are aware they are receiving a placebo. To address the question of whether conditioned placebo analgesia can persist in the ab ...[more]

PMID: 25617812

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Project description:BACKGROUND:Although routine administration of pharmacologic sedation or analgesia during mechanical ventilation in preterm neonates is not recommended, its use in clinical practice remains common. Alpha-2 agonists, mainly clonidine and dexmedetomidine, are used as adjunctive (or alternative) sedative agents alongside opioids and benzodiazepines. Clonidine has not been systematically assessed for use in neonatal sedation during ventilation. OBJECTIVES:To assess whether clonidine administered to term and preterm newborn infants receiving mechanical ventilation reduces morbidity and mortality rates. To compare the intervention versus placebo, no treatment, and dexmedetomidine; and to assess the safety of clonidine infusion for potential harms.To perform subgroup analyses according to gestational age; birth weight; administration method (infusion or bolus therapy); dose, duration, and route of clonidine administration; and pharmacologic sedation as a co-intervention. SEARCH METHODS:We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12) in the Cochrane Library, MEDLINE via PubMed (1966 to January 10, 2017), Embase (1980 to January 10, 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to January 10, 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. SELECTION CRITERIA:We searched for randomized controlled trials, quasi-randomized controlled trials, and cluster trials comparing clonidine versus placebo, no treatment, or dexmedetomidine administered to term and preterm newborns receiving mechanical ventilation via an endotracheal tube. DATA COLLECTION AND ANALYSIS:For the included trial, two review authors independently extracted data (e.g. number of participants, birth weight, gestational age, all-cause death during initial hospitalization, duration of respiratory support, sedation scale, duration of hospital stay) and assessed risk of bias (e.g. adequacy of randomization, blinding, completeness of follow-up). This review considered primary outcomes of all-cause neonatal death, all-cause death during initial hospitalization, and duration of mechanical ventilation in days. MAIN RESULTS:One trial, which included 112 infants, met the inclusion criteria for this review. Term newborn infants on mechanical ventilation with the need for continuous analgesia and sedation with fentanyl and midazolam were eligible for enrollment during the first 96 hours of ventilation. Study authors administered clonidine 1 ?g/kg/h or placebo on day 4 after intubation.We found no differences between the two groups in all-cause death during hospitalization (risk ratio [RR] 0.69, 95% confidence interval [CI] 0.12 to 3.98). The quality of the evidence supporting these findings is low owing to imprecision of the estimates (one study; few events). The median (interquartile range) duration of mechanical ventilation was 7.1 days (5.7 to 9.1 days) in the clonidine group and 5.8 days (4.9 to 7.9 days) in the placebo group, respectively (P = 0.070). Among secondary outcomes, we found no differences in terms of duration of stay in the intensive care unit. Sedation scale values (COMFORT) and analgesia scores (Hartwig) during the first 72 hours of infusion of study medication were lower in the clonidine group than in the placebo group. AUTHORS' CONCLUSIONS:At present, evidence is insufficient to show the efficacy and safety of clonidine for sedation and analgesia in term and preterm newborn infants receiving mechanical ventilation.

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Conditioned placebo analgesia persists when subjects know they are receiving a placebo.

Publications

Conditioned placebo analgesia persists when subjects know they are receiving a placebo.

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