Individuals with chronic pain have the same response to placebo analgesia as healthy controls in terms of magnitude and reproducibility

Power, Andrea; Brown, Christopher; Sivan, Manoj; Lenton, A; Rainey, Timothy; El‐Deredy, Wael; Jones, Anthony; Watson, Alison

doi:10.1097/j.pain.0000000000001966

Cited by 15 publications

(10 citation statements)

References 55 publications

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“…It is known that patients affected with chronic or neuropathic pain do not respond to pharmacological treatments [119]. However, recent research has suggested that individuals with chronic pain exhibit a similar placebo analgesic response (magnitude and reliability) to that exhibited by healthy controls [120]. Suppose our results are also valid for patients suffering from chronic pain with relatively low levels of active avoidance or fear personality traits.…”

Section: Discussionmentioning

confidence: 52%

ERP Indicators of Self-Pain and Other Pain Reductions due to Placebo Analgesia Responding: The Moderating Role of the Fight-Flight-Freeze System

Vecchio

Pascalis

2021

Brain Sciences

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This study evaluates the modulation of phasic pain and empathy for pain induced by placebo analgesia during pain and empathy for pain tasks. Because pain can be conceptualized as a dangerous stimulus that generates avoidance, we evaluated how approach and avoidance personality traits modulate pain and empathy for pain responses. We induced placebo analgesia to test whether this also reduces self-pain and other pain. Amplitude measures of the N1, P2, and P3 ERPs components, elicited by electric stimulations, were obtained during a painful control, as well as during a placebo treatment expected to induce placebo analgesia. The placebo treatment produced a reduction in pain and unpleasantness perceived, whereas we observed a decrease in the empathy unpleasantness alone during the empathy pain condition. The moderator effects of the fight-flight-freeze system (FFFS) in the relationships linking P2 and P3 amplitude changes with pain reduction were both significant among low to moderate FFFS values. These observations are consistent with the idea that lower FFFS (active avoidance) scores can predict placebo-induced pain reduction. Finally, in line with the revised Reinforcement Sensitivity Theory (r-RST), we can assume that phasic pain is an aversive stimulus activating the active-avoidance behavior to bring the system back to homeostasis.

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Section: Discussionmentioning

confidence: 52%

ERP Indicators of Self-Pain and Other Pain Reductions due to Placebo Analgesia Responding: The Moderating Role of the Fight-Flight-Freeze System

Vecchio

Pascalis

2021

Brain Sciences

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“…Secondly, the fact that dynamic changes in pain perception in both groups are best explained by different models also presents an interesting research avenue. Placebo analgesia gives insight into the endogenous pain modulation mechanisms [3], and it has been observed that great variability exists in the placebo response of patients [18]. This could indicate that different factors could be leading to dynamic changes in the pain perception of different patients, and therefore, it may be taken as an argument in favour of individualised or stratified medicine, widely considered an important goal in clinical pain science [21].…”

Section: Discussionmentioning

confidence: 99%

“…This phenomenon can provide insight into endogenous pain modulation mechanisms [3], which are important markers of chronic pain vulnerability, disability and treatment outcome [25]. Since considerable variability exists in the placebo response between individuals [16,18,24], understanding the differences in pain perception between those who are sensitive to placebo analgesia (responders) and those who are not (nonresponders) could help in the understanding of individual differences in endogenous pain control and treatment outcome.…”

Section: Introductionmentioning

confidence: 99%

Resistance to placebo analgesia is explained by greater reliance on somatic input: a Bayesian model comparison study

Delgado-Sanchez¹,

Trujillo-Barreto²,

Brown³

et al. 2022

Preprint

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In placebo analgesia, the expectation of pain reduction results in actual reduction in pain experience. Yet, there is substantial variability between participants in the magnitude of the placebo response, allowing a data-driven discrimination between placebo “responders” and “non-responders”. The mechanisms driving the difference between these groups remains unclear. Here we propose that placebo responders, when rating painfulness, place a higher relative weight on their prior experience relative to current nociceptive inputs. We analysed participants’ pain ratings from an experimental placebo paradigm, involving nociceptive laser stimulation and a fake analgesic cream. We compared three alternative linear predictive models that varied in the factors assumed to predict pain responses: either past experience, nociceptive stimulation or both. We carried out single trial inferences for each model using a Bayesian framework with belief updating priors on the prediction weights at each trial. Model comparison showed that dynamic changes in pain ratings in placebo responders is best explained by past experience, and in non-responders by both past experience and stimulation. This is the first account of placebo analgesia resistance being associated with greater nociceptive information processing. This conclusion fits with previous research highlighting the importance of attention to the body as a way to reduce the effect of expectancy-related bias. Our results also support the use of Bayesian models as phenotyping tools, which have potential uses for personalised medicine.

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“…While the effects of different sham stimulations on neural networks need to be further investigated, a placebo effect might be involved if those sham stimulations are experienced differently on the scalp. Studies examining whether chronic pain populations, including FMS, are more responsive to placebo than non-pain healthy controls show mixed findings [59][60][61] ; however, a systematic review investigating placebo-intervention against notreatment comparator groups in FMS found that the magnitude of placebo effects increases with the effect size of the active treatment 62 . While it is possible that a higher intensity sham stimulation would give rise to a stronger placebo response, we observed no significant differences in participants' guesses as to whether they received sham or active treatment between either sham group nor the active group.…”

Section: Discussionmentioning

confidence: 99%

Modulation of a Stable Neurobehavioral Trait Using Repetitive Transcranial Magnetic Stimulation: A Preregistered Randomized Controlled Trial

Faerman

Stimpson

et al. 2021

Preprint

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Hypnotizability, one’s ability to experience cognitive, emotional, behavioral, and physical changes in response to suggestions in the context of hypnosis, is a highly stable trait associated with increased functional connectivity between the left dorsolateral prefrontal cortex (L-DLPFC) and dorsal anterior cingulate cortex (dACC). We conducted a preregistered, triple-blinded, randomized controlled trial to test the ability of continuous theta-burst stimulation (cTBS) over a personalized neuroimaging-based L-DLPFC target to temporarily enhance hypnotizability. We tested our hypothesis in 78 patients with fibromyalgia syndrome (FMS), a functional pain disorder for which hypnosis has consistently been shown to be beneficial as a nonpharmacological treatment option. Pre-to-post cTBS change in Hypnotic Induction Profile scores (HIP; a standardized measure of hypnotizability) was significantly greater in the Active versus Sham group. Our findings suggest a causal relationship between L-DLPFC and dACC function and hypnotizability. Dose-response optimization should be further examined to formalize guidelines for future clinical utilization.Trial registrationClinicalTrials.govNCT02969707

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Individuals with chronic pain have the same response to placebo analgesia as healthy controls in terms of magnitude and reproducibility

Abstract: This is a repository copy of Individuals with chronic pain have the same response to placebo analgesia as healthy controls in terms of magnitude and reproducibility.

Cited by 15 publications

References 55 publications

ERP Indicators of Self-Pain and Other Pain Reductions due to Placebo Analgesia Responding: The Moderating Role of the Fight-Flight-Freeze System

ERP Indicators of Self-Pain and Other Pain Reductions due to Placebo Analgesia Responding: The Moderating Role of the Fight-Flight-Freeze System

Resistance to placebo analgesia is explained by greater reliance on somatic input: a Bayesian model comparison study

Modulation of a Stable Neurobehavioral Trait Using Repetitive Transcranial Magnetic Stimulation: A Preregistered Randomized Controlled Trial

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