Prefrontal cortex modulates placebo analgesia

Kempler, Péter; Candia, Victor; Folkers, Gerd; Schedlowski, Manfred; Schönbächler, Georg

doi:10.1016/j.pain.2009.09.033

Cited by 300 publications

(208 citation statements)

References 46 publications

Supporting

Mentioning

185

Contrasting

Unclassified

Order By: Relevance

“…Our experimental approach clearly confirms this age effect. The difference scores between baseline and post-treatment in the analgesia-expectation group were 5.6-times higher than those found in a healthy adult population with regard to heat pain tolerance and 3.6-times higher with regard to heat pain threshold using a similar paradigm (12). Several psychological and neurodevelopmental reasons may account for the larger PR in children.…”

Section: Placebo Analgesia Responsesmentioning

confidence: 52%

“…Clinical trials of local anesthetics (9,10) as well as a venipuncture study (11) emphasize the significance of PR in children. From a neurobiological perspective this is even more interesting since the prefrontal cortex (PFC) has repeatedly been implicated in the mediation of cognitive top-down expectation-related PR (12)(13)(14)(15) and given that this neural network undergoes considerable maturation during childhood (16,17). Surprisingly, to date there have been no experimental attempts to study PA in healthy children.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expectancy-Induced Placebo Analgesia in Children and the Role of Magical Thinking

Kempler

Kossowsky

Schwarz

et al. 2014

The Journal of Pain

Self Cite

View full text Add to dashboard Cite

Expectations and beliefs shape the experience of pain. This is most evident in context-induced, placebo analgesia, which has recently been shown to interact with the trait of magical thinking (MT) in adults. In children, placebo analgesia and the possible roles that MT and gender might play as modulators of placebo analgesia have remained unexplored. Using a paradigm in which heat-pain stimuli were applied to both forearms, we investigated whether MT and gender can influence the magnitude of placebo analgesia in children. Participants were 49 right-handed children (aged 6-9 years) who were randomly assigned -stratified for MT and gender -to either an analgesia-expectation or a controlexpectation condition. For both conditions, the placebo was a blue-colored hand disinfectant that was applied to the children's forearms. Independent of MT, the placebo treatment significantly increased both heat pain threshold and tolerance. The threshold placebo effect was more pronounced for girls than boys. In addition, independent of the expectation treatment, low-MT boys showed a lower tolerance increase on the left compared to the right side. Finally, MT specifically modulated tolerance on the right forearmside: low-MT boys showed an increase, whereas high-MT boys showed a decrease in heat pain tolerance. This study documented a substantial expectation-induced placebo analgesia response in children (girls > boys) and demonstrated MT and gender-dependent laterality effects in pain perception. The findings may help improve individualized pain management for children. PERSPECTIVE: The study documents the first experimental evidence for a substantial expectancy-induced placebo analgesia response in healthy children from 6 to 9 years of age. Moreover, the effect was substantially higher than the placebo response typically found in adults. The findings may help improve individualized pain management for children. Conflicts of Interest and Source of FundingThe authors declare that there is no conflict of interest. This research was supported by the University of Basel.Running Title: Placebo Analgesia and Magical Thinking in Children Krummenacher et al., 2014 1 Abstract Objective: Higher brain functions such as expectations and beliefs shape the experience of pain. This is most evident in context-induced placebo analgesia (PA), which was recently shown in adults to interact with the trait of magical thinking (MT).In children, PA and the possible relationship between PA and MT has remained unexplored.Methods: Using a lateralized heat-pain paradigm, we investigated the possible modulatory role of PA expectation and MT in response to nociceptive stimuli on the right and left forearm.Participants were 49 right-handed children (6-9 years). In a between-subjects design, half of them were either randomly -stratified for MT and gender -assigned to an analgesia-expectation or a control-expectation condition. Results:Results indicate that, independent of MT, the placebo procedure significantly increased both heat pain threshold (...

show abstract

Section: Placebo Analgesia Responsesmentioning

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Expectancy-Induced Placebo Analgesia in Children and the Role of Magical Thinking

Kempler

Kossowsky

Schwarz

et al. 2014

The Journal of Pain

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previous PET studies suggested a major role of the DLPFC in controlling pain perception by modulation of cortico-subcortical and cortico-cortical pathways [29]. In addition, several studies have highlighted the potential role of the DLPFC in placebo analgesia [30][31][32] and pain catastrophizing [33]. In a brain chemistry study of patients suffering from chronic back pain using in vivo single-voxel proton magnetic resonance spectroscopy ( 1 H-MRS), Grachev and colleagues [9] were able to demonstrate a depletion of N-acetyl aspartate and glucose within the DLPFC.…”

Section: Discussionmentioning

confidence: 99%

Brain structural and psychometric alterations in chronic low back pain

et al. 2013

View full text Add to dashboard Cite

Purpose Chronic low back pain (CLBP) is one of the most important pain disorders with increasing social and economic implications. Given that CLBP is a multidimensional process associated with comorbidities such as anxiety and depression, treatment of chronic low back pain is still a challenge. Advancement of in vivo brain imaging technologies has revealed increasing insights into the etiology and pathogenesis of chronic pain; however, the exact mechanisms of chronification of LBP remain still unclear. The purpose of the present study was to analyse the neurostructural alterations in CLBP and to evaluate the role of comorbidities and their neurostructural underpinnings.Methods In the present study we investigated a wellcharacterized group of 14 patients with CLBP and 14 healthy controls applying structural MRI and psychometric measures. Using an improved algorithm for brain normalization (DARTEL) we performed a voxel-based morphometry (VBM) approach. Correlation analyses were performed to evaluate the role of anxiety and depression in neurostructural alterations observed in CLBP. Results The psychometric measures revealed significantly higher scores on depression and anxiety in the patient population. VBM analysis showed significant decreases in grey matter density in areas associated with pain processing and modulation, i.e. the dorsolateral prefrontal cortex, the thalamus and the middle cingulate cortex. With respect to anxiety and depression scores, we did not observe any correlations to the structural data. Conclusions In the present study we found compelling evidence for alterations of grey matter architecture in CLBP in brain regions playing a major role in pain modulation and control. Our results fit the hypothesis of a ''brain signature'' in chronic pain conditions. The results of the psychometric assessment underline the importance of an interdisciplinary therapeutic approach including orthopedic, neurological and psychological evaluation and treatment.Keywords Chronic low back pain Á MRI Á Voxel based morphometry Á Dorsolateral prefrontal cortex Á Thalamus

show abstract

“…Recently, direct evidence has been supplied that fMRI responses related to painful heat stimulation can be reduced in the ipsilateral dorsal horn under placebo analgesia [28]. Also of note, permanent [29] or transitory [30] impairment of prefrontal cognitive functions results in the disruption of placebo analgesia.…”

Section: Three Neurotransmitters Have Been Identified In Placebo Analmentioning

confidence: 99%

Placebo mechanisms across different conditions: from the clinical setting to physical performance

Pollo

Carlino

Benedetti

2011

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

Although the great increase in interest in the placebo phenomenon was spurred by the clinical implications of its use, the progressive elucidation of the neurobiological and pharmacological mechanisms underlying the placebo effect also helps cast new light on the relationship between mind (and brain) and body, a topic of foremost philosophical importance but also a major medical issue in light of the complex interactions between the brain on the one hand and body functions on the other. While the concept of placebo can be a general one, with a broad definition generally applicable to many different contexts, the description of the cerebral processes called into action in specific situations can vary widely. In this paper, examples will be given where physiological or pathological conditions are altered following the administration of an inert substance or verbal instructions tailored to induce expectation of a change, and explanations will be offered with details on neurotransmitter changes and neural pathways activated. As an instance of how placebo effects can extend beyond the clinical setting, data in the physical performance domain and implications for sport competitions will also be presented and discussed.

show abstract

Prefrontal cortex modulates placebo analgesia

Cited by 300 publications

References 46 publications

Expectancy-Induced Placebo Analgesia in Children and the Role of Magical Thinking

Expectancy-Induced Placebo Analgesia in Children and the Role of Magical Thinking

Brain structural and psychometric alterations in chronic low back pain

Placebo mechanisms across different conditions: from the clinical setting to physical performance

Contact Info

Product

Resources

About