Cognitive and behavioral context of pain facilitation : Nocebo conditioning and uncontrollability-induced sensitization

Nocebo effects and uncontrollability are important psychological factors in pain facilitation and play a major role the context of acute and chronic pain. However, the precise mechanisms in both phenomena that lead to pain increase remain understudied. The general aim of the three studies contained in this thesis was to shed light on mechanisms of conditioning-induced nocebo effects and neuronal processes during uncontrollability-induced pain increase. For this purpose, experimental designs were employed that assessed the pain perception and its epiphenomena on multiple response channels (subjective verbal report, behavioral response, autonomic response, neuronal activity). In the first study, a conditioning procedure was developed without additional verbal suggestions or employment of cues that are prone to induce expectations of pain relief or worsening. The results indicated that conditioning can induce a subjective nocebo effect, even when subjects are contingency unaware (implicit conditioning). The decay of this conditioned response over time was observable in subjective as well as behavioral measures. Neither state nor trait anxiety or measures of anxiety specifically related to pain showed a correlation with this nocebo effect in the subjectively non-painful range. The second study adapted the conditioning procedure in order to induce nocebo-hyperalgesia. Further, the impact on autonomic measures was explored and relations between the nocebo response and personality traits were investigated. Nocebo-hyperalgesia as indicated by the subjective measure was successfully induced in part of the sample, independent from contingency awareness. Successfully conditioned subjects compared to non-successfully conditioned subjects showed to be habitually less anxious, received higher stimulus intensities despite comparable subjective sensation, and demonstrated increased heart rate and decreased HRV parameters. Motivational style and suggestibility were not related to the nocebo response. Study three investigated neural correlates of uncontrollability-induced pain increase. During controllable pain trials, subjects showed temporal summation, but adapted during controllable warm trials, as indicated by the behavioral measure. During the uncontrollable pain condition, subjective intensity ratings increased over the course of the individual trials, despite subjects received the identical nociceptive input that they had regulated to feel constant in the controllable condition. The additional pain increase in the pain trials, induced by uncontrollability, was mirrored in increased activation of pain processing brain regions, such as thalamus, insula, SII, and ACC. Importantly, activity in perigenual ACC and PAG drove the uncontrollability-induced pain increase. These results suggest that the loss of control leads to activation of a pro-nociceptive circuitry also assumed to play a role in placebo and nocebo effects that involve the pain modulatory regions PAG and pACC. In summary, these studies demonstrated a) the powerful impact of psychological factors, such as learning and uncontrollability, on pain perception, and b) proved the benefit of a multidimensional assessment of pain perception and its correlates. These results improve our understanding of pain facilitatory processes and have important implications for therapeutical interventions in pain conditions. They can further promote research in other fields, for example concerning the role of classical conditioning and neural processes in chronic pain

The underestimated significance of conditioning in placebo hypoalgesia and nocebo hyperalgesia

Placebo and nocebo effects are intriguing phenomena in pain perception with important implications for clinical research and practice because they can alleviate or increase pain. According to current theoretical accounts, these effects can be shaped by verbal suggestions, social observational learning, and classical conditioning and are necessarily mediated by explicit expectation. In this review, we focus on the contribution of conditioning in the induction of placebo hypoalgesia and nocebo hyperalgesia and present accumulating evidence that conditioning independent from explicit expectation can cause these effects. Especially studies using subliminal stimulus presentation and implicit conditioning (i.e., without contingency awareness) that bypass the development of explicit expectation suggest that conditioning without explicit expectation can lead to placebo and nocebo effects in pain perception. Because only few studies have investigated clinical samples, the picture seems less clear when it comes to patient populations with chronic pain. However, conditioning appears to be a promising means to optimize treatment. In order to get a better insight into the mechanisms of placebo and nocebo effects in pain and the possible benefits of conditioning compared to explicit expectation, future studies should carefully distinguish both methods of induction

Behavioral and electrodermal data on implicit nocebo conditioning using supraliminally presented visual stimuli

This article contains intensity and aversiveness ratings of electrical stimuli and data on electrodermal activity (skin conductance level and skin conductance response) during an implicit conditioning procedure. Further, answers from a questionnaire on contingency awareness are provided. The experiment consisted of three phases. In the acquisition, two types of visual stimuli (CS+ and CS-) were coupled to weakly and moderately painful electrical stimuli presented to the participants’ (N = 48) dominant hand. In the test phase, after both CS+ and CS- only the weakly painful electrical stimuli were presented. In the contingency test phase, no more electrical stimuli were presented and participants had the task to rate intensity and aversiveness as if an electrical stimulus had been presented. This phase served as a test for first-order contingency awareness. Afterwards participants filled in a questionnaire with five questions to assess their level of second-order contingency awareness. For more insight, please see Nocebo hyperalgesia induced by implicit conditioning (Bräscher and Witthöft, 2019)

The Underestimated Significance of Conditioning in Placebo Hypoalgesia and Nocebo Hyperalgesia

Placebo and nocebo effects are intriguing phenomena in pain perception with important implications for clinical research and practice because they can alleviate or increase pain. According to current theoretical accounts, these effects can be shaped by verbal suggestions, social observational learning, and classical conditioning and are necessarily mediated by explicit expectation. In this review, we focus on the contribution of conditioning in the induction of placebo hypoalgesia and nocebo hyperalgesia and present accumulating evidence that conditioning independent from explicit expectation can cause these effects. Especially studies using subliminal stimulus presentation and implicit conditioning (i.e., without contingency awareness) that bypass the development of explicit expectation suggest that conditioning without explicit expectation can lead to placebo and nocebo effects in pain perception. Because only few studies have investigated clinical samples, the picture seems less clear when it comes to patient populations with chronic pain. However, conditioning appears to be a promising means to optimize treatment. In order to get a better insight into the mechanisms of placebo and nocebo effects in pain and the possible benefits of conditioning compared to explicit expectation, future studies should carefully distinguish both methods of induction

The Measurement Quality of the Beck Depression-Inventory (BDI-II) in Different Clinical Samples: An Item Response Theory Analysis

Theoretischer Hintergrund: Das BDI-II ist ein Selbstbeurteilungsinstrument zur Erfassung des Schweregrads einer Depression. Es liegen kaum Analysen mit Modellen aus der Item-Response-Theorie (IRT) vor. Fragestellung: Wie hoch ist die Messgenauigkeit des BDI-II über die unterschiedlichen Ausprägungen des latenten Traits (Depressivität) hinweg und sind die Kategorien der Items jeweils aufsteigend geordnet? Methode: Anhand von sechs großen Datensätzen aus verschiedenen klinischen Bereichen wurden psychometrische Analysen mit dem Graded Response Model durchgeführt. Ergebnisse: In allen Stichproben fand sich eine hohe interne Konsistenz. Die Schwellenwerte waren mit Ausnahme von Item 6 („Bestrafungsgefühle“) geordnet. Gemäß Testinformationsfunktion misst das BDI-II im mittleren bis hohen Depressionsbereich sehr gut (Reliabilität > .90) und im unteren Bereich gut. Schlussfolgerung: Für das BDI-II ergibt sich eine hohe und relativ gleichbleibende Messpräzision über einen weiten Bereich des latenten Traits, weshalb es insbesondere im klinischen, aber auch im nicht klinisch relevanten Wertebereich zur Erhebung des Schweregrades einer Depression gut geeignet ist.Background: The Beck Depression Inventory (BDI-II) is a self-report instrument for assessing the severity of depression. To date, publications on psychometric properties based on item response theory (IRT) are largely missing. Objective: To determine how high the measurement precision is across the latent trait and whether the item categories are in ascending order. Methods: Using six large data sets from different clinical settings, we performed psychometric analyses using the graded response model. Results: We identified high internal consistencies in all samples. Apart from item 6 (“penalty feelings”), all categories were ordered. According to the Test Information Function, the BDI-II shows very good measurement precision (reliability > .90) in the moderate to high depression range, and good precision in the lower range. Conclusions: Our data revealed high and relatively stable measurement precision across a broad range of the depression construct. We consider the BDI-II to be well suited for assessing depression severity levels, particularly in clinical but also in nonclinical settings

Die Erfassung allgemeiner Wirkfaktoren in der Psychotherapie

<jats:p> Zusammenfassung: Theoretischer Hintergrund. Stundenbögen dienen einer standardisierten Prozessdiagnostik und Verlaufsdokumentation. Bislang vorliegende Instrumente werden in der Praxis häufig nicht eingesetzt, haben einen eingeschränkten Geltungsraum oder weisen psychometrische Schwächen auf. Der Mainzer Stundenbeurteilungsbogen (MSB) versucht allgemeine Wirkfaktoren ökonomisch zu erfassen. Ziel der Studie ist die Untersuchung des MSB in der Patienten- und Therapeutenversion hinsichtlich Faktorenstruktur, Itemstatistiken und Gütekriterien. Methoden: Der MSB wurde zu zwei Zeitpunkten (5. und 20. therapeutische Sitzung) in einer Stichprobe ambulanter Psychotherapiepatienten ( N = 4.608, N = 3.909) und deren Therapeuten ( N = 4.650 und N = 3.980 Bögen) untersucht. Die Faktorenstruktur wurde mittels explorativer und konfirmatorischer Faktorenanalysen untersucht und es wurden Reliabilitäts- und Validitätsanalysen vorgenommen. Ergebnisse: Ein Bifaktorenmodell mit drei Faktoren spiegelte weitgehend die theoretisch postulierte Struktur mit den Subskalen Therapiebeziehung, Problemaktualisierung und Problembewältigung wider, bei moderatem Modellfit. Maße der diskriminanten, konvergenten und prädiktiven Validität fielen zufriedenstellend aus. Diskussion: Der MSB ist ein reliables, valides und ökonomisches Instrument zu Erfassung der allgemeinen Wirkfaktoren Therapiebeziehung, Problembewältigung und Problemaktualisierung aus Patienten- und Therapeutensicht. </jats:p&gt

Differential Classical Conditioning of the Nocebo Effect: Increasing Heat-Pain Perception without Verbal Suggestions

Background: Nocebo effects, including nocebo hyperalgesia, are a common phenomenon in clinical routine with manifold negative consequences. Both explicit expectations and learning by conditioning are known to induce nocebo effects, but the specific role of conditioning remains unclear, because conditioning is rarely implemented independent of verbal suggestions. Further, although pain is a multidimensional phenomenon, nocebo effects are usually assessed in subjective ratings only, neglecting, e.g., behavioral aspects. The aim of this study was to test whether nocebo hyperalgesia can be learned by conditioning without explicit expectations, to assess nocebo effects in different response channels, and to exploratively assess, whether contingency awareness is a necessary condition for conditioned nocebo hyperalgesia.Methods: Twenty-one healthy volunteers were classically conditioned using painful and non-painful heat stimuli that followed two different cues. The conditioned nocebo effect was assessed by subjective ratings of perceived stimulation intensity on a visual analog scale and a behavioral discrimination task, assessing sensitization and habituation in response to the same stimulation following the two cues.Results: Results show a conditioned nocebo effect indicated by the subjective intensity ratings. Conditioned effects were also seen in the behavioral responses, but paradoxically, behavioral responses indicated decreased perception after conditioning, but only for subjects successfully conditioned as indicated by the subjective ratings. Explorative analyses suggested that awareness of the contingencies and the different cues was not necessary for successful conditioning.Conclusion: Nocebo effects can be learned without inducing additional explicit expectations. The dissociation between the two response channels, possibly representing the conditioned and a compensatory response, highlights the importance of considering different outcomes in nocebo responses to fully understand underlying mechanisms. The present results challenge the role of explicit expectations in conditioned nocebo effects and are relevant with implications in clinical contexts, e.g., when transient adverse effects become conditioned