Three muscle tensing tasks are used during the experiment: Tighten stomach task (S), tension the neck task (N), and safe comparison task: clenching the fist (F).
In the S condition, participants are instructed to tense their abdominal muscles for 60 seconds (respective muscle: musculus rectus abdominis). In the N condition, participants are instructed to tense their neck for 60 seconds (respective muscle: musculus trapezius). If participants have difficulties to tense their neck muscles, they are instructed to press their head against the backrest of their chair. Care is taken to ensure that the adolescents could continue to look on the screen, and electrodes do not receive any pressure. In the F condition, participants are asked to clench their fist of their dominant hand for 60 seconds (respective muscle: musculus brachioradialis).
Each trial consists of 4 phases: anticipation, exposure, recovery, and rating (Fig. 1). In the anticipation phase (90 seconds), a task-specific screen background colour (eg, green) is presented with instructions that the stomach/neck/fist tensing task will start shortly. In the exposure phase (60 seconds), participants are shown the same screen colour with instructions to tense the respective muscle groups. The recovery phase is indicated by a black screen with white text indicating a “Recovery” phase (60 seconds). After these 3 phases, participants are asked to draw a curve representing their fear during the 3 phases and rate their urge to avoid and leave the situation. Each trial ends with an intertrial interval of 3 to 9 seconds (Fig. 1).
The anticipation phase is accompanied by 5 startle probes. The first startle probe is delivered 5 or 15 seconds after the anticipation onset. The interval between 2 startle probes lasts for 10, 20, or 30 seconds (counterbalanced). The exposure phase is accompanied by 3 startle probes. The first startle probe is delivered at 5, 15, or 25 seconds after the exposure onset, and the interval between 2 startle probes lasts for 10, 20, or 30 seconds (counterbalanced). The recovery phase is also accompanied by 3 startle probes. The first startle probe is delivered 5, 15, or 25 seconds after the recovery onset, and the interval between 2 startle probes lasts for 10, 20, or 30 seconds (counterbalanced).
The trials are presented in one of the following different orders: (1) S F N F N S N S F, (2) N S F S F N F N S, and (3) F N S N S F S F N. The provocation paradigm lasts approximately 35 minutes (Fig. 2). Participants are instructed to perform the 3 muscle tensing tasks before the experiment (eg, “please tense your abdominal muscles now, so that we can check the signal”) and to practice the exercises while breathing naturally. The experiment is started only after the study investigator confirms appropriate EMG signals during these tasks.
Three different scripts with a length of approximately 20 words are used in each imagery condition: pain-specific imagery (P), fear imagery (F), and neutral imagery (N). Two of the aversive fear imagery scripts are based on previously published scripts.13 Scripts in the “pain-specific imagery” condition are individualized for each participant using a newly developed sensation questionnaire. Participants are asked about the frequency of different sensations in the pain area preceding pain episodes (or pain increases) and rate the unpleasantness and mark the location of the 3 most unpleasant sensations thereafter. “Standard” pain-specific aversive scripts (eg, “I feel a slight tension in the middle of my stomach. I can also feel a prickling in the middle of my stomach.”) are adapted by substituting the body sensation and location in the second sentence in each script with one of the individualized (unpleasant) sensations and associated locations. Thus, in the aforementioned “standardized” script, “prickling sensation” and “middle of my stomach” might be substituted with “tension” and “upper abdomen.”
After receiving detailed instructions, participants rate the emotional valence and arousal levels of each script using a computerized version of the Self-Assessment Manikin.7 Endpoints of valence and arousal ratings are specified according to previously published studies in children.34 Thereafter, instructions are presented to participants, including situations of being absorbed in everyday situations. Participants are instructed to imagine the situations/sensations described in the scripts vividly (as if they would really engage in them). They are instructed to imagine the situations with open eyes. The imagery trials begin with a test trial in which an additional script is presented. Each script is presented twice in a counterbalanced fashion, totalling 19 trials. All trials consist of a baseline (6, 7, or 8 seconds), a reading (12 seconds), an imagery (12 seconds), and a postimagery phase (23, 24, or 25 seconds). In 50% of the trials, startle probes are delivered at 2 time points during the imagery phase, one at second 3, 4, or 5 and another one at second 9, 10, or 11. In approx. 25% (4 of 18) of trials, one startle probe is delivered at second 3, 4, or 5, and in another approx. 25% (5 of 18) of trials, one startle probe is delivered at second 9, 10, or 11 of the imagery phase. One startle probe is delivered in 50% of the postimagery phases at second 13, 14, or 15 (Fig. 2). Scripts are presented at the end of the trials once again, and participants rate the scripts on 5 domains (vividness of imagery, fear, fear of pain, desire to avoid the situation, and pain). The imagery paradigm lasts approximately 22 minutes.
2.7.1. Provocation paradigm
A previous pilot study in adolescents with CH or CAP has already tested whether the provocation of internal bodily sensations results in increases in self-reported fear.19 Flack et al. showed that the perception of proximal interoceptive sensations appears to activate the fear system (measured by self-report) in adolescence with CAP. Adolescents with CH did not report higher fear or avoidance ratings. According to Flack et al., this effect may possibly be explained by the choice of the frown task. The corrugator supercilii muscle is used in everyday communication processes and is thus also activated during different emotional states. Frowning may have not elicited locally proximal interoceptive sensations in adolescents with chronic pain.
Based on these pilot results, various adjustments were made. The frowning task (contracting the corrugator supercilii muscle) was replaced by the “tensing the neck” task. In addition, self-report ratings were extended with psychophysiology measures (EMG, electrodermal activity, and ECG)—in particular, the assessment of fear-induced startle potentiation as an indicator of defence response mobilization. In addition, the following minor adjustments were made: The length of each phase was optimized (extension of the anticipation phase from 3 to 90 seconds and reduction of the provocation phase from 180 to 60 seconds). To ensure the validity of the paradigm, we added an additional question (“How similar were your physical sensations during the exercise to those that you usually feel before the pain?”) and an additional task (marking body locations, where participants have felt sensations during the provocation phase). Also, self-report measures were extended (eg, fear curve).
2.7.2. Imagery paradigm
The sensation questionnaire, imagery scripts, and recruitment strategies were tested in a pilot study, including 14 adolescents (age: mean [M] = 13.8, SD = 2.4) with CH or CAP recruited from the community and 20 HCs aged 11 to 18 years (age: mean [M] = 14.2, SD = 2.24). Pain was considered chronic if it was experienced at least once per week during the past 3 months. Results of our pilot study showed markedly higher self-reported avoidance ratings in adolescents with CAP (N = 8) and adolescents with CH (N = 6) compared to HCs (N = 20) during the imagery of interoceptive sensations at the pain location.
Several aspects of the imagery paradigm were adapted: We replaced one neutral imagery script, which showed differing valence ratings. Instructions are now read aloud by the study investigator (instead of including recorded audios in the experiment) to make sure that all participants feel comfortable to ensure high-quality psychophysiological data. One participant reported imagining the scripts during the reading phase and ruminating about her ratings during the imagery phase. Therefore, participants are instructed explicitly not to imagine the situation while reading the scripts but only during the imagery phase. We have also moved self-report ratings to the end of the trial to prevent this kind of behaviour. Many participants had difficulties to list 6 interoceptive sensations preceding pain episodes. Therefore, only the second sentence of each script is individualized to ensure that study participants have to list only 3 sensations preceding pain episodes.
22.214.171.124. A priori calculated sample size
Our analysis is based on our primary hypothesis that interoceptive stimuli proximal to the main pain will elicit greater defence response mobilization than distal stimuli in adolescents with chronic pain compared to healthy children using startle magnitude as the primary outcome. Previous studies in adults comparing startle magnitude during interoceptive threat between healthy adults high and low in anxiety sensitivity found small to medium effect sizes (eg, Ref. 36 [eta-squared = 0.106]). The stability of the emotion-modulated startle response has been shown to be high with correlations between measurements of r = 0.5.30 We based our sample size calculation on study results from adults. Given that increased startle overall magnitude has previously been reported during adolescence,40 this results in a conservative estimate of the requested sample size. At an alpha level of 0.05, the sample size of 33 per group (total sample size = 99) is suitable to detect the within–between interaction effect (moderate size, f = 0.145) with a power of 0.80.17 Taking a dropout of approx. 20% (although we observed a smaller dropout of 10% in previous studies25), results in a sample size of 40 per group (total sample size = 120).
2.8. Data analysis
2.8.1. Data reduction
Startle amplitude will be calculated by subtracting the mean baseline activity preceding the startle probe (−20 to 0 ms) from the peak muscle potential in the latency window of 31 to 150 ms. Startle responses, which are considered outliers (3 SDs from the mean), responses with eyeblink artefacts, excessive baseline activity, or other contaminations41 will be replaced by the average startle amplitude in the respective condition. Responses smaller than 2 × max amplitude preceding startle probe delivery (−20 to 0 ms) are classified as nonresponses and replaced with 0. Finally, the startle data will then be standardized (z score).23 Heart beat intervals, also referred to as RR intervals (intervals between peaks of QRS complex), and SCL will be reduced into 2-second bins. Changes in HR and SCL are determined by subtracting RR intervals and SCL during 2 seconds at the beginning of the anticipation phase (provocation) or before script presentation (imagery) from subsequent 2-second bins. Startle Z scores, changes in HR and SCL will be averaged for the anticipation, provocation, and recovery phase (provocation) and the imagery and postimagery phase (imagery) of each condition for use in inferential statistics. To determine resting high-frequency HR variability (HF-HRV) during the 5-minute resting phase at the end of the study, continuous RR-series will be dissected in 60-second bins (50% overlap), linearly detrended, and processed through an end-tapered Hamming window. The segments will then be subjected to fast Fourier transform, and HF-HRV will be calculated based on the log mean power (ms2) within the high-frequency band (HF-HRV; 0.15–0.40 Hz).
2.8.2. Data analysis plan for the provocation paradigm
To test the hypothesis that the provocation of sensations proximal to the main pain elicits a defensive response, repeated-measures ANOVAs will be conducted separately for each physiologic measure (ie, startle magnitude, HR, and SCL) including group (CAP, CH, and HCs) as a between-subjects factor and type of provocation task (ie, tighten stomach, neck task, and neutral task) as within-subjects factor.
2.8.3. Data analysis plan for the imagery paradigm
To test the hypothesis that the imagery of sensations proximal to the main pain location elicits a defensive response, repeated-measures ANOVAs will be conducted separately for each physiologic measure including group as a between-subjects factor and type of imagery script (pain-specific/fear/neutral imagery) as within-subjects factor.
We have described 2 paradigms for investigating defence response mobilization in children with chronic pain during anticipation, exposure, and imagery of interoceptive sensations locally proximal to the main pain region. Based on models of interoceptive fear conditioning, we expect locally proximal interoceptive sensations in both paradigms (ie, experienced and imagined interoceptive sensations) to elicit a mobilization of defence responses in adolescents with chronic pain. Defence response mobilization is examined using a multimodal assessment including measures of startle modulation, changes in HR, and SCL, as well as by self-reported fear. Results based on individualized pain-specific aversive imagery scripts might inform the development of standardized individualized imagery-based exposure treatments.
Thus far, only 4 studies have investigated interoceptive exposure in children and adolescents with mixed but generally promising results.1,20,25,49 These studies vary, however, considerably in the form of interoceptive exposure, the symptom provocation tasks used, the implementation of imagery-based tasks, the age of the children and adolescents, the study design, the outcome variables, and apparently, the study results. Two studies implemented symptom provocation tasks2,49 ranging from spinning while standing, a task from the audiovestibular domain, to running down the hall with a belt fastened around the belly, a disorder-specific task. Two studies used mental imagery in the form of imagining increases in pain intensity during exposure sessions.20,25 We are not aware of any systematic experimental work in adolescents with CH or abdominal pain, which incorporates psychophysiological measures to examine defence response mobilization after symptom provocation or imagery-based tasks. Thus, the 2 paradigms have the potential to close this research gap. Our research will therefore have important implications for future research and clinical practice. First, interoceptive exposure treatments may be optimized by incorporating specific tasks that are able to elicit a comprehensive fear response into interoceptive exposure treatment in adolescents with chronic pain. These tasks may either constitute symptom provocation tasks or imagery-based tasks. Second, a comparison of the 2 forms of interoceptive exposure—symptom provocation and imagery-based—may be warranted to reveal which form of exposure leads to significant reductions in key variables. Third, our research might point to possible mechanisms of change during interoceptive exposure treatments, particularly regarding psychophysiological measures. Thus, it might be possible that these treatments decrease fear of pain by desensitizing defensive networks.
Some limitations of the paradigms and the study design should be considered. Observations during our ongoing study have revealed that some adolescents have difficulties to differentiate between uncomfortable innocuous stimuli (eg, pressure sensation) and pain in the imagery paradigm. From a predictive coding perspective, ambiguous or noisy sensations can be considered painful, based on top-down expectations and previous experience.9,26 Thus, it may be difficult for adolescents to discriminate painful from nonpainful stimuli consistently. Some studies showed that associative fear learning influences perceptual discrimination,47,48 and that patients with chronic pain display a deficit in discrimination of muscle tension.21 On the other hand, not only innocuous stimuli but also mild pain may become a CS, which predicts more intense pain (US), analogue to mild sensations (CS) predicting sensations with a higher threat value (eg, hyperventilation; US), in panic disorder.6,24 Furthermore, given that previous research provided some evidence for different self-reported fear responses in adolescents with CH and adolescents with CAP,19 our project might shed light on disorder-specific patterns in defence responses when confronted with proximal interoceptive sensations.
We have proposed 2 paradigms—provocation and imagery, which will shed light on the defence response of adolescents with CH and abdominal pain, when confronted with or imagining interoceptive sensations locally proximal to their main pain. Data based on our paradigms might be useful for improving existing or developing new treatments to decrease fear of bodily sensations in adolescents with CH and abdominal pain, such as interoceptive exposure or interoceptive imagery exposure.
The authors have no conflict of interest to declare.
The authors thank Lena Jansen, Kim Opdensteinen, and Julia Müller for supporting our pilot project. The German Research Foundation (DFG) funded the research project (HE 5942/4-1 and SCHN 415/5-1).
Author contributions: P. Gruszka and L. Schaan were responsible for drafting, writing and revising the paper, and conception of figures. D. Adolph, C. Benke, and C.A. Pané-Farré were responsible for revising the paper. S. Schneider was responsible for the design and conception of the paper and revising the paper. T. Hechler was the principal investigator and responsible for the design and conception of the paper, supervision of the paper and the involved steps, revision of the drafts of the paper, and the final version of the paper.
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Keywords:© 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.
Pediatric; Chronic pain; Abdominal pain; Headache; Conditioning; Anticipation; Provocation; Imagery