w w w . e l s e v i e r . c o m / l o c a t e / p a i n

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The effect of distraction strategies on pain perception and the nociceptiveflexor reflex (RIII reflex)

Ruth Ruscheweyh a,b,⇑, Annette Kreusch a, Christoph Albers a, Jens Sommer c, Martin Marziniak a

a Department of Neurology, University of Münster, Münster, Germanyb Department of Neurology, University of Munich, Munich, Germanyc Department of Psychiatry, University of Marburg, Marburg, Germany

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

a r t i c l e i n f o

Article history:Received 3 March 2011Received in revised form 21 July 2011Accepted 16 August 2011

Keywords:DistractionSpinal nociceptionNociceptive flexor reflexMusicMental imageryTemporal summation

0304-3959/$36.00 � 2011 International Associationdoi:10.1016/j.pain.2011.08.016

⇑ Corresponding author. Address: Department oMunich, Marchionini-Str. 15, 81377 München, Germa

E-mail addresses: ruth.ruscheweyh@med.uni-muh@uni-muenster.de (R. Ruscheweyh).

a b s t r a c t

Distraction from pain reduces pain perception, and imaging studies have suggested that this may at leastpartially be mediated by activation of descending pain inhibitory systems. Here, we used the nociceptiveflexor reflex (RIII reflex) to directly quantify the effects of different distraction strategies on basal spinalnociception and its temporal summation. Twenty-seven healthy subjects participated in 3 distractiontasks (mental imagery, listening to preferred music, spatial discrimination of brush stimuli) and, in afourth task, concentrated on the painful stimulus. Results show that all 3 distraction tasks reduced painperception, but only the brush task also reduced the RIII reflex. The concentration-on-pain task increasedboth pain perception and the RIII reflex. The extent of temporal summation of pain perception and theextent of temporal summation of the RIII reflex were not affected by any of the tasks. These results sug-gest that some, but not all, forms of pain reduction by distraction rely on descending pain inhibition. Inaddition, pain reduction by distraction seems to preferentially affect mechanisms of basal nociceptivetransmission, not of temporal summation.

� 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

1. Introduction

Pain is subject to modulation by a variety of cognitive processes,including attention [6,56,63]. Both psychophysical and clinicalstudies have demonstrated that distraction from pain reduces painperception [4,30,35,39,40,57,59]. In contrast, increased attention topain, for example, in the form of hypervigilance to pain in chronicpain patients, is associated with increased pain perception[28,31,33,45].

Reduction of pain perception by distraction demonstrates theactivation of endogenous pain-inhibitory systems that may include(1) systems with a purely supraspinal action and (2) descendingpain inhibitory systems that modulate nociceptive transmissionat the spinal cord level [6,21,56,64]. The relative contribution ofthese 2 systems to pain modulation by distraction in humans iscurrently unknown. In monkeys, nociceptive responses of dorsalhorn neurons are increased when attention is directed towardsthe stimulus [9], suggesting involvement of descending systems.Imaging studies in humans have shown that distraction from pain

for the Study of Pain. Published by

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activates structures known to be at the origin of descending inhib-itory systems such as parts of the prefrontal cortex, the rostralanterior cingulate cortex, and the periaqueductal gray [4,57,59].Therefore, it has been proposed that distraction may act at leastpartly via activation of descending inhibitory systems [6,56,63].

Direct proof of this hypothesis requires quantification of spinalnociceptive activity. The nociceptive spinal flexion reflex (RIII re-flex) is one of the few currently available tools for quantificationof spinal nociception in humans [47,50]. Previous studies haveused the RIII reflex to investigate the effect of distraction by cogni-tive tasks, with conflicting results [15,17,54,66]. However, increas-ing cognitive load is only one of several strategies that may be usedto divert attention from pain. It is not currently known if simplecoping strategies used by pain patients to distract themselves frompain, such as engaging in mental imagery or listening to one’s pre-ferred music [8,22], activate descending inhibitory pathways. Sim-ilarly, it has not been determined if descending inhibition isengaged by intensely focusing on a nonpainful somatosensorystimulus.

Temporal summation of the RIII reflex and the concomitant painperception evoked by repetitive stimulation (1–3 Hz) [3,24] sharesproperties with the ‘‘wind-up’’ of nociceptive responses seen in ro-dent spinal dorsal horn neurons following repetitive afferent stim-ulation [26]. While temporal summation of the RIII reflex and

Elsevier B.V. All rights reserved.

Fig. 1. Outline of experimental procedures. Each participant attended 3 sessions on3 separate days. Each recording consisted of 5 blocks, as displayed in the lower partof the Figure. During blocks 2 and 4 of each recording, subjects performed 2different tasks (a ‘‘task set’’). Each task set consisted of the concentration-on-paintask and one of the 3 distraction tasks, resulting in 3 different task sets (task sets A–C). Order of task sets and order of tasks within sets were randomized. After task setC in session 3, an additional task set not directly related to distraction wasperformed that will be reported separately (not displayed).

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wind-up are N-methyl-D-aspartate (NMDA)-receptor-dependent[3,24,26], responses to single nociceptive stimuli are predomi-nantly mediated by a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate-receptor-dependent mechanisms[67]. Separate assessment of responses to single and repetitivenociceptive stimuli may therefore, within certain limits becauseof interactions between the 2 receptor systems, allow estimationof the effects of distraction on AMPA/kainate- and NMDA-recep-tor-dependent mechanisms of nociception, respectively.

Here, we investigated the effect of the 3 distraction strategiesoutlined above (mental imagery, listening to preferred music, spatialdiscrimination of brush stimuli) and the effect of concentrating onthe painful stimulus on (1) basal pain ratings and RIII reflexes and(2) the temporal summation of both parameters in healthy subjects.

2. Methods

2.1. Participants

The study was conducted in accordance with the Declaration ofHelsinki and was approved by the local ethics committee of theUniversity of Münster. Prior to participation, subjects gave writteninformed consent. Twenty-seven participants (age 24.4 ± 3.4 years,14 females) were recruited by advertisements on the universitycampus. Participants had to meet the following criteria: (1) age be-tween 18 and 40 years; (2) sufficient knowledge of the Germanlanguage; (3) no neurological, internal, or psychiatric conditions;(4) no intake of medication other than oral contraceptives; (5) nochronic or frequent pain conditions (mild day-to-day pain on <5 -days/month was allowed; self-report of pain complaints was as-sessed using a modified version of the official German PainQuestionnaire, issued by the German chapter of the InternationalAssociation for the Study of Pain [www.dgss.org]); and (6) no nic-otine, alcohol, or drug abuse. Subjects’ scores in the Beck Depres-sion Inventory (BDI [5]), the State-Trait Anxiety Inventory (STAI[51]) and the Pain Catastrophizing Scale (PCS [34,53]) were withinnormal limits (BDI 3.1 ± 3.2, STAI-Trait 32.6 ± 5.7, STAI-State32.9 ± 5.5, PCS 14.9 ± 8.8). On days of assessment, participantswere free of acute pain and had not taken analgesics within thepreceding 24 hours.

Each subject attended 3 experimental sessions on 3 days within2 weeks, with procedures as outlined in Fig. 1.

2.2. Recording and quantification of the RIII reflex

The RIII reflex was evoked and recorded from the lower limbaccording to previously described techniques (eg, [2,7,65]). Duringrecording, the subject sat comfortably in a reclining chair with legrests adjusted so that the knee of the recorded leg was flexed at�150�. Stimulation and recording was performed with a KeypointPortable EMG System (Medtronic, Alpine Biomed, Langefeld, Ger-many). Stimulation and recording sites were prepared by degreas-ing and lightly abrading the overlying skin. Electrical constantcurrent stimulation was delivered to the retromalleolar pathwayof the sural nerve with a bipolar bar electrode (distance betweenelectrodes 23 mm, Alpine Biomed). Each stimulus consisted of 5pulses of 1-ms duration, separated by 4 ms, resulting in a totalduration of 21 ms. Electromyographic responses were recordedfrom the ipsilateral biceps femoris (short head) via a pair of Ag/AgCl surface electrodes placed 4–5 cm apart over the muscle belly.Signals were amplified (up to 10,000 times) and band-pass filtered(20–3000 Hz). The segment between 60 ms before stimulation and440 ms after stimulation was displayed on the screen, digitized(24 kHz), and stored for offline analysis. The RIII reflex was identi-fied as a polyphasic muscle response appearing with an onset la-tency between 90 and 130 ms after onset of stimulation.

For quantification of the RIII reflex response, the reflex area wasobtained by integrating the rectified signal within a 50-ms analysiswindow starting between 90 and 120 ms after stimulation(mean ± SD: 103 ± 6 ms). The analysis window was positioned toinclude the RIII reflex while avoiding contamination by the nonn-ociceptive RII reflex and was kept constant throughout all record-ings taken from a given subject on the same day. Previous studieshave mostly used 40- to 100-ms wide analysis windows with afixed position (ie, the same for all subjects), starting at 80–100 ms after stimulation and ending at 130–200 ms after stimula-tion [2,7,38,42,49]. However, RIII onset latencies vary between 90and 130 ms after stimulation [65] and RII onset latencies vary be-tween 40 and 80 ms [13,65,66]. In our experience, an RIII reflex re-corded at 120–140% threshold intensity is usually not wider than50 ms, but may be preceded by an RII reflex extending beyond100 ms after stimulation. A flexible analysis window thus allowsthe analysis to be centered over the RIII reflex while avoiding con-tamination by the RII reflex (see Fig. 2A for an example). RII re-flexes were identified by onset latencies <80 ms and low

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stimulation thresholds with respect to pain and RIII thresholds. Inaddition, the RII reflex often (but not always) exhibited an oligo-phasic, monomorphic aspect, albeit with large variations in size,including failures, while the typical RIII reflex was polyphasic, lessconstant in shape, but more constant in size (see Fig. 2A for anexample). As compared to previous studies not reporting the needof adapting analysis windows (eg, [2,7,38,42,49]), or excluding databecause of overlap between RII and RIII reflexes (see Section 2.7),the incidence of RII reflexes seems to have been high in the presentstudy, possibly because we used a preparatory session and theexperimental design required long recording sessions. The RII re-flex has been reported to be present more regularly when subjectsget used to the experimental procedures [65].

2.3. Thresholds and stimulus–response curves

Stimulus–response curves were recorded by increasing stimula-tion intensity in 0.5-mA steps starting from 0.5 mA. Participantsrated the pain intensity of each stimulus on an 11-point numericalrating scale (NRS) from 0 (no pain) to 10 (strongest possible pain).The RIII threshold was defined as the stimulus intensity that firstevoked a reflex response exceeding an area of 100 lV ms. The painthreshold was determined as the stimulus intensity that firstevoked a painful sensation. Three consecutive RIII and pain thresh-olds were determined at the beginning and at the end of eachexperimental session and averaged. On each study day, one ofthe stimulus–response curves recorded at the beginning of theexperimental session was continued up to pain tolerance (Fig. 2Band C).

Previous studies have determined RIII thresholds either usingabsolute reflex size thresholds [3,37] or requiring reflex activityto exceed a confidence interval around the respective prestimulusbaseline activity [10,42]. Here, we opted for an absolute RIIIthreshold because this makes the RIII threshold independent fromthe baseline noise encountered during a specific recording. In ourhands, baseline areas (obtained by integrating the rectified signalbetween 100 and 150 ms after ‘‘stimulation’’ with 0 mA) were

Fig. 2. Analysis of RIII areas and stimulus response curves. (A) Analysis of RIII areas. Rwindow starting between 90 and 120 ms after stimulation, positioned to include the RIII rshows an example of 10 consecutive reflexes recorded during the baseline phase of a basrecording. The reflex consisted of 2 components, classified as RII and RIII components,thresholds (4.5 mA vs. 8 mA). Pain threshold was 7 mA. A standard analysis window of 90have significantly been contaminated by the inconstantly present RII reflex while exclu164 ms (shaded region). Bars, 200 lV, 50 ms. (B and C) Stimulus response curves. (Brepresentative subject are shown. Artifacts are truncated. The shaded region correspondsthe individual largest RIII reflex area recorded during ascending stimulation before tolerthe respective reflex threshold (absolute stimulation intensity minus reflex threshold).

42 ± 10 lV ms in session 1, 40 ± 8 lV ms in session 2, and39 ± 8 lV ms in session 3, with an overall range from 23 to66 lV ms. Based on these results, 100 lV ms was chosen as the re-flex threshold. Fig. 2C corroborates validity of this threshold, show-ing that it represented the turning point of the stimulus responsecurve.

2.4. Experimental protocol and analysis: basal RIII area and painperception

A stimulus intensity around 130% of the reflex threshold waschosen that reliably evoked reflexes of sufficient magnitude andwas well tolerated by the subject for the duration of the experi-ment. Pain intensity evoked by this stimulus intensity was3.5 ± 1.0 on the NRS. Test stimuli were delivered at 6-secondsintervals. As illustrated in Fig. 1, each recording consisted of 5 con-secutive 2-minutes blocks (20 stimuli per block). Blocks 1, 3, and 5were ‘‘no-task’’ baseline blocks and blocks 2 and 4 were taskblocks. One of the tasks was a distraction task, while the other con-sisted of concentrating on the pain evoked by sural nerve stimula-tion, in randomized order. Pain intensity ratings on the NRS werecollected at the end of each block. Subjects were instructed to pro-vide an average rating of the preceding 5 stimuli. At the end of eachrecording, subjects provided a rating of how much the tasks hadshifted their focus of attention away from pain or towards pain(on a scale from �5 to 5, with 0 indicating no shift of attentioncompared to the preceding baseline block and �5 and 5 indicatingthe strongest shift of attention away from pain or towards painimaginable, respectively). The currently used single-item shift ofattention rating is not a previously validated measure and has tobe interpreted with due caution. We adopted this approach be-cause single-item measures are easy to use even in complex exper-imental designs, and have recently demonstrated good reliabilityand validity [14,69]. Heart rate was continuously recorded usinga standard heart rate monitor that analyzes electrocardiographicsignals obtained via chest belt electrodes (Topline, Sigma Elektro,Neustadt/Weinstraße, Germany) and has been shown to deliver

III areas were obtained by integrating the rectified signal within a 50-ms analysiseflex while avoiding contamination by the nonnociceptive RII reflex. The illustrational RIII recording experiment and the overlay of all 100 reflexes obtained during theaccording to their onset latencies (73 ms vs. 114 ms after stimulation onset) and–150 ms (eg, [42], indicated by a bar below the overlay) or even 100–150 ms would

ding parts of the RIII reflex. The analysis window was therefore positioned at 114–) Original RIII reflexes during recording of the stimulus–response curve from ato the analysis window. Bars: 50 lV, 50 ms. (C) Reflex areas are given in percent of

ance was reached. The horizontal axis represents stimulation intensities relative toError bars are SEM.

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exact and robust measurements of heart rate (http://www.sigma-sport.com/en/produkte/pulscomputer/?gesamt=1&position=1).Heart rate readings were taken at the end of each block.

For analysis, RIII areas were calculated as described above andaveraged in blocks of 5 consecutive reflexes, resulting in 4 averagereflex size values per block that were used for analysis of baselinestability (see Section 2.7.) and for illustration (Fig. 3). Task effectswere quantified by expressing the pain rating or average RIII areawithin the task block in percent of the pain rating or average RIIIarea in the corresponding pretask block.

2.5. Experimental protocol and analysis: temporal summation of RIIIarea and pain perception

For temporal summation experiments, stimulus intensity wasreduced to around 120% of the reflex threshold so that temporalsummation of pain was well tolerated by the subjects. First, a sin-gle stimulus was given and the corresponding pain intensity ratingobtained. Ten seconds later, a train of 10 stimuli at 1 Hz was given,and the pain rating corresponding to the last stimulus of the trainwas obtained. Each experimental block lasted for approximately2 minutes and consisted of 3 consecutive single stimulations andtrains, separated by 30 seconds. The remaining experimental de-

Fig. 3. Task effects on the basal RIII reflex. Illustration of the mean task effects on the Rpretask RIII area is indicated by a dotted line. Error bars are SEM. Above each graph, repThe shaded region corresponds to the analysis window. Bars, A: 50 lV, 25 ms, (C–D) 25

sign was equivalent to that described above. Heart rates werenot recorded during temporal summation experiments.

The extent of temporal summation of the RIII within a givenblock was quantified by calculating the ratio between the averagereflex area evoked by stimuli 4–10 of the train and the average re-flex area evoked by stimulus 1 of the train and the single stimuluspreceding the train. The extent of temporal summation of pain per-ception within a given block was quantified by calculating the ratiobetween the average pain rating of the 10th stimulus of the trainand the single stimulus preceding the train.

2.6. Distraction and concentration tasks

At the end of session 1, subjects were briefed on the differenttasks scheduled for sessions 2 and 3 and received a written memofor reference. Before each experiment, subjects received detailedinstructions regarding the respective tasks. Care was taken not tocreate expectations with respect to an effect on pain intensity orthe direction of such an effect. Each task lasted for 2 minutes.

2.6.1. Mental imagery taskDuring the briefing in session 1, subjects were asked to use the

time before the next session to choose a pleasant experience they

III area. Each symbol represents the average of 5 consecutive reflexes. The averageresentative examples of original traces before, during, and after the task are shown.lV, 25 ms.

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would be able to vividly recall with visual, auditory, and somato-sensory details. During the experiment, subjects closed their eyesand engaged in the task for 2 minutes.

2.6.2. Music taskSubjects were instructed to bring a short piece of preferred mu-

sic. During the experiment, the first 2 minutes of this piece wereplayed to the subject over headphones.

2.6.3. Brush taskThe experimenter touched the fingers of the subject’s hand

(contralateral to sural nerve stimulation) with a soft brush whilethe subject looked in a different direction. Touch stimuli were pre-sented to each of the 5 fingers in an irregular pattern and at anirregular frequency, amounting to a total of about 60–80 stimuliduring the 2-minutes duration. The subject was instructed to countthose stimuli touching the middle and the index finger and presentthe result at the end of the task.

2.6.4. Concentration-on-pain taskSubjects were instructed to concentrate on the unpleasantness

of the painful sural nerve stimulation used to elicit the RIII reflex.The mental imagery and music tasks were chosen because they

represent frequently used everyday coping strategies for pain[8,22,58]. Listening to music, especially one’s preferred music,has been shown before to reduce both clinical and experimentalpain perception [36,62,68]. The generation of pleasant and engag-ing mental images, either evoked by the patient himself or with thehelp of a therapist or a professional audiotape, is often called (self-)guided imagery, and has successfully been used in the treatmentof clinical pain [25,32,58]. The brush task was chosen because wehad the feeling that intensely focusing attention on a heterotopicnonpainful somatosensory input during a spatial somatosensorydiscrimination task might be especially effective in distracting sub-jects from painful stimulation and therefore, likely to activateendogenous pain inhibitory systems. For the concentration-on-pain task, subjects were instructed to concentrate on the unpleas-antness of pain, because this has been reported to increase painratings more reliably than selectively focusing on the somatosen-sory aspects of pain [1,27].

2.7. Rejection of experiments

The principal aim of the study was to quantify the effect of eachtask in relation to pre- and posttask baseline. In the case of task ef-fects relative to baseline being small or inconclusive, the within-subject design would have allowed direct comparison of the effectsof each distraction task with its respective concentration-on-paintask, albeit with the drawback of not permitting separate analysisof the effects of distraction and concentration. However, sufficientstability of the RIII reflex within the pretask block was not alwaysachieved, presumably because the 2-minutes baseline period wastoo short for some subjects. In addition, posttask after-effects(either slow return to baseline or rebound effects, see also Fig. 3)sometimes precluded use of block 3 as a baseline for block 4 (seeFig. 1). Including only recordings with a stable baseline in block1 and no posttask after-effects in block 3 would have overly re-duced the number of experiments included in the analysis andbiased the analysis towards subjects that exhibit no posttaskafter-effects. Therefore, we abandoned the within-subject ap-proach and limited the study to comparison of task effects withpre- and posttask baseline, separately analyzing blocks 1–3(pre1-task1-post1) and 3–5 (pre2-task2-post2) of each recording.Experiments (each experiment consisting of 3 blocks as describedabove) were then rejected on one of 3 grounds: (1) Insufficient sta-bility of the RIII reflex area in the pretask block. More exactly, we

rejected all basal RIII experiments where the largest difference be-tween the 4 average reflex areas (averages of 5 consecutive re-flexes, as described above) constituting the pretask blockexceeded 30% of the corresponding total pretask average (45 of162 basal RIII experiments were rejected). For the temporal sum-mation experiments, baseline stability was more difficult to assessbecause only 6 reflexes evoked by single stimuli were available perblock. However, as temporal summation ratios are relative mea-sures, less affected by baseline fluctuations, temporal summationexperiments were accepted as long as detectable RIII reflexes wereevoked by all single stimuli (10 of 162 temporal summation exper-iments were rejected). (2) Interference of spontaneous muscleactivity with reflex quantification, arising especially in temporalsummation experiments, presumably because subjects found itmore difficult to relax in view of the higher pain intensitiesreached during temporal summation (6 of 162 basal RIII experi-ments and 24 of 162 temporal summation experiments were re-jected). (3) No clear separation of the RIII reflex from a precedingRII reflex. This was especially the case when the RII componentwas large and part of the RIII activity fell into the falling phase ofthe RII reflex. In these cases, data from the entire session had tobe rejected (4 subjects in session 2 and 2 subjects in session 3,amounting to 20 of 162 basal RIII experiments and 20 of 162 tem-poral summation experiments being rejected). In addition, onesubject could not participate in session 3 because of intercurrentillness (2 basal RIII experiments and 2 temporal summation exper-iments missing) and a reproducible RIII could not be recorded fromone subject in session 2 (4 basal RIII experiments and 4 temporalsummation experiments missing).

In total, valid basal RIII data were obtained in 14 subjects for themental imagery task, in 16 subjects for the music task, and in 16subjects for the brush task. Valid RIII temporal summation datawere obtained in 18 subjects for the mental imagery task, in 20subjects for the music task, and in 18 subjects for the brush task.For the concentration-on-pain task, data were averaged acrossthe 3 concentration-on-pain experiments, resulting in valid datafrom 22 subjects for the basal RIII recording and from 25 subjectsfor the temporal summation recording.

2.8. Statistics

Statistical analyses were performed using the Statistical Pack-age of Social Sciences, Version 15.0.1 for Windows (SPSS Inc, Chi-cago, IL, USA). Values are mean ± SD unless indicated otherwise.P < 0.05 was considered statistically significant.

Prior to the use of parametric statistics, significant deviationsfrom normal distribution were tested using the Kolmogorov–Smir-nov test. A significant deviation from normality was detected onlyfor age.

Cohen’s d was used as a measure of effect size [12]. For compar-ison of pain thresholds and RIII thresholds, a repeated-measuresanalysis of variance (ANOVA) was used with threshold type (painvs. RIII) and session (sessions 1–3 as outlined in Fig. 1) as within-subject factors.

One-sample t-tests were used for testing the effect of a giventask on the focus of attention. Because the subgroups having validRIII data for the different distraction tasks only partially over-lapped, not a repeated-measures ANOVA but a one-way ANOVAwas used to compare the effect of the different distraction taskson the shift of attention rating and on pain ratings. Because sub-groups having valid RIII data for the basal and temporal summa-tion experiments also overlapped only partially, unpaired t-testswere used to compare the shift of attention ratings achieved duringboth recording conditions within each of the tasks. For testing taskeffects on basal RIII areas, basal pain perception, temporal summa-tion ratios, and heart rates, repeated-measures ANOVA was con-

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ducted with time (pretask, task, posttask) as within-subject factor,followed by paired t-tests with Bonferroni correction where appli-cable. In the case of violation of the assumption of homogeneity ofvariances, we applied the Greenhouse–Geisser adjustment. Un-paired t-tests were used for detection of sex differences in task ef-fects on pain ratings and RIII areas. Pearson’s r was used to test forcorrelations except for correlations with age that were tested usingSpearman’s q. Correction for multiple testing was performed withthe Bonferroni adjustment, where applicable. Power analysis wasconducted using G�Power [20].

3. Results

3.1. Stimulus–response curves

Pain thresholds were significantly lower than RIII thresholds(pain threshold: 4.4 ± 2.1 mA, RIII threshold: 6.0 ± 2.1 mA,F[1,24] = 28.5, P < 0.001). Stimulus–response curves illustratethat, although thresholds were different, increase with stimulusintensity was parallel for pain ratings and RIII areas (Fig. 2Band C).

3.2. Effects of distraction tasks

3.2.1. Focus of attentionFor each task, subjects gave a rating of how much the task had

shifted the focus of their attention away from pain or towards pain(on a scale from �5 to +5). All 3 distraction tasks resulted in a sig-nificant shift of the focus of attention away from painful stimula-tion both during basal RIII recordings (mental imagery:�3.3 ± 1.1, T[13] = 11.6, Cohen’s d = 4.2; music: �3.0 ± 1.0,T[15] = 12.6, d = 4.2; brush: �3.7 ± 1.1, T[15] = 13.8, d = 4.8, allP < 0.001) and during temporal summation recordings (mentalimagery: �2.7 ± 1.1, T[17] = 9.4, d = 3.5; music: �3.2 ± 1.2,T[19] = 12.0, d = 3.8; brush: �3.7 ± 0.8, T[17] = 19.1, d = 6.5, allP < 0.001). The shift of the focus of attention was not significantlydifferent between basal and temporal summation experimentsfor any of the tasks. While there was no significant difference be-tween the shift of focus of attention achieved by the 3 distractiontasks during basal RIII recording, in the temporal summationexperiments the mental imagery task resulted in less shift of atten-tion than the brush task (F[2,53] = 4.4, P < 0.05, post hoc mentalimagery vs. brush, P < 0.05).

Table 1Task effects on basal RIII reflexes and pain ratings.

3.2.2. Heart ratesHeart rates were not significantly affected by the distraction

tasks during basal RIII recordings (mental imagery: pre: 62 ± 9beats per minute, task: 61 ± 11 beats per minute, post: 62 ± 9 beatsper minute, n = 14; music: 68 ± 10 beats per minute, 66 ± 11 beatsper minute, 69 ± 11 beats per minute, n = 16; brush: 66 ± 11 beatsper minute, 66 ± 12 beats per minute, 66 ± 11 beats per minute,n = 16).

3.2.3. Basal pain perception and RIII areasWhen subjects engaged in any of the 3 distraction tasks, pain

intensity ratings were significantly and reversibly reduced (Ta-ble 1). There was no significant difference between the amountsof pain reduction achieved by the 3 distraction tasks. Only thebrush task also induced a significant reduction of RIII areas duringthe task, and this was reversible upon termination of the task(Fig. 3, Table 1). The mental imagery task induced a rebound poten-tiation of RIII areas after the end of the task (Fig. 3, Table 1).

Correlations between task effects on RIII area and task effects onpain perception were positive for the music and brush tasks butdid not reach significance (Table 1). Task effects on pain perceptionand RIII areas were not predicted by age or by pain intensity atbaseline, and were not significantly different between males andfemales. For the mental imagery and brush tasks, there was a sig-nificant correlation between the task effect on pain perception andthe rating of the shift of attention reached during the task (mentalimagery: r = 0.60, n = 14, P < 0.05; brush: r = 0.61, n = 16, P < 0.05).No such correlations were detected for task effects on RIII area.

3.2.4. Temporal summation of pain and temporal summation of RIIIareas

Neither the temporal summation ratio of pain intensity ratingsnor the temporal summation ratio of RIII areas were significantlyaffected by the distraction tasks (Fig. 4, Table 2).

3.3. Effects of the concentration-on-pain task

3.3.1. Focus of attentionThe concentration-on-pain task resulted in a significant shift of

the focus of attention towards pain both during basal RIII recording(+3.3 ± 0.9, T[21] = 16.7, d = 5.1, P < 0.001) and during temporalsummation experiments (+3.3 ± 0.8, T[24] = 19.7, d = 5.8,P < 0.001), with no significant difference between basal and tempo-ral summation experiments.

Fig. 4. Task effects on temporal summation of the RIII reflex. (A) Illustration of arepresentative example of original traces from a temporal summation experimentinvestigating the effects of the brush task. Stimulus number indicates the number ofthe stimulus within the 1-Hz train used to evoke temporal summation. The shadedregion corresponds to the analysis window. Bars: 100 lV, 50 ms. (B) Illustration ofthe average task effects on temporal summation. Ratios were calculated asdescribed in Section 2. The average pretask ratio is indicated by a dotted line.Error bars are SEM.

Table 2Task effects on temporal summation of the RIII reflex and pain perception.

N RIII area temporal summation ratio

Pretask Task

Mental imagery 18 1.40 ± 0.25 1.52 ± 0.48Music 20 1.50 ± 0.35 1.54 ± 0.48Brush 18 1.36 ± 0.25 1.66 ± 0.76Concentration on pain 25 1.42 ± 0.26 1.48 ± 0.39

Values are temporal summation ratios within the specified experimental block (pretask,variance with time (pre, task, post) as within-subject factor was n.s. for all tasks and bo

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3.3.2. Heart ratesHeart rates were not significantly affected by the concentration

of pain task during basal RIII recordings (pre: 66 ± 9 beats per min-ute, task: 66 ± 10 beats per minute, post: 63 ± 9 beats per minute,n = 22).

3.3.3. Basal pain perception and RIII areasWhen subjects concentrated on painful stimulation, both pain

ratings and RIII areas increased significantly and reversibly (Table 1,Fig. 3). There was no significant correlation between the effect ofthe concentration-on-pain task on pain ratings and the effect ofthe task on RIII areas (Table 1). Task effects on pain perception orRIII areas were not predicted by age or pain intensity at baselineand were not significantly different between males and females.There was no significant correlation between task effects on painperception and the rating of the shift of attention achieved duringthe task.

3.3.4. Temporal summation of pain and temporal summation of RIIIareas

Neither temporal summation of pain perception nor temporalsummation of the RIII reflex was significantly affected by the con-centration-on-pain task (Fig. 4, Table 2).

4. Discussion

Major results of the present study are that (1) all 3 distractiontasks reduced pain perception but only the brush task also reducedthe RIII reflex, (2) the concentration-on-pain task increased bothpain perception and the RIII reflex, and (3) none of the tasks signif-icantly affected temporal summation of pain perception or tempo-ral summation of the RIII reflex.

4.1. Effects on basal pain perception and spinal nociception

All 3 distraction tasks used in the present study reduced painperception, demonstrating endogenous pain modulation. Endoge-nous pain modulation may have both purely supraspinal anddescending components [6,21,56,64]. In the present study, onlythe brush task significantly reduced a measure of spinal nocicep-tion, the RIII reflex, suggesting activation of descending paininhibitory systems by this task but not the other 2 distractiontasks. Given that the brush task produced the largest pain reduc-tions and shifts of attention, the effect of distraction on the RIIIreflex might be gradual, with only the strongest distractor reach-ing a significant effect. However, effect sizes were near zero forthe effects of mental imagery and music on RIII areas but largefor the brush task, while effect sizes were large for shifts of atten-tion and reductions of pain perception during all 3 tasks. There-fore, the differential activation of descending inhibition mightnot be related to attention itself but rather to the specific strate-gies used to divert attention from pain. The brush task is asomatosensory spatial discrimination task also placing some de-

Pain rating temporal summation ratio

Posttask Pretask Task Posttask

1.43 ± 0.27 1.73 ± 0.69 1.77 ± 0.87 1.80 ± 0.801.46 ± 0.37 1.87 ± 1.03 1.85 ± 0.95 2.01 ± 1.201.40 ± 0.24 1.68 ± 0.50 2.02 ± 1.45 1.77 ± 0.571.43 ± 0.32 1.80 ± 0.71 1.86 ± 0.72 1.80 ± 0.73

task, posttask, see Section 2) and given as mean ± SD. Repeated measures analysis ofth RIII ratios and pain rating ratios.

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mand on cognitive functions (eg, counting relevant stimuli). Tothe best of our knowledge, the effect of somatosensory discrimi-nation tasks on spinal nociception has not been evaluated. Previ-ous studies on the effect of cognitive tasks (eg, mental arithmetic)have been conflicting, showing that cognitive demand does notinvariably reduce the RIII reflex [15,17,54,66]. Further studies willhave to show which of the different components of the brush task(focusing on nonpainful somatosensory input, discrimination task,counting task) are responsible for activation of descending inhibi-tion. In contrast to the brush task, the mental imagery and musictasks achieve distraction by engaging in positive emotions evokedby personally relevant stimuli. Previous studies have suggestedthat positive emotions induced by viewing of pleasant (eg, erotic)pictures can reduce the RIII reflex [43] or have no effect [46], witharousal likely contributing to RIII reduction [44]. The currentlyused mental imagery and music tasks did not induce significantarousal, as indicated by unchanged heart rates. After cessationof the mental imagery task, a significant increase of RIII areaswas found that was not associated with increased pain ratings.Occasionally, rebound effects were also seen with the other dis-traction tasks. At present, the underlying mechanisms remainunclear.

In the present study, concentration on pain increased both painperception and spinal nociception, suggesting engagement ofdescending pain modulatory systems by focusing on pain. There-fore, the effect of distraction tasks may also depend on the pointof reference, which was the ‘‘no task’’ baseline in the present study,while functional imaging studies have sometimes contrasted dis-traction with concentration on pain [57,59].

In conclusion, present results suggest that in healthy subjects,activation of descending inhibition may be dependent on the spe-cific strategy used for distraction (ie, the specific cognitive, emo-tional, or other processes involved) rather than on the shift of thefocus of attention itself. Activation of descending pathways by dis-traction might be larger in chronic pain populations, because theirpoint of reference is shifted in a direction to larger attention to-wards pain [28,33,45]. This will have to be determined in separatestudies.

4.2. Effects on temporal summation

In the present study, neither temporal summation of pain per-ception nor temporal summation of the RIII reflex was significantlyaffected by any of the tasks. This suggests that these tasks selec-tively modulated the mechanisms underlying basal nociception,but not those underlying temporal summation, which are thoughtto roughly represent AMPA/kainate receptor-mediated and NMDAreceptor-mediated mechanisms, respectively [3,26,67]. An alterna-tive explanation would be that the increased pain intensitiesreached during temporal summation interfered with engagementin the distraction tasks [16], obscuring task effects on temporalsummation. However, this mechanism would be unlikely to ex-plain the lack of effect of the concentration-on-pain task on tempo-ral summation. Also, shift-of-attention ratings were notsignificantly different between basal and temporal summationexperiments.

Previous psychophysical studies investigating the interactionbetween endogenous pain inhibition activated by heterotopic con-ditioning noxious stimulation and temporal summation of painmostly report an effect on basal pain perception but not on the ex-tent of temporal summation [29,49,55], although preferential sup-pression of temporal summation has also been found [11,52]. Thepresent study extends these results towards pain modulation byattention and for the first time provides direct evidence for the lackof effect of distraction and concentration on pain on temporal sum-mation of spinal nociceptive transmission.

4.3. Use of the RIII reflex for assessment of spinal nociception

With the exception of spinal functional imaging [18], the RIIIreflex is currently the only tool available for assessment of humanspinal nociception. It is subject to some limitations. It is mediatedby primary afferent Ad fibers [19] and therefore not suitable toassess the effects of descending pain modulation on C-fiber-med-iated transmission. In the rat, nociceptive withdrawal reflexeshave been shown to best correspond to activity in a pool of widedynamic range deep dorsal horn interneurons [48]. There is cur-rently no proof that spinal nociception as quantified by the hu-man RIII reflex reflects ascending nociception, that is, the partof spinal nociceptive information that is relayed to the brain. Alack of correlation between the extent of pain modulation and RIIImodulation has been reported before [41,54] and was essentiallyreproduced in the present study. However, independent of thespecific task used, pain modulation in humans will likely alwaysinclude a supraspinal component. The relative proportion be-tween supraspinal and descending processes may be individuallydifferent, hampering detection of a correlation between the ex-tent of pain modulation and RIII modulation. In addition, pain rat-ings likely include the effect of C-fiber activity that is notreflected by the RIII reflex. While these issues have to be furtherinvestigated, the currently reported reduction of the RIII reflex bythe brush task and the increase of the RIII reflex by the concentra-tion-on-pain task fit well with current theories on activation ofdescending pain modulatory systems by cognitive processes andsuggest that the RIII reflex may be a useful tool to study spinalnociception.

4.4. Limitations

Due to our high standards on reflex quality and baseline stabil-ity, complete RIII data were not obtained from every subject. Poweranalysis indicates that the number of valid experiments (14–22 forbasal RIII recordings and 18–25 for temporal summation) was suf-ficient to detect medium to large effects (Cohen’s d P 0.6–0.8, [12])with a power of 0.8 at P < 0.05. As task effects on RIII areas and painratings were clear cut, exhibiting either large or near-zero effectsizes, sample sizes likely were sufficient in the present setting.One possible exception is the correlation between task effects onbasal RIII areas and the corresponding pain ratings in the brushtask, that amounted to r = 0.39 (n = 16), not reaching significance.Power analysis indicates that a sample size of 36 is needed to de-tect a correlation of this magnitude with a power of 0.8 at P < 0.05.

The present study investigated the effects of distraction strate-gies inspired from real life, not aiming at a separate assessment ofattentional, other cognitive, and emotional processes, which re-quires the use of elaborated crossover designs [27,60,61,64]. In-deed, our tasks frankly relied on emotion induction or onincreased cognitive load to achieve a shift of attention, and resultsreflect the total effect achieved by the different cognitive and emo-tional components involved, that may regulate pain perceptionindependently [27,60,61]. In addition, although care was takennot to create expectations with respect to the effects of tasks onpain perception, preexisting expectations may have contributedto pain and RIII modulation [6,23,63].

4.5. Conclusions

The present results show that the pain modulation achieved byconcentration on pain or different distraction strategies is mainlybased on modulation of basal pain perception, not temporal sum-mation. Effects on the RIII reflex suggest that activation of descend-ing pain inhibition depends on the specific distraction strategyused rather than on the shift of attention itself.

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Conflict of interest statement

The authors declare no conflicts of interest.

Acknowledgements

This work was supported by the fund ‘‘Innovative Medical Re-search’’ of the University of Münster Medical School (RU210904).In addition, we wish to thank Alpine Biomed (Langenfeld, Ger-many) for lending us the recording equipment.

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