effects of aversive classical conditioning on sexual ... · repeated pairing of a sexual stimulus...

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ORIGINAL RESEARCH PAIN Effects of Aversive Classical Conditioning on Sexual Response in Women With Dyspareunia and Sexually Functional Controls Stephanie Both, PhD, 1 Marieke Brauer, PhD, 2 Philomeen Weijenborg, MD, PhD, 1 and Ellen Laan, PhD 2 ABSTRACT Introduction: In dyspareuniaa somatically unexplained vulvovaginal pain associated with sexual intercourselearned pain-related fear and inhibited sexual arousal are supposed to play a pivotal role. Based on research ndings indicating that enhanced pain conditioning is involved in the etiology and maintenance of chronic pain, in the present study it was hypothesized that enhanced pain conditioning also might be involved in dyspareunia. Aim: To test whether learned associations between pain and sex negatively affect sexual response; whether women with dyspareunia show stronger aversive learning; and whether psychological distress, pain-related anxiety, vigilance, catastrophizing, and sexual excitation and inhibition were associated with conditioning effects. Methods: Women with dyspareunia (n ¼ 36) and healthy controls (n ¼ 35) completed a differential condi- tioning experiment, with one erotic picture (the CS þ ) paired with a painful unconditional stimulus and one erotic picture never paired with pain (the CS ). Main Outcome Measures: Genital sexual response was measured by vaginal photoplethysmography, and ratings of affective value and sexual arousal in response to the CS þ and CS were obtained. Psychological distress, pain cognitions, and sexual excitation and inhibition were assessed by validated questionnaires. Results: The two groups showed stronger negative affect and weaker subjective sexual arousal to the CS þ during the extinction phase, but, contrary to expectations, women with dyspareunia showed weaker differential responding. Controls showed more prominent lower genital response to the CS þ during acquisition than women with dyspareunia. In addition, women with dyspareunia showed stronger expectancy for the unconditional stimulus in response to the safe CS . Higher levels of pain-related fear, pain catastrophizing, and sexual inhi- bition were associated with weaker differential conditioning effects. Conclusions: Pairing of sex with pain negatively affects sexual response. The results indicate that a learned association of sex with pain and possibly decient safety learning play a role in dyspareunia. Both S, Brauer M, Weijenborg P, Laan E. Effects of Aversive Classical Conditioning on Sexual Response in Women With Dyspareunia and Sexually Functional Controls. J Sex Med 2017;14:687e701. Copyright Ó 2017, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved. Key Words: Dyspareunia; Pain; Sexual Dysfunction; Conditioning; Photoplethysmography INTRODUCTION Dyspareunia, a persistent or recurrent vulvovaginal pain associated with sexual intercourse (described as genito-pelvic pain/penetration disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) is a relatively common sexual complaint. Prevalence gures in premenopausal women range from 10% to 20%. 1,2 Research considering psychosomatic factors have reported evidence for a higher prevalence of (pre- viously diagnosed) anxiety and depression, 3,4 comorbidity with other chronic pain conditions, 5 increased pain hypervigilance and catastrophizing, 4,6,7 and hyperalgesia 8 in women with dys- pareunia, indicating that, in the pathogenesis of dyspareunia, similar emotional and cognitive mechanisms could be active as in other chronic pain conditions. 9,10 Importantly, apart from the vulvovaginal pain, women with dyspareunia report sexual dysfunction, more specically low sex- ual desire, and complaints of decreased sexual arousal and vaginal lubrication. 7,11e13 Whether these sexual complaints precede, follow, or develop parallel to the sexual pain complaints is unclear. In clinical practice, many women with dyspareunia report a loss of Received November 17, 2016. Accepted March 3, 2017. 1 Centre for Psychosomatic Gynaecology and Sexology, Leiden University Medical Centre, Leiden, The Netherlands; 2 Centre for Psychosomatic Obstetrics and Sexology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands Copyright ª 2017, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jsxm.2017.03.244 J Sex Med 2017;14:687e701 687

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Page 1: Effects of Aversive Classical Conditioning on Sexual ... · repeated pairing of a sexual stimulus with pain would result in decreased sexual arousal and in increased negative affect

ORIGINAL RESEARCH

PAIN

Effects of Aversive Classical Conditioning on Sexual Response in WomenWith Dyspareunia and Sexually Functional Controls

Stephanie Both, PhD,1 Marieke Brauer, PhD,2 Philomeen Weijenborg, MD, PhD,1 and Ellen Laan, PhD2

ABSTRACT

Received No1Centre forMedical Ce2Centre forCentre, Un

Copyright ªElsevier Inchttp://dx.do

J Sex Med

Introduction: In dyspareunia—a somatically unexplained vulvovaginal pain associated with sexual intercourse—learned pain-related fear and inhibited sexual arousal are supposed to play a pivotal role. Based on researchfindings indicating that enhanced pain conditioning is involved in the etiology and maintenance of chronic pain,in the present study it was hypothesized that enhanced pain conditioning also might be involved in dyspareunia.

Aim: To test whether learned associations between pain and sex negatively affect sexual response; whetherwomen with dyspareunia show stronger aversive learning; and whether psychological distress, pain-relatedanxiety, vigilance, catastrophizing, and sexual excitation and inhibition were associated with conditioning effects.

Methods: Women with dyspareunia (n ¼ 36) and healthy controls (n ¼ 35) completed a differential condi-tioning experiment, with one erotic picture (the CSþ) paired with a painful unconditional stimulus and oneerotic picture never paired with pain (the CS�).

Main Outcome Measures: Genital sexual response was measured by vaginal photoplethysmography, andratings of affective value and sexual arousal in response to the CSþ and CS� were obtained. Psychological distress,pain cognitions, and sexual excitation and inhibition were assessed by validated questionnaires.

Results: The two groups showed stronger negative affect and weaker subjective sexual arousal to the CSþ duringthe extinction phase, but, contrary to expectations, women with dyspareunia showed weaker differentialresponding. Controls showed more prominent lower genital response to the CSþ during acquisition than womenwith dyspareunia. In addition, women with dyspareunia showed stronger expectancy for the unconditionalstimulus in response to the safe CS�. Higher levels of pain-related fear, pain catastrophizing, and sexual inhi-bition were associated with weaker differential conditioning effects.

Conclusions: Pairing of sex with pain negatively affects sexual response. The results indicate that a learnedassociation of sex with pain and possibly deficient safety learning play a role in dyspareunia. Both S, Brauer M,Weijenborg P, Laan E. Effects of Aversive Classical Conditioning on Sexual Response in Women WithDyspareunia and Sexually Functional Controls. J Sex Med 2017;14:687e701.

Copyright � 2017, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Key Words: Dyspareunia; Pain; Sexual Dysfunction; Conditioning; Photoplethysmography

INTRODUCTION

Dyspareunia, a persistent or recurrent vulvovaginal painassociated with sexual intercourse (described as genito-pelvicpain/penetration disorder in the Diagnostic and StatisticalManual of Mental Disorders, Fifth Edition) is a relatively commonsexual complaint. Prevalence figures in premenopausal women

vember 17, 2016. Accepted March 3, 2017.

Psychosomatic Gynaecology and Sexology, Leiden Universityntre, Leiden, The Netherlands;

Psychosomatic Obstetrics and Sexology, Academic Medicaliversity of Amsterdam, Amsterdam, The Netherlands

2017, International Society for Sexual Medicine. Published by. All rights reserved.i.org/10.1016/j.jsxm.2017.03.244

2017;14:687e701

range from 10% to 20%.1,2 Research considering psychosomaticfactors have reported evidence for a higher prevalence of (pre-viously diagnosed) anxiety and depression,3,4 comorbidity withother chronic pain conditions,5 increased pain hypervigilanceand catastrophizing,4,6,7 and hyperalgesia8 in women with dys-pareunia, indicating that, in the pathogenesis of dyspareunia,similar emotional and cognitive mechanisms could be active as inother chronic pain conditions.9,10

Importantly, apart from the vulvovaginal pain, women withdyspareunia report sexual dysfunction, more specifically low sex-ual desire, and complaints of decreased sexual arousal and vaginallubrication.7,11e13 Whether these sexual complaints precede,follow, or develop parallel to the sexual pain complaints is unclear.In clinical practice, many women with dyspareunia report a loss of

687

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Figure 1. Cognitive behavioral model of dyspareunia. Figure 1 isavailable in color online at www.jsm.jsexmed.org.

688 Both et al

sexual desire and activity. Some women continue having sex,including painful intercourse, to satisfy their partner.14e16

A cognitive behavioral model of dyspareunia (Figure 1) in-tegrates the pain and sexual aspects of dyspareunia. According tothis explanatory model, an initial experience of pain can lead tofear of pain in new sexual situations. That fear can result indecreased sexual arousal and vaginal lubrication17 and increasedpelvic floor muscle tone tightening the vaginal entrance,18,19

which increases the likelihood of pain during attempted pene-tration. In addition, fear of pain can result in avoidance behaviorand, hence, in a lack of opportunity to overcome fear of pain,resulting in chronic dysfunction.10

The focus in this model on learned fear through initial painexperiences is in agreement with views that recognize an importantrole of basic learning mechanisms in chronic pain.20 These viewsemphasize that animals and humans are built with a system tosignal potential threat or pain and equipped with the capability tolearn to predict pain by associative learning mechanisms. How-ever, these adaptive associative learning mechanisms cancontribute to pain, pain-related distress, and disability when itresults in avoidance behavior and, hence, in a lack of opportunityto overcome fear of pain, facilitating chronic pain conditions.

One form of associative learning is classic conditioning. A painstimulus can be considered an unconditional stimulus (US) thatelicits fear, and conditional stimuli (CSs) can be stimuli thatprecede or coincide with the pain stimulus. Through repeatedpairing of stimuli with pain, these stimuli can elicit conditionedfear responses. Extended to pain conditioning in a sexual situa-tion, different stimuli, such as the naked partner or the sensationof specific caresses, can become signals for impending pain.When, during sexual encounters, repeated pairing of sexualstimuli and pain has occurred, previously appetitive sexualstimuli can elicit anticipatory defensive responses and impede thesexual arousal response. Recent studies in healthy sexuallyfunctional women have provided the initial evidence for negativeeffects of pain conditioning and fear on sexual response.21,22

Interestingly, experimental studies have indicated strongereffects of pain conditioning in patients with chronic pain.Compared with pain-free controls, patients with chronic backpain and headache showed enhanced conditioned muscularresponses and less extinction of these responses,23,24 and patientswith fibromyalgia showed enhanced aversively conditioned eye-blink reflexes.25 Although the number of studies in individualswith chronic pain is limited, and more research is needed, theinitial evidence suggests that enhanced pain conditioning mightbe involved in the etiology and maintenance of chronic painconditions.

In the present study, we investigated the effects of aversivepain conditioning on sexual arousal and affect in women withdyspareunia and sexually functional controls. It was expected thatrepeated pairing of a sexual stimulus with pain would result indecreased sexual arousal and in increased negative affect inresponse to this stimulus and that these conditioning effectswould be stronger in women with dyspareunia compared withsexually functional controls. Based on previous research,3,4,6,7 weexpected higher levels of trait anxiety, psychological distress,pain-related anxiety, vigilance, and catastrophizing in womenwith dyspareunia compared with controls, and we expectedhigher scores on these variables to be associated with strongereffects of pain conditioning on sexual arousal and affect. Also, weexamined whether the tendency toward sexual excitation andsexual inhibition differed between women with dyspareunia andcontrols and whether these tendencies were associated with eff-ects of pain conditioning on sexual arousal responses. Accordingto the dual control model, individuals differ in their propensityfor sexual excitation and sexual inhibition, a variability thatmight be genetically determined or might be the result of earlylearning experiences.26 Individuals with a propensity for sexualexcitation get easily aroused in response to sexual stimuli,whereas the propensity for sexual inhibition reflects easily losingone’s sexual arousal because of inhibiting cues. We hypothesizedthat individual differences in sexual excitation and inhibitionwould be related to the strength of the effect of pain conditioningand predicted that a stronger tendency for sexual inhibitionwould be associated with stronger pain conditioning effects andthat a stronger tendency for sexual excitation would be associatedwith weaker pain conditioning effects.

METHODS

Recruitment and InclusionIn previous sexual conditioning studies from our laboratory,

medium to large effects were observed.22,27 An a priori poweranalysis, with a chosen a value of 0.05 and a power of 80%,determined that a minimum of 26 women would be needed pergroup to detect large differences (d ¼ 0.8) in responding betweengroups. In the present study, 36 women with dyspareunia and 35controls participated. All women were paid (35V) for taking partin the study. Women with dyspareunia were recruited by sendinga letter to patients on the waiting list for treatment of

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Aversive Conditioning in Dyspareunia 689

dyspareunia at the outpatient clinic of psychosomatic gynecologyand sexology. In addition, women with and without sexual paincomplaints were recruited through advertisements at the uni-versities of Amsterdam and Leiden, in local newspapers, and onnoticeboards of regional health care centers. Following adherenceby e-mail, women were screened for eligibility by phone by atrained female experimenter who used a brief structured inter-view. After initial screening, women visited the hospital for abrief structured interview, based on the Diagnostic and StatisticalManual of Mental Disorders, Fourth Edition criteria for dyspar-eunia, about sexual functioning and psychiatric and somaticproblems and to complete the questionnaires. For women withdyspareunia, this visit also included an examination by a gyne-cologist, including the cotton-swab test,28 to examine provokedvulvodynia, a sharp, burning pain at the entrance of the vaginaprovoked by vestibular touch.

General inclusion criteria were age 18 to 45 years and, becauseof the heterosexual stimulus material, a heterosexual orientation.Additional inclusion criteria for women with dyspareunia werecomplaints of pain during at least 50% of (attempted) penilepenetration events, with a duration of complaints of at least 6months. Women with dyspareunia with and without provokedvulvodynia were included in the study. Inclusion criteria forwomen in the control group were sexual activity during the pastyear and no sexual problems. General exclusion criteria werepregnancy or lactation; affective, psychotic, or substance-relateddisorders; having undergone a hysterectomy or prolapse sur-gery; using medication that could affect sexual response; andmedical disorders that could influence sexual arousal or pelvicfloor responses or the measurement of these responses. Specificexclusion criteria for women with dyspareunia were a somaticexplanation of the pain complaints (eg, signs of a vaginal infec-tion or lichen scleroses) as confirmed by the physical examinationby the gynecologist or chronic vulvar pain unrelated to(attempted) intercourse.

Preceding participation, all women received written informa-tion including a description of the procedure, the pain stimula-tion, and the physiologic measurements. Participants were nottested during menstruation. The study was conducted in accor-dance with the Declaration of Helsinki and approved by thehuman subjects ethical review board of the Leiden UniversityMedical Centre (Leiden, The Netherlands). Informed consent,in which confidentially, anonymity, and the opportunity towithdraw from the experiment without penalty were assured, wasobtained from all participants.

Materials, Conditioning Procedure, andMeasurements

Conditional StimuliTwo explicit erotic pictures as used in previous studies21,22

served as CSs. Two pictures portrayed a nude heterosexualcouple engaging in sexual intercourse with the woman in thesuperior position. The two pictures differed in the male and

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female actors involved and the orientation of the picture (land-scape or portrait). The CSs were shown in the middle of acomputer monitor, approximately 1.5 m in front of the partic-ipant. The size of the pictures was 14 � 21 cm. During theintervals between pictures, a white screen was presented. One ofthe pictures (CSþ) was followed by the US, whereas the otherpicture (CS�) was never followed by the US. Assignment ofpictures as CSþ and CS� was counterbalanced acrossparticipants.

Pain StimulusThe pain stimulus (US) was an electro-cutaneous stimulus

with a duration of 50 ms delivered by a safe muscle stimulationapparatus (Grass S48, Grass Technologies, West Warwick, RI,USA) with an isolation unit. The pain stimulus was administeredby electrodes fastened at the wrist of the non-dominant arm. Thepain stimulus produces a painful, stinging sensation and has beenused in several experimental studies.17,29,30 The intensity of theUS was set at a level that the participant described as painful anddemanding some effort to tolerate.

A computer program developed at the University of Amster-dam (Amsterdam, The Netherlands; Versatile Stimulus ResponseRegistration Program) timed the administration of the picturesand the pain stimuli and the sampling of the physiologicmeasurements.

Conditioning Procedure and DesignThe experimental procedure involved differential conditioning

with one stimulus (the CSþ) being followed by the painfulstimulation (US) during the acquisition phase, whereas the otherstimulus (CS�) was never followed by a painful shock. Which ofthe two pictures served as the reinforced CS (the CSþ), or thenon-reinforced CS (the CS�) was counterbalanced across par-ticipants. During the entire experiment, measurements of genitalarousal were recorded. During the preconditioning and extinc-tion phases, ratings of subjective affect and subjective sexualarousal were collected.

In the preconditioning phase, participants viewed four non-reinforced presentations of the CSþ and four presentations ofthe CS� for 11 seconds each. Subsequently, in the acquisitionphase, the contingency between the CSþ and the US waslearned: the CSþ and CS� were presented 10 times each, and theCSþ was always followed by the US. The US was delivered for50 ms, starting 10 seconds after the onset of the CSþ. Theextinction phase consisted of four unreinforced CSþ pre-sentations and four unreinforced CS� presentations. There weretwo random stimulus orders for each phase, with the restrictionof only two successive presentations of each CS. Half the par-ticipants saw the pictures in order 1, and the other half saw thepictures in order 2.

There was no interval among the preconditioning, acquisition,and extinction phases. During the entire procedure, intertrialintervals were 20, 25, or 30 seconds. The order of the length of

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690 Both et al

the intertrial interval was random, with the restriction of onlytwo similar successive lengths. The procedure, timing of the US,and intertrial interval were adapted from previous studies thatdemonstrated a conditioned sexual response.21,22

The basic design for testing group and conditioning effectswas a 2 (group: dyspareunia vs controls) � 2 (stimulus: CSþ vsCS�) � (trial) design, with group as the between-subject variableand stimulus and trial as within-subject variables.

Genital ResponseGenital response was measured using a vaginal photo-

plethysmograph assessing vaginal pulse amplitude (VPA).31

Depth of the probe and orientation of the light-emitting diodewere controlled by a device (a 6- � 2-cm plate) attached to thebase of the photoplethysmograph. Participants were instructed toinsert the photoplethysmograph such that the plate touched theirlabia. The vaginal photoplethysmograph was sterilized by plasmasterilization. Genital response was measured continuously duringthe resting baseline, preconditioning, acquisition, and extinctionphases.

Galvanic Skin ConductanceTo determine autonomic nervous system arousal during the

conditioning procedure, skin conductance level (SCL) wasmeasured. SCL was measured using a pair of Ag-AgCl electrodes(Con-Med, Technical Department Psychology, University ofAmsterdam) attached to the middle phalanx of the middle andindex fingers of the non-dominant hand. The electrodes wereconnected to an input device with a peak-peak sine-shapedexcitation voltage (0.5 V) of 50 Hz. The signal was led through asignal-conditioning amplifier and the output was sampled at 100Hz by a 16-bit AD converter (NI-6224; National Instruments,Austin, TX, USA).

Subjective Affective and Sexual Arousal ValueParticipants were asked to rate, after each stimulus presenta-

tion, the affective value of the CSs by answering the question,“What kind of feeling does this picture evoke in you?” Thequestion could be answered, using a button box, on a seven-point scale that varied from very negative to very positive. Inaddition, the sexual arousal intensity of the CSs was rated byanswering the question, “To what degree do you find this picturesexually arousing?” The question could be answered on a seven-point scale that varied from not sexually arousing at all toextremely sexually arousing. The first question was presented atthe monitor 1 second after the end of picture presentation. Thetime the questions were shown was paced by the participant’sresponse, but had a maximum of 45 seconds each. Immediatelyafter answering the first question, the second question wasshown. For the benefit of the conditioning procedure, a consis-tent interval between the CS presentations was maintained. Afteranswering the questions, a white screen remained until the nextpicture was presented.

Other Measurements

Sexual FunctionData on sexual functioning were collected by the Female Sexual

Function Index (FSFI).32,33 The FSFI consists of six subscales:desire, arousal, lubrication, orgasm, satisfaction, and pain. Higherscores indicate better sexual function, and a total score lower than26.55 is considered indicative of sexual dysfunction.32 The FSFIhas good internal reliability and can differentiate well betweenclinical samples and non-dysfunctional controls.32

Sexual DistressThe Female Sexual Distress Scale (FSDS)32,34 was used to

assesses sexuality-related personal distress. The FSDS consists of12 items related to negative feelings about sexual functioning,such as sadness, guilt, and dissatisfaction. Higher scores indicategreater sexual distress, and a score higher than 7 is consideredindicative of clinically significant sexual distress. The FSDS hasgood internal reliability and can differentiate well between clin-ical samples and non-dysfunctional controls.32

Sexual Abuse HistoryData on sexual abuse experiences were collected with the

Sexual and Physical Abuse Questionnaire. This is a self-reportquestionnaire consisting of seven items that measure the pres-ence and severity of sexual and physical abuse experiences.35

AnxietyTo assess trait anxiety levels, the State-Trait Anxiety Inventory

(STAI36; Dutch adaptation37) was used. The STAI measuresstate (momentary, reactive) and trait (stable, dispositional) anx-iety and has 20 items for assessing trait anxiety and 20 items forstate anxiety. Higher scores indicate greater anxiety. The STAIhas good internal reliability and good test-retest reliability.37

Psychological DistressThe Symptom Check List (SCL-9038; Dutch adaptation39),

containing 90 items, was used to assess psychological distress. Ahigher total score indicates more psychological distress. The SCL-90 has good internal reliability and good test-retest reliability.32,39

Pain-Related Emotions and CognitionsTo assess pain-related anxiety, the Pain Anxiety Symptoms

Scale (PASS-20)40 was used. The PASS-20 consists of foursubscales: fearful evaluation of pain, cognitive anxiety, physio-logic anxiety, and flight and avoidance behavior. Higher scoresindicate higher levels of pain-related anxiety. The PASS-20 hasgood internal reliability and validity.32,41

To assess pain vigilance, the Pain Vigilance and AwarenessQuestionnaire (PVAQ)42,43 was used. The PVAQ consists oftwo subscales: attention for pain and attention for changes inpain. Higher scores indicate stronger attention for pain. ThePVAQ has good internal reliability and validity.43

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Aversive Conditioning in Dyspareunia 691

To assess pain catastrophizing, the Pain Catastrophizing Scale(PCS)44,45 was used. This scale consists of three subscales:rumination, magnification, and helplessness. Higher scoresindicate higher levels of pain catastrophizing. The PCS has goodinternal reliability and good test-retest reliability.44

Sexual Excitation and InhibitionThe Sexual Excitation and Sexual Inhibition Inventory for

Women (SESII-W)46,47 is a self-report questionnaire containing36 items. The SESII-W consists of two factors, the sexual exci-tation (SE) factor and the sexual inhibition (SI) factor. Higherscores on the factors indicate a stronger tendency for sexualexcitation and sexual inhibition. The internal consistency andtest-retest reliability of the Dutch version of the SESII-W aresatisfactory.47

ProcedureAn instructed female experimenter tested the participants

individually. On arrival at the laboratory, the experimenterexplained all the details of the procedure and the participant readand signed the informed consent form. Participants wereinstructed that the purpose of the experiment was to measureresponses to different erotic pictures and to pain stimuli. Theywere told that during picture viewing, pain stimuli would beprovided. The level of the pain stimulus was determined indi-vidually for each participant. The participant was exposed torepeated pain stimuli (50 ms) of increasing intensity until sherated the pain stimulus as “painful and demanding some effort totolerate.” The experimenter determined at what stimulus in-tensity level the participant considered the stimulus as painfulbut tolerable. After this procedure, the experimenter emphasizedthat the intensity of the stimulus would not be changed duringthe experiment. After determination of the pain stimulus, theparticipant inserted the vaginal probe privately. After insertion ofthe probe, the experimenter entered the participant room againto attach the skin conductance electrodes. After she left theroom, the experimental procedure started. The procedure startedwith an adaptation period of 2 minutes, followed by a 2-minutebaseline assessment of VPA and SCL, during which music waspresented. Then, the conditioning procedure started.

After the conditioning procedure, the participants completed abrief questionnaire in which they were asked to indicate on aseven-point scale, which varied from never to always, to whatextent, during the experiment, they expected the presentation ofthe CSþ and the CS� to be followed by the pain stimulus. Theyalso indicated on a five-point scale, which varied from not at allto strongly, to what extent they experienced the pain stimuli asunpleasant and how anxious they were for the pain stimuli.

Data Reduction, Scoring, and AnalysisVPA data were entered into a computer program (developed

by the Technical Support Department of Psychology, Universityof Amsterdam) that enables off-line graphic inspection of the

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data. Artifacts in the channel monitoring VPA are caused bymovements of the lower part of the body or by voluntary orinvoluntary contractions of the pelvic muscles. A two-passalgorithm for automatic artifact removal was used to analyzethe VPA data. After artifact removal, mean VPA level during the2-minute baseline period was calculated, and mean VPA duringthe 5 to 10 seconds after the CS was calculated. The period of 5to 10 seconds is based on data from our laboratory showing thatvaginal blood engorgement is a relatively slow physiologicresponse and, hence, that differences in responding might not beobservable during the first seconds after stimulus presentation.VPA change scores were calculated for each CS presentation bysubtracting mean resting baseline VPA from mean VPA after CSpresentation.

SCL data were measured as mean SCL during the 5 to 10seconds after the onset of the CS (first interval response [FIR])and the 10 to 15 seconds after the onset of the CS (secondinterval response [SIR]) to capture autonomic nervous systemresponses in anticipation of the pain stimulus and during orshortly after the delivery of the pain stimulus. SCL change scoreswere calculated by subtracting mean baseline SCL score fromeach SCL trial score.

Effects of the conditioning procedure on VPA, SCL, andratings of subjective sexual arousal and affect were tested withmixed-factor univariate analysis of variance (ANOVA) proced-ures (general linear model in SPSS; SPSS, Inc, Chicago, IL,USA), with stimulus and trial as within-subject factors and groupas a between-subject factor. The Greenhouse-Geisser correctionwas used to adjust for violation of the sphericity assumption intesting repeated measures designs.48 Preconditioning, acquisi-tion, and extinction phases were analyzed separately. Effect sizesare reported as proportions of partial variance (partial h2).49

To test whether individual differences in trait anxiety, pain-related anxiety, pain vigilance, and pain catastrophizing and inthe tendency toward sexual excitation and sexual inhibition wereassociated with conditioning effects, correlations were calculatedbetween the STAI trait, PASS-20, PCS, PVAQ, and SE and SIscores and the genital and subjective responses after the acqui-sition phase.

Owing to technical problems, VPA data were missing for twoparticipants, SCL data were missing for three participants, andsubjective ratings were missing for two participants. Therefore,analyses of the SCL data were run over 35 women with dys-pareunia and 33 controls, VPA data were run over 35 womenwith dyspareunia and 34 controls, and subjective ratings wererun over 35 women with dyspareunia and 34 controls.

RESULTS

Participant Characteristics and QuestionnaireScores

Table 1 presents the demographic characteristics and ques-tionnaire scores of the two study groups and test results. Mean

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Table 1. Demographic characteristics, sexual pain characteristics, and mean scores on sexual function, anxiety, and pain-related emotionand cognition questionnaires for women with dyspareunia and control group

Dyspareunia (n ¼ 36) Controls (n ¼ 35)

c2/F value P value Partial h2Mean SD Mean SD

Age (y) 25.4 6.3 25.5 5.2 0.01 .91 0.00Steady partner, n (%) 32 (88.9) 26 (74.3) 2.53 .14Children, n (%) 1 (2.8) 3 (8.6) 1.45 .48University, bachelor level, n (%) 17 (47.2) 22 (62.8) 1.16 .28History of sexual abuse, n (%) 15 (41.7) 7 (20.0) 3.89 .048†

Duration of pain complaints (y) 4.9 4.8Lifelong dyspareunia, n (%) 18 (50)Diagnosis of PVD, n (%) 27 (73)FSFI subscales*

Desire 3.43 0.93 4.13 0.85 10.85 .002‡ 0.14Arousal 4.30 1.38 5.15 1.14 7.82 .01‡ 0.10Lubrication 3.83 1.03 4.49 0.83 8.75 .004‡ 0.11Orgasm 4.29 2.05 5.02 1.43 3.86 .05 0.05Satisfaction 3.92 1.45 4.77 1.61 5.37 .02† 0.07Pain 1.42 1.13 4.98 2.09 80.22 <.001§ 0.54

FSFI full scale 21.11 6.32 28.54 5.71 27.02 <.001§ 0.28SCL-90 total 120.74 32.48 104.89 12.86 7.21 .01† 0.10STAI trait 36.83 10.24 31.66 5.55 6.96 .01† 0.10PASS subscales

Fearful evaluation of pain 3.58 3.80 3.60 2.78 0.00 .98 0.00Cognitive anxiety 8.72 5.76 9.77 3.76 0.82 .37 0.01Physiologic anxiety 6.42 4.75 5.91 4.20 0.22 .64 0.00Flight and avoidance behavior 8.03 4.44 7.97 3.34 0.004 .95 0.00

PASS full scale 26.75 16.32 27.26 10.56 0.02 .88 0.00PVAQ subscales

Attention for pain 16.72 6.77 16.60 6.66 0.01 0.94 0.00Attention for changes in pain 12.75 5.39 13.51 5.86 0.33 0.57 0.01

PVAQ full scale 29.47 11.23 30.11 11.38 0.06 .81 0.001PCS subscales

Rumination 6.69 3.65 5.83 2.67 1.29 .26 0.02Magnification 2.03 2.05 1.51 1.65 1.35 .25 0.02Helplessness 4.67 4.45 2.54 2.01 6.65 .01† 0.09

PCS full scale 13.39 9.37 9.89 5.26 3.75 .06 0.05SES subscales

Arousability 2.84 0.39 2.97 0.23 3.01 .06 0.06Sexual power dynamics 2.59 0.48 2.76 0.37 1.95 .17 0.03Smell 2.74 0.72 3.04 0.50 3.65 .06 0.06Partner characteristics 2.47 0.49 2.67 0.47 2.25 .14 0.03Setting 2.21 0.55 2.43 0.46 0.37 .55 0.01

SES full scale 2.55 0.30 2.79 0.20 6.03 .02† 0.09SIS subscales

Relationship importance 2.89 0.42 2.76 0.39 1.25 .27 0.02Arousal contingency 2.53 0.71 1.94 0.40 17.06 <.001§ 0.21Concerns functioning 2.69 0.65 2.52 0.34 4.04 .05 0.06

SIS full scale 2.74 0.47 2.49 0.23 10.6 .002‡ 0.15

FSFI ¼ Female Sexual Function Index; PASS ¼ Pain Anxiety Symptoms Scale; PCS ¼ Pain Catastrophizing Scale; PVAQ ¼ Pain Vigilance and AwarenessQuestionnaire; PVD ¼ provoked vulvodynia; SCL-90 ¼ Symptom Check List; SES ¼ Sexual Excitation Scale; SIS ¼ Sexual Inhibition Scale; STAI¼ State-TraitAnxiety Inventory.*Range for FSFI subscales: desire (1e6), arousal (1e6), lubrication (1e6), orgasm (1e6), satisfaction (1e6), and pain (1e6). Lower scores indicate worsesexual functioning.†P < .05; ‡P < .01; §P < .001.

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Table 2. Ratings of US painfulness and fear and US expectancy for women with dyspareunia and controls

Dyspareunia (n ¼ 36) Controls (n ¼ 35)

F P value Partial h2Mean SD Mean SD

Painfulness of US* 3.74 0.56 3.57 0.50 1.82 .18 0.03Fear of the US* 2.36 0.96 2.40 0.88 0.03 .86 0.00US expectancy at CSþ presentation† 6.03 1.15 5.74 1.40 0.87 .35 0.01US expectancy at CS� presentation† 4.09 2.05 3.03 1.65 5.64 .02§ 0.08Fear at CSþ presentation‡ 3.47 2.10 3.91 2.01 0.82 .37 0.01Fear at CS� presentation‡ 2.42 1.52 2.00 1.28 1.55 .22 0.02

CS� ¼ conditional stimulus without painful shock; CSþ ¼ conditional stimulus with painful shock; US ¼ painful unconditional stimulus.*Scoring 1 ¼ not at all to 5 ¼ very strong.†Scoring 1 ¼ never to 7 ¼ always.‡Scoring 1 ¼ not at all to 7 ¼ very strong.§P < .05.

Aversive Conditioning in Dyspareunia 693

age of the participants in the two study groups was 25 years(range ¼ 19e45 years). Most women had a steady partner, nochildren, and a high educational level. There were no significantdifferences between groups in demographic characteristics, butwomen with dyspareunia significantly more often had a historyof sexual abuse. As expected, the FSFI total score of the controlgroup was within the normal range, whereas the score in thedyspareunia group was in the sexual dysfunctional range. Allmean FSFI domain scores were significantly lower in thedyspareunia group than in the control group, except for theorgasm domain score. Table 1 also presents dyspareunia char-acteristics; mean duration of the pain complaints was 4.9 years(range ¼ 0.67e26.0 years), half the women with dyspareuniahad lifelong pain complaints, and in most women provokedvulvodynia was determined based on the cotton-swab test duringthe physical examination.

As presented in Table 1, women with dyspareunia scoredsignificantly higher on the trait anxiety scale and on theSCL-90. Scores on the PASS and PVAQ did not significantlydiffer between groups, but women with dyspareunia scoredsignificantly higher on the PCS helplessness subscale. Further-more, women with dyspareunia scored significantly lower on theSE factor and significantly higher on the SI factor comparedwith controls.

US CharacteristicsTable 2 presents US painfulness and fear and US expectancy

and fear at presentation of the CSþ and CS� for the women withdyspareunia and controls. There were no significant differencesbetween groups in painfulness or fear of the US. Also, fear of theUS at presentation of the CSþ and CS� did not significantlydiffer between the two groups. US expectancy at presentation ofthe CSþ was similar for the two groups; however, US expectancyat presentation of the CS� was significantly higher for womenwith dyspareunia compared with controls.

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Physiologic Data

Preconditioning PhaseFigure 2 presents a summary of SCL in response to CSþ and

CS� across preconditioning, acquisition, and extinction trials foreach group. Unexpectedly, the 2 (stimulus)� 4 (trial)� 2 (group)mixed ANOVA to verify equal SCL levels during presentation ofthe CSs in the preconditioning phase showed a significant maineffect of stimulus for SCL FIR and SIR (FIR F1,66¼ 7.66, P< .01,partial h2 ¼ 0.10; SIR F1,66 ¼ 5.73, P < .05, partial h2 ¼ 0.08).Mean SCL was higher during presentation of the CSþ than duringpresentation of the CS�. There were no significant effects of groupor group � stimulus interactions.

Figure 3 presents a summary of VPA to CSþ and CS� acrosspreconditioning, acquisition, and extinction trials for each group.The 2 (stimulus) � 4 (trial) � 2 (group) mixed ANOVA toverify equal VPA levels during presentation of the CSs in thepreconditioning phase also unexpectedly showed a significantmain effect of stimulus (F1,65 ¼ 5.66, P < .05, partialh2 ¼ 0.08). Mean VPA was higher during presentation of theCS� than during presentation of the CSþ. There was no sig-nificant main effect of group and no group � stimulus interac-tion. To control for the unexpected initial difference inphysiologic responding to the CSþ and the CS�, in all furtheranalyses of the SCL and VPA data, the mean difference betweenthe response to the CSþ and the CS� during the preconditioningtrials was included as a covariate.

Acquisition PhaseThe 2 (stimulus) � 10 (trial) � 2 (group) mixed analysis of

covariance (ANCOVA) of SCL FIR showed no significanteffects. However, the 2 (stimulus) � 10 (trial) � 2 (group)mixed ANCOVA of SCL SIR showed a significant main effectof stimulus (F1,576 ¼ 8.58, P < .01, partial h2 ¼ 0.12). Asexpected, SCL SIR was higher in response to the CSþ. Therewere no significant trial or group interactions.

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A

B

Figure 2. Panels A and B show skin conductance level FIR and SIR change scores, respectively, in response to the CSþ and CS� during thepreconditioning, acquisition, and extinction phases for women with dyspareunia and controls. Skin conductance level SIRs duringthe acquisition phase are responses to the CSþ and the unconditional stimulus. CS� ¼ conditional stimulus without painful shock;CSþ ¼ conditional stimulus with painful shock; FIR ¼ first interval response; SIR ¼ second interval response.

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Figure 3. VPA change scores in response to the CSþ and CS� during the preconditioning, acquisition, and extinction phases for womenwith dyspareunia and controls. Responses during the acquisition phase are responses to the CSþ and the unconditional stimulus.CS� ¼ conditional stimulus without painful shock; CSþ ¼ conditional stimulus with painful shock; VPA ¼ vaginal pulse amplitude.

Aversive Conditioning in Dyspareunia 695

The 2 (stimulus) � 10 (trial) � 2 (group) mixed ANCOVA ofVPA showed no significant main effect of stimulus but didshow a stimulus � trial interaction approaching significance(F9,540 ¼ 1.82, P ¼ .09, partial h2 ¼ 0.03) and a stimulus �trial � group interaction approaching significance (F9,540 ¼1.91, P ¼ .07, partial h2 ¼ 0.03). Separate analyses for the twogroups showed a significant stimulus � trial interaction in con-trols (F9,288 ¼ 2.70, P < .05, partial h2 ¼ 0.08), whereas nosignificant effects were found in the dyspareunia group. Com-parison of VPA responses to the CSþ and CS� at each acquisi-tion trial for the two groups separately showed significant orborderline significant lower VPA in response to the CSþ

compared with the CS� at trial 6 (F1,32 ¼ 8.34, P < .005, partialh2 ¼ 0.21), trial 7 (F1,32 ¼ 4.23, P < .05, partial h2 ¼ 0.12),trial 8 (F1,32 ¼ 3.48, P ¼ .07, partial h2 ¼ 0.10), and trial 10(F1,32 ¼ 3.05, P ¼ .09, partial h2 ¼ 0.09) in the control group,whereas only trial 1 (F1,32 ¼ 4.33, P < .05, partial h2 ¼ 0.12)and trial 7 (F1,32 ¼ 4.65, P < .05, partial h2 ¼ 0.12) showedsignificantly lower VPA in response to CSþ compared with theCS� in the dyspareunia group.

Extinction PhaseThe 2 (stimulus) � 4 (trial) � 2 (group) mixed ANCOVA of

SCL FIR and SIR showed no significant main or interactioneffects of group, stimulus, or trial. The 2 (stimulus)� 4 (trial)� 2(group) mixed ANCOVA of VPA showed a significant stimulus�trial � group interaction (F3,195 ¼ 3.04, P < .05, partial

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h2 ¼ 0.05). Separate analyses for the two groups showed nosignificant effects in the control group, whereas a significantstimulus� trial interaction was observed in the dyspareunia group(F3,96 ¼ 3.06, P < .05, partial h2 ¼ 0.09). Comparison of VPAresponses to the CSþ and CS� at each extinction trial for the twogroups separately showed a significant higher VPA in response tothe CSþ compared with the CS� for the dyspareunia group at trial3 (F1,33 ¼ 6.34, P < .05, partial h2 ¼ 0.16), whereas no sig-nificant differences in responding to the CSþ and CS� wereobserved on any trial in the control group (P > .3 for allcomparisons).

Subjective Affect Ratings

PreconditioningThe 2 (stimulus) � 4 (trial) � 2 (group) mixed ANOVA of

ratings of affect during the preconditioning phase did not showsignificant effects, indicating similar affect ratings to the CSþ andCS� and no differences between groups (P > .5 for allcomparisons).

ExtinctionFigure 4 presents a summary of affect ratings to CSþ and

CS� during the extinction trials for each group. The 2(stimulus) � 4 (trial) � 2 (group) mixed ANOVA of affectratings in the extinction phase showed a significant main effectof stimulus (F1,67 ¼ 18.42, P < .001, partial h2 ¼ 0.22) and a

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Figure 4. Mean affect ratings in response to the CSþ and CS� during the extinction phase for women with dyspareunia and controls.CS� ¼ conditional stimulus without painful shock; CSþ ¼ conditional stimulus with painful shock.

696 Both et al

stimulus � group interaction approaching significance(F1,67 ¼ 2.79, P ¼ .09, partial h2 ¼ 0.04). Affect ratings werelower to the CSþ, showing more negative affect in response to theCSþ compared with the CS�. This difference was less prominentin the dyspareunia group. There was no stimulus � trialinteraction, indicating no extinction of the conditioned affectiveresponse, which was confirmed by the observation of a significantlower affect rating at trial 4 for the CSþ compared with the CS�

(F1,64 ¼ 12.82, P < .001, partial h2 ¼ 0.17).

Sexual Arousal Ratings

PreconditioningThe 2 (stimulus) � 4 (trial) � 2 (group) mixed ANOVA of

ratings of sexual arousal during the preconditioning phase didnot show significant effects, indicating similar sexual arousalratings to the CSþ and CS� and no differences between groups(P > .6 for all comparisons).

ExtinctionFigure 5 presents a summary of sexual arousal ratings to CSþ

and CS� during the extinction trials for each group. The 2(stimulus) � 4 (trial) � 2 (group) mixed ANOVA of sexualarousal ratings in the extinction phase showed a significant maineffect of stimulus (F1,67 ¼ 12.75, P < .005, partial h2 ¼ 0.16)and a stimulus � group interaction approaching significance(F1,67 ¼ 3.28, P ¼ .07, partial h2 ¼ 0.05). Sexual arousal ratings

were lower to the CSþ, showing less sexual arousal of the CSþ

compared with the CS�. This difference was less prominent in thedyspareunia group. There was no stimulus � trial interaction,indicating no extinction of the conditioned sexual arousalresponse, which was confirmed by the observation of a significantlower sexual arousal rating at trial 4 for the CSþ compared with theCS� (F1,64 ¼ 8.31, P < .01, partial h2 ¼ 0.12).

Associations Between Conditional Responding andTrait Anxiety, Pain-Related Emotions andCognitions,and Sexual Excitation and Inhibition TendencyTo examine associations between the strength of the differ-

ential conditioning effects and levels of trait anxiety, psycho-logical distress, pain-related emotions and cognitions and thetendency toward sexual excitation and inhibition, we calculatedcorrelations between the magnitude of the differential physio-logic and subjective responses to the CSþ and CS� at the firstextinction trial (response to CSþ minus response to CS�) andthe trait anxiety, SCL-90, PVAQ, PCS, PASS, and SE and SIfactor scores (Table 3). There was a significant negative corre-lation between the PASS scores and the SCL SIR CSþ-CS�

difference scores and between the PCS scores and the SCL FIRCSþ-CS� difference scores. Higher pain anxiety and pain cata-strophizing scores were associated with less increased SCL inresponse to the CSþ compared with the CS�. Furthermore, therewas a significant positive correlation between SI factor scores andVPA CSþ-CS� difference scores; higher SI factor scores were

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Figure 5. Mean sexual arousal ratings in response to the CSþ and CS� during the extinction phase for women with dyspareunia andcontrols. CS� ¼ conditional stimulus without painful shock; CSþ ¼ conditional stimulus with painful shock.

Aversive Conditioning in Dyspareunia 697

associated with less decreased VPA in response to the CSþ

compared with the CS�.

In addition, we examined associations between levels of traitanxiety, psychological distress, pain-related emotions and cog-nitions and the tendency toward sexual excitation and inhibition,SCL and fear of the US, and US expectancy ratings (Table 4).There was a significant correlation between PASS scores and USexpectancy ratings at presentation of the CS�. Higher painanxiety scores were associated with stronger US expectancy atpresentation of the CS�.

Table 3. Correlations between trait anxiety, psychological distress,pain anxiety, pain catastrophizing, pain vigilance, sexual excitationand sexual inhibition and US expectancy, fear of US, and skinconductance level at US delivery in all women (N ¼ 61)

US expectancyat CSþ

US expectancyat CS�

Fear ofUS

SCL SIRat CSþ

Trait anxiety 0.06 0.18 �0.10 0.07SCL-90 0.06 0.12 0.09 �0.11PVAQ �0.08 0.05 �0.09 �0.05PASS 0.08 0.27* �0.06 �0.08PCS �0.06 0.23 0.08 �0.05SES �0.09 �0.05 0.01 0.10SIS 0.02 0.05 �0.07 0.07

CS� ¼ conditional stimulus without painful shock; CSþ ¼ conditionalstimulus with painful shock; PASS ¼ Pain Anxiety Symptoms Scale;PCS ¼ Pain Catastrophizing Scale; PVAQ ¼ Pain Vigilance and AwarenessQuestionnaire; SCL-90 ¼ Symptom Check List; SES ¼ Sexual ExcitationScale; SIR ¼ second interval response; SIS ¼ Sexual Inhibition Scale;US ¼ painful unconditional stimulus.*P < .05.

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DISCUSSION

This study investigated the effects of aversive pain condi-tioning on sexual arousal and affect in women with dyspareuniaand sexually functional controls. As expected, and in agreementwith previous studies,21,22 pairing of a sexual stimulus with apain stimulus resulted in decreased feelings of sexual arousal andincreased negative affect toward this stimulus. However, incontrast to expectations, the differences in affect and sexualarousal toward the stimulus that was paired with pain and thestimulus that was not paired with pain tended to be less prom-inent in women with dyspareunia than in controls. VPA re-sponses at the extinction trials did not show decreased genitalarousal toward the sexual stimulus that was paired with pain.However, during the acquisition phase, an inhibiting effect of thepain stimulation on VPA was observed over trials but was moreprominent in controls than in women with dyspareunia.Furthermore, women with dyspareunia showed, as expected,higher levels of anxiety, pain catastrophizing, and sexual inhibi-tion, but, in contrast to expectations, pain catastrophizing andsexual inhibition were not associated with stronger but withweaker differential aversive conditioning effects.

How can we explain these unexpected outcomes? Remarkably,the two groups showed a significant difference in US expectancy.They reported a similar US expectancy at presentation of theCSþ, but women with dyspareunia reported a stronger US ex-pectancy for the CS� compared with the controls. Thus, womenwith dyspareunia expected more strongly to receive the painstimulus at presentation of the “safe” stimulus, the stimulus thatwas never paired with pain. Possibly, because of the higher pain

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Table 4. Correlations between trait anxiety, psychological distress, pain anxiety, pain catastrophizing, pain vigilance, sexual excitation andsexual inhibition, and magnitude of conditioned subjective affect, subjective sexual arousal, vaginal pulse amplitude, and skin conductancelevel at first extinction trial

CSþ-CS� affect CSþ-CS� sexual arousal CSþ-CS� VPA CSþ-CS� SCL FIR CSþ-CS� SCL SIR

Trait anxiety 0.09 0.17 0.10 �0.01 0.01SCL-90 �0.08 �0.01 �0.03 �0.02 0.04PVAQ �0.07 �08 �0.05 �0.06 �0.04PASS �0.03 0.03 �0.14 �0.21 �0.24*PCS �0.03 0.05 �0.06 �0.28* �0.22SES �0.11 �0.16 �0.13 �0.08 0.09SIS 0.12 0.19 0.26* �0.16 �0.15

CS� ¼ conditional stimulus without painful shock; CSþ ¼ conditional stimulus with painful shock; FIR ¼ first interval response; PASS ¼ Pain AnxietySymptoms Scale; PCS ¼ Pain Catastrophizing Scale; PVAQ ¼ Pain Vigilance and Awareness Questionnaire; SCL ¼ skin conductance level;SCL-90 ¼ Symptom Check List; SES ¼ Sexual Excitation Scale; SIR ¼ second interval response; SIS ¼ Sexual Inhibition Scale; VPA ¼ vaginal pulseamplitude.*P < .05.

698 Both et al

expectancy at presentation of the safe sexual stimulus, and thusless discrimination between the safe and the unsafe stimuli,women with dyspareunia showed weaker differential VPAresponses to the two sexual stimuli during the acquisition phaseand weaker differential subjective affect and sexual arousal to thetwo stimuli.

Interestingly, in other conditioning studies in patient groupsin which one stimulus was paired with pain and another stimuluswas not, often no differential effects toward these stimuli wereobserved. In fact, studies with patients with anxiety disordershave shown increased fear responding to the threat stimulus andthe safety stimulus.50e54 Based on these observations, it has beenhypothesized that subjects with anxiety disorders fail in the in-hibition of fear, even during the appearance of safety signals.55

Recent studies also have observed deficient safety learning inindividuals with high trait anxiety, which is a known risk factorfor developing anxiety disorders.56 In this context, it is inter-esting that higher levels of anxiety have been observed in womenwith dyspareunia,3,4 including the present study, and that weobserved less prominent effects of differential aversive condi-tioning in this group.

Remarkably, similar learning deficits have been observed inpatients with pain. For example, in pain conditioning studies inpatients with fibromyalgia, after conditioning, novel stimuli eli-cited fear responses, irrespective of the perceptual resemblance tothe original CSþ and CS�, indicating non-differential general-ization of fear.57,58 The investigators suggested that this learningdeficit might be involved in the maintenance of chronic pain.When potential harm and safety are not successfully identified, itleads to sustained anxiety and fuels the spreading of fear andavoidance behaviors.20 Our observations of higher pain expec-tancy at presentation of the safe stimulus, less prominent dif-ferential genital responding to the CSs during acquisition, andweaker conditioning effects on subjective affect and sexualarousal in women with dyspareunia indicate that deficient safetylearning also might be involved in chronic sexual pain.

Thus, returning to our hypotheses, pairing of a sexual stimuluswith pain does result in more negative affect and lower feelings ofsexual arousal in response to that stimulus. However, ourobservations in women with dyspareunia suggest that it mightnot so much be enhanced pain conditioning, but rather deficientsafety learning, that is important in chronic sexual pain. Womenwith dyspareunia seem to expect pain at the safe stimulus and theunsafe stimulus. When potential harm and safety in sexual sit-uations are not adequately identified, this can lead to a gener-alized fear of sex and decreased sexual arousal and desire. This isin line with the observations of low sexual desire and complaintsof decreased sexual arousal and vaginal lubrication in womenwith dyspareunia.7,11,12

Apart from the unexpected outcomes in women with dys-pareunia, we unexpectedly did not replicate our previousobservations of decreased VPA in the extinction phase inresponse to the sexual stimulus that was paired with pain.Because the aversive conditioning procedure in the present studywas similar to the procedure in our previous studies,21,22 pro-cedural differences cannot account for this lack of replication.However, as noted earlier, in the present study, unexpectedly,VPA and SCL levels in response to the CSþ and CS� weresignificantly different in the preconditioning phase. This is hardto explain, because the two sexual pictures were carefully coun-terbalanced. We controlled statistically for these unexpecteddifferences, but it could have hampered the observation of dif-ferential conditioning effects. In addition, although most par-ticipants reported that they perceived the pain stimulus as fairlypainful, most reported that fear of the US was only moderate.Possibly, a more fearful pain stimulus would have resulted instronger and more consistent conditioning effects. However,reported pain and fearfulness of the US in the present study werenot lower than in our previous studies; therefore, a difference inUS intensity cannot explain lack of replication. We conclude thatthe effects of sexual conditioning measured by genital respondingare not strong and are inconsistent.

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Aversive Conditioning in Dyspareunia 699

For future studies, several improvements and additions shouldbe considered. The inclusion of an unpaired or randomizedcontrol group could help to distinguish learning about the CSþ

(enhanced pain learning) from learning about the CS� (deficientsafety learning). Also, expectancy ratings at each trial will provideinsight on the association of US expectancy and responses to theCSs over trials. It is important to determine whether the observedstronger pain expectancy at the “safe” CS in women with dys-pareunia is a robust phenomenon. Also, it would be interestingto investigate whether women with dyspareunia show non-differential generalization of conditioned responses byincluding stimuli that vary in perceptual resemblance to theoriginal CSþ and CS�. Furthermore, inclusion of a largernumber of extinction trials is needed to investigate resistance ofextinction of conditioned responses. In addition, given theimportant role of the pelvic floor muscle activity in sexual painproblems, it would be interesting to test the effects of aversivepain conditioning on pelvic floor muscle activity.19 Also, becauseof the suggestion of disgust as an important aversive factorinvolved in sexual dysfunction59,60 and evidence of disgust re-sponses to sexual stimuli in women with sexual pain disorders,60

it would be interesting to study the effects of repeated sex-disgustpairing.

Although we should be cautious of the generalizability of thestudy results, because women with dyspareunia who volunteer ina pain conditioning study that includes the insertion of a vaginalmeasurement device might differ from the clinical dyspareuniapopulation and the experimental setting is obviously differentfrom the experience of pain in actual sexual encounters, theresults from the present study have some important clinicalimplications. The results show that repeated pairing of a sexualstimulus with pain results in stronger negative affect anddecreased feelings of sexual arousal. Other findings from ourlaboratory showed that conditioned affect can be relativelypersistent.22 These findings emphasize the importance, as a firststep in treatment, to advise women with dyspareunia and theirpartners to refrain from painful penetration to prevent furtheracquisition of the link between sex and pain. Because womenwith dyspareunia can have the tendency to continue withintercourse despite pain because they see intercourse as their dutyin a heterosexual relationship,14 it is very important to explainthe rationale of this advice carefully to the couple. At the sametime, the findings point to the possibility that in subsequenttreatment, a combination of extinction and counterconditioning(learning a new opposite response) would plausibly be mosteffective to restore sexual arousal and positive affect toward sex.Importantly, our results indicate that women with dyspareuniamight have a tendency to expect pain even in response to “safe”sexual stimuli, which can result in sustained pain anxiety andavoidance behaviors. Prolonged avoidance and safety behavior,which could be strengthened by a tendency toward pain cata-strophizing and sexual inhibition, prevents confrontation withfeared stimuli and situations, precluding extinction of learned

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fear responses. Moreover, avoidance of even safe sexual situationswill hinder the recovery of positive sexual associations andthrough that desire for sex.10 In line with this, avoidance andpain catastrophizing have been identified as predictors of theoutcome of cognitive behavioral treatment of dyspareunia.61

Recent studies have shown that partner reactions are importantin this respect.62e64 Highly solicitous partners might encourageavoidance of sexual intercourse, which could prevent extinctionof fear toward penetration. Interestingly, a recently developedtherapist-aided in vivo exposure treatment for women with life-long vaginismus and their partners, with a strong focus on theprevention of avoidance behavior in the performance of pene-tration exercises, has been shown to be highly effective.65

Although exposure procedures in sexual pain problems have tobe handled with care, it would be interesting to investigatewhether systematic approaches to challenge avoidance behavioralso could improve cognitive behavioral treatment for patientswith dyspareunia.

Corresponding Author: Stephanie Both, PhD, Department ofPsychosomatic Gynaecology and Sexology, Leiden UniversityMedical Centre, Albinusdreef 2, 2300 RC Leiden, TheNetherlands. Tel: þ31-71-526-8032; fax: þ31-71-526-6950;E-mail: [email protected]

Conflicts of Interest: The authors report no conflicts of interest.

Funding: None.

STATEMENT OF AUTHORSHIP

Category 1

(a) Conception and Design

Stephanie Both; Marieke Brauer; Philomeen Weijenborg

(b) Acquisition of Data

Stephanie Both; Marieke Brauer; Philomeen Weijenborg

(c) Analysis and Interpretation of Data

Stephanie Both; Marieke Brauer; Philomeen Weijenborg;Ellen Laan

Category 2

(a) Drafting the Article

Stephanie Both

(b) Revising It for Intellectual Content

Stephanie Both; Marieke Brauer; Philomeen Weijenborg;Ellen Laan

Category 3

(a) Final Approval of the Completed Article

Stephanie Both; Marieke Brauer; Philomeen Weijenborg;Ellen Laan

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