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GENDER MEDICINE/VOL. 8, NO. 6, 2011

Relationship Between Resting Blood Pressure and Laboratory-Induced Pain Among Healthy ChildrenKelly Haas, MD1,2; Qian Lu, PhD3; Subhadra Evans, PhD3; Jennie C.I. Tsao, PhD3; and

onnie K. Zeltzer, MD3

1University of California, Irvine School of Medicine, Irvine, California; 2UCLA Pediatric ResidencyProgram, University of California-Los Angeles, Los Angeles, California; and 3Department of Psychology,University of Houston, Houston, Texas

ABSTRACTBackground: Adult studies have demonstrated that increased resting blood pressure (BP) levels correlateith decreased pain sensitivity. However, few studies have examined the relationship between BP and

xperimental pain sensitivity among children.Objectives: This study investigated the association between resting BP levels and experimental pain

olerance, intensity, and unpleasantness in healthy children. We also explored whether these BP–painelationships were age and gender dependent.

Methods: Participants underwent separate 4-trial blocks of cutaneous pressure and thermal pain stimuli,and 1 trial of a cold pain stimulus in counterbalanced order.

Results: A total of 235 healthy children (49.6% female; mean age 12.7 [2.9] years; age range 8–18 years)articipated. The study revealed specific gender-based BP–pain relationships. Girls with higher restingystolic BP levels were found to have lower thermal intensity ratings than girls with lower resting systolicP levels; this relationship was stronger among adolescent girls than among younger girls. Among youngirls (8–11 years), those with higher resting diastolic BP (DBP) levels were found to have lower coldntensity and unpleasantness as well as lower thermal intensity ratings than did young girls with loweresting DBP levels; these DBP–pain response relationships were not seen among adolescent girls.

Conclusions: Age, rather than resting BP, was predictive of laboratory pain ratings in boys. The findingssuggest that the relationship between BP and experimental pain is age and gender dependent. These aspectsof cardiovascular relationships to pain in males and females need further attention to understand theirclinical importance. (Gend Med. 2011;8:388–398) © 2011 Elsevier HS Journals, Inc. All rights reserved.

Key words: blood pressure, children, gender differences, laboratory pain.

Accepted for publication July 13, 2011. doi:10.1016/j.genm.2011.07.002

© 2011 Elsevier HS Journals, Inc. All rights reserved. 1550-8579/$ - see front matter

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INTRODUCTIONThe relationship between blood pressure (BP) andpain has attracted the increasing interest of painresearchers during the past 2 decades. It was pro-posed that increased resting BP levels would allowfor a more rapid stimulation of baroreceptor paininhibitory activity with sympathetic stimulation,thus leading to reduced pain.1 Studies amongadults have shown that hypertension is associatedwith decreased experimental pain responsivity.2–7

The adult offspring of hypertensives also showeddecreased pain responses to a variety of experi-mental pain stimuli compared with individualswithout a family history of hypertension.2,8

Among healthy adults with BP in the normalrange, there was also an inverse association bet-ween resting BP and pain responses, such that ahigher resting BP was correlated with lower labora-tory pain responsivity. This laboratory pain relation-ship has been demonstrated with both resting sys-tolic BP (SBP)1,2,8–27 and resting diastolic BPDBP).12,16,17 Although several experimental studiesnvolving adults have found an inverse relationshipetween resting BP and pain responses in both mennd women.15,16,20,23,26 others have demonstratedhis relationship in men only11,13,14,17,22 and in

women only,2,9,10,12,18,21,24 suggesting the necessityf examining gender differences in the BP–painesponse.

Despite convincing evidence of the relationshipetween BP and acute experimental pain responsesn adults, few studies have examined this relation-hip among children and adolescents. Ditto et al28

found that resting SBP was negatively correlatedwith finger pressure pain intensity ratings in boys.The same research group found resting SBP to benegatively correlated with finger pressure pain in-tensity and unpleasantness among male adoles-cents at a 5-year follow up.29 However, this longi-tudinal study only involved boys, and thus theBP–pain relationship among girls is unknown.There is also a dearth of information on how theBP–pain association may change as a function ofdevelopment.

The first goal of this study was to examine therelationship between resting BP and laboratory-in-

duced pain among children and adolescents, and to p

investigate how this association varied as a functionof gender and age. We hypothesized that resting BPwould be positively correlated with pain tolerance,and negatively correlated with pain unpleasantnessand pain intensity in healthy children and adoles-cents. We explored whether these BP–pain relation-ships were age and gender dependent.

The second goal of this study was to examinegender differences in BP in children and adoles-cents and explore whether such differences in BPaccount for gender differences in pain. Amongadults, gender differences have been noted in BP,with women displaying lower average resting SBPlevels than do men.20,30 Similarly, studies amonghildren and adolescents indicate that girls haveower resting SBP levels than do boys.31,32 Based onhe previous studies, we hypothesized that healthyemales would exhibit lower resting BP levels than

ales.Meta-analysis and review articles have suggested

hat adult women have greater experimental painesponses33 and higher prevalence of clinical painompared with men.34 Gender differences in ex-erimental pain responses are also evident amongdolescents for pressure and cold experimentalain stimuli, although it remains unclear what me-iates these gender differences.35–37 As studies

have shown that elevated resting BPs are generallyhigher in males than females, and also that higherBPs are associated with decreased pain measures, itseems that resting BP might be a potential media-tor for gender differences in pain responsivity. Abetter understanding of the factors that mediategender differences in pain sensitivity among chil-dren and adolescents can help to guide future clin-ical treatment of pain, and might help us to betterunderstand pain regulation and signaling.

METHODSParticipants

All recruitment and study procedures were ap-roved by the University of California, Los Ange-

es, Institutional Review Board (IRB), as well as theRBs of recruitment sites. Study participants wereecruited from a major urban area through massailings, posted advertisements, and classroom

resentations. Telephone interviews confirmed

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initial eligibility of 472 (96.5%) of the 489 individ-uals who were screened; 17 children (3.5% of thosescreened) were excluded due to use of medicationsor acute or chronic illnesses that might have af-fected study outcomes. An additional 228 (48%)individuals declined participation, mainly due tolack of parental interest (54%) or time (21%). Allparticipants completed IRB approved consent andassent forms for parents and children, respectively.Participants received a $30 video store gift certifi-cate and a t-shirt for their participation.

A total of 244 healthy children (124 female;50.8%) participated in the study. The participantshad a mean (SD) age of 12.7 (3.0) years (range,8–18 years), with ages of males (mean [SD], 12.4[3.0] years) and females (mean [SD], 13.0 [3.1]years) closely matched. The ethnic composition ofthe sample was 40.2% whites, 13.9% African-American, 9.8% Asian-American, 23.8% Hispanic,and 12.3% other. The socioeconomic status of theparents included 3.7% unskilled workers, 4.1%semi-skilled workers, 11.9% clerical/sales, 41.8%technical, and 34.8% professional. A total of 9participants did not have BP measurement re-corded, and were not included in the analysis.Thus, data from 235 healthy children (49.6% fe-male; mean age 12.7 [2.9] years; range 8–18 years)were used for analysis in this study.

Overview of ProcedureLaboratory sessions included the completion of

emographic characteristics and psychosocialuestionnaires and three laboratory pain tasks.wo experimenters conducted the laboratory ses-ions between 8 A.M. and 8 P.M. Parents and chil-ren were escorted into separate rooms, and didot have contact with one another during the ses-ions. After completing the questionnaires in auiet room, participants were seated in a chair inhe adjacent laboratory. Participants were in-tructed on the use of the visual analog scalesVAS) for rating pain intensity and unpleasantnessfter each task. After a 15-minute laboratory habit-ation period, resting SBP and DBP were measuredsing the Dinamap (Wipro GE Healthcare, Mil-aukee, Wisconsin) monitor 3 times with a 1-min-

te interval between each reading. t

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Participants then completed 3 laboratory painasks, including tactile pressure, heat, and cold pres-or. The pressure and heat tasks included 4 trials withubject-uninformed identical ceilings in a counter-alanced order across participants. A 2- to 3-minuteesting baseline period preceded the first trial of eachlock and a 1-minute resting period preceded each ofhe other 3 trials. Two sites were used for the pressurend heat tasks to avoid local sensitization or habitu-tion. Two intensities were also used to allow forreater variation in pain response. The cold pressorask consisted of 1 trial with a 3-minute uninformedeiling.

Laboratory Pain TasksPressure Task

The Ugo Basile Analgesy-Meter 37215 (Ugoasile, Collegeville, Pennsylvania) was used to ad-inister focal pressure through a Lucite point ap-

roximately 1.5 mm in diameter to the secondorsal phalanx of the middle finger and index fin-er of each hand. Two of the 4 trials had a pressuref 322.5g and 2 trials had a pressure of 465g. Eachrial had an uninformed ceiling of 3 minutes, andhere was a 1-minute rest interval between eachrial. A similar device was used in healthy andlinical pediatric samples (aged 5–17 years) with-ut adverse effects.38,39

Thermal TaskThe Ugo Basile 7360 Unit was used to administer

adiant heat 2 inches proximal to the wrist and 3nches distal to the elbow on both volar forearms.our trials with 2 infrared intensities (15, 20) weredministered with an uninformed ceiling of 20econds. There was a 1-minute rest interval be-ween each trial. Thermal pain tolerance was elec-ronically measured with an accuracy of 0.1 sec-nd. A comparable task was used in a sample agedto 17 years without adverse effects.40

The presentation order of both tasks (includingetting and site of exposure) was counterbalancedcross participants. Before each trial, subjects werenformed that they would be experiencing sensa-ions of discomfort that might eventually be per-eived as pain. Participants were instructed to con-

inue with the task as long as they could, but that

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they were free to end the task at any time if itbecame too uncomfortable or painful. All taskswere extensively piloted on volunteers in the tar-geted age range.

Cold Pressor TaskA commercial ice chest measuring 38 cm wide,

1 cm long, and 35 cm deep filled with 10°C wateras used for the cold pressor task. The ice chest

ontained a plastic mesh screen that separatedrushed ice from a plastic large-hole mesh armrestn the water. A pump circulated the cold water torevent local warming around the hand. Partici-ants were asked to keep their dominant hand inhe water for as long as they could with an unin-ormed ceiling of 3 minutes at a depth of 2 inchesbove the wrist.

Laboratory Pain MeasuresPain Tolerance

Pain tolerance was defined as the time in sec-nds elapsed from the onset of the pain stimuluso the participants’ withdrawal from the stimulus.

Pain Intensity and Pain UnpleasantnessA vertical sliding VAS was used to assess pain

ntensity and pain unpleasantness after each trial.he VAS is a brief, easily understood, and sensitiveo changes in pain. Previous research has shown itan be used by children 8 to 18 years old,41 and itas previously been used to rate pain in childrenuring laboratory pain tasks.42

The slider VAS used in this study had numbersrom zero at the bottom to 10 at the top. The scalelso ranged from white at the bottom to red at theop, as well as faces ranging from neutral at theottom to a negative facial expression at the top.articipants were told the slider VAS was like ahermometer that would measure their feeling or

ood, and they were instructed to slide the barlong the scale until the shade matched how muchain or discomfort they felt. Participants com-leted 3 practice ratings to ensure their compre-ension of how the VAS would be used during the

xperiment. i

ain IntensityImmediately after each laboratory pain trial,

articipants were asked to use the VAS to rate themount of pain they experienced during the task.articipants were asked, “At its worst, how muchain did you feel?” during the task.

ain UnpleasantnessImmediately after the participants rated pain in-

ensity, they were asked to use the VAS to rate themount of distress or bother they experienced dur-ng the task. Participants were asked, “At its worst,ow much did the task bother you?” Due to alter-tions in procedure during the study, pain un-leasantness ratings were only obtained for a sub-et (78%) of participants.

Blood Pressure Recording and AnalysisAfter a 15-minute laboratory habituation time pe-

iod, BP was measured 3 times using a Dinamaponitor with a 1-minute interval between each mea-

urement. The mean values of resting SBP and DBPeasurements were calculated for statistical analysis.

Statistical AnalysisAll variables were normally distributed except for

ressure tolerance and cold tolerance. These vari-bles were log transformed to produce normal distri-utions. Independent t tests were used to examineean differences in resting SBP and DBP levels be-

ween boys and girls for 2 age groups: children (8–11ears) and adolescents (12–18 years). Initial bivariateorrelation analysis was used to examine the associ-tion between BP and all experimental pain responseeasures among boys and girls separately.A set of hierarchical regression analyses were

sed to predict pain responses (ie, pain tolerance,ain intensity, pain unpleasantness) from the BPeasurements within girls and boys separately. In

lock 1, age was entered as a predictor. In block 2,BP and DBP were entered as predictors. In block 3,he interaction of SBP and age and the interactionf DBP and age were entered as predictors. Eachegression analysis was conducted for pain toler-nce, intensity, and unpleasantness for each tasks dependent variables (predicted variables). Con-inuous variables were centered for creating the

nteraction term.43

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RESULTSTable I shows descriptive statistics for BP andaboratory pain response for boys and girls. Inde-endent t tests did not reveal gender differences inesting SBP or DBP. However, further examinationhowed adolescent boys (12–18 years old) exhib-ted significantly higher resting SBP levels (meanSD] 110 [12] mm Hg) than adolescent girls (mean04 [0.5] mm Hg), with a mean difference of 6.1two-tailed P � 0.003); whereas there was no such

gender difference in SBP among children (8–11years old). No significant gender differences inDBP were found within the older and younger agegroups.

Table I. Descriptive statistics of study participants and la

Pain Measures

n Minimum

Boys Girls Boys Gir

Resting SBP 119 116 81.50 72.Resting DBP 119 116 43 42.BMI 92 92 13.65 12.Pressure tolerance 119 120 2.22 3.Pressure intenstity 119 120 0 0Pressure unpleasantness 93 94 0 0Heat tolerance 120 120 1.15 1.Heat intensity 120 120 0 0Heat unpleasantness 94 94 0 0Cold tolerance 119 120 4.73 5.Cold intensity 120 120 0 0Cold unpleasantness 94 94 0 0

BMI � body mass index; DBP � diastolic blood pressure; SBP �

Table II. Significant correlations between blood pressure

CharacteristicPressure

ToleranceThermal

ToleranceCold

Tolerance

BoysResting SBP 0.330†

Resting DBP

GirlsResting SBP 0.228* 0.196*Resting DBP

DBP � diastolic blood pressure; SBP � systolic blood pressure.*P �0.05.

†P �0.001.

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Table II shows results of bivariate correlationetween BP and pain response measures in boysnd girls, respectively. Results supported our initialypothesis that elevated resting BP would be asso-iated with lower pain response measures. Amongoys, higher resting SBP was associated withreater thermal tolerance and decreased thermalntensity ratings. Among girls, higher resting SBPas associated with greater pressure and thermal

olerance, and decreased cold intensity ratings.igher resting DBP was also associated with de-

reased cold intensity ratings among girls.Table III shows results from hierarchical re-

ressions predicting laboratory responses from BP

ry pain measures.

Maximum Mean SD

Boys Girls Boys Girls Boys Girls

38 127.67 105.36 102.52 11.71 11.0283.00 91.50 60.71 61.97 8.06 8.8641.19 45.64 21.18 21.25 5.15 5.5479.9 180 45.91 34.68 47.09 43.799.76 9.76 4.66 5.08 2.47 2.729.46 9.76 3.45 3.53 2.67 2.58

20.00 20.00 11.03 10.51 5.25 5.049.76 9.76 4.95 5.03 2.76 2.789.76 9.76 3.39 3.57 2.73 2.67

80 180 52.16 54.66 53.09 55.799.76 10 3.33 3.8 2.62 3.069.76 9.76 2.84 3.04 2.81 2.82

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and age among girls. Age was positively associatedwith pressure and thermal tolerance, and negativelyassociated with pressure and thermal intensity. TheSBP by age interaction was significant on thermalpain intensity, such that the inverse relationship be-tween SBP and thermal pain intensity was strongerin adolescent girls compared with younger girls (Fig-ure 1). The DBP and age interaction were significantfor cold and thermal intensity and cold unpleasant-ness, such that the inverse relationship between DBPand pain was more evident in female children thanin female adolescents. Figures 2 through 4 showhat female children (age 8–11 years) with low rest-

Table III. Significant results of heirarchical regression amomeasures.

Predictors (B)(IndependentVariables)

PressureTolerance

ThermalTolerance

ColdTolerance

Age 0.342† 0.480†

esting SBP 0.242*esting DBPesting SBP*ageesting DBP*age2 Change 0.154* 0.254† 0.027

DBP � diastolic blood pressure; SBP � systolic blood pressure;*P �0.05.†P �0.001.

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High SBP(>=103 mmHg)

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Figure 1. Plotted relationship between systolic bloodpressure (SBP) and thermal intensity ratings

among adolescent and younger girls.

ng DBP had greater cold intensity, cold unpleasant-ess, and thermal intensity ratings than those withigh resting DBP measurements. However, adoles-ent girls (age 12–18 years) had similar pain ratingsor these measurements regardless of their restingBP level. The interaction of BP and age explainedbout 6%, 9%, and 9% of variance of thermal in-ensity, cold intensity, and cold unpleasantness,espectively.

Table IV summarizes the results from hierar-chical regressions predicting pain responses fromBP and age among boys. Age was positively asso-ciated with all 3 tolerance measures, and nega-

ls: age and blood pressure as predictors of laboratory pain

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PressureUnpl.

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tively associated with pressure and thermal inten-sity, and pressure and thermal unpleasantness.The interactions between BP and age were not sig-nificant on any pain response among males.

DISCUSSIONWe hypothesized that resting BP would be posi-tively correlated with pain tolerance, and nega-tively correlated with pain unpleasantness andpain intensity in healthy children and adolescents.The hypotheses were supported among femalechildren for thermal intensity, cold intensity, andcold unpleasantness. More specifically, girls (8–11years) with low resting DBP levels displayed greatercold pain intensity, cold unpleasantness, and ther-mal intensity ratings than did those with highresting DBP levels (Figures 2–4). These relation-ships did not occur among female adolescents (age12–18 years) or boys of any age. In addition, theinverse relationship between SBP and thermal in-tensity was more intense among adolescent girlsthan among younger girls (Figure 1).

Our results are unique, as resting DBP ratherthan SBP was significantly related to cold painresponse measures as well as thermal intensity rat-ings among young girls. However, among adoles-cent girls, SBP was found to be related to thermalintensity ratings, which mimics findings amongadult studies. Previous studies among children

Figure 3. Plotted relationship between diastolic bloodpressure (DBP) and cold intensity ratings amongadolescent and younger girls.

found resting SBP and DBP to be correlated with

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pain response measures; however, these studies in-cluded only boys who were of similar age.29 Themajority of adult studies have found correlationsbetween resting SBP and experimental pain mea-sures, but a limited number of studies have foundthat resting DBP might be related to pain sensitiv-ity. Among adults, resting DBP has been negativelycorrelated with ischemic pain unpleasantness inboth men and women.16 Other studies involvingdults have found positive correlations betweenBP and thermal tolerance in women only12 or

men only.17 However, several other studies havefound no correlation between DBP and pain re-sponse measures for a variety of experimental paintasks among adults.14,20,22,23 Thus, research amongadults regarding the relationship between DBP andpain response measures is inconclusive.

Current research regarding BP and pain sensitiv-ity among children and adolescents is very limited.One longitudinal study found that resting DBPand SBP were positively correlated with pressurepain tolerance and negatively correlated with pres-sure pain intensity in a group of 19-year-old malesafter controlling for parental history of hyperten-sion and body mass index (BMI).29 These earlierdata contradict our results, which found that pres-sure tolerance, intensity, and unpleasantness werenot significantly associated with resting BP mea-surements among males. This might be due to theage difference in study participants; the previous

Figure 4. Plotted relationship between diastolic bloodpressure (DBP) and cold unpleasantness ratings

among adolescent and younger girls.

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K. Haas et al.

study included 119 males of similar age, whereasour study included 120 males ranging from 8 to 18years.29 Our study indicates that age, not restingBP, is a significant predictor of tolerance for all 3pain tasks, pressure and thermal intensity, andthermal unpleasantness among boys 8 to 18 yearsof age.

To our knowledge, there are no studies involv-ing female children or adolescents examining therelationship between resting BP levels and experi-mental pain sensitivity. Thus, our results indicat-ing that girls (8–11 years) with low resting DBPhave greater cold intensity and unpleasantness rat-ings and thermal intensity ratings than girls withhigh resting DBP levels are unique. It is unclearwhat mechanism leads to this relationship amongfemale children, but not among boys or femaleadolescents. Our results indicating that adolescentgirls with elevated resting SBP had lower thermalintensity ratings is also unique. It is unclear whythese relationships were found among girls but notboys.

Although age was associated with pressure andheat tolerance among females, resting DBP had aunique predictive value for self-reported variablessuch as cold unpleasantness and cold and thermalintensity among girls (8–11 years). It is unclearwhy this relationship among girls only occurredfor self-reported variables involving the cold pres-sor and thermal experimental pain stimuli. Studies

Table IV. Significant results of heirarchical regression amomeasures.

Predictors (B)0(IndependentVariables)

PressureTolerance

ThermalTolerance

ColdTolerance

Age 0.592† 0.695† 0.512†

Resting SBPResting DBPResting SBP*ageResting DBP*ageR2 Change 0.240† 0.434† 0.227†

B � Beta; DBP � diastolic blood pressure; SBP � systolic blood*P �0.05.†P �0.001.

among adults have shown that women rely more m

on external cues rather than internal physiologicalstate alone to determine their response to a stim-ulus.44 Self-reported variables require a participantto integrate their internal physiological responsewith external cues, such as visualization of thecold pressor water bath, color change of the handin water, or redness of the skin with the thermaltask. Perhaps the young girls in this study alsorelied on these external cues more than boys todetermine their subjective rating of pain intensityor unpleasantness.

In accordance with existing studies regarding BPin children and adolescents,31,32 our hypothesishat females would exhibit lower resting BP levelshan males was confirmed only among adolescentsor SBP. Adolescent males had significantly higheresting SBP levels than adolescent females. Thereere no gender differences for SBP in younger chil-ren; DBP did not differ between boys and girls

rrespective of age. This study indicates there areender and gender by age BP/experimental painelationships in children. However, further studiesre indicated to determine if resting BP is a medi-tor of gender differences in experimental painensitivity among healthy children and adoles-ents. These studies could help to clarify potentialender differences in pain regulatory pathways,uch as baroreceptor modulation or adrenergic sys-ems, and guide future clinical practice in pain

ys: age and blood pressure as predictors of laboratory pain

endent Variables

uresity

ThermalIntensity

ColdIntensity

PressureUnpl.

ThermalUnpl.

ColdUnpl.

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Most theories regarding the relationship be-ween resting BP levels and pain response mea-ures have focused on SBP rather than DBP. SBPnd DBP are regulated by several complex mecha-isms, including sympathetic tone and the renin–ngiotensin–aldosterone system. The relationshipetween resting BP levels and laboratory pain re-ponsivity might be explained by an interactionetween pain regulatory pathways and BP levelshrough sympathetic activation and modulationf descending pain pathways.1,13 Pain induces

sympathetic arousal, which increases BP levels andstimulates baroreceptors. One function of thebaroreceptors is to initiate a signaling cascade thatcauses pain inhibitory activity. One theory sug-gests that increased resting BP levels would allowfor a more rapid stimulation of baroreceptor paininhibitory activity with sympathetic stimulation.1

Another study indicated that it is the degree ofphasic baroreceptor stimulation, and not the toniclevel of stimulation, that is important, becauseparticipants reported less pain during systole thandiastole.45 Our data does not directly support thistheory, as female children with high DBP, not SBP,reported lower cold unpleasantness and intensitylevels. It is possible that this pain inhibitory sys-tem is regulated somewhat differently among chil-dren and adolescents than in adults.

A number of limitations to the study are worthnoting. Previous studies with adults have con-trolled for BMI during analysis, as this provides ameasure of obesity and might impact resting BPlevels. Initial correlation analysis indicated thatBMI was significantly correlated with age and rest-ing BP levels. Although we attempted to collectheight and weight information, BMI data wereavailable for only 184 of the 240 participants.However, additional analyses of these 184 partici-pants (data not shown) indicated that inclusion ofBMI in regression analysis did not alter the previ-ously mentioned results that were obtained with-out the inclusion of BMI. Future research in thisarea needs to be more vigilant about collectingBMI data, perhaps by increasing a sense of privacyduring weight measurement, as this may impactan adolescent’s willingness to be weighed. Future

studies might incorporate continuous BP monitor-

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ing throughout pain tasks to assess BP reactivityand its relationship to pain sensitivity among chil-dren. Another useful variable to evaluate in futurestudies would be a measure of anticipatory anxietybefore pain tasks to assess the relationship be-tween anxiety, resting BP levels, and laboratorypain sensitivity. Future studies might also addressthe role of sex steroid hormones and how the tim-ing of menarche might affect the BP–pain relation-ship as suggested in adult studies.46 Lastly, thisstudy was a cross-sectional study that determinedthe association between BP and pain responsivity,but no causation could be assessed. Longitudinalstudies or experimental studies would help to clar-ify the temporal or causal relationship between BPand pain.

CONCLUSIONFemale adolescents and adults report greater clin-ical pain and have greater experimental pain sen-sitivity than boys of similar age. Among adults,women generally have lower resting BP levels thando men of similar age and health status. Thesefindings indicate that BP might be involved ingender differences in pain responsivity. Our studyfound that for boys, age, rather than resting BP,was associated with experimental pain sensitivitymeasures. For girls, however, the relationship be-tween BP and pain responses varied as a functionof age. An interaction between age and resting DBPwas evident, such that girls (8–11 years) with highresting DBP levels displayed lower cold pain inten-sity and unpleasantness ratings as well as thermalintensity ratings than did girls with low restingDBP levels. Among adolescent girls, an interactionbetween age and resting SBP was found, indicatingthat girls with high resting SBP levels had lowerthermal pain intensity than those with low restingSBP levels. Our study points to future researchamong children and adolescents to examine BP asa potential mediator for gender differences in lab-oratory and clinical pain responsivity.

ACKNOWLEDGMENTSDr. Haas was the primary author of this article andperformed the statistical analysis under the super-

vision and guidance of the Pediatric Pain Program

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team, including Drs. Zeltzer, Tsao, Evans, and Lu.The authors have indicated that they have no con-flicts of interest regarding the content of thisarticle.

This study was supported by R01DE012754,awarded by the National Institute of Dental andCraniofacial Research (PI: Dr. Zeltzer), by UCLAGeneral Clinical Research Center Grant M01-RR-00865 (PI: Dr. Zeltzer), and by 1K01AT005093,awarded by the National Center for Complemen-tary and Alternative Medicine (PI: Dr. Evans).

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Address correspondence to: Subhadra Evans, PhD, Pediatric Pain Program, David Geffen School of Medicine at

90064. E-mail: suevans@mednet.ucla.edu.