Abnormal extracranial vasomotor response in migraine sufferers to real-life stress

Journal of Psychosomatrc Research, Vol. 31, No. 4, pp. 405-414, Printed in Great Britam

ABNORMAL

EXTRACRANIAL

MIGRAINE JAN

PAsscriiER,*t (Received

1993.

SUFFERERS PLONA

0022-3999193 %6.00+.00 Pergamon Press Ltd

VASOMOTOR TO REAL-LIFE

GOUDSWAARD*

27 May 1992; accepted

and JACOBUS

in revised form

RESPONSE

IN

STRESS F.

15 September

ORLEBEKE~ 1992)

Abstract-Temporal and digital pulse amplitudes, forehead temperature, heart rate, respiration rate and electrodermal activity of 37 migraine patients and 37 matched controls from a population of psychology students were recorded during three experimental sessions: adaptation, real-life stress (an examination) and experimental stress (an IQ test). Migraine sufferers showed significantly smaller pulse amplitudes of the temporal artery during the examination than the control group. No group differences were present in the other physiological measures. The findings are interpreted as indirect evidence for the symptom specificity hypothesis, which states that individuals with specific psychosomatic complaints display abnormal responses to stress in the relevant physiological system.

INTRODUCTION

and clinical studies have suggested that emotional stress is a major trigger factor for migraine attacks [ l-31 . In addition to these retrospective studies, several prospective investigations have been carried out using a diary in which the patients not only noted their headaches, but also the stress or the moods they experienced [4-91. The overall outcome, here, seems to be only slightly in favour of the hypothesis which states that stress is a causal factor for a migraine attack. The statement that stress is a causal factor for migraine headaches requires the determination of its mechanisms. Several decades ago, migraine headaches were considered to originate from a vascular pathophysiology; this view was based on the findings of Wolff [lo]. In later years, studies on the pathogenesis of migraine focused on cerebral phenomena, and extracranial vascular disturbances were considered to be the painful sequelae of central processes [ 1 l-161 . Recent focus on the role of 5-HT [ 171 and the beneficial effects of the 5-HT,, receptor agonist sumatriptan [ 181 has stirred new interest in the extracranial vascular abnormalities of migraine. Extracranial vascular responses of migraine patients to stress have been studied fairly extensively. Several investigators have found that the temporal artery blood flow of migraine patients was higher than that of control subjects [ 19,201. Other studies, however, did not report abnormal responses [21-231, or reported a decrease in the flow [24] . In addition, the general character of the stress response of the temporal artery has remained unclear, because some researchers found dilation [ 19-231 and others constriction of the artery [ 241 or equivocal responses [ 25-271. According to several authors [27,28] the studies performed so far involve the EPIDEMIOLOGICAL

*Institute of Medical Psychology and Psychotherapy, Erasmus University Rotterdam. TDepartment of Physiological Psychology, Vrije Universiteit, Amsterdam, The Netherlands. Address correspondence to: J. Passchier, Institute of Medical Psychology and Psychotherapy, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. 405

406

J. PASSCHIER et al.

limitations that most stressors were of a brief duration and that their relevance to the subject can be questioned. They recommend the use of stressors of long duration and with high salience. A second point of criticism is that the physiological stress responses of migraine patients have never been studied in real-life stress situations. Therefore, the present study focused on the measurement of extracranial vascular responses of migraine sufferers exposed to real-life stress and to a standard experimental condition of at least 1 hr. The study questions were: (1) Do migraine patients show an abnormal extracranial vascular response during stress in comparison with control subjects? (2) Are the differences in vascular response between migraine patients and controls specific or part of a general sympathetic response? METHOD Subjects

and selection

procedure

A population of psychology students were chosen because their curriculum made it possible to use a standardized real-life stressor in the form of an examination. A translated version of the Headache Questionnaire of Waters 1291 was sent to 3.50 undergraduate psychology students and was answered by 72%. The first two authors independently interviewed the subjects among the respondents who reported symptoms indicative of migraine (as described below) and a history of headaches during at least the past year with a minimum of two attacks or one relatively long-lasting headache period (more than 8 hr) per month. Each rater verified the headache history and symptoms on the Headache Questionnaire and gathered further information as described elsewhere [ 301. The diagnosis of the headache type was made on the basis of the definition of the Ad Hoc Committee on the Classification of Headaches [3 1] After selection, it appeared that none of the subjects reported prodromata; therefore they were all classified as common migraine sufferers. It should be emphasized that the selection method cannot rule out the possible inclusion of mixed muscle contraction migraine sufferers. Furthermore, our diagnosis took place before the Headache Classification of the International Headache Society was published. Reexamination of the subject characteristics showed that each person had migraine without aura according to this classification [32] A group of 37 common migraine sufferers (30 women, 7 men; mean age 21.6 yrs + 3.7 yr) participated in this study. From the same initial sample, 37 controls were selected who closely matched the migraine sufferers in terms of age and sex. As both groups were recruited from the same student population, it can be assumed that intelligence and socioeconomic background were largely similar. The 37 controls (30 women, 7 men; mean age 21.7 yrs f 3.6 yr) had an average of less than one, nonmigrainous, headache attack per month. None of the migraine sufferers or controls used any medication apart from an occasional aspirin or paracetamol tablet. Subjects were paid for their participation and gave their consent after having received extensive information about the experimental procedure. Measurement

and apparatus

Physiological measurements. The physiological recordings were made in an electrically shielded, soundproof room. Subjects were seated in an upright position behind a desk while reading or writing. EMG and vasomotor activity were measured; for the migraine sufferers the EMG electrodes and the photoplethysmographic transducer were applied to the side of the head where the pain was usually most severe. The investigation side was chosen at random for the controls and for the subjects with generally bilateral severe headaches. Physiological activity was recorded on a Beckman Type 702 polygraph and a Bell and Howell FM recorder. Analogue-digital conversion was carried out on-line by a PDP 1 l/O4 computer. The pulse amplitudes of the temporal and digital arteries were recorded by reflectance photoelectric transducers. The transducers were locally designed and built in order to obtain calibrated measures which are not contaminated by the effects of temperature. Another advantage of these transducers is that instead of relative measures, absolute measures can be analyzed. This was performed by using calibration media with similar reflective and elastic properties to those of the skin. Details of the construction of the transducers can be found in Goudswaard et al. [ 331. Temporal pulse amplitudes (TPA) were registered from the zygomatico-facial branch of the superficial temporal artery near the external auditory meatus. Digital pulse amplitudes (DPA) were registered in the distal phalanx of the middle finger of the non-writing hand. The EMGs of the m. frontalis, m. anterior temporalis and

Migraine

and stress

407

m. corrugator supercilii were recorded by means of three pairs of Ag-AgCl surface electrodes. For details on the EMG measurement, we refer to a previous publication on the EMG findings [34]. The heart rate (HR) was derived from the finger plethysmogram and the respiration rate (RR) was measured using a Philips strain gauge mercury belt, placed around the subjects’ chest. Forehead temperature (TEMP) was measured by a thermistor positioned on the forehead. Skin conductance (SC) and spontaneous skin conductance responses (SCRs) were registered by means of two active Siemens Ag-AgCl surface electrodes with an effective area of 0.5 cm* attached to the index and fourth fingers of the non-writing hand. Self-report measures. Subjects indicated their headache intensity on an 1 l-point scale, ranging from 0 to 10, during the task sessions. State anxiety was measured using a Dutch version of the STAI state (S-ANX) scale [ 35 ]

Subjects were medication-free during the period of registration. The experiment consisted of three separate registration sessions, beginning with an adaptation session, during which the subjects were familiarized with the measurement procedure. After the electrodes had been attached, the subjects were instructed to refrain from unnecessary body movements and take up their usual posture for reading or writing. After an adaptation period of 10 min, in which the subjects filled out S-ANX and sat reading quietly, the physiological activity was recorded over three 1-min periods separated by two-minute intervals. In a second session, the physiological activity was recorded before, during and after a psychology examination which was part of the subject’s curriculum. A baseline recording was made after 10 min of adaptation prior to starting the examination. The subjects recorded their headache intensity, completed the S-ANX and read quietly during the remaining time. After the subjects had commenced the examination, recordings were carried out immediately: during the first 5 min at 2 min intervals and from then on at intervals of 10 min until the subjects had completed the examination. A final recording was made after a post-stress recovery period of 10 min during which the subjects recorded their headache intensity (as experienced while taking the examination) and completed the S-ANX. In a third session, the subjects were given an intelligence test in the form of the Letter Series Test for inductive reasoning [ 361. This test took approximately 1.5 hr to complete and served as an experimental stress-stimulus of long duration. The investigation procedure applied in this session was identical to that in the second session. The sequence of the second and third sessions was randomized. Data reduction The amount of time needed to complete the examination or IQ test differed considerably across the subjects, resulting in various numbers of registration periods. Most of the subjects took about 1 hr (10 registration periods) to complete the examination and about 1.5 hrs (12 registration periods) to complete the IQ test. The three measurements from the adaptation session were averaged. For the examination we took the pre-stress baseline period, the first and last periods of the task and the post-stress recovery period. Corresponding periods were used for the IQ test session. Data analysis Firstly, separate ANOVAs were carried out to investigate the differences in physiological measures between the migraine subjects and controls. The ANOVAs had to be performed in two series because of the unequal number of measurement periods in the sessions. The first series of ANOVAs concerned the base levels and had two between subject factors, i.e. ‘group’ (migraine vs control) and ‘sex’ (female vs male) and one within subject factor, i.e. ‘session’, with three levels (adaptation, examination and IQ test). ‘Sex’ was included in the analyses because it was considered to be a potential systematic source of variance that had to be separated from the error variance (its effects are not reported because of the small number of participating males). Two orthogonal contrasts with equal weights for each cell were computed: the first between the adaptation session and the examination session, the second between the adaptation session and the IQ test session. The second series of ANOVAs was performed on the two task sessions, with the within subject factors ‘session’, now with two levels (examination versus IQ test) and ‘period’, with four levels (baseline, begin task, end task and recovery). In addition, ANOVAs were performed on each separate task session in case there was a significant group effect. Significant effects of task and period were analyzed by Student t-tests. Secondly, ANOVAs were performed on the migraine group for each task session separately to investigate whether the migraine sufferers who had developed a headache during the sessions responded differently from those who were headache-free. Finally, Student t-tests were performed on the S-ANX with ‘gmup’ as the independent variable, in order to determine the relevance of situational anxiety as a confounding variable of the effects found.

408

J. PASSCHIER et al. RESULTS

Migraine Table

versus controls I shows the significant

TABLE I.--SIGNIFICANT

EFFECTSOF THE ANOVAs

Independent variables Anovas Session

Group Anovas Group

Dependent* variables

F

WITH GROUP, SESSION AND PERIOD

P l-2

f-tests 2-3

3-4

on base-levels

x session

TEMP HR SC SCR

12.09 12.41 14.29 4.57


-

-

TEMP

3.55

< 0.05

-

-

4.46

including period TPA

Session

Period

Session

effects of the ANOVAs.

x Period

Group x Session x Period

< 0.05

-

TEMP HR RR SCR

28.71 51.32 7.67 16.61

< 0.001 < 0.001 < 0.01
-

TPA TEMP DPA HR SCR DPA HR SCR

25.04 7.43 50.46 116.76 34.19 9.90 9.29 3.81

< 0.001
TEMP

3.50

< 0.025

* * *

-

* * * *

*

*IQ

*EX *EX

*IQ

*TPA = temporal pulse amplitude; DPA = digital pulse amplitude; HR = heart rate; RR = respiration rate; TEMP = forehead temperature; SC = skin conductance; SCR = spontaneous skin conductance response. Significant r-tests within period are indicated by an asterisk (l-2: baseline vs begin; 2-3: begin vs end; 3-4: end vs recovery; EX: in examination only; IQ: in IQ-test only).

ANOVAs on base levels. No group effect was significant. There were a number of significant main effects of session. Additional t-tests revealed that HR was higher in the examination than in the adaptation session. In the IQ test session, SC and TEMP were significantly lower than in the adaptation session. TEMP, HR and number of SCRs were significantly higher during the examination than the IQ test. Finally, a significant group x session effect was found on TEMP. The t-tests revealed that the migraine sufferers had significantly higher TEMP in the IQ test than the control subjects. ANOVAs on task sessions including period. The only main effect of group involved TPAs: migraine sufferers had smaller TPAs than control subjects (see Fig. 1). ANOVAs on each separate session showed that this effect reached significance in the examination but not in the IQ test. Significant effects of session reflected higher TEMP, HR and RR and more SCRs in the examination than in the IQ test. The significant effects of period indicated a significant decrease from baseline to the beginning of the tasks in DPA and TEMP, and an increase in HR. From the beginning to the end of the tasks, a significant decrease was found in TPA, DPA and HR, and an increase in TEMP. Finally, the HR continued to decrease from the end

Migraine

409

and stress

Examination

IQ-test

TPA (arbitrary units)

TPA (arbitrary units) 0 35,

Arj B

1

I

2

3

1 I

4

5

1 I

I

I

6

8

9

7

I

1 I , AdB

10 11 12 R

12

3

4

5

6

7

8

,

I

7

8

910R

910R

Period

Penod

DPA (arbitrary units)

DPA (arbitrary urxts) 0 25,

0.25,

OL

Ad B

1

1

I

#

P

1

2

3

4

5

6

I

I

I

7

8

9

I

1

I

I

10 11 12 R

0.050 Lb AdB

I 12

3

,

I

5

6

I

Penod

Penod Forehead temperature

I 4

Forehead temperature

(“C)

(“C)

33 8 -S

-o-

Mlgralne

Control

-

33 7 1

-0.

Mlgralne

Control

h I,,,,,,

Ad B

1

2

3

4

5

I

I

6

7

I

8

9

I1

1

v

33 AdB

10 11 12 R

12

3

5

6

7

8

910R

Heart rate (beats/mln)

Heart rate (beats/ml@

90

90 --t

85

4

Period

Penod

-o-

Mlgratne

Control

85

t

1

0.

Mlgralne

Control

1

65-1 60

60 AdB

12

3

4

5

6

7

8

9101112R

Ad8

12

3

4

5

Period

Period

FIG. 1. Continued.

6

7

8

910R

,

410

J. PASSCHIERet al.

Examination

IQ-test Respiration rate (cycles/min)

20

20 --t

154-i+,

I

I

I

1

Migrame

8

1

1 -m-

Respiration rate (cycles/min)

I

8

- 0 - Control

1

1

8

1

19

’

Ad B 1 2 3 4 5 6 7 6 9 10 11 12 R

l&r

I

AdB

1

I

12

I

3

1 t

I

I

4 5 6 Period

Period

I

I

7

8

I

I

,

910R

Skin conductance (umho)

Skin conductance (umho)

12

12 --t

- 0 - Control

Migraine

Migrame

-o- Control

11 10

_-o_

9

Migraine

.a--o-

_

-o-

_

Control

_

_o--o* ‘D

a 7 6&r, Ad B

8 r

1

2

1 ,

3

4

1 r

a 1 8 8 8 a I

5 6 7 Period

8

9 IO 11 12 R

iw SLr, AdB

9 r

12

8 ,

3

0

,

r

910R

a

7, 6

0-Q

P----’

‘,\ 5

Migrame

‘o-

5

4 3 Ad 0

u ,

7

Spontaneous scrs (number)

Spontaneous scrs (number) 7I

2L-

8 ,

4 5 6 Period

1

2

3

4

I I 1 I I I ,

5 6 7 Period

0

I I

9 IO 11 12 R

24+, AdB

“tZ_Q

‘0

-o-

Control

‘o_ o-o-_o

‘0

1

12

I

I

3

1

I

1

4 5 6 Penod

I

I

7

8

1

I

t

910R

FIG. 1. Physiological measures as a function of group, session and period. The average for the adaptation session is presented at the far left of each graph (‘Ad’ on the X axis).

of the tasks to the recovery period. Significant session X period effects on DPA, HR and SCRs can be attributed to differential responses during the examination and the IQ test. Separate t-tests demonstrated that the increase in the HR from baseline to the beginning of the task only reached significance in the examination. Further, a significant decrease in DPA from beginning to the end was found in the IQ test only, and a significant decrease in the SCRs was found in the recovery period in the examination only. A significant group x session x period effect on TEMP can be attributed to a higher forehead temperature in the migraine group during the baseline of the IQ test.

Migraine and stress

State variables

411

during the tasks

Seventeen migraine sufferers reported having a headache during the examination and 14 during the IQ test (both mean intensities were low: 3.1). No significant physiological differences were found between the subjects who had a headache during the examination or the IQ test and those who were headache-free (see Table II). S-ANX during the examination or the IQ test was not significantly different between migraine sufferers and controls (each p > 0.19). S-ANX was significantly higher before the examination than before the other sessions (each p < O.OOl), and higher during the examination than during the IQ test @ < 0.01). DISCUSSION

Differences

in physiological

responses

of the groups

The main finding in the present study was that the migraine sufferers showed smaller pulse amplitudes of the arteria temporalis superficialis during the examination than the control subjects. This difference can be considered as specific because none of the other physiological measures differed between the groups. Moreover, a post-hoc ANCOVA on the TPA during the examination with the temporal EMG, HR and RR as covariates, showed that the difference between migraine sufferers and controls remained significant and that it was not mediated by activity of the cardiac, temporal and respiratory muscles. Further the state-anxiety scores in the migraine group were not higher than those in the control group, which suggests that the lack of temporal vasodilatation cannot be explained by a normal physiological response to abnormal mental stress in the migraine sufferers. The finding of an abnormal TPA-response in migraine patients confirms the symptom-specificity theory of Malmo and Shagass [37], which states that individuals with specific psychosomatic complaints display abnormal responses of the relevant physiological system when exposed to stress. DiYerences

in responses

to tasks

The examination seemed to be associated with higher HR and more SCRs than the IQ test. The subjects also demonstrated significantly higher state anxiety during the examination than during the IQ test. Overall, these findings indicate the presence of more stress in the examination session. The lack of consistent differences in physiological activity and state anxiety between the IQ test and the adaptation session might be attributed to the stressful aspects of the latter situation because it involved the subject’s first confrontation with the unfamiliar laboratory surroundings. The ‘period’ effects generally showed an increase in sympathetic activity from baseline to the beginning of the task and a decrement from the beginning of the task to the end of the recovery period, which also indicates that the stress manipulation was carried out successfully. The view expressed by several authors [27,28] that stressors have to be of long duration in order to elicit clear stress responses, was not confirmed in our study; generally the strongest reactions were found at the beginning of the tasks, while the physiological activity stabilized or diminished towards their end.

0.19 0.17 33.40 33.40

absent present

absent

present absent present

TPA

DPA

TEMP

absent present

base = baseline;

SCR

Ad = adaptation;

SD

(3.2) (3.9)

(6.8) (5.3)

(1.9)

(2.7)

(9.9) (16.7)

(0.13) (0.68) (0.41)

(0.15)

(0.17) (0.22)

ret = recovery.

5.5 7.3

10.3 13.1

16.1

absent present

present

SC

16.8

absent

RR

72.8 77.9

absent present

HR

0.20 0.25

Headache

Ad

4.6 4.7

9.5 8.5

16.8

17.3

73.7 71.0

0.20 33.23 33.37

0.20

0.17 0.26

base

3.9 3.6

10.3 8.8

17.7

17.1

74.0 73.0

0.16 33.06 33.13

0.17

0.16 0.18

begin

3.5 2.9

8.0 8.4

16.7

16.4

70.5 68.4

0.10 33.15 33.04

0.11

0.12 0.12

end

IQ test

2.8 2.6

7.2 8.2

15.5

16.2

66.1 64.1

0.17 33.03 32.92

0.11

0.13 0.14

ret

(2.3) (2.2)

(5.4) (3.2)

(3.6)

(1.8)

(9.4) (8.7)

(0.11) (0.60) (0.54)

(0.13)

(0.07) (0.14)

SD

5.4 6.7

8.7 13.3

17.6

17.0

78.8 75.8

0.16 33.49 33.48

0.20

0.27 0.18

base

4.7 6.3

8.9 13.0

18.8

17.9

86.5 79.6

0.10 33.44 33.43

0.09

0.21 0.15

begin

3.2 4.4

9.0 12.7

17.7

17.6

78.8 75.9

0.09 35.54 33.57

0.10

0.16 0.12

end

Examination

2.7 3.3

8.4 12.2

17.2

16.5

70.6 69.0

0.11 33.46 33.53

0.09

0.17 0.11

ret

(2.3) (1.9)

(4.7) (18.2)

(2.5)

(2.7)

(9.2) (9.9)

(0.08) (0.54) (0.49)

(0.06)

(0.12) (0.10)

SD

ACTIVITY WITHIN THE MIGRAINE GROUP DURING EACH SESSIONAS A FUNCTION OF THE HEADACHE STATE DURING THAT SESSION. MEAN SDS ACROSS THE SESSIONSARE BETWEEN PARENTHESES

Physiological variable

TABLE IL-PHYSIOLOGICAL

?-

F % B i;; P ~

?

Migraine and stress

Diferences

in physiological

responses

between

headache

413

states

On the basis of the vascular theory of migraine [lo] we expected that the subjects with a headache during the experiment would have shown more temporal artery dilatation than the other migraine subjects. No significant differences, however, were found between the migraine sufferers with and without a headache during the sessions. These headaches appeared to be relatively mild and did not urge the subjects to stay away from or to quit the task situation. It is possible that only a fullblown migraine attack is associated with Wolff’s increase in temporal artery flow. Further, considering the high prevalence of other headaches among migraine patients [ 381, the mild headaches during the tasks might have been tension headaches instead of migraine. Our finding that the TPAs of this subgroup were (insignificant) smaller than those in the headache absent subgroup indicates relative vasoconstriction and supports this tension headache explanation [ 391 . Post-hoc comparisons between the TPA of the headache absent patients and the control group revealed that a smaller TPA was still apparent in the first group. CONCLUSION

Migraine sufferers from a general population of psychology students showed a lack of vasodilatation of the temporal artery in response to a real-life stress load. This abnormal response was not related to any other peripheral vascular response or to sympathetic activity. It was specific in the sense that it was not mediated by anxiety, but it was partly attributable to the rise of a (mild) headache. In which extent this response reflects the prodromal stage of an impending migraine attack has to be investigated in a future study, in which patients who develop a (diagnostically confirmed) migraine attack following the stressor are compared with those who remain migraine-free. Acknowledgemenrs-The study was supported by a grant from the Nederlandse Wetenschappelijk Onderzoek (NWO; Dutch Organisation for Scientific Research) Psychomedical and Psychotherapeutical Research Rotterdam (CEPPOR).

Organisatie voor and the Centre of

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