ORIGINAL ARTICLE

Pain rather than induced emotions and ICU sound increases

skin conductance variability in healthy volunteers
€rt
€nther1,2, A. R. Schandl1,3, J. Berhardsson4, A. Bja
A. C. Gu a4, M. W € Sundin4, J. Alvarsson5,
allgren4, O.
6 1,3 1,3
M. Bottai , C.-R. Martling and P. V. Sackey
1
Section for Anesthesiology and Intensive Care, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
2
Department of Cardiothoracic Surgery and Anesthesiology, Karolinska University Hospital, Stockholm, Sweden
3
Department of Anesthesiology, Surgical Services and Intensive Care Medicine, Karolinska University Hospital Solna, Stockholm, Sweden
4 €
Division of Social Sciences, Department of Psychology, Mid Sweden University, Ostersund, Sweden
5
Marcus Wallenberg Laboratory, Department of Aeronautical and Vehicle Engineering, School of Engineering Sciences, Royal Institute of
Technology, Stockholm, Sweden
6
Unit of Biostatistics, Department of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

Correspondence Background: Assessing pain in critically ill patients is difficult. Skin

A. C. Gu€nther, Department of Cardiothoracic
Surgery and Anesthesiology, Karolinska
University Hospital, 17176 Stockholm, Sweden
E-mail: anders.gunther@karolinska.se
Conflicts of interest
The authors have no conflicts of interest.
Funding
Funding was supplied from by the Department
of Anesthesiology, Surgical Services and
Intensive Care Medicine, Karolinska University
Hospital Solna. A grant was supplied from
Vinnova Innovations Agency, Ministry of
Enterprise, Energy and Communications,
Stockholm, Sweden. The design of the study,
data collection, analysis, interpretation,
writing, and publication of the manuscript
were done by the authors without
participation or influence from any of the
funding sources.
Submitted 22 March 2016; accepted 6 May
2016; submission 5 October 2015.
conductance variability (SCV), induced by the sympathetic response to
pain, has been suggested as a method to identify pain in poorly commu-
nicating patients. However, SCV, a derivate of conventional skin conduc-
tance, could potentially also be sensitive to emotional stress. The
purpose of the study was to investigate if pain and emotional stress can
be distinguished with SCV.
Methods: In a series of twelve 1-min sessions with SCV recording, 18
healthy volunteers were exposed to standardized electric pain stimula-
tion during blocks of positive, negative, or neutral emotion, induced
with pictures from the International Affective Picture System (IAPS).
Additionally, authentic intensive care unit (ICU) sound was included in
half of the sessions. All possible combinations of pain and sound
occurred in each block of emotion, and blocks were presented in ran-
domized order.
Results: Pain stimulation resulted in increases in the number of skin
conductance fluctuations (NSCF) in all but one participant. During pain-
free baseline sessions, the median NSCF was 0.068 (interquartile range
0.013–0.089) and during pain stimulation median NSCF increased to
0.225 (interquartile range 0.146–0.3175). Only small increases in NSCF
were found during negative emotions. Pain, assessed with the numeric
rating scale, during the sessions with pain stimulation was not altered
significantly by other ongoing sensory input.
Conclusion: In healthy volunteers, NSCF appears to reflect ongoing
autonomous reactions mainly to pain and to a lesser extent, reactions to
emotion induced with IAPS pictures or ICU sound.

Editorial comment: what this article tells us

Variation in skin conductance is influenced by pain, emotions, and sound. The authors performed
a volunteer study to evaluate if variability in skin conductance to pain can be used as an analgesia
trigger. This method appears to identify mainly pain and responds less to emotions and ICU
sound. Trends rather than a single absolute number seem to better identify if the subject was in
pain.

Acta Anaesthesiologica Scandinavica 60 (2016) 1111–1120

ª 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd 1111
 €
A. C. GUNTHER ET AL.
Citation
Gu€nther AC, Schandl A, Berhardsson J, Bj€art
a
A, W € Alvarsson J, Bottai
allgren M, Sundin O,
M, Martling C-R, Sackey PV. Pain rather than
induced emotions and ICU sound increases
skin conductance variability in healthy
volunteers. Acta Anaesthesiologica
Scandinavica 2016
doi: 10.1111/aas.12751
Critically ill patients experience significant
levels of pain and discomfort while in the ICU.
During the ICU stay, patients may be exposed
to disease-related pain, as well as therapy-
induced pain. Unrelieved acute pain may lead to
negative physiological and psychological conse-
quences.1 Evaluation and treatment of pain in
ICU patients has shown to be associated with
shorter duration of mechanical ventilation and
ICU stay, as well as reduced adverse events.2–4
Assessing pain in ICU patients may, however,
be difficult as many ICU patients are not able to
communicate or self-rate their experience. So
far, the only method to assess pain in non-com-
municative patients has been by observing
behavioral indicators of pain.5,6
There has recently been growing interest in
palmar skin conductance variability (SCV) and
it has been suggested for detecting autonomous
responses to nociceptive stimulation.7–9
Skin conductance variability is derived from
traditional skin conductance measurement used
for monitoring autonomic nervous system acti-
vation in basic psychology research, and also in
research on populations with problems such as
phobias and post-traumatic stress.10,11 In short,
distress increases sympathetic activation of
palmar and plantar sweat glands, leading to
increased electrical conductivity (i.e., skin con-
ductance). Traditional skin conductance moni-
toring measures the change in absolute skin
conductance in response to a stimulus. In con-
trast, SCV is an online method that identifies
fluctuations of skin conductance caused by
ongoing palmar sweat release and reabsorp-
tion.7,8 Thus, SCV is less sensitive to individual
baseline skin conductance or body temperature
than absolute measures of skin conductance
and mirrors current sympathetic neuronal
activity.12,13
1112 ª 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
Skin conductance variability has shown to be
a valid method for pain assessment in post-
operative patients.14 Results from a recent study
in ICU patients indicated that pain induced SCV
changes in these patients.15 However, SCV
increased not only due to painful stimulation
but also appeared to increase due to emotional
stress as assessed with the Motor and Activity
Assessment Scale.15
Our aim was to, with an experimental design
in healthy subjects, investigate if SCV could dis-
tinguish between pain and emotional stress.
Moreover, we hypothesized that pain would be
perceived more intensely during simultaneous
potentially stressful exposures, namely negative
visual stimuli and ICU sound.
Methods
After approval from the regional ethics commit-
tee in Stockholm, Sweden, we conducted the
experiment at the Psychology Laboratory, at the
Department of Psychology, Mid-Sweden Univer-
€
sity, Ostersund, Sweden.
Participants
Twenty healthy volunteers (mainly psychology
students) were invited to the study and 18 par-
ticipated (seven men and 11 women with a
median age of 25 years, ranging from 20 to
53 years) in the study. One participant revealed
afterwards that he had scored pain levels falsely
high in the pain titration part of the experiment
and was therefore excluded. One participant did
not come for the experiment as planned. Rea-
sons for exclusion were pregnancy, chronic
pain, heart problems including pacemakers, or
the use of psychotropic drugs. All participants
signed an informed consent.
Acta Anaesthesiologica Scandinavica 60 (2016) 1111–1120

Procedure
Participants were seated in a chair in a quiet lab
room in front of a computer and were given
headphones. Electrodes for measuring skin con-
ductance were placed on the palmar side of the
left hand. A pain stimulator was placed on the
index finger of the right hand. Participants
could not see the investigators but were moni-
tored by a remote camera.
Each participant was exposed to twelve exper-
imental conditions (sessions), each lasting 60 s.
Between each session, there was a 1-min resting
period. The 12 sessions consisted of all possible
combinations of two pain states (pain/no pain),
three different emotion-inducing picture batter-
ies (positive, negative, or neutral), and two
sound states (sound/no sound). After each ses-
sion, a message on the screen instructed partici-
pants to relax until they heard a sound,
indicating the start of the next session.
Materials, apparatus and exposures
E-prime (Psychology Software Tools Inc,
Sharpsburg, PA, USA) was used to program the
experiment with triggers for electrical stimula-
tion, pictures, and sound playback, as well as
data collection from online self-reports.
Standardized electrical pain stimulation
Pain was induced with the Coulbourn Transcu-
taneous Aversive Finger Stimulator (Coulbourn
Instruments, Whitehall, PA, USA), with remote
triggering via Biopack Systems MP150 (BIO-
PACK Systems INC, Goleta, CA, USA). The
electrical stimulus was delivered to the distal
phalanges of the index and middle finger in
1 ms spikes set to 100 ms duration. To stan-
dardize the stimulation, pain was titrated indi-
vidually to a modified visual analog scale (VAS)
of 5 prior to the 30-min experiment.16 VAS 5
was chosen as a pain level encountered in ICU
patients, indicating clear need for analgesia. Par-
ticipants could change the position of the VAS
scale indicator, rating pain from ‘no pain’,
which was the first rating for all participants
prior to electrical stimulation, to ‘worst imagin-
able pain’. The back of the scale contained a
numbered scale, range 0–10, visible to the
Acta Anaesthesiologica Scandinavica 60 (2016) 1111–1120
ª 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
PAIN RATHER THAN EMOTION TRIGGER SCV
conductor of the trial. The Coulbourn device
was set at a starting point of 0.6 mA, after
which the mA was increased in increments of
0.3 mA until 2.3 mA and thereafter a final
increase to 4 mA. When the individual rated
pain as more than VAS 4 but less than VAS 6,
this level was used during the exposure session.
Participants received this standardized pain
stimulation during half of the 12 sessions. Elec-
trical stimulation was given at random intervals,
with a total of 24 electrical stimulations over the
1-min-long session (0.4/s). The order of the two
pain sessions was randomized over the four ses-
sions within each emotion block (described
below).
Emotion-inducing pictures
In order to induce three different emotions (pos-
itive, neutral, or negative), a total of 36 emotion-
ally charged pictures from the International
Affective Picture System (IAPS) were used (12
for each emotion).
International affective picture system is based
on large set of pictures used for standardizing
emotional stimulation. They are calibrated for
affective response and characterized primarily
by normative ratings of valence and arousal.17
Valence refers to the attractiveness (high
valence) or aversiveness (low valence) of an
object (or event/situation). Arousal refers to
how excited (high arousal) or calm the subjects
feel in response to an object/event/situation.
Both measures range from 1 to 9. Pictures were
selected to gain a variety of content and three
levels of emotional valence; 12 positive, 12 neu-
tral, and 12 negative pictures (Table 1). The pic-
tures were presented in a 1024 9 768
resolution, giving them a measurement of
22 9 18.7 cm on the computer screen.
The positive picture series portrayed for exam-
ple, smiling people and beautiful sceneries (IAPS
pictures: 2091, 2224, 4612, 4622, 4698, 5470,
5480, 5626, 5833, 7325, 7472, 7492). The neutral
picture series included innate objects, such as a
chair or a spoon (IAPS pictures: 7000, 7002, 7004,
7006, 7010, 7012, 7025, 7052, 7183, 7185, 7186,
7705). The negative picture series contained
images of death, threat, mutilation, and suffering
people and were chosen in order to resemble
unpleasant persecutory hallucinations and fears
1113
 €
A. C. GUNTHER ET AL.
Table 1 Mean and standard deviation (SD) for valence and arousal of the three series of emotionally charged pictures from international
affective picture system (IAPS). Data from IAPS standardized values of each picture ranging from 1 to 9.
Positive pictures (n 12)
Valence Arousal
Mean (SD) 7.2 (1.6) 5.1 (2.2)
Fig. 1. International affective picture system-like pictures with the
purpose to induce emotions. Examples of positive, neutral, and
negative emotion-inducing pictures. These pictures were not used in
the study. Source: Pixabay.com (Free pictures).
described by patients after their ICU stay (IAPS
pictures: 2811, 3063, 3068, 3150, 3168, 6230,
6250, 6830, 9000, 9301, 9490, 9599). According to
IAPS policy, pictures from the database cannot
be published. IAPS-like images, from pixabay.-
com (copyright-free), are included as similar
examples (Fig. 1).
In each 1-min session, the 12 pictures from
the same emotion category were shown twice
(n = 24), for 2.5 s each time. Each emotion-
inducing picture battery was shown in four
1114 ª 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
Neutral pictures (n 12) Negative pictures (n 12)
Valence Arousal Valence Arousal
5.0 (1.1) 2.8 (2.0) 2.4 (1.5) 6.1 (2.3)
consecutive sessions (emotion block). The order
of the three emotion blocks was randomized for
each participant (Table 2).
ICU sound
To simulate the background sound of an ICU
environment, an authentic daytime sound
recording from a fully occupied three-bed room
at the General ICU, Karolinska University
Hospital Solna, Sweden was used. The record-
ing included background sounds (from ventila-
tors and other machines), doctors and nurses
talking, and monitor alarms. The sound presen-
tation lasted for 60 s, with volume peaks at
80 dB. The order of sound/no sound in the four
sessions within each ‘emotion block’ was ran-
domized (Table 2).
Outcome assessment
Skin conductance variability measured with NSCF
The Med-Storm Stress Detector device (MED-
STORM Innovation AS, Oslo, Norway) was
used to measure SCV. In this measurement
application, used in most recent studies as well
as our study, SCV is reported as the number of
skin conductance fluctuations/second (NSCF).7,8
The criterion for the registration of a skin con-
ductance fluctuation was an amplitude between
skin conductance trough and peak of > 0.02
microsiemens (lS), as in previous studies.12,18,19
The fluctuations registered with this method
correlate with bursts of sympathetic neuronal
stimulation of the palmar sweat glands.12
Before the start of the session, three dispos-
able Ag/AgCl electrodes were attached to the
palmar surface of the participants hand: thenar
eminence (current electrode), hypothenar emi-
nence (measurement electrode), and just below
the second and third digits (reference electrode),
respectively. NSCF was measured during the
Acta Anaesthesiologica Scandinavica 60 (2016) 1111–1120

Table 2 Example of randomized exposures for an individual participant.
Negative emotion block Positive emotion block
Pain – – Pain Pain Pain
Sound – Sound – – Sound
entire experiment. Mean NSCF values over each
minute of exposure were used in the analysis.
Pain rating
After each 1-min session, participants were
instructed to rate pain on the screen in front. To
rate pain during the session, a modified numeric
rating scale consisting of 11 unnumbered hori-
zontal boxes on the computer screen was used.20
Pain was rated from ‘no pain’ to ‘worst pain
imaginable’ by ticking a box. For analysis,
boxes were later assigned values from 0 to 10
(in concordance with the VAS). The self-ratings
were followed by a 1-min resting phase.
Number of skin conductance fluctuations was
measured on the 18 participants across the 12
sessions, resulting in a total of 216 observations
(12 9 18 = 216) (Table 2). Each participant
rated pain six times, for a total of 108 self-
reports of pain. In all subjects, VAS was rated
as zero prior to the experiment sessions. These
values were included in the random-effect linear
regression model.
Statistical analysis
Power calculation was made for within-subjects
analysis with anticipated mean NSCF of 0.07
(Standard Deviation, SD 0.15) in non-painful
exposures and mean NSCF of 0.21 (SD 0.15) dur-
ing painful stimulation. With a sample size of 20,
with the alpha error < 0.05, power was 97%.
A within-subjects (2 9 3 9 2) analysis for
dependent measures was used. The dependent
variables NSCF and self-perceived pain (NRS)
were analyzed in two separate random-effect lin-
ear regression models. The participants’ random
effects were included to take into account the
potential correlation between the repeated mea-
sures in each subject. In each model, the predic-
tors of interest were type of pain stimulation (no
Acta Anaesthesiologica Scandinavica 60 (2016) 1111–1120
ª 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
PAIN RATHER THAN EMOTION TRIGGER SCV
Neutral emotion block
– – Pain – Pain –
Sound – – Sound Sound
pain/pain), emotion (positive, neutral, or nega-
tive), and sound (no sound/sound).
For regression analysis, we used the NSCF
from the session with neutral pictures, no elec-
trical stimulation, and no ICU sound as the
baseline. The same combination was also trea-
ted as the NRS 0 baseline condition in the
regression analysis of NRS. Based on the results
of the regression models, NSCF and NRS reac-
tivity were estimated for the different sessions.
The intra-individual correlation was also esti-
mated with Spearman0 s rho. Rho indicates the
correlation within individuals compared to the
group correlation. Rho 0.5 = substantial intra-
individual correlation, Rho 0 = all individuals
have the same values across sessions. Rho can
also be translated to the percentage of inter-
individual difference. Thus, a rho value of 0.55
equals an inter-individual difference of 55%, (a
substantial difference, indicating that the vari-
ability within the group is large).
Results with P-values of < 0.05 were consid-
ered statistically significant.
Results
Data for the mean, standard deviation, median,
interquartile range (IQR p25–p75), and full
range of NSCF for the 12 exposures sessions are
presented in Table 3.
NSCF and NRS during pain stimulation
The 18 individuals’ baseline session measure-
ment (neutral pictures, no electrical stimulation,
and no sound) rendered a median NSCF value
of 0.068 peaks/s (IQR p25–p75: 0.013–
0.089 peaks/s, respectively). In the 108 mea-
surements with pain stimulation, median NSCF
was 0.225 peaks/s (IQR p25–p75: 0.146–
0.318 peaks/s), respectively. The median NRS
during pain stimulation (all pain sessions) was
1115
 €
A. C. GUNTHER ET AL.

Table 3 Mean, median, and range data for number of skin conductance fluctuations in the 12 different sessions.

Number of skin conductance fluctuations during the experiment

Session Mean Standard deviation Median Interquartile range (p25–p75) Full range (min–max)

Neutral pictures 0.075 0.084 0.068 0.013–0.089 0–0.318

No sound
No pain
Neutral pictures 0.206 0.125 0.176 0.094–0.348 0.035–0.383
No sound
Pain
Neutral pictures 0.086 0.080 0.069 0.013–0.130 0–0.270
Sound
No pain
Neutral pictures 0.211 0.118 0.321 0.105–0.321 0.035–0.40
Sound
Pain
Positive pictures 0.087 0.090 0.043 0.018–0.137 0–0.283
No sound
No pain
Positive pictures 0.230 0.107 0.260 0.113–0.331 0.05–0.383
No sound
Pain
Positive pictures 0.089 0.068 0.068 0.033–0.154 0–0.203
Sound
No pain
Positive pictures 0.241 0.086 0.233 0.150–0.321 0.133–0.365
Sound
Pain
Negative pictures 0.116 0.146 0.068 0.029–0.163 0–0.6
No sound
No pain
Negative pictures 0.225 0.107 0.233 0.142–0.316 0.018–0.433
No sound
Pain
Negative pictures 0.099 0.095 0.051 0.029–0.156 0–0.318
Sound
No pain
Negative pictures 0.245 0.095 0.226 0.176–0.333 0.068–0.40
Sound
Pain

4, (IQR p25–p75: range: 2–6, respectively). All
but one subject demonstrated an elevation in
NSCF during pain stimulation (Fig. 2).
NSCF in relation to combined pain
stimulation, pictures, and sound
Pain stimulation increased NSCF significantly,
0.13 peaks/s from baseline, after adjusting for
picture-induced emotion and ICU sound
(P < 0.001) (Table 3, Fig. 3). Negative emotion
also increased NSCF significantly, 0.03 peaks/s,
after adjusting for the effect of ICU sound and
pain, (P < 0.05). Positive emotion and ICU
sounds did not impact NSCF significantly. The
intra-individual correlation rho 0.58 indicates
that 58% of the variability was due to inter-
individual differences.
NRS in relation to electrical stimulation,
pictures, and sound
As hypothesized, pain rating was increased,
with NRS 3.95 during pain stimulation

Acta Anaesthesiologica Scandinavica 60 (2016) 1111–1120

1116 ª 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
 PAIN RATHER THAN EMOTION TRIGGER SCV

Fig. 3. Mean number of skin conductance fluctuation values and 95%

confidence intervals for the 12 sessions from the random-effects
model.

Table 4 Changes in number of skin conductance fluctuation

(NSCF) and pain rating induced by pain stimulation, emotion, and
sound, based on random-effects linear regression.

Change in Change in
Variable N NSCF peaks/s pain NRS

Pain stimulation 108 0.13‡ 3.95‡

Positive emotion 72 0.02 0.10
Negative emotion 72 0.03* 0.36*
ICU sound 108 0.01 0.21
Rho§ 0.58 0.35
Fig. 2. Individual responses in number of skin conductance *P < 0.05; ‡P < 0.001. §Intra-individual correlation. NSCF, num-
fluctuation: effects of negative pictures, ICU sound, and pain ber of skin conductance fluctuations/second; NRS, numeric rating
respectively, compared to baseline session (neutral pictures, no scale.
sound, no pain).

(P < 0.001) (Tables 3 and 4, Fig. 4). Negative
emotion also increased VAS significantly but to
a much lesser extent, by 0.36 units (P < 0.05).
Positive pictures and ICU sound did not affect
NRS significantly. The intra-individual correla-
tion rho 0.35 indicates that 35% of the variabil-
ity was due to inter-individual differences.
The random-effect linear regression coeffi-
cients for NSCF as a NRS-dependent variable
implied that a 1-unit increase in NRS was asso-
ciated with a NSCF increase by 0.073 peaks/s
(P < 0.001). The intra-individual correlation rho
0.25 indicates that 25% of the variability was
due to inter-individual differences.
Acta Anaesthesiologica Scandinavica 60 (2016) 1111–1120
ª 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
Discussion
In our study, pain stimulation titrated to VAS 5
prior to the sessions, led to a distinct increase in
skin conductance variability, while emotions
induced by IAPS pictures and authentic ICU
sound had limited effects on NSCF.
Our interpretation is that in a controlled envi-
ronment, NSCF is more specific to pain than to
emotion. In a previous study of NSCF in criti-
cally ill ICU patients, many patients were
unable to self-report ongoing adverse percep-
tions.15 While non-painful adverse perceptions,
such as intense fear, hallucinations, or delusions
may lead to agitation, untreated pain itself may
also lead to agitation.21 The results of the
1117
 €
A. C. GUNTHER ET AL.
Fig. 4. Mean numeric rating scale values and 95% confidence
intervals for the six sessions with pain stimulation from the random-
effects model.
present study suggest that agitation noted in
some of these poorly communicating, intubated
patients may have represented an expression of
pain. Poorly treated pain has in fact been associ-
ated with agitated delirium.22
Pain, titrated to an individual VAS 5 in each
participant prior to the experiment, led to a med-
ian NSCF of 0.27. This is similar to the findings
from skin conductance variability studies in
post-operative and ICU patients. In these studies,
moderate pain, equivalent of VAS 4–5 was asso-
ciated with NSCF of approximately 0.25.14,15
The rho value for NSCF of 0.58, however,
indicates that there are substantial inter-indivi-
dual differences. This is depicted with the raw
data presented in Fig. 1 and Table 3. Thus, in
the clinical setting, NSCF changes in the indi-
vidual patient, in combination with clinical
assessment may be more relevant to follow than
to use a strict NSCF threshold value as an anal-
gesia trigger.
Currently, the most objective measures of pain
in poorly communicating ICU patients are com-
posite observer’s scales.5,24 These scales are bet-
ter than arbitrary assessment, in that inter-rater
variability may be reduced. Nonetheless, some
parameters common for the Clinical Pain Obser-
vational Tool (CPOT)5 and Behavioral Pain Scale
(BPS),24 such as poor ventilator compliance or
facial grimacing, might be observed for other rea-
sons than pain. Considering that pain was the
main determinant in NSCF increases and find-
ings from a previous study in ICU patients,15 our
interpretation is that NSCF may potentially be
considered as a complementary pain assessment
method in poorly communicating patients. The
potential benefits, however, need large-scale
evaluation. Further study of SCV monitoring in
1118
critically ill patients deemed in pain and receiv-
ing analgesics may be of value to confirm its role
and validity in this specific population.
Compared with the effect of pain, there were
only minor NSCF and NRS differences between
the different picture series, with negative pic-
tures increasing NSCF and NRS marginally
(Table 3). Affective modulation of autonomic
reactions to noxious stimulation has been stated
in earlier studies in which different emotion-
inducing picture series were presented during
nociceptive stimulation.25–27 In our study, the
reference values of valence and arousal of the
chosen IAPS pictures used in the three IAPS
picture series were sufficiently different to have
induced the proposed emotions according to the
IAPS paradigm which should further support
the finding of pain as the main determinant for
SCV increases.
We evoked pain intermittently with electrical
stimulation in otherwise healthy and drug-free
volunteers, in order to reduce the heterogeneity
in exposures and potential drug effects found in
critically ill ICU patients. One major difference
between our experimental setting and the real
ICU scenario is that the stimulations and inter-
pretation of these, as well as the autonomic
response in the two settings may be vastly dif-
ferent. The pain exposure in our study may
resemble procedural pain in relatively stable
and otherwise pain-free patients. Many ICU
patients, however, may suffer from ongoing
nociceptive inflammatory and in some cases
neuropathic pain. In parallel, they may be aware
of their life-threatening situation or be in delu-
sional fear (e.g., of staff trying to kill them).
Such fear may be more emotionally distressing
and perhaps lead to greater autonomous
responses than what can be mimicked in a
study in healthy volunteers. The same applies to
the connotation of ICU sound. For some ICU
patients, the alarms from a ventilator or monitor
are very intimidating, as this may indicate a
problem with life-supporting devices or vital
functions.28 Thus, while our study assessed
standardized stimuli in subjects able to self-
report, a significant limitation may be that these
volunteers are likely not as vulnerable and sen-
sitive to adverse stimuli as are critically ill
patients in the ICU. Additionally, it is unclear
whether some drugs, such as beta-blockers or
Acta Anaesthesiologica Scandinavica 60 (2016) 1111–1120
ª 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd

alpha-2-agonists, or severe critical illness might
interfere with sympathetic tone and responses
to stimulation. A future study in ICU survivors,
recently exposed to intensive care, could evalu-
ate if there are potentially larger SCV increases
to non-painful, adverse stimuli and as stated,
studies of critically ill patients with validated
pain assessment tools during stimulation and
analgesia are warranted.
In summary, skin conductance variability
increased mainly in response to pain and only
marginally in response to induced emotion or
ICU sound in healthy volunteers. Individual
trends rather than absolute thresholds appeared
to be relevant. In conclusion, skin conductance
variability, as defined in our study, reacts more to
pain (rated as VAS > 4 and < 6) than strongly
negative emotionally charged pictures in healthy
volunteers. There is a substantial degree of inter-
individual differences in skin conductance vari-
ability reactions. Skin conductance variability
can potentially be a supplement in assessing pain
in the critically ill, poorly communicating patient
but needs evaluation as a complement in the ICU
setting. Studies of skin conductance variability as
an adjunct to observational scales in the assess-
ment and treatment of pain in poorly communi-
cating ICU patients are warranted.
Acknowledgements
The authors thank Dr Ulrik Sartipy at the
Department of Cardiothoracic Surgery and
Anesthesiology, Karolinska University Hospital,
for great support during the manuscript phase
of this study.
References
1. Lindenbaum L, Milia DJ. Pain management in the
ICU. Surg Clin North Am 2012; 92: 1621–36.
2. Payen J-F, Bosson J-L, Chanques G, Mantz J, Labarere
J. Pain assessment is associated with decreased
duration of mechanical ventilation in the intensive
care unit: a post Hoc analysis of the DOLOREA study.
Anesthesiology 2009; 111: 1308–16.
3. Mansouri P, Javadpour S, Zand F, Ghodsbin F,
Sabetian G, Masjedi M, Tabatabaee HR.
Implementation of a protocol for integrated
management of pain, agitation, and delirium can
improve clinical outcomes in the intensive care
Acta Anaesthesiologica Scandinavica 60 (2016) 1111–1120
ª 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
PAIN RATHER THAN EMOTION TRIGGER SCV
unit: a randomized clinical trial. J Crit Care 2013;
28: 918–22.
4. Arbour C, Gelinas C, Michaud C. Impact of the
implementation of the critical-care pain observation
tool (CPOT) on pain management and clinical
outcomes in mechanically ventilated trauma
intensive care unit patients: a pilot study. J Trauma
Nurs 2011; 18: 52–60.
5. Gelinas C, Fillion L, Puntillo KA, Viens C, Fortier M.
Validation of the critical-care pain observation tool in
adult patients. Am J Crit Care 2006; 15: 420–7.
6. Sessler CN, Gosnell MS, Grap MJ, Brophy GM,
O’Neal PV, Keane KA, Tesoro EP, Elswick RK.
The Richmond Agitation-Sedation Scale: validity
and reliability in adult intensive care unit
patients. Am J Respir Crit Care Med 2002; 166:
1338–44.
7. Storm H. Changes in skin conductance as a tool to
monitor nociceptive stimulation and pain. Curr
Opin Anaesthesiol 2008; 21: 796–804.
8. Storm H, Fremming A, Odegaard S, Martinsen OG,
Morkrid L. The development of a software program
for analyzing spontaneous and externally elicited
skin conductance changes in infants and adults.
Clin Neurophysiol 2000; 111: 1889–98.
9. Storm H, Støen R, Klepstad P, Skorpen F, Qvigstad
E, Raeder J. Nociceptive stimuli responses at
different levels of general anaesthesia and genetic
variability. Acta Anaesthesiol Scand 2013; 57:
89–99.
10. De Pascalis V, Magurano MR, Bellusci A. Pain
perception somatosensory event-related potentials
and skin conductance responses to painful stimuli
in high mid and low hypnotizable subjects: effects
of differential pain reduction strategies. Pain 1999;
83: 499–508.
11. Lader MH. Palmar skin conductance measures in
anxiety and phobic states. J Psychosom Res 1967;
11: 271–81.
12. Wallin BG. Sympathetic nerve activity underlying
electrodermal and cardiovascular reactions in man.
Psychophysiology 1981; 18: 470–6.
13. Lidberg L, Wallin BG. Sympathetic skin nerve
discharges in relation to amplitude of skin
resistance responses. Psychophysiology 1981; 18:
268–70.
14. Ledowski T, Bromilow J, Wu J, Paech MJ, Storm
H, Schug SA. The assessment of postoperative pain
by monitoring skin conductance: results of a
prospective study. Anaesthesia 2007; 62: 989–93.
15. G€unther AC, Bottai M, Schandl AR, Storm H, Rossi
P, Sackey PV. Palmar skin conductance variability
and the relation to stimulation, pain and the motor
1119
 €
A. C. GUNTHER ET AL.
activity assessment scale in intensive care unit
patients. Crit Care 2013; 17: R51.
16. Price DD, McGrath PA, Rafii A, Buckingham B.
The validation of visual analogue scales as ratio
scale measures for chronic and experimental pain.
Pain 1983; 17: 45–56.
17. Lang PJ, Bradley MM, Cuthbert BN. International
affective picture system (IAPS): affective ratings of
pictures and instruction manual. Technical Report
A-8. Gainesville, FL: University of Florida, 2008.
18. Storm H, Shafiei M, Myre K, Raeder J. Palmar skin
conductance compared to a developed stress score
and to noxious and awakening stimuli on patients
in anaesthesia. Acta Anaesthesiol Scand 2005; 49:
798–803.
19. Gjerstad AC, Wagner K, Henrichsen T, Storm H.
Skin conductance versus the modified COMFORT
sedation score as a measure of discomfort in
artificially ventilated children. Pediatrics 2008; 122:
848–53.
20. Hullett B, Chambers N, Preuss J, Zambudio I,
Lange J, Pascoe E, Ledowski T. Monitoring
electrical skin conductance: a tool for the
assassment of postoperative pain in children?.
Anaesthesiology 2009; 111: 513–7.
21. Downie WW, Leatham PA, Rhind VM, Wright V,
Branco JA, Anderson JA. Studies with pain rating
scales. Ann Rheum Dis 1978; 37: 378–81.
1120 ª 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
22. Meier DE. Pain as a cause of agitated delirium.
Arch Intern Med 2012; 172: 1130.
23. Robinson S, Vollmer C. Undermedication for pain
and precipitation of delirium. Medsurg Nurs 2010;
19: 79–83.
24. Payen J, Bru O, Bosson J, Lagrasta A, Novel E,
Deschaux I, Lavagne P, Jacquot C. Assessing pain
in critically ill sedated patients by using a
behavioural pain scale. Crit Care Med 2001; 29:
2258–63.
25. Rhudy JL, Williams AE, McCabe KM, Russell JL,
Maynard LJ. Emotional control of nociceptive
reactions (ECON): do affective valence and arousal
play a role? Pain 2008; 136: 250–61.
26. Rhudy JL, Bartley EJ, Williams AE. Habituation,
sensitization, and emotional valence modulation of
pain responses. Pain 2010; 148: 320–7.
27. Godinho F, Magnin M, Frot M, Perchet C, Garcia-
Larrea L. Emotional modulation of pain: is it the
sensation or what we recall? J Neurosci 2006; 26:
11454–61.
28. Johansson L, Bergbom I, Persson Waye K, Ryherd
EBL. The sound environment in an ICU patient
room- a content analysis of sound levels and
patient experiences. Intensive Crit Care Nurs 2012;
28: 269–79.
Acta Anaesthesiologica Scandinavica 60 (2016) 1111–1120