QST in clinical practice

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Quantitative sensory testing (QST). English
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Article in Der Schmerz · January 2016
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2. Background
Quantitative sensory testing (QST) is a
psychophysical test method that investi-
gates the functional state of the somato-
sensory system of a test subject or pa-
tient with regard to the severity of clinical
signs by means of calibrated stimuli and
subjective perception thresholds [1]. The
presented test battery includes a validated
brief report for detecting the full somato-
sensory phenotype [2].
A standardized test procedure con-
ducted by trained investigators, precise
oral instructions given to the test subjects
for each test procedure to be performed,
and the presence of multicentrically raised
standard values of the German Research
Association for Neuropathic Pain (DFNS)
allow for good comparability of the col-
lected data and the clinical examination
within a reasonable period of time.
Based on international studies, testing
procedures were selected as parts of the
QST battery development that enable the
examination of all relevant somatosenso-
ry submodalities. These tests allow for an
evaluation of the function of unmyelinat-
ed C-fibers, thinly myelinated A-delta fi-
bers, and thickly myelinated A-beta fibers
including their projection pathways to the
brain.
Historical overview
In 1835, Weber established a two-point
discrimination as a standardized meth-
od for testing the ability to spatially dis-
tinguish two tactile stimuli from one an-
other. Today, this method has been estab-
lished as a typical part of sensory testing
within the clinical neurological examina-
tion [3]. It was von Frey who employed it
first in 1896 to determine in humans the
tactile sensation of horse and boar hair of
different stiffness and length [4]. Today,
nylon filaments or fiber optic cables are
used as von Frey filaments for QST. An
automated method for the quantification
of pressure, temperature perception, vi-
bration, and touch was introduced in 1978
by the research group led by Peter Dyck
[5]. This advancement led to the develop-
ment of additional procedures and instru-
ments, such as a thermal tester or pressure
algometer for the determination of ther-
mal or mechanical perception and pain
thresholds. The subsequently present-
ed QST battery of sensory tests was de-
veloped as part of the German Research
Network on Neuropathic Pain (DFNS)
and has been employed in Germany and
worldwide since 2002.
How does QST work?
According to the DFNS report, QST en-
tails a standardized battery of tests, which
consists of seven individual tests. During
the performance of the test, a total of 13
individual parameters are assessed to de-
termine and quantify the function of the
somatosensory nervous system [6]. This
examination method enables determi-
nation of the nociceptive properties and
non-nociceptive submodalities of differ-
ent groups of afferent nerve fibers and
central pathways [7]. The test procedure
is designed in such a manner so as to as-
sure that within 1 h a complete sensory
profile can be obtained, thus providing
an overview of the presence of sensory
plus or minus signs, such as hyperalgesia
or hypoesthesia (. Table 1). The proce-
dure for performing the tests is standard-
ized in all trained centers, always follow-
ing the same test sequences and the use of
the same calibrated thermal and mechan-
ical test stimuli.
While investigating, first, a clinically
or experimentally unaffected mirror im-
age body area ought to be tested which is
located opposite to the pain or test area.
This is followed by a test of the pain/test
area itself.
M. Mücke1,2 · H. Cuhls2 · L. Radbruch2 · R. Baron3 · C. Maier4 ·T. Tölle5 ·
R.-D. Treede6 · R. Rolke7
1 Department of General Practice and Family Medicine, University Hospital of Bonn, Bonn, Germany
2 Department of Palliative Medicine, University Hospital of Bonn, Bonn, Germany
3 Division of Neurological Pain Research andTherapy, Department of Neurology,
Christian-Albrechts-Universität zu Kiel, Kiel, Germany
4 Department of Pain Medicine, Berufsgenossenschaftliches Universitätsklinikum
Bergmannsheil, Ruhr University Bochum, Bochum, Germany
5 Department of Neurology, Klinikum rechts der Isar,Technische Universität München, Munich, Germany
6 Department of Neurophysiology, Center for Biomedicine and MedicalTechnology Mannheim
(CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
7 Department of Palliative Medicine, Medical Faculty RWTH Aachen University, Aachen, Germany
Quantitative sensory
testing (QST)
Schmerz
DOI 10.1007/s00482-015-0093-2
© Deutsche Schmerzgesellschaft e.V. Published
by Springer-Verlag Berlin Heidelberg - all rights
reserved 2015
1Der Schmerz
Übersichten
R. Baron, C. Maier,T.Tölle and R.-D.Treede: DFNS
steering committee.
English version of: Mücke M, Cuhls C, Radbruch
L, Baron R, Maier C,TölleT,Treede R-D, Rolke
R (2014) Quantitative sensorischeTestung.
Schmerz 28:635–648 DOI 10.1007/s00482-014-
1485-4

3. Application of psychophysical
testing methods
To determine the sensitivity of a patient
or subject to the defined test stimuli us-
ing QST, perception and pain thresholds
can be quantified. Available testing proce-
dures include the “method of levels” and
the “method of limits”—with varying ad-
vantages and disadvantages.
The“method of levels”
This is a sensory testing method, where-
by stimulation is applied repeatedly be-
low and then above the perception or
pain thresholds. After application of the
test stimuli, the subjects are asked about
the perception or painfulness of the stim-
ulus, specifically whether they are per-
ceived as painful or not. The threshold de-
termination is based on the stimulus in-
tensity at which 50 % of stimuli are detect-
ed. The disadvantage of this method is the
long study period required to determine a
threshold; furthermore, numerous repeat-
ed measurements for determining pain
stimuli just below or above the threshold
can lead to the development of sensitiza-
tion phenomena.
The“method of limits”
Another psychophysical method is the
“method of limits.” As part of this pro-
cedure, the perception and pain thresh-
olds are measured as the first identified
stimulus under increasing stimulus in-
tensities. In contrast to the “level” meth-
od, the “limit” method overrates the ac-
tual threshold, since the tested threshold
includes a reaction time artifact. The sub-
ject has yet to give feedback after reaching
the threshold, while the stimulus intensi-
ty keeps increasing further during the re-
action time. The advantage of this method
is the short investigation period until the
threshold determination is reached.
Thermal testing
Thermal testing examines the functional-
ity of thinly myelinated A-delta fibers and
unmyelinated C-fibers. It can be detected
with various computer-based thermal tes-
ters (. Fig. 1a and b). Most tests are sci-
entifically conducted using the Thermal
Table 1 Clinical signs, quantitative sensory testing, and possible underlying neurobiological mechanisms
Clinical signs Definition Quantitative sensory testing Possible underlying neurobiological mechanisms
Testing for presence of plus or minus signs
(tested peripheral fiber types)
Deafferentation Peripheral
sensitization
Central
sensitization
Plus signs Sensitivity to test stimuli
Hyperalgesia Increased pain
sensitivitya of
To heat … the skin Heat stimulation by means of thermotesting
(C, Aδ)
↓ ↑↑ →?
To cold … the skin Cold stimulation by means of thermotesting
(C, Aδ)
↓ → ↑?
For pinprick stimuli … the skin Calibrated needle stimuli (pinprick) (C, Aδ) ↓ ↑? ↑↑
For blunt pressure … deeper tissues Pressure algometer (C, Aδ) ↓ ↑? →?
Allodyniab Pain in response to non-
nociceptive stimulia
Brush, cotton swab, Q-tip (Aβ) to skin brushing → → ↑
Minus signs
Hypoesthesia
(thermal/
mechanical/other)
Decreased sensitivity
for nonpainful stimuli
Light cold stimulation by means of thermotest-
ing (Aδ), light heat stimulation by means of
thermotesting (C), von Frey filaments (Aβ), cali-
brated tuning fork (64 Hz, Rydel–Seiffer) (Aβ)
↓ → →, ↓c
Hypoalgesia
(thermal/
mechanical/other)
Decreased sensitivity
for painful stimuli
To cold/heat stimulus by means of thermotest-
ing (C, Aδ)Calibrated needle stimuli (pinprick)
(C, Aδ)Pressure algometer (C, Aδ)
↓ → →
Table modified according toWoolf and Mannion [15], Hansson et al. [13], Rolke [21].
↑ increased sensitivity to test stimulus during a clinical neurological examination, ↓ decreased sensitivity, → sensitivity unchanged or phenomenon not examinable, ? has
not been adequately studied or described in studies or is not yet generally accepted.
aIASP definition [22]; IASP International Association for the Study of Pain.
bThis term should be used only when it is known that the test stimulus does not activate any nociceptors.What is meant here is the dynamic tactile allodynia for slightly
moving tactile stimuli. A light brushing of the skin is the only established example (IASP 2008).
cA secondary tactile hypoesthesia was also observed in the context of central sensitization [23].
Table 2 Examination using mechanical stimuli
Stimuli Applied force (mN) Type of administration
von Frey filaments 0.25–512 Point by point
Needle stimulators 8–512 Punctate
Q-tip with a plastic holder 100 Stroking light touch
Soft brush 200–400 Stroking light touch
Cotton wool pad 2–4 Stroking light touch
2 Der Schmerz
Übersichten

4. Sensory Analyzer II (TSA 2001-II Ther-
mal Sensory Analyzer, Medoc Ltd., Is-
rael) and the MSA Thermal Stimulator
(SOMEDIC AB, Sweden).
A thermode with a Peltier element and
a cooling water system is placed on the
skin (. Fig. 1c and d) and by means of the
“limits method,” cold and warm thresh-
olds are determined, as well as the thermal
difference thresholds for the detection of
paradoxical heat sensations—followed by
cold pain and heat pain thresholds. The
contact surfaces of the respective ther-
modes amount to 9.0 cm2 (TSA II) or
12.5 cm2 (MSA), respectively. By press-
ing a stop button, which is connected to
a computer unit, a threshold value can be
determined in accordance with a contin-
uously increasing or decreasing tempera-
ture of the thermode contact surface (tem-
perature change of 1 °C/s)—starting from
a baseline temperature of 32 °C. In order
to ensure compliance with the appropri-
ate safety guidelines, the unit automati-
cally stops measurements when it reach-
es a temperature of 0° C or 50° C and re-
turns to the starting temperature of 32 °C
to avoid skin irritation.
The actual pain threshold is calculated
from three consecutive individual values
as an arithmetic average.
Mechanical detection threshold
To capture the mechanical detection
thresholds using the DFNS QST proto-
col, a set of standardized von Frey fila-
ments (Opti-hair2-set, Marstock nerve
test, Germany) is recommended. Glass
fiber filaments with a different diame-
ter and length as well as a spherical con-
tact surface of a diameter of about 0.5 mm
are used as von Frey filaments (. Fig. 2d;
[8]). To ensure accurate testing of the de-
tection threshold, the filaments are always
placed in the same manner until the fila-
ment shows an “s-shape” bending. The set
used for testing (. Fig. 2c) is composed of
filaments with the strengths of 0.25, 0.5,
1, 2, 4, 8, 16, 32, 64, 128, 256, and 512 mN.
The contact time with skin surface
during the testing should be about 2 s.
Since the von Frey filaments have round-
ed tips, low-threshold mechanorecep-
tors are preferably activated, which me-
diate the perception of a contact via A-
beta fibers. To determine the tactile de-
tection threshold, the geometric mean of
five above and below-threshold stimulus
intensities is determined using a modified
“level” method.
Mechanical pain threshold
To determine the mechanical pain thresh-
old, needle stimulators (pinprick, MRC
Systems GmbH, Germany) are employed.
The needle stimulators used consist of
blunt needles (. Fig. 2b) with a fixed
stimulation intensity of 8, 16, 32, 64, 128,
256, and 512 mN, as well as a blunt, cir-
cular skin contact surface with a diameter
of 0.25 mm. The needle tips, which are al-
ways the same, are housed in steel tubes,
in which there are different weights that
are responsible for each weight force to
be applied. The individual needle stimu-
lation devices (pinpricks) ought to be ap-
plied at perpendicular to the skin in five
test series of ascending and descending
stimulus intensity with a skin contact time
of about 1–2 s. This test allows one to cal-
Abstract · Zusammenfassung
Schmerz DOI 10.1007/s00482-015-0093-2
© Deutsche Schmerzgesellschaft e.V. Published by Springer-Verlag Berlin Heidelberg - all rights
reserved 2015
M. Mücke · H. Cuhls · L. Radbruch · R. Baron · C. Maier ·T. Tölle · R.-D. Treede · R. Rolke
Quantitative sensory testing (QST). English version
Abstract
Quantitative sensory testing (QST) is a stan-
dardized and formalized clinical sensitivi-
ty test.Testing describes a subjective (psy-
chophysical) method that entails a cooper-
ation of the person to be examined.With-
in its framework, calibrated stimuli are ap-
plied to capture perception and pain thresh-
olds, thus providing information on the pres-
ence of sensory plus or minus signs.The pre-
sented QST battery imitates natural ther-
mal or mechanical stimuli.The aim is to ac-
quire symptom patterns of sensory loss (for
the functioning of the thick and thin nerve fi-
bers) as well as a gain of function (hyperalge-
sia, allodynia, hyperpathia) with a simultane-
ous detection of cutaneous and deep tissue
sensibility. Most of the tested QST parameters
are normally distributed only after a logarith-
mic transformation (secondary normal distri-
bution)—except the number of paradoxical
heat sensations, of cold and heat pain thresh-
olds, and vibration detection thresholds. A
complete QST profile can be measured within
1 h. QST is suitable not only for clinical trials
but also in practice as a diagnostic method to
characterize the function of the somatosen-
sory system—from the peripheral nerve fi-
ber receptor to the projection pathways to
the brain.
Keywords
Quantitative sensory testing · QST · Pain
profile · Z-score · Somatosensory nervous
system · Somatosensory phenotype ·
Sensitivity test
Quantitative sensorischeTestung (QST)
Zusammenfassung
Die quantitative sensorischeTestung (QST)
ist eine standardisierte und formalisierte
klinische Sensibilitätsprüfung. Bei dem
subjektiven (psychophysischen)Verfahren
kommt es auf die Mitarbeit der zu unter-
suchenden Person an. Mit kalibrierten Reizen
werdenWahrnehmungs- und Schmerz-
schwellen erfasst, die Auskunft über das
Vorhandensein sensibler Plus- oder Minus-
zeichen geben. Die vorgestellte QST-
Batterie imitiert natürliche thermische oder
mechanische Reize. Ziel ist die Erfassung
von Symptommustern eines sensiblen
Funktionsdefizits sowie einer Funktions-
zunahme bei gleichzeitiger Erfassung der
Oberflächen- sowieTiefensensibilität. Die
meisten getesteten QST-Parameter sind
erst nach Logarithmierung normalver-
teilt (sekundäre Normalverteilung). Ein voll-
ständiges QST-Profil kann innerhalb einer
Stunde gemessen werden. Die QST eignet
sich für klinische Studien, aber auch in der
Praxis als diagnostischesVerfahren zur
Charakterisierung der Funktion des somato-
sensorischen Systems.
Schlüsselwörter
Sensibilitätsprüfung · Schmerzschwelle ·
Wahrnehmungsschwelle ·
Somatosensorisches Nerven- system ·
Hyperalgesie
3Der Schmerz

5. culate the actual mechanical pain thresh-
old using the “level” method as a geomet-
ric mean of five just above and five just
below the threshold stimulus intensities.
Stimulus/response functions—
mechanical pain sensitivity and
dynamic mechanical allodynia
To determine the mechanical pain sen-
sitivity of the skin and the possible pres-
ence of dynamic mechanical allodyn-
ia with light tactile stimuli, a set consist-
ing of the above-described needle stimu-
lators, a Q-tip, a soft brush, and a cotton
pad (. Fig. 2a) are used. This procedure
allows a statement about the stimulus/re-
sponse behavior following needle stimula-
tion and primarily nonpainful, light touch
stimuli. The stimuli are applied in a bal-
anced order (. Table 2).
The test subjects are asked to rate the
perception of the stimulus using a numer-
ical rating scale from 0 to 100 (0 = no pain;
100 = worst pain imaginable). The extent
of any dynamic mechanical allodynia is
determined in the same testing procedure.
The devices used for recording of allodyn-
ia(. Fig. 2a)exertsmallforcesontheskin:
cotton pad (3 mN), Q-tip (100 mN), and
a standardized brush (Somedic, Sweden:
200–400 mN). These three tactile stimu-
li are applied by the examiner to at least
a 2-cm-long skin area of the test subject
during a period of about 2 s (. Table 2).
Also here, the test subjects evaluate the
stimulus intensity using a numerical rat-
ing scale from 0 to 100. The light touch
stimuli are applied in a balanced test se-
quence intermingled with the needle
stimuli described above. The stimuli are
to be applied in five pseudo-randomized
sequences over the test area, each consist-
ing of three light touch stimuli and seven
needle stimuli. Overall, this testing proce-
dure comprises 50 stimuli (15 light touch
stimuli and 35 needle stimuli). All stimu-
li are to be applied with an inter-stimulus
interval of 10 s, so that the critical frequen-
cy for a potential windup phenomenon
cannot be achieved. The mechanical pain
sensitivity is calculated as the geometric
mean of all the individual numerical val-
ues for needle stimuli. Dynamic mechani-
cal allodynia is determined as the geomet-
ric mean of all the individual numerical
values for the light touch stimuli.
Windup phenomenon
To determine the windup phenomenon,
needle stimulators with an intensity of
256 mN are employed. For the more sen-
sitive skin of the face, only the 128 mN
pinprick should be used. In the determi-
nation of the windup phenomenon, the
sensitivity of the skin to a single stimu-
lus in the tested area is compared with the
sensitivity to a series of stimuli (10 nee-
dle stimuli). The stimulation is carried
out with a stimulus frequency of 1 Hz. To
comply with this frequency, as accurate-
ly as possible, the use of a metronome is
recommended. The test subject rates the
applied stimuli using a numerical rating
scale (single stimulus and entire stimulus
series). The application of a single stim-
ulus followed by a stimulus series is re-
peated five times. The windup ratio re-
sults from the perceived mean pain in-
tensity of a stimulus series divided by the
perceived pain intensity of an individu-
al stimulus [9]. In the spinal cord, wind-
up is a phenomenon of temporal summa-
tion that increases the response behavior
of wide-dynamic-range neurons when re-
petitive C-fiber input is present more than
once within a 3-second period.
Vibration detection threshold
For the determination of the vibration
threshold, the use of a Rydel–Seiffer tun-
ing fork (. Fig. 2e) at a vibration frequen-
cy of 64 Hz using an 8/8 scale is recom-
mended. The weights on the prongs of
the tuning fork reduce the vibration fre-
quency of 128 Hz (the tuning fork without
tines) to 64 Hz and allow a reading of the
8/8 scale during the examination. To veri-
fy the threshold values, the struck and vi-
brating tuning fork is placed on the test ar-
ea, if possible over a bony eminence, such
as the ankle of the foot. The test subject
indicates when the vibration of the tun-
ing fork is no longer felt. For this point
in time, the stimulus intensity is depicted
from the scale of the tuning fork. Follow-
ing a triple determination of the vibration
detection threshold, the arithmetic mean
value of the thresholds can be calculated.
The vibration threshold is the only test in
the entire QST method in which a “disap-
pearance-threshold” is determined. With
all other parameters, the perception of a
painful or nonpainful stimulus is deter-
mined.
Pressure pain threshold
The determination of the pressure pain
threshold is effected using a pressure al-
Fig. 1 8 ThermalTesting: a Modular Sensory Analyzer (MSA) bThermal Sensory Analyzer (TSA II).The
thermodes c and d, under flowing water pressure, are fixed onto the test area with Peltier elements
side, which, depending on the controls, result in cooling or heating of the skin.The thermal tester is in-
terfaced with a computer that controls the device and records the threshold determinations
4 Der Schmerz
Übersichten

6. gometer (for example, a Somedic Algom-
eter, Sweden) [10]. The pressure algom-
eter (. Fig. 2f) has a blunt rubber con-
tact surface (of approximately 1 cm2),
with which a pressure of 0–2000 kPa can
be applied. Depending on the type of de-
vice employed, the measurement accura-
cy amounts to about ± 3 %. The pressure
is built up continuously in increments of
0.5 kg/cm2s (50 kPa/s) [1]. The pressure
pain threshold is recorded as a kPa value,
by which the perception of pressure turns
for the first time into a painful sensation.
The pressure pain threshold is calculated
as an arithmetic mean following three re-
peated measurements.
Analyzing QST data correctly
For most QST parameters left-skewed
distributions can be observed, which can
then be transposed into a normal distri-
bution, but only after a logarithmic trans-
formation, as QST parameters are usual-
ly normally distributed in log space [2].
Giving pain intensity ratings a “0” value
can be frequently obtained, for example,
as part of the stimulus/response functions
for needle and light touch stimuli, where-
by the values’ logarithmic transformation
is not possible. To avoid missing data a
small constant (+ 0.1) should be added to
all pain evaluations before the log trans-
formation. This statistical maneuver is al-
so referred to as the Bartlett procedure and
its goal is not to lose any null values for the
evaluation of the logarithmic values [11].
All QST parameters, with the excep-
tion of the number of paradoxical heat
sensations, of cold and heat pain thresh-
olds and the vibration detection thresh-
olds should be logarithmically trans-
formed and then analyzed by means of
ANOVA and, for example, LSD post hoc
tests (. Fig. 3).
For individual cases, the findings may
be compared with multicentrically ob-
tained standard values (stratified by age,
gender, and area of stimulation); values
outside the 95 % confidence interval for
healthy volunteers are judged as patho-
logical. Since paradoxical heat sensations
and dynamic mechanical allodynia do not
occur in healthy individuals in most age
groups, their occurrences (values 0) are
to be generally considered as pathological.
Fig. 2 8 Mechanical testing: set for testing the mechanical pain sensitivity. Consisting of a, b needle
stimulators (pinpricks) of different intensity and Q-tip, cotton swab and brush. c von Frey filaments to
assess the mechanical detection threshold. dThe filaments are fiber optic cables with rounded tips.
e Neurological 64 Hz tuning fork with an 8/8 scale (Rydel–Seiffer) for checking the vibration detection
threshold. f Digital pressure algometer to determine the pressure pain threshold
log-transformation
difference from baseline (raw data; °C) difference from baseline (log-data; °C)
frequencyofobservations(%)
0
5
10
15
20
25
30
0
5
10
15
20
25
30
-0,3 -1,1 -1,9 -2,7 -3,5 -4,3 -5,1 -5,9 -6,7 -0,3 -0,4 -0,7 -1,0 -1,4 -2,1 -3,1 -4,6 -6,8
cold detection thresholds
distribution of raw data
cold detection thresholds
distribution of log-data
leftward
shifted
distribution
expected
distribution
Fig. 3 8 Cold detection thresholds are represented here in log intervals (X-axis) as raw data and log-
arithmically transformed data. On the left side, the figure shows a left-skewed distribution (nonpara-
metric). Following a log transformation, a secondary normal distribution shows up on the right side
5Der Schmerz

7. Area and tissue specificity
of sensory thresholds
A comparison of QST studies shows that
significant differences arise when con-
trasting the investigated areas of the body
for most QST parameters.
The emergence of regional differenc-
es in various parts of the body is other-
wise present for all parameters. For exam-
ple, the “pressure pain threshold” param-
eter (. Fig. 4) generally shows the lowest
possible score on the face. This is followed
by hand and foot. The reference literature
features various published reference val-
ues for the face, hands, feet, and the body
which correlate with the presented QST
protocol, which, in turn, can be signifi-
cant, especially for the evaluation of sen-
sory changes in, for example, postherpet-
ic neuralgia [12].
The tissue specificity plays an impor-
tant role in the determination of the in-
dividual QST parameters. For example,
there are distinct tissue-specific differenc-
es in the pressure pain threshold. Varia-
tion in tissue innervation may be decisive
for these differences. Soft tissues, such as
muscles, have a rather low pain threshold
compared with bones, for example [10].
Different pain sensitivity
of women and men
QST reference values of healthy test per-
sons serve as the basis for the evaluation
of pathological changes. Gender specific-
ity is of great importance for the creation
of QST reference values for healthy test
subjects as the basis for assessing patho-
logical changes in patients, as has been al-
ready established in other areas of medi-
cine, such as in determining the amount
of blood hemoglobin. As part of a coun-
trywide multicenter study conducted at
the German Research Network for Neu-
ropathic Pain (Deutscher Forschungsver-
bund Neuropathischer Schmerz, DFNS),
more than 180 healthy men and wom-
en were examined. The study examined
13 different QST parameters for the face,
hands, and feet, as recorded on both sides
for a younger and older age group. As
shown in . Fig. 5, men and women differ
in their sensitivity to pain. Women are sig-
nificantly more sensitive with respect to
the pain threshold—a finding whose exact
causes have not yet been elucidated.
upper cut-off
measurement range
range for detecting minus signs,
e.g., hypoalgesia to blunt pressure
range for detecting plus signs,
e.g., hyperalgesia to blunt pressure
range of reference data
upper end 95%
confidence interval of
reference data
mean
lower end 95%
confidence interval of
reference data
baseline (BL)
threshold(kPa)
face hand foot
BL
0
500
1000
1500
2000
PPT
---
+ + +
Fig. 4 8 The mean pressure pain thresholds differ between the face, hands, and feet. Pictured here are the mean values
± 1.96SD in accordance with the upper and lower limits of a 95 % confidence interval (= reference range) of healthy control
subjects. Mean values and reference ranges increase with the length of the neural pathways to the brain. Since the data anal-
ysis was carried out here with logarithmically transformed values, retransformation yields asymmetric distributions of the ref-
erence ranges as a result (modified according to Rolke et al. [1])
heat pain
***
temperature (°C) stimulus intensity (mN) stimulus intensity (kPa)
pinprick pain
***
pressure pain
***
no.ofobservations
32 34 36 38 40 42 44 46 48 50 52 54 10 30 100 300 200 300 400 500 600 800 10001000
Fig. 5 8 Shown here as an example are the adjusted distributions for sensitivity to pain in women (red distribution curve)
and men (blue distribution curves) for three selected pain stimuli. In this context, women are significantly more sensitive to all
pain stimuli: heat pain thresholds, mechanical pain thresholds for pinprick stimuli, and pressure pain thresholds; ANOVA; all
p 0.001
6 Der Schmerz
Übersichten

8. High intraindividual stability
of QST parameters in a
right–left comparison
Between the right and left side of the body,
no significant differences in QST param-
eters can be found (. Fig. 6). The intra-
individual comparison of the right and
left side of the body shows high correla-
tion coefficients (r = 0.78–0.97, all p val-
ues 0.001) for the comparison of all QST
parameters that have been presented here.
The r2-values range from 0.61 to 0.94, thus
indicating that systematic intraindividu-
al differences based on the comparison
of both sides of the body amount to be-
tween 61 and 94 % of the total variance of
the QST parameters. Thus, QST values
show a great “stability” when comparing
the right and left side of the human body.
Age effects on the
somatosensory phenotype
For QST parameters in healthy people,
there is an age dependency of almost all
investigated QST parameters. Thus, it was
shown that aging is correlated with an in-
crease in perception and pain thresholds.
The largest age-related effects were detect-
ed for cold pain thresholds, followed by
the vibration detection thresholds and the
heat pain thresholds.
Strengths and weaknesses
of the method
The concept of a mechanism-based pain
diagnosis using QST is based on the hy-
pothesis that the decrease or increase of
perception and pain thresholds point in-
directly to the underlying neurobiological
mechanisms (. Table 1). However, such
an interpretation of QST findings has not
yet been widely accepted, since it is un-
clear whether, for example, a set of the
same clinical signs (e.g., heat hyperalge-
sia) is caused by different mechanisms or
whether a single mechanism may result in
several clinical signs [13]. Animal research
and results from human surrogate mod-
els (e.g., by intradermal injections of low
amounts of capsaicin) serve best to prove
the relation between hyperalgesia for
pricking mechanical stimuli (pinprick hy-
peralgesia) and central nociceptive sensi-
tization [14]. The phenomenon of dynam-
ic mechanical allodynia (pain caused by a
light touch) may also reflect central sensi-
tization, whereas heat and pressure hyper-
algesia can be observed rather as part of a
peripheral sensitization of the nociceptive
system [1, 15].
Conclusions for clinical practice
QST is a formalized and standardized
clinical sensitivity test using calibrated
stimuli [16].The test allows the detec-
tion of sensory plus and minus signs such
as hypoesthesia or hyperalgesia. In con-
trast, the conventional electrophysiolo-
gy, such as neurography in the somato-
sensory system, remains essentially lim-
ited to the detection of a functional def-
icit.The tested area of the body, but not
the measured body side, has a signifi-
cant impact on the measured threshold.
The detection of the full somatosenso-
ry phenotype is feasible within a clinical-
ly reasonable time frame of about half
an hour per test area [1, 17].Thereby,
pain and temperature stimuli are trans-
mitted via the spinothalamic tract, while
touch and vibration stimuli are project-
ed over the posterior column of the spi-
nal cord into the brain. Accordingly, and
to some extent, QST allows for a formu-
lation of topodiagnostic statements that
could, however, also easily be obtained
in a clinical examination. According to
the current state of findings, QST is par-
ticularly suitable for conducting clinical
trials. Moreover, QST is extensively used
in clinical practice at centers of the Ger-
man Research Network for Neuropath-
ic Pain (DFNS; http://www.neuro.med.
tu-muenchen.de/dfns/e_index.html), as
well as internationally. Disease patterns
for which QST may be employed as a use-
ful diagnostic tool are, for example, neu-
ropathic pain in polyneuropathy (e.g., di-
abetic polyneuropathy or chemotherapy-
induced neuropathy), postherpetic neu-
ralgia, pain after peripheral nerve injury,
complex regional pain syndrome (CRPS),
pain associated with a tumor disease,
back pain, and fibromyalgia. A clinical
QST domain is the noninvasive diagnosis
of a small fiber neuropathy, which can al-
so be supplemented by skin biopsies in
specialized departments, so as to further
increase diagnostic reliability [18]. Even
in the early phase diagnostics, for exam-
ple, of diabetic neuropathy in children
and adolescents, QST can play an impor-
tant role [19]. For a simplified analysis of
studies indicating the QST values as“nor-
mal”or“pathological,”EQUISTA (QST da-
ta analysis system) offers a database-
based tool. A certification as a QST cen-
ter can be recommended on the grounds
of quality assurance if the procedure is
employed there clinically or for research
purposes on a regular basis [16, 20].
Fig. 6 9 Side-by-side
comparison (right
vs. left) for an exam-
ple of the pressure
pain thresholds over
the face, hands, and
feet.The pressure pain
thresholds on the right
and left side of the
body show a great sim-
ilarity, whereas the val-
ues differ significant-
ly over the face (closed
circles), hands (open tri-
angles), and feet (grey
rectangles)
7Der Schmerz

9. QST not only has clinical and experimen-
tal relevance, it can also be used as a
method to carry out expert reports. How-
ever, it ought to be noted here that QST
is a“subjective method”, and thus the co-
operation of the patient is crucial for its
correct employment.The QST results’
plausibility can be supplemented by oth-
er objective methods, such as neurogra-
phy, somatosensory-evoked potentials
(SEP), laser-evoked potentials (LEP), or
skin biopsies, but QST should not consti-
tute the sole basis for expert recommen-
dations.
Corresponding address
Dr. M. Mücke
Department of General
Practice and Family Medicine,
University Hospital of Bonn
Bonn
martin.muecke@
ukb.uni-bonn.de
Acknowledgment. We are indebted to the patients
and subjects who participated in the studies for their
consent and cooperation.
Compliance with
Ethical Standards
Conflict of interest. The authors declare that they
have no competing interests.
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