European Journal of Pain 10 (2006) 77–88

www.EuropeanJournalPain.com

Quantitative sensory testing: a comprehensive protocol

for clinical trials
a,b
R. Rolke , W. Magerl a, K. Andrews Campbell c, C. Schalber a, S. Caspari a,
F. Birklein b, R.-D. Treede a,*
a
Institute of Physiology and Pathophysiology, Johannes Gutenberg-University, Saarstr. 21, D-55099 Mainz, Germany
b
Department of Neurology, Johannes Gutenberg-University, Mainz, Germany
c
Department of Anatomy and Developmental Biology, University College, London, UK

Received 19 October 2004; accepted 3 February 2005

Available online 28 March 2005

Abstract

We have compiled a comprehensive QST protocol as part of the German Research Network on Neuropathic Pain (DFNS) using well
established tests for nearly all aspects of somatosensation. This protocol encompasses thermal as well as mechanical testing procedures.
Our rationale was to test for patterns of sensory loss (small and large nerve fiber functions) or gain (hyperalgesia, allodynia, hyper-
pathia), and to assess both cutaneous and deep pain sensitivity. The practicality of the QST protocol was tested in 18 healthy subjects,
21–58 years, half of them female. All subjects were tested bilaterally over face, hand and foot. We determined thermal detection and pain
thresholds including a test for the presence of paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a
64-Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus–response-functions for pinprick and
dynamic mechanical allodynia (pain to light touch), and pain summation (wind-up ratio) using repetitive pinprick stimulation.
The full protocol took 27 ± 2.3 min per test area. The majority of QST parameters were normally distributed only after loga-
rithmic transformation (secondary normalization) except for the frequency of paradoxical heat sensations, cold and heat pain
thresholds, and for vibration detection thresholds. Thresholds were usually lowest over face, followed by hand, and then foot. Only
thermal pain thresholds, wind-up ratio and vibration detection thresholds were not significantly dependent on the body region.
There was no significant right-to-left difference for any of the QST parameters; left-to-right correlation coefficients ranged between
0.78 and 0.97, thus explaining between 61% and 94% of the variance. This study has shown that a complete somatosensory profile of
one affected area and one unaffected control area, which will be necessary to characterize patients with a variety of diseases, can be
obtained within 1 h. Case examples of selected patients illustrate the value of z-transformed QST data for an easy survey of indi-
vidual symptom profiles.
! 2005 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All
rights reserved.

Keywords: QST; Sensory profile; Allodynia; Hyperalgesia; Hypoesthesia; Hypoalgesia; Paradoxical heat sensation; Data transformation; Z-scores

Abbreviations: ALL, Dynamic mechanical allodynia; CDT, Cold detection threshold; CPT, Cold pain threshold; DFNS, Deutscher Forschun-
gsverbund Neuropathischer Schmerz; HPT, Heat pain threshold; MDT, Mechanical detection threshold; MPS, Mechanical pain sensitivity; MPT,
Mechanical pain threshold; PHS, Paradoxical heat sensation; PPT, Pressure pain threshold; TSL, Thermal sensory limen; VDT, Vibration detection
threshold; WDT, Warm detection threshold; WUR, Wind-up ratio.
*
Corresponding author. Tel.: +49 6131 3925715; fax: +49 6131 3925902.
E-mail address: treede@uni-mainz.de (R.-D. Treede).

1090-3801/$32 ! 2005 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights
reserved.
doi:10.1016/j.ejpain.2005.02.003
78 R. Rolke et al. / European Journal of Pain 10 (2006) 77–88
1. Introduction
The assessment of patients with neuropathic pain may
utilize the following methods: clinical bedside examina-
tion, quantitative sensory testing (QST), questionnaires,
standard electrodiagnostic studies, laser evoked poten-
tials (LEP), functional neuroimaging (fMRI and PET),
and skin biopsy (Cruccu et al., 2004; Dworkin et al.,
2003). Whereas questionnaires are the formalized exten-
sion of taking the patient!s history, quantitative sensory
testing refers to a set of methods that extend the tradi-
tional neurological examination of somatosensory func-
tion (Greenspan, 2001; Gracely, 1999; Haanpää et al.,
1999). A great variety of quantitative testing procedures
has been published, each of which allows quantifying one
particular aspect of sensory function. At a consensus
conference convened in September 1997 in Boston by
Gary Bennett and David Borsook, it became apparent
that sophisticated methods of sensory testing are avail-
able to assess all aspects of somatosensory function that
may be of clinical interest (Arendt-Nielsen, 1997; Arezzo
et al., 1993; Cruccu et al., 2004; Dworkin et al., 2003;
Dyck et al., 1993a,b; Fields et al., 1998; Gescheider
et al., 2001; Gracely et al., 2003; Hansson and Lindblom,
1993; Shy et al., 2003; Tölle and Baron, 2002). However,
two major drawbacks limit their value: first, there is no
general agreement on standard procedures and every
sensory function may be assessed in a variety of ways
and even the same test instrument may give different out-
comes due to a variation of stimulation parameters, e.g.,
thermal thresholds as a function of the temperature ramp
(Yarnitsky et al., 1995). Second, performing a compre-
hensive battery of all those tests in any given patient will
eventually exceed the time constraints of clinical routine
by far (i.e., a maximum of 60–90 min per patient), thus
there is an urgent need for a comprehensive short form
QST protocol.
To address that issue we have compiled a standard-
ized comprehensive QST battery as part of a nationwide
multicenter research network (German Research Net-
work on Neuropathic Pain-DFNS; http://www.neuro.
med.tu-muenchen.de/dfns/e_index.html) that would
give profiles of somatosensory function for two body
areas (one affected and one normal area), and should
be performed within 1 h. In contrast to other studies
that restricted the assessment to thermal stimuli (Yarnit-
sky et al., 1995), we included both thermal and mechan-
ical test stimuli. In this respect, our QST protocol is
similar to the CASE IV system (Dyck et al., 1993b) that
was developed to assess loss of somatosensory function,
both in small fiber neuropathies (thermal thresholds)
and in large fiber neuropathies (tactile thresholds). Our
protocol extends beyond the CASE IV system, however,
by also assessing parameters of increased pain sensitivity
(hyperalgesia, allodynia, hyperpathia). For mechanical
pain we distinguish dynamic and two types of static
hyperalgesia (Brune and Handwerker, 2004; Kilo
et al., 1994; Koltzenburg et al., 1992; Ochoa and Yarnit-
sky, 1993). Pressure pain thresholds were included to as-
sess both cutaneous and deep pain sensitivity (Bendtsen
et al., 1996; Brennum et al., 1989; Treede et al., 2002).
Based on previously published studies the design of
the QST battery assembles a comprehensive list of robust
and validated short form tests representing measures of
all relevant submodalities of the somatosensory system,
namely:
! cold and warm detection thresholds (Fruhstorfer
et al., 1976; Gray et al., 1982; Yarnitsky and Spre-
cher, 1994);
! number of paradoxical heat sensations during the
thermal sensory limen procedure (Hansen et al.,
1996; Susser et al., 1999);
! cold and heat pain thresholds (Fruhstorfer et al.,
1976; Granot et al., 2003; Tillman et al., 1995; Yarnit-
sky et al., 1995);
! mechanical detection threshold (Bove et al., 2003;
Fruhstorfer et al., 2001; Von Frey, 1896; Weinstein,
1968);
! mechanical pain threshold and mechanical pain sensi-
tivity (Chan et al., 1992; Greenspan and McGillis,
1994; Magerl et al., 1998);
! dynamic mechanical allodynia (Baumgärtner et al.,
2002; LaMotte et al., 1991; Lindblom and Verillo,
1979; Magerl et al., 2001);
! temporal pain summation (‘‘Wind-up’’; Magerl et al.,
1998; Price et al., 1977, 1994; Sieweke et al., 1999);
! vibration detection threshold (Bolanowski et al.,
1988; Fagius and Wahren, 1981; Goldberg and
Lindblom, 1979; Hilz et al., 1998; Rydel and Seiffer,
1903; Talbot et al., 1968);
! pressure pain threshold (Chesterton et al., 2003;
Fischer, 1987; Jensen et al., 1986; Kilo et al., 1994;
Kosek et al., 1999; Rolke et al., 2005).
The aim of our QST protocol was to provide param-
eters for sensory loss (small and large fiber functions) and
sensory gain (hyperalgesia, allodynia, hyperpathia). We
tested the feasibility of this QST battery bilaterally over
three different body regions (face, hand, foot) in a single
center study for the following purposes: (1) to determine
the time needed to obtain a full somatosensory profile
for one test area, (2) to evaluate the psychometric prop-
erties of all parameters, (3) to propose standards for data
evaluation, and (4) to prepare a form of simple data pre-
sentation for clinical use in individual patients.
2. Methods
The whole battery was developed as part of the Ger-
man Research Network on Neuropathic Pain (DFNS)
 R. Rolke et al. / European Journal of Pain 10 (2006) 77–88 79

Fig. 1. QST-a battery of sensory tests: figure of methods. The standardized QST protocol assesses 13 parameters in seven test procedures (A–G). All
procedures are presented including a time frame for testing over one area. A. Thermal testing comprises detection and pain thresholds for cold, warm,
or hot stimuli (C- and A-delta fiber mediated): cold detection threshold (CDT); warm detection threshold (WDT); number of paradoxical heat
sensations (PHS) during the thermal sensory limen procedure (TSL) for alternating warm and cold stimuli; cold pain threshold (CPT); heat pain
threshold (HPT). B. mechanical detection threshold (MDT) tests for A-beta fiber function using von Frey-filaments. C. Mechanical pain threshold
(MPT) tests for A-delta fiber mediated hyper- or hypoalgesia to pinprick stimuli. D. Stimulus–response-functions: mechanical pain sensitivity (MPS)
for pinprick stimuli, and dynamic mechanical allodynia (ALL) assess A-delta mediated sensitivity to sharp stimuli (pinprick), and also A-beta fiber
mediated pain sensitivity to stroking light touch (CW = cotton wisp; QT = cotton wool tip; BR = brush). E. Wind-up ratio (WUR) compares the
numerical ratings within five trains of a single pinprick stimulus (a) with a series (b) of 10 repetitive pinprick stimuli to calculate WUR as the ratio:
b/a. F. Vibration detection threshold (VDT) tests for A-beta fiber function using a Rydel–Seiffer 64 Hz tuning fork. G. Pressure pain threshold (PPT)
is the only test for deep pain sensitivity, most probably mediated by muscle C- and A-delta fibers. For details regarding the testing procedures also see
Section 2.

and consists of seven tests measuring 13 parameters 2.1. Subjects

(Fig. 1). The tests can be grouped as follows:
! thermal detection thresholds for the perception of
cold, warm and paradoxical heat sensations,
! thermal pain thresholds for cold and hot stimuli,
! mechanical detection thresholds for touch and
vibration,
! mechanical pain sensitivity including thresholds for
pinprick and blunt pressure, a stimulus–response-
function for pinprick sensitivity and dynamic
mechanical allodynia, and pain summation to repeti-
tive pinprick stimuli.
To evaluate the properties of the QST battery we
tested a small sample of 18 healthy human subjects
(9 female, 9 male, mean age 38.1 ± 14.2 years, range
21–58 years). QST data over face (cheek), hand (dor-
sum) and foot (dorsum) on both sides of the body were
obtained within one experimental session. All subjects
were without pain medication for at least 24 h prior
to the investigation. The study was approved by the lo-
cal ethics committee (Landesärztekammer Rheinland-
Pfalz) and all subjects had given written informed
consent.

Since it was our aim to use simple hand-held de-
vices whenever available, we did not use an automated
vibrameter or pressure algometer, which are useful in
specialized sensory laboratory tests. For thermal
testing, no simple devices are available yet (Cruccu
et al., 2004).
2.2. Thermal detection, thermal pain thresholds and
paradoxical heat sensations
The tests for thermal sensation were performed using
a TSA 2001-II (MEDOC, Israel) thermal sensory testing
device (Fruhstorfer et al., 1976; Yarnitsky et al., 1995).
80 R. Rolke et al. / European Journal of Pain 10 (2006) 77–88
Cold detection threshold (CDT) and warm detection
threshold (WDT) were measured first. The number of
paradoxical heat sensations (PHS) was determined dur-
ing the thermal sensory limen procedure (TSL, the dif-
ference limen for alternating cold and warm stimuli),
followed by cold pain threshold (CPT), and heat pain
threshold (HPT). The mean threshold temperature of
three consecutive measurements was calculated. All
thresholds were obtained with ramped stimuli (1 "C/s)
that were terminated when the subject pressed a button.
Cut-off temperatures were 0 and 50 "C. The baseline
temperature was 32 "C (center of neutral range) and
the contact area of the thermode was 7.84 cm2. During
the experiment, the subjects were not able to watch the
computer screen. All thermal tests were first demon-
strated over an area that was not tested later during
the QST session.
2.3. Mechanical detection threshold for modified
von Frey filaments
Modified von Frey filaments (MDT) was measured
with a standardized set of modified von Frey hairs
(Optihair2-Set, Marstock Nervtest, Germany) that exert
forces between 0.25 and 512 mN (Fruhstorfer et al.,
2001; Von Frey, 1896; Weinstein, 1968). The contact
area of the von Frey hairs with the skin was of uniform
size and shape (rounded tip, 0.5 mm in diameter) to
avoid sharp edges that would facilitate nociceptor acti-
vation. The final threshold was the geometric mean of
five series of ascending and descending stimulus intensi-
ties (Baumgärtner et al., 2002).
2.4. Mechanical pain threshold for pinprick stimuli
Mechanical pain threshold (MPT) was measured
using a set of seven custom-made weighted pinprick
stimulators (flat contact area of 0.2 mm diameter) that
exert forces between 8 and 512 mN (Baumgärtner
et al., 2002; Chan et al., 1992; Magerl et al., 1998).
Again using the ‘‘method of limits’’, the final threshold
was the geometric mean of five series of ascending and
descending stimulus intensities.
2.5. Stimulus–response-functions: mechanical pain
sensitivity for pinprick stimuli and dynamic mechanical
allodynia for stroking light touch
Mechanical pain sensitivity (MPS) was tested using
the same weighted pinprick stimuli as for MPT. To ob-
tain a stimulus–response-function, these seven pinprick
stimuli were applied in a balanced order, five times each,
and the subject was asked to give a pain rating for each
stimulus on a 0–100 numerical rating scale ("0! indicating
‘‘no pain’’, and "100! indicating ‘‘most intense pain
imaginable’’).
Stimulus–response-functions for dynamic mechani-
cal allodynia (ALL) were determined using a set of
three light tactile stimulators (Baumgärtner et al.,
2002; LaMotte et al., 1991): a cotton wisp exerting a
force of "3 mN, a cotton wool tip fixed to an elastic
strip exerting a force of "100 mN, and a standardized
brush (Somedic, Sweden) exerting a force of "200–400
mN. The three tactile stimuli were applied five times
each with a single stroke of approximately 1–2 cm in
length over the skin. They were intermingled with the
pinprick stimuli in balanced order and subjects were
asked to give a rating on the same scale as for pinprick
stimuli.
2.6. Wind-up ratio – the perceptual correlate of temporal
pain summation for repetitive pinprick stimuli
In this test of temporal summation, the perceived
magnitude of a single pinprick stimulus was compared
with that of a train of 10 pinprick stimuli of the same
force repeated at a 1/s rate (128 mN, when tested over
face, and 256 mN, when tested over hand and foot).
The train of pinprick stimuli was given within a small
area of 1 cm2 and the subject was asked to give a pain
rating representing the pain at the end of the train using
a numerical rating scale. In contrast to the more sophis-
ticated technique of VAS-ratings at a 1/s rate (Magerl
et al., 1998) this method (modified from Sieweke et al.,
1999) is likely more appropriate for clinical routine
assessment. Single pinprick stimuli were alternated with
a train of 10 stimuli until both were done five times at
five different skin sites within the same body region.
The mean pain rating of trains divided by the mean pain
rating to single stimuli was calculated as wind-up ratio
(WUR).
2.7. Vibration detection threshold
Vibration detection threshold (VDT) test was per-
formed with a Rydel–Seiffer tuning fork (64 Hz, 8/8
scale) that was placed over a bony prominence (cheek,
processus styloideus ulnae, malleolus medialis). Vibra-
tion threshold was determined with three series of
descending stimulus intensities (Fagius and Wahren,
1981; Goldberg and Lindblom, 1979; Rydel and Seiffer,
1903).
2.8. Pressure pain threshold
The final test in the protocol was performed with a
pressure gauge device (FDN200, Wagner Instruments,
USA) with a probe area of 1 cm2 (probe diameter of
1.1 cm) that exerts pressure up to 20 kg/cm2/"200
N/cm2/"2000 kPa (Fischer, 1987; Kilo et al., 1994; Ko-
sek et al., 1999; Rolke et al., 2005). The pressure pain
threshold (PPT) is determined with three series of
 R. Rolke et al. / European Journal of Pain 10 (2006) 77–88
ascending stimulus intensities, each applied as a slowly
increasing ramp of 50 kPa/s.
2.9. Data evaluation
All data were analyzed for their distribution proper-
ties. We calculated skewness, kurtosis, Kolmogorov–
Smirnov!s d for raw data and log-transformed data.
The product of the geometric mean of skewness and
kurtosis combined and the geometric mean of Kolmogo-
rov–Smirnov!s d (for continuous test of normality of dis-
tribution) was calculated as a compound measure of
goodness of normality. Log-transformation was consid-
ered to be superior, when the ratio for raw data to log-
transformed data exceeded a factor of 3.
For pain ratings to pinprick and light touch a small
constant (+0.1) was added prior to log-transformation
to avoid a loss of zero rating values (Bartlett, 1947;
Magerl et al., 1998). All statistical calculations were per-
formed by using the Statistica software package, release
6.0 for Windows (StatSoft Inc., USA). Differences be-
tween areas (face, hand, foot), right and left sides of
the body were compared using a two-way analysis of
variance for repeated measures (ANOVA). Post hoc
comparisons were calculated using LSD-post hoc tests
(LSD = least significant difference). Log-data of thresh-
olds were retransformed to linear values representing the
original unit of each test.
2.10. Z-transformation of QST data to create profiles
of sensory changes
To compare a patient!s QST data profile with
control data independent of the different units of mea-
surement across QST parameters, the patient data were
Z-transformed for each single parameter by using the
following expression (Glass and Stanley, 1970; Gauss,
1863):
Z-score ¼ ðXsingle patient % Meancontrols Þ=SDcontrols :
This procedure results in a QST profile where all param-
eters are presented as standard normal distributions
(zero mean, unit variance). For clarity of data presenta-
tion we adjusted the algebraic sign of Z-score values for
each parameter so that it reflects the patient!s sensitivity
for this parameter. Z-values above ‘‘0’’ indicate a gain of
function when the patient is more sensitive to the tested
stimuli compared with controls, while Z-scores below
‘‘0’’ indicate a loss of function referring to a lower sen-
sitivity of the patient. Thus, elevations of threshold
(CDT, WDT, TSL, HPT, CPT, MDT, MPT, VDT,
PPT) resulted in negative Z-scores, whereas increases
in ratings (MPS, ALL, WUR) resulted in positive
Z-scores. Paradoxical heat sensations (PHS) were inter-
preted as a loss of thermodiscriminative function result-
ing in negative Z-scores. Even though QST specialists
81
are familiar with the concept of threshold elevations,
we decided to use this procedure, because the general
readership may find it conceptually easier to think in
terms of gain or loss of sensory function.
After this Z-transformation it is straightforward to
compare a single patient with the group mean of healthy
controls, since the 95% confidence interval (CI) of a
standard normal distribution is defined as follows:
95% CI ¼ Meancontrols ' 1:96SDcontrols :
3. Results
It was possible to obtain all QST data in all 18
healthy subjects at all sites tested. The testing procedures
were easily feasible with a mean duration of 27.0 ± 2.3
min for the full QST protocol tested over one test area.
Thus, assessing six sites in healthy subjects took about
3 h. In patients, assessment of two sites (one affected,
one normal area) is expected to be finished within 1 h.
3.1. QST report form
QST data were entered into an EXCEL-spreadsheet
(Microsoft, USA) automatically generating thresholds
and average ratings, and numbers of observed symp-
toms (in the case of PHS). These data are summarized
in a single sheet QST report form which eases compari-
son of the test and control areas (Fig. 2).
3.2. The majority of QST parameters are lognormally
distributed
Some QST parameters were not normally distributed,
but normal distribution was achieved by logarithmic
transformation (secondary normal distribution). A typi-
cal example is shown in Fig. 3 (warm detection thresh-
olds in the hand dorsum). Table 1 comprises skewness,
kurtosis and Kolmogorov–Smirnov!s d as markers to test
for normality of distribution in raw and log-transformed
data. Based on a weighted comparison of distribution
parameters we recommend to execute log-transforma-
tion in the following QST parameters: CDT, WDT,
TSL, MDT, MPT, MPS, ALL, WUR, and PPT.
3.3. QST procedures show highly significant differences
across test areas
There were highly significant differences between test
areas for most QST parameters (Table 2), except for
cold pain threshold (CPT), heat pain threshold (HPT),
wind-up ratio (WUR), and vibration detection threshold
(VDT). Differences between test areas could not be as-
sessed for paradoxical heat sensations (PHS) and dy-
namic mechanical allodynia (ALL) because there was
82 R. Rolke et al. / European Journal of Pain 10 (2006) 77–88

Fig. 2. QST report form. The QST report form allows easy comparisons of parameters over control vs. test site supplemented by the corresponding
Z-score compared to healthy age and gender matched subjects. These comparisons might be between different test areas, e.g., hand vs. foot in the case
of a patient with symmetrical neuropathy. Most important will be direct comparisons of right and left side of the body, e.g., in a patient with an
unilateral chronic pain syndrome over distal limb.

no significant occurrance of these parameters in healthy
subjects. Mean value differences across areas are illus-
trated in Table 1. Thresholds were usually lowest over
face, followed by hand and foot with the exceptions of
vibration detection threshold presenting the highest sen-
sitivity in the hand (Table 1), and stimulus–response-
function for pinprick presenting highest sensitivity over
face, followed by foot, then hand. No differences were
found between body sides (Table 2), and there were no
interactions between test area and body side. These find-
ings confirm that each area of the body needs its own set
of QST reference data. Due to the narrow age range and
small number of healthy subjects in the present study we
did not address age or gender differences.
3.4. Intra- and interindividual variability of QST data
Since there were no significant differences in thresh-
olds between the right and left sides of the body, nor
any significant interactions with other factors (Table 2),
we compared data for left and right body sides to assess
intra-individual variability of QST testing. The correla-
tion coefficients were highly significant (r = 0.78–0.97,
all p < 0.001), and their squared values indicate that
systematic interindividual differences accounted for
between 61% and 94% of the total variance of the
QST parameters. These findings suggest lower variabil-
ity of QST parameters within subjects than across
subjects.
3.5. QST profiles of Z-transformed data in selected
patients
To illustrate the potential use of QST profiles, Fig. 4
presents QST profiles of three selected patients. Some of
the Z-values were beyond the 95% confidence interval
(grey zone) of healthy subjects showing three different
patterns of sensory changes.
 R. Rolke et al. / European Journal of Pain 10 (2006) 77–88
Fig. 3. Warm detection threshold in the hand dorsum: distribution of
raw and log data. Some QST parameters are distributed normally in
log space. The raw data (a) of warm detection thresholds (difference
from baseline 32 "C) show significant differences comparing fitted and
observed distribution. The dotted line represents the fitted shape of the
normal (expected) distribution, which is significantly different from the
observed distribution of raw data (Kolmogorov–Smirnov!s d = 0.14;
p < 0.001). After log transformation with base 10 (b) warm detection
thresholds are distributed normally. The solid line in both (a) and (b)
represents the fitted normal distribution of log transformed data
without any differences between expected and observed distribution
parameters (Kolmogorov-Smirnov!s d = 0.08; p = 0.67).
Patient A (vibration induced vasospastic syndrome),
a 64-year-old man, complained about intermittent Ray-
naud-syndrome and painless dysesthesia of the right
hand after working for more than 20 years using a
chain-saw. Sensory conduction velocities of the median
and ulnar nerves were pathologically reduced, motor
conduction velocity was normal corresponding to the
lack of a motor deficit. Autonomic testing revealed
normal sudomotor function, but a slightly reduced heart
rate variability. The QST profile shows combined sen-
sory loss for large fiber (MDT, VDT) and small fiber
mediated stimuli (CDT, WDT, TSL).
Patient B (small fiber neuropathy), a 60-year-old
woman, suffered for more than 1 year from a severe
83
burning pain over feet with a stocking distribution.
Mean pain rating was 50 on a 0–100-numerical rating
scale. Conventional neurography over legs only demon-
strated a reduced amplitude (2.4 mV) of the peroneal
nerve but normal motor conduction velocity (51.8 m/s)
of that nerve. Somatosensory evoked potentials (SEP)
of the tibial nerve were normal (latency 41.0 ms, ampli-
tude 1.5 lV). Motor evoked potentials (MEP) were nor-
mal for hands and feet. The QST profile of this patient
shows a loss of sensory function only for thermal detec-
tion thresholds (CDT, WDT, TSL), which are mediated
by small nerve fibers. Cooling stimuli during the TSL
procedure were often mistaken as heating stimuli (para-
doxical heat sensations).
Patient C (chronic low back pain attributed to facet
joint arthropathy), a 45-year-old woman, complained
about permanent low-back pain of fluctuating intensity
for 7 years. Mean pain rating was 60 on a 0–100 numer-
ical rating scale. Clinically, there was neither sensory nor
motor loss attributable to any spinal root. Pain in-
creased upon dorsiflexion of the back, and paraspinal
segments L4 and L5 overlying the facet joints were sen-
sitive to local pressure bilaterally. The QST profile of
this patient shows a sensory gain beyond the normal
range for cold pain threshold (CPT), for sharp stimuli
(MPT, MPS), and blunt pressure (PPT).
4. Discussion
Our study shows that the present QST protocol con-
sisting of seven previously published tests examining
altogether 13 QST parameters covering all somatosen-
sory channels was feasible within a reasonable time of
about 1 h for two symmetrical areas of the body. Differ-
ences in thresholds over different body areas indicate the
need for calculating QST reference data for each area,
and for presenting data of individual patients relative
to those reference data. The lack of a side difference over
all areas suggests that side-to-side testing may give the
most sensitive results. Further studies need to evaluate
this QST battery regarding inter-observer reliability,
repeatability within defined time intervals, and validity
for mechanism-based diagnoses in patients with chronic
pain (Hansson et al., 2001; Jensen and Baron, 2003;
Woolf et al., 1998).
4.1. QST parameters vary significantly over areas
As in previous studies the body area over which QST
parameters were tested had a significant effect on most
QST parameters (CDT, WDT, TSL, MDT, MPT,
MPS, PPT). Generally lowest thresholds were found
over face, followed by hand and foot. The same regional
differences were seen in thermal pain thresholds (CPT,
HPT) but just failed to be significant due to the limited
84 R. Rolke et al. / European Journal of Pain 10 (2006) 77–88

Table 1
Distribution parameters: the majority of QST parameters are normally distributed only after logarithmic transformation (secondary normalization)
Parameter Mean ± SD Mean ± SD Skewness Kurtosis K–S 0 d Weighted Recommended data
(raw data) (log data) (raw/log) (raw/log) (raw/log) ratio transformation
(raw/log)
CDT (DT, "C) Face %0.67 ± 0.33 %0.213 ± 0.173 %2.28/1.01 6.51/1.04 0.25/0.19
Hand %0.91 ± 0.44 %0.081 ± 0.179 %1.67/0.81 2.30/0.28 0.20/0.12 6.92 Log
Foot %1.71 ± 1.47 0.187 ± 0.280 %0.13/%0.08 3.45/0.12 0.17/0.12
WDT (DT, "C) Face 1.05 ± 0.49 %0.019 ± 0.186 1.21/0.47 0.77/%0.55 0.18/0.13
Hand 1.87 ± 0.82 0.237 ± 0.173 1.63/0.23 3.66/0.75 0.14/0.08 5.90 Log
Foot 4.57 ± 2.30 0.615 ± 0.195 1.50/0.46 2.38/%0.34 0.17/0.11
TSL (DT, "C) Face 1.37 ± 0.84 0.056 ± 0.293 1.24/%1.11 0.88/3.90 0.24/0.16
Hand 2.81 ± 1.36 0.403 ± 0.200 1.55/%0.06 3.30/0.61 0.22/0.13 4.04 Log
Foot 6.80 ± 2.71 0.802 ± 0.165 1.01/0.21 0.83/%0.61 0.13/0.07
PHSa (x/3) Face 0±0 %1.000 ± 0
Hand 0±0 %1.000 ± 0 None
Foot 0.11 ± 0.40 %0.905 ± 0.321
CPT ("C) Face 10.36 ± 10.35 0.410 ± 1.021 0.53/%0.54 %1.21/%1.56 0.18/0.24
Hand 7.73 ± 7.82 0.436 ± 0.865 1.00/%0.82 0.11/%0.87 0.16/0.21 0.77 None
Foot 5.96 ± 7.74 0.202 ± 0.910 1.62/%0.35 1.77/%1.54 0.22/0.21
HPT ("C) Face 44.96 ± 3.31 1.652 ± 0.033 %0.77/%0.94 0.10/0.39 0.14/0.15
Hand 45.39 ± 3.60 1.656 ± 0.036 %0.63/%0.81 %0.09/0.34 0.10/0.11 1.21 None
Foot 45.80 ± 2.61 1.660 ± 0.025 %0.68/%0.79 %0.24/%0.002 0.14/0.15
MDT (mN) Face 0.21 ± 0.05 %0.682 ± 0.093 1.33/1.04 0.82/0.03 0.27/0.28
Hand 1.93 ± 2.08 0.124 ± 0.366 3.01/0.36 11.46/0.07 0.25/0.10 3.78 Log
Foot 3.52 ± 3.46 0.367 ± 0.413 1.93/%0.11 3.55/%0.29 0.18/0.09
MPT (mN) Face 55.7 ± 58.6 1.537 ± 0.456 2.17/%0.23 5.22/%0.49 0.22/0.10
Hand 129.3 ± 95.5 1.971 ± 0.394 0.99/%0.71 0.49/0.13 0.15/0.10 7.44 Log
Foot 88.2 ± 74.4 1.764 ± 0.452 1.28/%0.66 1.48/%0.13 0.16/0.12
MPS (rating) Face 1.79 ± 2.18 %0.039 ± 0.519 1.74/0.24 2.17/%0.96 0.23/0.11
Hand 0.65 ± 0.79 %0.409 ± 0.425 2.59/0.51 7.95/%0.45 0.28/0.11 7.76 Log
Foot 0.94 ± 1.11 %0.292 ± 0.471 1.49/0.61 0.94/%1.05 0.27/0.17
ALLa (rating) Face 0±0 %1.000 ± 0
Hand 0.001 ± 0.006 %0.995 ± 0.023 Logb
Foot 0.001 ± 0.003 %0.998 ± 0.013
WUR (ratio) Face 3.11 ± 2.10 0.419 ± 0.247 2.06/0.54 5.37/%0.31 0.18/0.12
Hand 2.67 ± 1.94 0.338 ± 0.268 1.45/0.74 1.01/%0.59 0.29/0.18 3.31 Log
Foot 3.20 ± 2.14 0.420 ± 0.271 1.05/0.44 %0.21/%1.14 0.20/0.13
VDT (x/8) Face 7.20 ± 0.75 %0.266 ± 0.500 %0.63/%0.43 %0.77/%1.30 0.21/0.20
Hand 7.66 ± 0.43 %0.564 ± 0.445 %1.30/0.24 1.35/%1.62 0.26/0.30 1.96 None
Foot 7.25 ± 0.86 %0.319 ± 0.517 %1.79/%0.23 4.09/%1.34 0.19/0.21
PPT (kPa) Face 212 ± 55.7 2.313 ± 0.113 0.62/0.01 %0.11/%0.20 0.11/0.08
Hand 512 ± 191.6 2.683 ± 0.152 1.13/0.37 1.24/%0.50 0.15/0.09 4.69 Log
Foot 572 ± 199.8 2.732 ± 0.154 0.46/%0.03 %0.71/%1.13 0.15/0.15
DT, difference from baseline temperature 32 "C; K–S 0 d, Kolmogorov–Smirnov!s d.
a
Paradoxical heat sensation (PHS) and allodynia (ALL) did not significantly occur in healthy subjects.
b
Recommendation on data transformation for allodynia (pain to light touch) was derived from patient studies and from studies of experimentally
induced hyperalgesia (Baumgärtner et al., 2002; Magerl et al., 2001).

sample size. These differences may not always represent
true regional differences, since stimuli, which were ap-
plied as increasing ramps of temperature or pressure
(CDT, WDT, TSL, CPT, HPT, PPT) always included
reaction time artefacts, following the rule that the longer
the distance to the brain, the larger the reaction time
artefact (see, e.g., Tillman et al., 1995; Yarnitsky and
Ochoa, 1991). In contrast, the higher sensitivity of the
hand to vibratory stimuli documented in previous stud-
ies (e.g., Goldberg and Lindblom, 1979) just missed
significance in our data (p = 0.08) and may even be
underestimated due to a reaction time artefact, since it
was measured as a disappearance threshold. The pain
thresholds for pinprick stimuli (MPT) constituted an-
other exception from the rule, since MPT was lower over
foot than hand, likely because the hands usually are
more exposed to environmental influences than feet,
e.g., ultraviolet radiation and exhibit a significant thick-
ening of the epidermis resulting in a higher mechanical
resistance to stimuli causing shear stress by very local-
ized strong indentations (Holbrook and Odland, 1974;
Plewig and Marples, 1970).
4.2. Z-score QST profiles for easy data analysis and
presentation
The abundance of tested parameters in the QST
protocol of the DFNS indicates the need for an easily
 R. Rolke et al. / European Journal of Pain 10 (2006) 77–88 85

Table 2
ANOVA and correlation analysis: QST data vary significantly over different areas with a lack of side differences
Factor Test area (1) Body side (2) 1 · 2 Interaction Side-to-side correlation
Parameter F p F P F p r p r2
CDT 31.1 <0.001 0.38 n.s. 0.67 n.s. 0.78 <0.001 0.61
WDT 89.4 <0.001 0.16 n.s. 2.47 n.s. 0.79 <0.001 0.62
TSL 64.3 <0.001 1.86 n.s. 1.46 n.s. 0.88 <0.001 0.77
PHS No significant occurrence of PHS in healthy subjects
CPT 2.80 n.s. 0.52 n.s. 0.08 n.s. 0.89 <0.001 0.79
HPT 0.97 n.s. 0.45 n.s. 0.26 n.s. 0.80 <0.001 0.64
MDT 77.5 <0.001 1.21 n.s. 0.82 n.s. 0.91 <0.001 0.83
MPT 11.2 <0.001 0.69 n.s. 1.56 n.s. 0.89 <0.001 0.79
MPS 5.92 <0.01 3.14 n.s. 0.56 n.s. 0.95 <0.001 0.90
ALL No significant occurrence of ALL in healthy subjects
WUR 2.76 n.s. 3.15 n.s. 1.16 n.s. 0.90 <0.001 0.81
VDT 3.21 n.s. 2.63 n.s. 0.30 n.s. 0.86 <0.001 0.74
PPT 160.0 <0.001 1.03 n.s. 1.65 n.s. 0.97 <0.001 0.94
F- and p-values as derived from 2-way ANOVA for repeated measurements (for list of abbreviations, see Section 2). For some parameters (PHS and
ALL) data exhibited close-to-zero variance and thus the near singular data matrix could not be inverted, i.e., ANOVA could not be calculated,
n.s. = not significant.

applicable standard presentation. At the same time, a
standard presentation has to account for the fact that
different parameters come in different units of measure-
ment and possible data ranges differ vastly across vari-
ables (e.g., 0–3 for PHS vs. 0.0–31.9 "C for CPT).
Moreover, a clear definition of hyper- and hypophe-
nomena is essential, if QST is to gain wider acceptance.
Grouping under the heading of ‘‘abnormal finding’’ as
often done in the existing literature is of little value
and may potentially obscure a view on mechanisms of
a pathology (Hansson et al., 2001). All of these require-
ments are fulfilled by the Z-transformed QST profiles as
presented for three selected patients in Fig. 4. To enable
the reader to interpret the meaning of a deviation from
normality, we adjusted the signs of the Z-score values in
such a way that they specify uniformly whether a change
represents gain or loss of sensitivity. For example, a
drop in pain threshold and an increase in suprathreshold
pain ratings both indicate a gain in pain sensitivity with
positive Z-scores (e.g., in MPT and MPS in patient C).
This way, we have chosen to present QST data accord-
ing to the general concept of ‘‘loss or gain of sensory
function’’, which has a longstanding tradition through-
out the neurological sciences. We suggest to use Z-trans-
formed QST data (i.e., data presentation as values from
a standard normal distribution of a reference database)
in order to judge the significance of sensory changes in a
single patient with reference to healthy controls.
The Z-transformation has to be done separately for
each QST parameter and for each area tested. Most of
the QST parameters required a logarithmic data trans-
formation to conform to a normal (Gaussian) distribu-
tion. For mechanical pain thresholds to blunt and
pricking stimuli, and for pain ratings this transforma-
tion had previously been identified as adequate (e.g.,
Magerl et al., 1998; Rolke et al., 2005). We have now ex-
tended those findings to mechanical and thermal detec-
tion thresholds (cf. Haanpää et al., 1999; Weinstein,
1968), but not thermal pain thresholds. Logarithmic
transformation of the latter are inadequate, since the
temperature scale is arbitrary and there is no natural
zero in the stimulus dimension. In contrast, the wind-
up ratio (Price et al., 1994; Vierck et al., 1997) like all
ratios follows a geometrical distribution, which is ade-
quately accounted for by logarithmic transformation
(cf. Magerl et al., 1998).
In the resulting Z-score QST profile the differences
between different areas like hands or feet become irrele-
vant due to site-specific normalization. Therefore, this
type of data presentation will allow at-a-glance identifi-
cation of symptom patterns, e.g., to identify local vs.
bilateral or generalized alterations of the somatosensory
system. Localized changes can easily be judged com-
pared to an unaffected control area, while generalized
changes can only be identified using absolute reference
values.
4.3. Strengths and limitations of quantitative sensory
testing
Quantitative sensory tests are psychophysical in
nature, with an objective physical stimulus but a subjec-
tive report from a patient or control subject as the
response. In contrast to electrophysiological, imaging
and biopsy techniques, QST requires cooperation from
the subject. The size of the effects of malingering and
other non-organic factors on QST findings is currently
unresolved (Shy et al., 2003), eliminating its use in
medico-legal matters. On the other hand, QST can as-
sess both large and small fiber function as illustrated
in patients A and B, whereas standard electrophysiol-
ogy is limited to large fibers (Cruccu et al., 2004).
86 R. Rolke et al. / European Journal of Pain 10 (2006) 77–88
Fig. 4. Z-score QST profiles of selected patients. Patient A (open
circles) presents the QST profile of a 64-year-old man suffering from
vibration induced vasospastic syndrome with an intermittent Ray-
naud-syndrome and painless dysaesthesia of the right hand after
working with a chain-saw for more than 20 years. The profile shows a
combined loss of sensory function for small fiber mediated stimuli
(note the thermal detection thresholds (CDT, WDT, TSL)), and for
large fiber mediated stimuli (note the mechanical detection threshold
for von Frey-filaments (MDT), and the vibration detection threshold
(VDT) outside the 95% confidence interval of the normal standard
distribution of healthy subjects = grey zone). Patient B (filled squares)
shows the QST profile of a 60-year-old woman with stocking
distributed burning pain over feet for more than 1 year. Main pain
was 50 on a 0–100 numerical rating scale. The QST profile confirms a
small fiber sensory neuropathy (note the cold (CDT), warm detection
thresholds (WDT), thermal sensory limen (TSL), and numbers of
paradoxical heat sensations (PHS) outside the normal range as
presented by the grey zone). Patient C (filled triangles) shows the
QST profile of a 45-year-old woman with chronic low back pain
attributed to facet joint arthropathy. The QST profile presents positive
sensory signs reflected by a gain of function for the mechanical pain
sensitivity to sharp (MPT and MPS), blunt stimuli (PPT), and for cold
pain (CPT).
Laser-evoked potentials allow functional assessment of
small fibers, but appear to be insensitive to gain of func-
tion (Treede et al., 2003). Thus, hyperalgesia and allo-
dynia are domains for QST as illustrated in patient C.
Other small fiber tests (sudomotor, heart rate variabil-
ity) assess the autonomic but not sensory system.
The high side-to-side correlations of all QST param-
eters predict that short-term test–retest reliability within
the same day should be high. However, formal determi-
nation of test–retest reliability over different time ranges
(1 day, 1 month, 1 year) as well as inter-observer reliabil-
ity are needed to assess the overall reliability of this QST
protocol. As mentioned in the recent American Acad-
emy of Neurology guideline (Shy et al., 2003), the
inter-observer reliability will depend on the quality of
training personnel to administer this QST battery in a
standardized fashion. Future studies should show repro-
ducible results on both healthy subjects and patients.
Such studies are under way in the German Research
Network on Neuropathic Pain (DFNS).
Validation of a procedure such as QST requires com-
parison with a gold standard. This is not an easy task,
because QST is not suggested to be a diagnostic test
for one particular disease entity. Instead, we and others
hope that QST will help in the mechanism-based diag-
nosis of pain (cf. Baron and Saguer, 1995; Baumgärtner
et al., 2002; Fields et al., 1998; Hansson et al., 2001;
Jensen and Baron, 2003; Woolf et al., 1998). Such mech-
anisms could include sensory deafferentation, central
sensitization or peripheral sensitization. Although the
patients presented in Fig. 4 lend themselves for a tenta-
tive mechanism-based interpretation, at present this
interpretation is largely based on conjecture and anal-
ogy. Studies on a preclinical level in human surrogate
models of pain and hyperalgesia with known mecha-
nisms of symptom induction are needed to be able to
connect a distinct pattern of sensory changes with an
underlying mechanism and hence establish discrimina-
tive validity. Such studies are already under way (e.g.,
Gustorff et al., 2004; Lang et al., 2004). An advantage
of the QST protocol presented here is that it covers
nearly all aspects of somatosensation and hence can be
used to identify the QST patterns for a wide variety of
mechanisms.
On a clinical level, external validity may be tested in
defined clinical cases and against other (objective) meth-
ods of assessment as was also suggested for all QST in
the current AAN Guidelines (Shy et al., 2003). Valida-
tion against gold-standards is only possible, where they
exist (e.g., clinical neurophysiology for large fiber neu-
ropathy). In reality, for many clinical situations there
is at best a ‘‘brass standard’’. In particular, small fiber
neuropathy cannot be identified at all by standard clin-
ical neurophysiology or light-microscope nerve biopsy,
and skin punch biopsy or laser evoked potentials are
only an emerging possible standard (Cruccu et al.,
2004). Along the same lines of clinical research, specific-
ity and sensitivity have to be estimated to establish the
relative importance of QST and other tests (as instruc-
tive examples see Fitzek et al., 2001; Jääskeläinen
et al., 2004).
4.4. Conclusions and clinical implications
The QST protocol of the DFNS, as described here,
packed an unprecedented wide range of tests, covering
nearly all aspects of somatosensation, into one short
form QST battery that is feasible both technically and
within the time constraints of clinical assessment. None
of the components in this QST battery is a new invention.
We intentionally included only tests that had some previ-
ous evidence for their validity and sensitivity. Distribu-
tion properties of these QST parameters and adequate
data transformation rules were established, which form
the basis of a simple way of data presentation as Z-score
QST profiles. This work has now to be extended to
 R. Rolke et al. / European Journal of Pain 10 (2006) 77–88
establish a population-based reference database, which is
currently developed by a nation-wide multi-center study
(DFNS – German Research Network on Neuropathic
Pain). Such a database will provide data on the age
and gender-dependence of all QST parameters. Inter-
observer and test–retest reliability have to be established
to confirm the adequacy of this QST protocol. Once val-
idated with known neural mechanisms and against exter-
nal standards, this protocol is expected to help in the
mechanism-based diagnosis of neuropathic pain.
Acknowledgements
This work was supported by BMBF Grant
01EM0107 (German Research Network on Neuropathic
Pain, DFNS), and MAIFOR Grants of the Johannes
Gutenberg-University, Mainz. We are indebted to the
subjects who participated in the study for their consent
and co-operation. We thank G. Günther and G. Schatt
for excellent technical support.
References
Arendt-Nielsen L. Induction and assessment of experimental pain
from human skin, muscle and viscera. In: Jensen TS, Turner JA,
Wiesenfeld-Hallin Z, editors. Proceedings of the 8th world congress
on pain, progress in pain research and management. Seattle: IASP
Press; 1997. p. 393–425.
Arezzo JC, Bolton CF, Boulton A, Casey KL, Dyck PJ, Cornblath D,
et al. Quantitative sensory testing: a consensus report from the
peripheral neuropathy association. Neurology 1993;43:1050–2.
Baron R, Saguer M. Mechanical allodynia in postherpetic neuralgia:
evidence for central mechanisms depending on nociceptive c-fiber
degeneration. Neurology 1995;45:S63–5.
Bartlett MS. The use of transformations. Biometrics 1947;3:39–52.
Baumgärtner U, Magerl W, Klein T, Hopf HC, Treede R-D.
Neurogenic hyperalgesia versus painful hypoalgesia: two distinct
mechanisms of neuropathic pain. Pain 2002;96:141–51.
Bendtsen L, Jensen R, Olesen J. Qualitatively altered nociception in
chronic myofascial pain. Pain 1996;65:259–64.
Bolanowski Jr SJ, Gescheider GA, Verrillo RT, Checkosky CM. Four
channels mediate the mechanical aspects of touch. J Acoust Soc
Am 1988;84:1680–94.
Bove GM, Robichaud DR, Grigg P. Three-dimensional load analysis
of indentation stimulators. J Neurosci Meth 2003;123:23–30.
Brennum J, Kjeldsen M, Jensen K, Jensen TS. Measurements of
human pressure–pain thresholds on fingers and toes. Pain
1989;38:211–7.
Brune K, Handwerker HO, editors. Hyperalgesia: molecular mecha-
nisms and clinical implications; 2004.
Chan AW, MacFarlane IA, Bowsher D, Campbell JA. Weighted
needle pinprick sensory thresholds: a simple test of sensory
function in diabetic peripheral neuropathy. J Neurol Neurosurg
Psychiatry 1992;55:56–9.
Chesterton LS, Barlas P, Foster NE, Baxter GD, Wright CC. Gender
differences in pressure pain threshold in healthy humans. Pain
2003;101:259–66.
Cruccu G, Anand P, Attal N, Garcia-Larrea L, Haanpää M, Jorum E,
et al. EFNS guidelines on neuropathic pain assessment. Eur J
Neurol 2004;11:153–62.
87
Dworkin RH, Backonja M, Rowbotham MC, Allen RR, Argoff CR,
Bennett GJ, et al. Advances in neuropathic pain: diagnosis,
mechanisms, and treatment recommendations. Arch Neurol
2003;60:1524–34.
Dyck PJ, O!Brain PC, Kosanke JL, Gillen DA, Karnes JL. A 4, 2, and
1 stepping algorithm for quick and accurate estimation of
cutaneous sensation threshold. Neurology 1993a;43:1508–12.
Dyck PJ, Zimmerman I, Gillen DA, Johnson D, Karnes JL, O!Brien
PC. Cool, warm, and heat-pain detection thresholds – testing
methods and inferences about anatomic distribution of receptors.
Neurology 1993b;43:1500–8.
Fagius J, Wahren LK. Variability of sensory threshold determination
in clinical use. J Neurol Sci 1981;51:11–27.
Fields HL, Rowbotham M, Baron R. Postherpetic neuralgia: irritable
nociceptors and deafferentation. Neurobiol Dis 1998;5:209–27.
Fischer AA. Pressure algometry over normal muscles. Standard values,
validity, and reproducibility of pressure thresholds. Pain
1987;30:115–26.
Fitzek S, Baumgärtner U, Fitzek C, Magerl W, Urban P, Thömke F,
et al. Mechanisms and predictors of chronic facial pain in lateral
medullary infarction. Ann Neurol 2001;49:493–500.
Fruhstorfer H, Lindblom U, Schmidt WG. Method for quantitative
estimation of thermal thresholds in patients. J Neurol Neurosurg
Psychiatry 1976;39:1071–5.
Fruhstorfer H, Gross W, Selbmann O. Technical note: von Frey hairs:
new materials for a new design. Eur J Pain 2001;5:341–2.
Gauss CF. Wahrscheinlichkeitsrechnung und Geometrie. In: Diete-
rich, editor. Werke: Gauss; 1863.
Gray L, Stevens JC, Marks LE. Thermal stimulus thresholds: sources
of variability. Physiol Behav 1982;29:355–60.
Gescheider GA, Bolanowski SJ, Hardick KR. The frequency selectiv-
ity of information-processing channels in the tactile sensory system.
Somatosens Mot Res 2001;18:191–201.
Glass GV, Stanley JC, editors. Statistical methods in education and
psychology; 1970. p. 534.
Goldberg JM, Lindblom U. Standardised method of determining
vibratory perception thresholds for diagnosis and screening in
neurological investigation. J Neurol Neurosurg Psychiatry
1979;42:793–803.
Gracely RH. Pain measurement. Acta Anaesthesiol Scand
1999;43:897–908.
Gracely RH, Grant MA, Giesecke T. Evoked pain measures in
fibromyalgia. Best Pract Res Clin Rheumatol 2003;17:593–609.
Granot M, Sprecher E, Yarnitsky D. Psychophysics of phasic and
tonic heat pain stimuli by quantitative sensory testing in healthy
subjects. Eur J Pain 2003;7:139–43.
Greenspan JD. Quantitative assessment of neuropathic pain. Curr
Pain Headache Rep 2001;5:107–13.
Greenspan JD, McGillis SLB. Thresholds for the perception of
pressure, sharpness, and mechanically evoked cutaneous pain:
effects of laterality and repeated testing. Somatosens Motor Res
1994;11:311–7.
Gustorff B, Samal D, Magerl W, Sycha T, Rolke R, Treede R-D.
Primary and secondary hyperalgesia in the human UV-B sunburn
model. Neuropathic pain – an international congress of NeuPSIG,
Book of abstracts; 2004. p. 64.
Haanpää ML, Laippala PA, Nurmikko TJ. Thermal and tactile
perception thresholds in acute herpes zoster. Eur J Pain
1999;3:375–86.
Hansen C, Hopf HC, Treede R-D. Paradoxical heat sensation
in patients with multiple sclerosis. Evidence for a supraspi-
nal integration of temperature sensation. Brain 1996;119:
1729–1736.
Hansson P, Lacerenza M, Marchettini P. Aspects of clinical and
experimental neuropathic pain: the clinical perspective. In: Hans-
son P, Fields HL, Hill RG, Marchettini P, editors. Neuropathic
pain: pathophysiology and treatment; 2001. p. 1–18.
88 R. Rolke et al. / European Journal of Pain 10 (2006) 77–88
Hansson P, Lindblom U. Quantitative evaluation of sensory distur-
bances accompanying focal or referred nociceptive pain. In:
Vecchiet L, Albe-Fessard D, Lindblom U, Giamberardino MA,
editors. New trends in referred pain and hyperalgesia; 1993. p. 251–
8.
Hilz MJ, Axelrod FB, Hermann K, Haertl U, Duetsch M, Neundörfer
B. Normative values of vibratory perception in 530 children,
juveniles and adults aged 3–79 years. J Neurol Sci 1998;159:219–25.
Holbrook KA, Odland GF. Regional differences in the thickness (cell
layers) of the human stratum corneum: an ultrastructural analysis.
J Invest Dermatol 1974;62:415–22.
Jääskeläinen SK, Teerijoki-Oksa T, Virtanen A, Tenovuo O, Forssell
H. Sensory regeneration following intraoperatively verified trigem-
inal nerve injury. Neurology 2004;62:1951–7.
Jensen K, Andersen HO, Olesen J, Lindblom U. Pressure-pain
threshold in human temporal region. Evaluation of a new
algometer. Pain 1986;25:313–23.
Jensen TS, Baron R. Translation of symptoms and signs into
mechanisms in neuropathic pain. Pain 2003;102:1–8.
Kilo S, Schmelz M, Koltzenburg M, Handwerker HO. Different
patterns of hyperalgesia induced by experimental inflammation in
human skin. Brain 1994;117:385–96.
Koltzenburg M, Lundberg LER, Torebjörk HE. Dynamic and static
components of mechanical hyperalgesia in human hairy skin. Pain
1992;51:207–19.
Kosek E, Ekholm J, Hansson P. Pressure pain thresholds in different
tissues in one body region. The influence of skin sensitivity in
pressure algometry. Scan J Rehabil Med 1999;31:89–93.
LaMotte RH, Shain CN, Simone DA, Tsai EFP. Neurogenic
hyperalgesia: psychophysical studies of underlying mechanisms. J
Neurophysiol 1991;66:190–211.
Lang S, Klein T, Magerl W, Treede R-D. Modality-specific sensory
changes parallel the induction of human nociceptive long-term
potentiation (LTP). Soc Neurosci Abstracts 2004 Program No.
644.17.
Lindblom U, Verillo RT. Sensory funtions in chronic neuralgia. J
Neurol Neurosurg Psychiatry 1979;42:422–35.
Magerl W, Fuchs PN, Meyer RA, Treede RD. Roles of capsaicin-
insensitive nociceptors in cutaneous pain and secondary hyperal-
gesia. Brain 2001;124:1754–64.
Magerl W, Wilk SH, Treede R-D. Secondary hyperalgesia and
perceptual wind-up following intradermal injection of capsaicin
in humans. Pain 1998;74:257–68.
Ochoa JL, Yarnitsky D. Mechanical hyperalgesias in neuropathic pain
patients: dynamic and static subtypes. Ann Neurol 1993;33:465–72.
Plewig P, Marples BM. Regional differences of cell size in the human
stratum corneum. Part I. J Invest Dermatol 1970;54:13–8.
Price DD, Hu JW, Dubner R, Gracely RH. Peripheral suppression of
first pain and central summation of second pain evoked by noxious
heat pulses. Pain 1977;3:57–68.
Price DD, Mao J, Frenk H, Mayer DJ. The N-methyl-D-aspartate
receptor antagonist dextromethorphan selectively reduces temporal
summation of second pain in man. Pain 1994;59:165–74.
Rolke R, Andrews Campbell K, Magerl W, Treede R-D. Deep pain
thresholds in the distal limbs of healthy human subjects. Eur J Pain
2005;9:39–48.
View publication stats
Rydel A, Seiffer W. Untersuchungen über das Vibrationsgefühl oder
die sogenannte, ‘‘Knochensensibilität’’ (Pallästhesie). Archiv für
Psychiatrie und Nervenkrankheiten 1903;37:488–536.
Sieweke N, Birklein F, Riedl B, Neundörfer B, Handwerker HO.
Patterns of hyperalgesia in complex regional pain syndrome. Pain
1999;80:171–7.
Shy ME, Frohman EM, So YT, Arezzo JC, Cornblath DR,
Giuliani MJ, Kincaid JC, Ochoa JL, Parry GJ, Weimer LH.
Therapeutics and technology assessment subcommittee of the
American academy of neurology. Quantitative sensory testing:
report of the therapeutics and technology assessment subcom-
mittee of the American academy of neurology. Neurology
2003;60:898–904.
Susser E, Sprecher E, Yarnitsky D. Paradoxical heat sensation in
healthy subjects: peripherally conducted by A delta or C fibres?.
Brain 1999;122:239–46.
Talbot WH, Darian-Smith I, Kornhuber HH, Mountcastle VB. The
sense of flutter-vibration: comparison of the human capacity with
response patterns of mechanoreceptive afferents from the monkey
hand. J Neurophysiol 1968;31:301–34.
Tillman DB, Treede R-D, Meyer RA, Campbell JN. Response of C
fibre nociceptors in the anaesthetized monkey to heat stimuli:
correlation with pain threshold in humans. J Physiol
1995;485:767–74.
Tölle TR, Baron R. Neuropathic pain. Basic principles for successful
therapy. MMW Fortschr Med 2002;144:41–4.
Treede R-D, Lorenz J, Baumgartner U. Clinical usefulness of laser-
evoked potentials. Neurophysiol Clin 2003;33:303–14.
Treede R-D, Rolke R, Andrews K, Magerl W. Pain elicited by blunt
pressure: neurobiological basis and clinical relevance. Pain
2002;98:235–40.
Vierck CJ, Cannon RL, Fry G, Maixner W, Whitsel BL. Character-
istics of temporal summation of second pain sensations elicited by
brief contact of glabrous skin by a preheated thermode. J
Neurophysiol 1997;78:992–1002.
Von Frey M. Untersuchung über die Sinnesfunctionen der menschli-
chen Haut. Erste Abhandlung: Druckempfindung und Schmerz.
Abhandlungen der mathematisch-physischen Klasse der Königli-
chen Sächsischen Gesellschaft der Wissenschaften; 1896. p. 23.
[Translated in: Handwerker HO, Brune K, editors. Classical
German contributions to pain research; 1987. p. 69–131].
Weinstein S. Intensive and extensive aspects of tactile sensitivity as a
function of body part, sex, and laterality. In: Kenshalo D,
Springfield R, Thomas C, editors. The skin senses; 1968. p. 195–
222.
Woolf CJ, Bennett GJ, Doherty M, Dubner R, Kidd B, Koltzenburg
M, et al. Towards a mechanism-based classification of pain?. Pain
1998;77:227–9.
Yarnitsky D, Ochoa JL. Warm and cold specific somatosensory
systems. Psychophysical thresholds, reaction times and peripheral
conduction velocities. Brain 1991;114:1819–26.
Yarnitsky D, Sprecher E. Thermal testing: normative data and
repeatability for various test algorithms. J Neurol Sci
1994;125:39–45.
Yarnitsky D, Sprecher E, Zaslansky R, Hemli JA. Heat pain
thresholds: normative data and repeatability. Pain 1995;60:329–32.