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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, Germany2  Department of Palliative Medicine, University Hospital of Bonn, Bonn, Germany3  Division of Neurological Pain Research and Therapy, Department of Neurology,

Christian-Albrechts-Universität zu Kiel, Kiel, Germany4  Department of Pain Medicine, Berufsgenossenschaftliches Universitätsklinikum

Bergmannsheil, Ruhr University Bochum, Bochum, Germany5  Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany6  Department of Neurophysiology, Center for Biomedicine and Medical Technology Mannheim

(CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany7  Department of Palliative Medicine, Medical Faculty RWTH Aachen University, Aachen, Germany

Quantitative sensory testing (QST)

SchmerzDOI 10.1007/s00482-015-0093-2

© Deutsche Schmerzgesellschaft e.V. Published by Springer-Verlag Berlin Heidelberg - all rights reserved 2015

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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, Tölle T, Treede R-D, Rolke R (2014) Quantitative sensorische Testung. Schmerz 28:635–648 DOI 10.1007/s00482-014-1485-4

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 to Woolf 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

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Übersichten

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

AbstractQuantitative 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.

KeywordsQuantitative sensory testing · QST · Pain profile · Z-score · Somatosensory nervous system · Somatosensory phenotype · Sensitivity test

Quantitative sensorische Testung (QST)

ZusammenfassungDie quantitative sensorische Testung (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 werden Wahrnehmungs- 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- sowie Tiefensensibilität. 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 diagnostisches Verfahren zur Charakterisierung der Funktion des somato-sensorischen Systems.

SchlüsselwörterSensibilitätsprüfung · Schmerzschwelle · Wahrnehmungsschwelle · Somatosensorisches Nerven- system · Hyperalgesie

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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) exert small forces on the skin: 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 Thermal Testing: a Modular Sensory Analyzer (MSA) b Thermal 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

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Übersichten

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. d The 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)

freq

uenc

y of

obs

erva

tions

(%)

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 thresholdsdistribution of raw data

cold detection thresholdsdistribution of log - data

leftwardshifteddistribution

expecteddistribution

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

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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-offmeasurement 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 ofreference data

meanlower end 95%confidence interval ofreference databaseline (BL)

thre

shol

d (k

Pa)

face hand foot

BL0

500

1000

1500

2000PPT

---

+ + +

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. o

f obs

erva

tions

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

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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

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. MückeDepartment of General Practice and Family Medicine,University Hospital of Bonn Bonnmartin.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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