Scandinavian Journal of Pain 9 (2015) 81–86

Contents lists available at ScienceDirect

Scandinavian Journal of Pain

journal homepage: www.ScandinavianJournalPain.com

Original experimental

Spatial summation of thermal stimuli assessed by a standardized,

randomized, single-blinded technique
Vibe Maria Rasmussen a,∗ , Catarina Ellehuus-Hilmersson b , Per Rotbøll-Nielsen c ,
Mads Utke Werner c
a
Department of Anesthesia, Vejle Sygehus/Sygehus Lillebælt, Kabbeltoft 25, DK 7100 Vejle, Denmark
b
Department of Internal Medicine, University Hospital of Skåne, SE 221 85 Lund, Sweden
c
Multidisciplinary Pain Center, Rigshospitalet, Copenhagen University Hospitals, Blegdamsvej 9, DK 2100 Copenhagen Ø, Denmark

h i g h l i g h t s

• Thermal thresholds were assessed by three contact thermodes (3.0, 6.3 and 12.5 cm2 ).
• A significant relationship between thermode size and thermal thresholds was demonstrated.
• Spatial summation was confirmed in a randomized, single-blind study design.
• The study demonstrates that data obtained with a 9 cm2 and 12.5 cm2 cannot be used interchangeably.
• Data from the present study enable estimation of thermal thresholds with differing thermode size.

a r t i c l e i n f o a b s t r a c t

Article history: Background and aims: Quantitative sensory testing of thermal perception (QTT) is a valuable method
Received 6 September 2014 in clinical and experimental assessment of the function of small nerve fibres. Previous studies have
Received in revised form indicated existence of spatial summation for warmth, cool and heat pain stimulation, but study designs
30 November 2014
and assessment methods have not always been mutually consistent. The aims of this study were, first,
Accepted 3 December 2014
to examine spatial summation of QTT by differently sized contact thermodes, and, second, to evaluate if
Available online 20 January 2015
these differences are significant from a clinical and scientific perspective.
Methods: Sixteen healthy subjects were included. Warmth detection (WDT), cool detection (CDT) and
Keywords:
Calibration
heat pain (HPT) thresholds were assessed in random order, with the stimulation areas of the contact
Equipment design thermodes of 3.0, 6.3 and 12.5 cm2 , blinded to the subjects. Assessments were made bilaterally at volar
Human part of the distal arm and medial part of the lower leg. Data analyses were by a mixed model with random
Perception effect for subject and fixed-effects for the variables, site (arm/leg), thermode area (ln thermode area) and
Quantitative sensory testing side (dominant/non-dominant), in addition to conventional pairwise non-parametric comparisons.
Thermal thresholds Results: Data from 2 subjects were excluded. In the remaining 14 subjects only 4 subjects were able to
identify the correct sequence of thermode sizes. The model demonstrated highly statistical significant
relationships regarding main effects: thermode area (P < 0.0001) and stimulation site (P < 0.0001; except
for CDT P = 0.011). The only significant interaction was between thermode area*site (P = 0.005) for CDT.
The study demonstrated in 17 of 18 possible comparisons between thermode size and stimulation site,
a significant spatial summation for WDT, CDT and HPT.
Conclusion: This randomized, single-blind study of thermal thresholds demonstrated spatial summation
and that considerable deviations may occur if values obtained with differing thermode sizes are used
uncritically.
Implications: Data from the present study enable interpolation of thermal thresholds with differing
thermode sizes, facilitating comparisons across studies.
© 2014 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

∗ Corresponding author. Tel.: +45 23321930.

E-mail address: [email protected] (V.M. Rasmussen).

http://dx.doi.org/10.1016/j.sjpain.2014.12.001
1877-8860/© 2014 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
82 V.M. Rasmussen et al. / Scandinavian Journal of Pain 9 (2015) 81–86

1. Introduction

Quantitative sensory testing (QST) of thermal perception

also known as Quantitative Thermal Testing (QTT) is a neuro-
physiological method used in clinical and experimental evaluation
of small nerve fibre function [1]. QTT is a “classical” psy-
chophysical method examining the relationship between a graded
thermal stimulus, and the perceived, subjective response, i.e.,
warmth, cool or heat pain. Assessment of warmth and heat
pain thresholds reflects unmyelinated C-fibre function, while cool
detection threshold is correlated to myelinated A␦-fibre function
[2,3].
Spatial summation denotes either a decrease in numerical
threshold-value accompanying increased stimulation areas, or an
increase in perceived stimulation intensity for increased stim- Fig. 1. The thermodes with identical exterior size (contact surface: 3.8 cm × 9.6 cm)
but with differing thermally active areas: 3.0 cm2 , 6.25 cm2 and 12.5 cm2 .
ulation areas with constant, stimulation intensity [4]. Spatial
summation has been observed for both non-noxious and noxious
thermal [5–7], and, mechanical stimulation [8]. 2.2. Methods
Advantageous use of QTT in clinical testing and in experimental
research requires the method to be standardized [9,10]. A number 2.2.1. Randomization procedure
of studies have contributed to standardization by evaluating the The study used a randomized, single-blind design. The num-
appropriate site of testing, effect of skin temperature, method for ber of subjects required to demonstrate a difference of 20% of the
threshold determination, the rate of temperature change, baseline mean in the compared samples with a variation observed from a
temperature of the thermode, and differences related to gender previous study [18] with the large thermode (heat pain thresh-
of test subjects [7,11–14]. The Peripheral Neuropathy Association old: mean [SD] = 48.0 ◦ C [1.5 ◦ C]) was calculated for double-sided
more than two decades ago recommended specific validation pro- ˛ = 0.05 (type I error of 5%) and ˇ = 0.20 (type II error of 20%,
cedures for thermo-electronic units [9,10], but these are rarely i.e., a power of 80%). The estimated number of subjects required
reported in QTT studies. The German Research Network on Neuro- was 16.
pathic Pain (DFNS) has conducted numerous studies, propagating QTT for warmth, cool and for heat pain were assessed by three
for improvement and development of standardized protocols thermodes with identical exterior size, but with different ther-
for QST [15,16]. The DFNS has implemented multicenter-studies mally active areas: 3.0 cm2 (1.2 × 2.5 cm2 ), 6.25 cm2 (2.5 × 2.5 cm2 )
procuring normative databases for different patient phenotypes, and 12.5 cm2 (5.0 × 2.5 cm2 ; Fig. 1). Thus six different testing
with established age- and gender-matched values [15]. Though sequences of thermodes were possible (small–medium–large,
studies in recent years show more general consensus on the use medium–large–small etc.). In order to get an even distribution of
of QST for the identification of subgroups of patients with different testing sequences, allowing en bloc randomization, three complete
underlying pain mechanisms, prediction of therapeutic outcomes sets of testing sequences were made. Paper slips with each of the
and quantification of therapeutic interventions in pain therapy 18 sequences indicated were each placed in an unmarked closed
[17], there still seems to be a lack of studies with standardized envelope and the envelopes were shuffled. Prior to each test an
procedures focusing on thermal stimulation areas, which may facil- envelope for each subject was drawn by the investigator. The sub-
itate interpretation of data across studies using differently sized jects were throughout the study kept blinded to thermode size and
thermodes. In the present study we therefore evaluated spatial the results of the threshold assessments. At the end of the session
summation of thermal thresholds with a standardized technique each subject was asked to indicate the testing sequence of the
using a randomized procedure blinded to the test subjects. The thermodes.
aims of this study thus were, first, to examine spatial summa-
tion of QTT by three contact thermodes with different thermal 2.2.2. Testing procedure
stimulation areas, and, second, to evaluate if these differences Test sites were the medial part of the lower leg and the volar
are of a relevant magnitude affecting clinical and experimental part of the distal arm. Subjects were instructed to shave the test-
acumen. sites on the legs at least one day prior to testing. Perception
thresholds were determined in a 2–3 h session. During the first
hour the procedure was explained, the test-sites were outlined
and a training session with the large thermode (12.5 cm2 ) was
2. Material and methods performed until the subjects seemed comfortable with the pro-
cedure [19]. Perception thresholds were determined in a specific
2.1. Subjects crossover sequence: leg on dominant side, non-dominant arm,
leg on non-dominant side and dominant arm. All tests took place
The study protocol was approved by the local ethics commit- in a quiet room with an ambient temperature of 22 ◦ C. Subjects
tee (Protocol no. H-KF-01-141-00) and informed written consent were seated in a comfortable reclined armchair with their legs
was obtained from all participants. Sixteen healthy, male sub- supported.
jects (20–28 years) were recruited. Subjects were recruited
from a register of volunteers participating in previous QST- 2.2.3. Assessment of thresholds
studies. The subjects were unaware of results from earlier Thermal stimuli were delivered by computer controlled contact
studies concerning spatial summation. The study was performed thermodes operating by the Peltier principle (Modular Sen-
in 2001 as a thermode calibration study for internal use at sory Analyzer, Somedic AB, Sweden). Baseline temperature was
our laboratory. After re-reading and re-examining the results adjusted to 32 ◦ C [7,12], and the ramp rate for both heating and
2014 we found the observations interesting for QST-interested cooling was set to ±1 ◦ C/s and the cut-off limits were 50 ◦ C and
researchers. 25 ◦ C, respectively. For warmth detection threshold (WDT) and cool
 V.M. Rasmussen et al. / Scandinavian Journal of Pain 9 (2015) 81–86 83

Table 1
Data from mixed model regression analysis with random-effect for subject and fixed-effects for the variables, site (arm/leg), thermode area (ln thermode area) and side
(dominant/non-dominant), for the outcomes warmth detection threshold (WDT), cool detection threshold (CDT) and heat pain threshold (HPT). WDT and CDT are numerical
values relative to baseline (32 ◦ C), while HPT are absolute values. No significant differences between sides were observed and these data were therefore excluded in the
model. Some examples of how the estimates are used: (1) if a thermode of 6.25 cm2 is used on the arm the estimated WDT (◦ C) = intercept + value for site + slope × ln
thermode area = 14.12 − 2.60 − 3.38 × ln 6.25 = 5.3 ◦ C; (2) if a thermode of 6.25 cm2 is used on the leg the estimated WDT (◦ C) = 14.12 − 0 − 3.38 × ln 6.25 = 7.9 ◦ C; (3) if a
thermode of 12.5 cm2 is used on the arm the estimated CDT (◦ C) = intercept + value for arm + slope × ln thermode area + thermode*site-interaction effect × ln thermode
area = 7.08 − 2.96 + (−1.90 + 0.80) × ln 12.5 = 1.3 ◦ C; (4) correspondingly, a CDT-estimate (12.5 cm2 thermode) for the leg = 7.08 + 0 + (−1.90 + 0) × ln 12.5 = 2.3 ◦ C.

Threshold Fixed-effect variables Estimate (◦ C) 95% CI (◦ C)

WDT Intercept 14.12 12.61 – 15.63

Site Arm −2.60 −3.37 – −1.82
Leg 0 –
Thermode (ln area) −3.38 −4.04 – −2.71

CDT Intercept 7.08 6.16 – 7.99

Site Arm −2.96 −4.02 – −1.89
Leg 0 –
Thermode (ln area) −1.90 −2.30 – −1.51
Thermode*Site Arm 0.80 0.24 – 1.36
Leg 0 –

HPT Intercept 50.70 49.48 – 51.92

Site Arm −0.63 −1.12 – −0.15
Leg 0 –
Thermode (ln area) −2.25 −2.67 – −1.83

detection threshold (CDT) the subject was instructed to press a but- 3.1. Mixed effect model
ton immediately when a change in temperature was perceived. For
heat-pain thresholds (HPT) the subject was instructed to press the In regard to WDT-data, no interactions attained significance in
button at the first sensation of pain or discomfort. Thermal thresh- the model, but the main-effects of site (F-test size = 43.8, P < 0.0001)
olds were determined as the median value of three consecutive and thermode area (F = 100.5, P < 0.0001) were significant. For CDT-
assessments randomly separated by an interval of 4–6 s. Median data a significant interaction between thermode area*site (F = 8.08,
values were chosen since assessments exceeding the cut-off limits P = 0.005) was observed and thus accordingly, the main-effects
for WDT and HPT, and CDT were assigned a value of 51 ◦ C, respec- of site (F = 30.0, P < 0.0001) and thermode area were significant
tively 24 ◦ C. (F = 112.9, P < 0.0001). In regard to HPT-data, analyses by the mixed
effect model and the Tobit regression model yielded nearly identi-
cal results indicating that the right censored data (5 of 14 subjects)
2.2.4. Statistics did not substantially affect the validity of the mixed effect model.
Statistical analyses were carried out using MedCalc (12.3.0.0, For the sake of consistency results of the HPT-analyses are therefore
Mariakerke, Belgium) and SAS 9.1.3 (SAS Institute Inc., Cary, NC, taken from the mixed effect model. No interactions attained signif-
USA) software. Data sets were initially assessed for normality by icance in the model, but main-effects of site (F = 6.6, P = 0.011) and
the Kolmogorov–Smirnov test and inspection of residual plots. thermode area (F = 113.6, P < 0.0001) were seen. The regression data
A mixed model with random effect for subject and fixed- from the mixed effect model are presented in Table 1, where four
effects for the variables, site (arm/leg), thermode area (ln thermode relevant examples of regression calculations also are presented.
area) and side (dominant/non-dominant), was used for each of
the outcomes: WDT, CDT and HPT. Non-significant (P > 0.05) fac-
tors, beginning with interactions, were excluded until all included 3.2. Pairwise comparisons
factors attained significance. HPT-data included cut-off values (all
values exceeding 50 ◦ C were given the value of 51 ◦ C) potentially Highly significant inverse relationships between stimulation
violating the assumption of a normal data distribution. Therefore a areas and thermal thresholds performed at the arms, were con-
Tobit regression model for right censored data [20],1 and including firmed for all thermode sizes (P < 0.001; Fig. 2A–C), except for CDT
a random effect for subject was tested and compared to the mixed (P = 0.04; medium vs. large thermode). Similar findings of spa-
effect model. tial summation were observed at the legs for all thermode sizes
Simple pairwise comparisons of all thresholds were by Wilcoxon (P < 0.001; Fig. 2A–C), in regard to WDT, CDT and HPT. The statis-
signed-rank test since HPT-data were non-parametrically dis- tical association was weaker for CDT (P = 0.002; small vs. medium
tributed. A double-sided significance value of 0.01 was chosen in thermode) and HPT (P < 0.009; medium vs. large thermode).
order to reduce the probability of inflicting a type I error due to The WDT and CDT were significantly lower for the arms com-
multiple comparisons. Data are presented as mean (95% confidence pared to the legs for all thermode sizes (P ≤ 0.0036; Fig. 2A and B).
interval [CI]) or median (non-parametric CI), as appropriate. No statistical differences in HPT were seen for the small (P = 0.10),
medium (P = 0.15) or large (P = 0.71) thermode.
In 17 of 18 comparisons regarding size of thermal heating area
3. Results (small, medium, large), thermal thresholds (WDT, CDT, HPT) and
stimulation sites (arm, leg) we observed a significant spatial sum-
Data from two individuals, #15 and #16, were excluded due to mation for QTT (Fig. 3).
a computer error.
3.3. Blinding procedure

1
Introduction to SAS. UCLA: Statistical Consulting Group. Available from Three of the 14 subjects were not able to indicate the correct
http://www.ats.ucla.edu/stat/sas/notes2/ (accessed 18.11.14). order of any of the thermodes, 7/14 identified the order of one of the
84 V.M. Rasmussen et al. / Scandinavian Journal of Pain 9 (2015) 81–86

Fig. 2. The panels illustrate (A) warmth detection threshold (WDT), (B) cool detection threshold (CDT) and (C) heat pain threshold (HPT) for the three thermodes
(small = 3.0 cm2 , medium = 6.3 cm2 , large = 12.5 cm2 ) for arms and legs. By convention WDT- and CDT-values represent temperatures relative to base-line (32 ◦ C), while
HPT-values represent absolute temperature values. Bar in box represents median value, box limits are 25th and 75th percentiles and whiskers are 2.5th and 97.5th per-
centiles. Outliers (circles) are located 1½ box height from the 2.5th percentile and extreme outliers (star) are located more than 2 box heights from the 2.5th percentile.
*P < 0.01, **P < 0.001, ***P < 0.0001.

thermodes correctly, while 4/14 were able to identify the correct with another study [12] a remarkably large difference in WDT,
sequence (chi-square P = 0.2). between the forearm and lower leg assessed by the small thermode,
was observed (Table 2). Interestingly a recent study observed a dif-
4. Discussion ference between body sides with a lower threshold for the left side
for HPT (Table 2) [1], a finding that is not corroborated in a very large
The present study showed significant spatial summation for study [15]. There is no obvious explanation, but since CDT-data are
thermal thresholds using calibrated, uniform contact thermodes comparable between the studies [1,15] and since the general vari-
with thermal active areas in the range of 3.0–12.5 cm2 . The medial ability in our measurements with the small thermode is of the same
lower leg and volar forearm were chosen for test-sites since these magnitude as that found in other studies (Table 2), it is not likely
are large enough for the thermodes to adjust properly to the skin that our findings represent a random error.
surface. These sites have been used in other studies of thermal In a large multicentre study (n = 180) by DFNS [15] presenting
thresholds, giving valid results [11,12]. In a study of determina- a standardized protocol, two different sizes of thermodes were
tion paradigm for thermal perception thresholds, the method of used to obtain reference values: 9.0 cm2 and 12.5 cm2 . The authors
limits by separate determinations, which is the method used in stated, that “The small difference in thermode size would at most
the present study, has been recommended since it is less time- lead to a 0.5 ◦ C difference in threshold” citing a previously published
consuming, and has a good reproducibility [13,21]. A baseline normative study [5]. From this cited study it appears that the dif-
of 32 ◦ C has previously been shown to give reproducible results ference in HPT between the thermal areas 9.0 cm2 and 12.5 cm2 , is
[12,22]. in the order of 0.9 ◦ C. However, no information on WDT and CDT is
Our threshold data are in general agreement with normative presented in the study.
data previously reported (Table 2). WDT and CDT were significantly The regression data presented in Table 1 indicate that dif-
lower for the volar forearm than for the lower leg, corroborating ferences in threshold-values, across the 9.0 cm2 and 12.5 cm2
data from several other studies [7,11,23,24]. Furthermore, there thermodes, assessed at the leg, for WDT, CDT, and HPT, are 1.1 ◦ C
were no differences in HPT between the two sites, which are in (0.9–1.3 ◦ C), 0.6 ◦ C (0.5–0.8 ◦ C) and 0.7 ◦ C (0.6–0.9 ◦ C), respectively.
agreement with a previous study [11]. However, in comparison The relative differences in WDT, CDT and HPT, comparing the
 V.M. Rasmussen et al. / Scandinavian Journal of Pain 9 (2015) 81–86 85

Table 2
Warmth detection threshold (WDT), cool detection threshold (CDT) and heat pain threshold (HPT) assessed with large and small stimulation area thermodes on different
locations on the arm and the leg. Data, reported as absolute values (◦ C), from Verdugo and Ochoa [22] (small: 3.8 cm2 , large: 12.5 cm2 . Mean [SD]), Hilz et al. [12] (small:
3.75 cm2 , large: 12.5 cm2 . Mean [SD]), Hagander et al. [11] (large: 13.34 cm2 , [2.5th–97.5th percentiles]) Neziri et al. [1] (large: 9 cm2 , mean [SD], male subjects, age 20–49)
and Verdugo et al. [21] (interpolated data: small: 3.0 cm2 , large: 12.5 cm2 ) compared with present study (small: 3.0 cm2 , large: 12.5 cm2 ).

WDT CDT HPT

Small Large Small Large Small Large

Verdugo et al. [21] Tarsal region – 36.4 – 29.5 – 43.9

(3.3) (1.9) (2.6)
Thenar – 33.5 – 30.6 – 44.6
(1.2) (0.4) (1.9)
Hilz et al. [12] Distal medial lower leg 36.5 34.9 27.7 29.1 – –
(2.3) (1.7) (2.2) (1.7)
Volar distal forearm 34.2 33.5 30.0 30.7 – –
(1.7) (0.7) (1.2) (0.6)
Hagander et al. [11] Dorsum foot – 34.3 – 31.4 – 43.7
(32.3–40.7) (28.2–31.8) (38.3–47.6)
Volar wrist – 32.6 – 31.5 – 42.9
(32.2–34.1) (30.6–31.8) (37.0–47.4)
Defrin et al. [5] Dorsum hand – – – – 46.5 43.6
Neziri et al. [1] Lateral malleolus, right side – – – – – 44.6
(3.0)
Lateral malleolus, left side – – – – – 43.4
(2.8)
Rasmussen et al. Medial lower leg 43.4 37.1 27.1 30.1 48.8 45.6
[Present study] (39.2–46.1) (36.1–38.6) (26.2–28.0) (29.5–30.5) (47.5–50.1) (44.4–46.8)
Volar forearm 38.7 35.2 29.2 30.8 47.7 45.2
(37.1–41.6) (34.3–36.1) (27.9–29.7) (30.1–31.1) (46.7–48.2) (43.5–45.9)

12.5 cm2 thermode with the 9 cm2 thermode, are 20%, 28% and thermodes were separated by 5 cm to 9 cm, while the former study
6%,2 respectively. These data indicate that considerable deviations used separation by 2.5 cm. It is likely that a sheet of only 0.3 mm
may occur if absolute values, across these thermode sizes, are used is not fully reliable as insulation of the heating surface, and there-
uncritically: a procedure that may lead to inaccurate clinical and fore the actual areas of testing could be inaccurate. Due to the very
scientific conclusions.
Data in the present study were evaluated for normality and
median values were reported. Data distributions in previous studies
were not reported and only mean values were given [12].
Furthermore, in the present study subjects were blinded to size
of stimulation area. QTT is a psychophysical assessment method
and it is reasonable to assume that awareness of the size of stim-
ulating area may affect accuracy of assessments. Blinding has not
routinely been used in studies of spatial summation. The number of
subjects estimating none, one or all of the thermodes correctly did
in the present study not differ from a random distribution. The like-
lihood of guessing none, one or all of the thermodes correctly is 1/3,
1/2 and 1/6, respectively. The numbers in the present study were
3/14, 7/14 and 4/14 (P = 0.2). This difficulty in assessing magnitude
of stimulation area by the test subjects has previously been recog-
nized [6]. This study was blinded using several circular thermodes,
the number of correctly reported activated thermodes occurred for
20–31% of the stimuli which was close to chance performance.
The importance of performing QTT with reliable, standardized
equipment is demonstrated in two studies arriving at conflicting
results with the use of different methods. One study regulated
stimulation areas by the number of thermodes and by changing
the heating aperture with application of 0.3 mm insulating plas-
tic material on the thermode [5]. The authors concluded that the
observed spatial summation of perceived heat pain intensity could
be attributed to a reduction in HPT. Thus spatial summation of pain
above heat pain threshold was eliminated. Another study [6] inves-
tigated the spatial summation of heat pain within and between
dermatomes. In contrast the conclusion was that summation does
exist also for supra-threshold heat stimuli. This study used five sep-
arate circular thermodes of the same size and spatial summation
was assessed by activating a variable number of thermodes. The Fig. 3. Thermal thresholds (◦ C) from the arm (mean values from both arms) as a
function of log thermode size (square cm) showing individual patient’s thermal
trajectories. Please, observe the dual y-axes: for heat pain thresholds (HPT) left y-
axis, for warmth detection thresholds (WDT) and cool detection thresholds (CDT)
the right y-axis. By convention HPT-values represent absolute temperature values,
2
In the calculation for HPT the threshold above 32 ◦ C is used (13 ◦ C). and, WDT- and CDT-values represent temperatures relative to base-line (32 ◦ C).
86 V.M. Rasmussen et al. / Scandinavian Journal of Pain 9 (2015) 81–86

different methods and equipment used in the two studies, the of nonautomated quantitative methods for examination of the patient with
results are largely incomparable. neuropathic pain. Clin J Pain 2009;25:632–40.
[4] Lautenbacher S, Nielsen J, Andersen T, Arendt-Nielsen L. Spatial summation of
heat pain in males and females. Somatosens Mot Res 2001;18:101–5.
5. Conclusions [5] Defrin R, Urca G. Spatial summation of heat pain: a reassessment. Pain
1996;66:23–9.
[6] Nielsen J, Arendt-Nielsen L. Spatial summation of heat induced pain within and
In conclusion, this standardized, randomized and single-blinded between dermatomes. Somatosens Mot Res 1997;14:119–25.
study of quantitative testing of thermal thresholds by standard- [7] Hilz MJ, Stemper B, Schweibold G, Neuner I, Grahmann F, Kolodny EH.
ized contact thermodes with stimulation areas of 3.0 cm2 , 6.3 cm2 Quantitative thermal perception testing in 225 children and juveniles. J Clin
Neurophysiol 1998;15:529–34.
and 12.5 cm2 confirmed spatial summation for warmth detection [8] Greenspan JD, Thomadaki M, McGillis SL. Spatial summation of perceived pres-
threshold, cool detection threshold and heat pain threshold. Thus, sure, sharpness and mechanically evoked cutaneous pain. Somatosens Mot Res
the area of the investigating thermode is an important variable in 1997;14:107–12.
[9] Quantitative sensory testing: a consensus report from the Peripheral Neurop-
the assessment of thermal thresholds, and standardization is highly
athy Association. Neurology 1993;43:1050–2.
recommended in order to facilitate interpretation of research data [10] Dyck PJ, O’Brien PC. Quantitative sensation testing in epidemiological and ther-
and normative data. apeutic studies of peripheral neuropathy. Muscle Nerve 1999;22:659–62.
[11] Hagander LG, Midani HA, Kuskowski MA, Parry GJ. Quantitative sensory testing:
effect of site and skin temperature on thermal thresholds. Clin Neurophysiol
6. Implications 2000;111:17–22.
[12] Hilz MJ, Stemper B, Axelrod FB, Kolodny EH, Neundorfer B. Quantitative thermal
perception testing in adults. J Clin Neurophysiol 1999;16:462–71.
Data from the present study are valuable in calibration pro-
[13] Hilz MJ, Glorius S, Beric A. Thermal perception thresholds: influence of
cedures, allowing estimation of thermal thresholds with differing determination paradigm and reference temperature. J Neurol Sci 1995;129:
thermode sizes, enabling important comparisons across studies to 135–40.
be made. The data also indicate that significant deviations, lead- [14] Riley III JL, Robinson ME, Wise EA, Myers CD, Fillingim RB. Sex differences
in the perception of noxious experimental stimuli: a meta-analysis. Pain
ing to erroneous clinical and scientific conclusions, may occur, if 1998;74:181–7.
absolute values, across these thermode sizes, are used uncritically. [15] Rolke R, Baron R, Maier C, Tolle TR, Treede RD, Beyer A, Binder A, Birklein
F, Bötefür IC, Braune S, Flor H, Huge V, Klug R, Landwehrmeyer GB, Mageri
W, Malhöfner C, Rolko C, Schaub C, Scherens A, Sprenger T, Valet M,
Conflicts of interest Wasserka B. Quantitative sensory testing in the German Research Network
on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain
M. U. Werner has received unrestricted research grants (admin- 2006;123:231–43.
[16] Rolke R, Magerl W, Campbell KA, Schalber C, Caspari S, Birklein F, Treede RD.
istered by the University Hospital administration) from Grünenthal Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur J
GmbH, Germany and Astellas Pharma A/S, Denmark. Pain 2006;10:77–88.
For the remaining authors, none were declared. [17] Pfau DB, Geber C, Birklein F, Treede RD. Quantitative sensory testing of neuro-
pathic pain patients: potential mechanistic and therapeutic implications. Curr
Pain Headache Rep 2012;16:199–206.
Acknowledgements [18] Werner MU, Perkins FM, Holte K, Pedersen JL, Kehlet H. Effects of gabapentin
in acute inflammatory pain in humans. Reg Anesth Pain Med 2001;26:
322–8.
The authors would like to thank Somedic AB, Box 194, SE 242 22 [19] Pedersen JL, Kehlet H. Hyperalgesia in a human model of acute inflammatory
Hörby, SWEDEN for providing the thermodes. pain: a methodological study. Pain 1998;74:139–51.
[20] Tobin J. Estimation of relationships for limited dependent variables. Economet-
rica 1958;26:24–36.
References [21] Greenspan JD. Quantitative assessment of neuropathic pain. Curr Pain
Headache Rep 2001;5:107–13.
[1] Neziri AY, Scaramozzino P, Andersen OK, Dickenson AH, Arendt-Nielsen L, Cura- [22] Verdugo R, Ochoa JL. Quantitative somatosensory thermotest. A key
tolo M. Reference values of mechanical and thermal pain tests in a pain-free method for functional evaluation of small calibre afferent channels. Brain
population. Eur J Pain 2011;15:376–83. 1992;115:893–913.
[2] Backonja MM, Walk D, Edwards RR, Sehgal N, Moeller-Bertram T, Wasan A, [23] Dyck PJ, Zimmerman I, Gillen DA, Johnson D, Karnes JL, O’Brien PC. Cool, warm,
Irving G, Argoff C, Wallace M. Quantitative sensory testing in measurement and heat-pain detection thresholds: testing methods and inferences about
of neuropathic pain phenomena and other sensory abnormalities. Clin J Pain anatomic distribution of receptors. Neurology 1993;43:1500–8.
2009;25:641–7. [24] Pedersen JL, Kehlet H. Secondary hyperalgesia to heat stimuli after burn injury
[3] Walk D, Sehgal N, Moeller-Bertram T, Edwards RR, Wasan A, Wallace M, Irving in man. Pain 1998;76:377–84.
G, Argoff C, Backonja MM. Quantitative sensory testing and mapping: a review