hyperalgesia =
ORIGINAL ARTICLE neuropathic pain
Pain-associated Mild Sensory Deficits Without Hyperalgesia
in Chronic Non-neuropathic Pain
Andrea Westermann, MD,* Anne-Kathrin Rönnau,* Elena Krumova, MD,*
Sabrina Regeniter, MD,* Peter Schwenkreis, MD,w Roman Rolke, MD,zy
Rolf-Detlef Treede, MD,J Helmut Richter,* and Christoph Maier, MD*
Objectives: A mixture of sensory loss and gain is a hallmark of
neuropathic pain. But hypesthesia and hyperalgesia also occur with
experimentally induced acute pain. Here, we assessed sensory
profiles in chronic non-neuropathic pain (osteoarthritis, OA) using
the quantitative sensory testing (QST) protocol of the German
Research Network on Neuropathic Pain (DFNS).
Methods: Twenty individuals with OA [mean pain intensity on the
numerical rating scale (NRS, 0-10): 5.6±1.5] were tested on the
painful and contralateral hand and compared with 20 healthy
volunteers matched for age, sex, and handedness.
Results: In the OA group, analysis of variance revealed increased
detection thresholds to tactile stimuli bilaterally and to thermal
stimuli restricted to the more painful hand (all P<0.05). Pin-prick
hypoalgesia was present restricted to the patients’ more affected
hand. Neither hyperalgesia nor allodynia was found. QST parameters
were correlated with average pain intensity (r between 0.48 and 0.51).
Conclusions: These results suggest that chronic non-neuropathic
pain may induce slight sensory impairment for large fiber function
(bilateral) and small fiber function (ipsilateral). However, all
changes are within the normal range, in contrast to patients with
neuropathy. Inhibition of central pathways by nociceptive input
and altered sensory processing due to disuse of the hand are
possible mechanisms. These functional sensory alterations do not
interfere with the diagnosis of neuropathy.
Key Words: osteoarthritis, quantitative sensory testing, sensory
profile, nociceptive pain, neuropathic pain
(Clin J Pain 2011;27:782–789)
Received for publication June 24, 2010; revised November 22, 2010;
accepted April 01, 2011.
From the *Department of Pain Management; wDepartment of
Neurology, Berufsgenossenschaftliches Universitätsklinikum Berg-
mannsheil GmbH, Bochum; zDepartment of Palliative Care,
University of Bonn; yDepartment of Neurology, University
Medical Center, Johannes Gutenberg-University, Mainz, Germany;
and JCenter for Biomedicine and Medical Technology Mannheim,
University of Heidelberg, Mannheim, Germany.
Supported by the German Ministry of Education and Research
(BMBF, grants 01EM0107 & 01EM0502 for the German Research
Network on Neuropathic Pain [DFNS]). The authors declare no
conflict of interest. Andrea Westermann and Anne-Kathrin
Rönnau have contributed equally to this study. This study is part
of the doctoral thesis of Anne-Kathrin Rönnau.
Reprints: Andrea Westermann, MD, Department of Pain Manage-
ment, BG Universitätsklinikum Bergmannsheil, Bürkle-de-la-
Camp-Platz 1, 44789 Bochum, Germany (e-mail: andrea.westermann
@ruhr-uni-bochum.de).
Copyright r 2011 by Lippincott Williams & Wilkins
782 | www.clinicalpain.com Clin J Pain
T actile hypesthesia has been described in chronic
neuropathic and non-neuropathic pain.1–3 In accor-
dance with that, we recently reported a bilateral increase of
thermal detection thresholds in patients with migraine,
tension-type headache, and local low back pain.4 However,
the limitation of this study was that only thermal thresholds
were assessed and the examination was carried out in a
nonpainful area. The reduction of tactile function as a
neurophysiological consequence of the activation of noci-
ceptive pathways, independent of the applied stimuli, was
shown for experimentally induced pain.5–8 Results of
experiments using animal models of osteoarthritis (OA)
have suggested that OA may lead to central sensitization.9
Therefore, to prove the concept of pain-induced tactile
hypesthesia, we analyzed this phenomenon in patients with
chronic localized, mostly unilateral, non-neuropathic pain.
A comprehensive standardized quantitative sensory testing
(QST) procedure including thermal and mechanical stimuli
was performed in accordance with the protocol of the
Germany Network on Neuropathic Pain (DFNS) in the
painful area of patients with OA.10
The aim of this study was to (1) investigate the
influence of OA pain on the sensory profile, particularly to
evaluate the occurrence of any loss of detection in
comparison with the contralateral area and with the control
group of healthy participants; (2) examine the frequency of
abnormal values in terms of hypesthesia and hyperalgesia
in comparison with the recently published results in patients
with neuropathy10,11; and (3) analyze whether these effects
are possibly associated with the average pain intensity or
functional hand impairment.
MATERIALS AND METHODS
Patients
This study was conducted in accordance with the
Declaration of Helsinki and according to the guidelines for
good clinical practice. After approval by the regional ethics
committee of the Ruhr-University Bochum (register num-
ber 1797) and after obtaining written informed consent, 20
individuals with (10 male) with painful (pain intensity Z3
on the 11-point numerical rating scale (NRS): 0=“no pain”
up to 10=“worst imaginable pain”) predominantly uni-
lateral (n=14) OA in the hand for more than 3 months and
without any changes in treatment for at least 1 month
before the investigation were enrolled. Participants with
bilateral OA had to present a pain-free or less painful hand
(pain intensity r2 on the 11-point NRS) with a distinctive
difference in pain intensity of at least 3 points on the 11-
point NRS in comparison with the more painful hand. The
 Volume 27, Number 9, November/December 2011
Clin J Pain  Volume 27, Number 9, November/December 2011
unaffected or less affected hand was used for intraindividual
comparison.
Participants with OA were recruited as follows: After
an initial telephone interview of 142 individuals with
presumed OA (patients of the Department of Plastic Surgery
and the Department for Pain Management at the University
Hospital Bergmannsheil Bochum), 25 agreed to participate
and fulfilled the study criteria. Those with severe internal
diseases (eg, diabetes mellitus, malignant tumor, peripheral
vessel disease), chronic and current low back pain,
pregnancy, amputations, peripheral or systemic neurological
disorders, or clinical signs of nerve dysfunction [decreased
vibration detection thresholds (VDT) over the malleolus
internus, alleviated or missing Achilles tendon reflexes] were
excluded (n=5). The diagnosis of OA was confirmed by
radiologic or histopathologic findings. Pain characteristics,
clinical findings, and QST profiles were recorded. Five
participants with OA took medication regularly (weak
opioids: n=2; nonsteroidal anti-inflammatory drugs: n=3),
whereas the remaining 15 took no pain medication. The
evaluation took approximately 3 hours and was performed
on 1 day by 1 examiner (A-K. R.). Twenty healthy volunteers
without any history of trauma or neurological or vascular
diseases were recruited from among students, members of the
hospital staff, or from among their friends and relatives. They
were matched to the participants with OA in sex, age, and
handedness and served as a control group.
Questionnaires
The personal and clinical data of the participants with
OA were assessed using a basic questionnaire, including the
assessment of average and maximum pain intensities during
the last 4 weeks before investigation and the current pain
intensity using the 11-point NRS. Furthermore, the
following questionnaires were also used:
 The German version 2.0 of the Disability of Arm,
Shoulder and Hand (DASH)12 assessed the function-
ality of the hands with regard to daily life (score 1, 30
items), leisure time (score 2, 4 items), and work (score 3, 4
items). A high score represented a major disability.
Complementary to the NRS, the DASH also includes a
6-point self-rated Likert scale for the assessment of
average pain intensity in the last week. According to the
median value of this parameter (4 points) all participants
with OA were classified into groups with moderate (<4
points) or severe (Z4 points) pain for a subsequent analysis.
 The German version of the Brief Symptom Inventory
documented the mean psychological burden (Global
Severity Index) during the last 7 days.13
 A 5-question-survey by Frettlöh et al14 based on Galer
and Jensen15 was used to assess neglect-like symptoms.
QST
The standardized QST protocol of the DFNS10 was
carried out bilaterally (hand palmar middle) and included
13 tests, which can be grouped as follows:
thermal detection thresholds for perception of cold
(cold detection threshold, CDT), warmth (warm detec-
tion threshold), and the number of paradoxical heat
sensations (PHS) during the procedure of alternat-
ing warm and cold stimuli (thermal sensory limen, TSL);
thermal pain thresholds for cold (cold pain threshold)
and heat (heat pain threshold, HPT) stimuli;
mechanical detection thresholds to light tactile stimuli
r 2011 Lippincott Williams & Wilkins
Pain-associated Mild Sensory Deficits
(mechanical detection threshold, MDT) and to vibration
(VDT);
mechanical pain testing including thresholds for pin-
pricks (mechanical pain threshold), pressure pain (pres-
sure pain threshold), the stimulus/response function for
pinprick sensitivity (mechanical pain sensitivity, MPS)
and dynamic mechanical allodynia, and the temporal
pain summation to repetitive pinprick stimuli also
known as wind-up ratio.
Participants were seated comfortably in a quiet room
with a constant temperature of approximately 221C. After
demonstration of each QST parameter (except for wind-up
ratio, VDT, and pressure pain threshold) on the skin beyond
the testing areas, QST was performed first on the contra-
lateral hand, (in healthy volunteers first on the right hand).
Statistical Analysis
In accordance with the distribution of normal values
assessed by the DFNS protocol,10 all QST values, except for
PHS, cold pain threshold, HPT, and VDT, were log
transformed to achieve a secondary normal distribution.
The calculation of the means of all raw data, the com-
parison with the reference data, and the evaluation of
abnormal values were performed in a fully automated manner
after QST completion using a custom-built tool. QST values
of the patients were compared with the values of the control
group of healthy participants by z-transformation:
Z  score ¼
ðMeansingle patient  Meanhealthy controls Þ=SDhealthy controls
A z-value above “0” indicates a gain (ie, the
participants with OA have lower thresholds and are more
sensitive compared with the mean of the control group of
healthy participants) and below “0” a loss (ie, the
participants with OA have higher thresholds and are less
sensitive compared with the mean of the control group of
healthy participants) of sensory function.
In addition, all absolute QST values of the participants
with OA were compared with the 95% confidence interval
of the revised normative database of the DFNS16 to assess
any abnormalities, such as hypoesthesia, hyperalgesia, or
hypoalgesia. If the values in both tested areas were within
the normal range, the side-to-side differences were analyzed
additionally using the published reference data for side-
to-side comparison.10 Owing to a wide range of normal
standard deviation values, small alterations within the
normal range might be detected only by determination of
side differences or by using a matched control group.
For group comparison a repeated analysis of variance
(ANOVA) was performed using the between-factor “group”
(healthy controls vs. participants with OA) and the within-
factor “side” (ipsilateral vs. contralateral hand). Further-
more, significant differences between the participants with
OA’s more affected hand and the healthy controls’ left hand
and between the participants with OA less affected hand and
the healthy controls’ right hand were attributed performing a
1-factorial ANOVA. Levene’s test was conducted to assess
the equality of variance between the different samples. Either
the Sidak post hoc test (in case of equal variance) or the
Dunnett test (in case of unequal variance) was used to
analyze the differences between groups.
Pearson correlations were performed between the
average pain intensity and hand impairment (both based
on DASH), between the average pain intensity based on
www.clinicalpain.com | 783
Westermann et al Clin J Pain  Volume 27, Number 9, November/December 2011

TABLE 1. Clinical Data of Osteoarthritis Patients and Healthy Volunteers

Osteoarthritis Participants (n=20) Healthy Volunteers (n=20)
Male 10 10
Age (y) 55.5±11.4, 41...76 56.1±9.4, 41...79
Right handed 17 17
Former or current employment
Office work 7 11
Labor work 12 8
Retired 7 2
Painful joint (n)
Pollex joint 12
Wrist 5
Herberden 1
Art. carpometa-carpale V 1
Art. carpometa-carpale II 1
Physical burden (n)
High 4
Medium 9
Low 7
Current pain medication
Nonopiods 3
Weak opioids 2
Duration of pain (mo)
Mean±SD, range 33±43, 3...156
Median 12
Current pain (NRS)*
Mean±SD, range 5.1±2.09, 1...10
Maximum pain last month (NRS)
Mean±SD, range 7.55±1.67, 4...10
Average pain last month (NRS)***
Mean±SD, range 5.55±1.5, 3...8
DASH module I (disability score)*
Mean±SD, range 39.4±15.44, 7.5...64.2
DASH module II (sport/music)*
Mean±SD, range 55.63±34.4, 0...100
DASH module III (work)**
Mean±SD, range
GSI (BSI) 57.5±27.02, 0...100
Mean±SD, range 44.55±11.29, 29...74
Noticeable (Z 63; n) 2
QUECH (neglect like symptoms)
Mean±SD, range 0.16±0.4, 0...1.4
Noticeable (>3; n) 0
Data are number per group (n), respectively means±SD.
*Significant difference between participants with OA with moderate and severe pain (*P<0.05, **P<0.01, ***P<0.001).
BSI indicates Brief Symptom Inventory; DASH, Disability of Arm, Shoulder and Hand; GSI, Global Severity Index; NRS,
numerical rating scale; QUEC, Questionaire CRPS-Hand.

DASH and the average pain intensity rated on the 11-point
NRS during the last 4 weeks, between QST parameters and
hand impairment, and between QST parameters and the
average pain intensity (in the last 4 weeks).
All data were analyzed using the Statistical Product
and Service Solutions (SPSS 11) and presented as mean±
SD. A P value <0.05 was regarded as significant. An r
coefficient between 0.7 and 0.5 was regarded as a moderate
correlation; r >0.7 was regarded as high correlation.
RESULTS
Participants With OA
All participatns with OA reported pain with an intensity
of 5.1±2.1 (mean±SD, NRS 0 to 10) on their affected hand.
Six women had a history of bilateral OA; however, only 1
side was relevantly affected by pain. Most (n=11) had
painful OA at least year (Table 1). Men (mean±SD:
52.5±10.2 y, range: 41 to 72) were slightly, but not
significantly, younger than women (mean±SD: 60.6±8.9 y,
range: 47 to 76) and also did not differ significantly in any of
the other evaluated clinical parameters. No patient had
clinical signs of joint inflammation.
Participants With OA Questionnaires
All participants with OA showed hand functionality
impairment, although covering a wide range (Table 1).
Leisure time and work impairment varied immensely
because of personal lifestyle. Those with severe pain
presented a significantly greater impairment of hand
functionality during daily life, leisure time, and work than
did those with only moderate pain (Table 1). Congruently,
correlations between patients’ average pain intensity and
DASH scores were medium to high (score 1 r=0.6,
P=0.008; score 2 r=0.6, P=0.013; score 3 r=0.7,
P=0.001). The correlation between the OA group’s
average pain ratings on the 6-point Likert scale included
in the DASH questionnaire and on the 11-point NRS was

784 | www.clinicalpain.com r 2011 Lippincott Williams & Wilkins

Clin J Pain  Volume 27, Number 9, November/December 2011 Pain-associated Mild Sensory Deficits

FIGURE 1. Sensory profiles (z score) of patients’ more affected (filled symbols) and contralateral (open symbols) hands compared with
the group of healthy volunteers (z score=0). Patients showed a significantly decreased sensory detection threshold for cold (CDT),
alternating temperatures (TSL), and mechanical pain stimuli (MPS) in their more affected hands, when comparing them with patients’
contralateral hands and volunteers’ hands. In addition, participants wtih OA showed a significantly lower sensory detection threshold for
mechanical stimuli (MDT) bilaterally compared with volunteers. Paradoxical heat sensations (PHS) or dynamic mechanical allodynia
(DMA) did not occur. #Significant difference between patients and healthy subjects (#P < 0.05, ##P < 0.01). *Significant difference
between patients’ more affected hands and their contralateral hands (*P < 0.05, **P < 0.01).

FIGURE 2. A to D, Detailed presentation of quantitative sensory testing (QST) parameters with significant differences within all repeated
measurements. The sensory function in patients is impaired ipsilaterally for the detection of cold [cold detection threshold (CDT), mean
± SEM; A], alternating temperatures [thermal sensory limen (TSL), mean ± SEM; B], and painful mechanical stimuli [mechanical pain
sensitivity (MPS), mean ± SEM; D], and bilaterally for non-painful tactile stimuli [mechanical detection threshold (MDT), mean ± SEM;
C]. The more affected hands are represented by filled symbols and the contralateral hands by open symbols (*P < 0.05, **P < 0.01).

r 2011 Lippincott Williams & Wilkins www.clinicalpain.com | 785

Westermann et al Clin J Pain  Volume 27, Number 9, November/December 2011

significant (r=0.6, P=0.008). Both subgroups (patients

TABLE 2. ANOVA of All Participants Using Repeated
Measurement With Diagnose as Between Factor and Laterality with severe and with moderate pain intensity) resembled
of Hands as 2-level Within Factor each other in their pain sites and each of them included 3
participants with bilateral OA.
Laterality Diagnose Interaction Neglect-like symptoms were not detected at all. The
QST Parameters F P F P F P mean psychological burden was well within the normal
CDT (C1) 3.3* NS 1.5 NS 11.6 <0.01
range (44.6±11.3; Global Severity Index). Two partici-
WDT (C1) 1.5 NS 0.0 NS 2.4 NS pants with OA presented a considerable psychological
TSL (C1) 1.2 NS 1.6 NS 6.2 <0.05 disorder, which consisted mainly of a fearful and depressive
PHS w w w w w w component during the last 7 days before investigation.
CPT (C1) 1.2 NS 0.1 NS 0.0 NS
HPT (C1) 0.3 NS 0.0 NS 4.8 <0.05 QST
PPT (kPa) 0.5 NS 0.3 NS 0.0 NS ANOVA revealed a significantly higher CDT and TSL
MPT (mN) 0.8 NS 1.3 NS 1.2 NS and a significantly lower MPS and HPT on the more
MPS (rating 0-100) 5.3 <0.05 1.4 NS 12.7 <0.01 painful hand in participants with OA (Figs. 1, 2), based on
DMA w w w w w w interactions between groups and side-to-side comparisons
WUR (ratio) 0.4 NS 0.3 NS 0.3 NS
(Table 2). In addition, ANOVA revealed a group difference
MDT (mN) 0.5 NS 7.8 <0.01 0.7 NS
VDT (x/8) 0.6 NS 0.0 NS 1.9 NS for the MDT (Table 2), which was significantly higher in
the OA group bilaterally (Fig. 2), although it was more
*This is the highest nonsignificant F value, corresponding to P=0.08. pronounced on the clinically more affected hand. None of
wPHS and DMA did not occur. the participants with OA presented any dynamic mech-
ANOVA indicates analysis of variance; CDT, cold detection threshold;
CPT, cold pain threshold; DMA, dynamic mechanical allodynia; HPT, heat anical allodynia or any PHS (Table 3).
pain threshold; MDT, mechanical detection threshold; MPS, mechanical Compared with the DFNS reference database, the
pain sensitivity; MPT, mechanical pain threshold; PHS, paradoxical heat frequency of abnormal values outside the 95% confidence
sensation; PPT, pressure pain threshold; QST, quantitative sensory testing; interval was 1.5% of all QST values on the affected side of
TSL, thermal sensory limen; VDT, vibration detection threshold; WDT,
warm detection threshold; WUR, wind-up ratio. both OA participants and healthy controls. This indicates
that individual abnormal values did not occur more

TABLE 3. Data of QST

Log-transformed Data*
Affected Hand Contralateral Hand
QST Parameters Participants With OA Healthy Controls P Participants With OA Healthy Controls P
CDT (C1) 0.249±0.179 0.114±0.155 <0.05 0.137±0.155 0.148±0.198 NS
WDT (C1) 0.299±0.142 0.246±0.204 NS 0.211±0.196 0.256±0.190 NS
TSL (C1) 0.513±0.177 0.335±0.284 <0.05 0.377±0.252 0.389±0.241 NS
PHS w w w w w w
CPT (C1)
HPT (C1)
PPT (kPa) 2.724±0.171 2.703±0.094 NS 2.732±0.158 2.709±0.082 NS
MPT (mN) 2.027±0.333 1.872±0.373 NS 1.954±0.344 1.881±0.282 NS
MPS (rating 0-100) 0.255±0.280 0.055±0.263 <0.05  0.089±0.288 0.090±0.283 NS
DMA w w w w w w
WUR (ratio) 0.301±0.190 0.249±0.240 NS 0.268±0.241 0.248±0.264 NS
MDT (mN) 0.161±0.501 0.535±0.307 <0.01  0.211±0.449 0.529±0.328 <0.05
VDT ( /8)
Data in Original Units*z
CDT (C1)  1.77 1.30 <0.05  1.37  1.41 NS
WDT (C1) 1.99 1.76 NS 1.63 1.80 NS
TSL (C1) 3.26 2.16 <0.05 2.38 2.45 NS
PHS w w w w w w
CPT (C1) 10.0±6.6 9.3±7.3 NS 10.9±5.6 10.1±7.8 NS
HPT (C1) 45.9±4.0 45.0±3.6 NS 45.3±3.9 45.9±3.4 NS
PPT (kPa) 530 504 NS 540 512 NS
MPT (mN) 106 75 NS 90 76 NS
MPS (rating 0-100) 0.56 0.88 <0.05 0.81 0.81 NS
DMA w w w w w w
WUR (ratio) 2.00 1.77 NS 1.85 1.77 NS
MDT (mN) 0.69 0.29 <0.01 0.62 0.30 <0.05
VDT ( /8) 7.7±0.4 7.8±0.3 NS 7.8±0.3 7.8±0.3 NS
*For CDT and WDT, differences from baseline-temperature (321C) are shown.
wPHS and DMA did not occur.
zRetransformed mean for log-normally distributed data. In the case of CPT, HPT, and VDT, mean of original data are shown.
CDT indicates cold detection threshold; CPT, cold pain threshold; DMA, dynamic mechanical allodynia; HPT, heat pain threshold; MDT, mechanical
detection threshold; MPS, mechanical pain sensitivity; MPT, mechanical pain threshold; PHS, paradoxical heat sensation; PPT, pressure pain threshold; QST,
quantitative sensory testing; TSL, thermal sensory limen; VDT, vibration detection threshold; WDT, warm detection threshold; WUR, wind-up ratio.

786 | www.clinicalpain.com r 2011 Lippincott Williams & Wilkins

Clin J Pain  Volume 27, Number 9, November/December 2011 Pain-associated Mild Sensory Deficits

TABLE 4. Partial Correlation of QST Parameters for Testing the Influence of the Factors Pain Intensity and Hand Impairment
Affected Hand Contralateral Hand
Hand Impairment Pain Intensity Hand Impairment Pain Intensity
QST Parameters r sig. r sig. r sig. r sig.
CDT log  0.365 NS 0.511 <0.05 0.031 NS 0.183 NS
WDT log  0.102 NS 0.478 <0.05 0.006 NS  0.007 NS
TSL log 0.112 NS 0.507 <0.05 0.069 NS  0.068 NS
CPT  0.264 NS 0.328 NS 0.012 NS 0.233 NS
HPT 0.188 NS  0.484 <0.05 0.181 NS  0.427 NS
PPT log  0.273 NS  0.143 NS 0.179 NS  0.304 NS
MPT log  0.005 NS  0.104 NS 0.086 NS  0.144 NS
MPS log 0.267 NS  0.221 NS 0.173 NS  0.099 NS
WUR log  0.254 NS 0.301 NS 0.055 NS 0.001 NS
MDT log 0.162 NS  0.014 NS 0.323 NS  0.138 NS
VDT 0.441 NS  0.246 NS 0.48 <0.05  0.45* NS
DMA — — — — — — — —
PHS — — — — — — — —
*This is the highest nonsignificant F value, corresponding to P=0.054.
CDT indicates cold detection threshold; CPT, cold pain threshold; DMA, dynamic mechanical allodynia; HPT, heat pain threshold; log, log-transformed
parameters; MDT, mechanical detection threshold; MPS, mechanical pain sensitivity; MPT, mechanical pain threshold; NS, not significant (P<0.05); PHS,
paradoxical heat sensation; PPT, pressure pain threshold; QST, quantitative sensory testing; TSL, thermal sensory limen; VDT, vibration detection threshold;
WDT, warm detection threshold; WUR, wind-up ratio.

frequently than by chance in any of the groups and
therefore data could be rated as being within the normal
range (Table 3).
Correlations and Subgroup Analysis
The thermal detection thresholds correlated significantly
with the average pain intensity (CDT: r=0.51, P=0.03; warm
detection threshold: r=0.48, P=0.04; TSL: r=0.51, P=0.03),
indicating that the higher was the pain intensity the higher was
the thermal detection thresholds over the more affected hand
(Table 4). HPT also correlated significantly with pain intensity,
although in an inverse manner (r, 0.48, P=0.04); that is, the
higher was the pain intensity the lower was the HPT. No sex
differences and no significant relationship between QST
parameters and hand impairment were found.
DISCUSSION
The aim of this study was to investigate the influence of
non-neuropathic pain, for example, OA-associated pain, on
the sensory profiles. In summary, all values were not outside
the normal range; however, in the intraindividual comparison,
participants with OA showed significantly higher perception
thresholds for thermal stimuli (CDT; TSL) in the affected
hand, which significantly correlated with the average pain
intensity. In addition, the MDTs were bilaterally higher in
comparison with the healthy controls. Another important
finding of this study was that chronic non-neuropathic pain
did not induce any signs of hyperalgesia; rather, an
ipsilateral hypoalgesia for MPS was found.
Sensory Function
The above-mentioned side difference of CDT in
combination with increased TSL might have been induced
by chronic non-neuropathic pain, especially because the
pain intensity correlated with increasing thermal detection
thresholds. MDT increased bilaterally, being a sign of loss
of Ab-function as previously described, for example, for
low back pain, OA, and myofascial pain.2,7,8,17,18
Such an impaired detection due to increasing pain
has already been discussed by Magerl et al6 after painful
capsaicin injections. They proposed that activation of
cutaneous nociceptive C-fibers most likely depo-
larized presynaptic inhibitory primarily afferent myelinated
A-fibers, which consecutively led to a selective spinal
inhibition of mechanoreceptive nerve fibers, thus inducing
secondary hypoesthesia. Geber et al,8 who could also
demonstrated secondary hypoesthesia during and after
experimentally induced pain, also discussed their findings
on the above-mentioned theory of secondary hypoesthesia
at the spinal cord level, although they also proposed
cortical changes in central plasticity. Both mechanisms may
also have a role in our findings, whereas for the bilateral
changes supraspinal mechanisms may be more relevant.19
Another traceable hypothesis to explain the associa-
tion of pain and hypoesthesia would be a disruption and
interference of the self-perception of the body, termed
“neuromatrix”20 or “body schema”,21 showing that not
only painful but also perceptive inputs are selected by the
first sensory gate.22 Therefore, they are processed slowly23
and weakly so that greater sensory stimuli are needed,24
indicating that ongoing pain might suppress sensitivity to
nonpainful stimuli, possibly because of a centrally mediated
impairment.4,5 These modulations of central processes
activating endogenous inhibitory mechanisms are also
discussed by Leffler et al7,17 and Kosek and Ordeberg.18
An additional assumption is that the documented
hypesthesia could also be partly explained by disuse,25
considering the fact that the factors “pain intensity”
and “hand functionality” were—as expected12,26—highly
bonded to each other (the greater was the pain the greater
was the daily life impairment) and no further influencing
factors were found. Possible distracting psychological dis-
orders did not interfere in this study, because no significant
ones were found. The documented disturbances of soma-
tosensory performance may be also partly explained by a
simple lack of tactile exercise due to disuse.
Hyperalgesia
Participants with severe pain showed lower values for
HPTs compared with the other participants with OA. The

r 2011 Lippincott Williams & Wilkins www.clinicalpain.com | 787

Westermann et al
origin of joint pain and the relation of joint degene-
ration and chronic pain still are relatively unknown. It is
known from experimental or clinical studies that, among
mechanical factors, cartilage degeneration products and
inflammatory mediators also cause activation of nocicep-
tors,9,27,28 and therefore peripheral sensitization of joint
afferents might also be 1 possible pain mechanism,28 which
could explain our findings of heat hyperalgesia in a
subgroup of participants with OA. However, no histo-
pathologic findings were available to further prove this
hypothesis. Furthermore, the joint inflammation cannot
explain the whole complex of joint pain and a few
investigators have discussed central activations.29
Finally, the present results imply that validity of QST
in the detection of neuropathy is unimpaired by non-
neuropathic pain, because compared with a normative data
base10 individual sensory profiles revealed, as expected, no
abnormal values in OA patients. Similar findings regard-
ing sensory function have been found for different chronic
nociceptive diseases such as headache or OA,4,7,8,17,18
although study designs differ greatly and comparison is
difficult. In contrast, radicular compression syndromes,
peripheral nerve lesion, or small fiber neuropathy was
associated with both abnormal positive and negative signs
assessed by QST.2,30,31
In contrast to our results, Gwilym et al29 found lower
detection thresholds (MDT) and a higher sensitivity for
punctuate stimulation with a 256 mN von-Frey filament in
the referred pain area in patients with hip OA. However,
they investigated a subgroup of patients with a neuropathic
pain component based on QST, a history of referred pain,
and typical neuropathic-like symptoms. To rule out any
interactions of neuropathic pain components, only patients
without abnormal clinical and neurological findings (ie,
without any decreased VDT, alleviated or missing mono-
synaptic stretch reflexes) were enrolled in this study.
Therefore, the differing results are understandable.
CONCLUSIONS
To summarize, chronic non-neuropathic pain induces
only a slight sensory impairment in contrast to neuropathic
pain. Thus, chronic nociceptive input without neuropathy
induces neither pathologic nerve fiber function nor hyper-
algesia. Hyperalgesia seems to be a sign that occurs pre-
dominantly in neuropathic pain. The detection threshold
shift should be considered in the assessment of borderline
values in case of patients with suspected neuropathy.
Though, the differentiation between nociceptive and
neuropathic pain and the validity of QST for individual
detection of neuropathy are unimpaired. Our study presents
bilateral results, which may be caused by central changes.
To prove the mechanism of secondary hypoesthesia, further
experimental studies are necessary.
ACKNOWLEDGMENTS
The authors are indebted to all participants for their
consent and cooperation.
REFERENCES
1. Pleger B, Tegenthoff M, Ragert P, et al. Sensorimotor
returning in complex regional pain syndrome parallels pain
reduction. Ann Neurol. 2005;57:425–429.
2. Freynhagen R, Rolke R, Baron R, et al. Pseudoradicular and
radicular low-back pain: a disease continuum rather than
788 | www.clinicalpain.com
Clin J Pain  Volume 27, Number 9, November/December 2011
different entities? Answers from quantitative sensory testing.
Pain. 2008;135:65–74.
3. Mailis Gagnon A, Nicholson K. Nondermatomal somatosen-
sory deficits (NDSDs): a neuropsychobiological phenomenon?
Pain. 2009;145:12–13.
4. Agostinho CM, Scherens A, Richter H, et al. Habituation and
short-term repeatability of thermal testing in healthy human
subjects and patients with chronic non-neuropathic pain. Eur J
Pain. 2009;13:779–785.
5. Apkarian AV, Stea RA, Bolanowski SJ. Heat-induced pain
diminishes vibrotactile Perception-A touch gate. Somatosens
Mot Res. 1994;11:259–267.
6. Magerl W, Wilk SH, Treede RD. Secondary hyperalgesia and
perceptual wind-up following intradermal injection of capsai-
cin in humans. Pain. 1998;74:257–268.
7. Leffler AS, Kosek E, Hansson P. Injection of hypertonic saline
into musculus infraspinatus resulted in referred pain and sensory
disturbances in the ipsilateral upper arm. Eur J Pain. 2000a;
4:73–82.
8. Geber C, Magerl W, Fondel R, et al. Numbness in clinical and
experimental pain: a cross-sectional study exploring the
mechanisms of reduced tactile function. Pain. 2008;139:73–81.
9. Neugebauer V, Schaible HG. Evidence for a central compo-
nent in the sensitization of spinal neurons with joint input
during development of acute arthritis in cat’s knee.
J Neurophysiol. 1990;64:299–311.
10. Rolke R, Baron R, Maier C, et al. Quantitative sensory testing
in the German Research Network on Neuropathic Pain
(DFNS): standardized protocol and reference values. Pain.
2006;125:197.
11. Maier C, Baron R, Tölle TR, et al. Quantitative sensory testing in
the German Research Network on Neuropathic Pain (DFNS):
somatosensory abnormalities in 1236 patients with different
neuropathic pain syndromes. Pain. 2010;150:439–450.
12. Germann G, Harth A, Wind G, et al. Standardisation and
validation of the German version 2.0 of the Disability of Arm,
Shoulder, Hand (DASH) questionnaire. Unfallchirurg. 2003;106:
13–19.
13. Franke GH. Brief Symptom Inventory von L. R. Derogatis
(Kurzform der SCL-90-R)—Deutsche Version (German). In:
BSI, Göttingen: Beltz Test GmbH, 2000.
14. Frettlöh J, Huppe M, Maier C. Severity and specificity of
neglect-like symptoms in patients with complex regional pain
syndrome (CRPS) compared to chronic limb pain of other
origins. Pain. 2006;124:184–189.
15. Galer BS, Jensen M. Neglect-like symptoms in complex
regional pain syndrome: results of a self-administered survey.
J Pain Symptom Manage. 1999;18:213–217.
16. Magerl W, Krumova EK, Baron R, et al. Reference data for
quantitative sensory testing (QST): refined stratification for age
and a novel method for statistical comparison of group data.
Pain. 2010;151:598–605. Epub 2010 Oct 20.
17. Leffler AS, Kosek E, Hansson P. The influence of pain intensity
on somatosensory perception in patients suffering from subacute/
chronic lateral epicondylalgia. Eur J Pain. 2000b;4:57–71.
18. Kosek E, Ordeberg G. Lack of pressure pain modulation by
heterotopic noxious conditioning stimulation in patients with
painful osteoarthritis before, but not following, surgical pain
relief. Pain. 2000;88:69–78.
19. Koltzenburg M, Wall PD, McMahon SB. Does the right side
know what the left is doing? Trends Neurosci. 1999;22:122–127.
Review.
20. Melzack R. From the gate to the neuromatrix. Pain. 1999;
82:121–126.
21. Schwoebel J, Friedman R, Duda N, et al. Pain and the body
schema: evidence for peripheral effects on mental representa-
tions of movement. Brain. 2001;124:2098–2104.
22. Bingel U, Rose M, Glascher J, et al. fMRI reveals how pain
modulates visual object processing in the ventral visual stream.
Neuron. 2007;55:157–167.
r 2011 Lippincott Williams & Wilkins
Clin J Pain  Volume 27, Number 9, November/December 2011
23. Moseley GL. Why do people with complex regional pain
syndrome take longer to recognize their affected hand?
Neurology. 2004;62:2182–2186.
24. Maihofner C, Decol R. Decreased perceptual learning ability in
complex regional pain syndrome. Eur J Pain. 2007;11:903–909.
25. Schwenkreis P, El Tom S, Ragert P, et al. Assessment of
sensorimotor cortical representation asymmetries and motor
skills in violin players. Eur J Neurosci. 2007;26:3291–3302.
26. Offenbacher M, Ewert T, Sangha O, et al. Validation of a
German version of the ’Disabilities of Arm, Shoulder and
Hand’ questionnaire (DASH-G) (German). Z Rheumatol.
2003;62:168–177.
27. Stone LS. Joint degeneration and chronic pain: still looking for
the missing link. Pain. 2009;141:185–186.
r 2011 Lippincott Williams & Wilkins
Pain-associated Mild Sensory Deficits
28. McDougall JJ, Andruski B, Schuelert N, et al. Unravelling the
relationship between age, nociception and joint destruction in
naturally occurring osteoarthritis of Dunkin Hartley guinea
pigs. Pain. 2009;141:222–232.
29. Gwilym SE, Keltner JR, Warnaby CE, et al. Psychophysical
and functional imaging evidence supporting the presence of
central sensitization in a cohort of osteoarthritis patients.
Arthritis Rheum. 2009;61:1226–1234.
30. Scherens A, Maier C, Haussleiter IS, et al. Painful or painless
lower limb dysesthesias are highly predictive of peripheral
neuropathy: comparison of different diagnostic modalities. Eur
J Pain. 2008;13:711–718.
31. Schüning J, Scherens A, Haussleiter IS, et al. Sensory changes
and loss of intraepidermal nerve fibers in painful unilateral
nerve injury. Clin J Pain. 2009;25:683–690.
www.clinicalpain.com | 789