Accepted: Tactile Acuity (Dys) Function in Acute Nociceptive Low Back Pain: A Doubleblind Experiment

PAIN Publish Ahead of Print
DOI: 10.1097/j.pain.0000000000001110
Tactile acuity (dys)function in acute nociceptive low back pain: a

doubleblind experiment
Wacław M. Adamczyk1,2, Oskar Saulicz3, Edward Saulicz1, Kerstin Luedtke1,4

1
Department of Kinesiotherapy and Special Methods in Physiotherapy, The Jerzy Kukuczka
Academy of Physical Education, Katowice, Poland
2
Pain Research Group, Institute of Psychology, Jagiellonian University, Kraków, Poland
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3
Regional Specialised Hospital No. 4, Bytom, Poland
4
Department of Orthopedics, University of Luebeck, Luebeck, Germany
Correspondence to: Wacław Adamczyk The Jerzy Kukuczka Academy of Physical
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Education ul. Mikołowska 72 40-065 Katowice, Poland phone number: (+48) 602 292 217 e-
mail address: w.adamczyk@awf.katowice.pl
Number of pages: 22
Number of figures: 5
Number of tables: 3
Supplementary files: 2
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Abstract
Research shows that chronic pain is related to cortical alterations that can be reflected in
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reduced tactile acuity, but whether acute pain perception influences tactile acuity has not been
tested. Considering the biological role of nociception, it was hypothesized that nociceptive
pain will lead to a rapid improvement in tactile acuity and that this effect is correlated with
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pain intensity and pain distribution. In this randomised double-blind controlled experiment
(trial no. NCT03021278), healthy participants were exposed to one of three experimental
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conditions: acute, nociceptive low back pain induced by saline injection, a sham-injection
(without piercing the skin) potentially inducing nocebo pain, or no intervention. Tactile acuity
was measured by a battery of tests, including two-point discrimination threshold (TPD),
before, during the pain experience and after it subsided. We found that TPD did not improve
but deteriorated during pain induction in the experimental group compared to the control
group (p < 0.001; ŋ2 = 0.20) and changed from 56.94mm (95% CI: 53.43 to 60.44) at baseline
to 64.22mm (95% CI: 60.42 to 68.02) during the pain experience. Maximum reported pain
was a significant predictor (β = 0.35, p < 0.01), and accounted for 26% of the variance in TPD
(p < 0.05). Other tests, point-to-point test and two-point estimation task changed with a
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Copyright Ó 2017 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
similar trend but did not reach significance. We concluded that acute, nociceptive pain does
not improve but deteriorates tactile acuity linearly. The biological role of the observed
phenomenon is unknown and therefore future studies should address this question.
Key words: tactile acuity; two-point discrimination; sensory dissociation; sensory

discrimination training; low back pain, pain mechanisms.
1. Introduction
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Available data support the view of chronic low back pain (CLBP) as a condition
mediated by changes in the brain. Indeed, the body of evidence suggests that CLBP is
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associated with central nervous system (CNS) alterations occurring as a result of
neuroplasticity [37,53,76]. It has been shown that cortical reorganization includes shifted
functional representation of the back in the somatosensory cortex [24], reduced gray [5,65]
and white matter [8,9] volumes, enhanced responsiveness to tactile [24] and noxious stimuli
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in the sensory cortex [26], decreased activation of pain-inhibitory pathways [25], and lower
activation thresholds for spinal reflexes [73]. Interestingly, some of these alterations seem to
be related to clinically observable features such as reduced tactile acuity, typically measured
as the two-point discrimination threshold [1,11,60,61].
A recent systematic review and meta-analysis on tactile acuity in low back pain
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patients and healthy controls [1] resulted in three general conclusions: Firstly, CLBP patients
had reduced tactile acuity compared to pain-free controls; patients needed an approximately
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1cm larger distance between two tactile stimuli to be able to perceive them as two separate
points. Secondly, almost all studies defined their CLBP population as “non-specific”. This
implies that pain mechanism underlying altered tactile acuity remain unknown. Thirdly, the
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systematic search revealed a knowledge gap regarding tactile acuity in acute spinal pain.
Interestingly, tactile acuity has never been investigated in any acute low back [1,11], acute
neck [45] and -to the best of our knowledge- other pain states.
Investigating tactile acuity in an early phase of pain may lead to better understanding
of the development of CLBP and of the mechanism underlying tactile acuity alterations.
Furthermore, it can answer the question whether the long-lasting pain or pain per se is critical
for the precision loss in the tactile sense. A previous attempt to identify a relationship between
the duration of CLBP and tactile acuity failed [11], probably because only data from chronic
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pain populations were available at the time. Evoking non-neuropathic pain in a laboratory
setting can also provide a deeper insight into the role of nociception in the processing of
tactile acuity. If the pain itself produces changes in the structure and function of the CNS
[29,62,63,68], it is reasonable to assume that tactile acuity is diminished even in acute pain.
Biologically, however, it is unlikely that nociceptive input would produce such unfavorable
changes within the brain [55]. The pervading view of nociception assumes that it is an
adaptive transmission of danger cues into the CNS [10,52] exhibiting neuroplastic changes
such as enlargement of receptive fields at the spinal level [56,77]. Thus, tactile acuity should
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be improved not deteriorated in acute pain states. Such adaptation would enable a more
precise localization and recognition of threat or danger [70,71].
In this randomised controlled study, participants were exposed to one of three
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experimental conditions: acute, nociceptive pain induced by saline injection, a sham-injection
(without piercing the skin) potentially inducing nocebo pain, or no intervention. Tactile acuity
was investigated before, during the pain experience and after it subsided. It was hypothesized
that nociceptive pain will lead to a rapid improvement in tactile acuity and that this effect is
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associated with pain-related variables such as pain intensity and pain distribution. It was also
hypothesized that sham-injections will have a similar but less pronounced effect.
2. Methods
This study was performed at the Academy of Physical Education in Katowice. The
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design of the study was established a priori according to a pre-registered protocol

(NCT03021278). The study was conducted in accordance with the Declaration of Helsinki
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and its protocol was approved by the local Bioethics Committee (No. 8/2016). Data were
reported according to the CONSORT checklist [49].
2.1. Participants
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Seventy healthy male participants (age between 18 and 35 years) were recruited for
the purpose of this study. Participants were excluded if they were left-handed, reported pain at
the time of examination, had any history of chronic pain, i.e. pain lasting more than three-
months, reported back pain episode lasting more than 24 hours within a month prior to
participation, reported comorbidities affecting the nervous system, cardio-vascular diseases,
psychiatric illnesses, any disease requiring systematic drug consumption, diagnosed scoliosis
or hypersensitive reaction to saline solution. To be included, participants had to have similar
tactile detection thresholds at both sides of the spine (L3 level). Tactile threshold was
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measured only once by Semmes-Weinstein filaments (Touch Test™, Sensory Evaluators) to
confirm study eligibility. Inclusion criteria were adapted from previous tactile acuity studies
on healthy subjects [4,12,13].
Thirteen participants did not meet the criteria. Therefore, 57 participants (mean age =
24.46 ± 4.28) were randomly allocated to one of three groups: experimental (n=19), sham-
injection (n=19) or control group (n=19). The included sample was recruited from the
community of the Academy of Physical Education by verbal announcements and social-media
advertisements published in Academic groups. Included participants were asked to provide
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written informed consent for participation prior to the experimental procedure. They were
informed that they could stop participating at any point during the study without providing a
reason for their withdrawal. Participants were compensated with vouchers (value of 25 PLN
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each) for their participation and all of them were fully debriefed at the end of the study.
2.2. Sample size
Because no previous published studies investigated tactile acuity changes in acute low
back pain, the sample size calculation was based on data from our own systematic review and
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meta-analysis [1] and previous cross-sectional data in healthy controls [4]. Based on the
reported mean difference of 9.49mm between chronic low back pain patients and healthy
controls and a standard deviation of 9.90mm, a total sample size of 57 participants (19 per
group) was required to detect a significant effect. The between group effect during the
experience of pain was therefore regarded as the primary outcome. Further statistical analyses
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detailed below were conducted at an exploratory level. The power calculation was performed
a priori for two-sided comparisons detailed in the section on “statistical analysis” below. The
calculation was performed in G*Power [22] (G*Power 3.1.9.2 statistical software) with the
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alpha level set at α=0.05 and 80% power.

2.3. Research team, blinding and randomisation
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Two investigators performed the experiment: one physician and one physiotherapist
(assessor). The physician was responsible for the randomisation, the blinding of the assessor,
the experimental manipulation (pain induction) and the behavioural data collection.
Randomisation was by drawing a card from the closed pool. The card included information on
group assignment and was drawn by the physician after collecting baseline tactile acuity data
(assessment 1). The mixed pool of randomisation cards assured that the randomisation
sequence was not known by the physician. The assessor performed the tactile acuity
assessments. The assessor was absent during the pain induction and randomisation
procedures, in order to maintain blinding towards the group allocation and the painful side.
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Participants were instructed to not reveal their pain experience during tactile acuity
assessments, thereby ensuring assessor blinding. In addition, participants were naïve to the
experimental hypotheses.
2.4. Study design and overview
Details regarding the time-frame of the study are presented in the Fig. 1. After the
screening procedure and preparation phase, participants were informed that the study included
two branches so they can either be assigned to the experimental group (with injection) or to
the control group without injection. In fact, participants were randomly assigned to one of
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three groups: experimental, sham-injection or control. Groups differed only in terms of the
specific manipulation. The experimental group was exposed to pain induced by intra-
muscular hypertonic saline injection. The sham-injection group was exposed to a sham-
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injection not piercing the skin but provoking a needle-like sensation with a PinPrick device.
No manipulation took place in the control group. Tactile acuity was assessed three times in
each of the groups: before the manipulation, at the time when the experimental group
perceived the maximum pain intensity and at the time when the experimental groups’ pain
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had subsided.
2.4.1. Preparation
Participants were comfortably positioned in prone with their lower back exposed
[13,75]. The assessor palpated the L3 spinous process [14], shaved and cleaned both sides of
the spine to reduce between and within-subject variability that might occur during tactile
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acuity assessment. A horizontal axis was drawn at the level of the L3 spinous process in order
to determine the locations for tactile acuity assessment and pain induction (see Fig. 2 for
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details). Tactile acuity was measured at a 5cm distance from the midline (Fig. 2). This
standardisation was in line with the protocol described in our previous study [4].
2.4.2 Tactile acuity assessment
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Tactile acuity was assessed in three sessions in each of the group. Sessions were
separated by 6-minutes intervals. The first session served as a baseline measure of tactile
acuity. The second session was performed after experimental manipulation, when the pain
induced by saline injection in the experimental group had not changed for a minimum of 30
seconds. Similarly to a previous study [72], this plateau phase was reached approximately
2:30 minutes after the injection (mean time: 2:29 ± 0:45). The plateau phase was identified by
tracking the individual participants' pain ratings every 30s. Starting the second tactile acuity
measurements individually ensured standardisation of the procedure, and ensured that tactile
acuity assessments were completed while participants experienced maximum back pain. The
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final measurements were performed after the pain in the experimental group had subsided to
explore if changes in tactile acuity were short- or long-lasting and if they were associated with
the pain experience. During each session, tactile acuity was assessed on the left and right side
of the spine. Each session included assessments consisting of three distinct tactile acuity tests:
TPD - two-point discrimination test [13], PTP - point-to-point test [4] and the recently
developed TPE - two-point estimation task [2]. Each test was performed in the previously
marked area (Fig. 2) by using mechanical sliding callipers (Powerfix, digital calliper: Z22855)
with a precision of 0.01mm. The order of the tests and the first side of measurement
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(left/right) were randomised. At the end of each measurement, the subject's back was cleaned
with alcohol to create similar conditions for subsequent sessions.
The two-point discrimination test was assessed along the horizontal line at L3 level
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(1L or 1R) according to a previously published protocol [4] (Fig. 2). In brief, the callipers
were applied to the pre-marked line until the very first blanching of the skin [48]. Testing
commenced with 0mm between the two calliper's tips. The distance was gradually increased
until participants were able to verbally report that two points had been touched instead of one
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[51]. Subsequently, the descending sequence was applied until the perception of one point.
This procedure was repeated twice so that the TPD score was based on the mean of 4
staircases, two ascending and two descending. Lower values indicate greater tactile acuity.
TPD performed at the lumbar area is characterised by good reliability [4,20,46].
Point-to-point test was performed according to a previously published protocol [4]. In
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brief, the examiner lightly stimulated one of the points ('1L' or '1R'). The participants were
instructed to indicate the stimulated point by using a pen. The assessor measured the distance
between the stimulated and the indicated point. Mean values of three repeated trials served as
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PTP scores that were used in the data analysis. Lower PTP values indicate greater tactile
acuity. Intra-rater reliability of PTP is generally acceptable [4,30].
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Two-point estimation test was used as a novel tactile acuity tool. The test measures the
precision of tactile perception and can also be used to reflect body image distortions [2],
frequently observed in patients with CLBP [51,57]. For the TPE test, two callipers were used,
one by the assessor and one by the participant. The assessor applied one tactile stimulus along
the horizontal line, with a 120mm horizontal separation between the callipers' tips [2]. The
aim of this stimulus was to evoke a tactile sensation perceived clearly as two distinct points
by all participants. Subsequently, participants were asked to manually indicate with their
callipers the distance they perceived (TPE score). Patients held the callipers that they could
only see the backside of the callipers and not the display. Three repeated measurements were
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performed and mean values were used in the analysis. Participants were unaware that the
same distance was used for each measurement but instructed to make a decision based on
their subjective perception. For analysis, the TPE score was calculated according to the
following formula: TPE score = 120mm - x, where “x” refers to the value (distance) indicated
by the given participant. Lower TPE values indicate greater tactile acuity. Intra-rater
reliability of TPE is excellent if performed at the lumbar area [3].
2.4.3. Experimental manipulation
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In the experimental group, acute, nociceptive low back pain was induced via 1.0 ml of
hypertonic (5% NaCl) saline bolus injection which is a commonly used model of acute low
back pain [31,32,66]. Saline solution was injected into the lumbar longissimus dorsi muscle
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50mm lateral to the L3 spinous process just above (5mm) the previously marked point '1L' or
'1R' (Fig. 2). Injections were performed by a trained physician under ultrasound imaging
guidance to ensure that each single injection was equally placed at a depth of 30mm [72]. The
side (left or right) of pain induction was randomised and counterbalanced across subjects. The
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needle insertion mark and the corresponding point on the opposite side of the body were
covered by placing a small piece of adhesive plaster. This procedure ensured assessor
blinding as he was unaware which body side was painful.
In the sham-injection group, a real needle was shown in full view to the participants to
imitate and enhance the anticipation of nocebo pain. During ultrasound examination, a
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pinprick sensation was produced by a weighted stimulus (flat contact area, 0.25 mm in
diameter; PinPrick; MRC Systems GmbH, Germany) applied perpendicularly to the skin just
above (5mm) the point '1L' or '1R' without piercing the skin. A stimulus of 512 mN was used
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because it has been validated as the force activating cutaneous nociceptors [28]. Single
stimulation of nociceptors was used to create a valid assertion of injection serving as the
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group with nocebo-like pain. Adhesive tapes covering stimulation and corresponding opposite
point were also provided. Blinding of the sham-injection condition allowed for the
comparison between tactile acuity change in the nociceptive condition (injection) and non-
nociceptive condition (sham-injection).
The control group was only screened by ultrasound imaging but was not exposed to
any intervention. Adhesive tapes were placed in the same way as in the previous two groups.
Participants were instructed to rest between tactile acuity assessments (Fig. 1). Results of the
control group enabled us to control for confounding factors such as the learning effect.
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2.5. Pain and fear measure
Pain and fear of pain were measured behaviourally on a Numerical Rating Scales
(NRS). The scale for pain intensity ratings ranged from 0 = “no pain” to 10 = “the worst pain
imaginable”. Fear of pain was measured only once, prior to the group allocation. It was rated
on a scale ranging from 0 = “not at all” to 10 = “very much”. Pain intensity was measured
individually just after saline/sham injection and monitored every 30 seconds until reaching a
plateau. If pain was still present after the second tactile acuity assessment the measurements
were continued until full recovery. In addition, participants were asked to indicate the
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distribution of the experienced pain by estimating the diameter of the circle every 30 seconds
[72]. Greater circle (diameter in cm units) referred to the greater distribution of pain (larger
body area affected). For better characterisation of the included sample, participants were
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asked to complete a set of questionnaires: The Pain Catastrophizing Scale (PCS) and the Fear
of Pain Questionnaire (FPQ-III).
2.6. Manipulation check questions
In order to check, whether the sham injection was detected by participants, a
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questionnaire was handed out at the end of experiment. Participants had to decide to which
group they had been allocated. If they picked the “group with injection” they had to decide if
they received a real saline solution injection (yes/no). The latter question was used to control
for successful manipulation. A similar procedure has been used in other sham-controlled
experiments [35,41]. Participants from the experimental and sham-injection groups were also
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asked to answer the question whether their pain was maintained during the second tactile
acuity assessment (yes/no).
2.7. Statistical analysis
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Baseline differences in descriptive statistics were analysed by one-way analysis of

variance (ANOVA) with “group” as a between-subject factor. The main analysis was
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performed using a repeated-measures ANOVA design, with “group” (experimental, sham-

injection and control) as a between-subject factor and “session” (assessment 1, 2 and 3) as a
within-subject factor. In order to test the hypothesis on tactile acuity improvement during pain
induction, F-tests were followed by planned comparisons on tactile acuity data from
assessment 1 versus assessment 2 in each of the group. To determine whether the magnitude
of tactile acuity improvement differed between the groups, planned comparisons were
performed on the difference in tactile acuity (assessment 1 vs. assessment 2) between
experimental and control group, and between sham-injection and control group. Exploratory
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comparisons were performed to check if the tactile acuity change normalised after the
experimental pain had subsided.
Although data from both sides (left/right) of the spine were collected, statistical
analyses were performed using the data representing the side which was randomly exposed to
pain. In the control group, there was no pain, but still the side for analysis was chosen
randomly. Collecting the data from the other side served only as a procedural requirement to
maintain blinding of the assessor.
Forward, stepwise multiple regression was performed as a secondary analysis to
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determine the degree to which tactile acuity change measured by e.g. TDP (∆TPD =
assessment 2 - assessment 1) is predicted by maximal and average pain intensity and maximal
and average pain distribution. Independent variables were chosen based on the findings from
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previous studies, showing that a change in tactile acuity is correlated with severity of reported
pain. All the analyses were conducted using the STATISTICA data analysis software, version
12 (StatSoft Inc., Tulsa, OK, USA), and the data were screened for normality assumptions
prior to the inferential analysis. The level of significance was set at p < 0.05.
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3. Results
3.1. Baseline differences

Table 1 shows the characteristics of the participants by experimental group. There
were no significant differences across groups for age (F(2,54) = 1.23; p > 0.05; ŋ2 = 0.04),
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body-mass (F(2,54) = 0.80; p > 0.05; ŋ2 = 0.03), height (F(2,54) = 0.44; p > 0.05; ŋ2 = 0.02), fear
of pain [trait] (F(2,54) = 0.91; p > 0.05; ŋ2 = 0.03), pain catastrophizing (F(2,54) = 1.14; p > 0.05;
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ŋ2 = 0.04), and fear of pain [state] (F(2,54) = 0.45; p > 0.05; ŋ2 = 0.02.). In addition, groups did
not differ in baseline tactile acuity: there were no significant differences for TPD threshold
(F(2,54) = 0.69; p > 0.05; ŋ2 = 0.02), PTP test (F(2,54) = 0.22; p > 0.05; ŋ2 = 0.01) and TPE task
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(F(2,54) = 0.05; p > 0.05; ŋ2 = 0.00). Table 2 shows mean and standard deviations of tactile
acuity tests across groups and sessions (Table 2).
3.2. Manipulation check
The main assumption of this experiment was that tactile acuity tests are performed
during acute nociceptive pain in the experimental group. Seventeen out of 19 participants
(89.5%) reported that they felt pain during the second tactile acuity assessment. In five
participants (26%) pain outlasted the second tactile acuity assessment. In the sham-injection
group, 11 participants (57%) reported pain after “injection”, but only two reported that they
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felt pain during the second tactile acuity assessment. No pain was reported by the control
group. ANOVA analyses confirmed a statistically significant main effect of “group” for the
outcomes pain intensity (F(2,54) = 71.04; p < 0.001; ŋ2 = 0.72), pain distribution (F(2,54) =
26.75; p < 0.001; ŋ2 = 0.50) and (estimated) pain duration (F(2,54) = 872.79; p < 0.001; ŋ2 =
0.97). Post hoc Tukey test results revealed that the experimental group experienced a
significantly higher mean pain intensity (p < 0.001), lasting for a longer time period (p <
0.001), and reported their pain at a larger body area (p < 0.001) compared to the sham-
injection group and control group (Table 3). Eleven out of 19 (58%) participants from the
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sham injection group indicated that they received real saline injection. Pain ratings and times
of reaching the plateau phase in individual subjects are reported in the Supplementary file 1
(available online at http://links.lww.com/PAIN/A504).
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3.3. Tactile acuity perception across groups
Repeated-measures ANOVA for TPD revealed a statistically significant main effect of
“session” (F(2,54) = 4.32; p < 0.05; ŋ2 = 0.07) and a marginally non-significant “session” x
“group” interaction (F(2,54) = 2.38; p = 0.056; ŋ2 = 0.08), indicating that participants had
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different TPD results in respect to the session, and that the size of this effect varied among
examined groups. Within-group planned comparison tests revealed a statistically significant
difference between assessment 1 and 2 in the experimental group (F(1,54) = 12.63; p < 0.001;
ŋ2 = 0.20), indicating that acute low back pain increased the mean TPD threshold (Fig. 3)
from 56.94mm (95% CI: 53.43 to 60.44) at baseline to 64.22mm (95% CI: 60.42 to 68.02)
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during the second assessment (acute pain). Furthermore, TPD thresholds normalised after the
experimental pain had subsided: the difference between assessment 1 and 3 was not
statistically significant (Table 2) and dropped from 64.22mm (95% CI: 60.42 to 68.02) during
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the second assessment (acute pain) to 60.80mm (95% CI: 57.50 to 64.10) at the third
assessment.
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The difference between assessment 1 and 2 was not significant in the sham injection
group (F(1,54) = 1.08; p > 0.05; ŋ2 = 0.02) but mean TPD thresholds showed the same direction
of change (Fig. 3). No significant change was observed in the control group (F(1,54) = 0.03; p >
0.05; ŋ2 = 0.00).
Between-group planned comparison tests for the difference between assessment 1 and
2 (∆TPD) revealed that the magnitude of this difference was significantly (F(1,54) = 6.90; p ≤
0.01; ŋ2 = 0.11) larger in the experimental group 7.29 (95% CI: 3.47 to 11.10) compared to
the control group -0.33 (95% CI: -3.71 to 3.05). No significant difference between sham-
injection and control group was found (see Fig. 4 and Supplementary file 2; available online
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at http://links.lww.com/PAIN/A504). Regression analysis revealed that the variable
“maximum reported pain” was a significant predictor (β = 0.35, p < 0.01) for the ∆TPD (DV)
in the first and final step of the regression model (Fig. 5). Maximum reported pain accounted
for a significant proportion of the variance in the ∆TPD, i.e. in the tactile acuity alteration
(COR R2 = 0.26, p < 0.05).
Repeated-measures ANOVAs for PTP results revealed no statistically significant main
effects or interaction (“session” x “group”), indicating that acute pain or sham-injection had
no effect on the PTP score (Supplementary file 2, available online at
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http://links.lww.com/PAIN/A504). However, PTP increased in the experimental group from
31.46mm (95% CI: 26.98 to 35.94.44) at baseline to 36.64mm (95% CI: 31.02 to 42.21)
during the second assessment (acute pain) with a trend for significance (F(1,54) = 3.19; p =
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0.079; ŋ2 = 0.06). No significant PTP change was observed in the sham-injection (F(1,54) =
0.46; p = 0.50; ŋ2 = 0.01) and the control groups (F(1,54) = 0.10; p = 0.75; ŋ2 = 0.01). Between-
group planned comparisons did not reveal statistically significant differences (see
Supplementary file 2, available online at http://links.lww.com/PAIN/A504; and Fig. 3).
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ANOVA for TPE scores revealed a statistically significant effect of “session” (F(2,54) =
3.12; p < 0.05; ŋ2 = 0.05). Within-group planned comparison tests did not reveal a significant
difference between session 1 and 2 in the experimental group (F(1,54) = 0.06; p > 0.05; ŋ2 =
0.00) and the sham-injection group (F(1,54) = 2.19; p > 0.05; ŋ2 = 0.04). A significant decrease
in TPE scores from 37.44mm (95% CI: 25.91 to 48.97) at baseline to 27.24mm (95% CI:
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15.15 to 39.33) during the second assessment (acute pain) was noted only in the control group
(F(1,54) = 5.37; p < 0.05; ŋ2 = 0.09), indicating for a strong learning effect for the TPE task.
The magnitude of this change was not significantly different from the magnitude observed in
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the experimental (F(1,54) = 2.14; p > 0.05; ŋ2 = 0.04) and sham-injection groups (F(1,54) = 0.35;
p > 0.05; ŋ2 = 0.01). See Fig. 3 and 4.
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4. Discussion
This study was aiming to address the hypothesis that the experience of pain leads to
measurable change in tactile acuity within the primary hyperalgesic area. And indeed, the
current data provides evidence that pain influences the precision of touch, yet the direction of
this change was contrary to the stated hypothesis. Tactile acuity was not improved but
deteriorated after the induction of acute, peripheral nociceptive low back pain. This effect,
although significant only in the results of the TPD, was also noticeable in the additional,
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novel measures of tactile acuity. Reduced tactile acuity cannot be explained by repeated
execution of TPD, as it was absent in the control condition. Moreover, the effect size was
significantly predicted by the perceived pain intensity according to the rule “the more severe
the pain was, the more it impaired tactile acuity”. Interestingly, deterioration did not occur in
the group exposed to the nocebo pain (sham-injection), although TPD results showed the
same direction of change.
The current literature confirms that nociception and pain play a biological role in
living organisms by triggering adaptive responses [10,52,54]. Acute pain promotes healing
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and body protective behaviour. Lack of this protection, for example in patients with
congenital insensitivity to pain [17,18], produces debilitating changes in homeostatic
regulations, and often leads to premature death. In humans, protection is ensured by motor
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[42], perceptual [70,71], hyperalgesic and allodynic responses [10]. As a consequence, non-
noxious tactile stimuli delivered to an area of injury are perceived as painful, and objects
related to such noxious stimuli are perceived as being closer to the body than objects not
associated with noxious stimulation [70,71]. It was expected to observe a similar trend in
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other sensory functions, i.e. tactile acuity. Intriguingly, these current results showed a
seemingly contrary effect.
One explanation of the current results is a hypoesthetic effect [40]. Pain triggered by
hypertonic saline injection is based on a mechanical as well as a chemical enhancement of the
sensitivity to mechanical stimuli. Excitation of muscle nociceptors is induced by mechanical
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damage of the muscle tissue itself, and by cell shrinkage caused by an increase in extracellular
osmolarity [27]. These processes may lead to a secretion of chemical substances such as
prostaglandin E2 or bradykinin and activation of Aδ and C fibres [39]. It has been shown in
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an experimental setting, that these cascades result in higher tactile, warm and cold thresholds
in the referred pain area [40]. This tactile hypoesthesia has been linked to altered tactile acuity
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in a variety of clinical populations with neuropathic [16,21,58,64,67] but not nociceptive pain
[2,51,75]. Another peripherally-driven effect accounting for tactile acuity deterioration is the
“touch-gate” phenomenon. As an analogy to the gate-control theory of pain, it has been
reported that vibrotactile thresholds are increased when thermal stimuli are delivered either
below or above pain thresholds regardless of attentional or arousal biases [6]. Gating tactile
stimuli by activation of the nociceptive system might delay the former and thus be a reason
for lower discriminating abilities.
However, our results cannot be explained by peripheral mechanisms, only. In the
current study, a linear trend between experienced pain and the magnitude of tactile acuity
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change was elucidated. This is particularly interesting, since all participants received the same
volume of hypertonic saline solution, hence the same “amount” of nociception lead to a
variety of subjective pain experiences. It is therefore concluded, that peripheral nociception
was not the exclusive mechanism to evoke tactile acuity changes. Instead, the perception of
pain played a crucial role in that change. This perspective can be supported by two facts:
Firstly, the nocebo intervention (sham-injection) triggered a similar pattern of tactile acuity
changes as measured by the TPD test, the most popular measure of tactile acuity [1,11]. It is
possible that the trend would have become significant in a larger sample and with more
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convincing nocebo-like verbal suggestion, inducing long-lasting pain without damage.
Secondly, TPD results returned towards normal when the pain had subsided (Fig. 3).
To the best of our knowledge, tactile acuity has not been addressed in the context of
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acute pain states in any previous studies despite a body of literature focusing on chronic pain
populations [19,34,38,50,51,60,64,69,75]. Our findings suggest that the pain itself might be
more important than cortical reorganisation, a phenomenon previously thought to be the main
cause for altered tactile acuity in e.g. CLBP. Reduced tactile acuity was not only reported for
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patients with CLBP [1,2,11], but also for chronic neck pain [15,38,50], complex regional pain
syndrome [44,59,60], osteoarthritis [7,69], rheumatoid arthritis [36], and recently in achilles
tendinopathy [19]. Our results are in line with the literature on chronic pain states and
therefore undermine the supposed relationship between chronic pain, tactile acuity and
cortical reorganisation. Although the latter was not directly investigated in the current study,
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it seems to be likely that even acute experimental pain produces some form of cortical
reorganisation [68]. Following this hypothesis, altered tactile acuity rather seems to be an
epiphenomenon co-existing physiologically with nociceptive CLBP and adaptive brain
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changes. Previous tactile acuity studies were conducted in populations with neuropathic
syndromes characterized by “negative signs and symptoms”. It is well documented that
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neuropathies are related to larger TPD scores, e.g. in patients with diabetes mellitus [21]
carpal tunnel syndrome [33], median neuropathy [16], postherpetic neuralgia [58] and
lumbosacral radiculopathy [64]. The current results, showing that a significant deterioration in
tactile acuity can be induced by peripheral nociceptive pain, contradicts the hypothesis that a
dysfunction in tactile function requires the injury within the peripheral nervous system
resulting in neuropathic pain.
Our study is the first to show that nociceptive pain itself is the cause for altered tactile
acuity. The results are robust. Firstly, the required sample size was estimated for testing the
main hypothesis by TPD test established as a primary outcome. As a result, experimental
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manipulation led to a statistically significant and strong effect (ŋ2 = 0.20). The effect cannot
be attributed to the fact that the test was repeated over-time, as the control group showed -
although not significant- a trend towards a learning effect, which has been described in other
studies utilizing TPD [23,47]. Secondly, the experimental manipulation was successfully
applied. The majority of participants experienced pain during the tactile acuity assessment.
Thirdly, the experimental procedure was performed with extreme caution and in a double
blinded manner: patients were not informed about the hypotheses tested, while the examiner
was not informed about group allocation and the side affected by pain. Blinding was not used
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in prior case-control studies [43,57,69,75], therefore the effect in chronic pain populations,
similar in magnitude (~10 mm) to the effect observed in the current study (7mm), could have
been overestimated. Fourthly, a novel control (sham-injection) paradigm was designed for the
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purpose of the current experiment. The hypothesis that tactile acuity can be changed even in
the total abscence of nociception is tempting. In the group exposed to sham-injection, a small
subgroup revealed a strong pain experience. It is highly likely, that, if the nocebo condition
would be enhanced, e.g. by adding verbal suggestion of strong hyperalgesia, the same
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significant change in tactile acuity as observed in the experimental group could be reached.
Future studies need to address these issues and replicate current findings. Finally, the primary
outcome was measured by reliable tools, especially by the TPD test. Hitherto, four
independent studies confirmed high intra-rater reliability of TPD test performed at the lumbar
area around L3 or L5 spinal level [4,13,20,46].
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Based on these current findings, some implications for pain science and clinical
practice should be acknowledged. Enhanced protection during acute pain is not reflected by
improving tactile acuity and future studies should account for the biological role of tactile
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acuity changes. Furthermore, sensory discrimination training (SDT), a therapy aiming to

restore cortical maps should be applied with caution until establishing a clear relationship
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between pain, tactile acuity and cortical changes in CLBP and other chronic conditions;
current findings question the mechanisms underlying cortical restoration as a mechanism
leading to pain reduction in CLBP [74]. Alternatively, if SDT indeed reduces pain, it should
be verified in acute as well as in chronic pain. Certainly, future studies should investigate
tactile acuity not only in the experimental setting, but also in clinical populations in order to
enhance the generalizability of our results. In addition, the effect of the experimental
procedure on tactile perception should be examined in a variety of pain models. For example,
we only monitored changes located at the area of primary hyperalgesia. To complement this
current study, capsaicin-based models of widespread pain could be performed and tactile
14
acuity should be monitored over-time for longer time-periods, in areas of referred pain as well
as in the hyperalgesic area. Lastly, the observed difference in tactile acuity was relatively
small, probably due to the body part exposed to tactile acuity measurement and pain. Tactile
acuity scores at the lumbar region are much higher than for other body locations, e.g. hand or
mouth [1,11]. Therefore, it is more likely to observe a more pronounced effect in locations
with relatively greater acuity at baseline.
To conclude, our study shows that altered tactile acuity is not only observed in chronic
but also in acute nociceptive low back pain. Deterioration occurs immediately after the pain
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induction and is related to the intensity of the pain perception, which question the causal role
of cortical reorganisation in the formation of chronic pain. Moreover, tactile acuity alteration
previously observed in neuropathic pain syndromes is associated with a nociceptive
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mechanism. The biological role of the observed deterioration is unknown and therefore future
experimental studies should address this question.
5. Acknowledgements
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The authors would like to express special thanks to Professor Andrzej Małecki and
Mrs Danuta Smykla from the Academy of Physical Education. Their help and support in
collecting the data, purchasing the equipment (PinPrick device; MRC Systems GmbH,
Germany) and realizing the whole project was outstanding and invaluable. Kindly thanks to
the research group at the Laboratory of Movement Analysis (Academy of Physical Education)
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for help with laboratory equipment; and special thanks to Tomasz Adamczyk (Logotech AA)
for important intellectual contribution to the project and support during all stages of the study.
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Wacław Adamczyk is supported by a scholarship awarded within the grant

2014/14/E/HS6/00415 from the National Science Centre in Poland.
Funding: This research did not receive specific funding, although it was performed as
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a part of a project funded by the Statutory Research Program for Young Researchers and PhD
Students at The Jerzy Kukuczka Academy of Physical Education (grant No AN-510-FMN-
1/2016)
Author Contributors: WA and KL developed the study design. WA wrote the first
and subsequent drafts of the paper with important intellectual content from all co-authors. The
study was performed and data were collected by WA and OS. WA was a director of the
research project and was supervised by two supervisors (ES and KL). WA performed all
15
required statistical analyses and their results were interpreted by all co-authors (KL, ES and
OS). All authors have approved the final version of the manuscript submitted for publication.
Competing interests: The authors have declared that no competing interests exist.
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7. Figure legends
Figure 1. Study design. Participants were randomly assigned to one of three groups although
they were informed only about two groups: with and without pain induction. Participants were
assessed during three separate sessions separated by ~6-minutes intervals. The first session
served as baseline. Between first and second session, experimental manipulation was
performed. Participants either received a real injection with saline solution (pain group), sham
injection or were instructed to rest for 6 minutes (control). Vertical arrows indicate pain
intensity and pain distribution monitoring. Pain was monitored every 30 seconds beginning
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from its induction. Note that in the experimental group, the second session was started
individually, i.e. when pain ratings were stabilised at a similar level (plateau phase). TPD -
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two-point discrimination test, TPE - two-point estimation test, PTP - Point-to-point test.
Figure 2. Determination of measurement sites. A horizontal axis was drawn at the L3 spinal
level. Three points were plotted on this axis. The reference ‘zero’ point overlapped with the
L3 spinous process, other two points '1-left (L)' and '1-right (R)' were marked laterally in
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respect to ‘zero’ point (5 cm apart). Tactile acuity was measured at point 1L and 1R. In case
of experimental or injection-control groups, pain was induced above (5mm) previously
marked points (1L or 1R). The place of the needle insertion was marked as a small circle on
the left side.
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Figure 3. Tactile dysfunction in experimentally induced, acute low back pain. (A) tactile
acuity measured by two-point discrimination threshold (TPD) was significantly reduced
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during acute low back pain with a similar non-significant trend after sham-injection. (B)
Tactile acuity measured by point-to-point (PTP) was significantly reduced during acute pain.
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(C) Acute and nocebo-like sham-injection reduced the significant learning effect for tactile
acuity assessment using the two-point estimation (TPE) task, that was observed in the control
group. Note: the greater the bars, the worse the tactile acuity. Error bars refer to standard error
of measurement. S1, session 1, S2, session 2, S3, session 3, *p < 0.05, ***p < 0.001.
22
Figure 4. Tactile acuity alteration in acute low back pain. Note: the magnitude of tactile
acuity alteration -expressed as the difference between the first and the second tactile acuity
assessment (delta TPD)- was significantly larger in the experimental group than in control
group.
Figure 5. Relationship between tactile acuity alteration and maximum reported pain.
Maximum reported pain during the experiment was a significant predictor of tactile
dysfunction (∆TPD) and was positively correlated with ∆TPD (β = 0.55, t = 2.70, p = 0.015).
Note: maximum reported pain accounted for 26% of the variance (F(1,17) = 7.31, p < 0.05).
D
TE
EP
C
C
A
23
Table 1. Descriptive statistics across examined groups
Sham-injection Experimental Control group

Variable
Mean SD Mean SD Mean SD
PCS 11.79 7.25 8.37 8.24 9.63 5.38
FPQ-III 63.68 19.92 62.26 16.26 56.11 18.84
Height 181.58 6.74 179.74 6.78 181.21 5.59
Mass 76.92 7.29 80.39 12.74 81.58 14.17
D
Age 24.37 3.24 23.42 4.19 25.58 5.14
Fear 2.79 2.10 2.37 2.06 2.11 2.51
TE
PCS, Pain Catastrophizing Scale, FPQ-III, Fear of Pain Questionnaire.
EP
C
C
A
1
Table 2. Mean values and standard deviations for tactile acuity tests
Experimental group Sham-injection group Control group

Test Session
Assessment 1 56.94ab 7.27 58.24 12.10 61.12 13.36
D
TPD Assessment 2 64.22a 7.89 60.36 11.54 60.79 11.08
b
Assessment 3 60.80 6.85 58.64 11.12 59.48 12.52
TE
Assessment 1 31.46 9.29 29.03 8.54 30.44 15.05
PTP Assessment 2 36.64 11.57 27.06 13.19 29.51 17.18
Assessment 3 35.03 12.85 29.28 10.24 30.59 15.27
EP
Assessment 1 84.88 20.42 84.12 21.45 82.56 23.92
TPE Assessment 2 85.97 21.09 90.63 25.14 92.76 25.09
Assessment 3 88.22 21.28 91.74 29.89 84.43 24.22
a
comparison of means assessment 1 vs. assessment 2 was statistically significant (p=0.001),
b
C
explorative comparison of means assessment 1 vs. assessment 3 was not statistically significant (p=0.06),
TPD - Two-point discrimination test,
C
PTP - Point-to-point test,
TPE - Two-point estimation test.
A
Note: Pain was induced during the second (2) tactile acuity assessment in experimental group and sham-injection group.
Table 3. Pain variables across experimental and sham-injection groups
Experimental Sham-injection Control group

Variable
Maximum pain intensity 4.63 2.06 0.74 0.73 0 0
Average pain intensity 3.84 1.75 0.54 0.64 0 0
Maximum pain distribution 5.05 3.05 2.03 3.68 0 0
Average pain distribution 3.93 1.67 1.24 2.41 0 0
Note: Pain intensity was expressed as a score on a 0-10 Numeric Rating Scale while pain distribution as a
D
size of the circle's diameter indicated by participants in centimetres. Pain measurements were performed
immediately after real (experimental group) or sham injection and were repeated every 30 seconds until reaching
a plateau phase. If pain was still present after second tactile acuity assessment the measurements were continued
until full recovery. The data presented in the table represent mean values of all performed measurements.
TE
EP
C
C
A
1
D
TE
EP
C
C
A
D
TE
EP
C
C
A
D
TE
EP
C
C
A
D
TE
EP
C
C
A
D
TE
EP
C
C
A

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Tactile acuity (dys)function in acute nociceptive low back pain: a

Wacław M. Adamczyk1,2, Oskar Saulicz3, Edward Saulicz1, Kerstin Luedtke1,4

Correspondence to: Wacław Adamczyk The Jerzy Kukuczka Academy of Physical

Key words: tactile acuity; two-point discrimination; sensory dissociation; sensory

design of the study was established a priori according to a pre-registered protocol

alpha level set at α=0.05 and 80% power.

2.4.3. Experimental manipulation

Baseline differences in descriptive statistics were analysed by one-way analysis of

performed using a repeated-measures ANOVA design, with “group” (experimental, sham-

3.1. Baseline differences

acuity changes. Furthermore, sensory discrimination training (SDT), a therapy aiming to

Wacław Adamczyk is supported by a scholarship awarded within the grant

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J. Sports Med. 2013;47:1085–1089.

Sham-injection Experimental Control group

Experimental group Sham-injection group Control group

Experimental Sham-injection Control group

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