RESEARCH ARTICLE

Cutaneous sensitivity in unilateral trans-tibial
amputees
Cale A. Templeton1, Nicholas D. J. Strzalkowski1,2, Patti Galvin3, Leah R. Bent1*
1 Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada,
2 Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada, 3 Wellington Ortho
and Rehab, Guelph, Ontario, Canada
* lbent@uoguelph.ca

Abstract
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Aim
To examine tactile sensitivity in the leg and foot sole of below-knee amputees (diabetic
n = 3, traumatic n = 1), and healthy control subjects (n = 4), and examine the association
between sensation and balance.

Method
OPEN ACCESS
Citation: Templeton CA, Strzalkowski NDJ, Galvin
P, Bent LR (2018) Cutaneous sensitivity in
unilateral trans-tibial amputees. PLoS ONE 13(6):
e0197557. https://doi.org/10.1371/journal.
pone.0197557
Editor: Sliman J. Bensmaia, University of Chicago,
UNITED STATES
Received: September 7, 2017
Accepted: May 5, 2018
Published: June 1, 2018
Copyright: © 2018 Templeton et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Data Availability Statement: All relevant data are
within the paper and its Supporting Information
files.
Funding: The authors received no specific funding
for this work.
Competing interests: The authors have declared
that no competing interests exist.

Vibration perception threshold (VPT; 3, 40, 250Hz) and monofilaments (MF) were used to
examine vibration and light touch sensitivity on the intact limb, residual limb, and homologous locations on controls. A functional reach test was performed to assess functional
balance.

Results
Tactile sensitivity was lower for diabetic amputee subjects compared to age matched controls for both VPT and MF; which was expected due to presence of diabetic peripheral neuropathy. In contrast, the traumatic amputee participant showed increased sensitivity for
VPT at 40Hz and 250Hz vibration in both the intact and residual limbs compared to controls.
Amputees with lower tactile sensitivity had shorter reach distances compared to those with
higher sensitivity.

Conclusion
Changes in tactile sensitivity in the residual limb of trans-tibial amputees may have implications for the interaction between the amputee and the prosthetic device. The decreased skin
sensitivity observed in the residual limb of subjects with diabetes is of concern as changes
in skin sensitivity may be important in 1) identification/prevention of excessive pressure
and 2) for functional stability. Interestingly, we saw increased residual limb skin sensitivity in
the individual with the traumatic amputation. Although not measured directly in the present
study, this increase in tactile sensitivity may be related to cortical reorganisation, which is
known to occur following amputation, and would support similar findings observed in upper
limb amputees.

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Skin sensitivity in amputees

Introduction
Sensory feedback from the glabrous skin on the foot soles has been shown to contribute to the
maintenance of standing balance and control of gait [1]. When foot sole cutaneous feedback is
reduced experimentally through cooling or topical anaesthetic, increased centre of pressure
(CoP) excursions are observed during quiet stance [2], and gait is altered [3]. Reductions in
afferent feedback as a consequence of age [4], diabetes [5], and Parkinson’s disease [6] have
also been shown to contribute to a decline in balance and altered gait patterns. Following
lower limb amputation, the cutaneous tactile information from the amputated foot sole is
lost which may present a considerable challenge to an amputees’ recovery of balance during
rehabilitation.
At the onset of rehabilitation, amputees exhibit an increased dependence on vision during
upright stance [7]. Interestingly, this increased dependence on vision returns to baseline following eight months of balance training [7], and it has been suggested that an up-regulation of
other sensory systems, such as proprioceptive feedback from the intact skin may help compensate for the loss of sensory feedback caused by the amputation [7, 8]. The skin that associates
with the prosthetic is of particular interest, as this area signals information regarding weight
bearing and pressure within the prosthetic, similar to the role of the foot sole in non-amputated individuals. Studies which have caused deafferentation via ischemic block in animals [9,
10] and humans [11] or cutaneous anesthesia [12] have shown that cortical reorganisation can
occur within minutes after sensation is lost, and human studies have shown deafferentation of
the upper limb led to increased sensory acuity and sensitivity in the neighbouring intact areas
[12–14]. Therefore, it is reasonable that cutaneous afferent feedback originating within the
prosthetic may become up-regulated (given more functional weighting) as it takes on the task
of weight bearing, and sensory role of the amputated foot. This up-regulation of residual limb
skin feedback could exhibit as reduced perception or two-point discrimination thresholds.
These changes are thought to be due to reorganisation within the central nervous system,
termed cortical reorganisation [15, 16]. Following amputation, areas of the somatosensory cortex which previously corresponded to the amputated limb become responsive to stimulation of
body regions corresponding to the neighbouring cortical areas [16, 17]. While the exact link
between altered cortical representations and changes in tactile sensation has yet to be identified, these cortical changes may represent an adaptation to the loss of sensory feedback following amputation [15, 18].
To date, research examining cutaneous sensation in lower limb amputees has largely used
qualitative measures (i.e. classifying sensation as “normal” or “impaired”) rather than capitalizing on controlled experimental designs [18, 19]. In addition, it is critical to consider the
nature of the amputation and include control limb comparisons. Individuals who have undergone amputation due to diabetes often have peripheral neuropathies which affect tactile sensation bilaterally; thus, amputees with diabetes should be analysed separately from traumatic
amputees, which has not been the case in all previous work [20]. Furthermore, MRI scans in
humans have shown that cortical reorganisation may be occurring in both hemispheres of the
brain following amputation, which suggests that bilateral changes in tactile sensitivity may be
occurring [21]. Therefore, it is important to compare skin sensation on the amputated limb
to healthy, non-amputated control subjects rather than to homologous locations on the intact
leg of amputee subjects. Finally, despite the frequent use of quantitative vibration perception
threshold (VPT) testing in the study of cutaneous sensation in the healthy population [22, 23],
it has yet to be used in amputees. VPT testing across different frequencies provides the advantage of varying the activation levels of different classes of cutaneous afferents [slowly adapting
type I and II (SAI and SAII) and fast adapting type I and II (FAI and FAII)]. SAI afferents

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Skin sensitivity in amputees

relay information about pressure application to the skin [22], while SAII respond to skin
stretch which occurs during joint movement [24]. FAI and FAII afferents provide information
about velocity of skin indentation, and in the foot sole, are important for signalling and
responding to dynamic events such as slips and trips [25]. Each of these afferent classes are
uniquely sensitive to different frequency ranges, which gives VPT testing the unique ability to
selectively activate different sensory channels [26, 27]. This information may provide insight
into how feedback from specific afferent classes adapts (upregulated or downregulated) following amputation.
The purpose of this study was to examine changes in tactile perception thresholds (sensitivity) of light touch and vibration in lower limb amputees and to relate these thresholds to functional balance. Monofilaments were used to assess light touch, and VPT was tested at three
frequencies (3, 40, 250Hz) to selectively target different populations of cutaneous receptors.
Functional balance (functional reach) was related to tactile sensitivity by correlating maximum
reach, and maximum excursions in CoP with changes in perception threshold at sites in contact with the prosthetic. It was hypothesized that traumatic amputees would show increased
sensitivity of the skin around the amputation compared to control subjects, while amputees
with diabetes would show decreased sensitivity compared to controls. Furthermore, we predicted that higher sensitivity scores at prosthetic sites would relate to better performance on
balance tests.

Subjects
Five amputees (all male) with unilateral trans-tibial amputations were recruited through a
rehabilitation medical practice located in Guelph, Ontario. Subjects were initially screened
and excluded if the time since amputation was less than 12 months or the residual limb was
less than 15cm long measured from the popliteal crease. The amputees were classified based
on the cause of amputation as either diabetic (n = 3, mean age = 59.3±11.5 years, range 48–
71 years), or traumatic (n = 1, age 52). Four diabetic amputees were tested however one subject was excluded from data analyses due to positive responses on all catch trials. All of the
four analysed amputee subjects were at least 2 years post amputation; 2 of the diabetic amputees were 2 years post and one was 20 years post. The traumatic amputee was 18 years post
amputation. In the diabetic group, two amputations were due to diabetic ulcer and one was
due to osteomyelitis associated with diabetes. The cause for the amputation in the case of the
individual with the traumatic amputation was due to a motorcycle accident 18 years prior to
study participation. Age and sex matched control subjects (n = 4, all male, mean age = 54.3
±6.6 years, range 46–62) were selected from the University of Guelph population. None of
the control subjects had a history of neurologic, visual or vestibular disorders, or systemic
disease. Phantom limb sensations were described qualitatively using a subject questionnaire.
Frequency of phantom limb sensations were described on a five-point scale from Never to
Very Often (daily or multiple times per day). All subjects provided written informed consent
prior to participation. The study protocol was approved by the Research Ethics Board at the
University of Guelph.

Materials and methods
Block 1: Tactile sensation testing
Tactile sensation testing included VPT and light touch monofilament thresholds (MF). VPT
was always performed first, as this was the most attention demanding portion of the protocol. Eight skin sites were examined in both control and amputee subjects (Fig 1A). All nonglabrous skin sites (i.e. all except heel) were lightly shaved prior to testing to remove any

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hair. On the amputated limb, two sites on the base of the residual limb were selected. The
exact locations of these sites varied slightly, but were never directly on bone or scar tissue
and were always on the back skin flap. Of the two residual limb sites, one site was located
medially (Site 1—medial residual) and one laterally (Site 2—lateral residual). The distance
from the popliteal fossa to the medial and lateral residual was measured and used to determine two homologous sites on the intact calf (Site 3—medial calf and Site 4—lateral calf).
These sites were 10-12cm distal to the popliteal crease on average. For controls, calf sites on
both legs were measured 10-12cm from the popliteal crease. The remaining sites were the
same for amputees and controls. The tibial sites (Sites 5 and 6) were measured 5cm distal to
the lateral tibia condyle on both legs. The quadriceps site (Site 7) was located 10cm proximal
to the patella in the midline of the leg; this was measured on the amputated limb for amputee
subjects and the right limb for control subjects. The heel site (Site 8) was in the middle of the
heel, 3cm anterior to the posterior border of the dominant foot for control subjects (right in
all cases) and the intact foot of amputee subjects. The order that sites were tested was randomized for both VPT and monofilament testing. Subjects lay on an adjustable treatment
bed in a supine or prone position depending on the site being tested, and their test leg was
supported with VersaForm pillows (Fig 1B).
Vibration sensitivity. VPT was measured at three frequencies (3, 40, 250 Hz) at each test
site. Each frequency was selected to provide a different quality of afferent feedback. Although
the ability to isolate different afferent classes in the foot sole with vibration is unlikely [27],
each afferent class does preferentially responds to different frequencies: SAI afferents (3 Hz),
FAI afferents (40 Hz) and FAII afferents (250 Hz) [26, 27]. Subjects had their eyes closed and
listened to brown noise during vibration testing. Sinusoidal displacements were delivered
using the moving coil of an electromagnetic vibrator (mini-shaker type 4810, Brüel and Kjaer,
Naerum, Denmark). The vibrator was mounted on a movable arm with a gimbal socket, allowing the probe to be positioned perpendicular to the skin (Fig 1B). VPT (μm) was measured
using a binary search method, details of which have been published previously [4, 28, 29].
Briefly, vibration stimuli were applied as 2-second bursts with ~3-seconds given in between stimuli. Subjects used a trigger to indicate when they perceived a vibration burst. Perceived stimuli resulted in a decrease in vibration amplitude while non perceived stimuli resulted in an
increase in vibration amplitude. Trials consisted of 11 vibration bursts, and VPT was the smallest perceived amplitude. Three trials were performed at each frequency and at each site. At
each site VPT was the average of the three trials. All three frequencies were examined at one
site in random order before examining the next site. VPT testing took 12 mins per site. Sinusoidal displacements were superimposed on an initial indentation produced by a controlled
preload force of 1N for 3Hz and 40Hz and 2N for 250Hz. Force (31 load cell, Honeywell, MN,
USA) and acceleration (model 2221D, Endevco, CA, USA) data were digitized at 1000Hz
using Spike software (CED 1401, Cambridge Electronic Design Limited, Cambride, UK). Displacement of the probe was sampled at 1000Hz and measured using a displacement sensor
(model RGH24Z, Renishaw, Glouscestershire, UK) which was able to resolve changes in displacement of 0.5μm.
Monofilament sensitivity. Light touch perception was assessed using Semmes-Weinstien
Monofilaments (MF) (North Coast Medical Inc., Gilroy, CA). MF threshold was determined
using the Dyck 4-2-1 method [30]. Subjects were instructed to provide a “yes” response whenever a stimulus was perceived with 90% confidence. Catch trials (no stimulus applied) were
presented randomly during the testing of each skin site (at least 1 catch trial was performed at
each site, and one was performed every 8–10 stimulations). Data were discarded if a subject
gave a “yes” response on >50% of catch trials. Threshold was determined as the lowest monofilament which could correctly be perceived 75% of the time.

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Skin sensitivity in amputees

Fig 1. A) Skin sites tested: medial residual (1), lateral residual (2), medial calf (3), lateral calf (4), intact tibia (5), amputated tibia (6), quadriceps (7), heel (8).
B) Image of mini-shaker experimental set-up.
https://doi.org/10.1371/journal.pone.0197557.g001

Block 2: Balance testing functional reach
The functional reach task [31] was used to assess standing balance. Subjects stood on a force
plate (model OR6-6, AMTI, Watertown MA) with their feet shoulder width apart. They were

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Skin sensitivity in amputees

Table 1. Mean (SD) probe displacement (μm) during vibration perception thresholds (VPT) across test sites and groups. Monofilament threshold data presented in
last row (g). Shaded cells indicate at least one subject in that group illustrated ceiling effects. No standard deviations are reported for Traumatic group due to low n (n = 1).
Amp / Left
Tibia
3 Hz

Intact / Right
Tibia

Heel

Control

426.54
(±127.80)

440.85 (±23.74)

Diabetic

850.19
(±272.50)

720.60 (±501.60)

670.83

704.42

40 Hz Control

Traumatic

110.71 (±32.59)

129.56 (±46.86)

Diabetic

354.14
(±200.20)

249.47 (±186.50)

Traumatic
250
Hz

Lateral
Residual

Medial
Residual

279.13 (±33.82) 386.71 (±58.23) 506.17 (±92.68)

Lateral Calf

Medial Calf

583.99
(±113.60)

524.65 (±32.18)

627.13
(±166.40)

1030.97
(±275.40)

1052.67
(±615.10)

1198.50
(±278.40)

436.92
(±229.50)

998.94
(±173.30)

917.00
(±394.20)

351.58

559.08

236.75

334.00

615.33

459.47

56.06 (±18.64) 175.38 (±31.76) 124.85 (±68.18) 123.77 (±34.43)

86.98 (±31.42)

120.17 (±25.71)

304.81
(±228.50)

178.28
(±136.40)

614.42 180.14 (±81.07)
(±125.70)

265.14
(±102.30)

384.03
(±103.50)

12.92

30.00

14.17

24.83

49.17

24.50

47.25

38.08

Control

7.90 (±5.15)

16.71 (±9.35)

4.17 (±2.50)

20.38 (±6.98)

30.50 (±4.15)

28.23 (±4.73)

22.25 (±10.40)

34.00 (±2.67)

Diabetic

34.26 (±6.49)

25.69 (±14.80)

31.64 (±1.83)

32.42 (±1.70)

32.92 (±1.88)

36.42 (±4.13)

29.83 (±5.67)

26.22 (±6.28)

2.92

7.25

3.33

4.67

13.83

7.58

11.33

19.00

Control

1.75 (±0.50)

2.00 (±1.40)

4.85 (±3.64)

1.10 (±0.66)

5.25 (±6.60)

1.35 (±0.47)

2.15 (±2.50)

2.20 (±2.50)

Diabetic

100.00 (±69.20)

42.30 (±51.50)

300.00 (±0.00)

1.00 (±0.00)

122.00
(±156.00)

108.00
(±166.00)

64.00 (±100.00)

62.00 (±101.00)

1.00

8.00

100.00

0.60

1.00

0.60

4.00

1.40

Traumatic
MF
(g)

Quad

Traumatic

https://doi.org/10.1371/journal.pone.0197557.t001

instructed to reach as far forward as comfortable without letting their heels come off the plate,
and then return to the standing position immediately. Amputees were instructed to reach
with the arm contralateral to their amputated limb, while control subjects reached with a selfselected arm. Amputee subjects wore their prosthetic device and associated footwear, and control subjects wore shoes during the reach. Forces and moments were sampled at 100Hz (CED
1401MKI, Cambridge Electronic Design, Cambridge UK) and video was recorded in the sagittal plane at a sampling rate of 30Hz (PowerShot XI, Canon, Japan). Maximum CoP excursion
and reach distance were measured. Two separate reaches were recorded for each participant
and averaged.

Data analysis and statistics
VPT were measured in peak-to-peak displacement (μm) of the probe and MF were measured
in grams of force (g). Maximum anteroposterior CoP excursion and reach distance (cm) were
measured for the functional reach task. Correlations were run between VPT and maximum
CoP as well as between VPT and maximum reach distance. For a subset of VPT and MF tests,
some subjects were unable to perceive the largest stimulus, resulting in a ceiling effect (see
Results, Table 1). Where statistical comparisons were not possible due to low subject size or
ceiling effects, trends were described. This was the case for 3 Hz and 250 Hz data for amputees
with diabetes, and 250 Hz data for control subjects (Table 1). Data were analysed for normality
(Shapiro-Wilk test) and homogeneity of variance (Levene’s test and Bartlett’s test) and were
subsequently analysed using parametric or non-parametric methods where appropriate. When
comparisons are made between amputees and controls, the dominant leg (right) of controls
was compared with the intact leg of amputees, and the non-dominant leg (left) of controls was
compared with the amputated limb. Due to non-homogeneity of variance, a Kruskal Wallis
test was used to assess differences between the control and amputee groups at 40 Hz VPT with
significance set at chi squared <0.05. The Kuskal Wallis test compares all groups and shows
that statistically significant differences exist, but is not able to show which comparisons are statistically different (as an ANOVA would). To test site differences at each frequency, individual

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one-way repeated measures ANOVAs were run within groups (3 Hz control, 40 Hz control
and 40 Hz diabetics) with significance set at p<0.05.

Results
Data from one traumatic amputee (male, age 52) and three diabetic amputees (n = 3, all male,
mean age 59.3±11.5 years, range 48–71) were used for analysis. The main finding of the present study were the different VPTs between diabetic and traumatic amputees and age matched
controls. Specifically, diabetic amputee subjects had decreased cutaneous sensitivity (i.e.
increased perception thresholds) at 40 Hz (chi square<0.0001), while the traumatic amputee
illustrated greater sensitivity (i.e. decreased perception thresholds), at 40 Hz and 250 Hz vibration at all sites compared to age matched controls.

Ceiling effects
The shaker apparatus used for VPT restricted the maximum displacement of the probe for a
given frequency (1500μm for 3Hz, 2000μm for 40Hz and 35μm for 250Hz). Pilot testing in
young healthy subjects (age 20–35) classified these probe displacements consistently as suprathreshold for perception. However, in the current work some subjects were unable to detect
the maximum displacement, and therefore true perceptual threshold could not be determined.
In these cases, the maximum displacement delivered to that subject was identified as threshold;
likely resulting in an underestimation of the true threshold. Data in which ceiling effects were
observed were not analysed statistically and are purely descriptive (Table 1). Data from the 40
Hz condition exhibited no ceiling effects across any of the groups and sites and therefore was
subjected to statistical analysis.

Cutaneous sensation
Amputees with diabetes. For all sensitivity measures (VPT and MF) amputees with diabetes showed markedly higher thresholds (lower sensitivities) compared to controls. Ceiling
effects were present at 3 Hz and 250 Hz VPT and only 40 Hz VPT data were analysed statistically. 40 Hz thresholds were significantly higher in the group with diabetes compared to the
control group (chi square < 0.0001; Fig 2). Although not analysed statistically (due to ceiling
effects), the group with diabetes also showed higher thresholds for 3 Hz and 250 Hz VPT as
well as MF when compared to controls (Table 1, Fig 3).
When examining site sensitivity differences within the group with diabetes, there was a
trend in which thresholds decreased as sites moved more proximal. The highest thresholds
were observed at the heel, and a decrease in threshold was observed as the sites moved more
proximal with the lowest thresholds observed at the quadriceps (greatest sensitivity) (Fig 2). A
strong trend was found for site, however, significant differences between sites were not found
at 40 Hz, likely due to low n (p = 0.0588) (Fig 2). This trend was also apparent for 3 Hz VPT
and MF data (Fig 3), but was not analysed statistically due to ceiling effects (Table 1). No
major trends were observed when comparing sites on the amputated limb to homologous sites
on the intact limb.
Traumatic amputee. The traumatic amputee had lower thresholds compared to controls
at both 40 Hz (Fig 4) and 250 Hz VPT (Fig 5). At the site of the amputated tibia, threshold sensitivity at 40 Hz was 86.6% lower (more sensitive) in the traumatic amputee compared to the
homologous site on controls; in fact for all sites examined the 40 Hz VPTs were lower in the
traumatic amputee compared to controls (Table 1). Even the smallest decrease in 40 Hz VPT
threshold was substantial at 51.5% (Table 1). 250 Hz VPT were also markedly lower in the
traumatic amputee compared to controls at all sites (Table 1, Fig 5). Interestingly, unlike

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Fig 2. 40Hz vibration perception threshold (VPT) (μm) of control (dark grey bars) and diabetic amputee (white bars) subjects across test sites. 40 Hz VPT is
higher in diabetic amputees compared to controls for all sites except the quadriceps. INSET: At 40 Hz amputees with diabetes illustrated significantly higher
thresholds compared to controls when averaged across sites 40 Hz (chi square < 0.0001). 3 Hz VPT followed a similar trend, however data were not analysed
statistically due to ceiling effects. Error bars represent standard deviation.
https://doi.org/10.1371/journal.pone.0197557.g002

controls who showed ceiling effects at 250 Hz, no ceiling effects were observed at any sites or
any frequencies in the traumatic amputee (Table 1). No prevailing trend was apparent for MF
or 3 Hz VPT between the traumatic amputee and controls.

Relationship between skin sensation and functional balance
Average reach distance of the control subjects was significantly longer (32.5cm ± 8.6) than the
amputees (17.7cm ± 6.7) and CoP excursion was also larger in control subjects (4.85cm ± 0.7)
compared to amputee subjects (2.10cm ± 0.7). VPT for three skin sites within the prosthetic
(amputated tibia, medial residual, lateral residual) were averaged (VPT prosthetic = VPTp)
and correlated to measurements during functional reach. A negative correlation was observed
between 3 Hz VPTp and reach distance (r2 = 0.9413) and 3 Hz VPTp versus CoP excursion
(r2 = 0.8264) such that reach distance and CoP excursion decreased with increasing 3 Hz
VPTp (Fig 6A and 6B). Due to the 3 Hz VPT ceiling effects this correlational finding is limited.

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Fig 3. Comparison of control (dark grey bars), diabetic amputee (white bars) and traumatic amputee (light grey bars) groups for monofilament
threshold. Diabetic amputees showed higher thresholds at all sites except for quadriceps when compared to controls. The traumatic amputee tended to
show lower thresholds on the amputated limb compared to homologous sites on controls. Comparisons within group across site can also be made. The
traumatic amputee shows higher thresholds on the intact limb (I tibia, medial calf, lateral calf) compared to the amputated limb (A tibia, med residual,
lateral residual). Bars indicate mean values, error bars indicate standard deviation.
https://doi.org/10.1371/journal.pone.0197557.g003

Although not statistically significant (p>0.05), 40 Hz VPTp was also found to correlate with
reach distance (r2 = 0.7407) and CoP excursion (r2 = 0.682) but without the confound of any
ceiling effects (Fig 6C and 6D). Overall these data suggest that amputees with lower perception
threshold perform better on functional measures of standing balance.

Fig 4. 40Hz vibration perception thresholds (VPT) for control (dark grey bars) and traumatic amputee (light grey bars) subjects across all sites. At
all sites the traumatic amputee had lower thresholds compared to control. Error bars indicate standard deviation. For control subjects, this standard
deviation is calculated from the deviation between subjects. For the traumatic amputee, this standard deviation is calculated from the deviation between
the 3 trials for that individual.
https://doi.org/10.1371/journal.pone.0197557.g004
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Fig 5. Box plot of vibration perception threshold (VPT) of amputees compared to controls at each frequency. Each box plot is based on all
observations for that group at a given frequency collapsed across sites. Bar in middle of box represents median. Top and bottom of box are 75th and 25th
quartiles respectively. Top whisker represents maximum value, bottom whisker represents minimum value. At 40 Hz, diabetic amputees show
significantly higher threshold compared to controls (chi square<0.0001) . Control subjects have significantly lower threshold at 40 Hz compared to 3 Hz
(chi square<0.0001) . Number of subjects for each group: control n = 4; diabetic n = 3; traumatic n = 1.
https://doi.org/10.1371/journal.pone.0197557.g005

Discussion
The current study examined cutaneous sensitivity in lower limb amputees using quantitative
methods. As hypothesized, amputees with diabetes illustrated higher thresholds (lower sensitivity) to vibration at all frequencies compared to control subjects, likely due to diabetic
peripheral neuropathy [32]. Interestingly, the one traumatic amputee tested showed an
increase in sensitivity for VPT testing at both 40 Hz and 250 Hz. While no mechanisms were
tested here, we discuss this finding below in the context of cortical reorganization following
amputation, and address the functional implications of skin sensitivity. We found that amputees with higher skin sensitivity at locations that interact with the prosthetic performed better
on the functional reach task, suggesting that skin in this region may provide important and
useful information to the amputee in the control of balance and gait and may be a beneficial

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Fig 6. Correlations of amputee subject 3Hz and 40Hz VPT (for skin sites contacting the prosthetic) with reach distance (A and C) and CoP
excursion (B and D) during functional reach test. The negative correlation shows subjects with high perception thresholds (low sensitivity) show shorter
reach distance and decreased CoP excursion. The traumatic amputee is marked with star, and the diabetic amputees are marked with diamonds. Ceiling
effects were observed for diabetic subjects at 3Hz VPT.
https://doi.org/10.1371/journal.pone.0197557.g006

target for rehabilitation strategies. Limitations based on low sample size and observed ceiling
effects have been considered throughout the paper, however we believe that the use of VPT to
examine the role of different skin afferents illustrates the potential for sensitivity changes in
amputees which has not been clearly shown in lower limb amputees previously.

Amputees with diabetes
As hypothesized, amputees with diabetes had increased perception thresholds for VPT and
MF compared to control subjects. This reduced sensitivity was evident bilaterally, and was statistically significant for 40 Hz VPT (chi square<0.05) with a trend observed at 3 Hz, 250 Hz
and for MF. This is not a surprising result, considering the high incidence of peripheral

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neuropathy known to occur with diabetes [33]. The observation that neuropathy can be
observed in the intact limb is consistent with the literature, however there has been limited
quantitative measurement to date to examine how proximally the neuropathy extends. In one
study that did examine progression of neuropathy, examination on the leg was limited to “normal” vs. “abnormal” sensation, rather than providing quantitative data [18]. Our results indicate that in diabetic amputees, neuropathy is present at least as high as 5 cm below the knee
(location of tibial site) in both the amputated and intact limbs as compared to controls. Interestingly, the quadriceps site thresholds were relatively similar compared to controls, which
suggests that despite the advanced stage of diabetes in these subjects, the neuropathy is
restricted to the distal limbs. These findings support the use of MF and VPT testing to quantify
disease progression in diabetic patients. Perception deficits were observed at all three frequencies, suggesting that the sensitivity of SAI, FAI and FAII afferents are all impacted by the
disease.
A lack of adequate skin sensation is of concern in the prosthetic sites as they play an important role in identifying excessive pressure or chafing in the prosthetic. A reduced capacity to
detect excessive pressures can lead to complications following amputation [34]. In addition,
the skin within the prosthetic may serve a similar sensory role to the sole of the intact foot as
an important source of sensory feedback during balance [1] and gait [35, 36]. Quai et al (2005)
showed that impaired vibration perception (abnormal vs normal perception assessed with a
tuning fork held against the skin) within the prosthetic of lower limb amputees was associated
with increased CoP sway in quiet stance, and that poor vibration sense was a strong predictor
of history of frequent falls in this population. Further, Kavounoudias et al (2005) found that a
decrease in skin sensitivity may contribute to a decrease in kinesthesia at the knee joint that
has been shown to occur in amputees with diabetes [8]. While we were unable to establish a
significant correlation between sensitivity and balance measures (low n), a strong trend indicated that subjects who showed increased thresholds (lower sensitivity) within the prosthetic
also exhibited a shorter reach distance and decreased CoP excursion. The strong correlation at
3 Hz is of particular interest as 3 Hz is believed to functionally target the SAI population of
afferents that convey pressure information. 3 Hz VPT has previously been linked to balance
performance [37] which suggests a role for pressure feedback in mediating the present reach
distance measurements. During a leaning task such as the functional reach, adequate pressure
perception, mediated by SAI afferents, may be vital in identifying how close the CoP traverses
toward the boundary of the base of support. Therefore, amputee subjects with improved pressure perception within the prosthetic may be more comfortable reaching forwards and placing
their CoP closer to the base of support boundary in this task. Unfortunately, these conclusions
are limited by ceiling effects in diabetic subjects for 3Hz VPT. Correlations were not as strong
for frequencies mediated by FAI afferents (40 Hz), although these were still in the moderate
range (R2 = 0.6820 for AP-CoP and R2 = 0.7407 for reach distance). FAI afferents are also likely
to be activated in the dynamic component of the functional reach task and would provide
information about friction and slip within the prosthetic, which may explain the observed correlations. No significant correlations were shown at this frequency either (P>0.05). If in fact
changes in tactile sensitivity can have a meaningful impact on functional balance, this provides
an area of focus during rehabilitation; to restore as much afferent feedback from the amputated
leg as possible through training or use of medication. Previous research has shown that the
application of subthreshold [38, 39], and suprathreshold [40] foot sole vibrations can improve
balance. Subthreshold vibrations are thought to leverage stochastic resonance lowering the firing threshold of the underlying mechanoreceptor afferents [39]; whereas step-synchronized
suprathreshold vibrations may facilitate balance reflex pathways [40]. Future research should
investigate if similar stimulation applied to the residual limb results in increased balance

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outcomes in lower limb amputees, as this may have implications for the design of feedback
prosthetics, particularly those which attempt to provide tactile feedback to the user.

Traumatic amputee
Compared to controls, the traumatic amputee showed much higher sensitivity to 40 Hz and
250 Hz vibration, and this was observed in both the intact and amputated limbs. These results
may of course reflect individual variability; however, the traumatic amputee did not show
increased sensitivity to monofilaments or 3 Hz compared to controls, suggesting a specific and
not a general increase in sensitivity. While we cannot rule out the possibility that this individual may have had some factors influencing their peripheral sensitivity (skin mechanics, receptor density), this possibility seems remote. It has been suggested that individuals are born with
a set number of mechanoreceptors, and it is likely there are a similar number of receptors
across individuals [41, 42]. Peters et al, (2009) did show that decreases in surface area (for
example small fingers) does increase tactile acuity as there is a greater density of receptors in
the same anatomical region [41]. While we did not measure circumference of the residual
limb, increased sensitivity of the traumatic amputee was also found on the intact limb, suggesting that it is likely not density driving the response. As such we feel we can rule out density of
receptors as the cause of increased sensitivity, and rather support the notion that there is an
increased influence of these remaining skin receptors on cortical firing and the observed
increase in sensitivity may contribute to the hypothesis that peripheral sensitivity changes are
a result of cortical reorganisation following amputation.
Amputation creates a rapid deafferentation that results in the associated brain regions
being taken over by neighbouring cortical areas with these changes progressing over time
[21,43]. Theoretically, this reorganisation results in an increased number of cortical neurons
devoted to the residual limb, resulting in increased tactile acuity and sensitivity [44]. This
model is supported by the observation that tactile acuity and sensitivity can be increased using
an acute experimental decrease in afferent feedback (via anesthetic) to neighbouring areas
[44,45]; which supports increased sensitivity observed in upper limb amputees [15,46]. In the
current work, the increase in sensitivity of the skin within the prosthetic of the traumatic
amputee may represent an adaptation to increase afferent feedback regarding the interaction
between the prosthetic and the residual limb in an attempt to overcome the challenge of loss of
feedback from the amputated foot sole. In addition, as the skin within the prosthetic becomes
involved in weight bearing, more (and different) afferent signals will be sent to the brain than
previously sent from that region of skin. Since it is known that increased afferent input can
result in cortical expansion and reorganisation [47–49], this increase in afferent feedback from
the residual limb may help strengthen the cortical reorganisation. Based on this hypothesis, it
is reasonable to expect a similar increase in afferent feedback in the residual limb of diabetic
amputees and subsequent increase in tactile sensitivity as a result of cortical reorganization.
However increased sensitivity was not observed in diabetic amputees, which is likely due to
the presence of significant peripheral neuropathy (reducing sensitivity) masking any central
changes. In addition, the presence of peripheral neuropathy would reduce the number of afferent signals sent to the brain from the residual limb, and therefore may reduce the degree of
cortical reorganization which takes place in this population.
The change in sensitivity at 40 Hz and 250 Hz (but not seen at 3 Hz) for the traumatic
amputee suggests a change in tactile information mediated primarily fast adapting afferents.
An up regulation of FAI and FAII mediated signals may be due to the functional relevance of
these ‘dynamic’ afferents, which code for information regarding velocity of indentation and
slips [22, 50]. Microneurographic recordings have shown FAI afferents to be the most

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prevalent afferent class in the glabrous skin of the foot sole, which highlights their importance
in postural control [25, 51]. The observation that FAI mediated perception is up-regulated in
the residual limb of the traumatic amputee suggests that feedback from the remaining areas of
skin may adapt to better serve the function of the amputated foot sole, as the residual limb has
now become the primary site of interaction between the amputee and the ground. In addition,
the FAII afferents are specialized to detect high frequency vibration, and respond to distant stimuli, capable of sensing distant vibration through a tool, footwear or prosthetic [50].
Phantom limb sensation character and frequency were investigated using a subject questionnaire. The traumatic amputee described experiencing phantom sensations (presence, pain,
burning and itching) very often (daily), whereas two diabetic amputees described phantom
sensations approximately once per month, and one diabetic amputee described experiencing
phantom sensations a few times per year. Based on work in upper limb amputees, Ramachandran and colleagues have suggested phantom sensations to be a kind of perceptual correlate
of cortical reorganization. It is thought that as afferent feedback from the surrounding area
“takes over” the brain areas previously corresponding to the amputated limb, and spontaneous
discharge of neurons in this area is misinterpreted as originating from the missing limb, causing a phantom sensation [52]. This hypothesis was strengthened by previous work showing a
correlation between cortical reorganization and perceived magnitude of phantom limb pain
[17,53]. However, recent work by Makin et al. (2015) has challenged the role of cortical reorganization of the somatosensory cortex in phantom limb sensations in upper limb amputees
[54]. This work has shown the extent of cortical reorganization in upper limb amputees may
be smaller than previously suggested, and that there is no correlation with phantom limb sensations, as has been previously shown. From our data we cannot conclude if the phantom
sensations are related to the magnitude of cortical reorganization in the traumatic amputee.
Although not shown in the current study, there is potential that the use of afferent feedback
of the residual limb for balance and gait may increase the amount of cortical reorganization
which occurs in lower limb amputees compared to upper limb amputees. In addition, the
mechanisms which may mediate changes in tactile sensation rather than phantom limb sensations following amputation should be investigated further.

Conclusion
As expected, tactile sensation was significantly lower in amputees with diabetes compared
to control subjects, however this decrease in sensitivity was limited to the distal limb. Due to
the role of the skin of the foot sole in balance and gait, increasing tactile feedback from skin
which interacts with the prosthetic may improve functional balance outcomes. Interestingly,
the traumatic amputee showed increased skin sensitivity relative to controls and also showed
the best performance on the functional reach test. While not confirmed with neuroimaging,
this increased sensitivity may be due to cortical reorganisation which is known to occur following amputation.

Supporting information
S1 Text. Supporting information vibration data.
(XLSX)
S2 Text. Supporting information monofilament data.
(XLSX)
S3 Text. Supporting information reach data.
(XLSX)

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Skin sensitivity in amputees

Author Contributions
Conceptualization: Cale A. Templeton, Leah R. Bent.
Data curation: Cale A. Templeton, Nicholas D. J. Strzalkowski, Leah R. Bent.
Formal analysis: Cale A. Templeton.
Funding acquisition: Leah R. Bent.
Investigation: Cale A. Templeton, Leah R. Bent.
Methodology: Cale A. Templeton, Nicholas D. J. Strzalkowski, Leah R. Bent.
Project administration: Cale A. Templeton, Leah R. Bent.
Resources: Patti Galvin, Leah R. Bent.
Software: Leah R. Bent.
Supervision: Nicholas D. J. Strzalkowski, Leah R. Bent.
Validation: Cale A. Templeton, Patti Galvin, Leah R. Bent.
Writing – original draft: Cale A. Templeton.
Writing – review & editing: Cale A. Templeton, Nicholas D. J. Strzalkowski, Patti Galvin,
Leah R. Bent.

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