Complementary Therapies in Medicine (2014) 22, 148—158

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Mode of action of cupping—–Local

metabolism and pain thresholds in neck
pain patients and healthy subjects
M. Emerich a, M. Braeunig b, H.W. Clement c,
R. Lüdtke d, R. Huber a,∗

a
Center for Complementary Medicine, Department of Environmental Health Sciences, University Medical
Center, 79106 Freiburg, Germany
b
Department Psychosomatic Medicine, University Medical Center, 79106 Freiburg, Germany
c
Department Child and Youth Psychiatry, University Medical Center, 79106 Freiburg, Germany
d
Karl und Veronica Carstens-Foundation, 45276 Essen, Germany
Available online 7 January 2014

KEYWORDS Summary
Objectives: Cupping worldwide has been part of traditional medicine systems and is in the
Lactate;
western world used as CAM therapy mainly for treating pain syndromes. The mode of action
Adenosin;
is up to now unclear. In order to investigate its mechanism we measured in parallel metabolic
Algometry;
changes in the tissue under the cupping glass and pressure pain thresholds.
Microdialysis;
Design and interventions: In 12 volunteers (6 healthy subjects and 6 patients with chronic neck
Subcutaneous tissue;
pain) a microdialysis system was implanted subcutaneously on both sides (left and right) above
Ultrasound
the trapezius muscle. After baseline measures cupping was performed at one randomly selected
side (left or right), the other side served as control. Every 20 min during baseline measures and
for 280 min after cupping, microdialysis probes for detection of lactate, pyruvate, glucose and
glycerin were taken. In addition, pain thresholds were measured before and after cupping with
algometry.
Results: Cupping resulted in a strong increase of lactate (beginning 160 min after cupping
until the end of the measurements) and the lactate/pyruvate ratio, indicating an anaerobe
metabolism in the surrounding tissue. Baseline pain thresholds were non-significantly lower in
neck pain patients compared to healthy controls and slightly increased immediately after cup-
ping (p < 0.05 compared to baseline close to the area of cupping in healthy subjects and on the
foot in neck pain patients). After 280 min no more significant changes of pain thresholds were
detected.
Conclusions: Cupping induces >280 min lasting anaerobe metabolism in the subcutaneous tissue
and increases immediate pressure pain thresholds in some areas.
© 2014 Elsevier Ltd. All rights reserved.

∗ Corresponding author at: Center for Complementary Medicine, Department of Environmental Health Sciences, University Medical Center

Freiburg, Breisacher Str. 115 B, 79106 Freiburg, Germany. Tel.: +49 761 270 82010; fax: +49 761 270 83230.
E-mail address: roman.huber@uniklinik-freiburg.de (R. Huber).

0965-2299/$ — see front matter © 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ctim.2013.12.013
Pain thresholds in neck pain patients
Introduction
Cupping is part of Arabian, Chinese and European tradi-
tional medicine systems and is used for many different
indications.1 The principle is a sucking method. The cupping
glass is applied to the skin, mostly to parts of the back of
the patient. Because of the vacuum, the skin is sucked into
the cupping glass, becomes red and warm, and shows, when
the vacuum is strong, signs of sub- and/or intracutaneous
bleeding (petechiae). Furthermore, moisture is sucked out
of the skin and, in case of wet-cupping, blood is collected
in the cupping glass.
Within western complementary medicine cupping is
mainly used to treat pain and we focused, therefore, on
this indication and on dry cupping. Regarding pain cupping
has been efficacious in controlled clinical studies for treat-
ment of neck pain,2—4 nocturnal brachialgia,5 osteoarthritis6
and rheumatoid arthritis.7 A recent review of 7 randomized
controlled studies found cupping to be promising for pain
treatment.8
The mode of action of cupping to reduce pain is, how-
ever, unclear. Different hypotheses have been reported.
‘‘Metabolic’’ hypothesis assume, that cupping decreases an
increased muscle activity which results in pain reduction
(1). The hypothesis is based on the fact, that neck pain
patients have been demonstrated in some studies to have
an increased muscle activity9—11 and an impaired blood flow
compared to healthy controls and in comparison between
the painful and not painful side of the neck.11,12 Muscle
tone and blood flow are inversely correlated in erector
spinae muscles.13 Cupping results in visible redness of the
skin of the treated area, local vasodilatation and has been
reported to improve microcirculation14 which might improve
these conditions. Also the glucose metabolism seems to
be disturbed in painful muscles of the neck because intra-
muscular lactate and pyruvate levels have been different
to neck muscles of healthy controls.11,15 Glucose metabo-
lites have not yet been investigated before during and
after cupping. In this study we therefore investigated the
local concentration of glucose metabolites in the area of
cupping.
‘‘Neuronal’’ hypothesis assume that cupping influences
chronic pain by altering the signal processing at the level of
the nociceptor, the spinal cord and also the brain.16,17 It is
expected that the activation of nociceptors by cupping and
other naturopathic reflex therapies can stimulate A␦ and C-
fibers with involvement of the spino-thalamo-cortical pain
pathway. Because the peripheral nociceptor is sensitized
by metabolic factors like lactate, adenosine triphosphate,
cytokines and others,18 metabolic and neuronal hypothe-
sis are linked together. Secondary aim of our study was
to study pain thresholds during cupping simultaneously to
metabolic changes. A further hypothesis explains clinical
effects through placebo mechanisms.
In a previous study we investigated the factors affecting
the main physical principle of cupping, namely the nega-
tive pressure in the cupping glass (volume, opening area of
the cupping glass, mode of creating the negative pressure,
experience of the caregiver) in order to standardize it.19
In the present study we wanted to test different hypothe-
ses by investigating local tissue metabolism at the site of
149
cupping and pain thresholds with established methods. To
detect potential disease related changes of pain thresholds
and local tissue metabolism the study was performed in
healthy volunteers and neck pain patients.
Patients and methods
Study design
Individually controlled, randomized, explorative monocen-
ter study.
Healthy volunteers and patients
6 healthy volunteers and 6 otherwise healthy patients with
chronic neck pain (male and female, age 18—50 years for
both groups) were recruited by public notice in the Univer-
sity Medical Center Freiburg. Chronic functional neck pain
had to persist since at least 12 weeks with an intensity of at
least 3 points on a rating scale from 0 (no pain) to 10 points
(maximum possible pain) at screening. Exclusion criteria for
neck pain patients were an organic cause (e.g. osteoporosis,
disk protrusion with neurological abnormalities) of the neck
pain, excluded by clinical examination and history. Exclusion
criteria for both groups were any acute or chronic disease
with the exception of allergies, skin disease on the back,
heat urticaria, treatment with anticoagulants, history of
bleeding disorders, history of alcohol or drug abuse, insuf-
ficient ability to understand German, pregnancy or breast
feeding or participation in another study throughout the
last three months. All participants gave their written con-
sent before inclusion in the study. Healthy volunteers and
patients received a compensation of 100 — Euro for partic-
ipation in the study. The study was approved by the ethical
committee of University Medical Center Freiburg, Germany.
Interventions
Algometry: Mechanical pain thresholds were measured with
an algometer (Somedics, Hörby, Sweden) in N/cm2 accord-
ing to the standardized protocol of Rolke.20,21 Briefly, on a
1 cm2 area of the left hand, left leg and on the left and
right lower back measurements were performed at base-
line (before cupping), immediately after cupping and 140
and 280 min after cupping. Each measurement comprised 3
measures. In each measure pressure with the algometer was
increased by 50 kPa/s until the subject/patient signalized
pain by pressing a button. Mechanical pain thresholds were
measured in N/cm2 . The mean of the respective three val-
ues was taken for further analysis. Because algometry could
have interfered with the microdialysis measures it was not
performed in the neck area but on the lower back.
Microdialysis: Microdialysis is an established method to
measure e.g. metabolic parameters in human tissues. It is
based on the principle of dialysis. A microfilament (CMA AB
Solna, Sweden), which contains the semipermeable mem-
brane, was inserted in the subcutaneous tissue on both sides
(right and left) of the subjects/patients neck with the help
of a spliceable CMA 63 microdialysis catheter under ster-
ile conditions. The length of the membrane was 30 mm, the
150
diameter was 0.9 mm, the molecular cutoff was 20.000 Da.
The respective tips of the microfilament were placed above
the trapezius muscle. The contralateral microfilament was
placed symmetrically and had the same distance to the
spine and the upper edge of the scapula. The distance
from the tip of the catheter to the surface of the skin was
measured by ultrasound (see below). The microfilaments
were connected with a CMA 106 syringe which contained
the CMA perfusion solution and inserted in a CMA 107
microdialysis pump. Flow rate of the pump was 0.5 ␮l/min.
The dialysate was collected in CMA microvials. 10 ␮l was
obtained each 20 min. After a run in phase of 40 min the
first dialysate was rejected. Then, until the end of the
study, after 420 min, every 20 min the microvials with the
dialysate were changed. The dialysate was kept frozen at
−20 ◦ C for further analysis. 5 probes from each side of the
neck, taken during 100 min, served as baseline measures.
100 min for baseline were chosen, because we have seen in
pre-study experiments that more than 60 min were needed
to reach steady state conditions. The dialysate obtained
during cupping was rejected because of the irregular flow
during this period. After cupping, microdialysis was con-
tinued for another 280 min (14 measures). 420 min after
implantation the microdialysis filament was removed and
the subjects/patients were allowed to go home.
Cupping: 140 min after implantation of the microdialy-
sis system on the right and left side above the trapezius
muscle, cupping was performed for 15 min above one of the
randomly selected sides in healthy volunteers or, in neck
pain patients, above the side with the predominant pain.
In addition, cupping was performed for 15 min on the con-
tralateral side of the lower back for the investigation of
pain thresholds. Cupping was always performed by the same,
experienced investigator. The volume of the cupping glass
was 168 ml, the opening area 15.7 cm2 . The cupping glass
was provided with a stopcock which could be connected
to a pressure gauge (GDH 200-12 Vakuummeter, Greisinger
Electronics, Germany) in order to measure the pressure in
the cupping glass. The negative pressure was obtained by
holding the flame of an alcohol soaked swab for 2 s in the
opening of the cupping glass and then immediately pressing
the cupping glass onto the skin.
Fig. 1 shows the areas of cupping, microdialysis and
algometry.
Outcome parameters
As parameters for microdialysis pyruvate, lactate, glucose,
glycerin and adenosine were selected. Pyruvate (88.06 Da)
is an intermediate of aerobe and anaerobe glycolysis and a
marker of degradation of carbohydrates. Lactate (90.08 Da)
results from non-oxidative metabolism of pyruvate. An iso-
lated increase of lactate can be caused by hypoxia or just an
increased metabolism. To discriminate these two reasons,
the lactate/pyruvate ratio is used. An increase of lactate
and the lactate/pyruvate ratio is proving hypoxia, because
cells reduce pyruvate to lactate during hypoxia.22 The lac-
tate/pyruvate ratio is, furthermore, established to estimate
the tissue oxygen supply in microdialysis studies.23 Glycerin
(92.1 Da) is an indicator of lipolytic activity in the subcuta-
neous tissue.24 It results from hydrolysis of triacylglycerides
M. Emerich et al.
and free fatty acids. Lipolysis is among others regulated
by the sympathetic nerve system (release of epinephrine)
and, therefore, can indicate changes of this system. Glu-
cose (180.06 Da) in the microdialysate is a marker of the
energy supply of the cell. From the rest of the re-frozen
dialysate, the nucleotide adenosine was analyzed, because
of its potential role for treating chronic pain.25
Analysis of the microdialysis parameters was performed
with a CMA 600 analyzer, measuring 20 probes in one session.
It is based on measuring photometric absorption after enzy-
matic degradation. The detection threshold is 0.1 mmol/l
for glucose and lactate and 0.01 mmol/l for glycerin and
pyruvate. Adenosin was analyzed post hoc from the rest of
the probes. Because of the low quantities baseline probes
1—3 and 4—5 as well as two post-cupping probes, respec-
tively, were pooled.
Ultrasound (Logiq P5, GE Medical Systems, 7.5 MHz
probe) was used to determine the depth of the catheter tip
in the tissue. It was measured in millimeter distance from
the surface of the skin. Furthermore, ultrasound was used
in a single subject to measure the thickness of the subcuta-
neous tissue before and after cupping.
The 6 neck pain patients rated the severity of their
neck pain with the standardized neck pain and disability
scale (NPDS) in the morning of the day when the investi-
gations were performed and one week later. The NPDS is a
20-item questionnaire that was specifically developed for
patients with neck pain and has been proven to be sen-
sitive, reliable and valid for measuring neck pain.26,27 It
distinguishes 6 grades of severity: 0—22 points = no to min-
imal, 23—40 points = mild, 41—57 points = moderate, 58—74
points = moderate to severe, 75—92 points = severe, 93—100
points = extremely severe.
All subjects/patients were contacted by telephone the
day after the investigation and were asked about side
effects. Neck pain patients additionally were contacted one
week after the experiment to fill in the NPDS.
Randomization and blinding
In healthy subjects the side of the trapezius muscle (right or
left) to be cupped was selected by unstratified randomiza-
tion according to a randomization list. Randomization was
concealed (drawing of a sealed opaque envelope). Neck pain
patients were asked to mark the most painful area on their
neck and this area was chosen for cupping.
Planning of sample size and statistics
For sample size calculations we assumed the mean differ-
ence of one of the microdialysis parameters between the
cupped and the control body side to be 1.0 standard devi-
ation, irrespective whether healthy or neck pain patients
were studied. If so n = 12 are needed to detect this effect
with a one-sample t-test and a statistical power of ß = 90%.28
Courses of outcome parameters were analyzed by gen-
eralized linear models for repeated measurements.29 These
models included patient identification, time, and status of
patient (healthy or diseased) as independent factors and
assumed the within subject correlation to be autoregres-
sive of first order. Treatment effects were estimated via
Pain thresholds in neck pain patients 151

Figure 1 Sites of interventions and measurements on the back. (A) On each side (left and right) of the neck microdialysis filaments
(dotted line) were inserted. Above one randomly selected side cupping (circle) was performed. (B) Area on the lower back where
pain thresholds were measured (dot). Cupping was performed on the contralateral side (dot with circle).

general estimation equations (GEE) by adequate two-sided
t-tests. Appropriate outcome parameters of microdialysis
were correlated with the intervention. For each parameter
p-values were multiply adjusted by the Bonferoni—Holm30
procedure.
Results
All 12 subjects and patients finished the study per protocol.
Except for the typical petechiae no side effects from cup-
ping or the microdialysis at the end of the experiment or
at follow up one day later were reported. Characteristics of
the participants are shown in Table 1. There were no differ-
ences between the groups regarding age, body mass index
(BMI), negative pressure in the cupping glass and depth of
the catheter in the tissue.
Single values of microdialysis parameters had to be
excluded from analysis because of pump dysfunction or
trapped air in the CME analyzer. The NPDS was reduced from
33.2 ± 13.5 before cupping to 27.7 ± 11.4 one week later.
The difference was not statistically significant.
Changes observed irrespective of groups
Algometry: The course of the pain thresholds after cupping
was heterogeneous. Analyzing the whole collective, no sig-
nificant changes in comparison to baseline could be found
(data not shown)
Microdialysis: Fig. 2 gives an overview of the course of
pyruvate, lactate, glucose and glycerin in the cupping area
of the whole collective in comparison to baseline. It shows
a strong increase of lactate about four standard deviations
with a plateau after 200 min which is accompanied by an
increase of pyruvate at half strength. Glycerin falls about
two standard deviations and slowly returns. Glucose shows
a short rise and falls back to normal. Table 2 shows the
mean differences between the area of cupping and the con-
trol area for pyruvate, lactate and glycerin and the results
of the GEE-ANCOVA analysis. For glucose, except at a sin-
gle time point 60 min after cupping (increase 0.6 mmol in
the cupping area, p = 0.002 adjusted to Bonferoni—Holm) no
significant changes and no time periods with a trend could
be found. Lactate significantly and consistently increased
also in comparison to the control area, with a maximum
152 M. Emerich et al.

Table 1 Characteristics of the study participants.

Healthy volunteers Neck pain patients Whole collective

N 6 6 12
Age (years) 24.7 ± 1.0 25.2 ± 1.3 24.9 ± 1.2
BMI kg/m2 21.6 ± 3.0 22.2 ± 1.7 21.9 ± 2.4
Gender (female/male) 4/2 4/2 8/4
Negative pressure in the cupping glass (hPa) 315 ± 64 283 ± 54 299 ± 59
Depth of the catheter in the tissue (mm)
Side of cupping 0.54 ± 0.11 0.53 ± 0.14 0.53 ± 0.12
Control side 0.53 ± 0.10 0.57 ± 0.07 0.55 ± 0.08
Pyruvate (␮mol/l) mean baseline
Side of cupping 86 ± 57 82 ± 27 84 ± 42
Control side 126 ± 50 95 ± 50 111 ± 50
Lactate (mmol/l) mean baseline
Side of cupping 0.8 ± 0.4 0.9 ± 0.3 0.9 ± 0.3
Control side 1.3 ± 0.8 1.6 ± 0.9 1.4 ± 0.8
Glycerin (␮mol/l) mean baseline
Side of cupping 131 ± 118 115 ± 42 123 ± 85
Control side 180 ± 137 92 ± 33 136 ± 106
Glucose (mmol/l) mean baseline
Side of cupping 2.9 ± 1.3 2.2 ± 0.6 2.6 ± 1.1
Control side 2.5 ± 0.8 3.0 ± 0.7 2.7 ± 0.8

220 min after cupping. 280 min after cupping values had not
returned to the level of the control area. Pyruvate slightly
and less consistently increased in comparison to the control
area, with a maximum 140 min after cupping. It returned to
the level of the control area after about 240 min. Only two
(after 140 and 180 min, see Table 2) adjusted p-values but
the most non adjusted p-values were significantly different
between 80 and 220 min after cupping (80 min, p = 0.041,
100 min, p = 0.033, 120 min, p = 0.121, 140 min, p < 0.001,
160 min, p = 0.127, 180 min, p = 0.003, 200 min, p = 0.040,
220 min, p = 0.049, all others p > 0.1). Glycerin showed an
initial strongly significant decrease 40—80 min after cupping
compared to the control side. As a trend levels remained
below the control side until the end of the experiment.

Figure 2 Time course of lactate, pyruvate, glucose and glycerin (changes in standard deviations and smoothed curves) of 6 healthy
volunteers and 6 neck pain patients (n = 12) after cupping. Baseline is taken from the first five probes before cupping at t = 0. After
replacing outliers by medians the individual signals are averaged to the mean. Thick lines are local polynomial fits.
 Pain thresholds in neck pain patients
Table 2 Differences between cupping area and control area for pyruvate, lactate and glycerin-levels in subcutaneous tissue. Positive values indicate an increase in the cupping
area. Mean changes, interval of confidence and p-values adjusted to Bonferoni—Holm are presented.

Time after Pyruvate (␮mol/l) Lactate (mmol/l) Glycerin (␮mol/l)

baseline (min)
Mean difference and p-Value Mean difference and p-Value Mean difference and p-Value
interval of confidence interval of confidence interval of confidence

20 16 (-5 to 37) 0.970 0.1 (-0.1 to 0.3) 1.000 −10 (-28 to 8) 0.319
40 6(-13 to 25) 0.970 0.0 (-0.3 to 0.3) 1.000 −51.6 (-84 to -19) 0.023
60 8 (-8 to 24) 0.970 0.3 (0.0—0.6) 0.235 −72 (-114 to -30) 0.009
80 25 (1—49) 0.436 0.6 (0.1—1.0) 0.068 −46 (-72 to -21) 0.005
100 18 (1—34) 0.396 0.0 (-0.6 to 0.6) 1.000 −50 (-85 to -14) 0.067
120 26 (-7 to 58) 0.970 0.5 (-0.2 to 1.2) 0.700 −42 (-93 to 9) 0.319
140 30 (13—47) 0.007 0.5 (0.1—0.9) 0.080 −37 (-71 to -3) 0.126
160 17 (-5 to 40) 0.970 0.7 (0.3—1.0) 0.003 −42 (-76 to -7) 0.113
180 27 (9—44) 0.036 0.7 (0.1—1.3) 0.180 −40 (-73 to -7) 0.113
200 27 (1—52) 0.436 0.9 (0.3—1.5) 0.026 −47 (-83 to -10) 0.113
220 34 (0—68) 0.437 1.4 (0.7—2.0) 0.001 −37 (-64 to -10) 0.079
240 19 (-7 to 45) 0.970 1.1 (0.5—1.6) 0.001 −38 (-68 to -8) 0.113
260 18 (-13 to 50) 0.970 1.2 (0.6—1.9) 0.003 −38 (-68 to -8) 0.113
280 29 (-9 to 66) 0.970 1.2 (0.4—2.0) 0.044 −23 (-52 to 5) 0.319

153
154
30
25
lactate/pyruvat ratiio
20
15
10
0
-100 -80 -60
Figure 3 Lactate/pyruvate ratio of medians of area of cupping and control side (n = 12).
The lactate/pyruvate ratio increased in the area of cupping
(Fig. 3). Adenosin did not significantly change during the
course of the study. There were no differences compared
to baseline or between the area of cupping and the con-
trol side (data not shown). Maximum lactate concentrations
correlated to the extent of the vacuum in the cupping glass
(r = 0.81, p = 0.049) in healthy subjects. On the control side
no correlation was found. Glycerin levels were, as a trend,
negatively correlated to the extent of the vacuum in the
cupping glass (r = −0.41, p = 0.180).
Ultrasound: Cupping resulted in an edema of the subcu-
taneous tissue, which was documented by ultrasound in one
subject. The thickness of the subcutaneous tissue increased
from about 5 mm before to 9 mm immediately after cup-
ping. 130 min after cupping it was 7.5 mm, 13 h later it was
reduced to 5.6 mm (Fig. 4A—D).
Comparison between healthy controls and neck
pain patients
Algometry: Baseline and course of the mechanical pain
thresholds after cupping are shown in Table 3. In all tested
areas healthy subjects had at baseline higher pain thresh-
olds than neck pain patients. The difference was, however,
not statistically significant (p > 0.05). Immediately after cup-
ping pain thresholds tended to increase in all tested areas
of neck pain patients (Table 3). A significant increase was
found on the foot (p = 0.019 adjusted to Bonferoni—Holm).
Healthy volunteers had only in the control area higher pain
thresholds in comparison to baseline (p = 0.02 adjusted to
Bonferoni—Holm). 140 min after cupping the pain thresh-
old on the foot in neck pain patients was lower than
before cupping (p = 0.019 adjusted to Bonferoni—Holm). Sig-
nificant differences between healthy subjects and neck
pain patients could be found on the foot immedi-
ately after cupping (p = 0.01 adjusted to Bonferoni—Holm,
Table 3).
Microdialysis: Comparing healthy volunteers and neck
pain patients baseline mean values for pyruvate, lactate,
glucose and glycerin were not different (p > 0.1). The course
M. Emerich et al.
control side
cupping
-40 -20 20 40 60 80 100 120 140 160 180 200 220 240 260 280
minutes
of the differences between the area of cupping and the con-
trol area separated for healthy volunteers and neck pain
patients are shown in Fig. 5A—D. For pyruvate and lac-
tate there were no significant cupping induced differences
between healthy volunteers and neck pain patients after
adjustment for multiple testing. Glycerin levels increased
on the control side in healthy volunteers after cupping
(Fig. 5C). Except 100 min after cupping (p = 0.031) the
differences were, however, not significant when adjusted
for multiple testing. Also for glucose differences between
healthy volunteers and neck pain patients could be found
(Fig. 5D). Healthy volunteers had non-significantly lower
values in the control area and non-significantly higher val-
ues in the cupping area without changes over time (data
not shown). This accumulated to in part (after 100, 180
and 220 min, adjusted p = 0.012, 0.015 and 0.001, respec-
tively) significantly higher differences between control area
and area of cupping in healthy volunteers. Neck pain
patients had a slightly higher and earlier increase of the
lactate/pyruvate ratio after cupping, compared to healthy
volunteers (Fig. 6). The adenosin concentration did not show
a group difference between neck pain patients and healthy
volunteers.
Baseline mean lactate values tended in neck pain
patients to correlate with the depth of the microdialysis
system under the skin (r = 0.68 and r = 0.67 in the area of
cupping and control side, respectively). In healthy subjects,
there was no correlation (r = 0.14 and 0.00, respectively).
Discussion
In our study we investigated effects of cupping on mechani-
cal pain thresholds and subcutaneous metabolic parameters
in order to test hypothesis about the mode of action of
cupping. For measuring metabolic parameters we chose
an individually controlled parallel design, comparing the
cupped and un-cupped side.
We found, that cupping significantly and long lasting
increases lactate levels in the subcutaneous tissue. The
increased lactate/pyruvate ratio proofs that the lactate
Pain thresholds in neck pain patients 155

Figure 4 (A—D) Thickness of the subcutaneous tissue above the trapezius muscle measured by ultrasound before and after cupping
with a negative pressure of 200 hPa. (A) Before cupping (0.47 cm), (B) immediately after cupping (0.89 cm), (C) 130 min after cupping
(0.75 cm) and (D) 18 h after cupping (0.56 cm).

resulted from hypoxia. The source of lactate can be from
the subcutaneous tissue itself, destroyed erythrocytes or the
underlying muscle, which is connected by blood flow with
the subcutaneous tissue.31
A mathematical model assuming similar conditions (diam-
eter of the cupping glass 5 cm, pressure −300 hPa, thickness
of the subcutaneous tissue 1 cm) as in our study showed,
that the pressure on the underlying muscle is still between
−250 hPa (upper part) and −180 hPa (lower part, about
3 cm from the skin), corresponding to 187.5 and 135 mmHg,
respectively.32 This means, that the blood flow in nor-
motensive subjects (systolic arterial pressure 120 mmHg) is
even in the underlying muscle completely suppressed during
cupping. Muscle tissue has, according to several microdial-
ysis studies33—35 at rest 2—3.5 times higher lactate levels
than subcutaneous tissue. The subcutaneous tissue itself
has only limited capacity to produce lactate. A recent C13 -
labeled-glucose based microdialysis study showed that only
about 25% of subcutaneous tissue lactate originates from
the subcutaneous tissue itself, the rest comes via blood
flow or diffusion from the muscle below.36 This indicates
that lactate originated in our study to a major part from
outside the subcutaneous tissue, namely from the underly-
ing trapezius muscle and/or from destroyed erythrocytes.

Table 3 Mechanical pain thresholds measured at different sites. Means and standard deviations of the group of healthy
volunteers and the group of neck pain patients (each n = 6) are presented.

Baseline (N/cm2 ) Immediately after 140 min after 280 min after cupping
cupping (N/cm2 ) cupping (N/cm2 ) (N/cm2 )

Healthy volunteers
Area of cupping (lower back) 332 ± 158 333 ± 181 321 ± 125 351 ± 179
Control area (lower back) 331 ± 180 370 ± 204* 315 ± 156 372 ± 208
Hand 185 ± 23 169 ± 37 188 ± 14 200 ± 27
Foot 317 ± 104 311 ± 96 326 ± 117 291 ± 68
Neck pain patients
Area of cupping (lower back) 280 ± 93 302 ± 55 308 ± 63 293 ± 80
Control area (lower back) 288 ± 109 300 ± 130 317 ± 88 304 ± 95
Hand 168 ± 41 185 ± 61 161 ± 53 180 ± 61
Foot 252 ± 74 283 ± 87* 234 ± 78* 259 ± 102
* p adjusted to Bonferoni—Holm <0.05 compared to baseline.
156 M. Emerich et al.

A 3,5 B
3
Healthy
Healthy

Lactate side difference mmol/l

Pyruvate side difference μmol/l

2,5 Neck pain 100,00
Neck pain
2
1,5 50,00
1
0,5 0,00

0
-0,5 -50,00

-1
-1,5 -100,00
-100 -50 0 50 100 150 200 250 300 -100 -50 0 50 100 150 200 250 300
Time aer cupping [min]
Time aer cupping [min]

C 150
D 3
100

Glucose side difeerence μmol/l

Glycerine side difference mmol/l

2 Healthy Neck pain

50
0 1

-50
0
-100
-150 -1

-200
Healthy -2
-250
Neck pain
-3
-300
-100 -50 0 50 100 150 200 250 300
-100 -50 0 50 100 150 200 250 300
Time aer cupping [min]
Time aer cupping [min]

Figure 5 (A—D) Means and standard deviation of subcutaneous lactate (A), pyruvate (B), glycerin (C) and glucose (D) in neck
pain patients (n = 6) and healthy controls (n = 6) before and up to 280 min after cupping. Side differences between cupping area and
control area (contralateral side of the neck) are presented. Higher values mean an increase compared to the control area.

The baseline lactate levels in our study are comparable to to exhaustion and is protective against potassium induced
other microdialysis studies in subcutaneous tissue reporting depression of muscle contraction during exercise.40,41 Fur-
0.8—1.8 mmol/l.36—38 thermore, moderate acute local metabolic acidosis results in
Lactate results, as well as hypoxia/hyperkapnia per local vasodilatation and increased blood flow42—45 by direct
se, in local acidosis.39 Lactate and acidosis have for a pH effects42 and augmenting nitric oxide release in vitro and
long time been regarded as responsible for organ damage. in vivo.46,47 Neck pain patients tend to have a decreased
Better controlled studies since the 1990s showed, how- blood flow and elevated muscle lactate levels in the trapez-
ever, that acidosis in skeleton muscle can prolong time ius muscle compared to healthy controls.11,12,48 Cupping

35
healthy
30 neck pain patients
lactate/pyruvat ratiio

25

20

15

10

0
-100 -80 -60 -40 -20 20 40 60 80 100 120 140 160 180 200 220 240 260 280
minutes

Figure 6 Lactate/pyruvate ratio of medians of neck pain patients and healthy controls in the area of cupping (n = 6).
Pain thresholds in neck pain patients
per se aggravates these features. After cupping, however,
vasodilatation can be observed and improved microcircu-
lation has been reported.13 This might, after a few days,
result in a reset to normal of the chronically disturbed inter-
play between nerval afferences, efferences and local tissue
metabolism in neck pain patients. Future studies should
directly measure muscle blood flow and muscle activity
before and after cupping.
In a controlled study3 a single cupping treatment resulted
in significantly less pain compared to controls 3 days later.
In our study NPDS scores decreased only slightly one week
after cupping. Our neck pain patients had no elevated tissue
lactate or pyruvate levels compared to healthy volunteers.
These differences to other studies may be explained by the
only mild symptoms and relatively short duration (mean 19
months) of our neck pain patients. The lactate/pyruvate
ratio, however, increased slightly more and earlier com-
pared to healthy controls (Table 1 and Fig. 5).
The decrease of glycerin in our investigation can be
explained by anti-lipolytic effects of acidosis. Acidosis
reduces the norepinephrine induced lipolysis.49 Further-
more, the subcutaneous edema (Fig. 3) might have
contributed to the decrease of glycerin. Glycerin release
of muscle tissue is only 20—25% of subcutaneous tissue.50 If
the edema fluid comes from the muscle it results in dilution
and decreased glycerin levels in the subcutaneous tissue.
Neuronal hypotheses assume, that cupping modulates
functional pain processing in neck pain patients. Indeed,
neck pain patients had in another pilot study lower mechan-
ical pain thresholds compared to controls.51 Corresponding,
our neck pain patients, had as a trend, lower baseline pain
thresholds than healthy controls. Up to now an effect of
cupping on pain thresholds has not been clearly demon-
strated. In two studies2,3 mechanical pain thresholds were
after cupping significantly higher than in waiting list controls
but no increase of pain thresholds compared to baseline was
reported. In our patients, initially after cupping pain thresh-
olds were at least in part significantly increased (Table 3).
This might be explained by counter irritation. 280 min later,
however, neither in the area of cupping nor in the control
area relevant changes compared to baseline or compared to
healthy controls could be found. A limitation is that we could
not measure the local cupping effect on the neck, because
this might have interfered with the microdialysis measures.
Taken together, short term increases of mechanical pain
thresholds have been for the first time demonstrated after
cupping. They last, however, for less than 280 min and are,
therefore, not related to the metabolic changes measured
by microdialysis.
Conclusions
Cupping induces >280 min lasting anaerobe metabolism in
the subcutaneous tissue and increases immediate pressure
pain thresholds in some areas.
Conflict of interests
The authors have no direct or indirect financial or personal
relation with the commercial identities mentioned in this
publication.
157
Role of the funding source
The study was financed without external funding.
References
1. Abele J. Das Schröpfen-Eine bewährte alternative Heilmeth-
ode. München: Urban & Fischer; 2003.
2. Lauche R, Cramer H, Choi KE, Rampp T, Saha FJ, Dobos GJ,
et al. The influence of a series of five dry cupping treatments
on pain and mechanical thresholds in patients with chronic non-
specific neck pain — a randomised controlled pilot study. BMC
Complement Altern Med 2011;11:63.
3. Lauche R, Cramer H, Hohmann C, Choi KE, Rampp T, Saha FJ,
et al. The effect of traditional cupping on pain and mechani-
cal thresholds in patients with chronic nonspecific neck pain:
a randomised controlled pilot study. Evid Based Complement
Alternat Med 2012;2012:429718.
4. Kim TH, Kang JW, Kim KH, Lee M, Kim JE, Kim JH, et al. Cup-
ping for treating neck pain in video display terminal (VDT)
users: a randomized controlled pilot trial. J Occup Health
2013;54(6):416—26.
5. Lüdtke R, Albrecht U, Stange R, Uehleke B. Brachialgia
paraesthetica nocturna can be relieved by wet cupping —
results of a randomised pilot study. Complement Ther Med
2006;14(4):247—53.
6. Teut M, Kaiser S, Ortiz M, Roll S, Binting S, Willich SN,
et al. Pulsatile dry cupping in patients with osteoarthri-
tis of the knee — a randomized controlled exploratory
trial. BMC Complement Altern Med 2012;12(October):184,
http://dx.doi.org/10.1186/1472-6882-12-184.
7. Ahmed SM, Madbouly NH, Maklad SS, Abu-Shady EA.
Immunomodulatory effects of blood letting cupping ther-
apy in patients with rheumatoid arthritis. Egypt J Immunol
2005;12(2):39—51.
8. Kim JI, Lee MS, Lee DH, Boddy K, Ernst E. Cupping for treat-
ing pain: a systematic review. Evid Based Complement Alternat
Med 2011;2011:467014.
9. Juul-Kristensen B, Clausen B, Ris I, Jensen RV, Steffensen RF,
Chreiteh SS, et al. Increased neck muscle activity and impaired
balance among females with whiplash-related chronic neck
pain: a cross-sectional study. J Rehabil Med 2013;45(4):376—84.
10. Park KN, Kwon OY, Ha SM, Kim SJ, Choi HJ, Weon JH. Comparison
of electromyographic activity and range of neck motion in violin
students with and without neck pain during playing. Med Probl
Perform Art 2012;27(4):188—92.
11. Sjøgaard G, Rosendal L, Kristiansen J, Blangsted AK, Skotte J,
Larsson B, et al. Muscle oxygenation and glycolysis in females
with trapezius myalgia during stress and repetitive work using
microdialysis and NIRS. Eur J Appl Physiol 2010;108(4):657—69.
12. Larsson R, Oberg PA, Larsson SE. Changes of trapezius muscle
blood flow and electromyography in chronic neck pain due to
trapezius myalgia. Pain 1999;79(1):45—50.
13. Masuda T, Miyamoto K, Shimizu K. Intramuscular hemodynamics
in bilateral erector spinae muscles in symmetrical and asymmet-
rical postures with and without loading. Clin Biomech (Bristol,
Avon) 2006;21(3):245—53.
14. Cui S, Cui J. Progress of researches on the mechanism of cupping
therapy. Zhen Ci Yan Jiu 2012;37(6):506—10.
15. Gerdle B, Lemming D, Kristiansen J, Larsson B, Peolsson M,
Rosendal L. Biochemical alterations in the trapezius muscle of
patients with chronic whiplash associated disorders (WAD) — a
microdialysis study. Eur J Pain 2008;12(1):82—93.
16. Musial F, Michalsen A, Dobos G. Functional chronic pain
syndromes and naturopathic treatments: neurobiological foun-
dations. Forsch Komplementmed 2008;15(2):97—103.
158
17. Musial F, Spohn D, Rolke R. Naturopathic reflex therapies for the
treatment of chronic back and neck pain. Part 1. Neurobiologi-
cal foundations. Forsch Komplementmed 2013;20(3):219—24.
18. Staud R. Peripheral pain mechanisms in chronic widespread
pain. Best Pract Res Clin Rheumatol 2011;25(2):155—64.
19. Huber R, Emerich M, Braeunig M. Cupping — is it reproducible?
Experiments about factors determining the vacuum. Comple-
ment Ther Med 2011;19(2):78—83.
20. Rolke R, Magerl W, Campbell KA, Schalber C, Caspari S, Birklein
F, et al. Quantitative sensory testing: a comprehensive protocol
for clinical trials. Eur J Pain 2006;10(1):77—88.
21. Rolke R, Baron R, Maier C, Tölle TR, Treede RD, Beyer A, et al.
Quantitative sensory testing in the German Research Network on
Neuropathic Pain (DFNS): standardized protocol and reference
values. Pain 2006;123(3):231—43.
22. Harken AH. Lactic acidosis. Surg Gynecol Obstet
1976;142(4):593—606.
23. Jansson K, Ungerstedt J, Jonsson T, Redler B, Andersson
M, Ungerstedt U, et al. Human intraperitoneal micro-
dialysis: increased lactate/pyruvate ratio suggests early
visceral ischaemia. A pilot study. Scand J Gastroenterol
2003;38(9):1007—11.
24. Dodt C, Lönnroth P, Wellhöner JP, Fehm HL, Elam M. Sympa-
thetic control of white adipose tissue in lean and obese humans.
Acta Physiol Scand 2003;177(3):351—7.
25. Zylka MJ. Pain-relieving prospects for adenosine receptors and
ectonucleotidases. Trends Mol Med 2011;17(4):188—96.
26. Goolkasian P, Wheeler AH, Gretz SS. The neck pain and disability
scale: test-retest reliability and construct validity. Clin J Pain
2002;18(4):245—50.
27. Blozik E, Kochen MM, Herrmann-Lingen C, Scherer M. Develop-
ment of a short version of the neck pain and disability scale.
Eur J Pain 2010;14(8):864e1—7e.
28. Dupont WD, Plummer WD. Power and sample size calcula-
tions for studies involving linear regression. Control Clin Trials
1998;19(6):589—601.
29. Diggle P, Liang K, Zeger S. Analysis of Longitudinal Data. Oxford:
Clarendon Press; 1994.
30. Holm S. A simple sequentially rejective multiple test procedure.
Scand J Stat 1979;6(2):65—70.
31. Cariou JL. 1984—1994: ten years of skin flaps. Improvements
and conceptual developments. Development of vascular con-
cepts, classification and clinical concepts. Ann Chir Plast Esthet
1995;40(5):447—525.
32. Tham LM, Lee HP, Lu C. Cupping: from a biomechanical perspec-
tive. J Biomech 2006;39(12):2183—93.
33. Hagström-Toft E, Enoksson S, Moberg E, Bolinder J, Arner P.
Absolute concentrations of glycerol and lactate in human skele-
tal muscle, adipose tissue, and blood. Am J Physiol 1997;273(3
Pt. 1):E584—92.
34. Rosdahl H, Hamrin K, Ungerstedt U, Henriksson J. Metabolite
levels in human skeletal muscle and adipose tissue studied with
microdialysis at low perfusion flow. Am J Physiol 1998;274(5 Pt.
1):E936—45.
M. Emerich et al.
35. Qvisth V, Hagström-Toft E, Moberg E, Sjöberg S, Bolinder J. Lac-
tate release from adipose tissue and skeletal muscle in vivo:
defective insulin regulation in insulin-resistant obese women.
Am J Physiol Endocrinol Metab 2007;292(March (3)):E709—14.
36. Gustafsson J, Eriksson J, Marcus C. Glucose metabolism in
human adipose tissue studied by 13C-glucose and microdialysis.
Scand J Clin Lab Invest 2007;67(2):155—64.
37. Jansson PA, Smith U, Lönnroth P. Evidence for lactate
production by human adipose tissue in vivo. Diabetologia
1990;33(4):253—6.
38. Jansson PA, Larsson A, Smith U, Lönnroth P. Lactate release from
the subcutaneous tissue in lean and obese men. J Clin Invest
1994;93(1):240—6.
39. Das JB, Joshi ID, Philippart AI. Continuous monitoring of pH in
the tissue mode: evaluation of a miniature sensor during acido-
sis and tissue hypoperfusion. J Pediatr Surg 1983;18(6):914—21.
40. Cairns SP. Lactic acid and exercise performance: culprit or
friend? Sports Med 2006;36(4):279—91.
41. Bandschapp O, Soule CL, Iaizzo PA. Lactic acid restores skeletal
muscle force in an in vitro fatigue model: are voltage-
gated chloride channels involved? Am J Physiol Cell Physiol
2012;302(7):C1019—25.
42. Aalkjaer C, Poston L. Effects of pH on vascular tension: which
are the important mechanisms? J Vasc Res 1996;33(5):347—59.
43. Aalkjaer C, Peng HL. pH and smooth muscle. Acta Physiol Scand
1997;161(4):557—66.
44. Modin A, Björne H, Herulf M, Alving K, Weitzberg E, Lundberg
JO. Nitrite-derived nitric oxide: a possible mediator of ‘acidic-
metabolic’ vasodilation. Acta Physiol Scand 2001;171(1):9—16.
45. Wang X, Wu J, Li L, Chen F, Wang R, Jiang C. Hypercapnic acid-
osis activates KATP channels in vascular smooth muscles. Circ
Res 2003;92(11):1225—32.
46. Hattori K, Tsuchida S, Tsukahara H, Mayumi M, Tanaka T,
Zhang L, et al. Augmentation of NO-mediated vasodilation in
metabolic acidosis. Life Sci 2002;71(12):1439—47.
47. Celotto AC, Restini CB, Capellini VK, Bendhack LM, Evora
PR. Acidosis induces relaxation mediated by nitric oxide and
potassium channels in rat thoracic aorta. Eur J Pharmacol
2011;656(1-3):88—93.
48. Rosendal L, Larsson B, Kristiansen J, Peolsson M, Søgaard
K, Kjaer M, et al. Increase in muscle nociceptive sub-
stances and anaerobic metabolism in patients with trapezius
myalgia: microdialysis in rest and during exercise. Pain
2004;112(3):324—34.
49. Hjemdahl P. Inhibition of the lipolytic response to nerve stimu-
lation during acidosis. Acta Physiol Scand 1976;98(1):80—4.
50. Bolinder J, Kerckhoffs DA, Moberg E, Hagström-Toft E, Arner P.
Rates of skeletal muscle and adipose tissue glycerol release in
nonobese and obese subjects. Diabetes 2000;49(5):797—802.
51. Javanshir K, Ortega-Santiago R, Mohseni-Bandpei MA,
Miangolarra-Page JC, Fernández-de-Las-Peñas C. Exploration
of somatosensory impairments in subjects with mechanical
idiopathic neck pain: a preliminary study. J Manipulative
Physiol Ther 2010;33(7):493—9.