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ORIGINAL ARTICLE
Effects of 15 consecutive cryotherapy sessions on the clinical
output of fibromyalgic patients
Lorenzo Bettoni &Felice Giulio Bonomi &Viviana Zani &
Luigia Manisco &Annamaria Indelicato &
Patrizia Lanteri &Giuseppe Banfi &Giovanni Lombardi
Received: 31 October 2012 /Revised: 26 March 2013 / Accepted: 19 April 2013 / Published online: 2 May 2013
#Clinical Rheumatology 2013
Abstract Fibromyalgia is a chronic widespread pain disor-
der in which, the neurogenic origin of the pain, featured by
allodynia and hyperalgesia, results from an imbalance in the
levels of neurotransmitters and consequently of the peripheral
pro- and anti-inflammatory mediators. Whole body cryotherapy
is a peculiar physical therapy known to relieve pain and inflam-
matory symptoms characteristics of rheumatic diseases, through
the regulation of the cytokine expression. The aim of this study
was to qualitatively evaluate the effects of cryotherapy on the
clinical output of fibromyalgic patients. A total of 100
fibromyalgic patients (age range 17–70 years) were observed;
50 subjects were addressed to cryotherapy, while the second
group (n=50) did not underwent to the cryotherapic treatment.
All subjects kept the prescribed pharmacological therapy during
the study (analgesic and antioxidants). The referred health status
pre- and post-observation was evaluated with the following
scales: Visual Analogue Scale, Short Form-36, Global Health
Status and Fatigue Severity Scale. Fibromyalgic patients treated
with cryotherapy reported a more pronounced improvement of
the quality of life, in comparison with the non-cryo treated
fibromyalgic subjects, as indicated by the scores of the qualita-
tive indexes and sub-indexes, that are widely recognized tools to
assess the overall health status and the effect of the treatments.
We speculate that this improvement is due to the known direct
effect of cryotherapy on the balance between pro- and anti-
inflammatory mediators having a recognized role in the modu-
lation of pain.
Keywords Fibromyalgia .Pain .Quality of life .Whole
body cryotherapy
Introduction
Fibromyalgia (FM) is a chronic widespread pain disorder
estimated to affect 0.5 to 5 % of adult Western populations
[1]. It is a persistent and debilitating condition with poten-
tially devastating effect on people's quality of life, limiting
their daily activities and, thus, imposing large economic
burdens on society [2].
In 2010, the American College of Rheumatology (ACR)
adopted new clinical criteria for diagnosing FM, based on a
widespread pain index and a symptom severity scale and
improved the previously used tender point examination [3,4].
The most important symptom of FM is represented by the
chronic widespread pain, and recent researches showed its
neurogenic origin; moreover, neuroimaging studies showed
that FM is associated with aberrant processing of painful
stimuli in the central nervous system [5]. Indeed it has been
postulated that the pain sense is the result of a neurochemical
L. Bettoni :L. Manisco
Reumatologia/CT, Ospedale di Manerbio,
A.O Desenzano del Garda, Italy
F. G. Bonomi
Dipartimento Cardio-vascolare, U.O. Cardiologia,
Humanitas Gavazzeni, Bergamo, Italy
F. G. Bonomi :V. Zani
Centro di Crioterapia Sistemica, Poliambulatorio Bongi,
Orzinuovi, Italy
A. Indelicato
Direzione Sanitaria, A.O Desenzano del Garda, Italy
P. Lanteri :G. Banfi :G. Lombardi (*)
Laboratory of Experimental Biochemistry and Molecular Biology,
I.R.C.C.S. Istituto Ortopedico Galeazzi, Via R. Galeazzi, 4,
20161, Milan, Italy
e-mail: giovanni.lombardi@grupposandonato.it
G. Banfi
Dipartimento di Scienze Biomediche per la Salute,
Università degli Studi di Milano, Milan, Italy
Clin Rheumatol (2013) 32:1337–1345
DOI 10.1007/s10067-013-2280-9
imbalance in the central nervous system that leads to a “central
amplification”of pain perception, with consequent allodynia
(heightened sensitivity to stimuli that are not normally painful)
and hyperalgesia (increased response to painful stimuli) [2]. At
the molecular level, this imbalance is due to a relative change in
the level of neurotransmitters and their receptors leading to a
hyperactivation of the ascending (pro-nociceptive) pathways
and, consequently, a depression of the descending (anti-
nociceptive) pathways [6]. In FM patients have been found
high cerebrospinal fluid levels of neurotrophins, i.e. nerve
growth factor, and tachykinins, i.e. substance P, which are
known to enhance the sensitivity of nociceptors and are also
involved in the inflammatory regulation [7]. Consequently,
high levels of the pro-inflammatory cytokines interleukin
(IL)-6, IL-8 and those of the anti-inflammatory IL-1ra, have
been found in the peripheral blood and skin of FM patients [8].
Particularly, IL-8 activates the sympathetic branch of the
nervous system and it increases nociceptive sensitivity [9].
Studies on pain showed that FM patients complain pain
at a lower threshold than healthy controls in response to
pressure (dolorimetry) on some body area [2,10].
Cold-based therapies are commonly used for relieving
pain symptoms, particularly in case of inflammatory dis-
eases, injuries and overuse symptoms, and in these two
latter cases, mainly in the field of sports medicine [11]. A
peculiar form of cold therapy or stimulation, namely whole
body cryotherapy (WBC), was proposed 30 years ago for
the treatment of rheumatic diseases: it consists of a brief
exposure (2 to 3 min) to very cold air (−110 to −160 °C) in
special temperature-controlled cryochambers, preceded by a
30-s-long preconditioning at −60 °C [11,12].
Into the chamber, subjects are minimally dressed by
wearing shorts (bathing suit), socks, clogs or shoes,
surgical mask, gloves, and a hat (or headband) covering
the auricles to avoid frostbite and they are invited to
move their fingers while walking and avoid holding
their breath [11].
The treatment is applied to relieve pain and inflammatory
symptoms caused by numerous disorders, particularly those
associated with rheumatic conditions, and it is recommended
for the treatment of arthritis, fibromyalgia and ankylosing
spondylitis. WBC has been shown to be not deleterious nei-
ther to lung function [13] nor to circulatory function [14].
Despite the wealth of literature on rehabilitation techniques,
published data on WBC in physiology or rehabilitation
programmes are very poor.
Conventional pharmacological treatments for FM are
based to chronic or cyclical assumption of anti-inflammatory
drugs to relieve symptoms associated with neuromodulatory
agents (i.e. tertiary amine tricyclics) acting at the central
nervous system level by diminishing the nociceptive signal-
ling [15]. Parallel, non-pharmacological treatment, mainly
based on the association of physical activity and cognitive-
behavioural therapy have garnered good evidence of effec-
tiveness in relieving pain symptoms [16].
Cold exposure has an immunostimulating effect due to
the enhanced noradrenaline response to cold which is de-
pendent on the relationship between core temperature de-
crease and duration of exposure. Limited are, instead, the
evidences of immunosuppression from short- or long-term
cold exposure [17]. WBC seems to act on the paracrine
signalling rather than on systemic immune functions. In fact,
WBC treatment is associated with an increase in the anti-
inflammatory cytokine IL-10, and a decrease in the pro-
inflammatory cytokines IL-2 and IL-8, supported by the
decrease in intercellular adhesion molecule 1 (ICAM-1).
The observation of a parallel decrease in prostaglandin E2,
synthesized at sites of inflammation where it induces vaso-
dilation and the increase of vascular permeability, confirmed
the anti-inflammatory protection [18]. Lubkowska and col-
leagues demonstrated that following ten consecutive WBC
sessions increases in leukocytes number, IL-6 levels, total
oxidative and antioxidative status occurred, indicating that
cryotherapy increases immunity [19]. More recently, the
same group confirmed the finding on IL-6 and on the
positive anti-inflammatory effects of WBC [20].
To our knowledge, there are very few works analysing
the possible beneficial effects of WBC treatment on FM. In
a 12-year-old review, Offenbächer and G. Stucki [21]
reported the results of two studies in which, besides the
different temperatures used, −150 °C [22]and−67 °C
[23], the cold therapy ameliorate symptoms better than
hot-based therapies. However, some considerations need to
be taken into account about these studies: the optimal dura-
tion of the treatment (number of exposures) and temperature
of exposure.
According to this background, with this study, we aimed
to evaluate the eventual beneficial effects of a cycle of
exposure to cryotherapy in a group of FM patients on a
series of qualitative parameters indexes of morbidity and of
quality of life.
Material and methods
Subjects and treatment protocol
The subjects involved in this study were submitted to the
treatment as specifically prescribed by their physician.
The study population was composed of 100 consecutive
subjects (94 females and 6 males), age range 17–70 years;
all patients had a primary diagnosis of FM (in agreement
with the ACR 2010 criteria[3,4]). Two homogeneous
groups were constituted based on the medical prescription
to WBC or not: the first, named WBC+, was composed of
50 subjects (46 females and 4 males; age range, 17–67 years)
1338 Clin Rheumatol (2013) 32:1337–1345
who underwent WBC while the second, named WBC−,was
composed of 50 subjects (46 females and 4 males; age range,
19–70 years) who did not underwent to the WBC treatment.
The WBC treatment protocol consisted of 15 sessions
consecutive sessions of WBC, as prescribed, performed in a
period of time of 3 weeks. The cryochamber functioning
was based on a heat exchanger cooling the air (previously
dehumidified) by using liquid nitrogen. Every single session
consisted of a preconditioning of 30 s at −60 °C and a 3-
min-long exposure at −140 °C. During the exposure, the
subjects were minimal clothed and to avoid frostbite they
wore shorts (bathing suit), socks, clogs or shoes, surgical
mask, gloves, and hat (or headband) covering the auricles.
Any sweat was dried before entering the cryochamber,
where the air was clear and dry. While in the cryochambers,
subjects were asked to walk within the chamber, to maintain
the fingers in motion and to avoid breath holding. The system
was automatically controlled, and security personnel was
always present. Each treatment was compulsorily followed
by 30 min of aerobic exercise (cycloergometer or treadmill).
During the study, all subjects were allowed to continue
the treatments (pharmacologic and/or antioxidants) they
were subjected to, before the observation.
The clinical features of the two groups of patients and the
WBC treatment protocol are summarized in Table 1.
Qualitative indexes
The following qualitative indexes were used to evaluate the
clinical output of the patients.
Visual Analogue Scale (VAS) is a well recognized tool
measuring the chronic pain intensity [24], visually representing
the amplitude of pain that the subject believed to warn.
A qualitative score of physical and mental health of FM
patients, at recruitment and following or not to WBC, was
obtained with the Short Form (SF)-36 (Medical Outcomes
Trust, Boston, MA), Italian version 1.6, a multipurpose,
short-form health survey composed of 36 questions, yield-
ing an eight-scale profile of scores on the quality of life [25].
Global Health Status (GH) is a self-assessment of the
healthy status based on a visual analogue score (0 = best,
100=worst) used to calculate the “Disease Activity Score”
for various rheumatic diseases [26].
The Fatigue Severity Scale (FSS) [27] is addressed to
evaluate, through 9 items and 7 levels of agreement, phys-
ical, social, or cognitive effects of fatigue (e.g., function,
work, motivation).
Statistical analysis
Statistical analysis was performed by GraphPad Prism v5.0
software (GraphPad Software Inc., La Jolla, CA, USA).
Normally distributed values, in the descriptive analysis, are
expressed as the mean ± SD while not parametric values are
described by median and range (5th–95th percentile). Nor-
mal distribution of values were assayed by Kolmogorov–
Smirnov normality test. The within-group comparisons (pre-
treatment vs. post-treatment) and between-groups compari-
sons (WBC treated vs. not treated for both time-points) were
performed by two-tailed paired ttest for normally distribut-
ed values, while Wilcoxon’s matched pairs test was used for
not-normally distributed values.
The significance level was set at 0.05.
Results
First of all, the two groups (WBC+ and WBC−) were not
significant different for mean age. The median VAS score at
the start of the study was 90.0 (76.0–100.0) in the whole
population while it was 90.0 (78.5–100.0) in the WBC+
group and 90.0 (75.0–100.0) in the WBC−group, without
evidencing any difference (p=0.086). At the second time-
point both group showed a decrease in VAS (p<0.0001).
The decrease was significantly greater in WBC+ than in
WBC−(p<0.0001).
The median FSS and GH scores were 57.5 (44.0–63.0)
and 90.0 (85.0–100.0), respectively, for the whole popula-
tion, 58.0 (44.0–63.0) and 90.0 (87.3–100.0) in the WBC+
and 57.0 (48.0–63.0) and 90.0 (85.0–100.0) in the WBC−,
without any difference between the two groups (p= 0.757
and p=0.630). Following the treatment, in the WBC+
group, both scores recorded significant decreases, to 27.0
(15.0–38.0), p<0.0001, the FSS, and to 30.0 (5.0–60.0),
p<0.0001, the GH; the same was for the WBC−group
(FSS: 46.0 (38.0–56.0), p<0.0001; GH: 80.0(55.0–95.0),
p<0.0001). However, the decreases in the WBC+ were
significantly greater (p<0.0001 for both scores). The
trends in VAS, FSS and GH scores are summarized in
Fig. 1.
The SF-36 score kept the same tendency toward improve-
ment for almost all the items: a substantial homogeneity
between the two groups at recruitment, an improvement in
the scores, for both groups, at the second time-point, a better
improvement in the WBC+ group observed after the treat-
ment. A summary of the trends in the SF-36 items is
reported in Fig. 2.
Discussion
Physiologically, the perception of pain involves two groups
of neural pathways. the ascending pathways through, the
peripheral nerves, transmit sensory signals, including noci-
ceptive signals, to the spinal and, thus, to the brain for
processing. Nociceptive signals are emitted by nociceptors,
Clin Rheumatol (2013) 32:1337–1345 1339
Table 1 Clinical features of the patients
WBC+ group WBC−group
ID Age Gender Diagnosis Secondary diagnosis ID Age Gender Diagnosis Secondary diagnosis
1 43 F FM Pollinosis, disc hernia 1 49 M FM Arthrosis, cephalgia
2 45 F FM / 2 33 F FM /
3 55 F FM Arthrosis, diabetes, hypertrophic arthritis
arterial hypertension
3 56 F FM Arthrosis, hypothyroidism
4 33 M FM Spondyloarthropathy, disc hernia 4 46 F FM Hypothyroidism
5 49 F FM Arthrosis, osteoporosis 5 53 F FM Hypothyroidism
6 50 F FM CFS 6 58 F FM CFS
7 52 F FM Sicca syndrome, lactose intolerance 7 32 F FM CFS
8 44 F FM Arthrosis, hypothyroidism 8 66 F FM Hypothyroidism, arthrosis
9 42 F FM Hypothyroidism 9 56 F FM /
10 58 F FM Arthrosis, cephalgia 10 45 F FM /
11 30 F FM Cephalgia 11 52 F FM Arthrosis
12 53 F FM Hypothyroidism 12 19 F FM Hypothyroidism
13 61 F FM MCS, spondyloarthropathy 13 45 F FM Spondyloarthropathy
14 28 F FM / 14 33 M FM Seronegative oligoarthritis
15 17 F FM / 15 26 F FM /
16 49 F FM Lactose intolerance, discopathy 16 30 F FM /
17 32 F FM / 17 56 F FM Radiculopathy
18 36 F FM / 18 56 F FM /
19 60 F FM GER, seronegative oligoarthritis 19 45 M FM Arterial hypertension hypertrophic
arthritis
20 57 F FM Diabetes, CFS, arterial hypertension
hypertrophic arthritis
20 38 F FM /
21 34 M FM / 21 62 F FM Arterial hypertension hypertrophic
arthritis
22 21 F FM Seronegative oligoarthritis 22 23 F FM /
23 57 F FM / 23 49 F FM Arthrosis
24 67 F FM Osteoporosis, nasal polyposis 24 70 F FM Discopathy
25 52 F FM Undifferentiated connectivities 25 59 F FM Arterial hypertension hypertrophic
arthritis, osteoporosis
26 58 M FM Arthrosis, chronic gastropathy 26 24 F FM /
27 52 F FM Arterial hypertension hypertrophic arthritis 27 26 F FM /
28 37 F FM Bronchial asthma 28 32 F FM CFS
29 64 F FM Arterial hypertension hypertrophic arthritis 29 35 F FM Arterial hypertension hypertrophic
arthritis
30 18 F FM / 30 45 F FM /
31 35 F FM / 31 44 F FM Diabetes
32 60 F FM / 32 41 F FM /
33 40 F FM / 33 43 F FM /
34 39 F FM / 34 49 F FM Arthrosis
35 42 F FM CFS 35 48 F FM Hypothyroidism, arthrosis
36 37 M FM / 36 50 F FM Diabetes
37 58 F FM Arterial hypertension hypertrophic arthritis 37 54 F FM /
38 41 F FM / 38 56 F FM /
39 49 F FM / 39 48 F FM Hypertrophic arthritis
40 53 F FM Hypothyroidism, arterial hypertension
hypertrophic arthritis
40 47 F FM MCS
41 54 F FM / 41 45 F FM /
42 56 F FM / 42 32 M FM Celiac disease
43 46 F FM Hypothyroidism 43 46 F FM /
1340 Clin Rheumatol (2013) 32:1337–1345
specialized receptors in the peripheral nerves, are acti-
vated by physical stimuli (i.e., changes in temperature,
pressure, impact). Descending pathways send modulato-
ry signals (facilitatory and/or inhibitory) from the brain
throughout the spinal cord to the periphery, tuning the
ascending nociceptive signals reaching the brain. A
number of neurotransmitters and neurochemicals are
involved in these signal transmission (e.g., norepineph-
rine, serotonin) [28,29].
In FM, these two pathways operate abnormally, resulting
in central amplification of pain signals, a phenomenon
named central sensitization. Indeed, many studies of FM-
related pain and hyperalgesia advocated the involvement of
spinal mechanisms, accordingly to the finding of enhanced
responses to somatic and cutaneous stimuli throughout the
pain matrix of the brain, including the thalamus, in FM [30,
31]. The pathogenesis of the pain amplification process is
not fully understood but is certain to be multifactorial.
An important role is surely played by the peripheral
nociceptors, but a number of findings strongly suggested
a central nervous system involvement that is or becomes
largely independent of peripheral nociceptive input [2].
However, it is still unclear whether these are due to
facilitating mechanisms within the brain (central amplifi-
cation), spinal sensitisation maintained by the input of
tonic impulses from somatic tissues, or abnormal mech-
anisms of descending facilitation from the brain toward
periphery [9]. Central amplification is likely determined
at least partially by genetics and modified by environ-
mental influences [32].
While in general population, perception of pain displays
a normal distribution on a bell curve, in FM population it is
skewed to the right: the more one moves to the right along
this distribution, the higher the “volume control setting”and
pain intensity becomes, irrespective of peripheral nociceptive
input [2,6].
An imbalance of pro- and anti-inflammatory cyto-
kines is assumed to play a role in the induction and
maintenance of pain. IL-1, IL-6, and IL-8 are pro-
inflammatory cytokines are known to mediate induction
and maintenance of pain and also in pain syndromes
[33], whereby IL-8 promotes sympathetic pain and IL-6
induces hyperalgesia, fatigue, and depression [34].
Therefore, it is likely that FM patients, who suffer from
generalized pain, may have an innate or acquired im-
balance in cytokine production and secretion.
A recently published systematic review of the literature
revealed that, even with some uncertainness, FM patients
had higher serum levels of IL-1ra, IL-6, and IL-8, and
higher plasma levels of IL-8, compared to controls [35]. In
two recent papers, Lubkowska and colleagues demonstrated
that WBC affects the inflammatory status by inducing an
imbalance towards the anti-inflammatory side. Particularly,
consecutive sessions of cryotherapy increased IL-6 and IL-
10 levels and lowered the IL-1αlevels [19,20]. Although
IL-6 is generally considered a pro-inflammatory cytokine, it
is known to induce the expression of anti-inflammatory
mediator (i.e. IL-1ra, IL-10) [19]. Furthermore, the authors
reported an increased leukocytes count and an improved
oxidative status after WBC, indicating an overall immune
activation [19].
Based on the link between the central pain with the
imbalance between pro- and anti-inflammatory molecules
and, thus, with the general referred status of the subject,
parallel to the know anti-inflammatory effects of WBC [11],
we speculated that consecutive sessions of cryotherapy
could have a positive impact on the referred qualitatively
measured pain.
Another possible explanation of the positive effects of
WBC, on the referred pain sensation, could be attributed to
changes in the nerve conduction induced by cryogenic tem-
peratures. It has been, indeed, postulated that cold therapy
could reduce pain via an alteration in nerve conduction
velocity. In their protocol setting, Algafly and George [36],
analyzed the effects of ice bath on nerve conduction and
pain sensation in healthy sportsmen. The results indicated
Table 1 (continued)
WBC+ group WBC−group
44 50 F FM Arthrosis 44 40 F FM Diabetes
45 51 F FM Seronegative oligoarthritis 45 55 F FM /
46 47 F FM / 46 45 F FM /
47 31 F FM Seronegative oligoarthritis 47 34 F FM /
48 35 F FM / 48 45 F FM /
49 43 F FM / 49 23 F FM /
50 30 F FM / 50 47 F FM Arthrosis, hypothyroidism
FM fibromyalgia, CFS chronic fatigue syndrome, MCS multiple chemical sensitivity, GER gastro-esophageal reflux
Clin Rheumatol (2013) 32:1337–1345 1341
that the data suggest that cryotherapy can increase PTH and
PTO at the ankle and this was associated with a significant
decrease in NCV.
The SF-36 measure physical, mental and social function-
ing. It is generic health status instruments that permit com-
parisons across groups with different health conditions and
they have been widely applied in studies worldwide [37].
SF-36 can currently be considered the most confidently
recommended qualitative scale to measure physical function
in rheumatoid arthritis for most research purposes even if it
has recognized limited content coverage [38]. It is important
to understand the health status burden of people with FM.
Health status data quantify impairments in physical, mental
and social functioning.
Such information can highlight areas where people with
FM experience particular difficulty and where healthcare
providers may be able to effect change in clinical status [39].
The VAS is the simplest method for assessing pain and
fatigue and was clinically relevant in more than 76 % of
patients with FM [40].
In our study, we found, despite a certain homogeneity
between the two groups at recruitment, a more pronounced
improvement of all the scores in the groups submitted to
WBC compared to the WBC−group. Particularly, the
perception of pain and fatigue, scored by the VAS scale,
decreased of 58 % in the WBC+ group while only
22 % in the WBC−group. Reductions of the same
magnitudes were manifest for FSS and GH scores.
For what concern the SF-36 scores, the same tendency
was overall evident.
The item 3 group (A to J), giving a score for the “physical
functioning”by analysing the daily activities, was improved
in both groups with the WBC+ group showed a better
output. However, the median scores of the two groups
already differed at recruitment: 23.0 (17.0–29.0) for
WBC+ and 24.0 (20.0–30.0) for WBC−. The item 4 group
(A to D) assign the “role-physical”score and they followed
the trend of item 3, as for items 7 (pain-magnitude) and
8 (pain-interface), grouped as “bodily pain”scores.
The items 1 and 11 are intended to evaluate the “general
health”: item 1 (EVGFP scale), indicating if the patient
health is excellent, very good, good, fair, or poor, and items
11C (health to get worse) and 11B (health excellent) signif-
icantly differed between the time-points in both groups and
between the groups at the second time-point; item 11A, sick
easier, ameliorated only in the WBC+ group, after the treat-
ment, even if the two groups were not significantly different
at both time-point; item 11B, as healthy, never changed.
Items 1, 3, 4, 7, 8 and 11 are used to evaluate the overall
“physical health”; the other items are, instead, intended to
the definition of the “mental health”.
Vitality is defined by the items 9A (full of life), 9E
(energy), 9G (worn out), 9I (tired): all of them did not
differed between the groups at recruitment, were improved
at the second evaluation with a greater positive effect in the
WBC+ group. Social functioning, items 6 (social-extent)
and 10 (social-time) showed an identical trend, as well as
the item 5 group (A, B, C) analysing the “role-emotional”
and the “mental health”item 9 group (B, C, D, F, H), even if
in the case of items 9C and 9D the starting point was already
different in the two groups, in favour of the WBC+ group.
In conclusion, with this study we found a positive effects
of WBC on the quality of life of a group of FM patients as
indicated by the improvement of a number of qualitative
Fig. 1 Trends in VAS, FSS and GH scores. The figure shows the scores
differences between the two groups pre- and post-observation and the
score modification between the two observations. Asterisks indicate the
level of statistical significance (*p<0.05; **p<0.01; ***p<0.001)
1342 Clin Rheumatol (2013) 32:1337–1345
Fig. 2 Trends in the SF-36
items. The figure shows the SF-
36 scores differences between the
two groups pre- and post-
observation and the score
modification between the two
observations. Asterisks indicate
the level of statistical significance
(*p<0.05; **p<0.01;
***p<0.001)
Clin Rheumatol (2013) 32:1337–1345 1343
indexes and sub-indexes, that are widely recognized tools to
assess the overall health status and the effect of the treat-
ments. Possible mechanisms by which WBC reduces the
pain sensation and fatigue, in FM patients, could reside in
the improvement of the balance between pro- and anti-
inflammatory mediators, having a recognized role in the
modulation of pain, and in the reduction of nerve conduc-
tion velocity of nociceptive ways.
Disclosures None.
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