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Effects of 15 consecutive cryotherapy sessions on the clinical output of fibromyalgic patients

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Abstract

Fibromyalgia is a chronic widespread pain disorder 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 inflammatory 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 qualitative 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 modulation of pain.
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 1770 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) 32:13371345
DOI 10.1007/s10067-013-2280-9
imbalance in the central nervous system that leads to a central
amplificationof 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]and67 °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 1770 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, 1767 years)
1338 Clin Rheumatol (2013) 32:13371345
who underwent WBC while the second, named WBC,was
composed of 50 subjects (46 females and 4 males; age range,
1970 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 (5th95th 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 Wilcoxons 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 (76.0100.0) in the whole
population while it was 90.0 (78.5100.0) in the WBC+
group and 90.0 (75.0100.0) in the WBCgroup, 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 (44.063.0)
and 90.0 (85.0100.0), respectively, for the whole popula-
tion, 58.0 (44.063.0) and 90.0 (87.3100.0) in the WBC+
and 57.0 (48.063.0) and 90.0 (85.0100.0) 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
(15.038.0), p<0.0001, the FSS, and to 30.0 (5.060.0),
p<0.0001, the GH; the same was for the WBCgroup
(FSS: 46.0 (38.056.0), p<0.0001; GH: 80.0(55.095.0),
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) 32:13371345 1339
Table 1 Clinical features of the patients
WBC+ group WBCgroup
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) 32:13371345
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 settingand
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 WBCgroup
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) 32:13371345 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 WBCgroup. Particularly, the
perception of pain and fatigue, scored by the VAS scale,
decreased of 58 % in the WBC+ group while only
22 % in the WBCgroup. 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
functioningby 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 (17.029.0) for
WBC+ and 24.0 (20.030.0) for WBC. The item 4 group
(A to D) assign the role-physicalscore and they followed
the trend of item 3, as for items 7 (pain-magnitude) and
8 (pain-interface), grouped as bodily painscores.
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 healthitem 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) 32:13371345
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) 32:13371345 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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... Table S1 illustrates the search strings employed during the electronic search and the number of records retrieved, Table 1 summarizes the quality and level of evidence of the selected articles, Table 2 presents their characteristics and Table 3 summarizes their outcomes and results. Two articles used a non-controlled study design [31,36], three articles used a non-randomized controlled study design [33,37,38], five articles used a randomized controlled study design [32,34,35,39], and one of them used a crossover design [40]. Five studies were conducted in Germany [31,32,[36][37][38], two in Italy [33,34], and one each in India [39], Spain [40], and Belgium [35]. ...
... Two articles used a non-controlled study design [31,36], three articles used a non-randomized controlled study design [33,37,38], five articles used a randomized controlled study design [32,34,35,39], and one of them used a crossover design [40]. Five studies were conducted in Germany [31,32,[36][37][38], two in Italy [33,34], and one each in India [39], Spain [40], and Belgium [35]. ...
... As mentioned above, evaluation of the quality of conference abstracts [31,32,34,39] was not included due to the different type of format that would have influenced the evaluation. Pain intensity, condition, state, or level was evaluated in eight studies [32][33][34][35][36][37][38]40]. Four studies assessed physical and mental health [33,35,39,40] while only one assessed global health status [33]. ...
Article
Full-text available
Currently, all available therapies for the control and management of fibromyalgia (FM) are mostly focused on relieving patients’ symptoms and improving their quality of life. The purpose of this review is to provide an up-to-date overview of the evidence supporting the beneficial effects of whole-body cryostimulation (WBC) in patients with FM and evidence-based guidance on the possible adjuvant use of WBC in the treatment of FM. We searched the most recent literature by retrieving 10 eligible studies, 4 of which were abstracts only, from a total of 263 records. Thermal stress caused by cryostimulation induces an analgesic effect, improving pain, redox balance, and inflammatory symptoms in an exercise-mimicking fashion. In addition, it reduces the feeling of fatigue, improves mood, and reduces mental health deterioration with positive consequences on depressive states and improved sleep quality. Although the studies included in this review are not of sufficient quality and quantity to draw definitive conclusions about the effectiveness of WBC in FM, initial evidence indicates WBC as a promising add-on option in the multidisciplinary treatment of FM, due to its rapid action and high patients’ compliance. The application of WBC protocols has the potential to expand therapeutic options for the treatment of FM and related disorders; however, larger, high-quality primary studies are still needed.
... To date, most studies have been focused on the effect of WBC on FM, reducing pain severity [40,53], impact of the disease [40], and improving quality of life [40,53,54]. However, preliminary evidence suggests that WBC may also improve sleep quality [42,54], physical functioning [55], and reduce depressive symptoms [41]. ...
... To date, most studies have been focused on the effect of WBC on FM, reducing pain severity [40,53], impact of the disease [40], and improving quality of life [40,53,54]. However, preliminary evidence suggests that WBC may also improve sleep quality [42,54], physical functioning [55], and reduce depressive symptoms [41]. ...
Article
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Pain severity, depression, and sleep disturbances are key targets for FM rehabilitation. Recent evidence suggests that whole-body cryostimulation (WBC) might be an effective add-on treatment in the management of FM. The purpose of this study was to evaluate the effects of an add-on WBC intervention to a multidisciplinary rehabilitation program on pain intensity, depressive symptoms, disease impact, sleep quality, and performance-based physical functioning in a sample of FM patients with obesity. We performed a randomized controlled trial with 43 patients with FM and obesity undergoing a multidisciplinary rehabilitation program with and without the addition of ten 2-min WBC sessions at −110 °C over two weeks. According to our results, the implementation of ten sessions of WBC over two weeks produced additional benefits. Indeed, both groups reported positive changes after the rehabilitation; however, the group that underwent WBC intervention had greater improvements in the severity of pain, depressive symptoms, disease impact, and quality of sleep. On the contrary, with respect to performance-based physical functioning, we found no significant between-group differences. Our findings suggest that WBC could be a promising add-on treatment to improve key aspects of FM, such as pain, depressive symptoms, disease impact and poor sleep quality.
... In total ten studies met the inclusion criteria. [68][69][70][71][72][73][74][75][76][77] Not all articles provided means, SDs and correlations in their tables. Within eight months time we managed to obtain all the necessary means and SDs that were missing from the corresponding or primary authors. ...
... In three cases authors were unable to provide them. 69,75,78 All collected data can be obtained from authors upon request. Table 2 provides an overview of the potential risk of bias of the included studies per article according to the Cochrane ROBINS-I tool. ...
Article
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Objective To give an overview of the nature and methodological quality of studies on whole body cryotherapy (WBC) as add-on intervention for mental health problems. Methods A meta-analysis according to PRISMA guidelines was conducted (Prospero registration: CRD42020167443). Databases MEDLINE, PsycINFO and the Cochrane Library were searched. Risk of bias was scored according to the Cochrane ROBINS-I-tool to which an extra bias-dimension of allegiance bias was added. Within and between Hedges’ g pooled effect sizes were calculated for the main aspect of mental health measured. Treatment efficacy was examined using a random effects model. Heterogeneity was examined through identification of visual outliers and by I² statistics. Results Out of 196 articles coming up from the search, ten studies met all inclusion criteria, six of which were (randomized) controlled trials. Together these studies report on a total of 294 participants receiving WBC. The within-group pooled effect size for mental health problems is large (Hedges’ g = 1.63, CI: 1.05-2.21), with high heterogeneity (I² = 93%). Subgroup analyses on depressive symptoms and quality of life (QOL) showed a diminution of heterogeneity to moderate. Effect sizes for depressive symptoms are very large (Hedges’ g = 2.95, CI: 2.44-3.45) and for QOL medium (Hedges’ g = 0.70, CI: 0.15-1.24). The between-group pooled effect size is medium (Hedges’ g = 0.76, CI: 0.17-1.36). Conclusions Results indicate preliminary evidence for WBC as efficacious add-on intervention for mental health problems, especially depressive symptoms. Further research in the form of RCTs with larger numbers of participants is needed.
... Whole-body cryostimulation (WBC) exposes patients to cryogenic temperatures, ranging from −110 • C to −140 • C, in an environmentally controlled cabin for 2-3 min. Such stimulus induces pain and inflammatory status reduction in different conditions [15][16][17][18] and induces improvements in depression, anxiety [19], functional status and fatigue [20], and quality of sleep [21]. It is widely used as a recovery technique after physical exercise in elite athletes [22] and the positive effects of 10 serial WBC sessions on PCC patients have been reported 1 month after discontinued treatment [23]. ...
Article
Full-text available
Given the severity and prevalence of post-COVID-19 symptoms in the general population, the identification of boosters for rehabilitation programs appears to be of paramount importance. The purpose of this case series is to provide some preliminary evidence about the role of whole-body cryostimulation (WBC) as an effective adjuvant for the recovery of patients with the post-COVID-19 condition (PCC). We recruited seven patients with previously confirmed SARS-CoV-2 infection and symptoms of PCC of different severities for a comprehensive rehabilitation program, including WBC. The main symptoms were dyspnea, chronic and muscular fatigue, chronic pain, and poor sleep quality. Moreover, some patients presented high levels of hematological markers of inflammation. Because we provided a range of interventions, including nutritional and psychological support along with physical exercise and physiotherapy, we could not determine to what extent WBC may per se have accounted for the clinical and functional improvements. However, for all reported cases, it was observed that the introduction of WBC sessions represented a turning point in the patient’s subjective and objective improvements related to health and functioning.
... Whole body cryotherapy, first introduced in Japan ( Yamaguchi, 1978), involves the exposure to extremely cold dry cryogenic gas, usually liquid nitrogen, in a chamber, typically with temperatures lower than -100°C. WBC can mitigate the symptoms of musculoskeletal conditions, including ankylosing spondylitis (Stanek et al., 2005), adhesive capsulitis (Ma et al., 2013) and fibromyalgia (Bettoni et al., 2013). The majority of clinical benefits reported in such studies are associated with the anti-inflammatory effect of cryotherapy as well as its pain reduction properties. ...
Thesis
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Whilst Whole Body Cryotherapy (WBC) has become an emerging tool for sport and exercise recovery, its overall efficacy remains contentious. This thesis addressed a variety of issues concerning the practice. Firstly, the impact of single WBC interventions for treating exercise-induced muscle damage (EIMD) is unclear. Secondly, the influence of inter-individual factors on WBC outcomes post-exercise remains an under-investigated area. Therefore the first main study explored the effects of age and body fat content on responses to WBC following downhill running, a commonly utilised eccentric exercise model for inducing muscle damage. WBC participants underwent cryotherapy (3 minutes, −120°C) one hour post- downhill run and control (CON) participants passively recovered (20°C). Despite the presence of EIMD, WBC significantly blunted (p=0.04) the decrease in muscle torque 24 hours after the downhill run. This response was significantly influenced by age, with young participants (<40 years) retaining their muscle strength more than older participants (≥45 years). WBC may therefore attenuate EIMD and benefit muscle strength recovery following eccentrically biased exercise, particularly for young males. A subsequent downhill run study investigated the influence of WBC timing post-exercise, a factor that could clarify optimal treatment usage. An additional objective was to compare the effects of WBC with cold water immersions (CWI) since the verdict regarding which cold modality is superior for recovery remains an on-going area of controversy. It was revealed that WBC 4 hours post-exercise was ineffective in treating EIMD markers, so applying WBC within one hour after exercise may be preferable to delaying by several hours. However, WBC was no more effective than CWI, meaning that the cost vs. reward implications of WBC treatments would need further reviewing. Finally, the implications of repetitive WBC during training programmes require further evaluation due to the possibility of repetitive cold interfering with long term adaptations. The final study investigated the impact of two weekly WBC treatments on adaptations to a 6 week strength and endurance training programme. It was found that WBC participants significantly improved their muscle strength comparatively to the CON group. However WBC did not improve their jump height (p=0.23) in contrast to the CON group (p=0.01). In conclusion, repetitive WBC does not appear to blunt strength training adaptations, although there may be an interference effect in the development of explosive power.
... Accordingly, cooling therapies have widely been used in sports medicine to accelerate recovery from muscle injuries due to its anti-inflammatory and analgesic virtues. Furthermore, body cooling (whole body cryotherapy) has been integrated in rehabilitation programs to treat several inflammatory diseases such as rheumatoid arthritis [24]; fibromyalgia [25]; ankylosing spondylitis [26]; multiple sclerosis [27] and even in treating the symptoms of anxiety and depression [28]. ...
Article
The sleep apnea syndrome (SAS) is a sleep related-breathing disorder with several features such a systemic inflammation, oxidative stress, a cognitive impairment and a poor sleep quality. Patients with SAS present an increased incidence of cardiovascular diseases. There is no real effective treatment that prevents and treats all of these illness symptoms. Cooling therapies are often used in sport medicine and in athletes after training and competitions to reduce inflammation, oxidative stress and to enhance sleep quality. In this short article, we hypothesize that the use of cooling therapies (whole body cryotherapy, cold-water immersion...) could be an efficient strategy to facilitate the treatment of SAS’ patients by reducing the level of systemic inflammation and oxidative stress and enhancing sleep quality.
... Les thérapies par le froid, locales et systémiques, sont largement utilisées pour soulager les symptômes de plusieurs maladies, et plus particulièrement les maladies inflammatoires chroniques, l'inflammation, la douleur, les spasmes musculaires, les oedèmes, les blessures et le syndrome de surentraînement [4,5] . ...
Technical Report
Full-text available
La Cryothérapie Corps Entier (CCE) et la Cryothérapie Corps Partiel (CCP) – regroupées sous le terme de Cryostimulation – sont de nouvelles techniques consistant à exposer le corps entier (tête exclue pour la CCP) à un froid extrême pendant une courte période (typiquement 3 minutes à -110 °C). Après exposition, les patients font état de certains bienfaits dont une diminution des douleurs, des gonflements au niveau des articulations et du niveau d’inflammation, accompagnée d’une relaxation musculo-squelettique et d’une augmentation de l’amplitude des mouvements. La cryostimulation est également efficace pour soulager les symptômes d’anxiété et de dépression ainsi que pour accélérer la récupération musculaire des athlètes. Toutefois, des preuves scientifiques solides de ces bénéfices restent à apporter. Une intensification des travaux de recherche est nécessaire pour identifier les variables clés induisant les bénéfices de la cryostimulation et pour définir et adapter les protocoles de soin (fréquence et paramètres d’exposition notamment). De plus, les questions de sécurité liées à l’utilisation de la cryostimulation sont essentielles, en particulier la prise en compte des contre-indications médicales et des risques physiques comme l’anoxie. Cela passe aussi par la certification des opérateurs et des dispositifs cryogéniques utilisés. https://iifiir.org/fr/fridoc/la-cryotherapie-corps-entier-cryostimulation-39-lt-sup-gt-e-lt-sup-gt-note-142805
Article
Study design Single arm, quasi-experimental study design. Background To describe the effects of whole-body cryotherapy on pain, disability, and serum inflammatory markers in patients with chronic low back pain. Methods A quasi-experimental trial was performed on adult patients between 18 and 65 years with chronic low back pain. After obtaining informed consent, participants underwent 20 sessions of whole-body cryotherapy (at −160 °C) during a 5-week time span. Patient reported pain and disability measures (Pain Numerical Rating Scale [PNRS], Oswestry Disability Index [OSI], and Roland Morris Questionnaire [RMQ]) were obtained at each of the twenty sessions. Blood samples were obtained to analyze serum inflammatory markers at baseline, 10th and 20th session. Results Forty-one participants were included in the study. A significant decrease was observed between the initial and final PNRS, ODI, and RMQ scores (p < 0.001). A significant reduction in the PNRS was found after 4 sessions of whole-body cryotherapy (p < 0.001). We observed decreasing values of pro-inflammatory serum marker IL-2 (p = 0.046) and a significant increase in the anti-inflammatory serum marker IL-10 (p = 0.003). No adverse events were reported during the study. Conclusions Whole-body cryotherapy is an effective therapy for pain and disability treatment in chronic low back pain. It also produces changes in serum markers of inflammation, decreasing pro-inflammatory markers and increasing anti-inflammatory markers.
Article
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Athletes, military personnel, fire fighters, mountaineers and astronauts may be required to perform in environmental extremes (e.g. heat, cold, high altitude and microgravity). Exercising in hot versus thermoneutral conditions (where core temperature is ≥1°C higher in hot conditions) augments circulating stress hormones, catecholamines and cytokines with associated increases in circulating leukocytes. Studies that have clamped the rise in core temperature during exercise (by exercising in cool water) demonstrate a large contribution of the rise in core temperature in the leukocytosis and cytokinaemia of exercise. However, with the exception of lowered stimulated lymphocyte responses after exercise in the heat, and in exertional heat illness patients (core temperature >40°C), recent laboratory studies show a limited effect of exercise in the heat on neutrophil function, monocyte function, natural killer cell activity and mucosal immunity. Therefore, most of the available evidence does not support the contention that exercising in the heat poses a greater threat to immune function (vs thermoneutral conditions). From a critical standpoint, due to ethical committee restrictions, most laboratory studies have evoked modest core temperature responses (<39°C). Given that core temperature during exercise in the field often exceeds levels associated with fever and hyperthermia (>39.5°C) field studies may provide an opportunity to determine the effects of severe heat stress on immunity. Field studies may also provide insight into the possible involvement of immune modulation in the aetiology of exertional heat stroke (core temperature >40.6°C) and identify the effects of acclimatisation on neuroendocrine and immune responses to exercise-heat stress. Laboratory studies can provide useful information by, for example, applying the thermal clamp model to examine the involvement of the rise in core temperature in the functional immune modifications associated with prolonged exercise. Studies investigating the effects of cold, high altitude and microgravity on immunity and infection incidence are often hindered by extraneous stressors (e.g. isolation). Nevertheless, the available evidence does not support the popular belief that short- or long-term cold exposure, with or without exercise, suppresses immunity and increases infection incidence. In fact, controlled laboratory studies indicate immuno-stimulatory effects of cold exposure. Although some evidence shows that ascent to high altitude increases infection incidence, clear conclusions are difficult to make because of some overlap with the symptoms of acute mountain sickness. Studies have reported suppressed cell-mediated immunity in mountaineers at high altitude and in astronauts after re-entering the normal gravity environment; however, the impact of this finding on resistance to infection remains unclear.
Article
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Purpose. To validate our hypothesis that a bisphosphonate (BP) having a nitrogen-containing heterocyclic ring on the side chain, and with no hydroxyl on the geminal carbon would possess increased activity, and better oral bioavailability due to enhanced solubility of its calcium complexes/salts and weaker Ca chelating properties. Methods. A novel BP, 2-(2-aminopyrimidinio)ethylidene-l,l-bisphosphonic acid betaine (ISA-13-1) was synthesized. The physicochemical properties and permeability were studied in vitro. The effects on macrophages, bone resorption (young growing rat model), and tumor-induced osteolysis (Walker carcinosarcoma) were studied in comparison to clinically used BPs. Results. The solubility of the Ca salt of ISA-13-1 was higher, and the log Ca: BP stability constant and the affinity to hydroxyapatite were lower than those of alendronate and pamidronate. ISA-13-1 exhibited effects similar to those of alendronate on bone volume, on bone osteolysis, and on macrophages, following delivery by liposomes. ISA-13-1 was shown to have 1.5–1.7 times better oral absorption than the other BPs with no deleterious effects on the tight junctions of intestinal tissue. Conclusions. The similar potency to clinically used BPs, the increased oral absorption as well as the lack of effect on tissue tight junction of ISA-13-1 warrant its further consideration as a potential drug for bone diseases.
Article
Full-text available
Fibromyalgia is a disorder characterized by chronic widespread pain in the presence of widespread tenderness, and multiple somatic symptoms. Since the publication of the American College of Rheumatology (ACR) 1990 classification criteria for fibromyalgia, research has proliferated and, in a relatively short period, investigators have begun to unravel the etiology and long-term impact of this complex condition. Although the ACR 1990 criteria have been central to fibromyalgia research during the past two decades, a number of practical and philosophical objections have been raised in relation to them. Principally these objections have centered on the use (or lack thereof) of the tender point examination, the lack of consideration of associated symptoms, and the observation that fibromyalgia might represent the extreme end of a pain continuum. In developing the ACR 2010 criteria, experts have sought to address these issues and to simplify clinical diagnosis. An implicit aim was to facilitate more rigorous study of etiology. The purpose of this Review is to summarize research to date that has described the epidemiology, pathology and clinical course of fibromyalgia, and to assess the probable impact of the ACR 2010 criteria on future research efforts.
Article
The analgesic effects of natural, thermoindifferent H2S full baths (20.4 mg H2S/l, 20 min) and cryochamber therapy (-67 C, 1-3 min) were compared with a shorn test without application in 17 patients with identified fibromyalgia syndromes (ACR criteria). Parameters measured were tenderness, heat pain and cryalgesia thresholds (pressure algometry, Peltier thermode) as well as actual pain intensity and general well-being (VAS). The pain thresholds were determined by comparing both forearms with one not being bathed or exposed to coldness. Following the natural sulphur bath, pain sensitivity was significantly or even very significantly increased in all qualities tested. Analogous effects were also observed after cryochamber therapy with a significantly slighter rise of the heat-pain threshold (p<0.05). The analgesic effects of the sulphurated bath could be demonstrated on the not bathed extremity as well, whereas they did not occur on the isolated arm in the cryochamber. After both applications, actual pain intensity and general well being were improved with high significance (- 12 to - 32%). Altogether it can be stated that both natural sulphur baths and cryochamber expositions are analgesically effective in fibromyalgia, the sulphur baths apparently acting systematically, the cryochamber mainly topically.
Article
In a cold air chamber with pre- and main chamber patients are treated in bathing suits with covered ears, hands, feet and an operation mask for 1/2 min up to 3 min at -110°C. Therapeutic effects are lowering of pain, improvement of joint function, as well as improvement of well being. Heartbeat and blood pressure will be influenced only very little in persons with normal RR. Admittance to the cold air chamber is possible when hypertension is well under control. Bronchospasm will decrease. Stenocardia was not observed. The cold air chamber treatment does not provoke stress. Neither ACTH nor cortisone or adrenalin increase after treatment. They rather decrease. The noradrenalin level is on the other hand increasing in serum. In rheumatoid arthritis T-helper lymphocytes decrease over more than 3 hours, while T-suppressor lymphocytes increase during that period. Indications for the whole body cryotherapy are chronic joint inflammation and chronic inflammation of the cervical spine, fibrositis and fibromyositis, connective tissue diseases and autoimmune diseases.
Article
Die analgetischen Wirkungen von natürlichen thermoindifferenten H2S-Vollbädern (20,4 mg H2S/I, 20 min) und Kältekammerexpositionen (-67°C, 1-3 min) wurden bei 17 Patienten mit nachgewiesenem Fibromyalgie-Syndrom (ACR-Kriterien) vergleichend zu einem Leerversuch ohne Anwendung geprüft, Meßparameter waren Druck-, Hitze- und Kälteschmerzschwellen (Pressure-Algometrie, Peltier-Thermode) sowie aktuelle Schmerzintensität und allgemeines Wohlbefinden (VAS). Die Schmerzschwellen wurden jeweils am Unterarm im Seitenvergleich bestimmt, wobei ein Arm nicht gebadet bzw. der Kälte ausgesetzt wurde. Nach dem Schwefelbad war die Schmerzempfindlichkeit in allen geprüften Qualitäten signifikant bzw. hochsignifikant angehoben. Analoge Wirkungen zeigten sich auch nach Kältekammertherapie, wobei die Anhebung der Hitzeschmerzschwelle signifkant schwächer war (p<0.05). Die analgetischen Effekte des Schwefelbades waren auch an der nichtgebadeten Extremität nachweisbar, während sie am kälteisolierten Arm in der Kältekammer nicht auftraten. Die aktuelle Schmerzintensität und das allgemeine Wohlbefinden wurden nach beiden Anwendungen hochsignifikant verbessert (-12 bis -32%). Insgesamt kann festgestellt werden, daß sowohl natürliche Schwefelbäder als auch die Kältekammerexposition bei Fibromyalgie analgetisch wirksam sind, wobei die Schwefelbäder offenbar systemisch, die Kältekammer überwiegend lokal wirken.
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Fibromyalgia is a chronic widespread pain disorder commonly associated with comorbid symptoms, including fatigue and nonrestorative sleep. As in the management of other chronic medical disorders, the approach for fibromyalgia management follows core principles of comprehensive assessment, education, goal setting, multimodal treatment including pharmacological (eg, pregabalin, duloxetine, milnacipran) and nonpharmacological therapies (eg, physical activity, behavioral therapy, sleep hygiene, education), and regular education and monitoring of treatment response and progress. Based on these core management principles, this review presents a framework for primary care providers through which they can develop a patient-centered treatment program for patients with fibromyalgia. This proactive and systematic treatment approach encourages ongoing education and patient self-management and is designed for use in the primary care setting.
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Cytokines are soluble proteins secreted mainly by immune cells and are key players in the induction and maintenance of pain. Pro-inflammatory cytokines are mostly algesic, while anti-inflammatory cytokines have analgesic properties. After the role of cytokines was shown in diverse animal models of pain, interest arose in the systemic and local regulation of cytokines in human pain states. Most clinical studies give evidence for an imbalance between pro- and anti-inflammatory cytokines in neuropathic and other pain states with pronounced pro-inflammatory cytokine profiles. Anti-cytokine treatment gives encouraging preliminary results and supports the notion of a crucial role of cytokines also in human pain states. Further research is needed for a better understanding of the mechanisms linking altered cytokine profiles to the sensation of pain.
Article
Cryotherapy is commonly used as a procedure to relieve pain symptoms, particularly in inflammatory diseases, injuries and overuse symptoms. A peculiar form of cold therapy or stimulation was proposed 30 years ago for the treatment of rheumatic diseases. The therapy consists in the exposure to very cold air in special cryochambers. The air is maintained at temperatures between -110 and -160°C. The treatment was named whole-body cryotherapy (WBC). It consists in a brief exposure to extreme cold in a temperature-controlled chamber. It 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. The aim of this study was to investigate the effects of different treatment of WBC on blood pressure (BP) and heart rate (HR) parameters in adult subjects characterized from non-pathological values of BP. Eighty subjects (36 females, 44 males, age range 19-80 years) submitted to 4-17 WBC applications for a total of 816 treatments were recruited. Immediately before and after each WBC application systolic and diastolic BP and HR were measured and recorded. We did not find significant differences in BP and HR (p > 0.05). WBC seems to be safe with respect to unwanted BP and HR alterations for adult patients. An individual monitoring of subjects is recommended over the treatment, but pathological changes of circulatory parameters can be considered rare and occasional.