Curr Rheumatol Rep (2014) 16:390
DOI 10.1007/s11926-013-0390-7
CHRONIC PAIN (R STAUD, SECTION EDITOR)
Effects of Obesity on Function and Quality of Life in Chronic
Pain Conditions
Laura-Isabel Arranz & Magda Rafecas & Cayetano Alegre
Published online: 22 November 2013
# Springer Science+Business Media New York 2013
Abstract Many people throughout the world have both
chronic pain and obesity. Overweight and obese people are
more prone to a proinflammatory state manifesting as meta-
bolic syndrome but also to a higher prevalence of chronic pain
comorbidities. Obesity and a high body mass index (BMI) are
associated with impaired functional capacity and reduced
quality of life (QoL) in patients with chronic pain conditions.
Systemic inflammation is not only involved in metabolic
syndrome but it also initiates and perpetuates chronic pain.
Changes in lifestyle, behavior, physical activity, and diet have
demonstrated benefits in functional capacity and QoL; there-
fore, patient assessment should tackle high BMI and metabol-
ic syndrome as part of the treatment of chronic pain. A
healthier lifestyle would lead to a lower inflammatory state
and consequently to an improvement in function and QoL in
overweight or obese patients who have chronic pain
conditions.
Keywords Obesity . Body mass index . BMI . Body weight .
Chronic pain . Fibromyalgia . Chronic widespread pain .
Osteoarthritis . Rheumatoid arthritis . Back pain .
Quality of life . Disability . Functionality
This article is part of the Topical Collection on Chronic Pain
L.<I. Arranz (*)
Department of Nutrition and Food Science, Faculty of Pharmacy,
University of Barcelona, Joan XXIII, s/n., 08028 Barcelona, Spain
e-mail: lauraarranz@ub.edu
M. Rafecas
Department of Nutrition and Food Science, Faculty of Pharmacy,
University of Barcelona, Barcelona, Spain
e-mail: magdarafecas@ub.edu
C. Alegre
Rheumatology Unit Hospital Universitario Quirón Dexeus,
Barcelona, Spain
e-mail: reumatologia.dex@quiron.es
Introduction
Chronic pain, the sensory experience of possible injury in some
part of the body, involves the nervous system and persists for
weeks, months, or even years. Many people suffer from chronic
pain; its prevalence is 30 % in US adults and is higher in
females [1]. The most common types of chronic pain in adult
patients are low back pain (LBP), arthritis, and fibromyalgia
(FM), all of which are disabling [2]. The situation may be even
worse in people who have more than one chronic pain condi-
tion, leading to poor functional capacity and decreased quality
of life (QoL). The impact of disease on functional status and
well-being is measured with health-related QoL (HRQoL),
which has been defined as the effect of medical conditions on
well-being and physical and mental function, reflecting the
functional effects of a disease as perceived by the patient.
At the same time, obesity is an increasing global health
issue with serious repercussions due to the increased potential
for development of comorbid conditions. Obesity is defined as
body weight greater than normal as the result of an abnormal
increase in body fat storage. It is categorized using body mass
index (BMI), as shown in Table 1, although it is recommended
that other measurements, such as waist circumference and
waist-to-hip ratio, be taken into account.
Obesity classes II and III are considered severe and morbid
obesity, respectively, and generally have more health implica-
tions. The two main causes are high-energy food intake,
especially through high fat intake, and low physical activity;
however, there are associated factors such as lack of sleep,
stress, metabolic disorders, and probably chronic inflamma-
tion. The health consequences of obesity are chronic diseases
such as diabetes mellitus type 2, dyslipidemia, coronary heart
disease, osteoarthritis (OA), sleep apnea, certain types of
cancers, and psychosocial problems. Chronic pain and limita-
tions in everyday functioning of overweight and obese indi-
viduals are the cause and consequence of comorbidities due to
a mechanical impairment of the musculoskeletal system,
which is caused by excessive weight but also by an increased
390, Page 2 of 8
Table 1 International classification of adult underweight, overweight,
and obesity according to body mass index
Classification BMI (kg/m2)
Underweight <18.5
Normal range 18.5–24.9
Overweight 25–29.9
Obese class I 30–34.9
Obese class II 35–39.9
Obese class III ≥40
BMI Body mass index
(Adapted from World Health Organization data [99])
chronic inflammatory state [3••, 4]. Although it remains un-
certain whether a common cause of obesity and chronic pain
exists, some studies reflect similar or equal mechanisms or
pathophysiologic processes, with systemic chronic inflamma-
tion as a possible key issue [3••], because it has been associ-
ated with increased joint inflammation and OA [5]. Systemic
inflammation is involved even in some rheumatic disorders,
increasing bone loss and fracture risk, and it is also known that
oxidized low-density lipoprotein induces the production of
proinflammatory factors and their receptors [6]. Moreover,
this circle of chronic/acute and central/peripheral inflamma-
tion probably is related to the fact that a sedentary lifestyle
contributes to obesity and, inversely, obesity exacerbates dis-
ability and consequently a sedentary lifestyle. The role a lack
of physical activity plays in weight gain emphasizes the fact
that, among people with pain and disabling conditions, obesity
rates are significantly higher [7].
Pain and obesity both have a negative effect on the QoL and
functional capacity of people of all ages and both sexes. Pain
management is the key to obese patients becoming more active
and achieving a better QoL [8•]. Inversely, weight management
is also a key factor for patients with chronic pain conditions who
have obesity as a comorbidity. Because of the implications these
relationships have for patient management, we conducted a
review of recent literature (2000–2013) on the effects of obesity
on chronic pain, focusing on functional capacity and QoL.
Obesity and Quality of Life and Disability
Obesity is the fifth leading global risk factor for mortality [9];
it leads to an increase in morbidity and is associated with
lower HRQoL and increased disability by increasing limita-
tions on daily life activities. Obese people have fewer years of
healthy life, report more health problems than normal-weight
subjects, and have more chronic diseases that increase phys-
ical disability and reduce normal functioning. Overweight and
obese individuals report more pain on bodily pain subscales of
HRQoL measurements [4, 10, 11].
Curr Rheumatol Rep (2014) 16:390
In general, it has been shown that an increase in body
weight corresponds to deterioration in QoL scores, specifical-
ly in the physical function and general health domains, but not
in mental scores [12•]. Most studies show that higher degrees
of obesity are associated with greater impairment and that
weight reduction, even if modest, is associated with enhanced
QoL [13, 14]. Moreover, the number of comorbidities corre-
lates with the degree of obesity, which also determines a worse
HRQoL [15]. Additionally, it is important to note that this
correlation is greater in women and elderly people [16].
Obese people face other problems that affect QoL, such as
difficulties in mobility, pain, and sleep quality. Obesity is
associated with insufficient sleep or poor sleep quality, and it
appears that overweight and obese individuals who eat less
have better perceived general health [17]. However, it is
known that a chronic lack of sleep (quantitative or qualitative)
is associated with weight gain, metabolic disorders, cardio-
vascular risk, worse immune function, higher systemic in-
flammation, and even psychiatric disorders [18–23].
Effects of Obesity on QoL and Function in People
with Chronic Pain
Obesity and chronic pain are increasing morbidities that neg-
atively affect function and well-being, and both have signifi-
cant public health consequences. Excess body weight, espe-
cially obesity, contributes to chronic pain, probably as a result
of two different mechanisms. The first mechanism is mechan-
ical stress on the whole skeletal system and joints; the second
is systemic proinflammatory status worsening widespread and
local pain. Inversely, chronic pain contributes to obesity main-
ly through physical inactivity as the direct result of fear of
movement or physical disability, causing deconditioning and
increasing pain [4, 24].
Perhaps one of the most direct studies assessing the effect of
BMI on patients with chronic pain evaluated pain severity,
disability, depression, anxiety, and QoL in 372 patients receiv-
ing or seeking treatment for chronic pain.[25]. The results
showed that increased BMI was associated with comorbid pain
disability, depression, and reduced physical function as mea-
sured by the SF-36 health survey. Moreover, other researchers
have suggested that pain may mediate the relationship between
increasing BMI and HRQoL, meaning that the effects of high
BMI on HRQoL are magnified in the presence of pain, and
highlighted that a change from high to normal BMI may
improve HRQoL [26]. Another study found that, among pa-
tients with class II or III obesity, higher BMI alone was not
directly associated with lower QoL; however, the presence of
LBP in the context of obesity was significantly associated with
reduced QoL, as measured by the EuroQoL questionnaire [15].
An interesting study examined the relationship among
obesity, body composition, foot pain, and disability. The
Curr Rheumatol Rep (2014) 16:390
results demonstrated that increasing BMI, specifically android
distribution of fat mass, was strongly associated with foot pain
and disability. In contrast, a beneficial effect of a gynoid
distribution of fat was observed, suggesting that the mecha-
nism of obesity’s effect on disability might be the result of
both a mechanical effect, by increasing the load on the skeletal
system, and a systemic effect related to metabolic factors
[27•]. It is important to consider that evidence exists
regarding the beneficial effect of weight loss treatment,
with either surgical intervention or lifestyle changes such as
exercise and diet, on HRQoL in obese patients with chronic
pain [28].
While obesity and pain reduce functional capacity and
QoL, making people less physically active and more de-
pressed, this situation might lead to reduced sleep, more stress,
a sedentary lifestyle, and consequently an increased chronic
inflammation status [29, 30]. Also, obese people with chronic
pain suffer more depressive symptoms than normal-weight or
overweight people with pain [4]. They have hedonic hunger
triggered by physical pain and associated with depression and
guilt, and experience emotional or “binge” eating, as well as
altered dietary choices, in response to pain [31••]. Many
studies have emphasized the fact that obese people with
chronic pain have difficulty with physical activity because of
physical disability, reduced self-efficacy due to pain, and
avoidance of movement because of the fear of pain [31••].
Because of this pain, but also because of fear of move-
ment, morbidly obese patients avoid physical activity,
which interferes with activities of daily living and par-
ticipation in social or recreational activities. Obese patients
have been shown to engage in greater catastrophizing behav-
ior [32], and those reporting poor self-rated health and a
depressed mood might be at a higher risk for pain chronicity
[3••, 33]. These events lead to a vicious circle: obesity leads to
avoidance of activity, depression, lack of sleep, and an in-
crease in pain, which leads to fear of movement, resulting in
further avoidance of physical exercise and worsening of obe-
sity and pain.
Obesity and BMI have a negative impact on QoL in people
with chronic pain conditions [26], and this impact is especially
significant in some populations, such as African Americans,
children, and adolescents. In the case of African Americans,
because they are more prone to obesity and chronic pain, the
impact of both conditions on QoL is greater. Being
African American is indirectly associated with lower
physical function and more pain-related disability [24].
In children and adolescents, co-occurring chronic pain
and obesity significantly exacerbate the impact chronic pain
would have alone on overall QoL. Compared with adults who
have an increased BMI correlated with depression and re-
duced QoL for physical function, the impact on children and
adolescents may be more extensive, affecting physical and
psychosocial domains [34].
Page 3 of 8, 390
Fibromyalgia
FM is a common and increasingly diagnosed chronic pain
condition with an unknown cause and a prevalence of around
2–4 %, depending on the country. FM patients have wide-
spread musculoskeletal pain and stiffness, general fatigue,
sleep disorders, cognitive impairment, and other symptoms
affecting their QoL. Recent reviews reveal that multidimen-
sional treatment approaches are most preferable: medications,
physical activity, relaxation techniques, and cognitive–behav-
ioral therapy are among the most useful approaches used
today to treat FM [35, 36]. FM has an enormous impact on
QoL, limiting daily life activities. The co-occurrence of FM
and obesity is high, around 30 % and even 45 %, respectively,
and it appears obesity plays a relevant role in the pathogenesis
of FM, although this relationship is uncertain [37–42].
It has been argued that obesity contributes to the presence of
FM and increases its severity [8•]. Obesity has been associated
with greater pain sensitivity to tender point palpation, reduced
physical strength, decreased flexibility, shorter sleep duration,
and greater restlessness during sleep [41]. The direct relation-
ship among BMI, functional capacity, and QoL has been ob-
served in these patients. Lower QoL and higher pain sensitivity
have been observed in overweight and obese individuals com-
pared with those of normal weight [43]. Additionally, obese
female FM patients seem to have higher levels of anxiety and
depression and worse QoL, cardiorespiratory fitness, agility,
and flexibility than their normal-weight peers [44]. In our study
of 103 females with FM, the results suggested a decrease in SF-
36 scores for physical and social function, emotional role, and
mental health in overweight and obese patients. An additional
analysis was performed for adipose body mass and lean mass
values, which were not equally related to the different domains
of QoL, suggesting that these relationships should be studied in
more depth [42]. Similar results were found in other studies,
with lower SF-36 scores in higher BMI groups, indicating
poorer QoL in the subscales of physical function, pain index,
general health perceptions, emotional role, and physical com-
ponent, with no significant group differences in SF-36 scores in
physical role, vitality, social function, mental health index, and
mental component [45].
Importantly, weight loss may improve physical functioning
in this chronic pain disorder [37]. In a20-week intervention of
behavioral weight loss treatment, patients lost an average of
4.4 % of their initial weight and improved FM symptoms, pain
interference, body satisfaction, and QoL [46]. Depression,
sleep quality, and tender point count of obese patients with
FM also improved significantly with weight loss [47].
Exercise, regardless of type, has benefits on FM symptoms
and functional capacity; however, improvements usually are
not maintained over time [48] because of attrition and fear of
movement with avoidance of physical activity, which is fre-
quent in FM patients [49, 50]. The findings suggest that
390, Page 4 of 8
behavioral weight loss treatment and exercise would benefit
the management of overweight/obese FM patients.
Osteoarthritis
OA is the most common form of arthritis and a leading cause of
disability among older people. Clinically, it is characterized by
joint pain, tenderness, limitation of movement, and various
degrees of local inflammation. The course of the disease varies;
it is often progressive, and the condition generally is not revers-
ible. A high BMI has been shown to be a likely risk factor for
development and progression of OA of the knees, the hips, and
possibly the hands [28]. There is strong evidence for the im-
portant relationship between the onset and progression of knee
OA and BMI. Obesity is an independent risk factor for incident
radiographic OA, and patients with the highest degree of obe-
sity are at greater risk of developing both symptomatic and
radiologic knee OA. However, the mechanisms for these rela-
tionships are not completely understood, and the data seem to
suggest that increased weight initiates a pathway of cartilage
degeneration before OA symptoms emerge [51, 52]. Therefore,
a possible mechanism by which increased adipose mass is
associated with joint damage might be related to the metabolic
effects of obesity on knee OA. It has been shown that serum
leptin levels are associated with the prevalence and incidence of
knee OA in females. Women with incident knee OA during a
10-year follow-up period had consistently higher serum leptin
levels compared with women without knee OA [53]. A high
BMI is present in most adults with knee OA, and it is a relevant
determinant of pain and functional loss in these patients
[54–56]. It has been reported that patients with a high BMI
and knee OA, specifically women, are at greater risk of having
symptoms [57]. Exercise adherence is associated with im-
proved physical function in overweight and obese older adults
with knee OA [58]. However, the combination of moderate
exercise and modest weight loss is most beneficial for pain
reduction and improvement of physical function in knee OA,
even more than diet or exercise alone [59, 60]. Fear of move-
ment was found to be increased in morbidly obese adults with
knee pain (mixed conditions such as postsurgical, acute, and
chronic) compared with their nonobese counterparts.
Therefore, obese patients might benefit from rehabilitation
that reduces their fear of movement to optimize their partici-
pation in rehabilitation activities and achievement of function-
al improvement [61].
Even small weight reductions (e.g., 10 % of initial weight)
have resulted in 28 % improved function [62]. Results are
even better with weight loss greater than 5 % achieved within
a period of 20 weeks [63]. When a formula-diet weight loss
program was used, beneficial effects were found independent
of type, with no difference between a 415-kcal/day and a 810-
kcal/day diet [64]. Massive weight loss after gastric surgery
Curr Rheumatol Rep (2014) 16:390
leads to improvement in pain and function and decreases low-
grade inflammation (joint biomarkers), suggesting even struc-
tural effects on cartilage [65]. Therefore, growing evidence
indicates that, regardless of the weight loss method, losing
weight is beneficial and reductions of body fat can reduce the
mechanical and biochemical stressors that contribute to joint
degeneration and greater disability [66••].
Behavior is a relevant issue to take into account. Better
functional abilities or self-efficacy for pain, physical activity,
and eating behavior seem to result in improved functional
capacity in OA patients [67]. Therefore, patient perceptions of
their self-efficacy may be relevant, because it has been reported
that borderline morbidly obese OA patients (BMI >38 kg/m2)
have higher levels of pain catastrophizing than non–morbidly
obese patients. This finding is associated with more frequently
reported pain, higher levels of binge eating, lower self-efficacy
in controlling eating, and lower weight-related QoL [32].
Additionally, a study of 105 overweight and obese patients with
knee OA found that depression symptoms were associated with
reported decreased function, increased knee stiffness, and more
walking impairment compared with nondepressed patients
[68]. Therefore, a psychological and cognitive–behavioral ap-
proach is needed.
Although knee OA is more prevalent in obese and overweight
individuals, similar associations between hip OA and obesity are
not apparent [69•]. An Australian survey of 1,157 individuals
with knee and hip joint disease showed that hip OA pain was
associated with greater BMI, and that patients classified as obese
had higher pain levels, worse physical function, markedly lower
QoL, and greater disease severity. Compared with healthy con-
trols, obese patients with hip OA had an extremely low HRQoL.
Combined exercise and weight loss programs might be a poten-
tial approach to improve physical functioning, pain, QoL, and
other related parameters in overweight patients with hip OA [70].
Total hip arthroplasty confers pain reduction and improvement in
QoL, irrespective of BMI [71]. However, although functional
improvement occurs after hip replacement, available evidence
indicates that obese patients are less likely to attain the same level
of physical function over the long term. Therefore, it is important
to include weight loss strategies in rehabilitation management
after total hip arthroplasty to maintain benefits and avoid wors-
ening of function [72].
Rheumatoid Arthritis
Rheumatoid arthritis (RA) is an autoimmune disease associ-
ated with significant disability, joint pain and destruction, and
chronic systemic inflammation. Old age and female gender
are risk factors for both the development and worse outcomes
of RA [73]. Obesity has been identified as a risk factor for RA
[51] and found to be independently associated with impaired
QoL [74, 75]. In RA, the impact of BMI and body
Curr Rheumatol Rep (2014) 16:390
composition on disease outcomes, such as disability, is un-
clear. However, obesity has the potential to affect functional
disability in RA in different ways: increasing BMI has been
associated with more bodily pain and greater disability from
the same amount of pain [11], obese patients may be less able
to use physical therapy effectively because of their body
weight, and obese patients may have an increased inflamma-
tory burden due to the metabolic activity of adipose tissue
[76••]. In a group of 1,246 patients with early inflammatory
polyarthritis, most of whom fulfilled the criteria for RA, class
II and III obesity was significantly associated with functional
disability affecting daily life activities [77].
Nevertheless, there is contradictory data in early RA. Normal
weight, which has health benefits for the general population,
turned out to be a risk factor for radiographic joint damage in
patients with RA [78]. In a recent large RA study, BMI was
associated with an increased risk of comorbidity, substantial
functional loss, increased pain, fatigue, and reduced general
QoL. However, overweight and obesity paradoxically seemed
to reduce the relative risk of all-cause and cardiovascular mortal-
ity across different age groups and durations of RA [79•]. The key
issue is that RA is associated with altered body composition but
not necessarily with changes in BMI. The chronic inflammatory
state of this disease triggers metabolic alteration, which, in com-
bination with an inactive lifestyle, frequently leads to degradation
of free-fat mass (skeletal muscle, bone, organs, skin), especially
muscle mass. Thus, the presence of reduced muscle mass (rheu-
matoid cachexia) in RA patients is frequent, and there is an
increased accumulation of fat mass, probably as a consequence
of the increased metabolic index and nutritional requirements
related to chronic inflammation status and glucocorticoid treat-
ments [80]. The association of RA with sarcopenia and increased
fat mass has been shown to be greater in women than in men [73,
81] Moreover, BMI rates tend to be similar to those of the general
population in some regions [76••], and the prevalence of over-
weight and obesity in RA patients might vary depending on their
geographic location [82], as well as the correlation of BMI with
functional capacity [83]. Additionally, it seems more important to
take into account the association of metabolic alterations and
central adiposity of patients with RA [81, 84] and, furthermore,
its relationship to functional capacity and QoL.
Low Back Pain
LBP, which may be triggered by physical injuries, is among
the most common chronic pain conditions and causes signif-
icant personal suffering and public health consequences.
Although a causal association between high BMI and suffering
from LBP remains controversial [28, 51], it is apparent from
some studies that obesity is associated with a higher LBP
prevalence [85, 86, 87•]. Moreover, it has been observed that,
in older patients with chronic LBP, the obese ones had higher
Page 5 of 8, 390
pain during walking and stair climbing and had lower lumbar
strength compared with the overweight [88], increased disabil-
ity, reduced physical HRQoL, pain, and comorbidities [89]. In
obese subjects with LBP, weight loss after bariatric surgery
significantly improved functional disability [90, 91], or, at least
in some studies, there was a positive trend for improvement in
the physical component of QoL scores [92]. The association of
overweight and obesity with LBP is stronger for women than
for men [85], and BMI predicts recurrence of LBP among
women [87•]. This might be the result of hormone-related
obesity, body fat mass distribution, or the proportion of lean
body mass/fat mass. In men, a high BMI may reflect a high
degree muscle mass, whereas, in women, it may indicate a
greater amount of adipose tissue. It also seems that metabolic
syndrome might be more prevalent in LBP patients (women
more than men) [93]. In a recent investigation, BMI was
associated with higher levels of back pain intensity and disabil-
ity, with positive associations between higher levels of low
back disability and total body, upper and lower limb, and fat
mass [94•]. The study highlights the importance of body com-
position because greater fat, but not lean mass, was associated
with high levels of LBP intensity and disability.
The effect of obesity on cognitive–behavioral pain treat-
ment for LBP patients has been studied, with lower responses
for obese than nonobese patients [95]. Physiotherapy is an-
other approach for managing LBP and improving QoL. A
recent study showed that, after a multimodal physiotherapy
program, nonobese patients with LBP demonstrated greater
improvement in disability, physical component, and QoL [96].
However, other studies reported that BMI does not seem to
influence the overall recovery from LBP in patients undergo-
ing physiotherapy [97]. Fear of movement seems to be greater
in obese LBP patients, and it predicts greater self-reported
disability. It may be useful to assess fear of movement in LBP
patient populations to identify individuals who are at in-
creased risk for chronic disability and who might benefit from
therapeutic strategies to overcome this fear [98].
Conclusions
Obesity is an increasingly prevalent problem characterized by
weight gain through excess food and fat intake and a sedentary
lifestyle. Adipose tissue is not only an energy store but also an
active organ involved in the regulation of inflammation.
Overweight and obese people are more prone to a proinflam-
matory state, manifested by metabolic syndrome but also by a
higher prevalence of chronic pain comorbidities. Patients who
have FM, OA, RA, LBP, or other chronic pain conditions have
worse functional capacity and QoL when obesity coexists. Most
studies of chronic pain conditions evaluating the effect of obesity
or BMI on QoL have noted that physical function and general
health perception are the most affected domains. Growing
390, Page 6 of 8
evidence suggests that chronic systemic inflammation may be
involved in the onset and perpetuation of chronic pain condi-
tions. Moreover, sedentary living is associated with systemic
inflammation, depression, lack of sleep, and poor self-rated
health, which are worsened by lack of exercise and an unhealthy
diet. As a result, obesity and pain reduce functional capacity and
QoL, creating a vicious circle that is difficult to interrupt.
For obese people with chronic pain conditions, changes in
lifestyle, behavior, physical activity, and diet have demonstrated
benefits in functional capacity and QoL. Therefore, more studies
are needed to assess the relationship among high BMI, metabol-
ic syndrome, and pain, including the impact of dietary changes,
individualized exercise, and cognitive–behavioral therapy that
reduces fear of movement, psychological and sleep disorders,
and stress. This approach would lead to healthier lifestyles and,
consequently, to better functional capacity and QoL in over-
weight or obese patients with chronic pain conditions.
Additional research is needed to provide more details about
the relationship between the pathophysiologic mechanism of
pain and excess body weight and their impact on functionality
and QoL. Current studies have used various methodologic
approaches in different populations. However, standardized
protocols are needed to study and compare various popula-
tions with different social, racial, and other critical character-
istics in different geographic settings. Available data suggest
the benefits of multidimensional management of patients with
chronic pain conditions and obesity, including analgesic drugs
but also weight loss diets, exercise, and cognitive–behavioral
therapy. Special attention should be paid to specific popula-
tions, such as children, women, and older individuals.
Acknowledgments This research received no specific grant from any
funding agency in the public, commercial, or nonprofit sector. The authors
are grateful to Rosanna Shand for her help in the linguistic revision of the text.
Compliance with Ethics Guidelines
Conflict of Interest Laura-Isabel Arranz, Magda Rafecas, and
Cayetano Alegre declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.
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