Journal of Bodywork & Movement Therapies 27 (2021) 723e730
Contents lists available at ScienceDirect
Journal of Bodywork & Movement Therapies
journal homepage: www.elsevier.com/jbmt
Prevention and Rehabilitation
Applying the understanding of central sensitization in practice
Matt Wallden a, *, Jo Nijs b, c, d
a
Matt Wallden Health & Performance, Surrey, UK
b
Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy,
Vrije Universiteit Brussel, Belgium
c
Chronic Pain Rehabilitation, Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Belgium
d
Department of Health and Rehabilitation, Unit of Physiotherapy, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of
Gothenburg, University of Gothenburg Center for Person-Centred Care (GPCC), Sahlgrenska Academy, Gothenburg, Sweden
1. Introduction
Developing an understanding central sensitization (CS), defined
in the accompanying editorial, is a key component in working
effectively with people who are in pain or are experiencing any of
the chronic overlapping pain conditions (Please see Table 1 in the
accompanying editorial “Before & beyond the pain e Allostatic
load, central sensitivity and their role in health and function”, by
Wallden & Nijs), ranging from conditions as diverse as temporo-
mandibular disorders, neck pain, osteoarthritis, low back pain, ir-
ritable bowel syndrome, restless leg syndrome, multiple chemical
sensitivity, or fibromyalgia. The accompanying papers in this
Rehabilitation Section investigate fibromyalgia and restless leg
syndrome making recommendations that may facilitate a return
toward health and function. Here, we offer other elements that may
also be beneficial in effectively addressing these “central sensitivity
syndromes” or chronic overlapping pain conditions (COPC) (Please
see Tables 2 & 3 in the accompanying editorial “Before & beyond
the pain e Allostatic load, central sensitivity and their role in health
and function”, by Wallden & Nijs).
Screening for CS is described briefly in the accompanying
editorial with algorithms presented in the referenced papers to
facilitate identification of individuals who may have CS. Addition-
ally, some interventions are proposed to help in working with
people experiencing persistent pain or COPC's.
2. Inflammation & injury
Inflammation has traditionally been viewed as the body's (or,
more specifically, the immune system's) response to infection or to
acute injury. However, in recent times, inflammation e and in
particular low-grade inflammation e has come under the spotlight
as a likely common pathway to chronic disease (Juster et al., 2010;
Scrivo et al., 2011; Rohleder 2014 Liu et al., 2017), as well as to
persistent pain (Yunus, 2015).
* Corresponding author.
E-mail address: matt@mattwallden.com (M. Wallden).
https://doi.org/10.1016/j.jbmt.2021.04.004
1360-8592/© 2021 Elsevier Ltd. All rights reserved.
As such, to help people experiencing either chronic disease and/
or persistent pain, addressing nutrition and lifestyle factors that
may be contributing to their inflammatory state is likely a useful
strategy in their return to optimal health and function.
Repeated environmental exposures to injury, inflammation and
stress in predisposed individuals, can result in a transition from
acute pain to chronic pain, in part through neuroinflammation (Ji
et al., 2018). As such, maximizing movement repertoire and opti-
mizing kinesthetic vocabulary and fluency may be an important
component in both prevention of and recovery from persistent
pain. Although trauma or overuse are often described as causative
in sports injury (Malfliet et al., 2017) and biomechanics can play a
role in the development of low back pain (LBP), and perhaps in the
persistent and/or recurrent nature of LBP (Cholewicki et al., 2019),
there is doubt whether biomechanics alone can provide the basis
for intervention. To date, the aetiology of overuse or repetitive in-
juries has mostly been related to biomechanical factors such as
technique, posture, training load and competition exposure; and
evidence suggests that repetitive stress to a tissue will initially
result in acute inflammation, which may progress to chronic
inflammation if those stressors are sustained (Solomonow et al.,
2012). Aside from creep to the passive tissues (ligaments, joint
capsules, discs, connective tissue) induced by repetitive loading,
alterations in muscular activity are also noted when inflammation
is present (Solomonow et al., 2012). Most traumatic injuries involve
nociceptive input, while overuse or repetitive injuries may include
a component of central sensitization pain (Malfliet et al., 2017) as
well as alteration to motoneuron firing as a result (Zugel et al.,
2018). This alteration in motoneuron firing typically involves inhi-
bition of the tonic motoneurons while pain is present. There is
growing evidence that central sensitization is present in at least a
subgroup of patients with sports-related problems and thus
applying this aspect of modern pain neuroscience in the biome-
chanical and neurophysiological intervention is a recommended
strategy.
Similarly, addressing nutritional habits that may be pro-
inflammatory, such as consumption of refined grains (Slim et al.,
2017), oxidised or hydrogenated fats (Longhi et al., 2017), pesti-
cides (such as glyphosate (Samsel and Seneff 2013)), while allowing
M. Wallden and J. Nijs
periods of fasting and/or ketogenesis (Nijs et al., 2014a) may all be
helpful in minimizing systemic inflammation among other
biochemical effects. See Dietary Connections with Central Sensitivity,
below, for more details.
3. Prolonged stress from allostatic load
Over-exposure to stressors in the forms of biomechanical,
biochemical (including nutritional), psychological, emotional,
electromagnetic and other stresses create allostatic load on the
individual which, in turn, results in over-production of the human
body of stress hormones (i.e., glucocorticoids) such as cortisol,
adrenaline and noradrenaline.
When the body is confronted with high levels of glucocorticoids
across time, the response can be resistance to their effects e both at
the cellular level (Cohen et al., 2012), compromising the effective
bidirectional communication between the nervous system and the
immune system; as well as within the central nervous system itself
- in particular, at the prefrontal cortex, insula, amygdala, and hip-
pocampus. Michopoulos et al. (2017) explain that chronic dysre-
gulation of the HPA-axis due to increased sympathetic tone (and
therefore decreased parasympathetic activity) may suppress the
ability of glucocorticoids to inhibit inflammatory process; thereby
having a direct effect on these brain regions, critical for the regu-
lation of fear and anxiety which, in turn, are implicated in persis-
tent pain and central sensitization.
Alongside these more direct effects of prolonged stress on the
nervous system and cellular function, a persistent state of sympa-
thetic arousal also impacts on digestive function, repair, sleep and
immune function. One of the primary causes of intestinal perme-
ability is prolonged exposure to stressors - or sympatheticonia
(Bland 1999; Camilleri 2019), and this compromise of the gut bar-
rier can impact on digestion, sensitize the immune system and may
contribute to conditions such as irritable bowel syndrome and
auto-immune conditions; as well as increasing the likelihood of
food sensitivities or reactions occurring; which continue the cycle
of inflammation.
Similarly, allostatic load; the combined effects of stress, and the
resultant over-production of glucocorticoids, can predispose to
many of the lifestyle syndromes of industrialised society, including
but not limited to cardiovascular disease, diabetes, cancer, Alz-
heimer's, upper respiratory infections, depression, poor wound
healing (Cohen et al., 2012), osteoarthritis and, in some of these
cases, central sensitization (Yunus, 2015).
It is of interest to note, also, that allostatic load can lead to raised
cardiovascular disease markers, which predict risk of development
of conditions such as lateral epicondylitis, Achille's tendinopathy,
rotator cuff injury and carpal tunnel syndrome (Hegmann et al.,
2017) which, in turn, may be drivers of, or driven by, central
sensitivity (Yunus, 2015).
4. Exercise, persistent pain and central sensitivity
One of the key interventions with the most evidence for effec-
tiveness in those experiencing persistent pain is exercise therapy e
or more accurately, therapeutic body movement. Movement is
fundamental in optimizing human health at many levels from
metabolic, to fluid dynamics, to biomechanical, emotional, cardio-
vascular, immunologic and many more besides.
4.1. The BDNF connection
One of the more fruitful connections that has been explored
with regard to movement's role in addressing persistent pain is its
effects on production of brain-derived neurotrophic factor (BDNF).
724
Journal of Bodywork & Movement Therapies 27 (2021) 723e730
BDNF, as the name implies, is a protein-based growth factor that is
produced in the brain e particularly in the glial cells - and facilitates
neuronal growth. However, it is not only produced in the brain; it is
also produced in the peripheral nervous system, the vascular
endothelium (Walsh and Tschakovsky 2018) and the muscles
(Matthews et al., 2009).
BDNF was only fairly recently discovered - in 1989 - its main role
being to build and maintain neural cell circuitry; helping form new
connections in the brain and nervous system (Ratey and Hagerman
2008). BDNF secretion is stimulated by exercise, which helps to
explain why exercise is such a good primer for learning and is
important in maintaining optimal brain health. Simply stated,
BDNF, gives neuronal synapses the tools they need to take in in-
formation, process it, associate it, remember it and put it in context
(Ratey and Hagerman 2008). However, it seems that in order to be
effective, the BDNF secretion must be associated with a bodily
response. You can't just inject BDNF and develop new neuronal
connections, according to Professor Cotman, Director of the Insti-
tute for Aging & Dementia at the University of California; you have
to respond to a stimulus in a novel, or meaningful, way (Ratey and
Hagerman 2008).
Stimulation of BDNF through exercise has also been used clini-
cally to help people with conditions such as depression and anxiety
(Sleiman et al., 2018; Ratey and Hagerman 2008; Yang et al., 2020).
However, it's not all good news; a growing body of evidence has
identified that BDNF (as well as other growth factors), have a
fundamental role in instigating and/or perpetuating hyperexcit-
ability in the central nervous system in those with central sensiti-
zation, especially in conditions such as neuropathic pain and
fibromyalgia (Nijs et al., 2014a). More specifically, BDNF functions
in the spinal cord to develop and maintain sensitization in the
dorsal horn, while, in the brain, it has been shown to facilitate
descending nociceptive drives.
Merighi et al. (2008) suggest that low doses of BDNF have
pronociceptive (pain perception-increasing) effects, while high
doses of BDNF have antinociceptive (pain perception-decreasing)
effects. However, Nijs et al. (2014b) point out that studies report-
ing the pain-relieving effects of BDNF in the spinal cord are
significantly outweighed by more recent ones demonstrating pain
facilitatory action of BDNF on the dorsal horn neurons. When
reviewing the literature, a more or less consistent picture arises
with both preclinical studies as well as human studies in people
suffering from chronic pain suggesting that BDNF levels are too
high in those having persistent pain (Nijs et al., 2015). On the
contrary, they also observe that BDNF facilitates dopamine avail-
ability which helps with descending nociceptive inhibition. In
short, the picture is far from clear-cut. Clinically, the question is,
should a treatment aim be to increase BDNF with all its potential
benefits, or to decrease BDNF to reduce this potential for sensiti-
zation? Or is BDNF no more than one out of many ‘messengers’
within the nervous system; one piece of a very large and complex
puzzle?
One suggested solution is to engage the individual in a time-
contingent approach to exercise (for example, ‘Perform the exer-
cise for 5 min, regardless of the pain’) over a symptom-contingent
approach (such as, ‘Stop the exercise once it hurts’). The rationale
for this is that in a state of CS the brain can produce pain and other
‘warning signs’ even when there is no (longer) actual tissue dam-
age. So, while a symptom-contingent approach may facilitate the
brain in its production of nonspecific warning signs like pain, a
time-contingent approach may actually serve to deactivate the
brain's top-down nociceptive facilitating pathways (Nijs et al.,
2014a). In addition, exercise serves to encourage the release of
endogenous opioids and endocannabinoids which can facilitate
analgesia in people experiencing persistent pain.
M. Wallden and J. Nijs
However, this doesn't fully address BDNF's role in helping or
hindering those with persistent pain. BDNF effects learning by
stimulating the connection or affinity between different neurons; in
the semblance of the famous notion: neurons that fire together wire
together (Hebb 2002). This BDNF-evoked “wiring together” of
neurons occurs through a process called long-term potentiation
(LTP) allowing memories to be formed (Ratey and Hagerman 2008;
Nijs et al., 2014b). Such LTP is functional inasmuch as it allows
learning by facilitating memory formation and storage but, in the
case of persistent pain, it may transition to becoming dysfunctional
or unhelpful, allowing the “memory” of acute pain to be stored in
those experiencing ongoing or persistent pain. CS is such an
example of unhelpful LTP, with LTP being responsible for at least
part of the sensory hypersensitivity, neuronal hyperexcitability and
overactive pain matrix (now labelled as the brain's ‘dynamic pain
connectome’) in patients with chronic pain and CS. Moreover, LTP
may be the primary mechanisms explaining CS.
BDNF is not only secreted when the body is exposed to exercise
stress or when there is pain, but is also produced when there is
nutritional stress, such as starvation or perceived starvation due to
ketogenesis (Ratey and Hagerman, 2008; Sleiman et al., 2016). Nijs
et al. (2014a) explain that habitual and regular exercise, in contrast
to temporary exercise, decrease BDNF levels, at least based on
preclinical studies. Such findings require confirmation in clinical
studies, but at least it fits within available evidence that exercise
therapy (in the long term) decreases CS in patients having chronic
pain (Arribas-Romano et al., 2020). So, it seems to be the novelty
element that drives BDNF levels upward. In an evolutionary
context, BDNF's function seems to be to facilitate learning; to move
away from pain, to learn when under stress, to develop new
movement skills and to improve cognitive capacity when food
supplies are scarce. Since BDNF serves as a key regulator of neural
circuit development and specifically mediates many activity-
dependent processes, including neuronal differentiation and
growth (Nijs et al., 2014b), this may highlight the importance of
channelling BDNF to the “right” places in the body; through
providing an optimal variety of stimuli. Much akin to the “SAID
Principle” (specific adaptation to imposed demands) in strength
and conditioning, if BDNF allows for neuronal growth and devel-
opment and its utilization is activity-dependent, then choosing
which activity(ies) to engage may be among the most fundamental
elements of a health & performance program for those experi-
encing persistent pain.
Therefore, utilizing such strategies; movement e and especially
novel movement; healthy diets or forms of structured fasting, such
as intermittent fasting; and engaging in learning, such as pain
neuroscience education or through exposure-based exercise in-
terventions, which, together, direct BDNF utilization toward help-
ful, functional and healthful development, may provide a useful
cocktail to help those experiencing symptoms and conditions
driven by central sensitization. See Fig. 1.
5. Dietary connections with central sensitivity
While it is beyond the scope of this brief practical paper to give a
comprehensive review of nutritional factors that can contribute to
CS, the aim is to provide some useful clinical examples for the role
nutrition may contribute in causation, treatment and prevention of
CS in patients having persistent pain.
5.1. Gut inflammation & central sensitivity
Somewhere in the region of 70e80% of the body's immune cells
can be found in the digestive tract (Furness et al., 1999). The reason
for this, of course, is that the digestive tract is the one region of the
725
Journal of Bodywork & Movement Therapies 27 (2021) 723e730
body where the physiological goal is to take something that is “non-
self” e another organism - and to incorporate it into the “self”. As
such, when there is inflammation in the digestive tract, the tight
junctions in the gut barrier can become permeable to macromol-
ecules creating what is termed “leaky gut syndrome”, or intestinal
permeability (IP), which is a common precursor or sequela to irri-
table bowel syndrome (IBS) and immune sensitization. IP and IBS
are important to have an awareness of in the context of persistent
pain; as both may affect local motor control (Wallden 2013), and IBS
can drive central sensitization, while IP creates immune sensitiza-
tion, which creates local inflammation, firing of visceral afferents,
affects the gut-brain axis (Holzer et al., 2017) and therefore may
contribute to descending forms of central sensitization.
Intestinal Permeability can be caused by exposure to one or
more of the following (Bland 2000; Camilleri 2019):

NSAID's

Antibiotics

Intestinal infection/dysbiosis

Maldigestion/malabsorption

Alcohol consumption

Ingestion of allergenic foods

Ingestion of offending chemicals (see glyphosate discussion
below)

Trauma (physical or mental emotional)

Sympatheticonia
Since these drivers of IP are common in the general population,
it is of little surprise that intestinal inflammation is the norm, rather
than the exception in industrialised cultures. Such gut inflamma-
tion impacts on the immune system which, via the gut-brain axis e
can ultimately drive stress responses and altered brain function
(Holzer et al., 2017). For example, only 1.4% of global farmland is
dedicated to organic production (Willer and Lernoud 2019), yet
Baudry et al. (2018) explain that, although chemical residues are
lower in organic foods, few studies have examined the effects of
non-organic food consumption with disease risk. In their own
study of 68,946 people, high organic food consumption, when
adjusted for other lifestyle factors, was inversely associated with
overall risk of cancer specifically (Baudry et al., 2018), while other
researchers found a positive correlation between use of glyphosate
(globally the most widely used herbicide on non-organic crops)
with certain cancers and with Celiac Disease incidence (Samsel and
Seneff 2013).
In Celiac disease, an abnormal immune response occurs in re-
action to eating foods containing gluten, which creates an inflam-
matory reaction in the small intestine. Though distinct conditions,
Celiac disease and inflammatory bowel disease have overlapping
symptomology, microbiotic changes, and genetic predisposition
(Pascual et al., 2014) and research has demonstrated that when
inflammatory bowel disease is active, musculoskeletal pain severity
is increased (Falling et al., 2020). Similarly, in irritable bowel syn-
drome (IBS), well established as one of the chronic overlapping pain
conditions, low-grade intestinal inflammation is known to play a
key role in the pathophysiology (Sinagra et al., 2016) with one or
more of the items in the list above being common contributors to
IBS. As discussed in the accompanying editorial, such low-grade
inflammation may be sufficient to create subthreshold drives
which, combined with other drives, are enough to create supra-
threshold effects at the corde as well as to impact on the gut-brain
axis e thereby driving or perpetuating persistent pain, bidirec-
tionally (Holzer et al., 2017).
To return to BDNF, part of its role in persistent pain is that it can
increase neuronal excitability by causing disinhibition in dorsal
M. Wallden and J. Nijs
horn (sensory) neurons in the spinal cord. The way this excitability
is reduced is through a process called glycine receptor-mediated
inhibition (Nijs et al., 2014b).
As explained above, BDNF release in response to acute ‘danger’
(such as inflammation or injury) seems adaptive e resulting in
increased awareness and learning; thereby serving a strong pro-
tective role (Nijs et al., 2014b). However, BDNF exposure may
become maladaptive in the chronic stage, in a similar way that
chronic production of glucocorticoids, such as cortisol; or to insu-
lin; or to leptin, becomes maladaptive chronically. This situation
echoes the adaptive inhibition of tonic motoneurons and tonic
muscle fibres which have a low threshold to stimulus, thereby, in a
functional environment, allowing them to engage early in a feed-
forward mechanism. However, it is this low same threshold
which means that, when nociceptive drives are present, they tend
to become inhibited first (Zügel et al., 2018). This may be adaptive
in acute pain, since tonic musculature typically exerts compressive
forces on joint structures but, chronically, these tonic motoneurons
and muscle fibres often do not resume their function even after the
pain has gone (Hides et al., 1996). An end-result of this tonic inhi-
bition is that phasic motoneurons attempt to compensate and take
over the role of both systems, which is inefficient both biome-
chanically and metabolically; and impacts negatively on fine motor
control.
This impact on motor control may be further compounded in the
presence of other overlapping pain syndromes, such as IBS (see
Wallden 2013 for more discussion). As both a driver of motor
control challenges, and a driver of central sensitization, IBS may
compound the propensity for compensation, fatigue, altered local
and systemic respiration, cumulative microstress, central sensiti-
zation and, ultimately, persistent pain.
Some of the simplest ways to work effectively with nutrition
clinically is to follow core principles, such as eating a diet that is
primarily natural, wholefood, organic wherever possible, balancing
the macronutrients, In their Systematic Review of nutritional fac-
tors which may interact with musculoskeletal pain, Elma et al.
(2020) found a variety of food exclusion approaches which may
be helpful in persistent pain, though there were many seemingly
conflicting results. Macronutrient intakes (protein, fats, carbohy-
drates) were assessed for impact, as were micronutrient de-
ficiencies, and some were found to potentially contribute to effects
on pain intensity and pain thresholds, amongst other symptomol-
ogy in persistent pain conditions. For example, some studies found
that protein, fat and sugar intake were associated with increased
pain intensity and lower pain thresholds, whereas others showed
that protein intake was associated with decreased pain intensity
and higher pain thresholds. Plant-based diets also showed some
promise in terms of reducing chronic pain e in spite of higher
protein diets offering benefits in some groups.
Possible rationale for such disparate findings may be, in part,
explained by biochemical individuality (Williams 1956; Wolcott
1998), where different nutrients affect different people in
different ways depending on the individual, their stress levels, their
underlying physiology, their microbiome and their genetics.
Another possible reason is that omnivorous diets are the norm in
most societies, whereas plant-based diets tend to be the domain of
those with an interest in health e and therefore a range of con-
founding factors may be introduced. A further reason for disparate
findings may be that, while macronutrients may be measured
within a prescribed diet, the quality of these macronutrients may
differ significantly. For example, meats from free ranging and
organically raised livestock typically shows higher levels of the
anti-inflammatory omega-3 fatty acids, while commercially reared
livestock typically shows higher levels of the pro-inflammatory
omega-6 fatty acids (Srednicka-Tober et al., 2016). Hence a pound
726
Journal of Bodywork & Movement Therapies 27 (2021) 723e730
of beef, or an egg may have exactly the same macronutrient pro-
portions, but very different biochemical profiles depending on
quality.
It might be predicted that identifying optimal nutritional in-
takes for those experiencing persistent pain will become a process
that must be customised to the individual; much like other ele-
ments of optimal care. General overtones, however, are likely to be
recommended, such as optimizing nutritional variety, freshness,
food quality, maintaining soluble fibre levels and avoiding known
pro-inflammatory compounds. For example, aberrant glial activity
has the potential to induce CNS sensitization via several mecha-
nisms, and is accompanied by increased tumor necrosis factor,
among other proinflammatory cytokines produced by glial cells
(Nijs et al., 2019). One member of the TNF family is B-cell Activating
Factor (or BAFF) and, while there is currently a lack of research in its
potential role in persistent pain, it is active in auto-immune con-
ditions associated with persistent pain, such as rheumatoid
arthritis, systemic lupus erythematosus (commonly associated
with fibromyalgia (Woolf 2011)), as well as other chronic wide-
spread pain conditions, such as migraine. Interestingly, BAFF is also
implicated in nutritionally driven conditions, such as Coeliac Dis-
ease (Fabris et al., 2007), as well as in allergies (Vincent et al., 2017),
which are often comorbid with conditions associated with chronic
widespread pain, such as fibromyalgia, chronic fatigue syndrome,
multiple chemical sensitivity and migraine (Martami et al., 2018).
Overall, using nutritional strategies which minimize immune
sensitization and reduce inflammation (or, at worst are not pro-
inflammatory) may be a useful contribution to managing persis-
tent pain. Nijs et al. (2019 summarise their nutritional findings in a
flow chart which has been expanded for this discussion (See Fig. 2).
There are innumerable factors that may be considered in a
nutritional approach to minimizing or addressing central
sensitivity - and for health in general. As discussed above, it
is likely that in the pursuit of health -through reducing
digestive stressors, hormonal stressors, biochemical
stressors and optimizing the microbiotic environment -
allostatic load will reduce, inflammation will reduce,
visceral afferent drives will reduce and central sensitization
will reduce and, ultimately, pain will reduce.
6. A biopsychosocial view of central sensitization
In this paper, a cursory review of potential movement and di-
etary interventions for those with CS has been offered, but there are
many other factors that can, and ideally should, be addressed; from
sleep habits (Nijs et al., 2018), to emotional processing (O'Sullivan
2018), and from pain neuroscience education (Nijs et al., 2019) to
assessing both conscious and unconscious belief patterns
(O'Sullivan 2018; Wallden and Chek 2018).
In much the same way that Hippocrates is credited with advising
to work with the person that has the disease, rather than to treat the
disease that has the person, Nijs et al. (2019) recommend that, rather
than focusing on treating CS as a pathophysiological process, clini-
cians are advised to treat individuals as biopsychosocial human be-
ings experiencing a state of chronic pain. This would include taking
CS into account when designing and delivering the intervention,
through explaining the concept of CS, addressing all factors that can
contribute to allostatic load, as well as focusing on long-term rather
than short-term effects of any intervention. At the same time it
implies that ‘treating’ CS cannot be the primary goal, as the main goal
M. Wallden and J. Nijs Journal of Bodywork & Movement Therapies 27 (2021) 723e730

Fig. 1. When an individual experiences a stressor, such as pain, anxiety, starvation or a new motor challenge, one physiological response is increased secretion of BDNF (brain-
derived neurotrophic factor) to facilitate learning. In an evolutionary context, this makes perfect sense as BDNF facilitates long-term potentiation between synapses e which is how
memories form. The memory of pain generators, a new motor skill or new ways to hunt or gather foodstuffs would be adaptive in nature. However, when pain is persistent, BDNF
secretion can facilitate nociceptive pathways of memory, making individuals remember or feel the pain long after the original tissue injury has healed. This can be considered
maladaptive. Utilizing novel strategies, such as exploring new motor skills, learning about and adopting new nutrition & lifestyle approaches, studying pain neuroscience,
considering what lessons can be learned from the original pain (or pain drivers), are strategies that may redirect BDNF into more optimal neuronal growth patterns.

should be improving the patient's quality of life. This can be best
achieved through having the patient pick their own preferred
(functional) goals (i.e., goal setting). As Wallden and Chek (2018b)
and Wallden and Lee (2019) suggest, finding a focus or goal beyond
the presenting symptomology may be a key component of effective
long-term goal setting.
The effective delivery of such a program requires both a holistic,
multimodal awareness of the clinician and, most likely, a good
interdisciplinary network of clinicians who can support in relevant
specialist areas; though, importantly, it is recommended that there
should be a single co-ordinating point of contact for the individual
seeking help.
While nutrition and exercise fall under the biopsychosocial
categorization as primarily “biological” factors that may drive or
reduce CS, they both may influence - and be influenced by - psy-
chological and sociological factors. As an example, less than 3 de-
cades ago it was extremely challenging to eat a gluten-free diet; in
part, because there were less gluten-free options in the food supply
chain, but largely because it was not considered socially acceptable
or normal. In the last 2 decades, as the food supply chain has
responded to scientific awareness and consumer demand, gluten
free food availability e and its consumption - have become more
acceptable and socially tolerated; indeed, welcomed by clinicians
and those who have found benefit from such a dietary change. In
the last decade, with the advent of the Paleo movement and
accessibility of online information pertaining to it (in tandem with
ongoing research), the realisation that a gluten free diet is, in re-
ality, highly accessible has become more of a social norm with
almost no stigma. This is an example of a social shift, which makes a
new habit more psychologically acceptable and attainable, and
which has a biological benefit to many.
In contrast, while exercise is not socially frowned upon, it may
still be socially less desirable than certain other cultural habits, such
as online entertainment, social media, social alcohol consumption,
television viewing, and so on. The result is a social norm that makes
a high level of self-motivation a prerequisite, in order for exercise to
be undertaken. So, while it is helpful to understand the actions that
one should ideally take, it is an entirely different matter to actually
take them (often referred to as the knowledge-action gap), and is
why exercise programs may fall into what is termed “the efficacy
trap” (see Beedie et al., 2016 as an example). This is where under-
standing and engaging with a biopsychosocial view is essential for
effective implementation.
Other examples of biopsychosocial factors that may contribute
to stressors that drive CS are interpersonal relationships; how the
“I” (the individual) interacts with the “We” (the group or tribe). In
clinical consultation, it is helpful for the practitioner to understand
they are not just working with the individual in front of them, but
the individual in the context of all their relationships. For example,
in a loving, nurturing environment, human beings e at all levels of
development - thrive (Stanhope et al., 1994). However, when love is
lacking, or there are more negative emotions in the present or
historical environment, not only does exposure to stress hormones
increase, but so does exposure to other markers of inflammation
(Fagundes et al., 2011). Across the lifespan, people who experience
supportive relationships have lower levels of systemic inflamma-
tion compared to people who have cold, unsupportive or conflict-
ridden relationships. Not only are the individual's current re-
lationships associated with inflammation, but previous relation-
ships can be as well. To glean an example of the effect of the living
environment on stress markers, children with stressed parents
have been shown to have higher inflammatory markers than
counterparts with less stressed parents; irrespective of their own
perceived stress levels (Fagundes et al., 2011). Research on marital
partnerships shows that trait anger and hostility predict the
development of coronary heart disease and systemic inflammation
which, in turn, is associated with high levels of C-reactive protein
(Smith et al., 2014); a clinical marker for acute-phase response to
both acute and chronic inflammation (Bennett et al., 2018).
Furthermore, and illustrative of the importance of a holistic

727
M. Wallden and J. Nijs Journal of Bodywork & Movement Therapies 27 (2021) 723e730

Fig. 2. Poor Nutritional Choices may both cause or arise from emotional stress, however, they have much further reaching effects, such as contributing to oxidative stress, increased
peripheral inflammation, gut inflammation and can negatively impact the microbiome. These latter two consequences can increase afferent vagal drives, influencing the gut-brain
axis and predisposing to further emotional stress. All of these factors, independently e or in conjunction with tissue injury, can increase pro-inflammatory cytokines (such as TNF-a
and BAFF) or activate toll-like receptors (TLR's), both of which excite the microglia in the central nervous system. The microglia are the primary producers of BDNF (brain-derived
neurotrophic factor), which stimulates learning and memory potentiation. Whether those memories are helpful (adaptive) or harmful (maladaptive) significantly depends on how
the individual interprets and engages with them (see Fig. 1 for more detail).

overview, Smith et al. (2014) found that in marital relationships
where hostility was present the level of C-reactive protein was
higher in both the giver and the receiver of the hostility. Under
conditions of chronic exposure to hostility, and the associated
biochemical milieu, a pro-inflammatory internal environment may
be created, or contributed to, resulting in increased susceptibility to
CS. As Smith et al. (2014) comment, there is a growing body of
literature highlighting the notion that the health effects of per-
sonality operate not only within individuals (as is most commonly
studied), but between them as well.
In a different light, the individual can exert some control over
their own physiological response to the stressors they are exposed
to within their relationships and life circumstances. In general,
stress management approaches integrated into a comprehensive
management for chronic pain address this important issue.
Research on gratitude, for example, has shown both an improve-
ment in heart-rate variability (a marker of vagal tone and stress), as
well as a reduction in inflammatory biomarkers, such as c-reactive
protein, interleukin-6 and tumor necrosis factor in those practicing
gratitude over and above the control group (Redwine et al., 2016).
As such, nurturing a psychosocial attitude of appreciation or
thankfulness for the people and circumstances that surround the
individual, focusing on the positive and looking for the benefits - or
what can be learned from a challenging personal situation, may
also be helpful in reducing factors contributing to CS.
Outside of these perhaps more evident (albeit complex) psy-
chosocial factors, there may be less obvious factors that are not so
easy to detect. For example, primary dysmenorrhea (which is
classified as one of the chronic overlapping pain disorders that may
arise from, or contribute to, CS) has been studied in traditional
cultures, where there are commonly rites of passage for children
728
moving into adulthood. For females, initiation rites are typically
conducted at the menarche. In one study of 185 Colombian women,
ten different traditional initiation rites were identified (such as
blessing by a healer, time in isolation, emesis, and following a
prescribed diet (Zuluaga and Andersson, 2013). When figures were
adjusted to account for age, education, community, parity and use
of family planning, those women not completing all rites were
more likely to report dysmenorrhoea than those who did so
(p ¼ 0.01 Fisher exact). Those who did not complete all rites re-
ported increased severity of dysmenorrhoea (p ¼ 0.00014), thus
suggesting that, in this context, meeting with traditional societal
norms and thereby harnessing a group identity seems to exert a
biological benefit in respect of the risk of developing dysmenorrhea
(Zuluaga and Andersson, 2013).
7. Conclusion
As the subject areas just superficially explored in this editorial
have illustrated, central sensitization, allostatic load and their as-
sociation with chronic inflammation, hormonal dysregulation and
persistent pain, are fields of medicine in which linear approaches
are most likely to be doomed to failure. To create a successful
program of rehabilitation for people experiencing these states,
clinicians must design individually tailored, multimodal treatment
plans which include pain neuroscience education, cognition-
targeted, time-contingent exercise therapy, sleep management,
stress management, dietary intervention, alongside other broader
social and cultural considerations, as well as a longer-term focus in
order to achieve optimal outcomes (Nijs et al., 2019).
M. Wallden and J. Nijs Journal of Bodywork & Movement Therapies 27 (2021) 723e730

References 1148-y. Epub 2016 Jan 11.

Malfliet, A., Leysen, L., Pas, R., Kuppens, K., Nijs, J., Van Wilgen, P., Huysmans, E.,
Goudman, L., Ickmans, K., 2017. Modern pain neuroscience in clinical practice:
Arribas-Romano, A., Fernandez-Carnero, J., Molina-Rueda, F., Angulo-Diaz-
applied to post-cancer, paediatric and sports-related pain. Braz. J. Phys. Ther. 21
Parreno, S., Navarro-Santana, M.J., 2020 Oct 1. Efficacy of physical therapy on
(4), 225e232. https://doi.org/10.1016/j.bjpt.2017.05.009, 2017 Jul-Aug, Pub-
nociceptive pain processing alterations in patients with chronic musculoskel-
lished online 2017 May 19.
etal pain: a systematic review and meta-analysis. Pain Med. 21 (10), 2502e2517.
Martami, F., Jahromi, S.R., Togha, M., Ghorbani, Z., Seifishahpar, M., Saidpour, A.,
https://doi.org/10.1093/pm/pnz366.

s, B., Seconda, L., Latino-Martel, P., 2018. The serum level of inflammatory markers in chronic and episodic
Baudry, J., Assmann, KE., Touvier, M., Alle
migraine: a case-control study. Neurol. Sci. 39 (10), 1741e1749. https://doi.org/
Ezzedine, K., Galan, P., Hercberg, S., Lairon, D., Kesse-Guyot, E., 2018. Association
10.1007/s10072-018-3493-0, 2018 Oct.
of Frequency of Organic Food Consumption With Cancer RiskFindings From the
Matthews, V.B., Astro € m, M.B., Chan, M.H., Bruce, C.R., Krabbe, K.S., Prelovsek, O.,
NutriNet-Sante  Prospective Cohort Study. JAMA Intern Med. https://doi.org/
Akerstro €m, T., Yfanti, C., Broholm, C., Mortensen, O.H., Penkowa, M., Hojman, P.,
10.1001/jamainternmed.2018.4357. Published online October 22, 2018.
Zankari, A., Watt, M.J., Bruunsgaard, H., Pedersen, B.K., Febbraio, M.A., 2009.
Beedie, C., Mann, S., Jimenez, A., Kennedy, L., Lane, A.M., Domone, S., Wilson, S.,
Brain-derived neurotrophic factor is produced by skeletal muscle cells in
Whyte, G., 2016. Death by effectiveness: exercise as medicine caught in the
response to contraction and enhances fat oxidation via activation of AMP-
efficacy trap! Br. J. Sports Med. 50 (6) https://doi.org/10.1136/bjsports-2014-
activated protein kinase, 2009 Jul Diabetologia 52 (7), 1409e1418. https://
094389. Epub 2015 Feb 12.
doi.org/10.1007/s00125-009-1364-1. Epub 2009 Apr 22.
Bennett, J.M., Reeves, G., Billman, G.E., Sturmberg, J.P., 2018. InflammationeNature’s
Merighi, A., Salio, C., Ghirri, A., et al., 2008. BDNF as a pain modulator. Prog. Neu-
way to efficiently respond to all types of challenges: implications for under-
robiol. 85 (3), 297e317, 2008.
standing and managing “the epidemic” of chronic diseases. Front. Med. 5, 316.
Michopoulos, V., Powers, A., Gillespie, C.F., Ressler, K.J., Jovanovic, K., 2017. 2017.
https://doi.org/10.3389/fmed.2018.00316.
Inflammation in fear- and anxiety-based disorders: PTSD, GAD, and beyond.
Bland, J., 2000. Nutritional Management of the Underlying Causes of Chronic Dis-
Neuropsychopharm. Rev. 42, 254e270.
ease. The Institute for Functional Medicine. Seminar Series, London.
Nijs, J., Van Houdenhoved, B., Oostendorp, R., 2010. 2010. Recognition of central
Camilleri, M., 2019. Leaky gut: mechanisms, measurement and clinical implications
sensitization in patients with musculoskeletal pain: application of pain
in humans. Gut 2019 (68), 1516e1526. https://doi.org/10.1136/gutjnl-2019-
neurophysiology in manual therapy practice. Man. Ther. 15, 135e141.
318427.
Nijs, N., Malfliet, A., Ickmans, K., Baert, I., Meeus, M., 2014a. Treatment of central
Cholewicki, J., Breen, A., Popovich Jr., JM., Reeves, P., Sahrmann, SA., van Dillen, LR.,
sensitization in patients with ‘unexplained’ chronic pain: an update. Expet
Vleeming, A., Hodges, PW., 2019. Can Biomechanics Research Lead to More
Opin. Pharmacother. 15 (12), 2014.
Effective Treatment of Low Back Pain? A Viewpoint-Counterpoint Debate.
Nijs, J., Meeus, M., Versijpt, J., Moens, M., Bos, I., Knaepen, K., Meeusen, R., 2014b.
J. Orthop. Sports Phys. Ther. 49 (6), 1e32. https://doi.org/10.2519/
Brain-derived neurotrophic factor as a driving force behind neuroplasticity in
jospt.2019.8825. May 2019.
neuropathic and central sensitization pain: a new therapeutic target?, 2015 Apr
Cohena, S., Janicki-Devertsa, D., Doyleb, W.J., Millerc, G.E., Frankd, E., Rabine, B.S.,
Expert Opin. Ther. Targets 19 (4), 565e576. https://doi.org/10.1517/
Turner, R.B., 2012. Chronic stress, glucocorticoid receptor resistance, inflam-
14728222.2014.994506. Epub 2014 Dec 18.
mation, and disease risk. www.pnas.org/cgi/doi/10.1073/pnas.1118355109. € Yilmaz, S.T., Mullie, P., Vanderweeen, L., Clarys, P., Deliens, T.,
Nijs, J., Elma, O.,
Elma, O., Yilmaz, ST., Deliens, T., Coppieters, I., Clarys, P., Nijs, J., Malfliet, A., 2020. Do
Coppieters, I., Weltens, N., Van Oudenhove, L., Malfliet, A., 2019. 2019. Nutri-
Nutritional Factors Interact with Chronic Musculoskeletal Pain? A Systematic
tional neurobiology and central nervous system sensitisation: missing link in a
Review. J. Clin. Med 9, 702. https://doi.org/10.3390/jcm9030702, 2020.
comprehensive treatment for chronic pain? Br. J. Anaesth. 123 (5), 539e543.
Fabris, M., Visentini, D., De Re, V., Picierno, A., Maieron, R., Cannizzaro, R., Villalta, D.,
https://doi.org/10.1016/j.bja.2019.07.016.
Curcio, F., De Vita, S., Tonutti, E., 2007. Elevated B cell-activating factor of the
Nijs, J., Mairesse, O., Neu, D., Leysen, L., Danneels, L., Cagnie, B., Meeus, M.,
tumour necrosis factor family in coeliac disease. Scand. J. Gastroenterol. 42,
Moens, M., Ickmans, K., Goubert, D., 2018. Sleep disturbances in chronic pain:
1434e1439, 2007.
neurobiology, assessment, and treatment in physical therapist practice. Phys.
Fagundes, C., Bennett, J., Derry, H., Kiecolt-Glaser, J., 2011. Relationships and
Ther. 98 (5), 325e335.
inflammation across the lifespan: social developmental pathways to disease.
Nijs, J., Meeus, M., Versijpt, J., Moens, M., Bos, I., Knaepen, K., Meeusen, R., 2015.
Soc. Pers. Psychol. Compass 5 (11), 891e903. https://doi.org/10.1111/j.1751-
Brain-derived neurotrophic factor as a driving force behind neuroplasticity in
9004.2011.00392.x, 2011 November.
neuropathic and central sensitization pain: a new therapeutic target? Expert
Falling, CL., Stebbings, S., Baxter, DG, Gearry, RB., Mani, R., 2020. Central Sensiti-
Opin. Ther. Targets 19 (4), 565e576.
zation Inventory Mediates the Relationship Between Inflammatory Bowel Dis-
O'Sullivan, P.B., Caneiro, J., O'Keeffe, M., Smith, A., Dankaerts, W., Fersum, K.,
ease Activity and Worse Musculoskeletal Pain Experiences. https://doi.org/10.
O'Sullivan, K., 2018. Cognitive functional therapy: an integrated behavioral
1111/papr.12821.
approach for the targeted management of disabling low back pain. Phys. Ther.
Fleming, K.C., Volcheck, M.M., 2015. Central Sensitization Syndrome and the Initial
98 (5), 408e423.
Evaluation of a Patient with Fibromyalgia: A Review. Rambam Maimonides
Pecina, M., Martinez-Jauand, M., Love, T., Heffernan, J., Montoya, P., Hodgkinson, C.,
Med. J. 6 (2), e0020. https://doi.org/10.5041/RMMJ.10204, 2015 Apr, Published
Stohler, C.S., Goldman, D., Zubieta, J.K., 2014. Valence-specific effects of BDNF
online 2015 Apr 29.
Val66Met polymorphism on dopaminergic stress and reward processing in
Furness, J.B., Kunze, W.A., Clerc, N., 1999. Nutrient tasting and signaling mechanisms
humans. J. Neurosci. 34 (17), 5874e5881.
in the gut. II. The intestine as a sensory organ: neural, endocrine, and immune
Ratey, J.J., Hagerman, E., 2008. Spark e how exercise will improve the performance
responses. Am. J. Physiol. 277 (5), G922eG928. https://doi.org/10.1152/ajp-
of your brain. Quercus 38.
gi.1999.277.5.G922, 1999 Nov.
Redwine, L., Henry, B.L., Pung, M.A., Wilson, K., Chinh, K., Knight, B., Jain, S.,
Hebb, D.O., 2002. Organization of behaviour e a neuropsychological theory. Psy-
Rutledge, T., Greenberg, B., Maisel, A., Mills, P.J., 2016. Pilot randomized study of
chol. Press, 2002. ISBN 978e0805843002.
a gratitude journaling intervention on heart rate variability and inflammatory
Hegmann, K., Thiese, M., Kapellusch, K., Merryweather, A., Bao, S., Silverstein, B.,
biomarkers in patients with stage B heart failure. Psychosom. Med. 78 (6),
Wood, E., Kendall, R., Foster, J., Drury, D., Garg, A., 2017. Association between
667e676. https://doi.org/10.1097/PSY.0000000000000316, 2016 Jul-Aug.
epicondylitis and cardiovascular risk factors in pooled occupational cohorts.
Rohleder, N., 2014. 2014. Stimulation of systemic low-grade inflammation by psy-
BMC Muscoskel. Disord. 18 (227), 2017.
chosocial stress. Psychosom. Med. 76, 181Y189.
Hides, JA., Richardson, CA., Jull, GA., 1996. Multifidus muscle recovery is not auto-
Samsel, A., Seneff, S., 2013. Glyphosate, pathways to modern diseases II: Celiac
matic after resolution of acute, first-episode low back pain. Spine 21, 1996,
sprue and gluten intolerance. Interdiscipl. Toxicol. 6 (4), 159e184. https://
2763e9.
doi.org/10.2478/intox-2013-0026, 2013.
Holzer, P., Farzi, A., Hassan, A.M., Zenz, G., Jac˅an, A., Reichmann, F., 2017. Visceral
Scrivo, R., Vasile, M., Bartosiewicz, I., Valesini, G., 2011. Inflammation as “common
inflammation and immune activation stress the brain. Front. Immunol. 8, 1613.
soil” of the multifactorial diseases. Autoimmun. Rev. 10, 369e374, 2011.
https://doi.org/10.3389/fimmu.2017.01613.
Sinagra, E., Pompei, G., Tomasello, G., Cappello, F., Morreale, G.C., Amvrosiadis, G.,
Ji, R.R., Nackley, A., Huh, Y., Terrando, N., Maixner, W., 2018. Neuroinflammation and
Rossi, F., Monte, A.I.L., Rizzo, A.G., Raimondo, D., 2016. Inflammation in irritable
central sensitization in chronic and widespread pain. Anesthesiology 129 (2),
bowel syndrome: myth or new treatment target?, 22 World J. Gastroenterol. 21
343e366. https://doi.org/10.1097/ALN.0000000000002130, 2018 August.
(7), 2242e2255, 2016 February.
Juster, R.-P., McEwen, B., Lupien, S., 2010. 2010. Allostatic load biomarkers of chronic
Sleiman, S., Henry, J., Al-Haddad, R., El Hayek, R., Haidar, E., Stringer, T., Ulja, D.,
stress and impact on health and cognition. Neurosci. Biobehav. Rev. 35, 2e16.
Karuppagounder, S., Holson, E., Ratan, R., Ninan, I., Chao, M., 2018. Exercise
Kosek, E., Cohen, M., Baron, R., Gebhart, GF., Mico, J-A., Rice, ASC., Rief, W.,
promotes the expression of brain derived neurotrophic factor (BDNF) through
Sluka, AK., 2016. Do we need a third mechanistic descriptor for chronic pain
the action of the ketone body b- hydroxybutyrate. eLife 5, 15092. https://
states? Pain - Topical Review 2016 International Association for the Study of
doi.org/10.7554/eLife.15092, 2016.
Pain. https://doi.org/10.1097/j.pain.0000000000000507.
Slim, M., Molina-Barea, R., Garcia-Leiva, J.M., Rodríguez-Lopez, C.M., Morillas-
Liu, Y.-Z., Wang, Y.-X., Jiang, C.-L., 2017. Inflammation: the common pathway of
Arques, P., Rico-Villademoros, F., Calandre, E.P., 2017. The effects of a gluten-free
stress-related diseases. Front. Hum. Neurosci. 11, 316. https://doi.org/10.3389/
diet versus a hypocaloric diet among patients with fibromyalgia experiencing
fnhum.2017.00316.
gluten sensitivityelike symptoms - a pilot, open-label randomized clinical trial.
Longhi, R., Almeida, R.F., Machado, L., Duarte, M.M.M., Souza, D.G., Machado, P., de
J. Clin. Gastroenterol. 51 (6), 500e507. https://doi.org/10.1097/
Assis, A.M., Quincozes-Santos, A., Souza, D.O., 2017. Effect of a trans fatty acid-
MCG.0000000000000651, 2017 Jul.
enriched diet on biochemical and inflammatory parameters in Wistar rats,
Sleiman, SF., Henry, J., Al-Haddad, R., El Hayek, L., Haidar, EA., Stringer, T., Ulja, D.,
2017 Apr Eur. J. Nutr. 56 (3), 1003e1016. https://doi.org/10.1007/s00394-015-
Karuppagounder, SS., Holson, EB., Ratan, RR., Ninan, I., Chao, MV., 2016. Exercise

729
M. Wallden and J. Nijs
promotes the expression of brain derived neurotrophic factor (BDNF) through
the action of the ketone body b- hydroxybutyrate, 5, p. e15092. https://doi.org/
10.7554/eLife.15092, 2016.
Smith, TW., Uchino, BN., Bosch, JA., Kent, RG., 2014. Trait hostility is associated with
systemic inflammation in married couples: An actorepartner analysis. Biol.
Psychol 102, 51e53 (2014).
Solomonow, M., He Zhou, B., Lu, Y., King, KB., 2012. Acute repetitive lumbar syn-
drome: A multi-component insight into the disorder. J. Bodyw. Mov. Ther 16,
134e147 (2012).
Srednicka-Tober, D., Baranski, M., Seal, C., Sanderson, R., Benbrook, C.,
Steinshamn, H., Gromadzka-Ostrowska, J., Rembiałkowska, E., Skwarło-
Sonta, K., Eyre, M., Cozzi, G., Larsen, M.K., Jordon, T., Niggli, U., Sakowski, T.,
Calder, P.C., Burdge, G.C., Sotiraki, S., Stefanakis, A., Yolcu, H., Stergiadis, S.,
Chatzidimitriou, E., Butler, G., Stewart, G., Leifert, C., 2016. Composition differ-
ences between organic and conventional meat: a systematic literature review
and meta-analysis. Br. J. Nutr. 115, 994e1011. https://doi.org/10.1017/
S0007114515005073, 2016.
Stanhope, R., Wilks, Z., Hamill, G., 1994. Failure to grow: lack of food or lack of love?
Prof. Care Mother Child 4 (8), 234e237, 1994 Nov-Dec.
Vincent, FB., Saulep-Easton, D., Figgett, WA., Fairfax, KA., Mackay, F., 2017. The BAFF/
APRIL system: Emerging functions beyond B cell biology and autoimmunity.
Cytokine Growth Factor Rev. 24, 203e215 (2013).
Wallden, M., 2013. The primal nature of core function: in rehabilitation & perfor-
mance conditioning. J. Bodyw. Mov. Ther. 17, 239e248, 2013.
Wallden, M., Chek, P., 2018. The ghost in the machine e is musculoskeletal medicine
lacking soul? J. Bodyw. Mov. Ther. 22 (2), 438e448.
Walsh, J.J., Tschakovsky, Michael E., 2018. Exercise and circulating BDNF: mecha-
nisms of release and implications for the design of exercise interventions. Appl.
́ ́
730
Journal of Bodywork & Movement Therapies 27 (2021) 723e730
Physiol. Nutr. Metabol. 43 (11), 1095e1104. https://doi.org/10.1139/apnm-2018-
0192, 2018.
Williams, R., 1956. Biochemical Individuality. Keats Publishing, New Canaan, CT.
Willer, H., Lernoud, J., 2019. The World of Organic Agriculture. Statistics and
Emerging Trends 2019. Research Institute of Organic Agriculture (FiBL), Frick
and IFOAM e Organics International, Bonn. Available at. www.organic-world.
net/yearbook/yearbook-2019.html.
Wolcott, W., Fahey, T., 2000. The Metabolic Typing Diet. Doubleday, London.
Woolf, C.J., 2011. Central sensitization: implications for the diagnosis and treatment
of pain. Pain 152 (3 Suppl. l), S2eS15. https://doi.org/10.1016/j.pain.2010.09.030,
2011 March.
Yang, J., Tan, J., Zheng, L., Lu, C.X., Hou, W.Q., Liu, Y., Li, Q.F., Li, J.X., Cheng, D., Luo, X.,
Zhang, J., 2020. Plasma BDNF and TrkB mRNA in PBMCs are correlated with
anti-depressive effects of 12-weeks supervised exercise during protracted
methamphetamine abstinence. Front. Mol. Neurosci. 2020 (13), 20.
Yunus, M., 2015. Editorial Review: An Update on Central Sensitivity Syndromes and
the Issues of Nosology and Psychobiology. Curr. Rheumatol. Rev. 11, 70e85,
2015.
Zügel, M., Maganaris, CN., Wilke, J., Jurkat-Rott, K., Klingler, W., Wearing, SC.,
Findley, T., Barbe, MF., Steinacker, JM., Vleeming, A., Bloch, W., Schleip, R.,
Hodges, PW., 2018. Fascial tissue research in sports medicine: from molecules to
tissue adaptation, injury and diagnostics. Br. J. Sports Med. 52 (23), 1497.
https://doi.org/10.1136/bjsports-2018-099308, 2018 Dec, Epub 2018 Aug 2.
Zuluaga, G., Andersson, N., 2013. Initiation rites at menarche and self-reported
dysmenorrhoea among indigenous women of the Colombian Amazon: a
cross-sectional study. BMJ Open 3, e002012. https://doi.org/10.1136/bmjopen-
2012-002012.