Journal of Bodywork & Movement Therapies (2015) 19, 526e543

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FASCIA SCIENCE AND CLINICAL APPLICATIONS: EXTENSIVE REVIEW

A unifying neuro-fasciagenic model of

FASCIA SCIENCE AND CLINICAL APPLICATIONS: EXTENSIVE REVIEW

somatic dysfunction e Underlying

mechanisms and treatment e Part II
Paolo Tozzi, MSc Ost, DO, PT a,b,*

a
School of Osteopathy C.R.O.M.O.N., Rome, Italy
b
C.O.ME. Collaboration, Pescara, Italy

Received 3 October 2014; received in revised form 20 February 2015; accepted 24 February 2015

KEYWORDS Summary This paper offers an extensive review of the main fascia-mediated mechanisms un-
Fascia; derlying various therapeutic processes of clinical relevance for manual therapy. The concept of
Somatic dysfunction; somatic dysfunction is revisited in light of the several fascial influences that may come into
Fascial dysfunction; play during and after manual treatment. A change in perspective is thus proposed: from a noci-
Fascial mechanisms; ceptive model that for decades has viewed somatic dysfunction as a neurologically-mediated
Osteopathic phenomenon, to a unifying neuro-fascial model that integrates neural influences into a multi-
manipulative factorial and multidimensional interpretation of manual therapeutic effects as being partially,
treatment; if not entirely, mediated by the fascia. By taking into consideration a wide spectrum of fascia-
Osteopathic models; related factors e from cell-based mechanisms to cognitive and behavioural influences e a
Fascial treatment; model emerges suggesting, amongst other results, a multidisciplinary-approach to the inter-
Fascial release; vention of somatic dysfunction. Finally, it is proposed that a sixth osteopathic meta-model
Manual therapy e the connective tissue-fascial model e be added to the existing five models in osteopathic
philosophy as the main interface between all body systems, thus providing a structural and
functional framework for the bodys homoeostatic potential and its inherent abilities to heal.
2015 Elsevier Ltd. All rights reserved.

Introduction restrictive barrier, described as a functional limit that

abnormally diminishes the normal physiologic range
In osteopathic practice there are three main manual ap- (E.C.O.P., 2011a). This is maintained until tensions modify;
proaches that are directed towards the fascia: 1) direct 2) indirect approach e tissues are brought away from the
approach e the affected tissue is brought against the restrictive barrier while a position of ease (a balanced

* School of Osteopathy C.R.O.M.O.N., Rome, Italy.

E-mail address: pt_osteopathy@yahoo.it.

http://dx.doi.org/10.1016/j.jbmt.2015.03.002
1360-8592/ 2015 Elsevier Ltd. All rights reserved.
A unifying neuro-fasciagenic model of somatic dysfunction: Part 2
tension in all planes and directions) is found and main-
tained up to a release; 3) combined approach e both the
point of ease and the restrictive barrier are consecutively
engaged in an interactive fashion (Ward, 2003). Although
myofascial and fascial-ligamentous release techniques are
the most commonly applied fascial approaches amongst
American osteopathic physicians (Johnson and Kurtz, 2003),
there are a multitude of fascia related techniques that
utilize various levels of aggressiveness (Sergueef and
Nelson, 2014), from balanced ligamentous tension tech-
nique to counterstrain, from articulatory to cranial and
visceral techniques, including soft tissue work from inhibi-
tory pressure to effleurage manoeuvres.
Osteopathic treatment of fascia has shown to be effec-
tive for a wide variety of conditions, from local musculo-
skeletal causes, such as acute joint injury (Eisenhart et al.,
2003) to general mood disorders such as depression (Plotkin
et al., 2001). Other non-osteopathic manual modalities
have shown similar results, possibly because of the common
therapeutic influence and stimulation of the myofascial
complex (Simmonds et al., 2012).
Several mechanisms may underlie therapeutic changes
in the fascia.
Fascia-related mechanisms involved in the
treatment of somatic dysfunction
Structural changes
Structural modifications in the connective tissue may occur
immediately or just after treatment and may account for the
palpable changes following manipulation. Myofascial release
of the thoracolumbar fascia in patients with chronic low back
pain has shown an increase in thickness of fascial layers that
remained for at least 24 h (Blanquet et al., 2010). This sug-
gests a sustained change in the architecture and/or hydra-
tion of the fascia being worked on. In addition, US
measurements applied immediately before and after manual
intervention, showed highly significant differences in
collagen fibre density and orientation in the structure of the
matrix in the dermis, reflecting palpable differences in ten-
sion and regularity (Pohl, 2010). These findings are consistent
with the re-organization and remodelling of collagen fibres,
which have been suggested to result from myofascial work
(Martin, 2009) through a breakdown of abnormal collagen
cross-links and an increased matrix hydration.
Since abnormal palpable findings (such as altered
texture) in connective tissue might be related to abnormal
cross-links between collagen fibres, it has been shown that
human fibroblasts respond better to cyclical (3 min stress-3
minutes relaxation, of about 7% of their length) rather than
static stretch by increasing the production of collagenase
by 200% (Carano and Siciliani, 1996).
This enzyme has a potential role in collagen remodelling
in dysfunctional tissue by breaking cross-linking peptide
bonds, thus preventing excessive connective tissue forma-
tion, as occurs during wound healing. However, the repet-
itive mechanical stretch-induced collagenase activity can
also be suppressed by hormonal (oestradiol and progester-
one) influences (Zong et al., 2010), as might occur during
the menstrual cycle or in hormonal therapy.
527
A static load may also break abnormal tissue collagen
crosslinking and stimulate fibroblast differentiation under
the influence of IL-6, with a potential role in tissue repair
and remodelling (Hicks et al., 2012; Khan and Scott, 2009).
In addition, the duration of the load appears to be a sig-
nificant factor. It seems that brief periods of stretching may
decrease the effects of TGF-b1 production of additional
collagen, thus reducing the risk of fibrosis or scarring
(Langevin et al., 2006). Scars may generate pain syndromes
that can be relieved by a direct manual approach to the
involved connective tissue (Kobesova and Lewit, 2000), and
this could be applied in the first 12 h following surgery to
reduce inflammatory reactions and the risk of adhesion
FASCIA SCIENCE AND CLINICAL APPLICATIONS: EXTENSIVE REVIEW
formation (Chapelle and Bove, 2013).
Cell-based mechanisms
As will be described in this section, various forms of manual
loading, whether sustained or cyclical, that differ in di-
rection, speed, magnitude and frequency, appear to exert a
strong impact on cell behaviour, gene expression and tissue
remodelling through growth factors and enzyme activation.
Several cell-based mechanisms may potentially repre-
sent crucial factors in the achievement of a palpable
release during manual fascial work. Some of these are
described in Table 1.
Fibroblasts in vitro and in vivo have shown an almost im-
mediate response to traction, pressure and shear forces,
followed by a series of changes in chemical signalling path-
ways and gene activation, ATP release, actin polymeriza-
tion, and also differential stretch-activated calcium channel
signalling (Wall and Banes, 2005; Stoltz et al., 2000).
Although most of the proposed mechanisms may require
hours or even days before producing desirable effects on
tissue texture and function, some of them may take place
within minutes from the starting point of a therapeutic
manouver. Langevin et al. (2013) note that in response to
sustained changes in tissue length, fibroblasts may rapidly
modulate such tension by remodelling their cytoskeleton
and changing their contractile apparatus. Within minutes
they could remodel their cell-matrix contacts (focal adhe-
sions) along the direction of tissue stretch (Ciobanasu et al.,
2013; Geiger et al., 2009), or expand microtubule network
and actomyosin activation so as to maintain tensional
homoeostasis through an equal counter-tension (Eastwood
et al., 1998). This may produce a counterforce in the ma-
trix tension that might be palpable. Tensional load appears
to be perceived by the cell at a nuclear level too. Ex vivo and
in vivo studies demonstrate that fibroblasts respond within
minutes to mechanical stretching by dynamically remodel-
ling their cytoskeleton with perinuclear redistribution of
alpha-actin (Langevin et al., 2005, 2006; 2010). Although this
property of rapidly responding to mechanical stress appears
to be specific to areolar connective tissues only, it remains
significant for fascial work because loose connective tissues
form the interface between subcutaneous and perimuscular
layers, and are potentially engaged in manual interventions.
However, cytoskeletal remodelling failed to occur when
distinct matrix properties were produced in gel, as for
denser and stiffer connective tissue with increased cross-
linked collagen (Abbott et al., 2013). This shows the
 528 P. Tozzi

Table 1 Cellular mechanisms that may be involved in the manual fascial treatment of somatic dysfunction.
Fibroblast response
Collagen response
Mechano-coupling
FASCIA SCIENCE AND CLINICAL APPLICATIONS: EXTENSIVE REVIEW
Strain direction, frequency and duration of a (therapeutic) load may influence fibroblast
morphology, function and behaviour (Grinnell, 2003; Wang et al., 2004). When equi-radially
applied, it may lead to reduction of proinflammatory mediators and decrease of fibroblast
proliferation, possibly linked to clinical improvements in range of motion and reduction of
pain/inflammation (Standley and Meltzer, 2008).
Collagen synthesis and architecture responds to mechanical loading (Kjaer et al., 2009;
Thomopoulos, 2006), hence a therapeutic load may stimulate connective tissue remodelling
and repair.
Physical load produces a transduction into various chemical signals, leading to a modulation of
cell metabolism and response, changes in intracellular biochemistry and gene expression
(Ingber et al., 2014; Chiquet et al., 2009), depending on the type, duration, amplitude and

frequency of the load being applied (Lavagnigno et al., 2003).

Cellecell communication
Effector cell response
Stimulus in one location leads to a perturbation of distant cells, although these have not
received any direct mechanical stimulus (Lu and Thomopoulos, 2013; Wall and Banes, 2005).
Therefore a therapeutic load may produce beneficial effects even at distance to where it is
applied.
Appropriate mechanical loading stimulates protein synthesis at the cellular level, promoting
tissue repair and remodelling (Hardmeier et al., 2010; Wang et al., 2012) as well as cell
proliferation and migration in wound healing, by sensitizing fibroblasts to nitric oxide (Cao
et al., 2013b)

intrinsic interdependence between matrix and cell proper-
ties on determining the tissue response to a mechanical load.
During manual fascial techniques, the operator may feel
various tissue responses to the applied load that are
described as resistance or give to the stretch. Interest-
ingly, the mechanical loading of fascia causes changes
through activation of fibroblast response and the different
receptors present in the fascial tissue, leading to modulation
of myofascial contraction (Hicks et al., 2014). Spontaneous
contractions in fascia suggest the existence of an intrinsic
tension or pre-stress in the collagen scaffold (Staubesand
et al., 1997); and when an additional load alters this
tensional balance, so that the fascia is distended, the myo-
fibroblasts contract and resist this (Tomasek et al., 2002).
Various studies in vitro have demonstrated different cell
behaviours depending on the type, magnitude and fre-
quency of the artificial load being applied, and may be
clinically relevant to understand how tissues respond to
different modalities of intervention.
Fibroblasts and myofibroblasts are both highly respon-
sive to magnitude (Cao et al., 2013a), direction (Eagan
et al., 2007), frequency and duration (Meltzer and
Standley, 2007) of a (therapeutic) load, and can regulate
cell activity, proliferation or apoptosis (Meltzer et al.,
2010), mainly by influencing ion conductance, gene
expression and secretion of inflammatory mediators. In
particular, the secretion of IL-6 and IL-1 by fibroblasts
under equibiaxial stretch can exert powerful pro or anti
inflammatory responses, potentially leading towards
beneficial or detrimental matrix remodelling and cell
behaviour (Tsuzaki et al., 2003). A concomitant autocrine
and paracrine release of ATP may also serve as a negative
feedback mechanism to limit activation of destructive
pathways (Tsuzaki et al., 2003); and all of these factors may
influence the clinical efficacy of fascial treatment.
Although there were differences in degree and form,
most studies showed that heterobiaxial or cyclic short
duration strains can produce inflammatory reactions and
increased (occasionally reduced) fibroblast proliferation,
whereas a completely reversed pattern was observed with
equibiaxial or acyclic long-duration strains. In the latter,
even a normalization of the apoptotic rate was found
(Meltzer et al., 2010). This means the fascial tissue may
respond better to balanced and sustained stretch rather
than intermittent and unequal loads.
The force and duration of tension applied may also be
relevant. It has been shown that high magnitude (thera-
peutic) load (from 9% to 12% elongation) can produce an up-
regulation of ECM proteins, while increasing magnitude and
duration (1e5 min) loads induce cytokine and growth fac-
tors secretions (Cao et al., 2013a). These results are
consistent with those obtained by Yang et al. (2005), where
large-magnitude loads caused pro-inflammatory responses,
and cyclic (0.5 Hz per 4 h), uniaxial, small-magnitude
stretching produced anti-inflammatory reactions in human
tendon fibroblasts. Similarly, brief, moderate amplitude
(20e30% strain), static stretching of connective tissue
in vivo and ex vivo has been shown to decrease TGF-b1and
collagen synthesis, thus preventing soft tissue adhesions
(Bouffard et al., 2008).
In conclusion, brief, light/moderate, balanced, static or
slow cyclic strains appropriately applied to fascia may be
sensed at the cellular level and transduced in normalizing
tissue structure and function.
It is worth noting that while fibroblast cell orientation,
including cell shape and cytoskeleton, changes in a non
linear fashion according to different magnitudes of applied
cyclic load (Faust et al., 2011), the response of fibroblasts
to mechanical loading is also dependent on cell orientation.
In cells oriented parallel to a given cyclic stretch, higher
levels of alpha-smooth muscle actin were found to be
expressed; whereas fibroblasts that were perpendicular to
this showed higher activity levels of secretory phospholi-
pase A(2) which has a potential inflammatory role (Wang
et al., 2004). This indicates that therapeutic loads
applied differently with respect to tissue tension (that
A unifying neuro-fasciagenic model of somatic dysfunction: Part 2
presumably corresponds to cell orientation) may produce
different cell and tissue responses. Finally, secretion of IL-6
was significantly induced by 15 min of cyclic biaxial me-
chanical stretching after 4 and 8 h in human tendon fibro-
blasts, suggesting that inflammatory reactions following
manual intervention may be partially caused by IL-6
secretion (Skutek et al., 2001).
Neuromuscular interaction
Fascial oriented work may produce beneficial effects by
activating various receptors in the connective tissues that
elicit a series of neuromuscular reflexes. According to
Schleips neurobiological model (2003), these types of
events occur together with concomitant autonomic and
viscoelastic changes, and are more likely to explain the fast
tissue responses that a therapist perceives during fascial
techniques.
Although the dermis is the first tissue to be loaded during
manual treatment, evidence suggests that therapeutic ef-
fects such as inhibition on hypertonic muscle and presum-
ably on the myofascial complex, do not originate from
mechanical stimulation of superficial cutaneous mechano-
receptors (Merkel, Meissner receptors) during manual
therapy (Morelli et al., 1999). Similarly, deep receptors such
as Golgi tendon organs mainly exist in the myofascia, joint
capsules and myotendinous junctions (Jami, 1992), and are
unlikely to come into play during fascial treatment because
they have a high threshold that makes them respond to
strong and fast manual stimulus, to which they quickly adapt
(Pickar and Wheeler, 2001). This is why Golgi organs have
been mostly implied as being involved in neurophysiological
explanations that underlie the efficacy of spinal manipula-
tion (Pickar, 2002) and not of fascial treatment. In contrast,
Pacinian corpuscles are present in dense connective tissue
and deep fascia (Benjamin, 2009) and tend to quickly adapt
to stimuli, hence they respond better to rapid or intermit-
tent compression and vibrations (Bell et al., 1994) applied to
the myofascia, myotendinous junctions and deep capsular
layers. They are thought to respond to such stimuli by
enhancing proprioceptive feedback and by maintaining
muscle tone (Zimny and Wink, 1991). The type of thera-
peutic force needed to activate Pacinian corpuscles may be
applied in some manual interventions such as in high-
velocity manipulation or vibratory techniques.
Finally, Ruffinis endings are mainly located in joint
capsules and in the dense connective tissue (Halata et al.,
1985), including fascia (Yahia et al., 1992). They have a
slow adaptation to the stimuli being applied, and are thus
generally sensitive to slow, sustained or rhythmic deep
pressures, and in particular to lateral (perpendicular) tissue
stretches (Van der Wal, 2012). These kind of forces are
normally applied in most fascial techniques, such as myo-
fascial release.
Although these receptors have traditionally been
described as being organized in parallel arrangements, they
have more recently been shown to be functionally related
within a musculoskeletal and connective tissue continuum
that is in series (Van der Wal, 2009). Mechanoreceptors are
mainly concentrated in the transitional areas within the
continuum of the muscle-connective tissue-skeletal unit,
529
and serve to optimize transmission and control of forces.
Thus, because of the architecture, receptors can also be
stimulated by changes in muscle tension without skeletal
movement, or by skeletal movement without change in
muscle tension. (Van der Wal, 2009). A similar concept of
inter-tissue continuity has been advanced by Benjamin
et al. (2008), who re-elaborated the existence of the so-
called supertendons. This term refers to the tendon
network formed by the anatomically intrinsic interrelation
of fascia, tendon sheaths, joint capsules, retinacula, fat
pads and bursae, in which the function of the whole is
greater than that of its individual parts (Benjamin et al.,
2008). Such supertendinous structures may be critical for
FASCIA SCIENCE AND CLINICAL APPLICATIONS: EXTENSIVE REVIEW
the understanding of neuromuscular control. In fact,
cadaveric experiments and computer simulations have
shown that the distribution of tensions through these
super-structures regulates how force is distributed
distally, acting as a switching function of a logic gate that
nonlinearly enables different torque production capabil-
ities (Valero-Cuevas et al., 2007). This would demonstrate
the existence of a non-neural somatic logic that is able to
elaborate information at a macroscopic scale without
requiring neural processes. Therefore it is plausible that an
interaction of afferent impulses might come at different
frequencies and modalities from such a connective tissue
complex, including ligaments. The latter are apparently
capable of eliciting inhibitory ligament-muscular reflexes
with consequent inhibitory effects on related joint muscles
(Solomonow, 2009; Voigt et al., 1998), although this has not
yet been demonstrated to occur during manual therapy.
According to Schleips neurobiological model, the im-
mediate effects that occur during fascial release are
mediated through Ruffinis endings and interstitial mecha-
noreceptors that are abundant in fascia. The latter are
polymodal receptors (responsive to different kinds of
stimulation): some of them are very low threshold and
respond more to light tissue stretching, while others are
more sensitive to rapid pressure (Sandku hler, 2009). They
may also account for haptic perception (the sense of touch
through proprioception and somatosensory perception) in
the whole body (Schleip et al., 2014). It has been suggested
that they may exert an influence on autonomic activity (by
decreasing sympathetic activity) and on the central nervous
system, producing an indirect effect on haemodynamics
(vasodilation and plasma extrusion) and tissue viscoelas-
ticity together with a descending inhibition of muscular
tone (Schleip, 2003).
Some of the free nerve endings present in the interstitial
myofascial tissue have been defined as interoceptors, since
they inform the brain about physiological tissue conditions
such as temperature, pH and visceral changes (Craig, 2002).
In particular, tactile C-fibres have been recently discov-
ered in the human subcutaneous connective tissue. How-
ever, whereas classically C-fibres are described as
nociceptors or chemoreceptors, these tactile C-fibres are
low-threshold mechanoreceptive receptors accounting for
an alternative and distinctive system signalling touch in
humans (Bjo rnsdotter et al., 2010). It appears that activa-
tion of these unmyelinated sensory fibres, for example
during gentle touch therapy, relay signals to the insular
cortex, the medial prefrontal cortex, the dorso-anterior
cingulate cortex (but not to the somatosensory areas)
 530
(McGlone et al., 2014), where sensory and affective infor-
mation are integrated giving rise to limbic touch, with
resultant downstream effects on interpersonal touch,
affiliative behaviour, psycho-endocrine function, immune
system, autonomic regulation and pain modulation
(Olausson et al., 2010).
The classical nociceptive model, instead, proposes that
indirect fascial techniques may modulate muscle tone and
related fascial tension by decreasing mechanical stress and
neural inputs (Van Buskirk, 1990). This may in turn reduce
the activity of nociceptors and of the correspondent facil-
itated spinal level that by neurological reflex may produce
a consequent modulation of autonomic activity on blood
FASCIA SCIENCE AND CLINICAL APPLICATIONS: EXTENSIVE REVIEW
and lymphatic flow. Finally, in response to the proprio-
ceptive input, the central nervous system may change
muscle tone, allowing the therapist to follow myofascial
paths of least resistance until a palpable release is
perceived (Minasny, 2009).
Autonomic influence
Somatic dysfunction has been traditionally related to
correspondent facilitated spinal levels and aberrant auto-
nomic activity that in turn influences various visceral
functions (Korr, 1979; Beal, 1985). Interestingly, autonomic
adrenergic fibres have been found in fascia (Tanaka and Ito,
1977), with a plausible major role on vasomotor control of
intrafascial blood vessels (Tesarz et al., 2011). It has been
suggested that therapeutic touch may produce stimulation
of pressure-sensitive mechanoreceptors in the fascia (Ruf-
finis and interstitial receptors), followed by a para-
sympathetic response (Schleip, 2003). This in turn may
induce a change in local vasodilatation and tissue viscosity,
together with a lowered tonus of intrafascial smooth mus-
cle cells, and such a response has been partially demon-
strated. Both massage therapy and myofascial osteopathic
treatment have been shown to produce an increase in vagal
efferent activity, as shown by changes in heart rate (Field
et al., 2010), even in healthy subjects (Giles et al., 2013);
while other forms of fascia oriented manual therapy (Danis
Bois method) may produce an upregulation of para-
sympathetics with an influence on blood shear rate and
blood flow turbulence (Quere et al., 2009). At the same
time, a modulation of hypersympathetic activity may take
place (Henley et al., 2008), normalizing various haemody-
namic parameters, with improvement of endothelial func-
tion (Lombardini et al., 2009), and anxiety levels
(Fernandez-Perez et al., 2008). However, reduced psycho-
logical distress, anger status, anxiety levels and perceived
pain have also been associated with an increase of sym-
pathetic activity and heart rate following manual therapy
(Hatayama et al., 2008; Toro-Velasco et al., 2009).
Viscolelastic changes
Biological structures exhibit viscoelastic properties and
responses under mechanical loads (Kucharova et al., 2007),
with significant changes depending on chronological age
(Doubal and Klemera, 2002). Generally, the stronger and
more rapidly that a load is applied to organic materials, the
more rigidly will the tissue respond, up to the point when
P. Tozzi
the elastic potential of tissues is exceeded and a plastic
deformation occurs (Ja ger, 2005).
Traditionally, it has been suggested that most of the
immediate tissue changes following manual fascial work
may be the result of a colloidal change in the fascia, which
means a transformation of the ground substance from a
dense solid-like state (gel) to a more fluid (sol) state (Rolf,
1962). However, a 3D mathematical model for fascial
deformation has rejected the idea that palpable sensa-
tions of tissue release following manual therapy may be
due to plastic deformations of firm type of fascia, such as
the fascia lata and plantar fascia, whereas this may be
possible in thin and more elastic types of fasciae
(Chaudhry et al., 2008). Schleips neurobiological model
has instead proposed that following proprioceptive stim-
ulation the Ruffinis endings and interstitial fascia mech-
anoreceptors may be involved in efferent control of the
vasodilation and increase of plasma extravasation via
autonomic activation (Schleip, 2003). This would initiate
ECM viscosity changes. Nevertheless, there is evidence
that a similar phenomenon may take place within minutes
of a tensional load being applied and as the result of cell-
matrix-induced regulation of fluid flow that is independent
of neurological activation. Langevin et al. (2011) have
demonstrated that static tissue stretch of areolar con-
nective tissue (w20e25 %) causes fibroblast cytoskeletal
remodelling via activation of focal adhesion complexes
and initiate signalling pathways mediated by Rho kinase.
This in turn leads to remodelling of the cells focal adhe-
sions and actomyosin activation that develops counter-
tension. The latter process allows surrounding tissue to
relax further and achieve a lower level of resting tension.
The study has shown that by changing shape, fibroblasts
can dynamically modulate the viscoelastic behaviour of
areolar connective tissue through Rho-dependent cyto-
skeletal mechanisms.
Fluid dynamics
The mechanism described above may also potentially
regulate extracellular fluid flow into the tissue and protect
against osmotically-driven swelling when the matrix is
stretched (Langevin et al., 2013). The flow of water in the
ECM depends on the opposing forces between the osmotic
pull of under-hydrated glycosaminoglycans and the active
restraint of the tensioned collagenous network as the result
of fibroblast activity. Therefore, as long as the tension in
the matrix is maintained by fibroblasts, water is prevented
from entering the tissue (Reed et al., 2010). During the
acute onset of inflammation, however, the matrix swells as
inflammatory mediators disrupt the cell-matrix contacts,
causing a drop in matrix tension and interstitial fluid pres-
sure, and allowing water to be sucked into the matrix
(Reed and Rubin, 2010). A (therapeutic) stretch lasting for a
few minutes could then e potentially e un-restrain the
matrix and promote transcapillary fluid flow and temporary
matrix swelling. Fibroblasts, in turn, can either release
their matrix contacts e resulting in a further drop of
interstitial fluid pressure e or remodel the contractile
cytoskeleton and adhesive matrix contacts, so as to develop
a counter-tension sufficient to restore tension equilibrium
A unifying neuro-fasciagenic model of somatic dysfunction: Part 2
(Langevin et al., 2013). This model would also fit with the
fascial hydrodynamic response reported by Schleip et al.
(2012). In response to mechanical stimuli, such as
compression and stretch, fascia may exhibit a sponge-like
behaviour, showing a squeezing and refilling response
under the opposing forces of the restraint of collagen
network and the osmotic pull of proteoglycans complex.
Interestingly, the fluid pressure might increase more
during tangential oscillation (2e4 Hz) and perpendicular
vibration (15e60 Hz) with respect to the fascial layer than
during constant sliding or back-and-forth motion, as pre-
dicted by 3D mathematical modelling methods (Roman
et al., 2013; Chaudhry et al., 2013). This would cause the
flow to occur more around the edges of the area under
manipulation e due to an increased pressure gradient e
producing an enhanced lubrication and an improved sliding
potential between fascial layers and muscle tissue. Thus,
the use of vibratory and oscillatory techniques e and not
just constant sliding motions e should be considered,
especially when interstitial fluid dynamics need to be
improved such as in the case of fibrotic tissue.
Interstitial flow also induces fibroblast-to-myofibroblast
differentiation as well as collagen alignment and fibroblast
proliferation, playing an important role in fibrogenesis and
tissue repair (Ng et al., 2005). Furthermore, it appears to
affect intracellular processes (calcium signalling, protein
secretion) and influence fibroblast activities such as
growth, proliferation, differentiation, alignment, adhesion,
migration (Dan et al., 2010), including tissue morphogen-
esis, remodelling and embryonic development (Rutkowski
and Swartz, 2007) through mechanisms such as direct
shear stress, matrix-cell transduction and autologous
gradient formation. Interstitial flow may also be enhanced
by the interplay of calcium ion concentration and unbound
water oscillations (Lee, 2008), whose respective electric
and pressure gradients improve the transport of oxygena-
tion and nutrients in the tissues. Since fluid flow in the ECM
is likely to transport metabolic and messenger substances
(Meert, 2012), it may indeed play a role in restoring
homoeostasis where it has been compromised. For
instance, it could improve drainage of inflammatory medi-
ators, so decreasing chemical irritation and nociceptive
stimuli to nerve endings, hence leading to a reset of aber-
rant reflexes underlying somatic dysfunction.
Endocrine-immunity response
The evidence suggests that manual therapy focussed on
myofascial tissues could cause hormonally mediated effects
that persist for several days and modulate the
hypothalamic-pituitary-adrenal axis and immune function
(Rapaport et al., 2012, 2010; Morhenn et al., 2012). How-
ever, such hormonal response does not occur following
isolated articulatory techniques such as the osteopathic
technique known as rib raising directed towards enhanced
thoracic mobility, respiration efficiency and lymph-flow
(Henderson et al., 2010). Interestingly, the response to
myofascial treatment can differ quite profoundly depend-
ing on the frequency of therapeutic sessions. Consistently
with results from a previous study (Rapaport et al., 2010), a
once-a-week intervention demonstrated patterns of change
531
in circulating lymphocyte markers and cytokine expression,
while twice-weekly sessions increased oxytocin levels and
production of pro-inflammatory cytokines, together with
decreased arginine vasopressine and cortisol levels
(Rapaport et al., 2012). Hormonal changes were sustained
for up to four days, while cyotokines changes persisted for
up to eight days. In another study, the increase of oxytocin
was also correlated with a decrease in adrenocorticotropin
hormone following manual work (Morhenn et al., 2012).
Oxytocin, in particular, could play a role as an endogenous
pain controlling system. It has been demonstrated that,
following manual intervention, increased levels of this
hormone have been found in plasma and periaqueductal
FASCIA SCIENCE AND CLINICAL APPLICATIONS: EXTENSIVE REVIEW
grey matter, exhibiting anti-nociceptive effects possibly
through interaction with the opioid system (Lund et al.,
2002). Furthermore, oxytocin appears to be strongly
related to the formation of social bonds as well as of
interpersonal bonding involving trust (Lieberwirth and
Wang, 2014), thus influencing the psychosocial dimension
of the individual.
The benefits of osteopathic manipulation, including
myofascial work, have also been related to a remarkable
increase in nitric oxide (NO) concentration in the blood
following therapeutic intervention (Salamon et al., 2004).
This has been demonstrated to occur in equal amounts to
that released during moderate physical exercise
(Overberger et al., 2009). Similarly, results obtained from
in vitro studies have confirmed this possibility. For
instance, acyclic biophysical strain on normal human
dermal fibroblasts has shown a three-fold increase in NO
when applied at 10% magnitude for 72 h (Dodd et al.,
2006). In addition, an increased sensitivity to NO via
phosphokinase signalling, together with a 12.2% increase in
NO secretion, were found in fibroblasts following modelled
myofascial release (Cao et al., 2013b). This suggests a po-
tential clinical role for NO in wound healing by promoting
cell proliferation and migration. NO is an important sig-
nalling molecule whose known beneficial effects (Tota and
Trimmer, 2011), may explain some of the therapeutic re-
sults following fascial work. It may be involved in promot-
ing tissue repair and collagen synthesis, improving clinical
symptoms and functions following injury (Bokhari and
Murrell, 2012); in smooth muscle relaxation and angiogen-
esis (Ziche and Morbidelli, 2000); in neurotransmission
(Garthwaite, 2008) as well as in the response to immuno-
gens (Wink et al., 2011).
There is a strong possibility that the physiological effects
of myofascial work may be in part due to stimulation of the
endocannabinoid system (McPartland et al., 2005). This
system affects fibroblast remodelling and may play a role in
fascial reorganisation by diminishing nociception and
reducing inflammation in myofascial tissue (McPartland,
2008). Osteopathic treatment, including myofascial work
to specific sites of somatic dysfunction, has demonstrated a
change in the concentration of several circulatory noci-
ceptive biomarkers in patients with chronic low back pain
(Degenhardt et al., 2007). Amongst other results, the in-
crease in N-palmitoylethanolamide (an endogenous fatty
acid amide with potent analgesic and anti-inflammatory
properties) was found 30 min after intervention, at a con-
centration two times greater than that observed in control
subjects.
 532
Finally, it has been proposed that fascial work may
enhance cytokine pools from actively proliferating fascial
fibroblasts (Willard et al., 2010), which may be delivered
beyond the sites being treated via intrafascial blood flow
(Bhattacharya et al., 2005).
Epigenetics
Mechanical forces seem to be crucial regulators of cell
behaviour and tissue differentiation by affecting gene
regulation at the epigenetic level, therefore producing an
heritable reduction of DNA methylation (Arnsdorf et al.,
FASCIA SCIENCE AND CLINICAL APPLICATIONS: EXTENSIVE REVIEW
2010). In other words, mechanical stimulation can pro-
duce durable alterations in gene expression during cell
lineage commitment (Arnsdorf et al., 2010). It can be
speculated that a therapeutic mechanical load might pro-
duce the same sort of effects. These epigenetic changes
may also regulate extracellular matrix composition,
inflammation, angiogenesis and fibroblast activity involved
in tissue repair and function (Bavan et al., 2011). Mechan-
ical signals applied in the form of vibration to hydrogel-
encapsulated fibroblasts in culture have also been demon-
strated to be a critical epigenetic factor in regulating the
microenvironment of the ECM. In particular, they produce
significant increases in glycosaminoglycans and decreases in
collagen, thus providing a basis for reducing tissue adhe-
sions and improving connective tissue function (Kutty and
Webb, 2010).
Respiration
Traditionally, patient respiratory cooperation has been
used in osteopathic practice to assess and treat vertebral,
appendicular, cranial, visceral and soft tissue dysfunc-
tions, including myofascial ones, especially in acute pre-
sentations (Kimberly, 1949). It has also been used to
promote patient relaxation, or divert his/her attention.
Most osteopathic fascial techniques may require a respi-
ratory co-operation when holding tissues at the barrier
point, or while keeping them at a balance point. Suther-
land, in particular, proposed it as a specific tool to exag-
gerate dysfunction and induce correction: . the
respiratory movement picks up the abnormally related
parts and swings them into motion in unison with contig-
uous parts (In Hoover, 1945). Such respiratory contribu-
tion may play a role in relaxation of the myofascia and
improvement in joint mobility, indeed breathing fre-
quency seems to be synchronized with cerebral electrical
activity (Busek and Kemlink, 2005) and to produce both a
mechanical effect on resting myofascial tissue (Cummings
and Howell, 1990) and to have a neurological influence on
non-respiratory muscles (Kisselkova and Georgiev, 1979).
This shows the interaction of respiration with the muscu-
loskeletal system. Furthermore, breathing frequency has
the ability to be synchronised with oscillations in blood
pressure (De Burgh Daly, 1986), heart rate (Song and
Lehrer, 2003) and lymphatic flow (Zawieja, 2009),
together with being amplified due to resonance effects
between these systems (Courtney, 2009). Through fre-
quency entrainment, pulmonary respiration may also
potentially modulate autonomic activity (Gilbey, 2007),
P. Tozzi
together with peripheral blood flow and therefore body
temperature (Ahmed et al., 1982). All these interactions
appear to be centrally coupled, interconnected and
modulated (Dick et al., 2009, 2014), hence suggesting
pulmonary respiration as an entry point for the homoeo-
static potential of the body during treatment.
Vibratory and oscillatory activating forces
Oscillations and vibrations are frequently applied as acti-
vating forces in many fascial manoeuvres. Sutherland
(1990) suggested the benefits of vibration applied to the
lymphatics, while Mitchell (1999) proposed vibrations as a
way to counteract the myotactic reflex in hypertonic
muscles. Fulfords percussion hammer, in particular, is
proposed as an effective tool to treat fascial dysfunctions
by applying beneficial vibrational frequencies to the
affected tissue (Fulford and Stone, 1997). Interestingly,
fascial tissue seems to display a physiological oscillatory
behaviour at a cellular level. Castella et al. (2010) have
shown that myofibroblastic contractions exhibit periodic
oscillation periods of approximately 100 s (1 c.p. 100 s),
modulated by periodic intracellular calcium oscillations.
These in turn are mediated via cell adherence junctions
(Follonier Castella et al., 2010) that could explain the in-
crease of calcium oscillation frequencies in myofibroblasts
when an increased mechanical load is applied and trans-
mitted through such intercellular junctions. In turn, this
also induces reactive changes in the contractile cell
behaviour (Godbout et al., 2013).
Research suggests that vibration and oscillation of
different amplitude, forces or frequencies (from 8 to
110 Hz), applied from seconds to 45 min, and whether
manually or artificially induced, may have an influence on a
variety of body functions, such as: modulating spinal
excitability (Kipp et al., 2011) and pain perception in both
healthy and chronic patients (Kosek and Hansson, 1997);
increasing tissue blood perfusion with the increase of
vibratory load (Fuller et al., 2013); enhancing fascial
interstitial fluid flow, as suggested by a mathematical
model (Roman et al., 2013); increasing oxygen saturation
and improving pulmonary mechanism and perfusion
(Doering et al., 1999); modulating blood flow in different
cerebral areas (Coghill et al., 1994); improving joint range
of motion (Bakhtiary et al., 2011) and reducing muscle
stiffness (Peer et al., 2009); enhancing wound healing
processes and regeneration of vessels by also reducing local
oedema and general congestion (Leduc et al., 1981);
regulating the microenvironment of the ECM at an epige-
netic level, when applied to fibroblasts in vitro (Kutty and
Webb, 2010); and improving cognitive performance in
both healthy and pathological conditions (Fuermaier et al.,
2014). Furthermore, manual low frequency oscillations may
induce myofascial relaxation by influencing motoneuron
excitability (Newham and Lederman, 1997), or by producing
an inhibitory effect on vestibular nuclei, hence inducing a
psychogenic relaxation (Ayres, 1979). As Littlejohn stated
(1902): There is no function of the body that does not
have peristaltic or rhythmic vibrations . the power of
osteopathic treatment occurs from its effect upon physio-
logic oscillations.
A unifying neuro-fasciagenic model of somatic dysfunction: Part 2
Bioenergetic interactions
All cells appear to generate and detect electromagnetic
fields, ranging from kHz to the visible part of the electro-
magnetic spectrum (400e790 THz) (Cifra et al., 2011).
These fields may be forms of non-chemical cell signalling
able to influence cell proliferation rate and morphology
(Rossi et al., 2011). In addition, such electromagnetic sig-
nals may be amplified by ion channels, with ionic flow
oscillating at various coherent frequencies as an intracel-
lular sensing system (Galvanovskis and Sandblom, 1997).
Furthermore, ion channels and pumps seem to modulate
endogenous transmembrane resting voltage potential that,
in turn, may regulate cell proliferation, migration and dif-
ferentiation, serving as an informational signalling pathway
(Adams and Levin, 2013). Importantly, this is a mediator of
large-scale anatomical polarity with an effect on gene
regulation pathways, hence influencing tissue morphogen-
esis, development and regeneration (Levin, 2014). Inter-
estingly, endogenous electrical potentials may promote
epithelial cell migration and wound healing (Zhao, 2009), as
well as angiogenic responses in endothelial cells (Zhao
et al., 2004). This phenomenon is mediated by polarized
activation of multiple signalling pathways that include ki-
nases, membrane growth factor receptors and integrins.
Fibroblasts in particular have shown to be highly responsive
to endogenous electrical fields, by aligning themselves
perpendicular to the electrical current and consequently
modulating their motility (Guo et al., 2010). They also seem
to respond to exogenous electricity; exposure to electrical
stimulation of 50 or 200 mV/mm promotes wound healing
by enhancing growth factor secretion, skin fibroblast
migration and fibroblast to myofibroblast differentiation
(Rouabhia et al., 2013).
Therefore, electromagnetic fields appear to be strictly
related to ionic flow and oscillations, and these in turn are
highly responsive to mechanical tension via stretch-
activated calcium channels (Follonier Castella et al.,
2010). (Therapeutic) mechanical pressure or electrical
stimulation may be amplified and propagated by proton
currents or coherent oscillations and polarization waves
throughout the organism (Pang, 2012). Such proton con-
duction may be coupled with electron transfer (Cukier and
Nocera, 1998) and with hydrogen-atom translocation along
the watereproteins complex (Cukier, 2004). In this sense, it
can be speculated that fascia combines the property of a
sol-liquid conductor and of a crystal generator system due
to the liquid crystal continuum of the matrix, which can
generate and conduct direct currents as well as vibrations.
Hypothesis. A yet more interesting possibility is that the
liquid crystalline continuum of the body matrix may function
as a quantum holographic medium, recording patterns of
local activities interacting with a globally coherent field.
During bodywork an interaction of vibrational, biomagnetic
and bioelectric fields between therapist and client may take
place. This would allow an exchange of information about
the history and the present status of the living matrix, which
is encoded in cell and tissue structure, and which is
accessable holographically by tuning to the appropriate
frequencies (Oschman and Oschman, 1994). The result may
533
be the balancing of resonant vibratory circuits. Osteopathic
manipulative treatment may entrain such physiological
phenomena, restoring harmonic resonance where disso-
nance is present (McPartland and Mein, 1997).
Finally, the human body has been demonstrated to emit
ultra-weak photons in the visible part of the electromag-
netic spectrum (380e780 nm) and in the range from 1 to
1000 photons  s 1  cm 2 (Schwabi and Klima, 2005). This
property is the result of cellular metabolic activities and
appears to be enhanced by increased oxidative processes
(Rastogi and Pospsil, 2010). The quantum state of photons
emitted by a subject could be in a coherent state and un-
FASCIA SCIENCE AND CLINICAL APPLICATIONS: EXTENSIVE REVIEW
dergoing constant variations (Van Wijk et al., 2008), dis-
playing a typical anatomic percentage distribution pattern,
depending on the individuals condition and vitality. Photon
emissions may be used by cells and tissues as a modality of
communication, independently from chemical and cell-to-
cell contact signalling (Scholkmann et al., 2013). They
may also represent an informational and regulatory system
(Kucera and Cifra, 2013) affecting at least energy uptake,
cell division rate and growth correlation (Fels, 2009). This
property may be deregulated or altered in case of
dysfunction or disease e including those affecting connec-
tive tissue e and related to a generally high oxidative status
of the organism (Popp, 2009). Interestingly, the emissions
intensity decreases with a reduction in body temperature
and oxygen concentration (Nakamura and Hiramatsu,
2005), while it reduces in long-term practitioners of medi-
tation, as a probable reflection of different free radical
reactions in the organism (Van Wijk et al., 2006). This ev-
idence suggests the integrative use of additional strategies
such as nutritional care, appropriate physical activity,
mind-body therapy to enhance therapeutic effects of
manual treatment of somatic dysfunction by reducing the
general oxidative status in patients.
Additional strategies
- Physical Exercise
Specific physical training programs for fascial tissue may be
applied (Schleip and Mu ller, 2013), implying elastic recoil,
slow and dynamic stretching, rehydration practices and
proprioceptive refinement. It has been demonstrated that
the elastic storage capacity and subsequent recoil of the
elastic energy in tendons may significantly increase, with a
decrease in stiffness, following physical exercise programs
(Ishikawa and Komi, 2004; Reeves, 2006), without affecting
fascial thickness (Uzel et al., 2006). Furthermore, fascia-
specific stretching protocols may produce long-term bene-
fits where there is chronic fascial pain and improve physi-
ological function and patient satisfaction (Digiovanni et al.,
2006).
- Nutrition
A tryptophan or atherogenic diet may increase oxidative
damage in muscles, with infiltration of inflammatory cells in
muscular fascia (Ronen et al., 1999). Instead, an anti-
 534
inflammatory diet may provide a natural approach to
reduce inflammation, also in the case of musculoskeletal
conditions (Marcason, 2010). It mainly implies a reduction
of intake of saturated fatty acids, with an increase of plant-
based food (Pomari et al., 2014), beverages rich in poly-
phenolic catechins (such as green tea), cold water fish
(Kris-Etherton et al., 2002), culinary herbs and spices with
anti-inflammatory effects e such as ginger and turmeric e
(Tapsell et al., 2006). In particular, a group of aromatic
ketones, called chalcones, present in several plants such as
licorice and mulberry, have been linked with immunomo-
dulation, anti-inflammatory and anti-oxidant activities
(Yadav et al., 2011). For example: avocado and soybean
FASCIA SCIENCE AND CLINICAL APPLICATIONS: EXTENSIVE REVIEW
oils, etc, contain biologically active compounds that are
able to produce long-term beneficial effects in the symp-
toms of osteoarthritis (Ragle and Sawitzke, 2012); devils
claw has been used to treat degenerative disorders of the
musculoskeletal system, and for its pain-relieving, anti-in-
flammatory and anti-oxidant actions (Akhtar and Haggi,
2012); crude extract of blueberries, rich in phenolic acids
and flavonoids, have anti-nociceptive and anti-
inflammatory properties (Torri et al., 2007); and extracts
from plants such as Phyllanthus corcovadensis have
demonstrated potent anti-nociceptive effects (Gorski
et al., 1993). Finally, the balance in the omega 6/omega
3 ratio in dietary patterns is crucial for the maintenance of
health (Go mez Candela et al., 2011), as well as for the
prevention and management of inflammatory conditions
(Simopoulos, 2009), or as an adjunct treatment for chronic
arthritis (James and Cleland, 1997).
- Meditation
Mindfulness meditation and breath therapy seem to play
a role in improving quality of life and sense of coherence in
people who start with a low health assessment (Fernros
et al., 2008). In particular, mindfulness-based treatment
may reduce cortisol level, proinflamatory cytokines and
blood pressure (Carlson et al., 2007), with enhanced out-
comes for health and quality of life in chronic disease,
including musculoskeletal disorders (Merkes, 2010).
Furthermore, when associated with home meditation prac-
tice, it may ameliorate pain intensity and functional limi-
tations in chronic musculoskeletal conditions (Rosenzweig
et al., 2010). Breath therapy integrating body awareness,
breathing, meditation and movement appears to produce
significant improvement in chronic low back pain and coping
skills (Mehling et al., 2005). Finally, yoga intervention may
reduce pain and catastrophizing, increase acceptance of the
condition and alter total cortisol levels in people with
chronic disorders (Curtis et al., 2011). Even more, it may
improve functional disability in people with chronic low back
pain (Holtzman and Beggs, 2013), with both short and long-
term effectiveness (Cramer et al., 2013).
Placebo
Placebo effects are complex phenomena, possibly mediated
by specific physiological and neural mechanisms, but these
are currently poorly understood (Miller et al., 2013). In the
field of manual therapy, the term placebo effect is taken to
P. Tozzi
mean not only the narrow effect of an imitation intervention
but also the broad amalgam of nonspecific effects present in
any patientepractitioner relationship, including attention;
communication of concern; intense monitoring; diagnostic
procedures; labelling of complaint; and alterations pro-
duced in a patients expectancy, anxiety, and relationship to
the illness (Kaptchuk, 2002). Traditionally, placebo is
thought of as a nuisance in clinical and pharmacological
research, and controls are employed to filter out non-
specific, undesired and psychological effects that may
interfere with the results from a particular therapeutic
intervention. However, it is likely that an individuals un-
derstanding of the intervention influences the effects of any
given therapeutic approach, showing the importance of
placebo in clinical, scientific and physiological fields
(Oeltjenbruns and Scha fer, 2008). This then drives research
to further our understanding of the underlying mechanisms,
which is needed in order to maximize therapeutic results in
clinical practice (Walach and Jonas, 2004). Placebo anal-
gesia is now considered as a biological phenomenon,
implying both opioid and non-opioid mechanisms (Carlino
et al., 2011) that are measurable through brain imaging
technologies and that can be pharmacologically blocked and
behaviourally enhanced (Greene et al., 2009). It seems to be
dependent on frontal cortical areas that generate and
maintain cognitive expectancies, which in turn may be
reinforced by dopaminergic reward pathways (Faria et al.,
2008). Finally, the ability of placebo to modulate periph-
eral immune reactivity is plausible (Pacheco-Lo pez et al.,
2006), although other placebo responses result from less
conscious processes, such as classical conditioning in the
case of immune, hormonal, and respiratory functions (Price
et al., 2008). Recent research on placebo response, placebo
analgesia and nocebo has shown how the psychosocial
aspect of every treatment is crucial in determining the na-
ture and degree of a placebo effect, affecting both research
and clinical practice (Koshi and Short, 2007; Marchand and
Gaumond, 2013). Alternative and complementary medi-
cine may also have an enhanced placebo effect, compared
with mainstream medicine, through a ritual-based perfor-
mative efficacy (Kaptchuk, 2002).
Cognitive-behavioural factors and multidisciplinary
approach
Manual therapeutic intervention should never be focused
on the dysfunctional or symptomatic area exclusively, apart
from in some presentations such as time-limited emergency
situations. Instead, the multidimensional aspect of pain
should be considered, especially for chronic patients (Lima
et al., 2014), with respect to the tenet of the body, mind
and spirit unity (Rogers et al., 2002). Therefore, in order to
approach the totality of an individual (not just a pain),
including his/her social environment, it is necessary to
wisely apply biopsychosocial models (Flor and Herman,
2004) e considered as congruous with osteopathic princi-
ples (Penney, 2010) e as well as interdisciplinary paradigms
(Gatchel, 2005), which resonate with osteopathic philoso-
phy (Mackintosh et al., 2011). Instead of just treating a
dysfunction, health should be promoted through a saluto-
genic process (Antonovsky, 1979) that is guiding the patient
A unifying neuro-fasciagenic model of somatic dysfunction: Part 2
from the cure of the disease to the protection and poten-
tiation of their own health and quality of life. Information
and education are the key tools to guide the patient and
his/her social environment through such a process, where
the operator may just be a catalyst for the change to take
place (Gafni et al., 1998). In addition, the social coherence
of interdisciplinary and inter-sectorial action is crucial to
support health-related quality of life (Drageset et al., 2009)
as well as the process of health through the course of life
(Eriksson and Lindstrom, 2008).
Maladaptive behaviours, fears and emotional experience
of pain, catastrophism, helplessness, expectations, thrust,
cognitive factors, faith, beliefs and personality all need to
be addressed in a comprehensive and integrative concep-
tual model that is applied to the clinical assessment,
treatment and management of patients with pain, and in
particular when pain is persistent (Keefe et al., 2004;
Nicholas et al., 2011). These factors should be identified
and managed as far as reasonably possible in order to
support and promote active coping strategies (Jensen
et al., 1991), mechanisms of self-efficacy (Bandura, 1982)
and an empowerment process (Haldeman et al., 2008).
These mechanisms may increase tolerance for pain through
endogenous opioid activation, when confronted with a
painful stimulus (Bandura et al., 1987). Conversely, pa-
tients with chronic pain and high levels of depression tend
to experience and rate their pain as more severe (Parmelee
et al., 1991). Probably through a similar process, a patients
attitude may strongly influence the effect of myofascial
treatment. For instance, patients with cancer-related fa-
tigue who had a positive attitude towards manual therapy
showed a significant (p > .05) increase of immune response
(IgA), compared to the control group, following myofascial
release (although no difference was found in the pressure
pain threshold) (Ferna ndez-Lao et al., 2012a). Further-
more, a positive patient attitude may positively modulate
the impact of manual therapy compared to a placebo group
(Fernandez-Lao et al., 2012b).
A multidisciplinary approach is paramount to achieve
the most desirable clinical outcomes, especially in chronic
patients (Pergolizzi et al., 2013), also those with musculo-
skeletal pain (Hildebrandt et al., 1996) and even in a pri-
mary care setting (Kim et al., 2010). Multidisciplinary
rehabilitation programs have been demonstrated to be
more effective than the care given by independent physi-
cians in patients with chronic low back pain, when orga-
nized with the cooperation of local health-care providers in
the community (Lang et al., 2003). Its clinical imple-
mentation may extend to include relaxation training,
biofeedback, hypnosis, imagery, cognitive-behavioural
therapy (Golden, 2002), social reinforcement and time-
contingent medications, but it may also require the inter-
action of rehabilitative, occupational, pharmaceutical,
surgical, orthesic, psychological and nutritional care. Group
therapy programs also seem to produce good results. For
instance, patients with chronic musculoskeletal pain
improve their self-awareness and active coping strategies,
with a decreased pain experience, when participating in
group sessions of experience-oriented learning programmes
(Steen and Haugli, 2001).
Psychological support that deals with the patients
relationship difficulties (such as those related to marital
535
status) may also be included, if appropriate, since it ap-
pears to have a strong impact on the rehabilitation process
of those with chronic musculoskeletal disorders (Hamberg
et al., 1997), and improve immune function and cardio-
vascular health (Kiecolt-Glaser and Newton, 2001; Kiecolt-
Glaser et al., 2010).
The interaction between mind, body, behaviour, and the
environment is thus a crucial factor affecting the patients
physical and psychological health, and is used in mind-
body medicine clinics to treat stress-related or chronic
conditions by improving disease coping strategies and the
overall quality of life (Gimpel et al., 2014).
FASCIA SCIENCE AND CLINICAL APPLICATIONS: EXTENSIVE REVIEW
Conclusion
It is evident that various factors may interplay with myo-
fascial structure and function as well as with its ability to
respond to treatment. The effects of manual fascial in-
terventions can be local (as tissue texture changes),
segmental (as via neurological response) and global (as
through hormonal effects) in extent, and may occur at
different intervals e ranging from minutes to weeks e after
a given input, with many interacting mechanisms influ-
encing tissue properties and behaviours, including placebo
(Fig. 1). Some of these factors are strongly supported by the
available evidence whereas others need further investiga-
tion. Nevertheless, connective tissue may serve as a trait
dunion of all these elements, potentially representing a
meta-system (Langevin, 2006) that coherently influences
structure and function of the whole organism and the
interaction between its constituents.
In the light of what has been presented in this work, the
author suggests an integration of the existing five osteo-
pathic models e structural, respiratory-circulatory, meta-
bolic, neurologic and behavioural (E.C.O.P., 2011b). These
are conceptual models of assessing, treating and caring for
patients in osteopathic practice. They are all based on
anatomy, physiology, biochemistry and psychology princi-
ples, providing five specific lenses through which osteo-
paths may interpret and approach patients. In other words,
they provide five different relations of structure and func-
tion, reflecting five different physiological modalities of
body adaptation to inner and outer stressors. They are
normally used in integration in osteopathic practice to
release dysfunctional patterns, restore function and pro-
mote health (Seffinger et al., 2011). In particular, the
musculoskeletal system has traditionally been presented as
the main interface of these models (Hruby, 1992), by
influencing and maintaining communication with all the
other body functions. Korr (1976) defined it as the primary
machinery of life, indicating the musculoskeletal system
as more than just a framework which supports and contains
the viscera of the body, but as the main dynamic compo-
nent of the living body through which we function, live,
move, interact and express ourselves. However, the major
element through which the musculoskeletal system in-
fluences the bodys response in health and disease has been
traditionally indicated as the nervous system. As an alter-
native, this paper suggests that fascia might be the over-
looked somatic component interplaying between the
musculoskeletal system and its function as the primary
 536 P. Tozzi
FASCIA SCIENCE AND CLINICAL APPLICATIONS: EXTENSIVE REVIEW

Figure 1 Fasciagenic treatment effects. The diagram shows the possible effects of manual fascial treatment, reinforced by
activating forces to prompt release. These effects may occur at different times, ranging from minutes during or after intervention,
to days and week, producing several tissue responses and changes that normalize somatic dysfunction features (tissue texture
changes, asymmetry, restriction of motion, tenderness). Additional strategies may reinforce the therapeutic effects of manual
work to fascia. The psychosocial-behavioural aspect could also ultimately influence and be influenced by these processes.

machinery of life also because of the shared embryologic
origin. As suggested by the work of Blechschmidt and
Gasser (2012), each connective tissue in the body pre-
sents a functional and anatomical continuity, due to their
common embryologic origins in the mesoderm, although
loading demands acting through and upon tissues can
determine their differentiation by influencing fibre
arrangement, length, and density.
In addition, due to the multi-functional nature and
ubiquitous structure of fascial tissue e that makes it a
unique component in the musculoskeletal apparatus e the
author suggests the addition of a sixth meta-model that
integrates but also transcends the musculoskeletal system
itself, the connective tissue-fascial model. This is the only
tissue providing intracellular and extracellular connection
as well as communication at all levels between each body
system; it offers various mechanisms for information sig-
nalling together with several forms of transducing infor-
mation; it is an embodying structure that expresses
coherent functions from molecular to macroscopic scales,
allowing their constant interdependence in health as well
as in disease e all features that no other musculo-skeletal
element can display to this extent. This sixth osteopathic
model is the true interface between all body systems, by
laying between and playing within the other models; by
integrating and coordinating their activity; by pervading
their essence, but also transcending their contingent na-
ture; and finally by providing a structural and functional
framework for the bodys homoeostatic potential and its
inherent abilities to heal. By its nature, it is the only model
that resonates with A.T. Stills original intention: . this
philosophy (of Osteopathy) has chosen the fascia as a
foundation of which to stand . (Still, 1899).
In conclusion, rather than defining bits and pieces of this
body wide fascial structure (Stecco, 2014) e as if it is just a
dead tissue to be surgically dissected and named in its single
components, and separated from surrounding tissues e the
author recalls Hollinshead (1974): descriptions of fascia
tend to be confusing . all connective tissue in the body is
continuous with all other connective tissue. Thus, in one
sense, a fascia has no beginning and no end, and any
description of fascias is necessarily somewhat arbitrary.
This concept of intrinsic multi-tissue continuity has been
advanced by various authors, who highlighted the structural
and functional interrelationship between muscular, fascial,
ligamentous, capsular and articular components. Such
whole-body connection has been referred to as ectoskele-
ton (Wood Jones, 1944), ligamentous complex system
A unifying neuro-fasciagenic model of somatic dysfunction: Part 2
(Willard, 1997), dynament (Van der Wal, 2009), and
supertendon (Benjamin, 2009), with subtle differences
despite the same basic principle. Therefore, fascial form and
organization should be considered and understood as a living,
pulsating, oscillating, coherent whole, responding to and
differentiating according to physical, chemical and psycho-
logical forces; as a single structural continuum interacting
with a multitude of regulatory functional properties.
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