Medical Hypotheses 153 (2021) 110624

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Medical Hypotheses
journal homepage: www.elsevier.com/locate/mehy

Visceral pain, mechanisms, and implications in musculoskeletal

clinical practice
E.A. Pacheco-Carroza
Health Sciences Faculty, Universidad San Sebastián, General Lagos 1022 Valdivia, 56 2632500, Chile

A R T I C L E I N F O A B S T R A C T

Keywords: The global impact of visceral pain is extremely high, representing a significant portion of all forms of chronic
Musculoskeletal pain pain. In musculoskeletal practice, at least one-third of people with persistent noncancerous pain report recurrent
Visceral pain abdominal, pelvic, or chest pain symptoms.
Referred pain
Visceral pain can be felt in several different areas of the body and can migrate throughout a region, even
Differential diagnosis
though the site of origin does not appear to change. Traditionally, clinicians have examined musculoskeletal pain
through a reductionist lens that ignores the influence of the visceral system on musculoskeletal pain.
The hypothesis presented is that visceral pain has an important influence on developing and maintaining
different types of musculoskeletal pain through processes within the peripheral or central nervous systems, as a
result of a visceral nociceptive stimulus generated by pathoanatomical or functional alterations.
The hypothesis predicts that a consideration of the function of the visceral system in musculoskeletal pain
conditions will improve clinical outcomes, moving beyond a linear model and adopting a more holistic approach,
especially in the more complex groups of patients.

Introduction productivity [3].

The global impact of visceral pain is extremely high, representing a
significant portion of all forms of chronic pain [1]. Surveys have shown
prevalence rates among adults of 20% for chest pain, 25% for inter­
mittent abdominal pain, and 16–24% for pelvic pain in women [2]. The
vast majority of these cases do not require surgical intervention.
Approximately 30–40% of all secondary care gastroenterology consul­
tations involve functional abdominal pain. This creates tremendous
pressure on the healthcare system, affecting an estimated 10–15% of
Europe and U.S. populations, with consequential costs that are esti­
mated to exceed US$ 40 billion [3].
Among all functional bowel disorders, irritable bowel syndrome
(IBS) is the most common (about 18–20% of the patient population) and
prevalent of the gastrointestinal disorders. In women, the chronic pelvic
pain presenting a prevalence of approximately 15% [4]. In population
studies in both the USA and the UK, persistent non-cyclical pelvic pain
has been estimated to affect about 16% of individuals [5]. In the case of
primary dysmenorrhea, at least 50% of menstruating women suffer
intense and often disabling abdominal or pelvic symptoms [6]. This is
one of the most common gynecologic complaints in young women and
contributes to economic burdens associated with lost workdays and
The co-occurrence of multiple pathologies (i.e., hypertension, dia­
betes, obesity, cardiovascular diseases, metabolic and inflammatory
diseases, affective disorders, myofascial, pain syndromes, visceral pain
syndromes, fibromyalgia, and joint diseases) in adult patients is very
frequent, occurring in 55–98% of cases [7]. In musculoskeletal practice,
at least one-third of people with persistent noncancerous pain (e.g., fi­
bromyalgia, chronic fatigue syndrome, and chronic low-back pain)
report recurrent abdominal, pelvic, or chest pain symptoms [8–11]. This
situation worsens the basic pathology, probably by increasing the
excitability of the central nervous system (CNS), thus amplifying its
symptomatology [9] and is identified as a strong contributor to the
suffering and disability of this group of patients [12,13].
Knowledge about the mechanisms of visceral pain production and its
implications for human health has increased considerably in recent
years, thanks to advances in technology and the use of new study designs
[2,14,15]. This has led to a greater understanding of its implications,
especially for musculoskeletal clinical practice.
Traditionally, the evaluation of musculoskeletal pathology in clinical
practice considers a series of steps that, in general terms, seeks to collect
information on psychosocial factors, comorbidities, lifestyle habits, and
physical examination, limiting the evaluation of the visceral system to

E-mail address: andres.pacheco@uss.cl.

https://doi.org/10.1016/j.mehy.2021.110624
Received 15 December 2020; Received in revised form 25 May 2021; Accepted 3 June 2021
Available online 6 June 2021
0306-9877/© 2021 Elsevier Ltd. All rights reserved.
E.A. Pacheco-Carroza Medical Hypotheses 153 (2021) 110624

the search for serious pathologies that require urgent medical treatment
[16,17].
A biopsychosocial approach requires an understanding of the human
being from a perspective that considers the interaction of different sys­
tems and their relationship with the social environment in the con­
struction of the painful experience. This approach attempts to
disentangle the interactions of these complex systems and their inter­
action, with a reductionist paradigm, and it may overlook the
complexity of some types of musculoskeletal syndromes, thus limiting
our understanding and clinical results.
For an approach within a biopsychosocial model, our article pro­
poses that the clinical reasoning model should consider the functioning
of the visceral system and its role in the onset and eventual chron­
ification of musculoskeletal pain.
We also propose that the implementation of a more holistic frame­
work, based on a general classification of visceral pain, contributing
factors, impact on the CNS, and potential clinical features, will enhance
our understanding of musculoskeletal practice. It will also encourage
multidisciplinary treatment and, ultimately, improve clinical outcomes.
Another characteristic of visceral pain is that pathoanatomical
findings in the visceral system do not always correlate with the intensity
of the reported symptoms, as in the case of chronic pancreatitis, where
the degree of pancreatic involvement may not correlate with the in­
tensity of the reported symptoms or laboratory findings.
Functional disorders, such as IBS, appear to have no structural
changes that justify their symptoms, presenting high levels of pain,
extraterritorial symptoms, and disability [20]. Experience demonstrates
that stimuli such as the traction of the mesentery and the forces of
distension and compression of esophagus, stomach, bladder, colon,
rectum, uterus, and small intestine are effective stimuli to trigger the
painful response [18,21–23]. Other stimuli, such as electrical, thermal,
hypoxic, and chemical, can activate nociceptive pathways in time, if the
pattern and frequency are consistent enough [18]. In time, their
perpetuation is capable of generating increased sensitivity in the nerve
endings, expanding their receptive fields and facilitating inflammatory
responses, which results in the enhancement of nociceptive mechanisms
[18].

What is already known about the mechanism of visceral pain? Visceral referred pain

Visceral pain
There is a general consensus that pain can eventually be generated
directly from the viscera. What is not yet commonly agree is whether or
not a viscera presents specialized nociceptors [18].
As in pain of musculoskeletal origin, it is possible to identify clear
causes of visceral pain. An example of this is cancer of visceral origin,
where the growth of the tumor produces a large number of stimuli that
activate the nociceptive pathways (e.g., chemicals released by cancer
cells, immune cell activations, distension or obstruction of luminal or­
gans, and nerve damage) [19].
Visceral pain can be felt in several different areas of the body and can
migrate throughout a region, even though the site of origin does not
appear to change. Sites of referred pain can be located in the head or
neck, thoracic, abdominal, or pelvic region, where the somatic and
visceral structures share innervation at the same spinal segments(Fig. 1)
[6].
Currently, there are a large number of proposed theories on how this
somatovisceral integration occurs in the peripheral, spinal and the
supra-spinal levels. However, the precise neural mechanism under
which this phenomenon occurs remains a question mark [24].
In spite of the above, the scientific literature presents us with a
considerable amount of experimental evidence that supports the

Fig. 1. Visceral referred pain. Visceral innervation and its spinal projection. They are populations of neurons (N) that respond to harmful and non-harmful stimuli.
Central projections of visceral afferents make synapsis in second order visceral-somatic neurons in lamina I, V and X of the dorsal shaft and simultaneously receive
somatic inputs from the same dermatome. The neuron projections ascend to the thalamus and midbrain. Supraspinal pathways, which include the spinothalamic,
spinoreticular, and spinomesencephalic tracts [114]. Spnilothalamic tract ends with the thalamocortical fibers then project to the primary somatosensory cortex,
important for somatotopic sensory discrimination and localization of visceral and somatic stimuli. The spinoreticular tract, conducts sensory information from the
spinal cord to the reticular formation that involved mainly in the reflexive, affective, and motivational properties of such stimulation. The spinomesencephalic tract
fibers project in the brain stem, periaqueductal gray, locus coeruleus, and dorsal reticular nucleus. These projections transmit sensory input to cingulate cortex and
insula, that are involved with the processing of noxious visceral and somatic information [115].

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E.A. Pacheco-Carroza
plausibility of the phenomenon at the level of the spinal cord [24–27].
Referred pain pathways
The visceral splanchnic afferents converge at the posterior pole level
in plates I, II, and IV (Fig. I) and correspond to approximately 10% of all
afferent information entering the spinal cord, presenting an extensive
and divergent intra-spinal distribution [28].
All second order neurons located in the posterior horn, which receive
a visceral input simultaneously (Fig. 1), process information from so­
matic structures such as the skin and muscles [2,4]. These neurons
normally respond to somatic stimuli and rarely to information of visceral
origin. However, in cases where the nociceptive stimulus is persistent,
the dorsal horn responds due to the temporal summation at the CNS.
This information travels to a small area of the somatosensory region that
is usually not stimulated. As it is not common, this new stimulus is
interpreted as a somatic origin, obtained as a result of neurogenic
extravasation in areas of the skin, muscular hyperalgesia, and changes in
muscle tone. Its presentation will be maintained in the intervals in which
there is no visceral pain and may even remain a long time after recovery
from the primary disease [29–31].
Another proposed neural pathway is via the phrenic nerve, which
provides complete motor innervation to the diaphragm and sensitivity
innervation to its central tendon and regions of the peritoneum [32,33].
This can be damaged due to non-traumatic mechanisms, such as poly­
neuropathy, and mononeuropathy in patients with diabetes mellitus
[34,35] or through direct stimulation by mechanical compression, in­
flammatory response, or ischemic processes [36]. It function as a plau­
sible neural pathway of nociception into the upper quarter, due to its
anastomosis with the brachial plexus [37] is responsible for motor
symptomatology and referred pain in the neck, shoulder and pectoral
regions, anterior region of the arm, and medial and lateral regions of the
elbow [38–41].
The vagus nerve is a visceral neural pathway made up of 80–90%
sensory afferent fibers that carry important sensory information from
the visceral system to the CNS [42]. It is activated by gastrointestinal
and pancreatic hormonal stimuli, mechanical alterations of the mucosa,
changes in osmolarity, and the intake of macronutrients through the diet
and has important interaction with gut microbiota, being an important
modulator of the emotional state, as well as behavior, memory con­
struction, and nociception [43,44].
There is evidence that suggests that visceral nociceptive information
is transmitted by spinal and vagal pathways [45]. The characteristics of
the vagal sensory endings include discriminative responsiveness to
potentially noxious mechanical and chemical stimuli, peripheral sensi­
tization and with a potential capacity to induce central sensitization;
however, much of this information fails to reach the level of conscious
perception [46,47].
In the brain, the vagal afferents are projected to the solitary tract’s
nucleus located within the brain stem and to the anterior cingulate
cortex. These regions are important pre-emotional processing regions.
Therefore, it has been suggested that the vagal input can contribute
mainly to the construction of affective/emotional states, rather than to
the sensory and discriminative aspects of pain [43,48].
There is growing evidence that the vagus nerve is able to modulate
nociception [43,49] by medullary inhibition in the dorsal horn [50] and
activation of the nucleus of the solitary tract that innervates the nuclei of
the raphe and locus coeruleus, which subsequently activate the down­
ward inhibition pathways in pain [44,51]. Their interaction with the
intestinal microbiome seems to be very relevant in this function.
Recently, several studies in animal models have shown that intestinal
microbiota play an important role in the development of visceral pain
[52] through systemic mechanisms and direct stimulation of the vagus
nerve afferents, being able to directly modulate the dorsal root ganglia
neuronal excitability and neuro-inflammation in the peripheral and
central nervous systems under chronic pain conditions [53]. It has been
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Medical Hypotheses 153 (2021) 110624
found to be altered in individuals with stress, anxiety, and depression
[54] as well as in patients with IBS [55–57] chronic pelvic pain [58]
chronic fatigue syndrome [59,60] rheumatoid arthritis [61] spondylium
arthropathies [62] and patients with fibromyalgia [63].
Pain and the brain-gut axis
It is well known that sensory stimuli are not transformed into a
painful response; they are only interpreted as such when they reach the
brain. In the process, this response can be modulated by different factors
related to subjective experience and influenced by cultural learning, the
meaning of the situation, attention, and other psychological variables
[64]. This applies to pain in general, including visceral pain.
In this sense. a biopsychosocial approach is needed. This requires an
understanding of the neurobiological processes that can affect pain, both
peripheral and central, with knowledge of the contributing psychosocial
factors. In this regard, the constant two-way communication between
the brain and the digestive system is relevant. The “brain-gut axis” is a
theoretical model depicting bidirectional neural pathways linking
cognitive, emotional, and autonomic centers in the brain to neuroen­
docrine centers, the enteric nervous system, and the immune function
[65].
In the case of patients suffering from mild or moderate visceral pain,
there are factors associated with the intestine (i.e., motility, infections,
damage, dietary habits, and hormonal changes) that can directly affect
the activity of afferent neurons in the visceral system. Similarly, other
factors, such as stresses and abuse, comorbid psychiatric diagnoses, and
poor coping, may affect gastrointestinal health [66,67]. This type of
stimuli, sustained over time, can generate adaptations in the CNS (such
as those found in musculoskeletal persistent pain states), affecting not
only the processing of pain-related inputs, but also the outputs, as seen
in an individual’s psychological state, cognitive processes, behavior,
immune systems, endocrine systems, and motor systems [3,15,68,69].
Hypothesis
The hypothesis presented is that visceral pain has an important in­
fluence on developing and maintaining different types of musculoskel­
etal pain through processes within the peripheral or central nervous
systems, as a result of a visceral nociceptive stimulus generated by
pathoanatomical or functional alterations.
The hypothesis also proposes that the increased sensitivity of the
visceral system, by means of chemical, ischemic, or compressive stimuli,
can be a cause of acute musculoskeletal pain without necessarily pre­
senting the characteristics of a medical emergency. In other cases, it can
behave as an important factor in the perpetuation of persistent pain,
avoidance behaviors, and psychoemotional suffering. This causes
further deterioration of movement and quality of life for patients with
musculoskeletal pain
Evaluation of the hypothesis
Visceral pain and the musculoskeletal system
The biopsychosocial model proposes that the pain experience and the
resulting responses stem from the interaction of biological characteris­
tics, behavioral factors (lifestyle, stress, health beliefs), and social con­
ditions (cultural influences, family relationships, social support) [70].
Therefore, considering the effect of the different types of visceral pain
seems to be appropriate (Fig. 2).
In clinical practice, visceral pain is considered an important red flag
that requires urgent medical referral [71] occurring as a result of
structural, chemical, or compressive damage of its structural compo­
nents (e.g., pericarditis, pulmonary embolism, pneumonia, infections,
etc.). This is the denominated true visceral pain [2]. Clinically, it is
characterized by vague and diffuse pain. The patient will cover the
E.A. Pacheco-Carroza Medical Hypotheses 153 (2021) 110624

Fig. 2. Visceral pain interaction model. This figure displays the relation from visceral peripheral mechanisms (more common) to central mechanism pain (less
common) and its multisystemic repercussions. It is possible to observe how the true visceral pain is recognized as a medical emergency. According to the involvement
of the visceral structure, the referred pain it may be associated to autonomic symptoms (e.g. nausea, vomiting, cold sweat and emotional responses). However, this
does not happen in all cases, making it sometimes difficult to diagnose. Finally, Functional visceral pain is associated with a large number of contributing factors.
According to the degree of involvement of the nervous system and the duration of the condition, the symptomatology can be varied (i.e., local or generalized referred
pain, hyperalgesia, dysfunctions in motor control, alterations in the psycho-emotional state, changes in the immune and neuroendocrine response).

affected surface with his hand, accompanied by a position of flexion of
the trunk. The territories that most commonly refer symptoms are in the
middle zone of the thorax and the abdomen, either anterior or posterior,
together with the epigastric region [2]. It is possible to find clear neu­
rovegetative signs, such as the presence of nausea, vomiting, cold
sweats, changes in heart rate, changes in blood pressure, sudden drops in
blood glucose, and increased frequency of urination, among others, as
well as strong emotional reactions like anxiety, anguish, and the “feeling
of imminent death” [72] which turn out to be a medical emergency. The
mechanisms that explain this phenomenon are widely documented
[2,15,27]. The theory of visceral-somatic convergence indicates that
there are stimuli of somatic and visceral origin in the spinal cord that
converge in common ways, towards the superior centers [4] and are
capable of producing referred pain in regions where metameric inner­
vation is shared. It has been suggested that these same mechanisms may
act as contributors to the onset or chronification of musculoskeletal
pain, in the absence of the aforementioned clinical behavior.
Sometimes, true visceral pain can occur directly as referred pain, in
the absence of the above-mentioned physical and emotional response
[73] which makes differential diagnosis difficult. Referred pain with
hyperalgesia (sometimes with cyclic behavior) is characteristic,
accompanied by changes in trophism of the deep layers of the body wall,
namely an increased thickness of the subcutis and a tendency to muscle
atrophy [40,74,75]. In this context, the differential diagnosis becomes
complex, especially in the area of musculoskeletal evaluation, where it is
very common that the attention is directed towards neuro­
musculoskeletal structures. It is proposed that these types of conditions
should be considered in the differential diagnosis of acute and chronic
musculoskeletal pain, particularly when imaging tests in musculoskel­
etal structures do not show signs that justify the symptomatology [71].
The situation can be more complicated in cases of functional visceral
disorders. These are the most prevalent forms of visceral pain and
represent unexplained symptoms that have no readily identifiable in­
fectious, anatomical, or metabolic basis. Functional visceral pain
symptoms are diffuse, poorly localized, and often confused with other
disorders [76]. Having symptoms of cramping, abdominal pain, bloat­
ing, constipation, and/or diarrhea and lower abdominal pain can be
related with an episode of infection or inflammation, genetic back­
ground, stress, anxiety, and early-life adverse events (history of severe
pain, abuse, or trauma in childhood) [4].
An interesting phenomenon in this group of patients is that of
visceral somatic convergence, when two different viscera share meta­
meric innervation. This generates a summative response at the level of
the dorsal horn neurons [77,78] mixing two different functional

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disorders. Thus, the functional disorders, along with real visceral pain,
considerably amplify the symptomatic response [79].
It is well known that this type of visceral pain is associated with
neuroplastic changes in pain processing areas (especially those of long
duration), which are responsible for the extraterrotoriality spread and
chronification of the symptoms [15,75,80].
It is proposed that this group of patients can eventually suffer
persistent musculoskeletal pain in the absence of alterations in muscu­
loskeletal or visceral structures. The problem is that this statement is
only half true, since they can present neuroplastic changes, but these are
due to the maintenance of a peripheral nociceptive visceral stimulus
over time.
Clinical evaluation of visceral pain from structural causes alone is not
sufficient for a specific diagnosis. Imaging modalities can increase the
accuracy of the diagnosis. The specific use of techniques such as simple
radiography, CT scans, MRI, or ultrasound can be useful in scenarios
with complex pain resolution [81]. Ultrasound is widely used by phy­
sicians and physiotherapists to diagnose musculoskeletal pathologies. It
has the major advantages of safety, cost, and availability, and it can be
repeated as often as necessary. However, it is regarded as more operator-
dependent than the other modalities [82].
In some musculoskeletal pain syndromes, one of the difficulties in
dealing with functional visceral pain is that there are no structural ab­
normalities that can be used objectively. Diagnoses based on physical
examination and the use of questionnaires seem appropriate. Giamber­
ardino [69] explanation that it is possible to determine the presence of
hyperalgesia and changes in muscle tone in the regions where visceral-
somatic metameric innervation is shared, using simple procedures (skin
sensitivity, subcutis sensitivity, and muscle sensitivity) and the repro­
duction of symptoms to regions of referred pain by palpation of the
abdominal wall, may have clinical utility for the detection of referred
pain.
Questionnaires such as The ROME IV criteria [83] gather specific
information for this type of condition and allow a more accurate diag­
nosis, monitor progression, and establish clear criteria for research. In
this group of patients, anxiety may be an important endogenous stressor,
perpetuating different types of functional visceral pain.
Even in the absence of external stressors, the overall prevalence of all
types of anxiety in these patients is much higher [65]. The use of
questionnaires such as the specific gastrointestinal symptom anxiety
scale during the interview [84] can be helpful in determining potential
relationships between visceral symptoms, psychosocial factors, and
musculoskeletal pain. This is an important point, because in the pres­
ence of high levels of anxiety, conventional treatments seem to be less
effective [65].
The hypothesis is that these conditions may be an important sensi­
tizing factor of the nervous system for the development of persistent
musculoskeletal pain during the entire life cycle. Therefore, they should
be considered in the evaluation and treatment of musculoskeletal pa­
thologies. For this reason, we propose that it is highly probable that a
large number of patients who are treated in clinics and hospitals for
musculoskeletal conditions can present history or some type of visceral
pain as a comorbidity that may be contributing to their suffering.
In some patients, this will be a more determining factor; in others, it
will just be a finding. However, we believe that the association should be
considered within the evaluation and in an eventual multidisciplinary
treatment.
Testing the hypothesis
In an effort to support the hypothesis, we refer to the work of
Martinez-Barenys [36] which investigated the constant and severe pain
that commonly occurs (75% of patients) in the ipsilateral shoulder
following epidural analgesia. The aim of this study was to investigate the
effect of phrenic nerve infiltration (PNI) compared with suprascapular
nerve block. The results showed that shoulder pain intensity was
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Medical Hypotheses 153 (2021) 110624
significantly lower in the PNI group, which supports that irritation of the
pericardium and/or mediastinal-diaphragmatic pleural surfaces results
in pain that is referred to the shoulder via the phrenic nerve. It is
believed that this neural pathway may explain cases of visceral tumors
that generate upper quarter symptoms in the absence of suggestive red
flag signs, confusing them with musculoskeletal pathologies (i.e., hem­
ifacial pain [85] shoulder stiffness and unspecific pain [86] snapping
shoulder, shoulder impigment [87]) In the same way, this can be the
cause of unspecific and diffuse pain in the neck and the shoulder (i.e.,
thymus tumor [88] diaphragmatic tumors [89] liver damage [39]
peritoneal abscess [90] foreign body in the spleen [91] pulmonary
embolism [39]).
Another interesting study is that conducted by Vecchiet [92] who
employed the mechanical stimulus of a sigmoid colon in healthy vol­
unteers, inducing nonalgogenic sensations in the lower abdomen, peri­
neum, and upper part of the lumbar. With repeated stimulus, the referral
areas increased progressively, and the sensation became painful. Other
studies in humans have obtained similar responses through the appli­
cation of different stimuli (mechanical, chemical, electrical) [93–95]. It
is reasonable to suggest that this process of pain referred by temporal
summation may be an explanation for diverse case reports of visceral
referred pain in the spine, as a single symptom [91,92] (i.e., duodenal
ulcers [93] leiomyoma of the bladder [94] pulmonary embolism [96]
acute myocardial infarction [97] lumbar aortic aneurysm [98] adeno­
myosis and endometriosis [99]). In the same way, it is possible to find
these types of associations in less dangerous visceral conditions. A study
that explored the prevalence of lower back pain in 38,050 people
considered the presence of “normal” gastrointestinal functional symp­
toms (e.g., constipation, hemorrhoids, and other gastrointestinal prob­
lems) as variables, concluding that there is a strong association between
these two conditions and that this association intensifies as the number
of functional gastrointestinal symptoms increases [12].
These different neural pathways are capable of generating acute
viscero-somatic responses and promoting persistent pain states, gener­
ating adaptations in pain processing centers [77] and are able to sensi­
tize peripheral receptors to non-painful stimuli [95,96]. This was
demonstrated by Giamberardino [69] who showed that hyperalgesia
only appears in visceral conditions that are painful, irrespective of the
nature of the visceral trigger (organic or dysfunctional). Another
example is the case of dysmenorrhea, which is a painful functional
condition, with a high prevalence among women. They report high
levels of pain in regions such as the lower abdomen, lower back, neck,
and lower extremities, as well as headaches [97,98] A similar situation
occurs in gastroesophageal reflux. It has been estimated that between
20% − 60% of patients have head or neck symptoms in the absence of
considerable heartburn or histological changes in the esophagus
[99,100] and is also recognized as an important contributing factor in
the chronification of pain in the temporomandibular joint [101].
In cases of more severe persistent visceral pain (IBS), there are
typical symptoms of central sensitization (generalized myalgia, sleep
disturbances, stiffness, fatigue, headaches, fibromyalgia, and panic
disorder [8,102–106]) with a two times higher prevalence of back pain
surgeries [107]. This association seems to be repeated in adults with a
history of functional abdominal pain in childhood, who presented
higher rates of musculoskeletal pain and headaches [81] as well as
mental health problems compared to the control group. Regardless of
whether the gastrointestinal symptoms have been resolved or not
[81,108,109] they can be responsible for cyclical referred pain, which is
aggravated by some types of food, hormonal action, drugs, or the stress
of daily life, perhaps mediated by neuroplastic changes and an increase
in the reactivity of the CNS.
These types of conditions can be made more complex by the phe­
nomenon of viscero-visceral convergence. There are cases of women
diagnosed with IBS and dysmenorrhea who report high levels of men­
strual pain, stress, anxiety, and muscular hyperalgesia in the lumbar
region compared to the control group. The intensity of symptoms
E.A. Pacheco-Carroza
decreased significantly with dietary interventions targeted at the man­
agement of IBS [110]. A similar situation occurs in women who suffer
from kidney stones with dysmenorrhea and/or endometriosis. They
have a significantly higher rate of renal colic and back pain with
hyperalgesia when compared to women who only have urinary kidney
stones and whose dysmenorrhea was successfully treated with hormone
therapy; the renal colic rates were equal to the control group [68].
Even though visceral pain has been shown to be related to the
presence of musculoskeletal pain, the question is whether it is possible to
determine which are the best evaluative tools that present the best cost
benefit in musculoskeletal practice and what type of interventions are
best suited for each particular case. Creating new clinical perspectives
that take into account the influence of the visceral system could answer
these questions. Identifying the methods by which these influences are
integrated into an intervention design is the task of future research and
is the intention behind this hypothesis.
Visceral pain and clinical implications
In patients with musculoskeletal pain with visceral disorders, there
can be an important sensitization of the nervous system [15] which will
contribute to tissue inflammation, non-anatomical distribution of
symptoms, alterations of the mechanisms of downward inhibition,
alteration of motor control, emotional distress, pain-related fear, and
decreased movement [9]. This can promote a sedentary lifestyle and the
maintenance of harmful dietary habits, such as the consumption of
highly processed foods and high sugar drinks, which have been proven
to be amplifiers of the painful experience [111] and end up perpetuating
the vicious circle.
The mechanism presented in this paper is compatible with the
complex natural history of musculoskeletal pain variability (i.e., the
waxing and waning of symptoms, symptom distribution, and disability
in persistent conditions) and the effect of harmful life habits, which are
so common in our times.
The potential for acute exacerbation of symptoms may be triggered
by any type of stimulus that is intense enough and is sustained over time.
The activation can be carried out by different peripheral stimulus on the
visceral receptors (i.e., smooth muscle spasm, change in vascular pres­
sures, locally increased inflammatory cytokines, activation of the sym­
pathetic system, decreased tissue pH, or oxygen content) [18].
This information generates an increase in the excitability of the CNS,
provoking hyperalgesia and referred pain, tissue inflammation, changes
in muscle tone, and alterations in motor control in regions where
metameric innervation is shared. These, together with other factors such
as positions maintained over time, physical inactivity, and psychosocial
factors, progressively build up the reason for the patient’s consultation
and a potential chronification of symptoms.
In cases of persistent visceral pain, others factors, like a history of
abuse, psychiatric comorbidities, and poor coping skills, become more
important triggers [67]. In some cases, it can activate unspecific
musculoskeletal symptoms and a feeling of generalized discomfort, due
to the interoceptive alterations present in this group of patients. On the
other hand, patients with widespread musculoskeletal pain may, in time,
present with gastrointestinal functional alterations and visceral pain [8]
due to the bidirectional communication between systems.
The proposed model links the area of visceral and somatic pain
research into a comprehensive and testable model that plausibly ex­
plains why a patient with musculoskeletal pain (acute or persistent) may
be influenced by the health of the visceral system. The factors that can
sensitize the visceral system, its influence on sensitizing the nociceptive
neural pathways, their connections at the CNS level, and the influence of
the formation of the painful experience are not generally considered
within the clinical evaluation of musculoskeletal pain syndromes.
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Medical Hypotheses 153 (2021) 110624
Discussion & implications for future research
The proposed model presented in this paper predicts that a consid­
eration of the function of the visceral system in musculoskeletal pain
conditions will improve clinical outcomes, moving beyond a linear
model and adopting a more holistic approach, especially in the more
complex groups of patients.
There is a growing body of evidence of the role of visceral health in
aspects as variable as mental health, learning, and musculoskeletal pain,
among others. Research should continue to identify and understand
these relationships, especially in terms of determining their role in the
health of the musculoskeletal system.
Currently, there is limited literature that examines the potential
impact of classifying patients with musculoskeletal pain according to the
current or historical presence of visceral pain; nor are there studies
exploring the impact of different approaches to visceral pain on
musculoskeletal health according to their type or severity.
Interestingly, a recent systematic review reported that “Chronic pain
severity also shows a positive relation with fat and sugar intake in
osteoarthritis, and pain threshold shows a positive association with
protein intake in fibromyalgia. However, the mechanisms behind this
interaction are still uncertain, and more high-quality studies that
investigate the underlying mechanisms of the interaction between
chronic musculoskeletal pain and nutrition are needed” [111].
Despite significant advances in the understanding of musculoskeletal
pain and the wide variety of approaches available to date, it has not been
possible to stop the exponential increase in persistent pain worldwide
[112]. Therefore, it is important that future studies in the field of
musculoskeletal pain develop and implement intervention programs
that consider visceral pain as a potential sensitized source of the nervous
system. For example, more research is needed on the prevalence of
visceral pathology in various painful musculoskeletal syndromes, its
impact on quality of life, and how to manage these conditions, consid­
ering multidisciplinary approaches. It may be possible to mitigate or
suppress musculoskeletal pain and modify other psychosocial variables,
such as stress levels, anxiety, and cognition, through interventions that
considers the health of the visceral system.
Conclusion
Theoretical models that introduce an approach involving the inter­
action of complex systems should be included in the musculoskeletal
pain field in an effort to try to improve the clinical outcomes of persis­
tent, hard-to-manage conditions.
It is in this sense that a model that considers visceral pain as a po­
tential contributor to musculoskeletal pain, from its most dangerous
conditions to its most common manifestations, can be very helpful,
contributing to the understanding of pain as an experience, involving
multiple body systems, and its interaction with environmental factors.
There is a rejection by some clinicians when considering visceral
pain as an influential factor within clinical practice. This might happen
because of the idea that visceral pain is only relevant as a red flag. A
change in mindset could create a paradigm shift that allows further
development of clinical research in this area, enabling us to identifying
patient profiles that could benefit from multidisciplinary approaches.
It is interesting to note that the understanding of visceral pain was,
for a long time, based only on an extrapolation of the neurophysiological
mechanisms that explain somatic pain. Currently, because of the ad­
vances in science, there is a growing body of literature that shows the
opposite: visceral pain is a singular clinical entity with unique mecha­
nisms that generate important local and systemic influences [113].
The mechanisms by which the visceral system can generate or
amplify musculoskeletal symptoms, and changes in mood and behavior
are supported by literature [15,51,52] being very relevant in under­
standing the painful experience from a biopsychosocial approach.
The model offered here uses core anatomy and neurophysiology
E.A. Pacheco-Carroza
based in experimental studies to introduce a hypothetical new paradigm
of the evaluation of musculoskeletal pain conditions and aims to achieve
a better understanding of the multiple interactions of the musculoskel­
etal system with the rest of the body.
It is expected that the new paradigm offered here will become a
source of new questions that will lead to future research. This research
will provide evidence of these relationships, optimizing treatment,
detecting new potential risk factors or designing new and better in­
terventions that consider the health and repercussions of the visceral
system in the pain experience, designing programs from a bio­
psychosocial and multidisciplinary approach.
Grant support
I would like to thank Professor Carlos Cruz-Montecinos of the
Physiotherapy Department of the Universidad de Chile for his guidance
in writing this article.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
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