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Relating Chronic Pelvic Pain and Endometriosis to Signs of Sensitization and Myofascial Pain and Dysfunction

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Chronic pelvic pain is a frustrating symptom for patients with endometriosis and is frequently refractory to hormonal and surgical management. While these therapies target ectopic endometrial lesions, they do not directly address pain due to central sensitization of the nervous system and myofascial dysfunction, which can continue to generate pain from myofascial trigger points even after traditional treatments are optimized. This article provides a background for understanding how endometriosis facilitates remodeling of neural networks, contributing to sensitization and generation of myofascial trigger points. A framework for evaluating such sensitization and myofascial trigger points in a clinical setting is presented. Treatments that specifically address myofascial pain secondary to spontaneously painful myofascial trigger points and their putative mechanisms of action are also reviewed, including physical therapy, dry needling, anesthetic injections, and botulinum toxin injections.
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Relating Chronic Pelvic Pain and Endometriosis to Signs of
Sensitization and Myofascial Pain and Dysfunction
Jacqueline V. Aredo, BS1, Katrina J. Heyrana, MD, PhD2, Barbara I. Karp, MD1, Jay P. Shah,
MD3, and Pamela Stratton, MD1
1National Institute of Neurological Disorders and Stroke, Clinical Center, Intramural Research
Program NIH, Bethesda, Maryland 2Department of Obstetrics and Gynecology, University of
Rochester Medical Center, Rochester, New York 3Rehabilitation Medicine Department, Clinical
Center, Intramural Research Program NIH, Bethesda, Maryland
Abstract
Chronic pelvic pain is a frustrating symptom for patients with endometriosis and is frequently
refractory to hormonal and surgical management. While these therapies target ectopic endometrial
lesions, they do not directly address pain due to central sensitization of the nervous system and
myofascial dysfunction, which can continue to generate pain from myofascial trigger points even
after traditional treatments are optimized. This article provides a background for understanding
how endometriosis facilitates remodeling of neural networks, contributing to sensitization and
generation of myofascial trigger points. A framework for evaluating such sensitization and
myofascial trigger points in a clinical setting is presented. Treatments that specifically address
myofascial pain secondary to spontaneously painful myofascial trigger points and their putative
mechanisms of action are also reviewed, including physical therapy, dry needling, anesthetic
injections, and botulinum toxin injections.
Keywords
endometriosis; chronic pelvic pain; sensitization; myofascial trigger points; botulinum toxin
Chronic pelvic pain (CPP), defined as pain below the umbilicus for at least 6 months in
duration, is one of the most common clinical manifestations of endometriosis. Between 71
and 87% of women with CPP have laparoscopically proven endometriosis lesions,1 but
lesion location correlates poorly with the locations that patients identify as their most intense
areas of pain.2,3 Treatments for endometriosis have focused on hormonal therapies and
surgery, both of which target ectopic endometrial lesions. This approach can control the
extent of disease but often fails to provide a durable solution for associated pelvic pain.
Central sensitization and myofascial pain secondary to active (i.e., spontaneously painful)
myofascial trigger points (MTrPs) likely constitute another source of initiation,
amplification, and perpetuation of pain. Either could easily propagate pain-related symptoms
Address for correspondence: Pamela Stratton, MD, National Institute of Neurological Disorders and Stroke, Intramural Research
Program NIH, Bldg. 31, Room B2B32, 9000 Rockville Pike, Bethesda, MD 20892 (strattop@mail.nih.gov).
HHS Public Access
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Semin Reprod Med
. 2017 January ; 35(1): 88–97. doi:10.1055/s-0036-1597123.
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in women even after surgical and medical/hormonal treatment for endometriosis has been
optimized.
Unfortunately, both central sensitization and myofascial dysfunction are frequently
overlooked in the evaluation, diagnosis, and treatment of CPP associated with endometriosis.
In addition, many gynecologists have not received training in the assessment of myofascial
dysfunction, instead evaluating pelvic pain according to standard gynecological practice. In
this review, we will examine CPP related to endometriosis from a pain-centered perspective,
and discuss how sensitization and MTrPs are crucial components in the chronic pain women
experience that warrant a more comprehensive evaluation and targeted treatment.
Neural Mechanisms in Endometriosis-Associated Chronic Pelvic Pain: The
Dynamic Role of Sensitization
Pain is an unpleasant, subjective experience arising from the central nervous system (CNS)
that normally alerts and protects the body from potentially noxious stimuli.4 Chronic pain,
however, is pathological in itself, and often persists well after an inciting stimulus or injury
has resolved. It is a result of functional and structural rearrangements of the CNS that both
sustain the perception of pain and facilitate its expansion to distant regions.5 Given that
endometriosis is a disease in which hormonally dependent, inflammatory, ectopic
endometrial lesions engage the reproductive, endocrine, vascular, musculoskeletal, and
neuronal systems, there are several factors that may contribute to CPP. This section will
provide a model for CNS engagement in pain with endometriosis, and explain how
myofascial dysfunction may develop from and reinforce this relationship6 (Fig. 1).
Few hypotheses address the question of how ectopic endometrial lesions activate the nervous
system. One likely mechanism involves the innervation of lesions through neural sprouting
of sensory and sympathetic fibers that innervate nearby blood vessels.7 Since endometrial
lesions must be vascularized to survive and grow,8 the branching of blood vessels during
lesion development permits the simultaneous invasion of nerves, as the same factors that act
on sprouting blood vessels act on nerve fibers.9 Nerve growth factor (NGF), in particular,
promotes neurite outgrowth from sensory neurons and nociceptors10; is found in high levels
in peritoneal, deep adenomyotic, and ovarian endometriosis lesions11; and is associated with
greater nerve fiber density in peritoneal endometriosis lesions compared with normal
peritoneum.12 Newly sprouted nerve fibers may facilitate direct communication between the
endometrial growths and the CNS, establishing a bridge for central integration of visceral
sensory input.
Direct innervation of ectopic lesions by sensory and sympathetic nerve fibers has been
confirmed in studies using a rat model13 and in women with endometriosis.14 Furthermore,
their presence correlates with the severity of pelvic pain and dysmenorrhea.15 Sensory fibers
that innervate endometrial lesions are calcitonin gene-related peptide (CGRP)-positive,13,14
indicating that they include C-fiber nociceptors.16 Nociceptors respond to noxious stimuli in
the periphery, and are especially sensitive to immune and inflammatory factors which are
prevalent in endometriosis.
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The peritoneal fluid of women with endometriosis contains elevated levels of tumor necrosis
factor-α, interleukin (IL)-1, IL-6, IL-8, IL-10, RANTES, monocyte chemotactic protein-1,
and prostaglandins E2 and F, all of which directly sensitize or activate nociceptors or trigger
the release of activating substances from nearby cells.17 NGF found near endometriosis
lesions also activates nociceptors and recruits mast cells, which release inflammatory
molecules with degranulation.10,18
Repeated or prolonged activation of nociceptors results in lowering of their activation
threshold, a state known as peripheral sensitization.19 Once activated, nociceptors
themselves can facilitate sensitization by secreting neuropeptides such as substance P and
CGRP that are produced (by the dorsal root ganglion) and released antidromically into
peripheral tissue following repeated stimulation.20,21 These substances induce vasodilation,
increase local vascular permeability, and recruit and activate immune cells, causing
neurogenic inflammation.22 Changes also occur along the peripheral terminals of
nociceptors that permit further sensitization, such as the addition of new receptors to the cell
membrane and the increased expression of existing receptors.19 In addition, although many
visceral nociceptors are initially functionally silent even with intense stimulation, they may
be activated after being sufficiently sensitized by inflammation.23 Thus, peripheral
sensitization ultimately increases the excitability of nociceptors.
Ongoing nociceptor activation generates an afferent bombardment of noxious information
into the dorsal horn of the spinal cord.19 This process, in turn, induces structural and
functional changes throughout the spinal cord and more rostral structures, which ultimately
lead to central sensitization and evoked exaggerated responses to peripheral stimuli (Fig. 1).5
Furthermore, these dynamic alterations within the central circuitry can amplify and
perpetuate the perception of pain long after the initiating pathology resolves.5 Central
sensitization is manifested clinically as allodynia (pain to a non-noxious stimulus),
hyperalgesia (increased pain to a noxious stimulus), and referred pain (perceived pain
outside of the area of noxious stimulation).
Two aspects of central sensitization that are especially relevant to women with CPP and
endometriosis are viscerosomatic convergence and the viscerosomatic reflex. Visceral
afferents constitute only 2 to 7% of all afferent fibers that pass through each dorsal root
ganglion and synapse onto the spinal cord.24,25 As a result, almost all spinal neurons that
receive visceral input also receive somatosensory input from the muscle and skin, through a
process known as viscerosomatic convergence.26 Convergence of inputs hinders precise
localization and discrimination of sensory information.27 It is also the basis for referred
pain, and explains why visceral pathologies are commonly felt as pain in somatic structures
(particularly muscles) innervated by the same spinal segment. Furthermore, since visceral
afferent fibers terminate over several spinal segments above and below the segment level of
input, referred pain may be present in areas remote from the affected visceral organ,26,28 an
effect demonstrated in a rat model and in humans.29,30 Overall, viscerosomatic convergence
explains how ongoing noxious visceral input can sensitize multiple areas of the spinal cord,
generating the broad areas of allodynia, hyperalgesia, and referred pain seen with somatic
dysfunction.31
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Another consequence of central integration of visceral input is the development of the
viscerosomatic reflex. Visceral nociceptors converge with somatic nociceptors onto
interneurons in the spinal cord that activate both alpha and gamma motor neurons
innervating skeletal muscle.32 Ongoing visceral input can produce increased muscle tone
and spasm, usually in the area of pain referral. In addition, “guarding reflexes,” which
involve heightened sacral reflexes that are triggered by visceral pain and inflammation,
could contribute to muscle tightening and result in pelvic floor dysfunction.33 These
mechanisms may create an environment prone to generating or activating MTrPs.
The Contribution of Active Myofascial Trigger Points to Chronic Pelvic Pain
Myofascial pain arises from dysfunction in the muscle and surrounding connective tissue.
Despite being a common clinical problem with a lifetime prevalence of up to 85% in the
general population,34 myofascial pain is an underdiagnosed and often overlooked
component of nonarticular musculoskeletal pain. A hallmark of its diagnosis is the presence
of MTrPs in the symptomatic region, which are small, palpable, hyperirritable nodules
located on taut bands of skeletal muscle and that are in a sustained state of contracture.35
They can be spontaneously painful (i.e., active) or painful only upon perturbation (i.e.,
latent), and they often refer pain in predictable patterns. MTrPs may also cause motor and
autonomic disturbances, and affect the function of visceral organs.35 MTrPs are commonly
found in many chronic pain conditions, and, when active, typically present as a regional pain
syndrome.
MTrPs can be found throughout the body, including the pelvic floor, where they may refer
pain to the urethra, vagina, rectum, coccyx, sacrum, lower back, lower abdomen, and
posterior thighs.36 MTrPs may also refer pain from these muscles back to the pelvic
region,30,35–37 making myofascial pelvic pain difficult to localize. Dyspareunia, dyschezia,
and dysuria are the most common symptoms among women with myofascial pelvic pain,
though these symptoms can also reflect coincident gynecological, gastrointestinal, and
urological conditions.36
In general, MTrPs are believed to occur secondary to muscle overload or overuse. They are
also associated with a variety of medical conditions including those of metabolic, visceral,
endocrine, infectious, and psychological origin.35,37 Within the pelvic floor, previous
gynecological surgeries, childbirth, injury, sexual abuse, dyspareunia, and improper
mechanics may all contribute to MTrP formation.37 MTrPs can also develop secondary to
visceral disease.35 Studies have shown that MTrPs are associated with endometriosis38 and
interstitial cystitis/painful bladder syndrome39 as well as other gynecologic, genitourinary,
and gastrointestinal conditions, such as vulvodynia, irritable bowel syndrome, coccygodynia,
and urethral syndrome.36,40 MTrPs compound the pain experienced with any of these
conditions. Abdominal and pelvic MTrPs were commonly found in women with CPP and
current biopsy-proven endometriosis, and, adjusting for any history of endometriosis,
women with MTrPs were most likely to present with signs of sensitization in one clinical
study.38
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A myofascial component to pelvic pain adds another dimension to a patient’s disease and
requires its own diagnosis and treatment. Once formed, MTrPs can become a self-sustaining
source of pain even after the visceral insult has resolved.41 Active MTrPs, in particular, serve
as a source of ongoing nociception; they can reduce pain thresholds, enhance visceral and
referred pain, and sensitize the nervous system.42 In regard to endometriosis, MTrPs that
develop secondary to disease could sustain the pain and dysfunction despite lesion removal
and hormonal management.
Clinical Evaluation for Endometriosis-Related Pelvic Pain and Sensitization
Given the multifaceted nature of CPP associated with endometriosis, clinical evaluation
benefits from a systematic, interdisciplinary approach that includes a targeted pelvic
examination and a broader neuro-musculoskeletal pain assessment. Table 1 presents a
summary of this clinical assessment and complements the standard approach for a
gynecological assessment by focusing on evaluating pain related to endometriosis rather
than the lesions themselves or other noted pathology.
When taking a medical history, practitioners focus on the details regarding the history of
endometriosis and CPP. Often, having the patient complete a pain calendar for a menstrual
cycle can help reveal patterns of pain associated with menstruation and hormonal
fluctuations. Past and current treatments (pharmaceutical, hormonal, surgical, etc.) for
endometriosis or pain and the outcomes for each treatment aid to inform treatment options.
The pelvic examination for active MTrPs explores the external and internal pelvic areas as
well as the abdomen using only a single digit or one hand. This approach isolates areas of
tenderness and allows for assessment of myofascial dysfunction and sensitization. Since
abdominal wall muscle pain can refer to the pelvis,35 all regions of the abdominopelvic
region are examined for allodynia and diffuse tenderness, which can be signs of
sensitization.41 The abdomen is assessed for the number and location of abdominal muscle
MTrPs, and the severity of pain elicited with palpation. Sacroiliac (SI) joint tenderness is
also assessed.
The pelvic exam begins with an external assessment of the pelvic floor muscles for improper
positioning, trauma, or scars, followed by having the patient contract and relax her pelvic
floor muscles to assess for myofascial pain or hypertonicity. Using a single digit, the
examiner then individually palpates the pelvic floor muscles, first externally and then
internally, starting anteriorly with the superficial perineal muscles and moving posteriorly to
the coccyx, noting MTrPs, taut bands, or generalized tenderness that reproduce the patient’s
pain. The sphincter ani, levator ani, coccygeus, and obturator internus most commonly
harbor MTrPs.43 MTrPs in these muscles are not usually nodules, but instead are taut bands
that are tender, span the distance of the fiber, and are noticeably in spasm.30 Performing the
exam slowly and pausing when pain is elicited often gives the best insights into the degree
and extent of MTrP activation and local spasticity.
Bladder and urethral tenderness as well as uterosacral, forniceal, and vaginal tenderness and
nodularity are also examined using a single digit. A bimanual exam can then be performed
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to assess central uterine tenderness. Recording the pattern of abdominopelvic tenderness as
well as the location and pattern of worst pain provides a framework for considering pelvic
pain triggers.
To supplement the pelvic examination, a brief neuro-musculoskeletal pain assessment can
identify signs of widespread pain, central sensitization, and myofascial dysfunction. Each
dermatome and myotome is evaluated with the patient reporting when pain is evoked (Table
1). Dermatomes are assessed for allodynia and hyperalgesia bilaterally over the skin,
approximately 2.5 cm lateral to each spinal process. Allodynia is assessed using the pinch-
and-roll technique or by brushing the skin with a thin microfilament, while hyperalgesia is
assessed by scratching the skin with the edge of a paper clip or Wartenberg pinwheel. The
myotome is assessed for the presence of MTrPs. By examining a series of muscles spanning
the length of the body, the examiner can evaluate the distribution of myofascial dysfunction
and extent of overall sensitization.
These complementary exams together provide a more complete assessment of patients with
CPP associated with endometriosis. The pelvic exam is valuable for identifying pelvic floor
tenderness and spasm, which may be potential triggers for persistent pain and may warrant
directed treatment. The neuro-musculoskeletal exam identifies alterations in pain perception
beyond the pelvic muscles, placing the pelvic exam findings in the broader perspective of
global neuromuscular and myofascial dysfunction.
Myofascial Release Techniques for Chronic Pelvic Pain
Treatment for pelvic pain associated with endometriosis warrants identification and therapy
directed to the pathological findings that generate and sustain pain symptoms. Since a
myofascial source may contribute to endometriosis-associated CPP even after hormonal and
surgical treatment has been undertaken, a growing number of practitioners are exploring
pain management methods that directly address myofascial pain.
One set of treatment is collectively known as myofascial release, which involves physical
therapy and other manual techniques including deep pressure massage, stretching
techniques, joint mobilization, and foam rollers, often in combination with teaching about
strategies used to manage pain, including breathing and relaxation exercises.37,44 This dual
approach addresses physiological and psychological components of chronic myofascial pain,
alleviates MTrP-related pain, and furnishes patients with coping strategies to redirect their
focus during a painful episode. Small studies tout the effectiveness of these techniques in the
treatment of myofascial pelvic pain, including one retrospective study which showed that
physical therapy benefits up to 63% of patients who attempt it.37,45 However, no
randomized, controlled trials have compared physical therapy with the standard of care for
endometriosis patients with MTrPs.
MTrP injection, with or without a topical anesthetic (wet or dry needling, respectively), is
another common form of myofascial treatment being studied. The theoretical basis of MTrP
injection is that entry into a hypercontracted muscle causes mechanical disruption that
interrupts the aberrant sensory signals that cause MTrP formation.44 Direct injection of a
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local anesthetic such as lidocaine is thought to further blunt the ability to transmit pain
signals through these hyperactive neural networks, providing additional pain relief that may
be more durable than needling of MTrPs alone. Prospective studies using dry needling have
not been performed in the pelvic region. However, dry needling in other body regions has
been shown to reduce pain and is non-inferior to wet needling, though pain relief from MTrP
anesthetic injections is longer lasting.44,46 For CPP patients with MTrPs in the abdominal
wall, direct injections with lidocaine provided superior clinical response rates to physical
therapy out to 12 weeks after treatment,47 and small studies of CPP patients who received
lidocaine injections in the pelvic musculature report pain relief as well.48,49
Botulinum Toxin Type A: Alleviating Hypertonicity to Lessen Myofascial
Pelvic Pain Associated with Endometriosis
Botulinum toxin (BTX) is the first-line therapy for focal dystonias, and is an increasingly
common treatment for other neuromuscular conditions arising from excessive muscle
activity.50,51 Randomized, controlled trials evaluating the effectiveness of BTX in relieving
myofascial pain in the neck, cervicothoracic region, shoulder, and upper back have generated
mixed results.52–54 There have been a limited number of studies to date, including two
double-blind, placebo controlled trials, evaluating BTX injection into pelvic floor muscles
for CPP. Further investigation is required to explore this approach, including optimization of
dosage and injection technique; however, the current evidence suggests that BTX may be
effective in treating endometriosis-associated CPP.
The clinical efficacy of BTX in treating spasticity, dystonia, hemifacial spasm, overactive
bladder, and migraine has been well established. BTX is a neurotoxin produced by
Clostridium botulinum
that irreversibly blocks acetylcholine release at the neuromuscular
junction.55 This action prevents the transmission of signals that stimulate muscle fibers.
When the dose is carefully titrated, excessive muscle contraction and spasm can be eased
without muscle paralysis. Clinically, a reduction of muscle spasm and associated pain
results.55 Skeletal muscle strength decreases within 2 to 5 days after injection, reaches its
nadir within 2 weeks, and recovers gradually after that. The effects of BTX on the
neuromuscular junction are irreversible, requiring new motor axon regeneration and
restoration of the neuromuscular junction. The period of clinical efficacy typically lasts 3 to
6 months for approved indications, so that reinjection is required to maintain benefit. The
safety of repeated BTX injection has been established through over 20 years of clinical use.
Two toxin serotypes (A and B) and several brands of toxin are currently commercially
available.
The duration of therapeutic effects, well-characterized muscle relaxant activity, and evidence
of direct analgesia make BTX an ideal candidate for treatment of myofascial CPP in the
setting of endometriosis. Several case studies and small trials have examined the utility of
BTX injections for treatment of various types of CPP (Table 2). The first documented
gynecologic use for BTX in 1997 included electromyography (EMG) to identify hyperactive
areas of the anterior vaginal wall in a woman with vaginismus. A series of two injections
over 7 weeks resolved bladder, urethral, and vaginal pain symptoms.65 A subsequent series
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of studies from Australian researchers examined type A BTX for the treatment of levator ani
spasm and showed a reduction in resting pelvic floor pressure by manometry as well as a
statistically significant improvement in dyspareunia and nonmenstrual pelvic pain.56,59,61,66
A randomized placebo-controlled trial from this same group examining type A BTX for 60
women showed that only improvement in nonmenstrual pelvic pain was unique to the
treatment group, implying that dry needling may contribute to pain relief at MTrPs.56 Other
groups have observed benefits of BTX injections for dysmenorrhea and quality of life in
patients with pelvic floor spasm.62–64 Unfortunately, not all studies have shown efficacy; in
a small randomized controlled trial examining 60 women with vestibulodynia, a low dose of
type A BTX into the vestibule did not significantly improve pain or quality-of-life measures
at 3 or 6 months after injection compared with placebo.57 It is likely that differences in dose,
dilution, muscle selection, and injection technique contributed to the differences seen in
these studies’ outcomes. Further research is needed on each of these aspects of BTX
treatment.
At our center, we conducted a randomized placebo-controlled pilot study in which seven
women with CPP, most of whom had laparoscopically confirmed endometriosis, received
either 100 U onabotulinum toxin A diluted into 4 mL of saline or placebo injected
transvaginally into the areas of pelvic floor spasm in the levator ani muscles under EMG
guidance (data not published). The injections were part of a comprehensive approach to
pelvic pain after surgical treatment of endometriosis in which patients could also choose to
use hormonal contraceptives, progestin-releasing intrauterine devices (IUDs), analgesics,
and have pain and palliative care therapy including massage, acupuncture, and mind–body
therapies.
Women in both active drug and placebo groups experienced improvement in pain. The
duration of pain improvement was longer in those who received BTX (3.5 weeks for BTX
vs. 1 week for placebo). Women receiving BTX were more likely to be able to quantify the
extent and duration of benefit from injection, whereas those who received placebo reported
benefit in vague terms. These findings suggest, as in the Abbott et al study, that dry needling
of MTrPs may have provided at least some brief pain relief to women in the placebo
group.56 These preliminary data are difficult to interpret, as those receiving BTX had lower
overall pain severity prior to injection than those in the placebo group (3.6 vs. 8.5 on VAS
scale from 0 to 10). However, these data were promising enough that we are now conducting
a double-blind, placebo-controlled study of BTX for CPP in women with surgically
documented endometriosis (NCT01553201).
BTX is, thus, a promising treatment for endometriosis-associated CPP. With regard to the
myofascial contribution to CPP characterized by MTrPs of muscle fibers that are in a
prolonged state of contracture, BTX may be effective in relaxing the muscles of the pelvic
floor that are unlikely to respond to surgery or hormonal therapy, and that may not respond
to myofascial release techniques.
BTX may also have direct analgesic effects that complement the effects on muscle
relaxation.68 Although BTX is highly specific for cholinergic neurons, it has shown
additional effects on the secretion of peripheral and central neurotransmitters in culture and
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in mouse models.68 These studies have shown a decrease in the release of proinflammatory
neuropeptides such as substance P and CGRP, a resultant decrease in inflammation, and
alterations in intracellular trafficking patterns that, altogether, may contribute to an overall
decrease in pain and inflammation.68
In addition, the effects of BTX on pain may not be limited to peripheral benefits. The
inflammatory nature of the endometriosis lesions as well as the abnormal contracture of
MTrPs all contribute to a feed-forward mechanism that eventually restructures how pain is
centrally processed and experienced. Research studies have shown that the release of the
MTrPs is followed by a corresponding decrease in the levels of substances associated with
pain and inflammation around the area of treatment.69,70 Lowering the levels of these
proinflammatory molecules reduces the barrage of noxious input from the periphery that
cause maladaptive changes within the CNS.71 Thus, BTX may not only target the peripheral
sources of CPP but can also work in conjunction with the usual gynecologic treatments in
endometriosis to reduce peripheral and central sensitization and restore normal pain and
sensory information processing.
Conclusion
It is important to consider CPP associated with endometriosis from a global pain-centered
perspective, as MTrPs and sensitization appear to contribute significantly to the clinical
manifestations. While direct innervation of endometrial lesions may set the stage for visceral
nociception and peripheral sensitization, over time, central sensitization creates a process for
pain sustention that is independent of the initial pathology and is potentially reversible.41
Viscerosomatic convergence may not only provide the means for pain referral to somatic
structures but also govern the reflex that induces muscle spasm and the eventual formation
of MTrPs. Painful MTrPs, in turn, may serve as an additional source of nociceptive input,
and become a key component of CPP. Their deactivation through a targeted intervention may
be a critical aspect to reversing central sensitization and improving pain associated with
endometriosis.
Acknowledgments
This work was funded by the Intramural Research Program of the National Institutes of Health, the NIH Clinical
Center, and the National Institute of Neurological Disorders and Stroke.
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Fig. 1.
Nervous system engagement by endometrial lesions gives rise to different types of pain. (a)
This figure illustrates how endometrial lesions can engage the nervous system to give rise to
different types of pain associated with endometriosis and comorbid conditions. (1) Typical
laparoscopic view of pelvic organs from the umbilicus. Inset demonstrates a deeply
infiltrating lesion on the left uterosacral ligament. Both peptidergic sensory (blue) and
sympathetic nerve fibers (green) sprout axon branches (red dashed lines) toward this lesion.
Estradiol and sympathetic-sensory coupling drive peripheral sensitization (red asterisk) of
new sensory fibers within the lesion. (2) Central sensitization (red asterisk) is propagated at
synapses between sensitized peripheral nerve fibers and neurons in the sacral spine. This
central sensitization is modulated differently from and can eventually become independent
of peripherally sensitizing signals. (3) Although input from pelvic peripheral afferent fibers
typically synapse with dorsal root ganglia in the sacral spine, branches of the fibers extend to
other segments (blue dashed lines), and can propagate sensitization at distant spinal cord
segments (red dashed lines). (4) Normally, multiple intersegmental spinal synaptic
connections exist to coordinate bodily functions (double-arrowed black lines). In
pathological pain conditions, this communication can alter processing of nociceptive and
non-nociceptive sensory information in remote segments (“remote central sensitization, red
asterisks). Via (3) and (4), increased nociception propagates into distant spinal segments. (5)
Multiple afferent (blue) and efferent (green) pathways exist between the CNS and PNS with
terminal connections in the brain. Input from sensitized spinal neurons can affect activity
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throughout the neuroaxis (red asterisks), altering normal processing of nociceptive and non-
nociceptive information. Alterations in processing can occur on the medial cortical surface;
the lateral prefrontal, frontal, and parietal lobes; and within the temporal lobe (dotted black
ellipses). These influences can propagate signals independent of peripheral sensitization
associated with lesions. (b) Muscles of the pelvic floor feed into sensitization pathways in
the same manner as endometrial lesions. All mechanisms outlined can cause endometriosis-
associated pain in the pelvis and at distant sites. (Reprinted with permission from Stratton
and Berkley.3)
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Aredo et al. Page 16
Table 1
Clinical evaluation of endometriosis-related pain and sensitization
Patient History
History of endometriosis
Method of diagnosis
Previous and current treatments with their outcomes
Gynecologic and obstetric history
Menses: duration of flow, cramping, spotting, regularity, infertility, desire for future children
Gynecologic conditions, history of sexually transmitted infections
Current hormonal therapy
Surgery (type, findings, and treatment)
General medical history
Medical conditions
Headaches/migraines, depression, anxiety
Bowel and bladder symptoms suggestive of irritable bowel and painful bladder
Current medications/allergies
History of chronic pelvic pain
Duration, frequency (intermittent, constant)
Any temporal relationship to menstrual cycle (ovulation, menstruation, etc.)
Alleviating and exacerbating factors
Other pain conditions
Previous and current treatments with their outcomes
Gynecological Examination – Evoked Pain Assessment
Abdominal wall
Location and pattern of tenderness (diffuse, focal, not localized)
Allodynia
Myofascial trigger points (number, location, severity of pain)
Perineum
Improper positioning, trauma, scars
Observe pelvic floor muscle contraction and relaxation
Pelvic region
Superficial perineal muscles for muscle spasm and tenderness
Pelvic floor muscles: myofascial trigger points, taut bands, tenderness
Bladder and urethral tenderness
Uterosacral, forniceal, and vaginal tenderness and nodularity
Central uterine tenderness
Pattern of pelvic tenderness (diffuse, focal, not localized)
Location of worst pain
Neuro-Musculoskeletal Examination
Dermatome:
Allodynia via pinch and roll technique
a
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Hyperalgesia via Wartenberg pinwheel
a
Myotome
b
Regional/abdominopelvic muscles: rectus abdominis, external oblique, iliacus and gluteus maximus
General muscles: temporalis, masseter, upper trapezius, supraspinatus, adductors, vastus medialis
a
Assess spinal segments paraspinally, bilaterally in the region of pain. Record which segments have allodynia and hyperalgesia. If most segments
are affected, then add segments above and below to assess the extent of sensitization.
b
Palpate bilaterally for myofascial trigger points in region of pain and throughout the body; identify as pain free or painful (latent or active) by
region or in general. Integrate the pelvic and neuro-musculoskeletal examination findings with the clinical presentation.
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Table 2
Clinical studies evaluating botulinum toxin type A treatment for chronic pelvic pain
Study type Authors (year) NTotal BTX-A dose Areas injected Outcomes
Randomized controlled trial Abbott et al56 (2006) 60 Onabotulinum-toxin A 80 U Puborectalis and pubococcygeus
bilaterally Both treatment and placebo groups had
reductions in dyspareunia and pelvic floor
pressure BTX-A group alone showed
improved nonmenstrual pain
Petersen et al57 (2009) 64 Onabotulinum-toxin A 20 U Musculus bulbospongiosus No improvement compared with placebo at
3 and 6 mo; both treatment and placebo
groups had pain reduction at 6 mo
Prospective open-label study Ghazizadeh and
Nikzad 58 (2004) 23 Abobotulinum-toxin A 150–400 U Puborectalis at 3 points bilaterally Dyspareunia and vaginismus subjectively
improved
Jarvis et al59 (2004) 12 Onabotulinum-toxin A 40 U Puborectalis and pubococcygeus
bilaterally Dyspareunia and dysmenorrhea significantly
improved Significant reduction in resting
pelvic floor muscle pressure
Bertolasi et al60 (2009) 39 Type A toxin not otherwise specified up to 8
repeat cycles over 120 wk Levator ani Dyspareunia, levator ani hyperactivity by
EMG improved Improvements in subjective
pain, function, and quality of life by
standardized pelvic pain surveys
Nesbitt-Hawes et al61
(2012) 37 Onabotulinum-toxin A 100 U Puborectalis and pubococcygeus
bilaterally 26 women received single injection 11
women received two or more injections
Dyspareunia, nonmenstrual pelvic pain, and
vaginal pressures significantly improved in
both groups
Morrissey et al62 (2015) 21 Onabotulinum-toxin A Up to 300 U Levator ani Dyspareunia and sexual dysfunction
significantly improved Significant reduction
in pelvic floor muscle tenderness, resting
pressures, and in maximum contraction
pressures
Retrospective cohort study Adelowo et al63 (2013) 29 Onabotulinum-toxin A 100–300 U Individualized tender and
contracted points in the pelvic
floor muscles
Levator tenderness on palpation significantly
improved
Self-reported urinary incontinence decreased
significantly
Case series Romito et al64 (2004) 2 Abobotulinum-toxin A 40–80U Levator ani Complete resolution of pelvic pain and
spasm
Case report Brin and Vapnek et al65
(1997) 1 Onabotulinum-toxin A Two 10 U injections
then 40 U after 7 wk Anterior vaginal wall muscles Vaginal, bladder, and urethral spasms
subjectively improved
Thomson et al66 (2005) 1 Onabotulinum-toxin A Two 40 U injections
then two 80 U injections, ~20 wk apart Puborectalis and pubococcygeus
bilaterally Dyspareunia, dysmenorrhea, and dyschezia
improved after each injection
Reduction in pelvic floor muscle manometry
readings
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Study type Authors (year) NTotal BTX-A dose Areas injected Outcomes
Park and Paraiso67
(2009) 1 Type A toxin not otherwise specified. 40 U Levator ani and pubococcygeus Unresolved postsurgical dyspareunia
improved
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... MTrPs can be present in any skeletal muscle, including the pelvic floor (PF), where they can refer pain to the urethra, vagina, rectum, coccyx, sacrum, lower back, lower abdomen, and posterior thighs, as well as muscles in other body locations such as the back or hip; all of these cause pain to the pelvic area [39,42]. MTrPs may also be responsible for other symptoms compatible with some gynecological, gastrointestinal, and urological disorders or conditions [42,43]. ...
... MTrPs can be present in any skeletal muscle, including the pelvic floor (PF), where they can refer pain to the urethra, vagina, rectum, coccyx, sacrum, lower back, lower abdomen, and posterior thighs, as well as muscles in other body locations such as the back or hip; all of these cause pain to the pelvic area [39,42]. MTrPs may also be responsible for other symptoms compatible with some gynecological, gastrointestinal, and urological disorders or conditions [42,43]. We found studies in which the presence of MTrPs in the abdominal and pelvic musculature may be highly prevalent in patients with CPP [42,[44][45][46]. ...
... MTrPs may also be responsible for other symptoms compatible with some gynecological, gastrointestinal, and urological disorders or conditions [42,43]. We found studies in which the presence of MTrPs in the abdominal and pelvic musculature may be highly prevalent in patients with CPP [42,[44][45][46]. ...
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There is limited information on myofascial trigger points (MTrPs) and specific symptoms of chronic pelvic pain and, more specifically, dysmenorrhea. The objective of this study was to determine whether patients suffering from primary dysmenorrhea present alterations in mechanosensitivity and pain patterns, and greater presence of MTrPs in the abdominal and pelvic floor muscles. A case-control study was carried out with a total sample of 84 participants distributed based on primary dysmenorrhea and contraceptive treatment. The sample was divided into four groups each comprising 21 women. Data on pain, quality of life, and productivity and work absenteeism were collected; three assessments were made in different phases of the menstrual cycle, to report data on pressure pain threshold, MTrP presence, and referred pain areas. One-way ANOVA tests showed statistically significant differences (p < 0.01) between the groups, for the Physical Health domain and the total score of the SF-12 questionnaire, and for all the domains of the McGill questionnaire; but no significant differences were found in the data from the WPAI-GH questionnaire. Statistically significant data (p < 0.01) were found for mechanosensitivity in the abdominal area and limbs, but not for the lumbar assessment, within the group, with very few significant intergroup differences. The frequency of active MTrPs is higher in the groups of women with primary dysmenorrhea and during the menstrual phase, with the prevalence of myofascial trigger points of the iliococcygeus muscle being especially high in all examination groups (>50%) and higher than 70% in women with primary dysmenorrhea, in the menstrual phase, and the internal obturator muscle (100%) in the menstrual phase. Referred pain areas of the pelvic floor muscles increase in women with primary dysmenorrhea.
... El SDMF en la musculatura del suelo pélvico es una de las causas más frecuentes de dolor pélvico crónico en la mujer, ya sea como entidad sindrómica o asocia do a otras causas orgánicas de dolor (12). Ha sido reportado que el 87 % de los focos de endometriosis encontrados en intervenciones laparoscópicas tiene poca respuesta terapéutica, además de no tener una relación clara con la zona de dolor de las pacientes y, por tanto, en los últimos años el SDMF ha cobrado importancia como posible etiología (13). ...
... Los puntos de dolor miofascial pélvico de la mujer no solo generan síntomas dolorosos con la estimula ción de la banda tensa, sino que afectan de manera negativa la calidad de vida y favorecen procesos de sensibilización central y periférica al dolor, lo cual difi culta la respuesta de las intervenciones (14). A pesar de ser una condición ginecológica y urológica frecuente, la mayoría de los médicos de estos campos no reciben formación suficiente sobre el diagnóstico y tratamiento de esta entidad (12). ...
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Introducción: El síndrome de dolor miofascial del suelopélvico en la mujer es una causa frecuente de dolor agu­do y crónico, en ocasiones superpuesto a otras entida­des patológicas. Es secundario a la sobrecarga mecánicamuscular que favorece la aparición de puntos gatillo. Objetivo: Describir una entidad dolorosa frecuente,su fisiopatología y posibilidades de tratamiento. Metodología: Se realizó una revisión de la literaturacon términos Mesh en inglés y español en las bases dedatos Embase, Pubmed, Lilacs, Sage, Google Acede­mics y Scielo desde el año 1983 hasta el año 2021.Se encontraron 240 artículos y fueron seleccionados50, basados en su impacto clínico. Resultados: El dolor pélvico afecta a más del 50 %de las mujeres mayores de 35 años. Existen diferentescondiciones clínicas que favorecen la sobrecarga mecá­nica muscular y la formación de puntos miofascialesdolorosos. El diagnóstico es clínico, pero se puedensolicitar estudios imagenológicos. El tratamiento incluyevarias modalidades: terapia física, psicoterapia, farma­coterapia e intervencionismo con aguja seca, estimula­ción eléctrica y toxina botulínica. Conclusión: El síndrome miofascial en la muscula­tura pélvica femenina es una condición prevalente quedebe ser considerada dentro del diagnóstico de dolorpélvico y abordada de manera multidisciplinaria.
... Due to the extended period of exposure to pain signals in endometriosis, the body is prone to reclassifying this pain as threatening, altering the normal modulation of this pain (10). During central sensitization, signals of pain are abnormally processed resulting in experiences of pain becoming heightened and exaggerated (10)(11)(12). Simultaneously, peripheral sensitization results from the repetitive and prolonged stimulation of a patient's nociceptors, as occurs in endometriosis, progressively lowering the threshold for activation (10,12). Women with chronic pelvic pain, with or without a surgically-confirmed diagnosis of endometriosis, show significantly lower pain tolerances than healthy controls (4). ...
... During central sensitization, signals of pain are abnormally processed resulting in experiences of pain becoming heightened and exaggerated (10)(11)(12). Simultaneously, peripheral sensitization results from the repetitive and prolonged stimulation of a patient's nociceptors, as occurs in endometriosis, progressively lowering the threshold for activation (10,12). Women with chronic pelvic pain, with or without a surgically-confirmed diagnosis of endometriosis, show significantly lower pain tolerances than healthy controls (4). ...
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Endometriosis is a chronically painful, invasive, inflammatory disease, with limited treatment options and long delays to diagnosis, which impacts 10% of females in New Zealand. Introduction As part of a larger group discussion study, this paper covers three themes associated with endometriosis patient experiences: intensity of pain, diagnostic tool shortcomings and perspectives of treatment options. Materials and methods The goal of this research was the inclusion of patient voices to guide research priorities. In early 2022, 50 New Zealand endometriosis patients participated in anonymous, asynchronous, text-based group discussions on the VisionsLive platform. The patients ranged in age from 18–48. The patients answered 50 questions, 23 text-based and 27 quantitative, and then took part in online group discussions. Results and discussion The average age of symptom onset was 15.3 years, while the average delay from symptom onset to a working or surgically confirmed diagnosis was 7.91 years. The top five reported symptoms within the cohort were pain-based, and the participants discussed the many impacts of this pain on their work and education. The four main diagnostic tools employed on this cohort were abdominal ultrasound (72%), transvaginal ultrasound (68%), laparoscopy (82%) and sharing their symptom history with a medical practitioner (88%). The most common emotions patients experienced following receiving a diagnosis of endometriosis were relief (86%), feeling overwhelmed (54%), and anger (32%). The main treatments offered to this cohort were pain relief (96%), laparoscopic surgery (84%) and the combined oral contraceptive pill (80%). Of these three treatments, only laparoscopic surgery was viewed positively by the majority of users, with 67% considering laparoscopy an effective treatment, compared to 46% of users for pain relief, and 25% of users for the combined oral contraceptive pill. Conclusions Gathering the voice of patients revealed that long delays to diagnosis and dismissal by medical practitioners frequently manifests as a reaction of relief by patients once diagnosed. Results also showed treatment options such as pain relief and hormonal medications were often considered ineffective, but were routinely offered as the first, or only, options for patients. It is therefore important that both quicker routes to diagnosis and more effective treatment options be developed.
... CS is characterized by alterations in the central nervous system that increase responsiveness to pain leading to hypersensitivity [15,16]. CS has been shown to play a role in numerous chronic pain conditions, including chronic pelvic pain [17][18][19]. Specifically, repeated experiences of nociceptive input from the reproductive organs and viscera, as is the case with PD, can result in neuronal hypersensitivity and hyperalgesia and can change how the brain processes pain-related information [15,16,20]. Brain imaging studies have shown altered brain structure and function in women with PD compared to controls, even during non-painful cycle phases [21][22][23]. ...
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Introduction Dysmenorrhea and mastodynia are the most common gynecologic pain causes in women of all ages and races during their reproductive life. The following study aimed to show the influence of two POP´s in the development of dysmenorrhea and mastodynia after nine months of use. Material and methods A total of 858 women with 6691 drospirenone (DRSP) cycles and 332 women with 2487 desogestrel (DSG) cycles were analyzed. Women included in this study were all child-bearing potentials, at risk of pregnancy, agreeing to use only the study medication for contraception for the duration of the study medication treatment, aged 18 to 45. Results At screening, 168 (19.6%) of the 858 patients using DRSP and 64 (19,3%) of the DSG patients reported that they had suffered from dysmenorrhea within six cycles prior to the first visit before starting with the medication. 20,2% of the DRSP and 10,9% of the DSG group had a sever dysmenorrhea. After 9 cycles this was reduced to 0,6% and 3,1% respectively. In total, 96 women (11.2%) in the DRSP and 49 (14,8%) experienced mastodynia within six cycles before the screening. Of these 91.6% in the DRSP group and 91,8% in the DSG group had no or mild mastodynoa at follow-up. Discussion The progestins 4 mg and desogestrel 0,075 mg showed a marked effect in the non-contraceptive aspects of dysmenorrhea and mastodynia so that new possibilities are opened for these two benign gynecological diseases. Future studies must reaffirm these first data.
... In this case, nociceptive information continues to reach the spinal cord despite no peripheral problems, and leads to central sensitization which results in allodynia (light touch perceived as painful) and visceral hyperalgesia (abnormal and painful perception of visceral stimuli such as micturition). 6 As regards neurological aspects, some authors have suggested the involvement of the amygdala, the hippocampus, the ventral striatum, and the medial prefrontal cortex, which govern emotions and expectations. 7 Others have pointed out the importance of epigenetic modulation in chronic pain. ...
Article
Background: Pelvic pain has cognitive, behavioral, sexual, and emotional consequences. Nurses involved in pelvic floor rehabilitation clinics have contacts with patients reporting chronic pain and should know the most appropriate service for patient referral, to submit the problem to professionals capable of correctly assessing and managing the condition. Furthermore, in some countries nurses can use conservative methods to treat the painful symptoms inside a multidisciplinary team such as breathing retraining, biofeedback, and noninvasive neuromodulation. This paper aims to provide an overview of the literature regarding the role of rehabilitation nurses in dealing with patients suffering from chronic urogenital pelvic pain or urogenital painful syndromes, inside a multidisciplinary team. Methods: Scoping review on Pubmed, CINAHL, Embase, Scopus, Web of Science including trials, reviews, case studies or series, and other descriptive studies regarding the role of nurses inside the multidisciplinary team in the management of males and females presenting chronic pelvic pain (CPP) or chronic pelvic pain syndrome (CPPS). Results: The 36 papers included in this review allowed answering research questions in four areas of nursing: collecting basic information, referring the person to appropriate services, evidence-based nursing interventions for CPP and CPPS, and proper documentation. Clinical history and assessment of breathing pattern, Muscular assessment and research of trigger points are the main points of data collection. Techniques for muscular relaxation and breathing retraining are important aspects of treatment, as well as biofeedback and noninvasive neuromodulation where the law allows nurses to practice such techniques. The McGill pain questionnaire and the pain inventory of the International Pain Society allow systematic data collection and handover. Conclusion: Rehabilitation nurses work inside multidisciplinary teams when dealing with persons suffering from pelvic pain; further research is needed as our comprehension of the underlying pathophysiological mechanisms of CPP and CPPS evolve.
... In fact, these symptoms could be related to endometriotic disease and adenomyosis requiring hormonal therapy. Otherwise, they could be related to other causes, such as central sensitivity syndrome, pelvic floor dysfunction, interstitial cystitis requiring a different diagnostic and therapeutic management (38). ...
Article
Objective: To evaluate transvaginal sonography (TVS) findings after laparoscopic partial cystectomy for bladder endometriosis and to correlate postsurgical ultrasound findings with symptoms. Material and methods: A retrospective study including women who underwent laparoscopic partial cystectomy for bladder endometriosis. Within 12 months after surgery, TVS examination was conducted in all patients to evaluate the bladder morphology, and the presence of any postsurgical sonographic findings of the pelvis. Painful symptoms were assessed using a visual analogue scale. Results: A total of 40 women were included. At the follow-up visit, 25 patients were receiving medical treatment while 15 had declined post-surgical therapy and had tried to conceive. The presence of bladder deep-infiltrating endometriosis (DIE) was found in nine (22.5%), fibrotic thickening of the bladder wall was found in 15 (37.5%), and normal bladder morphology was observed in 16 (40%). There was a correlation between anterior adenomyosis and bladder DIE, and fibrotic thickening of the bladder. Patients with TVS signs of bladder DIE and anterior adenomyosis suffered more dysmenorrhea and dysuria than patients with normal bladder. Conclusion: Post-operative TVS can detect the alteration of pelvis and could explain the causes of the persistence of symptoms.
... It can be a pain syndrome on its own, for example, due to repeated or chronic muscular overload that eventually originates trigger points in the muscle or fascia [3]. However, myofascial pelvic pain is frequently associated with urological, gynecological, and colorectal pain syndromes [4][5][6]. The presence of MTrPs in the symptomatic region is the distinctive feature of the syndrome. ...
Article
Context Despite the high prevalence of a myofascial pain component in chronic pelvic pain (CPP) syndromes, awareness and management of this component are lacking among health care providers. Objective To summarize the current state of the art for the management of myofascial pain in chronic primary pelvic pain syndromes (CPPPS) according to scientific research and input from experts from the European Association of Urology (EAU) guidelines panel on CPP. Evidence acquisition A narrative review was undertaken using three sources: (1) information in the EAU guidelines on CPP; (2) information retrieved from the literature on research published in the past 3 yr on myofascial pelvic pain; and (3) expert opinion from panel members. Evidence synthesis Studies confirm a high prevalence of a myofascial pain component in CPPPS. Examination of the pelvic floor muscles should follow published recommendations to standardize findings and disseminate the procedure. Treatment of pelvic floor muscle dysfunction and pain in the context of CPP was found to contribute to CPP control and is feasible via different physiotherapy techniques. A multidisciplinary approach is the most effective. Conclusions Despite its high prevalence, the myofascial component of CPP has been underevaluated and undertreated to date. Myofascial pain must be assessed in all patients with CPPPS. Treatment of the myofascial pain component is relevant for global treatment success. Further studies are imperative to reinforce and better define the role of each physiotherapy technique in CPPPS. Patient summary Pain and inflammation of the body’s muscle and soft tissues (myofascial pain) frequently occurs in pelvic pain syndromes. Its presence must be evaluated to optimize management for each patient. If diagnosed, myofascial pain should be treated.
Article
Background and aim Endometriosis affects 10–15 % of women and girls in reproductive age which reduces their quality of life and encompasses social and economic consequences. Hence, this study aimed to evaluate a more reliable diagnostic approach using oncomiR-21 expression analysis in patients with mild and severe endometriosis to improve the quality of life with early diagnosis and timely management. Methods We first established an in vitro culture system to conduct a transfection experiment for establishing relationship between oncomiR-21 and PTEN. Further, we evaluated differential expression levels of an oncomiR-21 in 45 histologically graded endometrial biopsy tissues and validated in plasma samples of respective women with mild, and severe, and chocolate cyst in South Indian population using SYBR Green-based RT-qPCR analysis. Results Transfection results showed negative correlation between oncomiR-21 and PTEN expression levels specifically in severe forms of the disease. Similar to findings in tissue samples for oncomiR-21 expression levels, significantly higher values for endometriosis Grades I & II (8.23 ± 0.76, p < 0.01), endometriosis Grades III & IV (11.51 ± 3.47, p < 0.001), and Chocolate Cyst (13.37 ± 3.68, p < 0.001) was observed. Correlation analysis showed that the best outcome can be measured using oncomiR-21 expression analysis almost similar in tissue as well as plasma samples to distinguish all three categories of endometriosis patients from controls. Conclusion This study revealed that quantitative analysis of circulating oncomiR-21 in plasma samples can be used as a potential molecular tool for early detection and discrimination of mild and severe forms of endometriosis and risk of malignant transformation for timely diagnosis and improved management of endometriosis patients.
Article
Study objective To assess prevalence of Central Sensitization (CS) and its association with demographic and clinical factors in patients with endometriosis. Design Single center, observational, cross-sectional study. Setting Tertiary center. Patients Consecutive patients with endometriosis referring to center from January 15, 2022 to April 30, 2022. Interventions For each enrolled patient, demographic and clinical data were collected and the presence of CS was measured using the Central Sensitization Inventory (CSI) questionnaire (score ≥40). Measurements and Main Results Primary study outcome was CS prevalence, while secondary study outcomes were the associations between demographic and clinical factors and CS. The 95% confidence intervals (CI) for CS prevalence were obtained with the Bayesian-derived Jeffreys method, while the associations between CS and demographic and clinical factors were evaluated with the chi-squared test and the Fisher's exact test, where appropriate. The variables significantly associated with CS were then included in a multivariable logistic regression model. The significance level was set at 0.05 for all analyses. During the study period, 285 eligible women were enrolled. CS prevalence was 41.4% (95% CI: 35.8–47.2). At univariable analysis, infertility, moderate-to-severe pain symptoms (except for dyschezia), altered bowel movements, postero-lateral parametrium involvement, hormonal therapy failure (HTF) and most of Central Sensitivity Syndromes (CSSs) were significantly associated to CS occurrence. Multivariable analysis only confirmed the significant association of CS with moderate-to-severe chronic pelvic pain, postero-lateral parametrium involvement, HTF, migraine or tension-type headache, irritable bowel syndrome and anxiety or panic attacks. Conclusions CS has a high prevalence in patients with endometriosis, especially in those with moderate-to-severe chronic pelvic pain, postero-lateral parametrium involvement, HTF, and three CSSs (i.e. migraine or tension-type headache, IBS, anxiety or panic attacks). Given the association with HTF, identifying CS through CSI might be useful to counsel the patient and to choose multimodal treatment.
Article
Introduction and hypothesis: The relationship between external lumbar, hip, and/or pelvic girdle pain and internal vaginal pelvic floor myofascial pain is not well described. We assessed this relationship in a cohort of adult women. Methods: The cohort included women ≥ 18 years old who received care for external lumbar, hip, and/or pelvic girdle pain (reported or elicited on physical examination) who then underwent internal vaginal myofascial levator ani pain assessments, in a tertiary care Female Pelvic Medicine and Reconstructive Surgery pelvic pain clinic over a 2-year period (2013 and 2014). Results: The cohort of 177 women had an average age of 44.9±16.0 years, an average body mass index of 27.2±7.0 kg/m2, and the majority (79.2%) were white. Most patients presented with a chief complaint of pelvic (51.4%), vulvovaginal (18.6%), and/or lumbar (15.3%) pain. Women who reported symptoms of lumbar, hip, or pelvic girdle pain were more likely to have pain on vaginal pelvic floor muscle examination than women without this history (OR, 7.24; 95% CI, 1.95-26.93, p=0.003). The majority (85.9%) of women had bilateral internal vaginal pelvic floor myofascial pain on examination. Conclusions: Although participants did not describe "vaginal pelvic floor myofascial pain," the high detection rate for internal vaginal pelvic floor myofascial pain on clinical examination highlights an opportunity to improve treatment planning. These findings suggest that the vaginal pelvic floor muscle examination should be part of the assessment of all women with lumbar, hip, and/or pelvic girdle pain. The relationship between this finding and clinical outcomes following directed treatment warrants additional study.
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Objective: Botulinum toxin injection has been applied for pain relief in various chronic pain syndromes. Recently, systematic review studies reported inconclusive effects of Botulinum toxin in myofascial pain management. The present study aimed to demonstrate the efficacy and safety of Botulinum toxin type A (BTxA) (Botox®) injection for pain reduction in myofascial trigger point (MTrP) of the upper trapezius muscle. Material and Method: Thirty-three patients with 48 MTrP on the upper trapezius muscles over three months with moderate to severe pain intensity diagnosed at physical medicine and rehabilitation outpatient department were recruited between December 2011 and March 2012. Eligible patients were blinded and randomly injected with single 0.2 ml (20 IU) of BTxA for 24 MTrP and 0.2 ml of 0.9% NaCl solution for 24 MTrP at the most tender trigger point on the upper trapezius muscle. All patients were advised for stretching exercise and ergonomic adaptation throughout the study. At 3- and 6-week after injections, visual analogue scale (VAS), the pressure pain threshold (PPT), and reported adverse effects were measured. Results: Both BTxA and control groups demonstrated statistically significant differences in VAS reduction and increased PPT after 3 weeks and 6 weeks compared with before treatment. There were no statistically significant differences in VAS reduction from baseline between the two groups at 3- and 6-week after treatment. A statistically significant difference in improvement of PPT from baseline and 6-week after BTxA injection compared with 0.9% NaCl group was shown (1.0±0.9 and 0.5±0.7, p = 0.036). There was mild degree side-effects that spontaneous resolved within one week in both groups without significant difference in percentage. No severe adverse effects were reported during the study. Conclusion: The efficacy in VAS reduction of a single 20 IU of Botulinum toxin type A (Botox®) injection was not different from 0.9% NaCl for myofascial trigger point at the upper trapezius muscle. However, Botulinum toxin type A (Botox®) showed statistically significant more increased in pressure pain threshold at 6-week after injection without severe adverse effects.
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Background: Chronic pelvic pain is a common condition among women, and 10 to 30 % of causes originate from the abdominal wall, and are associated with trigger points. Although little is known about their pathophysiology, variable methods have been practiced clinically. The purpose of this study was to evaluate the efficacy of local anaesthetic injections versus ischemic compression via physical therapy for pain relief of abdominal wall trigger points in women with chronic pelvic pain. Methods: We conducted a parallel group randomized trial including 30 women with chronic pelvic pain with abdominal wall trigger points. Subjects were randomly assigned to one of two intervention groups. One group received an injection of 2 mL 0.5 % lidocaine without a vasoconstrictor into a trigger point. In the other group, ischemic compression via physical therapy was administered at the trigger points three times, with each session lasting for 60 s, and a rest period of 30 s between applications. Both treatments were administered during one weekly session for four weeks. Our primary outcomes were satisfactory clinical response rates and percentages of pain relief. Our secondary outcomes are pain threshold and tolerance at the trigger points. All subjects were evaluated at baseline and 1, 4, and 12 weeks after the interventions. The study was conducted at a tertiary hospital that was associated with a university providing assistance predominantly to working class women who were treated by the public health system. Results: Clinical response rates and pain relief were significantly better at 1, 4, and 12 weeks for those receiving local anaesthetic injections than ischemic compression via physical therapy. The pain relief of women treated with local anaesthetic injections progressively improved at 1, 4, and 12 weeks after intervention. In contrast, women treated with ischemic compression did not show considerable changes in pain relief after intervention. In the local anaesthetic injection group, pain threshold and tolerance improved with time in the absence of significant differences between groups. Conclusion: Lidocaine injection seems to be better for reducing the severity of chronic pelvic pain secondary to abdominal wall trigger points compared to ischemic compression via physical therapy. Trial registration: ClinicalTrials.gov NCT00628355. Date of registration: February 25, 2008.
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Current evidence suggests that botulinum neurotoxins (BoNTs) A1 and B1, given locally into peripheral tissues such as skin, muscles, and joints, alter nociceptive processing otherwise initiated by inflammation or nerve injury in animal models and humans. Recent data indicate that such locally delivered BoNTs exert not only local action on sensory afferent terminals but undergo transport to central afferent cell bodies (dorsal root ganglia) and spinal dorsal horn terminals, where they cleave SNAREs and block transmitter release. Increasing evidence supports the possibility of a trans-synaptic movement to alter postsynaptic function in neuronal and possibly non-neuronal (glial) cells. The vast majority of these studies have been conducted on BoNT/A1 and BoNT/B1, the only two pharmaceutically developed variants. However, now over 40 different subtypes of botulinum neurotoxins (BoNTs) have been identified. By combining our existing and rapidly growing understanding of BoNT/A1 and /B1 in altering nociceptive processing with explorations of the specific characteristics of the various toxins from this family, we may be able to discover or design novel, effective, and long-lasting pain therapeutics. This review will focus on our current understanding of the molecular mechanisms whereby BoNTs alter pain processing, and future directions in the development of these agents as pain therapeutics.
Book
This important book fills a need in the developing area of Pain Medicine, providing physicians with an up-to-date resource that would detail the current understanding about the basic science underlying the mechanism of action of the various CAM therapies used for pain, summarizing the clinical evidence both for efficacy and safety, and then end with practical guidelines about how such treatments could be successfully and safely integrated into a Pain practice.
Article
High-tone pelvic floor dysfunction (HTPFD) is a debilitating chronic pain disorder for many women with significant impact on their quality of life (QoL). Our objective was to determine the efficacy of electromyography-guided onabotulinumtoxinA (Botox; Allergan, Irvine, Calif) injections in treating patient's perception of pelvic pain and improving QoL measurement scores. This is a prospective pilot open-label study of women with chronic pelvic pain and HTPFD who have failed conventional therapy between January 2011 and August 2013. Botox injections (up to 300 U) were done using needle electromyography guidance, from a transperineal approach, to localize spastic pelvic floor muscles (PFMs). Data were collected at baseline, 4, 8, 12, and 24 weeks after injections. This included demographics; Visual Analog Scale (VAS) scores for pain and dyspareunia; validated questionnaires for symptoms, QoL, and sexual function; Global Response Assessment scale for pelvic pain; digital examination of PFM for tone and tenderness; and vaginal manometry. Side effects were also recorded. Out of 28 women who enrolled in the study, 21 completed the 6-month follow-up and qualified for analysis. The mean (SD) age was 35.1 (9.4) years (range, 22-50 years), and the mean (SD) body mass index was 25 (4.4). Comorbidities included interstitial cystitis/bladder pain syndrome (42.9%) and vulvodynia (66.7%). Overall, 61.9% of subjects reported improvement on Global Response Assessment at 4 weeks and 80.9% at 8, 12, and 24 weeks post injection, compared with baseline. Of the subjects who were sexually active at baseline, 58.8% (10/17), 68.8% (11/16), 80% (12/15), and 83.3% (15/18) reported less dyspareunia at 4, 8, 12, and 24 weeks, respectively. Dyspareunia Visual Analog Scale score significantly improved at weeks 12 (5.6, P = 0.011) and 24 (5.4, P = 0.004) compared with baseline (7.8). Two of the 4 patients who avoided sexual activity at baseline secondary to dyspareunia resumed and tolerated intercourse after Botox. Sexual dysfunction as measured by the Female Sexual Distress Scale significantly improved at 8 weeks (27.6, P = 0.005), 12 weeks (27.9, P = 0.006), and 24 weeks (22.6, P < 0.001) compared with baseline (34.5). The Short-Form 12 Health Survey (SF-12) showed improved QoL in the physical composite score at all post injections visits (42.9, 44, 43.1, and 45.5 vs 40 at baseline; P < 0.05), and in the mental composite score at both 12 and 24 weeks (44.3 and 47.8 vs 38.5, P = 0.012). Vaginal manometry demonstrated significant decrease in resting pressures and in maximum contraction pressures at all follow-up visits (P < 0.05). Digital assessment of PFM (on a scale from 0 to 4) showed decreased tenderness on all visits (mean of 1.9, 1.7, 1.8, 1.9; P < 0.001) compared with baseline (2.8). Reported postinjection adverse effects included worsening of the following preexisting conditions: constipation (28.6%), stress urinary incontinence (4.8%), fecal incontinence (4.8%), and new onset stress urinary incontinence (4.8%). Electromyography-guided Botox injection into PFM could be beneficial for women with refractory HTPFD who have failed conservative therapy.
Article
The intent of this paper is to discuss the evolving role of the myofascial trigger point (MTrP) in myofascial pain syndrome (MPS) from both a historical and scientific perspective. MTrPs are hard, discrete, palpable nodules in a taut band of skeletal muscle that may be spontaneously painful (i.e. active), or painful only on compression (i.e. latent). MPS is a term used to describe a pain condition which can be acute or, more commonly, chronic and involves the muscle and its surrounding connective tissue (e.g. fascia). According to Travell and Simons, MTrPs are central to the syndrome-but are they necessary? Although the clinical study of muscle pain and MTrPs has proliferated over the past two centuries, the scientific literature often seems disjointed and confusing. Unfortunately, much of the terminology, theories, concepts, and diagnostic criteria are inconsistent, incomplete, or controversial. In order to address these deficiencies, investigators have recently applied clinical, imaging (of skeletal muscle and brain), and biochemical analyses to systematically and objectively study the MTrP and its role in MPS. Data suggest that the soft tissue milieu around the MTrP, neurogenic inflammation, sensitization, and limbic system dysfunction may all play a role in the initiation, amplification, and perpetuation of MPS. The authors will chronicle the advances that have led to the current understanding of MTrP pathophysiology and its relationship to MPS, and review the contributions of clinicians and researchers who have influenced and expanded our contemporary level of clinical knowledge and practice. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.
Article
To evaluate sensitization, myofascial trigger points, and quality of life in women with chronic pelvic pain with and without endometriosis. A cross-sectional prospective study of women aged 18-50 years with pain suggestive of endometriosis and healthy, pain-free volunteers without a history of endometriosis. Patients underwent a physiatric neuromusculoskeletal assessment of clinical signs of sensitization and myofascial trigger points in the abdominopelvic region. Pain symptoms, psychosocial, and quality-of-life measures were also assessed. All participants with pain underwent laparoscopic excision of suspicious lesions to confirm endometriosis diagnosis by histologic evaluation. Patients included 18 with current, biopsy-proven endometriosis, 11 with pain only, and 20 healthy volunteers. The prevalence of sensitization as measured by regional allodynia and hyperalgesia was similar in both pain groups (83 and 82%) but much lower among healthy volunteers (15%, P<.001). Nearly all women with pain had myofascial trigger points (94 and 91%). Adjusting for study group, those with high anxiety (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.004-1.099, P=.031) and depression (OR 1.06, 95% CI 1.005-1.113, P=.032) scores were more likely to have sensitization. Pain patients with any history of endometriosis had the highest proportion of sensitization compared with the others (87% compared with 67% compared with 15%; P<.001). Adjusting for any history of endometriosis, those with myofascial trigger points were most likely sensitized (OR 9.41, 95% CI 1.77-50.08, P=.009). Sensitization and myofascial trigger points were common in women with pain regardless of whether they had endometriosis at surgery. Those with any history of endometriosis were most likely to have sensitization. Traditional methods of classifying endometriosis-associated pain based on disease, duration, and anatomy are inadequate and should be replaced by a mechanism-based evaluation, as our study illustrates. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00073801. LEVEL OF EVIDENCE:: II.
Article
To determine the prevalence of myofascial pain and the outcome of transvaginal pelvic floor physical therapy for the treatment of chronic pelvic pain caused by myofascial pelvic pain in a tertiary care facility. A retrospective chart review was performed on all women who presented to our facility between January 2005 and December 2007. Those diagnosed with myofascial pelvic pain and referred for transvaginal pelvic floor physical therapy over this 3-year period were evaluated. Participants with an initial pain score of > or = 4, myofascial pelvic pain on examination, and who attended 2 or more physician visits were included in the analysis. Patient physical examination findings, symptoms, and verbal pain ratings were reviewed. In all, 146 (13.2%) of 1,106 initially screened patients were diagnosed with myofascial pain. Seventy-five (51%) of the 146 patients who were referred for physical therapy were included, and 75% had an initial pain score of > or = 7. Pain scores significantly improved proportional to the number of physical therapy visits completed, with 63% of patients reporting significant pain improvement. Transvaginal physical therapy is an effective treatment for chronic pelvic pain resulting from myofascial pelvic pain.
Article
Clinical management of endometriosis is limited by the complex relationship between symptom severity, heterogeneous surgical presentation, and variability in clinical outcomes. As a complement to visual classification schemes, molecular profiles of disease activity may improve risk stratification to better inform treatment decisions and identify new approaches to targeted treatment. We use a network analysis of information flow within and between inflammatory cells to discern consensus behaviors characterizing patient subpopulations. Unsupervised multivariate analysis of cytokine profiles quantified by multiplex immunoassays identified a subset of patients with a shared "consensus signature" of 13 elevated cytokines that was associated with common clinical features of endometriosis, but was not observed among patient subpopulations defined by morphologic presentation alone. Enrichment analysis of consensus markers reinforced the primacy of peritoneal macrophage infiltration and activation, which was demonstrably elevated in ex vivo cultures. Although familiar targets of the nuclear factor κB family emerged among overrepresented transcriptional binding sites for consensus markers, our analysis provides evidence for an unexpected contribution from c-Jun, c-Fos, and AP-1 effectors of mitogen-associated kinase signaling. Their crucial involvement in propagation of macrophage-driven inflammatory networks was confirmed via targeted inhibition of upstream kinases. Collectively, these analyses suggest a clinically relevant inflammatory network that may serve as an objective measure for guiding treatment decisions for endometriosis management, and in the future may provide a mechanistic endpoint for assessing efficacy of new agents aimed at curtailing inflammatory mechanisms that drive disease progression.