Travel trigger points - Molecular and osteopathic perspectives

Abstract

The proposed etiology of Travell trigger points (TrPs) has undergone a fundamental revision in recent years. New research results suggest that TrPs are evoked by the abnormal depolarization of motor end plates. This article expands the proposed etiology to include presynaptic, synaptic, and postsynaptic mechanisms of abnormal depolarization (ie, excessive release of acetycholine [ACh], defects of acetylcholinesterase, and upregulation of nicotinic ACh-receptor activity, respectively).
This working hypothesis regarding the etiology of TrPs has changed the approach to treating TrPs. As an example, Travell and Simons abandoned the application of ischemic compression to TrPs; instead the authors adopted several techniques associated with osteopathic medicine (ie, muscle-energy, myofascial, counterstrain; high-velocity, low-amplitude). Scientists are now proposing and reporting the results of new approaches using capsaicin, a vanilloid-receptor agonist, and ACh antagonists (eg, dimethisoquin hydrochloride, botulinum toxin, quinidine, linalool). The purpose of this article is to review these new concepts and describe new resulting approaches to the treatment of TrPs.

Full text

244 • JAOA • Vol 104 • No 6 • June 2004
The proposed etiology of Travell trigger points (TrPs) has
undergone a fundamental revision in recent years. New
research results suggest that TrPs are evoked by the
abnormal depolarization of motor end plates. This article
expands the proposed etiology to include presynaptic,
synaptic, and postsynaptic mechanisms of abnormal depo-
larization (ie, excessive release of acetycholine [ACh],
defects of acetylcholinesterase, and upregulation of nico-
tinic ACh-receptor activity, respectively).
This working hypothesis regarding the etiology of
TrPs has changed the approach to treating TrPs. As an
example, Travell and Simons abandoned the application
of ischemic compression to TrPs; instead the authors
adopted several techniques associated with osteopathic
medicine (ie, muscle-energy, myofascial, counterstrain;
high-velocity, low-amplitude). Scientists are now proposing
and reporting the results of new approaches using cap-
saicin, a vanilloid-receptor agonist, and ACh antagonists
(eg, dimethisoquin hydrochloride, botulinum toxin, quini-
dine, linalool). The purpose of this article is to review
these new concepts and describe new resulting approaches
to the treatment of TrPs.
J
anet G. Travell, MD, (1901–1997) was an internist in gen-
eral medicine who developed an interest in spinal manip-
ulation in the 1940s,1but later shifted her focus to myofascial
trigger points (TrPs). In 1955, she relieved then–Senator John
F. Kennedy of disabling back pain (after he endured a failed
diskectomy in 1944 and laminectomy in 1954).2Travell’s
ensuing post as White House physician, followed by the
publication of her two-volume “Red Bible,” Myofascial Pain
and Dysfunction: The Trigger Point Manual,3,4 coauthored with
David G. Simons, MD, brought prominence to her approach
for treating TrPs.
Travell defined a TrP as “a hyperirritable spot in skeletal
muscle that is associated with a hypersensitive palpable
nodule in a taut band. The spot is tender when pressed and
can give rise to characteristic referred pain, motor dysfunc-
tion, and autonomic phenomena.”5An example of this is
shown in Figure 1. The taut band of muscle is best charac-
terized as a palpable, ropy structure.
Palpation is a reliable diagnostic criterion for locating
TrPs in patients.6The reliability of diagnosing TrPs is similar
to the reliability of diagnosing tender points in the counter-
strain system developed by Lawrence H. Jones, DO.7An
interrater-reliability study of this counterstrain system demon-
strated that clinicians agreed 73% of the time (= 0.45); the
palpation of patients’ TrPs proved more reliable than the
standard osteopathic TART examination.7(TART is a
mnemonic for the four criteria of somatic dysfunction: tissue
texture abnormality, asymmetry, restriction of motion, and
tenderness.7)
Myofascial trigger points can be inactivated by a variety
of approaches, including osteopathic manipulative treatment
(OMT), massage therapy, ultrasound therapy, “spray and
stretch,” as well as needling (acupuncture or injection). A
full account that describes the diagnosis and treatment of
Travell TrPs is provided by Kuchera and McPartland in
Foundations for Osteopathic Medicine.8This article serves as a
companion piece to Kuchera and McPartland’s chapter in
Foundations, describing a new working hypothesis regarding
the etiology of TrPs and the way in which this new hypoth-
esis changes our treatment of these points. Most of the mate-
rial in this article was mistakenly deleted from the final ver-
sion of the Foundations chapter.
Proposed Etiology of TrPs
The 1999 edition of Travell and Simons’ Myofascial Pain and Dys-
function: The Trigger Point Manual5proposes an “integrated
hypothesis” regarding the etiology of TrPs. Such an integrated
hypothesis involves local myofascial tissues, the central nervous
system (CNS), and biomechanical factors.
A biopsy of local myofascial tissue in the vicinity of TrPs
revealed that the tissues contained “contraction knots,”
described as “large, rounded, darkly staining muscle fibers
and a statistically significant increase in the average diameter
of muscle fibers.”9Electromyographic (EMG) studies of TrPs
have indicated spontaneous electrical activity (SEA) in TrPs,
while adjacent muscle tissues are electrically silent.10 These
intersecting discoveries led Travell and Simons to implicate
dysfunctional motor end plates as the underlying etiology of
TrPs. The terms motor end plates and neuromuscular junction
From Unitec Institute of Technology in Auckland, New Zealand.
Address correspondence to John M. McPartland, DO, MS, Faculty of
Health & Environmental Science, Unitec Institute of Technology, Private Bag
92025, Auckland, New Zealand.
E-mail: jmcpartland@unitec.ac.nz
REVIEW ARTICLE
McPartland • Review Article
Travell Trigger Points—Molecular and Osteopathic Perspectives
John M. McPartland, DO, MS

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McPartland • Review Article
Acquired Defects
Many ion channels and neuroreceptors are expressed by more
than one gene. These genetic subtypes are expressed in cells in
different parts of the body for different needs and at different
points in the life cycle. Dysregulated expression of these genes
will produce acquired defects. To illustrate this mechanism,
consider the 16 genes that encode nAChR subunits. The gene
that encodes a CNS nAChR may become dysregulated in a
muscle cell and may begin producing CNS nAChRs in the
motor end plate. Couple this dysfunction with tobacco
smoking. Nicotine normally activates CNS AChRs and not
motor end plate AchRs. If dysregulated, however, CNS
nAChRs become expressed in motor end plates. Nicotine
would then activate those receptors in motor end plates, poten-
tially causing TrPs.
Single genes may also become dysregulated should they
express splice variants. Splice variants are alternative ways
in which a gene’s protein-coding sections (exons) are joined
together to create a messenger ribonucleic acid molecule and
its translated protein. For example, AChE expresses several sub-
types that are produced by alternative splicing of the single
AChE gene.17 These subtypes are induced under psycholog-
ical, chemical, and physical stress.18
The simple upregulation of certain genes may lead to
muscle hyperexcitability and evoke TrPs in muscles. For
example, L-type and N-type Ca2channels are upregulated by
factors associated with physical and psychological stress,19,20
as well as by nicotine.21 Patients with TrPs and long-term mus-
culoskeletal pain should avoid tobacco smoking, as well as
excess caffeine.22 Caffeine upregulates activity at motor end
plates by acting as an agonist of ryanodine receptors23 and an
antagonist of adenosine A2A receptors.24
Motor End Plate Dysfunction Cascade
When a motor end plate becomes dysfunctional, several per-
verse mechanisms cause it to persist as a TrP. The excessive
muscle contraction compresses local sensory nerves, which
reduces the axoplasmic transport of molecules that normally
inhibit ACh release.25,26 The sustained muscle contraction also
compresses local blood vessels, reducing the local supply of
oxygen. This impaired circulation, combined with the increased
metabolic demands generated by contracted muscles, results
in a rapid depletion of local adenosine triphosphate (ATP).
The resultant “ATP energy crisis”5triggers presynaptic and
postsynaptic decompensations. In the nerve terminal, ATP
directly inhibits ACh release,27 so depletion of ATP increases
ACh release. In the muscle cell, ATP powers the Ca2pump,
which returns calcium to the sarcoplasmic reticulum. Hence,
loss of ATP impairs the reuptake of Ca2, which increases
contractile activity—a vicious cycle.9
The ATP energy crisis cascades into a local release of
chemicals that activate or sensitize nociceptive nerves in the
region, including bradykinins, cytokines, serotonin, histamine,
potassium, prostaglandins, leukotrienes, somatostatin, and
are interchangeable, although the first term describes structure
and the latter reflects function. Both terms refer to the point
where -motor neurons contact their target muscle fibers. (See
Figure 2 for a schematic drawing of a motor end plate.) The cor-
relation between motor end plates and TrPs (“myalgic spots”)
was first elucidated in a study conducted by Gunn and Mil-
brandt in 1977.11
Travell and Simons attributed motor end plate dysfunc-
tion to an excessive release of acetylcholine (ACh) from the
presynaptic motor nerve terminal.5,9 Acetylcholine released
into the synaptic cleft rapidly activates nicotinic ACh receptors
(nAChRs) on the postsynaptic muscle membrane, leading to
a muscle action potential and muscle contraction (Figure 2).
Travell and Simons’ hypothesis of a presynaptic dysfunction,
however, is only one way to interpret the results of EMG
studies. As the EMG electrodes are placed in postsynaptic
muscle fibers, the increased SEA measured in TrPs could be
attributed to the result of presynaptic, synaptic, or postsy-
naptic dysfunction.5All of these dysfunctions can be inherited
(genetic) or acquired.
Genetic Defects
Gene mutations frequently arise as nucleotide polymorphisms
(SNPs, pronounced “snips”) and microsatellite polymorphisms.
Single nucleotide polymorphisms are common deoxyribonu-
cleic acid (DNA) variations among individuals, caused by a
single-point mutation. Microsatellite polymorphisms are
mutated DNA loci that contain nucleotide repeats. Pellegrino
et al12 implicated genetic factors in the formation of TrPs.
Genetic defects of motor end plates can be presynaptic,
synaptic, or postsynaptic.13 Presynaptically, the release of ACh
depends on the calcium ion (Ca2) concentration in the -
motor nerve terminal. Excessive release of ACh may be caused
by defects of L-type and N-type voltage-gated Ca2chan-
nels.14 An Internet search of the SNP catalog maintained by the
National Center for Biotechnology Information (available at:
http://www.ncbi.nlm.nih.gov) reveals 695 reports of L-type
Ca2channel mutations and 57 reports of N-type Ca2channel
mutations. Thus, a genetic cause for excess ACh release may
be quite common.
Synaptically, ACh is normally inactivated by the enzyme
acetylcholinesterase (AChE) (Figure 2). Genetic defects of AChE
may cause excess ACh to remain in the synaptic cleft.13
Postsynaptically, a gain-of-function defect of nAChR may
confer muscle hyperexcitability, a hallmark of Travell TrPs. The
nAChR is an assembly of 5 subunits; at least 16 genes encode
nAChR subunits that combine in a variety of ways.15 Thus,
nAChR is particularly susceptible to mutation defects. The
nAChR in the motor end plate expresses different subunits than
nAChR expressed in the CNS or in the autonomic nerves.
Gain-of-function mutations result in the overexpression of
nAChRs in the muscle cell membrane, as well as resulting in
nAChRs that are hypersenstive to ACh. These mutations also
result in nAChRs that become constitutively active.16

246 • JAOA • Vol 104 • No 6 • June 2004
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McPartland • Review Article
substance P.9This chemical activation and sensitization of
nociceptors accounts for TrP tenderness. Sensitizing substances
may also generate a focal demyelination of sensory nerves.
Demyelination creates abnormal impulse–generating sites
(AIGS) capable of generating ectopic nociceptive impulses.28
CNS and Biomechanical Factors
The CNS and biomechanical factors also contribute to the for-
mation and maintenance of TrPs. A persistent barrage of noci-
ceptive signals from TrPs will eventually sensitize the CNS, a
process termed central sensitization. This process accelerates in
the presence of AIGS and their associated ephaptic crosstalk
(cross-excitation) with neighboring autonomic nerves. Travell
and Simons’ view of the CNS as an “integrator” of TrPs is
interchangeable with Korr’s description29 of the CNS as an
“organizer” of somatic dysfunction. According to Travell and
Simons, the sensitized dorsal horn becomes a “neurologic
lens,” consolidating other nociceptive signals converging on the
same segment of the spinal cord, including other somatic dys-
functions and visceral dysfunctions.5
Biomechanical factors that stress muscles (eg, acute
trauma, repetitive microtrauma) contribute to TrP dysfunc-
tion. Further, biomechanical stress of a cold muscle is a key
factor in the formation of TrPs,3-5 as cooling muscles apparently
upregulate nAChR activity at the motor end plates.30 The
revised edition of Travell and Simons’ manual emphasizes
the relationship between TrPs and nearby articular dysfunc-
tions. In the manual, the authors correlate suboccipital TrPs
with occipitoatlantal (OA) dysfunctions, semispinalis capitus
TrPs with OA dysfunctions and atlantoaxial dysfunctions,
and splenius TrPs with upper thoracic articular dysfunctions.5
Postural disorders often contribute to the perpetuation
of TrPs. For example, postural strain of the suboccipital mus-
cles may cause TrPs in these muscles,5leading to further dete-
rioration in muscle structure and function. Such deterioration
may result in radiating pain (Figure 1) and atrophic changes.31
Suboccipital muscles contain a high density of propriocep-
tors,32 so atrophic changes lead to a loss in proprioceptive bal-
ance and loss of proprioceptive “gate control” at the dorsal
horn, giving rise to chronic pain syndromes.31
Considerations for Osteopathic Medicine
Twenty years ago, Travell and Simons treated TrPs with
“ischemic compression” by applying heavy thumb pressure on
TrPs, sufficient to produce skin blanching.3In the 1999 edition,
Travell and Simons recommend applying gentle digital pres-
sure to TrPs.5This fundamental change is anchored in Travell’s
ATP energy crisis model, which characterizes TrPs as centers
of tissue hypoxia. Thus, deep digital pressure that produces
additional ischemia is not beneficial. Travell and Simons named
their new technique “trigger point pressure release.”5Applying
a “press and stretch” technique is believed to restore abnor-
mally contracted sarcomeres in the contraction knot to their
normal resting length. It is an indirect technique that uses the
barrier-release concept, in which the finger “follows” the
releasing tissue.
During the past 20 years, Travell and Simons developed
an appreciation for OMT, though they learned of it from Euro-
pean allopathic physicians. The authors began treating TrPs
with a muscle-energy technique they called the “Lewit tech-
nique.”3Karl Lewit, MD, from the Czech Republic, developed
his technique after working with Fred L. Mitchell, Jr, DO,
Philip E. Greenman, DO, and other osteopathic physicians.33
A Dutch variation of Lewit’s method, the “Gaymans-Lewit
technique,” evolved after Gaymans met osteopathic physi-
cians in New York City in the early 1970s.34 Travell and Simons
subsequently cited Mitchell and Greenman and described
muscle energy and myofascial release.4
Travell and Simons’ revised edition of their manual advo-
cates muscle energy, counterstrain, myofascial release, and
Figure 1. Trigger point of the left rectus capitis posterior
major (marked by an X) and its referred pain pattern (stip-
pling). (Adapted in part from Travell et al.
3
)

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McPartland • Review Article
Other New Approaches for Treating TrPs
Travell and Simons recommend dimethisoquin hydrochlo-
ride ointment (Quotane) for massaging TrPs in superficial
muscles such as the orbicularis oculi, frontalis, and occipi-
talis.3Dimethisoquin, a local anesthetic, inhibits voltage-gated
Na() channels (conferring its anesthetic effect) but also acts
as a noncompetitive inhibitor of nAChRs (IC50 = 2.4 M).35 The
anesthetic’s potency is significantly greater than that of lido-
caine (IC50 = 52 M) and procaine (IC50 = 240 M). Further,
dimethisoquine is uniquely selective for the nAChR subtype
expressed in the neuromuscular junction.
Massage with capsaicin cream (0.075%, available over
the counter) is useful for treating TrPs located in surgical
scars,36 which are particularly refractory to treatment.5Cap-
saicin selectively binds to the vanilloid receptor (VR1).37 Vanil-
loid-receptor activation triggers an influx of Ca2into neuron
terminals, which initiates neurotransmitter release. Repeated
exposure to capsaicin, however, causes VR1s to become desen-
sitized. This mechanism explains the seemingly paradoxical use
of capsaicin as an analgesic.36-38 Vanilloid receptors are also
expressed in brain regions that modulate the emotive and
cognitive aspects of pain (eg, preoptic area, locus ceruleus,
hypothalamus, striatum).38 It has been hypothesized that mod-
ulating the expression of VR1s and their endogenous ligand
(anandamide) may be one of the central mechanisms of OMT,38
parallel to the potential effects of OMT on endorphins.39
Needling is sometimes necessary to inactivate TrPs. For
thousands of years, Chinese medicine has treated TrPs with
acupuncture.40 Travell began needling TrPs with syringes in
1942, injecting them with procaine.41 Procaine was later
replaced by saline solution,42 which was later replaced by
“dry needling”—without any fluid in the syringe43—bringing
the procedure full circle to what is essentially acupuncture. The
“dysfunctional motor end plate hypothesis” has led to the
injection of botulinum toxin, which causes an irreversible
blockade of ACh release in the TrP.44
Injecting TrPs with quinidine should be tested in a clinical
trial, as quinidine decreases presynaptic ACh release (via its
well-known blockade of L-type Ca2channels) and down-
regulates nAChRs (a postsynaptic mechanism). In one trial,
quinidine appeared to restore AChE activity.45 Diltiazem also
merits investigation. It is an L-type Ca2channel blocking
agent that corrects myopathies caused by defects in AChE
activity.46
Travell and Simons recommended a diet adequate in
vitamins and minerals for the prevention of TrPs.3Supple-
menting the diet with phosphatidylcholine has been recom-
mended,47 but this may actually provoke TrPs in a portion of
patients. As choline is a percursor to ACh, an nAChR gain-of-
function mutation may enable choline to directly activate the
mutated receptors.48
Another new approach in treating TrPs are herbal med-
ications. As an estimated 50% of patients with long-term mus-
culoskeletal pain take herbal remedies, it behooves osteopathic
other OMT techniques for treating TrPs and associated artic-
ular somatic dysfunctions.5In addition, high-velocity, low-
amplitude thrust techniques are illustrated, hearkening back
to Travell’s early interest in spinal manipulation.1
Figure 2. The motor end plate—proposed site of trigger point dys-
function.
Top illustration: The junction between the

-motor neuron and
the muscle fiber. The

-motor neuron terminates in multiple swellings
termed synaptic boutons. Bottom illustration: presynaptic boutons are
separated from the postsynaptic muscle cell by the synaptic cleft.
Within each bouton are many synaptic vesicles containing ACh, clus-
tered around dense bars (Db). The Db is the site of ACh release into
the synapse. Across the synapse from the Db, the postsynaptic muscle
cell membrane forms junctional folds that are lined with nicotinic ACh
receptors (nACh). ACh released into the synapse activates nACh
receptors, then is inactivated by the acetylcholinesterase enzyme
(AChE). (Adapted in part from Kandel et al.
58
)

248 • JAOA • Vol 104 • No 6 • June 2004
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physicians to understand the mechanisms of these medica-
tions.49 Herbal remedies and essential oils that are recom-
mended for treating myofascial pain include lavender (Lavan-
dula angustifolia), lemon balm (Melissa officinalis), rosemary
(Rosmarinus officinalis), kava kava (Piper methysticum), skullcap
(Scutellaria lateriflora), passionflower (Passiflora incarnata), Rose
(Rosa spp), and valerian (Valeriana officinalis).47 Nearly all of
these herbs contain linalool, a monoterpene compound that
inhibits end plate activity by reducing ACh release (a presy-
naptic mechanism) and by modifing nAChRs (a postsynaptic
mechanism).50 Marijuana (Cannabis spp), which also produces
linalool,51 also effectively treats myofascial pain syndromes.52
Marijuana’s efficacy may also be attributed to tetrahydro-
cannabinol, an N-type Ca2channel blocker.53 Tetrahydro-
cannabinol inhibits ACh release in the CNS54; this inhibition is
thought to occur at motor end plates, as motor nerve terminals
express cannabinoid receptors.54
Conclusion
Travell and Simons’concepts regarding TrPs have converged
with osteopathic medicine’s concept of somatic dysfunction.
This convergence is also seen in Travell and Simons’ approach
to the treatment of TrPs, which in many ways resembles the
OMT used in Chapman reflex points,55 Jones’ counterstrain
points,56 and the progressive inhibition of neuromuscular
structures (PINS) technique.57 Armed with a better under-
standing of the molecular basis underlying myofascial pain syn-
dromes, clinicians hope that Travell and Simons’ approach
will continue to coevolve with osteopathic concepts.
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McPartland • Review Article