RESEARCH IDEAS

Trigger Points and Central Modulation—A New Hypothesis

Mark J. L. Hocking, BVSc
J Muscoskeletal Pain Downloaded from informahealthcare.com by University of Bristol on 07/19/10

ABSTRACT. Objective: A new hypothesis is proposed to explain the pathogenesis, symptoma-

tology, and treatment of the trigger points [TrPs], which define the myofascial pain syndrome
[MPS].
Hypothesis: TrPs are formed due to sustained α-motoneuron plateau depolarization, which
is maintained by one of two different central nervous system [CNS] mechanisms. “Antecedent”
TrPs are formed in withdrawal reflex agonist muscles due to central sensitization of the C fiber
nociceptive withdrawal reflex [NWR], visceromotor reflex [VMR], or nociceptive jaw-opening
For personal use only.

reflex [NJOR]. “Consequent” TrPs result in withdrawal reflex antagonist muscles due to compen-
satory reticulospinal or reticulo-trigeminal motor facilitation. Afferent nociceptive signals arise
from both latent and active TrPs. However, latent TrPs are not spontaneously painful, because of
complete inhibition of nociceptive transmission at the spinal cord or trigeminal nucleus [SC/TN]
levels. Marked SC/TN sensitization [especially with a reduced antinociceptive functional reserve]
may overwhelm the brainstem antinociceptive mechanism, going beyond the MPS into the gen-
eralized allodynia of the fibromyalgia syndrome [FMS]. The principal brainstem nuclei involved
in TrP sensory and motor modulation have other diverse homeostatic roles; therefore TrP-induced
brainstem dysfunction may contribute to the pathogenesis of a variety of sensory, motor, and au-
tonomic disorders. Treatment involves noxious stimulus-induced transient inhibition of the CNS
mechanisms that sustain TrPs. This allows stretching of the contractured muscle fibers to resolve
the TrP local energy crisis, and to reverse muscle nociceptor and CNS sensitization.
Conclusion: This hypothesis proposes that TrPs result in the muscles due to sustained α-
motoneuron plateau depolarization. Descending inhibition normally ensures that most TrPs remain
latent, but FMS may result if this inhibitory mechanism is overwhelmed.

KEYWORDS. Myofascial pain syndrome, trigger points, central sensitization, ventromedial

medulla, descending modulation

INTRODUCTION a veterinarian who frequently treats the TrPs of

dogs, I cannot reconcile some of my clinical ob-
In this paper I propose a new hypothesis for servations with current TrP hypotheses. These
the pathophysiology of trigger points [TrPs]. As observations include the following: first, the

Mark J. L. Hocking, BVSc, Gladesville Veterinary Hospital, Gladesville NSW, Australia.

Address correspondence to: Mark J. L. Hocking, BVSc, Gladesville Veterinary Hospital, 449 Victoria Road,
Gladesville NSW 2111, Australia. E-mail: mark.j.hocking@hotmail.com
Journal of Musculoskeletal Pain, Vol. 18(2), 2010
Available online at www.informaworld.com/WJMP


C 2010 Informa Healthcare USA, Inc. All rights reserved.
186 doi: 10.3109/10582452.2010.483964
 Hocking
most clinically relevant TrPs [those that restrict
stride and distort posture] are found predomi-
nantly in flexor muscles. Second, after treatment
of all TrPs in a lame limb, the lameness will
sometimes shift to another limb. Third, despite
it being obvious that not all canine TrPs are ac-
tive [multiple TrPs are usually found in the lame
limb and TrPs are also typically found in the
non-lame limbs], it is normally impossible to
determine which TrPs in a lame limb are active
and which are latent. All TrPs feel similar, pal-
pation elicits similar pain reactions, and appro-
priate stimulation induces a similar local twitch
J Muscoskeletal Pain Downloaded from informahealthcare.com by University of Bristol on 07/19/10
response.
I have brought together relevant information
from numerous sources in an effort to explain my
observations. These sources include the human
TrP literature [readers are referred to Travell and
Simons (1) and Mense and Simons (2) for a com-
prehensive TrP review] and published pain and
other neurophysiological experimental research.
My hypothesis attempts to explain the pathogen-
esis, symptomatology, and treatment of TrPs in
For personal use only.
both humans and other vertebrates. It may also
help to solve the larger puzzle of pain and pro-
vide insight into the pathogenesis of a variety of
other incompletely understood sensory, motor,
and autonomic disorders.
Fundamental Trigger Point
Pathophysiological Mechanism
I propose that TrPs do not form due to a criti-
cal abnormality of neuromuscular function at the
motor endplate of an extrafusal skeletal mus-
cle fiber (3), but are the result of the chronic
expression of an intrinsic α-motoneuron prop-
erty, the plateau potential. A plateau potential
is a sustained partial depolarization of an α-
motoneuron that may persist for at least several
seconds after synaptic excitation has reduced
or ceased (4). α-Motoneurons may exhibit the in-
trinsic membrane property of bistability, where
they are stable at either of two different mem-
brane potentials: a less excitable, more hyper-
polarized state and a more excitable, partially
depolarized plateau state (5, 6). Repeated plateau
potential activation leads to α-motoneuron
warm-up, where there is a decreased threshold
for, and increased duration of, plateau poten-
tials (7). Sustained partial depolarization of the
α-motoneuron increases the release of acetyl-
choline packets at the motor endplate. This man-
187
ifests electrically as endplate noise, which can be
recorded by needle electromyogram at the active
locus of a TrP.
I propose that centrally maintained α-
motoneuron plateau depolarization, rather than
an intrinsic disorder of the motor endplate, is
the fundamental pathophysiological mechanism
which perpetuates the local muscle contracture
associated with a TrP. Warm up of α-motoneuron
plateau depolarization is maintained by one
of two different central nervous system [CNS]
mechanisms, resulting in two essentially differ-
ent types of TrPs, which I call “antecedent” and
“consequent” TrPs. Antecedent TrPs are sus-
tained by central sensitization of the C fiber
polysynaptic withdrawal reflexes: the NWR,
the VMR, and the NJOR. Antecedent TrPs are
formed in withdrawal reflex agonist muscles,
which are generally, but not exclusively, flexor
muscles. Consequent TrPs are sustained by tonic
reticulospinal or reticulo-trigeminal facilitation
of plateau potentials in withdrawal reflex an-
tagonist α-motoneurons. Consequent TrPs are
formed in withdrawal reflex antagonist muscles,
which are generally, but not exclusively, exten-
sor muscles.
Pathophysiology of Antecedent Trigger Points
The withdrawal reflexes are complex polysy-
naptic reflexes, mediated by spinal cord or
trigeminal nucleus [SC/TN] neural circuitry that
facilitate either rapid withdrawal from a poten-
tially damaging acute stimulus or ongoing im-
mobilization of an injured area to prevent further
damage and allow healing. Activation of the
NWR typically results in simultaneous contrac-
tion of ipsilateral limb flexor muscles and re-
ciprocal inhibition of ipsilateral limb extensor
muscles to effect the withdrawal. Simultaneous
contraction of contralateral limb extensors and
reciprocal inhibition of contralateral limb flexors
may also result via the interconnected crossed
extensor reflex mechanism to prevent the animal
from overbalancing. The VMR is another spinal
reflex that may also cause contraction of skele-
tal muscles but as a result of visceral afferent,
rather than somatic or cutaneous afferent nox-
ious input. The NJOR leads to contraction of
jaw opening muscles and reciprocal inhibition
of jaw closing muscles as a result of orofacial
noxious input.
 188 JOURNAL OF MUSCULOSKELETAL PAIN
I suggest that sustained stimulation of pe-
ripheral nociceptors for cutaneous, somatic, or
visceral C afferent neurons is a precondition
for the formation of antecedent TrPs. Such
sustained noxious stimulation may result from
traumatic injury, inflammatory disease, or sen-
sitization of nociceptors in other TrPs. Only
ongoing C fiber-mediated nociceptive transmis-
sion to the SC/TN leads to central sensitiza-
tion of the above-mentioned withdrawal reflex
mechanisms, resulting in sustained efferent α-
motoneuron activation of agonist muscles and
simultaneous inhibition of antagonist muscles.
J Muscoskeletal Pain Downloaded from informahealthcare.com by University of Bristol on 07/19/10
The reflex response to C nociceptor input is a
low level of muscular contraction, compared to
the reflex response to myelinated afferent input
that is monitored with most methods of behav-
ioral observation or standard electromyographic
recording (8).
Central sensitization is a process that re-
sults in an increase in efficiency of synaptic
transmission between neurons and an increased
excitability and prolonged discharge [plateau de-
For personal use only.
polarization] of postsynaptic neurons following
certain forms of repeated or sustained synaptic
excitation. Prolonged noxious stimulation that
activates C afferent neurons leads to SC/TN cen-
tral sensitization at the various synapses of the
activated polysynaptic withdrawal reflex mech-
anism/s [e.g., in the SC, plateau potentials can
be evoked by primary sensory afferents in both
dorsal horn [DH] neurons and motoneurons (9)]
(10–12). Sustained application of an appropriate
nociceptive conditioning stimulus, even at low
levels, is sufficient to maintain DH central sen-
sitization (13). Dorsal horn central sensitization
leads to an enhanced pain sensation [secondary
hyperalgesia] and reduced pain threshold [allo-
dynia]. The synaptic and postsynaptic mecha-
nisms of central sensitization are complex, but it
is clear that they result in plateau depolarization
of the postsynaptic neuron due to progressive ac-
tivation of L-type calcium channels (10, 12, 14).
Facilitation of the C fiber withdrawal reflexes
due to SC/TN central sensitization both predis-
poses to antecedent TrP formation and helps per-
petuate these TrPs. The NWR persists during
sleep (15), so ongoing activation of the NWR
may maintain antecedent TrPs indefinitely.
Lamina V wide dynamic range [WDR, con-
vergent, multireceptive] SC/TN neurons are
likely to be critically involved in the pathogen-
esis of antecedent TrPs. Lamina V WDR neu-
rons may show graded responses to innocuous
and noxious mechanical stimuli, noxious heat,
noxious cold, and noxious muscle or visceral
stimuli (16). They respond to repetitive C fiber
activation with a windup discharge [central sen-
sitization] and are intercalated in the withdrawal
reflex pathway (16, 17).
I propose that warm up of α-motoneuron
plateau depolarization, which is maintained by
central sensitization of the C fiber withdrawal
reflexes, leads to an ongoing low-level increase
in acetylcholine packet release at the motor
endplates of both active and latent antecedent
TrPs. The axons of α-motoneurons in the plateau
state exhibit a low-level increase in electroneu-
rogram activity, most visible when action poten-
tials are blocked (6), which closely resembles
recordings by needle electromyogram of end-
plate noise from the active locus of a TrP. The
low-amplitude motor endplate potentials of end-
plate noise cause ongoing partial depolarization
of the postjunctional membrane and subsequent
focal sustained contractile activity of the mus-
cle sarcomeres in the immediate vicinity of the
motor endplate zone (18).
Persistent contractile activity of these sarcom-
eres leads to a local energy crisis, as explained by
the current energy crisis hypothesis. This states
that ongoing contraction squeezes shut the cap-
illaries that supply the nutritional and oxygen
needs of that region, which simultaneously has
an increased metabolic demand (19). The se-
vere but local energy crisis leads to a failure
of relaxation of the sarcomeres [a contracture]
due to an inadequate local supply of adeno-
sine triphosphate, which is required by the Ca2+
pump that returns calcium ions to the sarcoplas-
mic reticulum to terminate contractile activity
(19). Histopathologically, the localized contrac-
ture of a segment of muscle fiber around the mo-
tor endplate appears as a contraction knot (20).
Each motoneuron controls between 300 muscle
fibers and 1,500 muscle fibers in postural and
limb muscles (21), so central facilitation of α-
motoneuron discharge would predispose to the
simultaneous formation of multiple contraction
knots. If contraction knots develop in enough
muscle fibers, a palpable nodule and restriction
in stretch range of motion of the muscle would
result. I propose that sustained low-level mo-
toneuronal activity is sufficient to maintain the
TrP local energy crisis and muscle fiber contrac-
ture for an indefinite period.
 Hocking
The energy crisis and profound hypoxia that
develop around the motor endplate zone of a
skeletal muscle containing a TrP lead to sen-
sitization of local nociceptors, as nociceptive
sensory nerves [and small blood vessels and
postganglionic sympathetic nerves] are normally
part of the same neurovascular bundle that in-
cludes the motor nerve (22). I propose that af-
ferent nociceptive signals arise from sensitized
local muscle nociceptors in both latent and active
TrPs.
I suggest that concurrent alteration of local
sympathetic neuronal activity, which leads to
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vasodilation in the vicinity of a TrP, is a mecha-
nism that has evolved to counter the microvascu-
lar compromise and marked hypoxia that occur
within a TrP. This altered sympathetic neuronal
activity can explain both the adjacent thermo-
graphic hotspot and outer shell of increased oxy-
gen tension associated with a TrP (23).
As the sensitized type IV [C fiber] muscle
nociceptors within antecedent TrPs contribute
further to C fiber nociceptive afferent input and
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induce further withdrawal reflex central sensiti-
zation, antecedent TrPs may self-perpetuate long
after the initiating noxious stimulus has ceased.
Muscle C fibers are more effective than cuta-
neous C fibers at inducing prolonged facilita-
tion of the NWR (24). By increasing the NWR
central sensitization, antecedent TrPs may lead
to the formation of other TrPs in synergistic
[flexor] muscles and also cause ongoing recipro-
cal inhibition and motor dysfunction of antago-
nist [extensor] muscles. The involvement of the
sensitized NWR mechanism in the pathogene-
sis of antecedent TrPs can explain the reported
clinical observation of shortened, hyperexcitable
agonist, and functionally weakened antagonist
muscles [e.g., tight iliopsoas/tensor fasciae latae
and weak gluteal muscles (25)].
Sustained partial depolarization of the α-
motoneurons that supply affected muscle fibers
influences, but does not prevent, normal action
potential stimulation of muscular contraction.
Electromyographically, a muscle containing a
TrP shows an absence of motor unit action po-
tentials at rest, but an increased responsiveness
when the muscle is voluntarily contracted and
loaded (26).
Supraspinal centers are critically involved
in descending modulation [a shifting balance
between facilitation and inhibition] of the
withdrawal reflex mechanisms, SC/TN central
189
sensitization, and ascending nociceptive trans-
mission. Only in the presence of sufficient de-
scending facilitatory command does input from
muscle or joint flexor reflex afferents activate
α-motoneurons (27, 28).
The activation of the NWR by noxious stim-
ulation anywhere on a limb does not lead to
one stereotypical muscular response. The NWR
mechanism has a modular organization [the cu-
taneous receptive field for each limb muscle, or
few synergistic muscles, corresponds to the skin
area withdrawn upon contraction of the effec-
tor muscle[s] when the limb is in the standing
position (29)], so ongoing noxious stimulation
of different areas would result in antecedent TrP
formation in different combinations of agonist
muscles. Noxious stimulation of some limb ar-
eas results in the NWR-mediated contraction of
ipsilateral extensor muscles (29).
Withdrawal reflex mechanisms develop in
utero. The reflex responses of neonates are exag-
gerated compared to adults, and the NWR synap-
tic connections are fine-tuned over the postnatal
period, with a depression of the overall response
and an individuation and restriction of the re-
sponse to an isolated withdrawal movement (30).
The lamina V WDR neurons that are intercalated
in the withdrawal reflex pathway and are thought
to play a major role in pain are organized muscu-
lotopically, rather than somatotopically, during
development by movement-induced patterns of
primary afferent activity (16).
Ascending Nociceptive Transmission
At the SC/TN DH, nociceptive information
from muscle is transmitted from primary af-
ferent neurons to second-order neurons, which
then project to supraspinal centers (31). Almost
all postsynaptic projection neurons with input
from nociceptive muscle afferents also process
information from other receptors in other tis-
sues (31). The WDR neurons, which may re-
spond to noxious or innocuous input from
cutaneous, somatic, or visceral receptors, in-
clude both neurons that project in ascending
pathways and interneurons involved in polysy-
naptic reflexes (32). Within the SC DH, nocicep-
tive information from the viscera, skin, and other
organs is subject to extensive processing by a di-
versity of mechanisms, which may enhance or
inhibit its transfer to higher centers (33).
 190 JOURNAL OF MUSCULOSKELETAL PAIN
Nociceptive signals may be transmitted to a
wide variety of supraspinal centers via multiple
parallel ascending pathways (31, 34). Many pro-
jection pathways decussate at the ventral com-
missure, before ascending on the contralateral
side of the SC (31, 34). It is likely that the
properties and terminations of the nociceptive
impulse-carrying ascending projections [i.e., the
fiber type, terminal topographic organization,
number of synapses crossed, and function of
contacted postsynaptic neurons] help to decode
the character and physiological effects of pain.
Muscle [TrP] pain is typically conducted slowly,
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poorly localized, and may lead to considerable
disruption of homeostasis (35). This is probably
because of substantial transmission through un-
myelinated axons, less distinct topographic or-
ganization of terminals, polysynaptic projection
to cerebral centers, and termination at diverse
brainstem centers [which mediate the physio-
logical response to pain].
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Supraspinal Modulation
I propose that brainstem, especially
medullary, centers are integrally involved
in the pathophysiology of TrPs and now
consider these supraspinal mechanisms. A
highly interconnected complex of brainstem
nuclei facilitates or inhibits ascending sensory
[including nociceptive] and descending motor
and autonomic transmission, predominantly via
projections to the SC/TN. Supraspinal centers
that are critically involved in the descending
modulation of pain include the brainstem nora-
drenergic nuclei [A5, locus ceruleus, A7 nuclei]
and the medullary reticular formation and raphe
nuclei [especially the rostral ventromedial
medulla/ventromedial medulla [RVM/VMM]
and the caudal medullary subnucleus reticularis
dorsalis [SRD, dorsal reticular nucleus]] (33,
36). These brainstem centers project to the
SC/TN DH, where the ascending nociceptive
signal may be enhanced or inhibited [bidirec-
tionally modulated]. These centers may also
modulate pain-related responses via ascending
projections (36).
Under resting conditions, descending inhibi-
tion dampens excessive sensitivity to noxious
stimulation (33). This role may be counter-
balanced by descending facilitation, which
enhances the signal to noise ratio for the per-
ception of noxious stimuli (33). Activation of a
single supraspinal pain modulatory center may,
via contrasting mechanisms, simultaneously
trigger both descending inhibition and facilita-
tion of nociception (33). Ordinarily, the output
of brainstem nociceptive inhibitory neurons is
greater than the output of brainstem nociceptive
facilitatory neurons, but this balance is labile
(37) and may be shifted in either direction by
internal or external factors. Therefore, these
centers usually maintain a resting level of
nociceptive inhibitory tone [reversible SC block
typically results in an increased responsiveness
of nociceptive DH neurons (38, 39)]. However,
pain inhibitory mechanisms may be intensi-
fied either endogenously, e.g., during sleep,
stress-induced analgesia, exercise-induced
analgesia, and attentional modulation of pain, or
exogenously, e.g., during stimulation-induced
analgesia and after pharmaceutical administra-
tion. The balance may be shifted under other
circumstances [injury, illness, stress, fatigue] to
facilitate ascending nociceptive transmission.
I propose that afferent nociceptive signals
arise from both latent and active TrPs, but the
signals from latent TrPs are completely inhibited
at the SC/TN DH by tonically active descending
antinociceptive mechanisms mediated by these
brainstem centers [so latent TrPs are clinically
quiescent with respect to spontaneous pain, but
may show all the other clinical characteristics of
active TrPs (40)]. That is, despite the existence of
a continuum of nociceptor sensitization between
latent and active TrPs, only active TrPs are spon-
taneously painful because the signal from latent
TrPs is actively blocked before reaching con-
sciousness [unless the latent TrP is palpated or
its nociceptive signal is otherwise augmented].
The level of descending antinociceptive tone is
probably primarily regulated by the brainstem
pain modulatory centers in direct response to the
intensity of the incoming ascending nociceptive
signal.
The Ventromedial Medulla
The VMM contains an important cluster of
nuclei that are involved in both the facilitation
and inhibition of sensory [including nocicep-
tive], autonomic, and motor functions. These
nuclei include the midline raphe nuclei [nucleus
raphe magnus [NRM], nucleus raphe obscurus
 Hocking
[NRO], and nucleus raphe pallidus [NRP]] and
the adjacent reticular formation nuclei [nucleus
reticularis gigantocellularis, nucleus reticularis
magnocellularis [NRMC, nucleus reticularis gi-
gantocellularis pars alpha] and nucleus reticu-
laris paragigantocellularis lateralis] (33, 41–43).
I propose that the VMM is critically involved in
both facilitation and inhibition of TrP formation
and TrP nociception, as well as in the treatment
of TrPs.
Neurons in the VMM mostly provide di-
rect descending projections to all levels of the
SC/TN, but those in different areas of the VMM
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have preferential projections through different
spinal funiculi and preferential laminar desti-
nations. Cells in the rostrally located NRM,
NRMC, and nucleus reticularis paragigantocel-
lularis lateralis [RVM] tend to project through
the dorsolateral funiculus to target the DH, those
in the rostral part of the NRP/NRO project via
the lateral funiculus to target the intermediate
horn [including the intermediolateral cell col-
umn], and those in the caudal NRP/NRO project
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through the ventrolateral and ventral funiculi to
target the ventral horn (43).
I suggest that the primary function of the
VMM is to regulate SC/TN neuronal and reflex
excitability. By altering the excitability of neu-
rons at the SC/TN level, neurons in the VMM
may simultaneously facilitate and inhibit as-
cending noxious and innocuous sensory trans-
mission and facilitate and inhibit descending
autonomic and motor activity. Because of this
bidirectional influence on the excitability of neu-
rons at all segmental levels and in all laminae of
the SC/TN [and at brainstem somatic and au-
tonomic motor nuclei], the VMM has been re-
ported to be involved in the regulation of very
diverse bodily functions. Reported functions of
the VMM include nociceptive and innocuous
sensory modulation; modulation of locomotion
and basal muscle tone; modulation of auto-
nomic activity [heart rate, blood pressure, respi-
ration, thermoregulation, digestion, micturition,
and sexual function]; regulation of cortical
arousal and sleep; control of SC/TN central
sensitization and reflex activity [including the
NWR]; and supply of neurotransmitters to spinal
and supraspinal sites (42–45).
The VMM contains a mixed population of
neurons that have either phasic or tonic and
facilitatory or inhibitory effects on sensory
[including nociceptive], autonomic, and motor
191
functions at the SC/TN level. Pharmacological
or electrical stimulation of the RVM can pro-
duce either facilitation or suppression of no-
ciception or motor activity, depending on the
subgroups of neurons activated and the state of
the sleep/wake cycle at the time of stimulation
(44). Several overlapping classification systems
of the RVM neurons have been described, which
depend on different in vivo/in vitro characteris-
tics. The RVM neurons can be broadly divided
into phasically active non-serotonergic neurons
and tonically active serotonergic neurons.
The non-serotonergic RVM neurons include
on-, off-, and neutral-cells. These neurons
have an irregular discharge pattern and/or a
high mean discharge rate (41). The RVM on-
and off-cells have been shown to phasically
modulate nociceptive transmission in opposite
directions in the anesthetized rat. The on-cells
facilitate nociceptive transmission, are directly
inhibited by µ-opioids, and their activity is
thought to be facilitatory [or in fact obligatory]
for certain types of persistent pain (46). The
off-cells are thought to have a net inhibitory ef-
fect on ascending nociceptive transmission and
are indirectly activated by µ-opioids (45). In
the anesthetized rat, on- and off-cells discharge
in bursts that are timed reciprocally (43). The
RVM on- and off-cells are likely to rapidly en-
hance and inhibit, respectively, the nocifensive
reflex responses to repeated noxious stimulation
(47, 48).
Most studies report that a minority of
spinally projecting VMM neurons is serotoner-
gic (43, 49). Morphologically distinct serotoner-
gic VMM neurons are typically active in a tonic
manner [they have a slow and steady, but not nec-
essarily regular discharge] (41, 50). The seroton-
ergic RVM cells are not likely to play a role in
phasic nociceptive modulation, but instead are
likely to serve a tonic function, perhaps mod-
ulating nociceptive transmission in accordance
with changing behavioral or social states (50).
As with the RVM non-serotonergic neurons, dif-
ferent subclasses of the RVM serotonergic neu-
rons may facilitate or inhibit nociceptive trans-
mission at the SC/TN DH (50, 51). The NRM
and NRMC serotonergic neurons are the major
source of serotonin in the SC/TN DH (50).
I propose that an inhibitory subclass of the
RVM serotonergic neurons is the cell type pri-
marily responsible for the complete inhibition
of nociceptive signals that arise from latent
 192 JOURNAL OF MUSCULOSKELETAL PAIN
TrPs, although RVM off-cells, SRD neurons, and
brainstem noradrenergic neurons may also in-
hibit TrP pain. As TrPs accumulate and as-
cending nociceptive transmission intensifies, the
“tonic” inhibitory activity of these serotonergic
neurons increases, and as TrPs are treated, this
antinociceptive activity reduces so that only the
most sensitized TrPs are consciously perceived
to be painful [active].
Descending pathways may modulate
nociceptive transmission at the DH via an inter-
action with primary afferent terminals, ascend-
ing projection neurons, intrinsic excitatory and
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inhibitory interneurons, and the terminals of
other descending pathways (33).
The VMM may suppress [or in some circum-
stances facilitate] both the NWRs [including the
C fiber NWR (52) and the VMR (53)] and SC/TN
central sensitization, and therefore inhibit [or
facilitate] the formation of antecedent TrPs. The
VMM may modulate the C fiber withdrawal
reflexes by acting on sensory, interneuronal, and
motor components of the SC/TN reflex arcs. The
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RVM is involved in inhibitory feedback mecha-
nisms that counteract the windup [central sensi-
tization] phenomenon and trigger long periods of
inhibition (52). Transection of the ipsilateral dor-
solateral funiculus removes the RVM-mediated
descending inhibition of multireceptive [WDR]
spinal neurons and disproportionately prolongs
the after-discharge [sensitization] component of
their response to noxious stimulation (39). The
RVM may also facilitate the development and
maintenance of SC/TN sensitization [SC tran-
section or inactivation of the RVM attenuates
secondary hyperalgesia and central sensitization
in several models of persistent pain (54)].
The VMM receives projections from suprab-
ulbar motor facilitatory and inhibitory areas, and
plays an important role in the modulation of pha-
sic [locomotion] and tonic [basal muscle tone]
motor activity (44).
The RVM facilitates and inhibits visceral
nociceptive transmission at the DH (55). The
VMM might facilitate or inhibit most autonomic
functions by modulating descending output
as well as somatovisceral and viscerosomatic
reflexes [including the VMR]. This modulation
of autonomic function is possible because the
VMM projects, via monosynaptic and disy-
naptic routes, to preganglionic sympathetic and
parasympathetic neurons that, after synapsing,
target most autonomic tissues (43).
The Ventromedial Medulla and Sleep
Some VMM neurons might aid in the produc-
tion of a coherent behavioral state, such as wak-
ing, slow wave sleep [SWS], or paradoxical sleep
[PS], rapid eye movement sleep], by specifically
reconfiguring the sensitivity of spinal circuits to
external and internal stimuli (43). The VMM
neurons are involved in the modulation of many
sleep-related functions, including sensory mod-
ulation [including antinociception], PS muscle
tone suppression [atonia], visceral and somatic
reflex modulation, and cortical arousal control.
The spontaneous activity of the RVM neurons
alters across the sleep–wake cycle [most nox-
ious on-, neutral- and unclassified neurons are
wake-active, having a higher discharge rate dur-
ing waking than in SWS, whereas most off-cells
are SWS-active, showing a higher firing rate in
SWS than during waking (56)]. The off-cell ac-
tivity during sleep has been proposed to suppress
the alerting reaction evoked by external stimu-
lation, thereby allowing an animal to maintain
the sleep state (45). The serotonergic NRM neu-
rons discharge at their highest rates during ac-
tive waking, at progressively decreasing rates
during quiet waking, and SWS, and are almost
silent during PS (57). Lower levels of the VMM-
derived serotonin in the SC/TN during SWS [in
comparison to waking] would explain the dis-
inhibition of motor withdrawals from noxious
stimulation during SWS [rats have an enhanced
paw withdrawal from noxious heat during SWS
compared with waking] (15, 43). During PS,
RVM neuronal activity contributes to muscle
atonia by causing hyperpolarization of the cra-
nial and spinal motoneurons (44, 58). Conserva-
tion and replenishment of brainstem serotonin is
likely to be an essential role of sleep [especially
PS, when brainstem serotonergic neuronal activ-
ity is the lowest].
Sensory Gating
The VMM may modulate [facilitate or in-
hibit] ascending transmission of innocuous tac-
tile and thermal, as well as noxious, sen-
sory information at the SC/TN DH level
(45). The activity of the SC/TN WDR neu-
rons [which have cutaneous, somatic, and vis-
ceral receptive fields] is profoundly influenced
by the RVM descending modulation (59). I
 Hocking
propose that a tonic level of descending in-
hibition helps regulate the differential percep-
tion of cutaneous, somatic, and visceral sensory
input. Wide dynamic-range neurons are likely
to be preferentially activated by cutaneous in-
put, with lesser sensitivity to somatic input
and least to visceral input. Tonically active
descending inhibition more strongly inhibits
DH WDR neuronal responses to deep somatic
[muscle, tendon, joint] input in comparison
to cutaneous input (60). Different spinal
projection patterns of C fibers arising from dif-
ferent peripheral tissues would be a factor in this
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variable WDR neuronal activation and also con-
tribute to the difficulty in localizing muscle and
visceral pain. Cutaneous fibers have the most
focused and dense spinal projections, visceral
afferents have the most wide-ranging and dif-
fuse projections, and those innervating muscles
are intermediate in their spinal projections (61).
Therefore, the RVM descending modula-
tion usually allows cutaneous sensation, some
somatic, and no visceral sensation. However,
For personal use only.
changes in the RVM descending inhibition or fa-
cilitation of [or central sensitization of] the WDR
neuronal activity can alter the perception of nox-
ious or innocuous sensation from these sources.
Pathophysiology of Consequent Trigger Points
Having considered the pathophysiology of an-
tecedent TrPs, I now consider the pathophysiol-
ogy of consequent TrPs. I propose that conse-
quent TrPs are formed due to tonic reticulospinal
or reticulo-trigeminal facilitation of plateau po-
tentials in the withdrawal reflex antagonist α-
motoneurons. Consequent TrPs develop in with-
drawal reflex antagonist muscles, which are gen-
erally, but not exclusively, extensor muscles. I
suggest that this facilitatory mechanism evolved
to augment posture, counteract C fiber with-
drawal reflex reciprocal inhibition of antago-
nist muscles, and counteract postural changes
induced by antecedent TrPs.
As with sensory transmission at the DH, it is
likely that different subclasses of the VMM neu-
rons mediate either phasic or tonic and facilita-
tory or inhibitory modulation of α-motoneuron
activity at the ventral horn. I propose that
tonic activity of the VMM serotonergic neu-
rons, which typically facilitates extensor mo-
tor activity [and extensor α-motoneuron plateau
depolarization] and suppresses flexor activity,
193
predisposes to consequent TrP formation. This
tonic activity may change in magnitude or direc-
tion under certain circumstances [injury, illness,
stress, fatigue, and sleep], which would disin-
hibit flexor motor activity and predispose to an-
tecedent TrP formation.
Microstimulation of different sites in the
medullary reticular formation predominantly
leads to ipsilateral limb flexion, contralateral
limb extension, and ipsilateral head turning (62).
I propose that these asymmetric motor effects
counteract contralateral noxious stimulation-
induced spinal reflexes [NWR and crossed ex-
tensor reflex] and thus help to maintain posture.
Descending facilitation of motor activity may
lead to reciprocal effects on ipsilateral flexor
and extensor muscles, and opposite reciprocal
effects on contralateral flexor and extensor mus-
cles by acting on segmental [including commis-
sural] spinal interneuron circuits.
The tonically active VMM serotonergic neu-
rons, which project to the SC, facilitate postural
muscle tone (63). Rats with denervation of de-
scending serotonergic and noradrenergic path-
ways do not show impairment of general motor
ability but show a tendency to less erect posture
(64). Fatigue may have a prominent CNS compo-
nent, reflecting a disfacilitation of motor output
[the activity of medullary [NRO, NRP] seroton-
ergic neurons decreases steadily as a cat fatigues
during prolonged treadmill locomotion] (65). In
the case of the NJOR, the jaw closing muscles
are the antagonists that would be reciprocally
inhibited during sensitization of the reflex and
so reticulo-trigeminal motor facilitation would
predispose to consequent TrP formation in these
muscles.
Serotonin of supraspinal origin [of which the
VMM is the major source] shifts α-motoneurons
from the stable hyperpolarized state, with little or
no neuronal activity, to the stable partially depo-
larized plateau state, with tonic neuronal activity
(6). After acute SC transection [when brainstem-
derived neuromodulators are lost], motoneurons
caudal to the injury lose [albeit temporarily] their
ability to produce plateau potentials (66).
Brainstem Pain Modulatory Center
Sensitization and Dysfunction
I propose that as TrPs accumulate and
the level of DH central sensitization and as-
cending nociceptive transmission increase, the
 194 JOURNAL OF MUSCULOSKELETAL PAIN
activity of the brainstem pain modulatory cen-
ters increases concurrently, so that pain from
only the most sensitized TrPs is perceived [active
TrPs], while most, if not all, TrPs remain latent.
Long-term noxious stimulation is characterized
by a progressive reinforcement in mechanisms of
descending inhibition, reflecting the recruitment
of descending pathways originating in the RVM
and noradrenergic nuclei, and this enhancement
of descending inhibitory “tone” counterbalances
excessive nociceptive input and mitigates pain
(33).
It has been suggested that “[d]ue to the
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progressive exhaustion or dysregulation of
descending inhibition, to its limited efficacy,
or to a loss of responsiveness of downstream
mechanisms mediating its effects, descending
inhibition may be unable to combat long-term
painful states” (33). I propose that the formation
of large numbers of TrPs may overwhelm the
anti-nociceptive reserve of the brainstem pain
modulatory centers. This is especially likely
when the simultaneous formation of many TrPs
For personal use only.
[through generalized noxious stimulation and
immobility] leaves less time for pain modula-
tory center functional adaptation. Any genetic
weakness, nutritional deficiency, or metabolic
disturbance affecting relevant neurotransmitter
or neuronal activity would lessen the brainstem
pain modulatory center functional reserve and
lower the threshold for, and increase the severity
of, dysfunction-related symptoms. Because
many, often co-localized, neurotransmitters and
receptor types are probably involved in TrP
antinociception, the neurotransmitter/receptor
couple with the least functional reserve [the
“weakest link”] would fail first. Failure of
different neurotransmitter/receptor couples,
with differing actions, could manifest as a
variety of overlapping sensory, motor, and
autonomic disorders with associated myalgia.
Disorders
I consider it likely that TrP formation, TrP-
maintained SC/TN central sensitization, and
subsequent sensitization and disequilibration of
VMM and other supraspinal pain modulatory
center functions are important factors in the
pathogenesis of a wide variety of idiopathic or
incompletely understood disorders. These disor-
ders could include localized, regional, and gen-
eralized pain disorders and disorders of sleep,
mood, development, and motor and autonomic
functions.
There is wide acceptance that individual mus-
cle active TrPs commonly contribute to a vari-
ety of local or referred, chronic or episodic pain
disorders. As any skeletal muscle can develop
TrPs (67), TrPs may cause pain to be perceived
almost anywhere in the body. Pain may arise di-
rectly from sensitized nociceptors within TrPs,
from nerves entrapped by TrP taut bands, and
from nociceptors in other nonmuscular tissues
affected by TrP-induced muscular tension [in-
cluding enthesopathy].
TrPs, instead of occurring singly or randomly,
are normally found in patterned regional or gen-
eralized groupings [with active TrPs far less
common than latent TrPs (67)]. A regional my-
ofascial pain syndrome [MPS] typically involves
one [or up to a few] active TrPs, as well as
multiple latent TrPs, in the affected region [as
well as latent TrPs in other regions]. Regional
pain disorders in which TrPs may play a fun-
damental role include tension-type headache,
frozen shoulder, and nonspecific neck and low
back pain [currently up to 90 percent of human
low back pain cases are labeled as nonspecific,
in which no specific pathophysiological mech-
anism can be identified (68)]. In addition, TrPs
may act as a factor in the etiology of osteoarthri-
tis by increasing mechanical joint wear due to
joint compression [if TrPs occur in transarticu-
lar muscles] and postural change, as well as by
altering regional sympathetic reflex activity. The
MPS would be accompanied by central sensiti-
zation at both SC/TN and brainstem pain modu-
latory center levels, although in most cases any
resulting brainstem dysfunction would be com-
paratively mild.
The formation of large numbers of TrPs [se-
quentially or more particularly simultaneously],
especially when there is a lesser brainstem
antinociceptive reserve, may overwhelm the
brainstem’s capacity for descending nociceptive
inhibition and lead to generalized pain disorders,
including fibromyalgia syndrome [FMS]. Gen-
eralized TrP pain disorders involve not only pain
arising directly from TrPs but also generalized
hyperalgesia and allodynia, due to the resulting
SC/TN central sensitization and overwhelmed
descending antinociceptive mechanism. Gener-
alized TrP pain disorders are typically more
prevalent in females than males [adult women
 Hocking
are four to seven times more likely to have FMS
than adult men (69)]. This is likely due to a
lower rate of serotonin synthesis in the female
brain [the mean rate of serotonin synthesis in
the human brain has been found to be 52 percent
higher in normal males than in normal females
(70)]. In most patients, chronic localized or re-
gional muscle pain precedes the development of
FMS, which is associated with longstanding or
permanent central sensitization of the DH WDR
neurons and disinhibition of pain due to impaired
endogenous descending pain modulation (71).
There are measurable alterations in the NWR in
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headache (72), FMS (73), and other pain disor-
ders.
Central sensitization of the NWR, maintained
by afferent input from TrPs, would result in on-
going reflex inhibition of antagonist [extensor]
motor activity and reflex facilitation of agonist
[flexor] motor activity. This motor disturbance
and associated postural change lead to an aug-
mentation of compensatory reticulospinal facil-
itation of extensor motor activity and inhibition
For personal use only.
of flexor activity. Marked sensitization and sub-
sequent dysfunction of brainstem motor modu-
latory centers, due to overwhelming numbers of
TrPs, would lead to a weakening of this com-
pensatory mechanism and a worsening of pos-
ture. The resulting disfacilitation of motor output
would also contribute to fatigue.
I have suggested that altered sympathetic
neuronal activity in the vicinity of a hypoxic TrP
results in compensatory vasodilation. A regional
or generalized MPS could result in sufficient
vasodilation to alter thermoregulation and ther-
mal tolerance. TrPs may directly induce visceral
disturbance and dysfunctions by somatovisceral
[reflexive] mechanisms (74). Dysfunction of
brainstem pain modulatory centers due to
overwhelming TrP nociception may contribute
to the development of other [often concomitant]
autonomic disturbances, including alterations to
heart rate, respiration, blood pressure, micturi-
tion, sexual function, and thermoregulation.
Most patients with persistent TrP pain have
difficulty in sleeping and show abnormal sleep
patterns when monitored in a sleep laboratory
(75). The pain of active TrPs may lead to at-
tentional disruption of sleep. In addition, TrP
nociception-induced VMM neuronal dysfunc-
tion may contribute to insomnia, nonrestorative
sleep, and attenuation of sleep muscle atonia.
195
The VMM serotonergic neuronal sensitiza-
tion and subsequent dysfunction, due to over-
whelming TrP nociception, may also be a factor
in the etiology of certain mood disorders that are
associated with low serotonin levels and somati-
zation. Although somatic changes are generally
considered to be a consequence of psychiatric
illness, it is possible that in some cases bodily
changes actually precede and contribute to the
neuronal dysregulation that leads to mood dis-
orders, such as clinical depression and anxiety.
The nociception-induced brainstem pain modu-
latory center dysfunction could then amplify the
somatization through disequilibration of sen-
sory, motor, and autonomic functions. It is well
established that depression occurs more fre-
quently in individuals with a variety of chronic
pain syndromes [including FMS, chronic mus-
culoskeletal pain, and headache] than in those
without pain (76, 77). Patients with major
depression have increased sensitivity to deep
somatic pain and reduced sensitivity to pha-
sic cutaneous pain (77). The VMM seroton-
ergic neuronal dysfunction and compensatory
enhanced phasic antinociceptive mechanisms
could explain these abnormal sensitivities.
Ontogenetically, TrPs may arise when the
neural and reflexive mechanisms underlying
their development are sufficiently organized.
This is likely to occur in utero. Perinatal de-
velopment of a generalized MPS would result
in SC/TN central sensitization [including α-
motoneuron plateau depolarization], significant
changes in muscle tone, and interference with
the normal postnatal tuning of reflexes and mat-
uration of motor control. Appropriate postna-
tal tuning of the NWR system also depends on
the normal functioning of supraspinal centers
[neonatal SC transection results in the persis-
tence of neonatal reflex patterns in adult rats]
(78). It is possible that the developmental mo-
tor dysfunction of spastic cerebral palsy may
result from the perinatal development of gener-
alized [or significant regional] MPS, as well as
from perinatal damage to supraspinal reflex tun-
ing centers. If the generalized MPS arose later
in infancy when reflexes were already tuned and
the motor cortices were organized, such devel-
opmental disturbance of motor function would
not result. It could be that TrP formation in ju-
veniles may be an important etiological factor
in the development of later osteoarthritis due to
 196 JOURNAL OF MUSCULOSKELETAL PAIN
the susceptibility of rapidly growing joints to
disturbance.
Treatment of Trigger Points
I propose that most of the generally accepted
treatments for TrPs in fact involve the strong
and transient inhibition of the CNS mechanisms
that sustain the α-motoneuron plateau depolar-
ization, which perpetuates TrPs. This inhibition
of the centrally sensitized C fiber withdrawal
reflexes or reticulospinal/reticulo-trigeminal
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motor facilitation is predominantly mediated by
brainstem centers and is induced by a variety of
noxious counter-stimulation techniques.
Noxious stimulus-induced suppression of the
C fiber withdrawal reflexes involves activa-
tion of descending inhibitory mechanisms medi-
ated by various brainstem nuclei [primarily the
nuclei of the VMM but also other centers, in-
cluding the SRD]. Sham-operated rats [with an
intact neuraxis] show a strong noxious stimulus-
For personal use only.
induced inhibition of the C fiber NWR, which
lasts about 20 minutes (52). Spinalization or cau-
dal medullary transection prevents the noxious
stimulus-induced inhibition of the NWR and in-
stead leads to a long-lasting facilitation of the
reflex (79). This indicates that supraspinal cen-
ters mediate the noxious inhibitory control [al-
though the inhibition is effected at SC level].
Inactivation of the entire RVM profoundly re-
duces the noxious stimulus-induced inhibition
of the C fiber NWR but does not block this in-
hibition completely (52). This indicates that the
RVM and other supraspinal centers mediate the
NWR inhibition.
The SRD mediates diffuse noxious inhibitory
controls, a mechanism in which most WDR and
some nociceptive-specific neurons, at all seg-
mental levels of the SC/TN DH, can be strongly
inhibited by noxious stimulation of any part of
the body [apart from the excitatory receptive
field of the inhibited neuron] (32, 80, 81). It
has been shown that diffuse noxious inhibitory
controls operate in normal human subjects, with
painful heterotopic conditioning stimuli induc-
ing simultaneous depression of the sensation of
pain and the NWR evoked by electrical stimula-
tion of the sural nerve (82).
Neurons that exhibit bistable behavior can be
switched between the two stable levels of ex-
citability by short-lasting excitatory or inhibitory
input (6). The brainstem-mediated inhibition of
SC/TN neuronal activity involves several mech-
anisms, including hyperpolarization of the post-
synaptic neuronal membrane (58, 83, 84). Strong
activation of descending inhibition would tem-
porarily reduce α-motoneuron activity by shift-
ing the motoneuron membrane potential from
the more excitable, partially depolarized plateau
state to the less excitable, hyperpolarized state.
Temporary hyperpolarization of previously
partially depolarized α-motoneurons removes
the low-grade efferent stimulus that helps per-
petuate both antecedent and consequent TrPs.
Although contractured muscle is highly resistant
to stretch, this temporary suppression of neural
mechanisms that maintain the TrP local energy
crisis causes interruption of the actin–myosin in-
teraction, which allows stretching of the contrac-
tured muscle fibers to full length. At full stretch
range of motion, overlap between myofibril actin
and myosin molecules is greatly reduced, which
reduces muscle contractile activity and energy
consumption to almost zero and restores blood
perfusion and oxygenation via decompression of
the local capillary bed (85). This normalization
of local perfusion reverses the TrP local energy
crisis and muscle nociceptor sensitization.
Reversal of TrP muscle nociceptor sensitiza-
tion reduces withdrawal reflex afferent activity,
which helps to reverse central sensitization of
the SC/TN [including withdrawal reflex central
sensitization]. By diminishing NWR sensitiza-
tion, appropriate treatment of antecedent TrPs
counters further facilitation of withdrawal reflex
agonist muscle activity, which limits TrP recur-
rence in the treated muscle and propagation of
TrPs to synergistic muscles. Treatment of an-
tecedent TrPs also reverses NWR reciprocal in-
hibition of antagonist extensor muscles. For ex-
ample, treatment of TrPs in the hip flexors often
improves the strength and reduces the inhibition
of the antagonist gluteal muscles (25). However,
inappropriate treatment of the more frequently
painful consequent TrPs alone [and not the an-
tecedent TrPs] exacerbates the main antecedent
TrP problem and postural disturbance. Subse-
quent pain relief is not long-lasting, because
compensatory reticulospinal motor facilitation
persists.
Treatment of the most sensitized TrPs in the
body [active TrPs] decreases ascending nocicep-
tive transmission, which lowers the pain thresh-
old by reducing brainstem pain modulatory
 Hocking
center descending antinociceptive tone. This fre-
quently causes the next most sensitized latent
TrP to become painful [become active]. When
an active “TrP has been successfully eliminated,
the pain pattern may shift to that of an earlier,
key TrP which also must be inactivated” (86).
As TrPs are sequentially treated, there is a grad-
ual reduction in the modulatory output from the
VMM and other brainstem pain modulatory cen-
ters, lessening the central sensitization of these
nuclei and allowing a gradual normalization
of any central sensitization-related dysfunction.
Because of the sensory, motor, and autonomic
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modulatory roles of the nuclei involved in TrP
antinociception, treatment of TrPs may lead to
an improvement in a variety of sensory, motor,
and autonomic dysfunctions. Systematic treat-
ment of active and latent TrPs may therefore
lead to an amelioration, or in some cases cure,
of a variety of pain disorders and some disor-
ders where pain is not prominent, by causing a
shift toward homeostasis of brainstem pain mod-
ulatory center, SC/TN, muscle nociceptor, and
For personal use only.
muscular function.
There are a wide variety of traditional and
modern techniques that have been used [know-
ingly or unknowingly] to prevent or treat TrPs
in humans. Preventative techniques usually in-
volve regular stretching of the muscles and most
treatment methods involve noxious counter-
stimulation [with increased effect if immediately
followed by stretching].
Noxious counter-stimulation techniques used
to treat and control the pain of TrPs involve
stimulation of nociceptors that are usually lo-
cal [within the TrP or the overlying skin] but are
sometimes well distant to the TrP. It is likely that
strong segmental noxious stimulation causes the
most profound inhibition of the CNS mecha-
nisms that perpetuate TrPs. Such noxious stim-
ulation often induces a spinal reflex-mediated
local twitch response of the muscle containing
the TrP during treatment.
Noxious counter-stimulation techniques are
of variable efficacy. The most efficacious
counter-stimulation techniques used to treat TrPs
include pressure release, superficial and deep
dry needling, TrP injection, vapocoolant skin
stimulation, and low-frequency transcutaneous
electrical nerve stimulation [over the TrP]. The
efficacy of cutaneous counter-stimulation tech-
niques [superficial dry needling and vapocoolant
application] indicates that TrP treatment in-
197
volves CNS mechanisms and does not neces-
sitate physical damage to the affected area of
muscle.
Less efficacious counter-stimulation tech-
niques may treat some TrPs, but their main effect
on TrPs involves the activation of descending
antinociceptive mechanisms that help to control
pain. Traditional noxious counter-stimulation
techniques involve the application of noxious
temperature [thermal pools, saunas, moxibus-
tion], massage [many cultures have their own
form], and needle insertion [acupuncture]. More
recently devised counter-stimulation techniques
include spinal manipulation [chiropractic], soft
tissue manipulation [osteopathy], conventional
transcutaneous electrical nerve stimulation, me-
chanical vibration, and therapeutic ultrasound.
Injection of botulinum A toxin [Botox] into
TrPs is an effective treatment but at the expense
of post-injection muscle function. Botox injec-
tion into TrP-active loci totally destroys endplate
function, effectively denervating those muscle
fibers (87). No other pharmaceuticals are re-
ported to be useful in the treatment of TrPs,
although a variety of pharmaceuticals can re-
duce the peripheral and central sensitization that
predispose to TrP formation and provide some
TrP pain relief.
Because full lengthening of a muscle mar-
kedly reduces energy consumption and restores
perfusion, stretching also plays a crucial role in
the prevention of TrPs. In the incipient stage of
energy deficit prior to contracture or after a TrP
is treated, regular stretching of the muscle should
prevent a TrP from forming or reforming. Daily
passive stretch exercise (88) protects against the
formation of TrPs and maintains flexibility. The
prevention of TrPs helps to explain the utility
of traditional systematic stretching techniques,
such as yoga and tai chi, as well as regular exer-
cise. Lack of stretching during prolonged immo-
bility, accompanied by ongoing noxious stimu-
lation, strongly predisposes to TrP formation.
Evolutionary Development
The neural mechanisms responsible for TrP
formation, nociception, and antinociception are
primitive and are likely to occur, with varying
degrees of complexity, in all vertebrate species.
In many cases the same neurotransmitter act-
ing on the same receptor type exhibits opposite
 198 JOURNAL OF MUSCULOSKELETAL PAIN
effects on nociception at brainstem and SC level,
which suggests that brainstem pain modulatory
mechanisms may have started to develop at the
earliest differentiation of the neuraxis into brain
and SC. There would presumably be a strong
evolutionary selection pressure acting to refine
these neural mechanisms to provide the optimum
balance between nociception and antinocicep-
tion, so that only the most relevant [severe] pain
signals are perceived and the rest inhibited be-
fore reaching consciousness. Over the course of
evolution, an ever more complex and finely tuned
nociceptive control system has presumably de-
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veloped to give animals the greatest chance of
survival to reproductive age. Now there are a
multitude of neurotransmitters and other media-
tors involved in the transmission and modulation
of nociceptive processing in the DH and higher
centers (33).
The development of an upright stance dur-
ing human evolution would have required an
augmentation of the reticulospinal motor mod-
ulatory mechanisms that maintain posture and
For personal use only.
counter the NWR. This evolutionary adaptation
would explain the frequent localization of ac-
tive TrPs on the posterior extensor aspect of the
human torso.
Suggestions for Further Research
Reliable localization or treatment of TrPs re-
quires cooperation and communication between
the [human or companion animal] patient and the
practitioner. Although treatment of TrPs is possi-
ble under sedation or general anesthesia, reduced
or absent vocal or gestural feedback makes it
considerably more difficult to ascertain that a
TrP has been located and has responded appro-
priately to treatment. Methodical treatment of
most TrPs, as would be required to validate cer-
tain parts of this hypothesis, would be very dif-
ficult, if not impossible, with laboratory animals
such as rodents and rabbits. The need for co-
operation and communication is likely to make
dogs and humans the most useful subjects for
TrP research.
Many of the neuronal mechanisms that
I suggest are involved in the pathogene-
sis and treatment of TrPs have been indi-
vidually described through neurophysiological
research on humans or laboratory animals.
However, confirming that these mechanisms
are involved in the way I propose would re-
quire considerable research effort. Some appro-
priate further investigations could include the
following:
• Investigating whether plateau depolariza-
tion of α-motoneurons is responsible for the
endplate noise detectable at the active lo-
cus of a TrP, by making concurrent electro-
physiological recordings at axon and motor
endplate levels.
• If so, testing whether these partially depo-
larized α-motoneurons become hyperpolar-
ized during the treatment of a TrP by mak-
ing similar electrophysiological recordings
during the treatment.
• Investigating whether two main types of
TrPs [antecedent and consequent] exist,
e.g., by comparing the efficacy of treating
TrPs in anterior flexor muscles versus pos-
terior extensor muscles in human nonspe-
cific neck or low back pain.
• Testing whether central sensitization of the
C fiber withdrawal reflexes is involved in
the pathogenesis of antecedent TrPs, by
measuring a reduction in the amplitude of
the C fiber NWR several days after method-
ical treatment of antecedent TrPs.
• Verifying whether SC/TN and brainstem
pain modulatory center sensitization is as-
sociated with MPS and is reversible upon
treatment of most TrPs, e.g., by measur-
ing sensitization indicators in cerebrospinal
fluid or using advanced imaging tech-
niques such as positron emission tomog-
raphy [PET] or functional magnetic reso-
nance imaging [fMRI].
• Investigating whether TrP-induced CNS
sensitization and dysfunction are involved
in the pathogenesis of a variety of disorders,
including FMS and depression [this could
be done by comparing the response of a
population of affected patients to methodi-
cal treatment of latent and antecedent TrPs
versus control treatments, e.g., treatment of
active TrPs only].
• Investigating if brainstem-mediated
antinociceptive mechanisms completely
inhibit the nociceptive signals from la-
tent TrPs, so that only active TrPs are
spontaneously painful, by systematically
treating human or canine TrPs in three
body quadrants and determining whether
 Hocking
pain results in the nontreated quadrant
[with lameness being an indicator of
spontaneous pain in a dog].
Experimental Design
I now outline the design of a specific prospec-
tive randomized controlled clinical trial that
could be undertaken to test whether two main
types of TrPs [antecedent and consequent] exist.
I hypothesize that in cases of human nonspecific
low back pain, treatment of all TrPs in ante-
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rior lumbar and hip flexor muscles would pro-
vide larger and more persistent improvements in
measured pain and health status outcomes than
treatment of all TrPs in posterior lumbar and hip
extensor muscles.
Adult patients [aged between 18 and 70 years]
with chronic [persisting for more than three
months] nonspecific low back pain [pain of the
low back, either with or without leg pain, which
is not associated with major trauma, spinal steno-
For personal use only.
sis, radiculopathy, or other specific cause] would
be eligible for inclusion in the trial. Patients
having received any prior treatment would be
eligible for inclusion, but pregnant or obese pa-
tients whose anterior lumbar muscle TrPs could
not be safely or effectively treated would be
excluded.
Patients would be randomly assigned to one
of two treatment groups. Subjects in the in-
dex group would receive treatment of all la-
tent and active TrPs in the lumbar and hip
flexor muscles [quadratus lumborum, iliopsoas,
rectus abdominis, abdominal obliques, gluteus
medius/minimus anterior part, sartorius, rectus
femoris, tensor fasciae latae, pectineus, adduc-
tor longus/brevis, and gracilis]. Subjects in the
control group would receive treatment of all la-
tent and active TrPs in the lumbar and hip exten-
sor muscles [longissimus thoracis, spinalis tho-
racis, iliocostalis lumborum, lumbar multifidi,
gluteus maximus, gluteus medius/minimus pos-
terior part, biceps femoris long head, semitendi-
nosus, semimembranosus, and adductor mag-
nus posterior part]. Any localized tender spot
in a taut muscle band, with or without patient
pain recognition, which shows a slow crescendo
and then rapid decrescendo in pain intensity
upon application of constant non-ischemic digi-
tal pressure, would be defined as a TrP. In both
the groups, each TrP would be treated using
199
such digital pressure constantly applied until the
pain intensity rapidly diminishes [after approxi-
mately one minute] and the treated muscle would
then be gently stretched to full length. During
each treatment session this process would be re-
peated on each TrP in the target flexor or extensor
muscles in the index or control groups, respec-
tively, until no further TrPs could be found in the
target muscles. In both index and control groups,
a treatment session would be given on weeks 1, 2,
4, and 8. Subjects would be blinded to the study
hypothesis. Any concomitant therapy should be
avoided or minimized.
I propose that the outcomes to be evaluated
shall include pain, back-specific health status,
generic health status, lost working days due to
back pain, and patient satisfaction (89). Vali-
dated pain and health status measures that could
be used to evaluate primary outcomes include
a 100-point visual analog pain scale to assess
overall back pain and the Roland–Morris Dis-
ability Questionnaire (90) to assess back-specific
health status. These measures would be as-
sessed for each subject prior to each of the four
treatment sessions and then at months 4, 6, 9,
and 12.
Whether each subject achieves a 30 percent
minimal clinically important improvement (89)
in each pain or health status score, compared
to the baseline, would be calculated at each of
the subsequent seven assessments. At each as-
sessment, any difference in the percentage of
subjects in the index or control groups that make
such an improvement in each outcome measure
would be analyzed for statistical significance. I
predict that a higher proportion of subjects in
the index group will make minimal clinically
important improvements in measured pain and
health status outcomes. I also predict that such
improvements in measured outcomes will per-
sist at more subsequent assessments of the index
group. The sample size required to achieve sta-
tistical significance would be best determined
through a pilot study, although I estimate that
a sample of 60 to 100 subjects in each group
would be sufficient.
CONCLUSION
In this paper I have proposed a new hypothesis
for the pathophysiology of TrPs, i.e., TrPs result
from nociception-induced CNS plasticity, rather
 200 JOURNAL OF MUSCULOSKELETAL PAIN
than from an intrinsic disorder of the motor end-
plate. If this hypothesis is correct, it will justify
an increased emphasis on the prevention of TrPs
by regular systematic stretching and a more me-
thodical approach to treatment, with targeting of
antecedent and latent TrPs. However, only with
an improved understanding of underlying patho-
physiology will there be a general acceptance of
the importance of TrPs and better management
of the MPS and other disorders.
Declaration of interest: The author reports
no conflict of interest. The author alone is re-
J Muscoskeletal Pain Downloaded from informahealthcare.com by University of Bristol on 07/19/10
sponsible for the content and writing of this
paper.
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Submitted: June 26, 2008
Revision Accepted: April 8, 2009