2. Introduction
Terms used to describe sensations of deep tissue pain, such as ‘‘cramping’’, ‘‘aching’’ and ‘‘tearing’’
Assessment of musculoskeletal pain is also complicated by its characteristics, unlike the typically localized pain that
arises from insults to the skin, myalgia is often diffuse and more likely to evoke referred pain
Decreased blood flow to the skeletal muscle that impairs oxygen supply sufficient to inadequately meet the metabolic
demands of the tissue is a feature of multiple clinical conditions in which patients often report deep tissue pain
While the most frequent source of myalgia across ages is either overuse or traumatic injury
Numerous basic and clinical reports have shown that ischemic conditions are able to generate muscle pain
3. Nociceptor
Receptor molecules that
are particularly
important for the
function of muscle
nociceptors are
Acid-sensing ion
channels (ASICs) that
open at a low tissue pH
P2X3 receptors that are
activated by binding
adenosine triphosphate
(ATP)
Transient receptor
potential receptor
subtype 1 (TRPV1) that is
sensitive to high
temperatures and low pH
4. Muscle tone
Skeletal muscles are
described as voluntary,
but even relaxed
muscles are almost
always slightly
contracted, a
phenomenon called
muscle tone
Muscle tone does not
produce active
movements, but it
keeps the muscles firm,
healthy, and ready to
respond to stimulation
The contractions
maintained by the
activity of muscle
spindle afferents (1a)
that have
monosynaptic
connections with alfa
motor neurons
The pathway is the
same as that for the
stretch reflex, and the
muscle tone was called
reflex tone, particularly
important for
antigravity muscles
Discharges in muscle
spindles are dependent
on the activity of
gamma motor neurons,
which are influenced
by descending (mainly
extrapyramidal) motor
pathways
5. Other receptor non nociceptor (proprioceptor)
Muscle spindles are complex
receptive structures that
consist of several specialized
intrafusal muscle fibers
Muscle spindles measure the
length and the rate of length
changes of the muscle, with
increasing velocity of the
length change
Their discharge frequency
decreases during contraction
of the muscle
The main central effect of the
muscle spindle Ia fiber is
excitation of the homonymous
muscle
The Ia fiber has
monosynaptic connections
with the a-motor neuron, the
function of these connections
can be tested with one of the
tendon jerks, for instance the
patellar reflex
7. Golgi tendon organ
Golgi (tendon) organs
measure the tension of
the muscle
Their location is the
transition zone between
muscle and tendon
The supplying fiber is
the Ib afferent, whose
structure is identical to
the Ia fiber (thick myelin
sheath and high
conduction velocity)
The main central action
of the Golgi organ is
inhibition of the
homonymous muscle
Muscle spindles and
Golgi organs are
proprioceptors, they
measure the internal
state of the body
9. Excitation-contraction coupling (EC coupling)
Excitation-contraction (E-C) coupling is the
sequence of events by which transmission
of an action potential along the sarcolemma
causes myofilaments to slide
The action potential is brief
and ends well before any
signs of contraction are
obvious
As you will see, the electrical
signal does not act directly
on the myofilaments,
instead, it causes the rise in
intracellular levels of
calcium ions, which allows
the filaments to slide.
10.
11. Active & passive properties of a muscle
In resting and relaxed muscle, a small number of cross-bridges between
myosin heads and actin filaments are slowly cycling and thus generate tensile
force
Muscle tone is modulated by the nervous system (active properties), but
part is intrinsic to cellular-level physiology (passive properties)
These cycling cross-bridges may be measurable as viscoelastic tone, they
also exhibit thixotropic behavior, this cross-bridge mechanism is
independent of electrical activity
Thixotropy (thixis: stirring, shaking and trepo: turning or changing) is the
history-dependent change in fluid viscosity: the longer the applied shear
stress, the lower the viscosity, the viscosity of a liquid decreases when it is
agitated.
12. Contractile activity
Contractile activity may occur in two different active
forms
Electrogenic contraction, i.e., muscle tension
resulting from electrogenic muscle contraction, the
term electrogenic refers to the fact that the alfa motor
neurons and the neuromuscular junction are active
under these conditions (EMG activity is present)
Electrogenic spasm, which can be defined as
pathological involuntary electrogenic contraction of
long duration, spasm in this sense is also always
accompanied by EMG activity
13. Blood supply of a muscle
Skeletal muscle has a rich blood supply, this is understandable because
contracting muscle fibers use huge amounts of energy and require almost
continuous delivery of oxygen and nutrients via the arteries
Muscle cells also give off large amounts of metabolic wastes that must
be removed through veins if contraction is to remain efficient
Muscle capillaries, the smallest of the body’s blood vessels, are long and
winding and have numerous cross-links, features that accommodate
changes in muscle length
They straighten when the muscle stretches and contort when the muscle
contracts
14. Excess Postexercise Oxygen Consumption
(EPOC)
Whether or not fatigue occurs, exercise
alters a muscle’s chemistry dramatically
For a muscle to return to its preexercise
state, the following must occur:
Its oxygen reserves in myoglobin must be
replenished
The accumulated lactic acid must be
reconverted to pyruvic acid
Glycogen stores must be replaced
ATP and creatine phosphate reserves
must be resynthesized
16. Mechanical stimuli
Mechanical stimuli : high intensity
such as squeezing or pinching the
muscle are effective stimuli for
muscle nociceptors
Do not respond to
physiological muscle
stretch, contractions,
and weak pressure
stimuli
The stimulus intensity
required for activating
a muscle nociceptor is
usually lower than that
for causing persistent
tissue damage
17. Chemical stimuli
Chemical stimuli : The effects of
most chemical stimulants on
nerve endings are mediated by
specific molecular receptors that
are located on the surface of the
nerve membrane
Binding of the stimulant to the
receptor molecule results either in
the opening of cations channel
(Na+,Ca++) or in changes in the
state of activation of intracellular
second messenger systems
Receptors that are strongly
excited by ischemic contractions
but not by contractions under
physiological conditions are
considered pure chemo-
nociceptors (sensitized by the
ischemia to the mechanical forces
of the contractions)
18. Adenosin Triphospate (ATP)
Adenosine triphosphate
(ATP) binds to the purinergic
membrane receptor P2X3
and opens an ion channel
that is permeable for small
cations, mainly Na+
The ATP concentration in
muscle cells is particularly
high, in the millimolar range
Muscle cells require a lot of
ATP, not only for contraction
but also as an energy source
for the calcium pump that
transports the Ca++ ions
back into the sarcoplasmic
reticulum after contraction
ATP is released from muscle
cells when the cell or its
membrane is damaged, for
instance during trauma and
inflammation, when injected
intramuscularly in humans,
ATP causes pain
19. Protons (H+)
Protons (H+ ions) are
among the most important
chemical stimuli for muscle
nociceptors, because almost
all pathological alterations
of a muscle are associated
with a drop in tissue pH
A pH value of around 6 is
known to occur in inflamed
or ischemic tissue, the pH 5
solution eliciting the largest
response
20. Inflammatory substances
Binding of the
stimulant to the
receptor molecule
changes the activity
state of the
intracellular second
messenger systems
The three
substances have
long been known to
sensitize and excite
muscle group IV
receptors
The classic
inflammatory
substances are
bradykinin (BKN),
serotonin (5-
hydroxytryptamine,
5-HT) and
prostaglandin
21. Important chemical substances
Two activating chemical substances are particularly important for the
generation of muscle pain: adenosine triphosphate (ATP) and protons (H+
ions)
ATP activates muscle nociceptors mainly by binding to the P2X3 receptor
molecule, H+ mainly by binding to the receptor molecules TRPV1
(transient receptor potential vanilloid 1) and ASICs (acid-sensing ion
channels)
These receptor molecules are channel proteins that span the membrane of
the nerve ending and mainly permit Na+ ions to enter the neuron (neural
excitation)
A drop in pH is probably one of the main activators of peripheral
nociceptors, as many painful disturbances of muscle are associated with
low pH in muscle tissue
22. Muscle spasm
Spasm can be defined as an
involuntary, longer-lasting
contraction of a muscle or a
muscle group, If the
contraction is painful, it is
often called cramp
Contractions of a few
minutes duration are usually
not painful, unlike sustained
muscular contractions
Spasm and cramp in the
sense of this definition are
associated with
electromyograph (EMG)
activity
If chronic involuntary
shortening of a muscle
occurs without EMG activity,
the term contracture is more
appropriate (visoelastic
properties of muscle)
23. Muscle spasm
The resulting ischemia is associated with the release of pain producing substances that sensitize muscle
nociceptors include bradykinin, ATP, and H+-ions
A mechanism underlying the pain is that the muscle compresses its own blood vessels if it exceeds a certain
level of force (for most muscles, approximately 30% of maximal contraction force)
Mechanical strain during eccentric exercise causes one-half sarcomere nonuniformity and overstretching
of sarcomeres beyond filament overlap, leading to “popped sarcomeres.”
Concentric muscle contractions do not cause exercise-induced muscle damage, but exercise-induced
muscle damage is evident after isometric contractions at a long muscle length and eccentric muscle
contractions, even at low intensity
24. If muscles contract under ischemic conditions, pain develops within about 1 min, IV afferent units are
activated during ischemic contractions, the low tissue pH during ischemic work is an important factor
for the pain
This pressure corresponds to approximately 10–20% of maximal voluntary contraction
It has been shown that intramuscular pressures exceeding 20–40 mmHg (depending on the size of the
muscle) may partially or completely arrest blood flow in the muscle
Interestingly, even at moderate levels of exercise during cycle ergometry, muscle pain can develop
within a few minutes
25. Chronic work-related myalgia
Large, fast fatigable muscle fibers store more glycogen than the small fibers, therefore, the glycogen stores of the small
fibers are easily exhausted, and if the circulation is impeded, they cannot be replenished, the resulting lack of ATP in small
fibers is likely to lead to painful contractures
Depletion of energy resources, chemically bound energy is stored in muscle in the form of glycogen
However, normally this vasoconstrictor influence is counteracted by metabolic substances released from the muscle, if this
balance is disturbed, sympathetic activity could lead to vasoconstriction, even in a working muscle
Increased activity in the sympathetic nervous system, during muscle work, the sympathetic nervous system is activated
and muscle arterioles are under control of the increased sympathetic outflow
Muscle ischemia, little as 10–20% of maximal voluntary contraction of a muscle may be sufficient for occluding the
microcirculation of that muscle