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Musculoskeletal Pain

Dewi Irawati
Department of Physiology
Medical Faculty Universitas Indonesia

Objectives

Definition, classification and characteristics


Molecular and cellular neurophysiology

Transduction
Transmission
Perception
Modulation, integration and synaptic plasticity
Sensitization (peripheral/central)

Factors affecting

Genetic
Emotion
Cognitive
Behavior

Objectives

Special muscle pains - Ischemic,


Cramp, DOMS (Delayed Onset Muscle
Soreness)
Problem musculoskeletal pain,
especially RSI (Repetitive Strain
Injury)
The basic of musculoskeletal pain
management

What is Pain?

An unpleasant sensory and


emotional experience Merskey and Bogduk, 1994
Pain is recognized as a complex
phenomenon derived from sensory
stimuli
Pain is interpreted by the individual

There are no biological markers for pain


Self-reporting is the most accurate
evidence of pain

Pain

An unpleasant sensory and emotional


(psychological) experience associated with
actual or potential tissue damage, or
described in terms of such damage.
(Association for the Study of Pain)

Four main dimensions:

Sensory-discriminatory
Affective and emotional
Cognitive
Behavioral

Pain

A complex experience embracing


physical, mental , social, and
behavioral processes,
compromising the quality of life
of many individuals.
(SSI Commission For Evaluation of Pain)

Pain

Major symptom in many medical


conditions, and can significantly
interfere with a person's quality of life
and general functioning.
Motivates us to withdraw from
potentially damaging situations, protect
a damaged body part while it heals, and
avoid those situations in the future.

How does pain occur?

It is initiated by stimulation of
nociceptors in the
peripheral nervous system, or by
damage to or malfunction of the
peripheral or
central nervous systems.

Why is it Important to
Focus on Pain?

A symptom most expected and most feared by


dying patients.
Unrelieved pain can have enormous
physiological and psychological effects
Pain negatively affects the quality of life by
impairing daily functions, social relationships,
sleep and/or self worth.
Although pain can be relieved in up to 90%
cases, many patients receive inadequate or no
treatment

Unrelieved Pain
Chronic (moderate to severe) pain
Often reported by patients as
OUT OF CONTROL
They had not found adequate relief
despite new advanced pain
medications

Consequences

Inadequate pain management

Attitude of doctors, nurses


and patient
Fear of drug usage (narcotics)
Insufficient knowledge
Laws and regulation

Somatic Pathways

Receptor

Sensory neurons

Threshold
Action potential
Primary medulla
Secondary thalamus
Tertiary cortex

Integration

Receptive field
Multiple level

Neurologic transmission
of pain stimuli
.

Adequate noxious
stimuli
depolarizes
specific receptors
action potential
occurred
conducted along
the primary
afferent fibers to
projection
neurons in the
substantia
gelatinosa at the
dorsal horn of the
spinal cord, where
the "gating"
mechanism
occurs.

TRANSDUCTION AND TRANSMISSION

Transduction occurs as the energy of the stimulus is converted


to electrical energy.
Transmission of the stimulus takes place when this energy
crosses into a nociceptor at the end of an afferent nerve fiber.
Two types of peripheral nerve fibers conduct painful stimuli:
the fast, myelinated A-delta fibers and the very small, slow,
unmyelinated C-fibers.
A-fibers send sharp, distinct sensations that localize the
source of the pain and detect its intensity.
C-fibers relay impulses that are poorly localized, burning, and
persistent. For example, after burning a finger, a person
initially feels a sharp localized pain as a result of A-fiber
transmission. Within a few seconds the pain becomes more
diffuse and widespread as a result of C-fiber transmission.

Connections between primary


afferent fibers and the spinal cord

AP along primary
nociceptor afferent causes
the release of transmitters
(eg, glutamate and P
substance) from the nerve
terminal which then
stimulates secondary
neurons in the dorsal horn
of the spinal cord, which in
turn send the noxious
signal to the brain. AP
action potential. (Courtesy
of Elan Corporation)

http://www.springerimages.com/Images/MedicineAndPublicHealth/1-10.1007_s11916-

Connections
There
is a very
precise laminar
fibers
organization of
the dorsal horn of
the spinal cord;
subsets of
primary afferent
fibers target
spinal neurons
within discrete
laminae.

between primary afferent


and the spinal cord

The
unmyelinated,
peptidergic C
(red) and
myelinated A
nociceptors
(purple),
terminate most
superficially,
synapsing upon
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2852643

afferent fibers and the spinal


cord
The unmyelinated,
non-peptidergic
nociceptors (blue)
target small
interneurons (blue) in
the inner part of
lamina II.
By contrast, innocuous
input carried by
myelinated A fibers
terminates on PKC
(yellow) expressing
interneurons in the
ventral half of the
inner lamina II.
A second set of
projection neurons
within lamina V
(purple) receive
convergent input from
A and A fibers.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC285264

Somatic
Pathways
A subset of the
projection neurons
crosses over to the
opposite side of the
spinal cord ascend
to the higher centers
in the brain via the
spino-thalamic tracts,
to the thalamus and
higher centers of the
brain, including the
reticular formation,
limbic system, and
somato-sensory
cortex, providing
information about the
location and intensity
of the painful
stimulus.

Anatomy of the pain pathway

Other projection neurons engage


the cingulate and insular
cortices via connections in the
brainstem (parabrachial nucleus)
and amygdala, contributing to
the affective component of the
pain experience.
This ascending information also
accesses neurons of the rostral
ventral medulla and midbrain
periaqueductal gray to engage
descending feedback systems
that regulate the output from the
spinal cord.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC285264

PERCEPTION

When pain stimuli reach the cerebral


cortex, the brain interprets the signal;
processes information from experiences,
knowledge, and cultural associations; and
perceives pain.
Thus, perception is the awareness of
pain. The somatosensory cortex identifies
the location and intensity of pain, and the
associated cortex determines how an
individual interprets its meaning.

Perceptual categories

Pricking (First pain)

Quality: sharp
Temporal: Initial pain sensation Brief
PNS axons: A fibers
CNS pathway: Somatosensory to thalamus &
cortex

Perceptual categories

Burning (second pain)

Quality: Dull, aching


Unpleasant
Temporal: Later, more long-lasting pain
sensation
PNS axons: C fibers
CNS: Formatio resticularis
Periaqueductal gray
Hypothalamus
Central thalamus

MODULATION

Once the brain perceives the pain, the body


releases neuromodulators, such as endogenous
opioids (endorphins and enkephalins), serotonin,
norepinephrine, and gamma aminobutyric acid.
These chemicals hinder the transmission of pain
and help produce an analgesic, pain-relieving
effect.
This inhibition of the pain impulse is called
modulation. The descending paths of the efferent
fibers extend from the cortex down to the spinal
cord and may influence pain impulses at the level
of the spinal cord.

Neural Pain Pathway


Stimulation of the
descending
pathways can reduce
and even abolish
some forms of pain.
Many animals (and
humans) appear to
tolerate pain and
show very few
behavioural
alterations following
a painful insult. This
may be due in part
to the central
inhibitory effects and
in part to other
biological factors.

The diagram shows pathways coming from the


brain down to the spinal cord.
http://iris.uwaterloo.ca/ethics/animals/CCAC_modules/modul

Musculoskeletal Pain
Pain induced by
musculoskeletal disorder
(skeleton, muscles, cartilage, tendons,
ligaments, joints, and other
connective tissue)

Musculoskeletal Pain - Background

Commonest cause of acute and


chronic pain
Acute: muscle cramps, ankle sprains
etc
Chronic: e.g. pain from arthritis and
low back pain very widespread
problems
Important protective role. Protects
joints from overuse. Joint damage
develops in pain-insensitive

Musculoskeletal Pain
Characteristic of host
Biological: genetics, sex, endogenous pain control
Psychological: anxiety, depression, coping, behavior
Cognitive

Environment
Disease
History
Present disease

Pai
n

Socialization
Lifestyle
Traumas
Cultural: expectations, upbringing,
role

What are muscle


Nociceptors?

Sensory receptors that responds to


potentially damaging stimuli
Free nerve endings
Located in the muscle membrane,
joints,

Classification of afferent nerve


fibers
Different terminology used for muscle or joint nerves from
that used for cutaneous nerves

Fibre type

Muscle/Joint

Cutaneous

Small myelinated

Group III

A-delta

Non-myelinated

Group IV

Types of Group III and IV afferent


units

Nociceptors. The majority. Most


polymodal, some mechanical, some
sleeping/silent . No obvious difference
between Group III and IV (unlike skin).
Ergoreceptors. Only muscle, not joints.
Respond to muscle contraction and to
normal metabolites (e.g. lactate).
Thermoreceptors. Small numbers of
sensitive thermoreceptors have been
described from skeletal muscle.

NOCICEPTORS

One particular nociceptor, vanilloid receptor-1


(VR1), relays sensory messages to the brain in
response to thermal and painful chemical stimuli
generally regarded as the major pain sensor.
When the cellular environment becomes acidic,
both VR1 and a second nociceptor - acid sensing
ion channels (ASICs) - are activated.
P2X receptors, the ionotropic receptors activated
by ATP, is underscored by the variety of pain
states in which this endogenous ligand can be
released. P2X receptors can be involved in pain
mechanisms both centrally and in the periphery.

Somatosensory specificity:

Sensitization

An increase in the excitability of


neurons more sensitive to stimuli
or sensory inputs
Two forms:

responsiveness is increased, so that


noxious stimuli produce an exaggerated
and prolonged pain
thresholds are lowered so that stimuli
that would normally not produce pain
now begin to (allodynia)

Peripheral Sensitization

A reduction in threshold and an


increase in responsiveness of the
peripheral ends of nociceptors
Contributes to the pain
hypersensitivity found at the site of
tissue damage and inflammation

Sensitization of joint and muscle


nociceptors

Inflammation produces marked


sensitization in many joint and
muscle nociceptors.
Silent (sleeping) nociceptors start
to fire when inflammation occurs.

Inflammatory Pain

Central Sensitization

Increase in the excitability of neurons


within the central nervous system
normal inputs begin to produce
abnormal responses
Altered strength of synaptic
connections between the nociceptor
and the neurons of the spinal cord
(activity-dependent synaptic plasticity).
Involving many transmitters

Spinal cord neurons responding to


noxious musculoskeletal stimuli

Afferents terminate predominantly in lam I


and V (like noci cutaneous afferents; unlike
non-noci muscle afferents)
Only responding to strong, noxious, inputs
(noci specific)
Wide dynamic range neurons with deep
somatic fields are found
Central sensitization in response to muscle
or joint inflammation is readily seen;
thresholds fall and receptive fields enlarge

Inflammatory pain from muscle and


joint

Inflammation is a major cause of


muscle and joint pain, e.g.
rheumatoid arthritis
Nociceptor sensitization play a large
part
Strong evidence for central
sensitization
Stimulation of muscle nociceptors is
very effective in generating spinal
cord wind-up

Special muscle pain

Ischemic muscle pain

Contraction with reduced blood


supply
Prolonged contraction
Major problem in elderly with
peripheral vascular disease
(Intermittent claudication)
Angina is ischemic muscle pain from
the heart
Several metabolic diseases cause
exercise-induced ischemic pain

Special muscle pain

Cramp

Due to ischemia
Can be due to locally generated contractions
(contractures) in some metabolic diseases
Usually exercise induced EIC (or EAMC exercise associated
muscle cramps)

Excessive contraction driven by motor nerve firing


Occurs in fatigue muscle
Can sometimes be relieved by stretch
Some theories claim potassium or calcium or
magnesium are more important than sodium or
water.

Special muscle pain

DOMS

Delayed onset muscle soreness


8 hours post exercise several days
Associated with eccentric contraction
e.g. running downhill
Reduced on repetition of exercise
Probably triggered by slowly
developing inflammation

Musculoskeletal pain conditions of


uncertain cause

Fibromyalgia

Low back pain

RSI

Musculoskeletal pain conditions of uncertain cause

Fibromyalgia

Prevalence 1-2%
Widespread muscle ache/pain
Local tender points
Unknown cause (has been used as criterion for
diagnosis)

Psychological factor?

Musculoskeletal pain conditions of uncertain cause

Low back pain

Most common chronic pain problem


Cause sometimes clear e.g. disc
protrusion
Often no obvious pathology
Often work-related A major
economic problem, as well as health
issue.

Musculoskeletal pain conditions of uncertain cause

Repetitive Strain Injury - RSI

Nearly as common as low back pain


Affects a relative young age group
Work related? (Patient usually think so blame
keyboard or light industrial work)

Often leads to job loss add stress to


already stressful situation

Musculoskeletal pain conditions of uncertain cause

Repetitive Strain Injury - RSI


What is evidence for organic disease in RSI?

Sensory changes. Elevated vibration


threshold, reduced flare (Greening, J., Lynn, B. &
Leary, R. (2003). Pain, 104 (1-2), 275-281)

Changes in the median nerve environment


sufficient to impede normal sliding during
limb movements (Greening, J. et al. (2001) J Hand Surg
(UK, Europ) 26B, 401-406)

Animal models show repetitive low force


movements can cause tissue damage (Barbe
M F et al (2003) J Orthop.Res 21(1):167-176)

Hypothetical scheme to explain


NSAP (National Standards Assessment
Program)

Psychosocial factors

Stress

Altered periRepetitive
pheral nerve
mechanical
environment.
stress
Multiple sites
Musculoskeletal
tissue
inflammation

Ectopic
firing
(+Nervi
nervorum?)

Central
nociceptive/
pain
systems

PAIN

Nociceptor
sensitization

From Lynn, 2005, Textbook of Pain, 5th ed

Pain Management

Non Pharmacology

Physical
Exercise

Surgical

Acupuncture

Psychotherapy
Psychology

Physically
Tranquilizer

Massage

Anesthetic
Drugs

Pain
Killers
Drugs

Pharmacology

Musculoskeletal Pain

Summary

Most common cause of acute and


chronic pain
Pain is a warning signal that helps to
protect the body from tissue damage
and has an essential function in
survival.
There are 4 steps in pain mechanism:
transduction- transmission- modulation/sensation and perception .

Musculoskeletal Pain

Summary

Plentiful of muscle and joint


nociceptors, readily sensitized
The role of cerebral cortex in pain
perception is to modulate
nociceptive impuls.
Special muscle pains such as cramp
(ischemia) and DOMS (inflammation)
are reasonably well understood

Musculoskeletal Pain

Summary

Important chronic musculoskeletal


pain conditions (fibromyalgia, LBP,
RSI) are less well understood.
Neurological aspects may be more
important
The treatment of musculoskeletal
pain is based on pain mechanisms
and pathways

Useful web-sites

http://www.georgiapainphysicians.com/l2
_edu_pharma_mod2_slides.htm
http://www.archway.ac.uk/Activities/Depar
tments/SHHP/current/Pain/fop2j_cramp.htm
http://cme.medscape.com/viewarticle/495
071
http://www.wellcome.ac.uk/en/pain/microsi
te/science4.html
http://www.physsportsmed.com/issues/199
9/11_99/schwellnus.htm

Thank
You