Pain is an unpleasant sensation which is a primarily
protective mechanism that is meant to bring to conscious
awareness that tissue damage is occurring or is about to
occur.
PAIN
• The sensation of pain is accompanied by motivated behavioral responses
(such as withdrawal or defense) as well as emotional reactions (such as
crying or fear).
• Also, unlike other sensations, the subjective perception of pain can be
influenced by other past or present experiences (for example, heightened
pain perception accompanying fear of the dentist or lowered pain
perception in an injured athlete during a competitive event).
• Pain is detected by pain receptors also called “Nociceptors”.
• Pain is said to be a sensation and an emotion.
• Adaptation to pain is poor.
• Pain receptors are specific for Pain but not for the stimulus.
COMPONENTS OF PAIN:
1. Nociception: the body’s detection and signaling of noxious events.
2. Pain: the conscious perception or recognition of the nociceptive
stimulus, and
3. Suffering: the individual’s reaction to pain with emotional, somatic and
autonomic effects along with efforts to avoid or escape pain. (This
reaction differs from person to person & is influenced by age, sex,
culture and personality; the reaction is also affected by the intensity &
duration of pain.)
TYPES OF PAIN
SHARP PAIN
• Also called Physiologic pain.
• Quick in onset.
• Felt within 0.1 sec if a pain
stimulus is applied.
• Sharp & pricking. Also categorized
as acute pain & electric pain.
• Well localized. It is not felt in
many deeper tissues of the body.
• E.g. needle puncturing the skin,
knife cutting a skin, burn.
• Conducted by A-delta fibers.
DULL PAIN
•
•
•
•
•
•
•
•
Also called Pathologic pain or chronic
pain. It includes inflammatory and
neuropathic pain.
Slower in onset.
Starts after 1 second of application and
increases slowly over many seconds &
sometimes minutes.
Greater duration and less localized. It
can lead to almost prolonged and
unbearable suffering.
It is associated with tissue destruction.
Dull, aching pain, slow pain, throbbing
pain, nauseous pain.
It can occur in skin and deeper tissues.
Conducted by C type fibers.
Pain Receptors & their Stimulation
• The pain receptors in the skin and other tissues are all free nerve endings.
• They are widespread in:
- superficial layers of the skin.
- certain internal tissues, such as the periosteum, the
arterial walls, the joint surfaces, and the falx and tentorium in
the cranial vault.
- Deeper tissues are only sparsely supplied with pain endings.
• Pain can be elicited by multiple types of stimuli. They are classified as:
1. Mechanical,
2. Thermal, and
3. Chemical pain stimuli.
In general, fast pain is elicited by the mechanical and thermal types of
stimuli, whereas slow pain can be elicited by all three types.
Pain receptors DO NOT ADAPT AT ALL or if they do, very little.
1.
2.
3.
4.
Tissue Damage
Tissue Ischemia
Chemical substances
Muscle spasm
MECHANISM OF PAIN PRODUCTION
1. Tissue Damage
2. Tissue Ischemia
• When a tissue does not receive the required amount of
blood supply, it becomes painful in a very short time, it
becomes painful in a vey short time.
• Thus, if the blood supply is stopped to the upper limb
by applying a tourniquet, pain appears within 3-5
minutes. If the forearm of the same limb is forced to
exercise, the pain appears within 15-20 seconds.
• Myocardial ischemia, Angina Pectoris and intermittent
claudication are examples of pain due to tissue
ischemia.
Mechanism of Pain production (cont.)
3. Chemical Substances
Some chemicals that excite the chemical type
of pain:
1.
Bradykinin
2.
Histamine
3.
Serotonin
4.
Acetylcholine
5.
Potassium ions
6.
Proteolytic enzymes.
Some chemicals like Substance P and
Prostaglandins enhance the sensitivity of pain
endings but do not excite them directly.
Other chemicals may get deposited in
different tissues of the body and cause pain,
such as urates depositing in the synovial
membranes of joints leading to gouty arthritis
which is a very painful condition.
4. Muscle Spasm
• When muscle spasm, the
blood supply is decreased
leading to decrease in oxygen
supply, increased metabolites
collecting at the site leading to
pain.
• The contracted muscle
compresses its own blood
vessels leading to more
ischemia and more pain.
• This sets up a vicious cycle or a
positive feedback cycle.
ASCENDING PATHWAYS
ASCENDING PATHWAYS
Three-neuron pathways:
• Primary sensory
neurons:
- From external receptors
- Travel through dorsal roots of
spinal cord
• Secondary neurons:
- Make up tracts in spinal cord
and brainstem
• Tertiary neurons:
- From thalamus to primary
sensory cortex
- Travel through internal
capsule
• For conscious perception:
Spinothalamic system
Medial Lemniscal system
• For unconscious perception:
Spinocerebellar
Spino-olivary
Spinotectal
Spinoreticular
1.
2.
Anterior Spinothalamic Pathway: Crude touch, itch, tickle & pressure
Lateral Spinothalamic Pathway: Pain & temperature
ANTEROLATERAL SYSTEM
•
•
The Anterolateral system is made up of:
Anterior Spinothalamic Pathway
Lateral Spinothalamic Pathway
The anterior spinothalamic tract carries fibers for crude touch, tickle, itch and
pressure while lateral spinothalamic carries fibers for pain and temperature.
• There is a double system of pain innervation in the Lateral Spinothalamic tract:
1. NEOSPINOTHALAMIC PATHWAY: For FAST pain carried by A-delta fibers
2. PALEOSPINOTHALAMIC PATHWAY: For Slow pain carried by C fibers.
Because of this double system of pain innervation, a sudden painful stimulus often
gives a "double" pain sensation: a fast-sharp (also called First pain) that is transmitted
to the brain by the Aδ fibers, followed a second or so later by a slow (Second pain)
that is transmitted by the C fibers.
• The A-delta and C fibers carrying pain & temperature information from the body
terminates in the dorsal horn of the spinal cord.
- A-delta fibers terminate in lamina I, V and X (Lamina marginalis of the
gray matter)
- C fibers terminate in lamina I and II (substantia gelatinosa of the gray
matter)
• The distinct termination patterns of A-delta and C fibers in the spinal cord suggest
that the messages are kept separate so that feel two distinct types of pain.
• The primary afferent fibers for pain in the head enter the brainstem through the
trigeminal nerve. The trigeminal distribution includes fibers for both the head and
toothache pain.
• Glutamate is the NT for the pathway for Fast pain while Substance P is the NT for
the pathway for Slow pain.
Even though all pain receptors are free nerve endings, these
endings use two separate pathways for transmitting pain
signals into the central nervous system. The two pathways
mainly correspond to the two types of pain-a fast-sharp pain
pathway and a slow-chronic pain pathway.
ANTERIOR & LATERAL
SPINOTHALAMIC TRACT
Receptors (Mechanoreceptors, Thermal & Pain receptors)
↓
• Fast Pain carried by A-delta fibers (6-30 m/sec)
• Slow Pain carried by Type C fibers (0.5-2 m/sec)
↓
First Order Neuron
↓
Posterior root ganglion (Cell bodies)
↓
Fibers ascend or descend 1-2 spinal cord segments where they are called the
Tracts of Lissaeur
↓
On entering the spinal cord, the pain signals take one of the two pathways:
Neospinothalamic pathway
--Paleospinothalamic pathway
Lamina I of dorsal horn
Lamina II & III of dorsal horn
(Lamina marginalis)
(Substantia Gelatinosa)
↓
↓
Second order neurons
Second order neurons
↓
↓
Decussate immediately through the anterior commissure & then
ascend in the anterior & lateral columns of the opposite side of the spinal cord.
Ascend through the brainstem (medulla, pons & midbrain)
as the Spinal Lemniscus (where fibers of Anterior & Lateral
Spinothalamic tract ascend together in the lower part of
medulla)
↓
Thalamus (VPL nucleus)
Some fibers carrying the slow pain also relay to the Reticular
area, Tectal area and Periacquiductal gray region giving rise to
SPINOTECTAL and SPINORETICULAR tract
↓
Third Order neurons
↓
Somatosensory Cortex
(Some fibers carrying the fibers for slow pain also terminate in
the hypothalamus)
THE ANTEROLATERAL PATHWAY
Why you CANNOT sleep when you are in pain?
• Electrical stimulation in the reticular areas of
the brain stem and in the intralaminar nuclei
of the thalamus, the areas where the slowsuffering type of pain terminates, has a strong
arousal effect on nervous activity throughout
the entire brain. In fact, these two areas
constitute part of the brain's principal "arousal
system." This explains why it is almost
impossible for a person to sleep when he or
she is in severe pain.
What can be done when a person is
suffering from intractable and severe
pain?
Effect of Lesion
Anterior Spinothalamic Tract:
• The destruction of this tract produces little if any tactile
disturbances as touch is also carried in DCML.
• Bilateral lesion of this tract leads to loss of sensations of crude
touch, itch and tickle below the lesion.
• The unilateral lesion of the tract causes loss of sensation below the
level of the lesion.
Lateral Spinothalamic Tract:
• The bilateral section of the tract leads to total loss of pain and
temperature sensations on both sides below the lesion.
• The unilateral lesion causes loss of pain (analgesia) and
temperature (thermoanesthesia) below the level of the lesion on
the opposite side. The contralateral sensory loss extends to a level
one segment below that of the lesion owing to the oblique crossing
of fibers.
DIFFERENCES BETWEEN DCML & ANTEROLATERAL
SYSTEM
DCML
1.
2.
3.
4.
Large, myelinated fibers
Mechanoreceptors.
High velocity: upto 70 meters/ sec.
Spatial orientation is highly
developed. High degree of
localization.
5. Transmits the sensations:
• Tactile localization
• Two-point discrimination
• Pressure
• Stereognosis
• Propriception
• Vibration
ANTEROLATERAL SYSTEM
1.
2.
3.
4.
5.
•
•
•
•
•
•
Small diameter, myelinated as
well as unmyelinated fibers.
Multiple types of receptors.
Low velocity: 1-15 m/sec
Poor spatial orientation. Low
degree of localization.
Transmits the sensations:
Pain
Thermal
Itch
Tickle
Crude touch
Crude pressure
The fibers of this pathway convey proprioceptive impulses to
the cerebellum. It has 2 divisions:
1. Anterior Spinocerebellar Tract
2. Posterior Spinocerebellar Tract
THE SPINOCEREBELLAR TRACT
SPINOCEREBELLAR TRACTS
Anterior Spinocerebellar Tract
• Proprioceptive information.
• Also contains fibers from
the motor pathways so that
the cerebellum is kept
informed about the state of
the motor neuron activity.
• Fibers cross over but then
cross back again the
cerebellar peduncles.
• Terminate in the
cerebellum.
Posterior Spinocerebellar Tract
• Uncrossed.
• Carries information mainly from
the muscle spindle and the
tendon organs of the trunk and
lower limb, regarding position
and movement of individual limb
muscles.
• Axons enter the posterior gray
column and terminate in the
nucleus dorsalis (Clark’s column).
• Ascend on the same side to
terminate in the cerebellar
cortex.
• Fast conducting.
PAIN SUPPRESSION “ANALGESIA”
SYSTEM OF THE BRAIN
• The degree to which a person reacts to pain
varies tremendously. This results partly from a
capability of the brain itself to suppress input
of pain signals to the nervous system by
activating a pain control system, called an
analgesia system.
• Thus, the analgesia system can block pain
signals at the initial entry point to the spinal
cord.
ANALGESIA SYSTEM of
the Brain
It consists of three major components:
(1) The periaqueductal gray and
periventricular areas of the
mesencephalon and upper pons
surround the aqueduct of Sylvius
and portions of the third and
fourth ventricles. Neurons from
these areas send signals to
(2) the raphe magnus nucleus, a thin
midline nucleus located in the
lower pons and upper medulla, and
the nucleus reticularis
paragigantocellularis, located
laterally in the medulla. From these
nuclei, second-order signals are
transmitted down the dorsolateral
columns in the spinal cord to
(3) a pain inhibitory complex located
in the dorsal horns of the spinal
cord. At this point, the analgesia
signals can block the pain before it
is relayed to the brain.
Gate control
Theory of Pain
•
•
•
•
Transmission in nociceptive
pathways can be interrupted by
actions within the dorsal horn of
the spinal cord at the site of
sensory afferent transmission.
This gate mechanism is operated
by a balance between excitation in
large and small peripheral nerve
fibers.
An excess of impulses in large
nerve fibers results in the closure
of the gate and non-production of
pain; on the other hand, relative
excess of impulses in small nerve
fibers opens the gate and produces
pain sensation.
Deep and visceral pain can be
decreased by applying irritating
substances to the skin overlying
deep structures. This is the basis of
the use of the Counterirritation for
the relief of deep and visceral pain.
OPIOIDS
• Opioids are commonly used analgesics (chemicals that relieve the pain)
that can exert their effects at various places in the CNS, including the
spinal cord and dorsal root ganglion.
• The different opioids are:
1. Endorphins: split products of POMC, made in the Pituitary gland as well
as CNS. In the CNS, they decrease perception of pain (analgesic). They
are up to 30 times more analgesic than morphine.
2. Enkephalins: are synthesized in the chromaffin cells of the adrenal
medulla & released with catecholamines when sympathetic nervous
system is stimulated,e.g in stress.
3. Dynorphin: has been detected in the duodenum, posterior pituitary and
hypothalamus.
There are interneurons in the superficial region of the dorsal root ganglion
where nociceptive afferents terminate. Opioid receptors (OR) are located on
the terminals of nociceptive fibers and on dendrites of dorsal root horn
neurons .
Activation of OR results in a decrease in release of glutamate and substance P
leading to reduced transmission of from nociceptive afferents.
Irritation of a visceral organ frequently produces pain that is felt
not at that site but in a somatic structure that may be some
distance away. Such pain that is referred to a somatic structure is
called Referred Pain.
REFERRED PAIN
REFERRED PAIN
• E.g: Cardiac pain may be
referred to the right arm, the
abdominal region, or even the
back, neck or jaw.
When pain is referred, it is usually
to a structure that developed from
the same embryonic segment or
dermatome as the structure in
which the pain originates. E.g, the
arm and heart have the same
segmental origin.
CONVERGENCE –PROJECTION
THEORY: The basis for referred
pain may be convergence of
somatic and visceral pain fibers on
the same second-order neurons in
the dorsal horn that project to the
thalamus & then to
somatosensory cortex.
HYPERALGESIA
• It is an exaggerated response
to a noxious stimulus.
• Chemicals released at the site
of injury further directly
activates receptors on sensory
nerve endings leading to
inflammatory pain.
Nociceptors become more
SENSITIVE…..
• There is also release of
substance P and bradykinin,
which can further sensitize
nociceptive terminals.
ALLODYNIA
•
•
•
It is a sensation of pain in response
to a normal, painless stimulus.
E.g. painful sensation from a warm
shower when the skin is damaged
by sunburn.
Damaged nerve fibers undergo
sprouting, so fibers from touch
receptors synapse on spinal dorsal
horn neurons that normally receive
only nociceptive input. This
explains why painless stimuli can
induce pain after injury. The release
of substance P and glutamate leads
to excessive stimulation of NMDA
receptors on spinal neurons, a term
called “wind up” that leads to
excessive activity of pain
transmitting pathway.
It is the area of the cerebral cortex that receives primary sensory
impulses directly from the relay centers in thalamus. It has 3 parts:
1. Somatosensory Area –I
2. Somatosensory Area- II
3. Association Cortex
The term somesthetic cortex is reserved for Somatosensory Area-I only.
SOMATOSENSORY CORTEX
Somatosensory cortex- I
• It is also called the Primary
Somesthetic area.
• It comprises of area 3,1,2.
• The sequence of distribution of
body areas is represented by a
sensory homunculus which is a
small figure of a man showing the
size of the various parts of the
body in proportion to
distribution.
• Lips occupy the greatest area
followed by the face and the
thumb. This is because many
more receptors lie in the lips than
in any other part of the body.
Somatosensory cortex- II
•
•
Its function is not well known.
It seems to be concerned more with the
spinothalamic tract and pain sensibility.
• It further elaborates the sensory input
received by Somatosensory Area I.
Somatosensory Association Area:
• These are Brodmann’s area 5 & 7.
• It receives information from area I & II
and also from the visual cortex and the
auditory cortex and thalamus.
• This area is responsible for decoding
the sensory information.
• Removal of this area causes
amorphosynthesis (loss of appreciation
of form of objects).
THE SENSORY HOMUNCULUS
What happens when Area-I is damaged?
• The sense of fine touch, position, stereognosis are most
affected. Higher functions are lost. Crude touch is intact
which shows that this is done in the thalamus.
• Two-point discrimination is decreased.
• Subject cannot judge the weight of an object.
• Astereognosis occurs.
• Fine grade changes in temperature are not appreciated.
• Orientation of different body parts relative to each other is
lost. (Proprioception)
• Pain is least affected but is poorly localized and poorly
graded.
PHANTOM LIMB
PAIN
It is defined as pain felt by
an amputee that seems to
be located in the missing
limb.
The theory explaining it is
that brain can recognize if
sensory input is cut off.
The area of the brain that
once received input from
the leg and foot now
responds to stimulation of
the stump, in exactly the
same way it did when the
limb was attached.
Mirror box therapy is used
for treatment of Phantom
limb pain.