 The International Association for the Study

of Pain (IASP) has defined pain as :

‘…an unpleasant sensory and emotional

experience associated with actual or
potential tissue damage, or described in
terms of such damage’.
Physic/ Psycologic/
sensory emotional

PAIN
Why pain is important to
the human body ??
 Protective function  withdrawal
reflex response to an acute noxious
stimulus
 Avoidance of potentially harmful
situations and possible injury
 Pain  the 5th vital sign
Based on the duration of pain :

 Acute pain :
 Somatic pain
▪ Superficial somatic pain
▪ Deep somatic pain
 Visceral pain
 Reffered pain

 Chronic pain
 Acute pain :

 Pain that arises suddenly and temporarily. This pain is

characterized by autonomic nervous activity such as:
tachycardia, hypertension, hyperhidrosis, pallor and
midriasis and facial changes.

 Most forms of acute pain are self-limited or resolve

with treatment in a few days or weeks.
 Chronic pain :
 Prolonged pain may be months without signs of
autonomic activity except acute attacks. The pain may
be a pain that persists after wound healing (illness /
surgery) or initially in the form of acute pain and then
settle for more than 3 months.
 Biopsychological disease
 Causes of chronic pain :
▪ Cancer pain
▪ Non-cancer pain
Based on the neurobiologic process of pain :
 Nociceptive pain (Acute pain)
 Somatic pain
▪ Superficial somatic pain
▪ Deep somatic pain
 Visceral pain
 Reffered pain

 Inflamatory pain (Protective pain)

 Pathologic pain
 Neuropatic pain
 Disfunctional pain
 Nociceptive pain (acute pain) :
 Pain arising from the activation of nociceptors by
powerful stimuli that threaten the integrity of human
tissue

 Such strong stimuli may be mechanical, thermal (heat /

cold) or chemical stimuli

 This pain is characterized by autonomic nervous activity

such as: tachycardia, hypertension, hyperhidrosis, pallor
and midriasis and behaviour changes.
 Nociceptive pain (acute pain) :
 Somatic pain :
- Superficial somatic pain :
Pain that stimulus comes from the skin,
subcutaneous tissue and mucous membranes. Pain
is usually felt as burning, sharp and localized

- Deep somatic pain :

Dull pain and unlocalized due to stimulation of
scletal muscle, bone, joints, connective tissue
 Nociceptive pain
 Visceral pain :
▪ Pain due to stimulation of visceral or membrane
organs covering it (pleuraparietalis, pericardium,
peritoneum). This type of pain is subdivided into
localized visceral pain, localized parietal pain, visceral
and parietal reffered pain.
▪ Commonly innervated by C nerve fibers
 Nociceptive pain
 Reffered pain :
▪ Pain that occurs at a different location from the origin
organ (eg. Shoulder pain at the left side caused of
miocardial infacrtion; flank pain caused of renal or
ureter disease)
▪ The area of pain is innervated by the same spinal
segment with its original pain as nerve impulses from
the skin and viscera are join
▪ Mechanism : afferen nerve transmitted wrong
perception
 Inflamatory pain :
 Pain that arises due to the inflammatory process
following the tissue damage or infection.
 Characterized by the onset of spontaneous pain in the
absence of a stimulus
 In this condition occurs hyperalgesia and allodynia
 As a protective pain because it avoids movement or
touch on the inflamed area.
 Eg. Toothache, abcess
 Pathologic pain
 No function as protective pain
 Maladaptive caused by change in nervous system
 Not as a symptom of tissue damage but its a nervous
system disease
 Pathologic pain
 Neurophatic pain :
▪ Pain that is preceded or caused by lesions or primary
dysfunction of the peripheral nervous system.
▪ This is caused by injury to peripheral nerve fiber
pathways, infiltration of cancer cells in nerve fibers,
and the cutting of peripheral nerves.
▪ Eg. Post Herpetic Neuralgia (PHN), trigeminal
neuralgia, phantom pain post limb amputation.
 Pathologic pain
 Disfunctional pain :
▪ If there is no evidence of nerve damage or dysfunction
both peripheral and central nerves.
▪ The main picture is a chronic complaint, can be spread
throughout the body or in a specific area of the body,
accompanied by strengthening of pain signal or
abnormal sensitivity to pain.
▪ Prominent symptoms are spontaneous pain without a
strong stimulus or inflammation
▪ Eg. Fibromyalgia, irritable bowel syndrome, tension
headache, etc.
Based on the degree of pain :
 Mild pain :
 The pain disappears, especially during daily activities
and before bed
 Moderate pain :
 A continuous pain, disturbed activity that is only lost
when the patient sleep.
 Severe pain :
 Pain continuously throughout the day, the patient can
not sleep and often awake due to pain
 One of the most important functions of the
nervous system is to convey information
about the threat of bodily harm
 The nerve that detects the pain is called
nociception.
 Nociception includes conveying peripheral
information from specialized receptors on
tissues (nociseptors) to the central structures
of the brain.
 The components of pain system :

 Special receptors called nociceptors, in the

peripheral nervous system, detect and screen out
the intensity and type of noxious stimuli. (1st
order neuron )

 The primary afferent nerve (A-delta and C nerve

fiber) transmits noxious stimulus to CNS.
 The components of pain system :

 The dorsal horn of the spinal cord is the site of the

relationship between the primary afferent fibers
with the second neuron and the complex site of
the relationship between local excitation and
interneurone inhibitors and the descending tract
of inhibitors of the brain.
 The components of pain system :

 The nosiseptic asending tract (eg, lateral and

ventral spinothalamic tract) conveys signals to
higher areas of the thalamus. (2nd order)

 The thalamo-cortical tract that connects the

thalamus as the central relay of sensibility to the
cerebral cortex in the post central gyrus. (3rd
order)
 The components of pain system :
 Higher area involvement in painful feelings,
affective components of pain, memory of pain
and pain associated with motor responses
(including withdrawal response).

 The system of descending inhibitors alters the

nosiseptic impulses that come at the level of the
spinal cord.
 It is a receptor that is the free nerve endings
of the sensory nerves
 Not special like Corpus Meissner or Paccini
 Scattered throughout the body especially on
the skin, muscles, tissues, joints, viscera,
meninges or blood vessels
 Plays a role in detecting strong stimulus
(noxious stimulus)
 There are 2 type of stimulus :
 Noxious stimulus
 Innocous stimulus

 Nosiseptor can only respond to strong stimulus

 High Threshold Nociceptors

 Respons to :
 Mechanic stimulus  Mechanoreceptors
 Thermal stimulus  Thermoreceptors
 Chemical stimulus  Chemoreceptors
 Sensory afferent nerve fibers
 Pain is conducted along three neuronal pathways
that transmit noxious stimuli from the periphery to
the cerebral cortex

 The cell bodies of primary afferent neurons (first

order neuron) are located in the dorsal root ganglia,
which lie in the vertebral foramina at each spinal cord
level.

 Each neuron has a single axon that bifurcates, sending

one end to the peripheral tissues it innervates and
the other into the dorsal horn of the spinal cord.
 Sensory afferent nerve fibers

 In the dorsal horn, the primary afferent neuron

synapses with a second-order neuron whose axon
crosses the midline and ascends in the contralateral
spinothalamic tract to reach the
thalamus.

 Second-order neurons synapse in thalamic nuclei with

third-order neurons, which in turn send projections
through the internal capsule and corona radiata to the
postcentral gyrus of the cerebral cortex
 Primary afferent nerve fibers
 2 type of sensory afferent :
▪ Primary afferent nerve fiber deliver a
weak stimulus (innocous stimulus) that
feels painless  Aβ nerve fiber
▪ Primary afferent nerve fiber deliver a
strong stimulus (noxious stimulus) that
feel as pain  Aδ and C nerve fiber
 There are 5 electrophysiological
processes that follow a process of
nociception :
 Transduction
 Conduction
 Modulation
 Transmission
 Perception
 PERCEPTION

TRANSDUCTION

TRANSMISSION
MODULATION
CONDUCTION
 Transduction
 Changes in excitatory pain (noxious
stimuli) into electrical activity on sensory
nerve endings.
 Algesic substances such as prostaglandins,
serotonin, bradykinin, leukotriene, P
substance, potassium, histamine, lactic
acid, and others will activate or sensitize
pain receptors.
 Transduction
 For thermal stimulus  Transient
Receptor Potential Vanilloid 1 (TPRV
1)  pain at temp >42°C
 For cold stimulus  Transient
Potential Melastatin (TPRM) or
Transient Receptor Potential Ankyrin
1 (TPRA 1)  pain at temp <12°C
 Transduction
 Afferent A delta and C nerve fibers are
sensory nerve fibers that have the
function of forwarding the sensory pain
from the periphery to the central nervous
system.
 The interaction between an algesic
substance with a pain receptor causes the
formation of a pain impulse.
 Conduction
 The process of propagation and
amplification of the action potential from
the end of the nerve to the dorsal horn of
the spinal cord.
 Involves the A-delta and C nerve fibers,
both of which have differences in receptor
and neurotransmitter which are released
in the dorsal horn of the spinal cord
 Conduction
 The A-delta nerve fibers :
▪ myelinated
▪ impulse propagation faster
▪ sensitive to the thermal and mechanical
stimulus (mechanothermal nociceptors)
▪ Neurotransmiters release : glutamate
 Conduction
 The C nerve fibers :
▪ unmyelinated
▪ impulse propagation slower
▪ sensitive to the thermal, mechanical and
chemical stimulus (Polymodal
nociceptors)
▪ Neurotransmiters release : glutamate and
P substance (polypeptida)
 Modulation
 Interaction between the endogenous
analgesic system (endorphins, NA, 5HT)
and the input of pain into the dorsal
horn of spinal cord.
 The pain impulses passed on by the A-
delta and C fibers to the nociception
neurone cells in the dorsal horn of the
spinal cord are not all transmitted to the
central via the spinothalamic tract.
 Modulation
 If the incoming impulse is more
dominant, then the patient will feel the
sensible pain.
 If the effect of a stronger inhibition
system, then the patient will not feel
sensible pain.
 Transmission
 The process of moving electrical impulses
from the first neuron to the second neuron,
occurs in the dorsal horn of the spinal cord,
then rises through the spinothalamicus
tract to the thalamus and midbrain.

 From thalamus turns into a third neuron to

the cerebral cortex in somatosensorik,
where pain is felt in the form of localization,
intensity and duration
 Transmission
 Through the spinoreticular tract to
the thalamus then to the limbic
system where the emotional pain
is felt to be anxious, frightened or
crying
 Perception
 A very complex process that still unclear
known until now.
 From functional MRI (fMRI) show that in
areas of the brain that are consistently
activated in an acute pain are
somatosensorik, insula, anterior cingulate
cortex, prefrontal cortex and thalamus
play a role in pain perception  “Pain
Matrix”
 Perception
 Somatosensory plays a role in sensory
of pain and limbic systems in
emotional aspect of pain.
 Then pain is “an unpleasant sensory
and emotional experience”
 Gate Control Theory of Pain
 Descenden Inhibition
 Gate Control Theory of Pain
 First proposed by Ronald Melzack and
Patrick Wall in 1965 to illustrate the
neuronal network underlying pain
modulation (a neurologic “gate”) in the
spinal dorsal horn.
 Gate Control Theory of Pain
 According to this theory  painful
information is projected to the
supraspinal brain regions if the gate is
open, whereas painful stimulus
is not felt if the gate is closed by the
simultaneous inhibitory impulses
 Gate Control Theory of Pain
 Ex., rubbing the skin at the bumped area
activates large-diameter myelinated afferents
(Aβ), which are “faster” than Aδ fibers or C
fibers conveying painful information.
 These Aβ fibers deliver information about
pressure and touch to the dorsal horn and
override some of the pain messages (“closes
the gate”) carried by the Aδ and C fibers by
activating the inhibitory interneurons in the
dorsal horn
 Descenden Inhibition
 Periaquaductal Grey (PAG) and Rostral
Ventromedial (RVM  important place in
inhibition process descenden modulation

 Both of them have many opioid

receptors and endogenous opioids
 Descenden Inhibition
 This descending inhibition ends in the
dorsal horn of the spinal cord and inhibits
the transmission of pain

 This inhibition is monoaminergic, using

noradrenaline and serotonin as
neurotransmitters
 Sensitization of nociceptors by
proinflammatory mediators so that the
threshold of activation decreases followed by
a larger response

 Damage to tissue or surgery will lead to the

release of inflammatory mediators 
produce “sensitizing soup”
 There are two very important mediators :
 ATP derived from the destruction of tissue
cells that will stimulate direct nociceptors
 Prostaglandin synthesis from arachidonic
acid that sensitizes nociceptors so that they
are easily aroused with greater responses
 This peripheral sensitization causes a weak
stimulus that is not normally perceived as
pain now perceived as pain  Allodynia

 Induced by neurohormonal changes in the

area of injury or inflammation

 To suppress this process can be done by

suppressing proinflammatory mediators,
especially prostaglandins  NSAID
 A condition in which the excitability of central
central nervous neurons in the spinal cord is
increased, so a normal stimulus will result in
an abnormal response

 In this condition low threshold nerve fibers

can activate neurons in the spinal cord that
normally just response to noxious stimulus.
 One form of central sensitization is wind-up of
dorsal horn neurons
 The second form of central sensitization is a
heterosynaptic activity-dependent plasticity
that outlasts the initiating stimulus for tens of
minutes
 Other forms of central sensitization include
long-term potentiation, transcription-
dependent central sensitization, loss of
inhibition, and rearrangement of synaptic
contacts
 This central sensitization process shows that
the nervous system is not a hardwire, but
has the ability to change like plastic 
Neuroplasticity

 This plasticity should disappear after wound

healing is complete, but if settled after the
healing period is complete then this will be
able to become chronic pain
 Acute pain will cause changes in the
body.
 Pain impulses by afferent fibers 
forwarded to :
 nociception neurone cells in the dorsal
horn of the spinal cord,
 neuron cells in the anterolateral horn
and anterior horn of the spinal cord
Respiratory system :

 Increased metabolic rate  increased body

oxygen demand and carbon dioxide production
 increase in minute ventilation  increase in
the work of the respiratory system

 Decreased thoracic wall movement 

decreases tidal volume and functional residual
capacity  leads to the occurrence of
atelectasis, intrapulmonary shunting,
hypoventilation and hypoxemia.
Cardiovascular system :

 Vasoconstriction  decreased tissue

perfusion  tissue hypoxia

 Change of body hemodynamics such as

hypertension, tachycardia and increased
systemic vascular resistance.

 Pain causes an increase in myocard oxygen

demand  lead to myocardial ischemia
Gastrointestinal system :
 Sympathetic nerve stimulation  increases the
resistance of the sphincter and decreases the
motility of the gastrointestinal tract  ileus 
abdominal dystention  decrease lung
expansion
 Hypersecretion of gastric acid  ulcers and
along with decreased intestinal motility,
potentially leading to aspiration pneumonia.
 Nausea, vomiting, and constipation.
Urogenital system :

 Sympathetic nerve stimulation increase

increases sphincter tone and decreases
urinary motility  urinary retention
Urogenital system :

 Sympathetic nerve stimulation increase

increases sphincter tone and decreases
urinary motility  urinary retention
Endocrine system :
 Stress increases catabolic hormones
(catecholamines, cortisol, and glucagon) and
decreases anabolic hormones (insulin and
testosterone).
 Patients develop a negative nitrogen balance,
carbohydrate intolerance, and increased lipolysis.
 The increase in cortisol, renin, angiotensin,
aldosterone, and antidiuretic hormone results in
sodium retention, water retention, and secondary
expansion of the extracellular space
Hematology system :

 Stress-mediated :
 increases in platelet adhesiveness
 reduced fbrinolysis,
 hypercoagulability
Immune system :

 The neuroendocrine stress response :

 Produces leukocytosis
 Depress the reticuloendothelial system.
 Predisposes patients
to infection.

 Stress-related immunodepression may

also enhance tumor growth and metastasis
Psychological Effects

 Anxiety and sleep disturbances are

common reactions to acute pain.
 With prolonged duration of the pain,
depression is not unusual. Some
patients react with frustration and anger
that may be directed at family, friends,
or the medical staff
 Tanra, A.H., Aribawa, I.G.N.M, Widana, W. 2017.
Patofisologi Nyeri dalam Dasar Manajemen Nyeri &
Tatalaksana Multi Teknik Patient Controlled
Analgesia. Sagung Seto. Jakarta. Hal. 1-31
 Rosenquist, R.W., Vrooman, B.M.2013. Chronic Pain
Management in Morgan & Mikhail’s Clinical
Anesthesiology 5th ed. McGraw-Hill Education, LLC.
New York. USA. pp. 1023-1039.
 Macres, S.M., Moore, P.G., Fishman, S.M. 2017.
Acute Pain Management in Clinical Anesthesia 8th
ed. Wolters Kluwer. Philadelphia. USA. pp. 3919-
3939.
 Yang, H., Bie, B., Naguib, M.A. 2015. Pain
Physiology in Stoelting’s Pharmacology and
Physiology in Anestetic Practice 5th ed.
Wolters Kluwer Health. USA. pp. 205-215.
 Sarantopoulos, C. 2006. Pain Pathway and
Mechanism in Pain Medicine The Requisites in
Anesthesiology. Mosby, Inc. USA.pp. 1-14