Introduction to Pain

Andi Husni TANRA

Professor of Anesthesiology
Department of Anesthesiology, IC and Pain Management
Faculty of Medicine Hasanuddin University
Makassar
 What is pain?
Poisons

Tissue damage

Release of mediators

Stimulation of nociceptors

Transmission to CNS

2
How do we feel pain?
In normal situation!

Pain
Transmission
Perception
Modulation

Conduction
Noxious
stimulus
Transduction
Stimulate
Nociceptors
 Regarding to the function of pain. 
TWO KINDS OF PAIN
*Good Pain, is an alarm symptom, tell us that something
wrong in our body Acute Pain, pain with nociception
(nociceptive pain). alarm protection.
Disini nyeri seperti bel rumah  bunyi kl ada tamu

*Bad pain, is a disease entity, no nociception,

nothing wrong but patient feel severe pain  makes patient
suffering Chronic Pain.
Disini nyeri seperti bel rumah yg korsleting  tidak ada
tamu tapi bel rumah bunyi terus.
The word “pain” derives
from latin word “poena”
meaning“punishment”.
congenital insensitivity to pain ( chennelopathy)
CHRONIC PAIN vs ACUTE PAIN
Chronic pain is misleading or over simplistic. The key
distinction between acute & chronic is not the
DURATION of pain, but
chronic pain is pain that
 PERSIST
 BEYOND HEALING
 BEYOND NOCICEPTION
 BEYOND EXPECTION
 DIFFICULT TO TREAT.
(symptom is disproportionate)
 NO BIOLOGICAL MEANING.
 IT CAUSED SUFFERING AND BEHAVIOR CHANGES
 Bad Pain
Phantom Limb Pain
After limb amputation
 Two type of pain syndrome
 Stump pain
 Phantom pain
 The incidence of phantom pain varies
from 50% - 85%
 About 40% of amputees having
severe phantom pain
ACUTE PAIN
Acute pain is pain that
 Associated with tissue damage or nociception.
 Has biological meaning.
 Has tendency to recover as nociception is vanished.
 Symptom is slightly proportionate.
 It caused protection for further damage  Good
Pain
 Prototipe dari acute pain  postoperative pain
Clinical Features
of Postoperative Pain

 ALLODYNIA
 HYPERALGESIA

PATHOPHYSIOLOGICAL PAIN Vanished after

(CLINICAL PAIN) healing process finished
So pain, between acute & chronic pain
is absolutely different ;
 Different in etiology
 Different in pathophysiology
 Different in diagnosis
 Different in treatment
HAROLD MERSKEY (psychiatrics) proposed
definition of pain, which was accepted by
IASP (International Association for Study of Pain 1979)

PAIN IS “AN UNPLEASANT SENSORY AND EMOTIONAL EXPERIENCE

ASSOCIATEDWITH ACTUAL OR POTENTIAL TISSUE DAMAGE, OR
DESCRIBED IN TERM OF SUCH DAMAGE”
Nyeri adalah perasaan sensorik dan emosional yang tidak menyenangkan
akibat adanya kerusakan jaringan yang nyata atau yang berpotensi rusak
atau tergambarkan seperti kerusakan tersebut.

The problem lies in the word unpleasant.

Pain is more than unpleasant.
 The great merits of this definition
1. Pain is unpleasant sensory and unpleasant emotional
experience. Kata tidak menyenangkan harus ada  nyeri
2. Pain usually associated with actual tissue damage 
Nociceptive pain or acute pain  PAIN WITH
NOCICEPTION
3. Pain may occur with potential tissue damage (noxious
stimulus)  PHYSIOLOGICAL PAIN  withdrawal- reflex.
4. Pain is described in term of such damage, although nothing
wrong in his/her body  but patient feel severe pain,
PAIN WITHOUT NOCICEPTION  CHRONIC PAIN
Classification of Pain
 Based on Duration: Acute and Chronic.
 Based on Clinical Context:
• Postsurgical
• Malignancy related
• Neuropathic
• Degenerative .
 Based on Organ
- Headache
-Pelvic pain
-Lowback pain
 Based on Pathophysiological -Mechanism :
- Nociceptive pain
- Neuropathic pain
Most Accepted Classification:

 Nociceptive pain = tissue injury

(Acute pain)
 Somatic Pain
 Visceral Pain

 Neuropathic pain = nerve injury

(chronic Pain)
Mechanism of Nociceptive pain.
Pain
Transmission
Perception

Modulation

Conduction
Noxious
stimulus Transduction
Stimulate

Nociceptors
Nociceptive Pain is pain that generated
from nociceptors. Nyeri yang dibangkitkan
dimulai dari nosiseptor

1. NOCICEPTORS
What is a nociceptor?  reseptor nyeri
Nociceptors are peripheral sensory
neurons that respond selectively to
noxious stimuli (Stimulus kuat).
Or A number of receptors/channels that
sense damage
VR1 - vanilloid receptor family
ASICs - respond to low pH
P2X receptors - respond to ATP
TRPs receptors – respond temp.
Chemical sensors - prostaglandins,
Diciptakan Tuhan guna melindungi diri kita
dari bahaya.
 Tissue damage and pain in the periphery
ATP
capsaicin Mechanical?
heat DRG
COX1/2

H+
cold
PGs warm ATP

C-fibre
TRPVs ASICs EPs TRPs P2X
Na+, K+,
Ca2+
channels
2. SENSORY NERVE
AFFERENT
 Sensory Nerve
Afferent

 Sensory afferent n.f.

connecting receptors to
the CNS 
(Centripetal)

 Motor afferent n.f. is

connecting CNS to
muscle or gland 
(centrifugal).
Anatomy of peripheral sensory nerve fibers

A

C A
 Two sensory afferent neurons
1. Large myelinated A fibers, very fast conduction velocity. Respond to
innocuous stimuli
2. Small myelinated A & C unmyelinated fibers, have slow conduction
velocity. Respond to noxious stimuli

Large
fibers A

Dorsal root
ganglion Dorsal Horn
A
Small
fibers
C Peripheral sensory
Nerve fibers

Modified by AHT
Afferent Synaptic in DHN

Substantia
Marginal layer
gelatinosa
A Medial

A

C
Lateral

Nucleus
proprius
 Characteristic of A and C-fiber
A Fiber
Rapid Conduction

MechanoThermal Glu
Nociceptors
First Pain

C-Fiber
Slow Conduction Glu
Polimodal
Nociceptors sP
Secound
Pain
 Two distinct responses to a noxious stimulus
FIRST PAIN and SECOUND PAIN

• First pain: sharp and pricking,

well-localised and brief.
Responded by
A Fiber mechanoreceptors , conveyed
First Pain
by Ad fiber.
Secound Pain • Second pain: dull and diffuse
and prolonged . Responded by
polimodal nociceptors ,
C Fiber conveyed by C fiber

Modified by AHT
 The Role of A fiber
Although in normal condition A fiber does not response to
noxious stimuli, but it plays a big role in NORMAL
SENSATION.

A

Without A fiber, any noxious stimuli will perceive

as BURNING PAIN (TN, HZ)
Role of nociceptors and
primary afferent neurons
are:

1. TRANSDUCTION
2. CONDUCTION
 TRANSDUCTION
TRANSDUCTION
Process whereby noxious
Pressure
stimuli are translated
into electrical activity at
the sensory endings of
nerve Heat

Chemical
“Noxious Soup”
1. TRANSDUCTION PROCESS
(NOCICEPTORS ACTIVATION and CONDUCTION)

Local &
Vescular
Mediators- Action Potential
Ca++
Bradykinin,
Cytokines Peptides- TRP Na+
Histamine, sP, CCK,
5HT. CGRP

Traumatic
Tissue Mediators-
Injury K+, H+,
ATP,PGE

In Creased Neural
Synthesis Mediators- TRP Ca++
Pro Epine,
Inflammatory Norepine
Generator
Cytocaines
Potential
-(IL) 1
-IL-6
TRP (Transient Receptor Potential) Ion
Channel is a Transducer molecules. Modified by AHT
R. Sinatra 2007
 Transduction and Conduction Process

Ca2+

K+
K+

Na+

1. Transduction 3. Propagation (conduction)

2. Spike Initiation 4. Transmission

Modified Meliala, 2006

 Neuron III Persepsion

Transduction

Mechanical Conduction
Transmission
Modulation
Neuron II
Thermal

Neuron I

Chemical

Modified by AHT
3. MODULATION in DHN
Dorsal Horn neurons of SC
Plays a big role in pain perception
Is the first gate to control pain.
Nociception (Pain) is born in DHN

Lehmann, K. A.: From the first stimulus to pain memory. UN. Cologne, 2000 36
 Modulation in Dorsal Horn Neurons
Done by Descending neurons & Interneurons

Modulation at DH 37
SITES OF ENKEPHALIN BINDING IN SPINAL CORD.
PLAYED BY DESCENDING INHIBITORY AND INTRNEURON INHIBITORY FIBER

Enkephalinergic
Interneuron
(Inhibitory)

Primary
Nociceptive
Presynaptic Opioid
Fiber
Receptors
(-)

ENK ENK

Postsynaptic
Opioid Glutamate
Receptors Receptors ENK
(-)
Descending
(+)
Enkephalinergic
Fiber (Inhibitory)

ENK

Spinal Sensory
Neuron
Modified by AHT
Modulation
Peranan Modulasi dalam kehidupan

 Peran modulasi inilah yang membuat persepsi nyeri menjadi

sangat subyektif.
 Ransangan yang sama dirasakan berbeda oleh tiap orang. (
latar belakang yang berbeda)
 Bahkan R yang sama dirasakan berbeda oleh orang yg
sama kr kondisi emasionalnya berbeda.
 Suatu Nyeri mamiliki 3 dimensi;
1. Cognitive ( dimana dan intesitas nyeri)
2. Affective ( arti dari suatu nyeri)
3. Emotional ( atensi thp nyeri )
Pain is very Subjective
feeling
Pain has multidimensional experience
1. sensory – discriminative
 Identifies the intensity, type and location of pain
2. Affective – motivational
 Assessing the injury the meaning of injury
3. Emotional – behavioral component
 Attention, mood and behavioral due to pain
Thus, the role of DHN, is the place
where interaction between afferent
ascendern input and descedern
input.

1. MODULATION
2. TRANSMISSION
4. ASCENDING PATHWAYS
 Pain

Medulation
Descending
modulation Dorsal Horn

Ascending Dorsal root

Conduction
input ganglion

Transduction
Spinothalamic Peripheral
tract nerve

Trauma
Peripheral
nociceptors

Adapted from Gottschalk A et al. Am Fam Physician. 2001;63:1981, and Kehlet H et al. Anesth Analg. 1993;77:1049.
Modified by AHT
5. DESCENDING MODULATING
PATHWAYS
 Brain is a huge
Pharmacetucal
Ascending Descending
pathways pathways
Factory.
 Descending Modulatory
Cortex
Systems

PAG
Opioids

NRM LC

5-HT - - Enkephalin - Norepinephrine

Opioids
Dorsal homs

Modified by AHT
Begitu kuatnya proses
Desendern sehingga orang ini
seperti tidak punya Otak.
Perception is on the brain, so
No brain no pain.
 How pain perception is processed, still obscured, and
Where pain perceptions in the brain still unclear.

Noxious perception?
Pain A number of theories:
Perception Brain
SS
1. Specificity theory by Descartes
SS Limbic Cortex
(16 century)
Sensory Cortex
Thalamus 2. Gate control theory by Melzack
and Wall (i965)
3. Sensitization theory by Woolf et
al (1990 an)
1. Specificity theory
Descartes
(17th Century)

Pain was
faithfully
transmitted
from
periphery to
brain
Modified by AHT
NO BRAIN, NO PAIN
2.GATE CONTROL THEORY by MELZACK and Wall

Central Descending
Control Modulation

Large
fibers

Ascending Action
System

Small
fibers Dorsal Horn “Gate”

The Gate control theory of pain processing. T = Second-order transmission cell; SG = substantia
gelatinosa cell.
Modified by AHT
Prof. Hyodo
Prof. Hyodo
3.Sensitization theory ,
by Woolf et in 1990
 :After the tissue injury, sensitization in the
periphery and centrally ns is occurred.
 HYPERALGESIA : RANGSANG KUATYANG NORMAL
DIRASAKAN NYERI KINI LEBIH NYERI
 ALLODYNIA: RANGSANG LEMAHYANG NORMAL TIDAK
TERASA NYERI KINI TERASA NYERI
After tissue damage it occurs peripheral
and central sensitization

Worst Pain

“Hyperalgesia” Normal
Response

No Pain
Allodynia

Increasing Stimulus Intensity

Stimulus response alteration observed with hyperalgesia

Nonsteroidal Anti Inflammatory Drugs (NSAID)
-Aspirin - Paracetamol not NSAID
-Ibuprophen Pain
-Ketoprophen
-Ketorolac
Prostaglandine
-Etc. Anti
CycloOxyganase
Enzym
Tissue Injury Arachidonic Acid
Secondary hyperalgesia
(allodynia)

Primary hyperalgesia
So, there are three
possibilities how do
we feel pain.
1. Nociception with Pain
Pain

Inhibition
CNS Modulation
Excitation

Nociception exp. normal situation

Noxious stimulus with Pain
2. Nociception without pain
Pain
X Inhibition
CNS Modulation
Excitation

Example:
Stress Induced Analgesia
Nociception
Noxious stimulus without Pain
3. Pain without nociception
Pain

Inhibition
CNS Modulation
Excitation

X Example: Phantom Pain

Nociception Neurophatic Pain
Pain without noxious stimulus
New concepts of
ACUTE PAIN TREATMENT
Target Point of Analgesic Agents
Ketamin
Acetaminophen

Perception

Modulation Transduction

Transduction

Transmission
Modulation

Modify by AHT
 SEKIAN
Terima Kasih Banyak

Semoga Ada Manfaatnya