ANATOMY and PHYSIOLOGY

of PAIN.


Nociceptors.
Primary afferent neuron
Dorsal horn Neurons
Ascending pathway
Descending control of pain
Pathophysiology
Peripheral Sensitization
Central Sensitization
Pain perception.
OBJECTIVES
Pain can be defined as the conscious awareness
of actual or potential tissue injury.
Pain is involving:
1. Nociceptors activation by mediators released
from injured tissue and nerves'.
2. Afferent transmission /conduction to the spinal
cord and processing within the dorsal horn and
supra spinal center.
3. Pain perception is depend on the net result of
interaction between Acendern in put and
decendern control.
4. In general, pain is an alarm mechanism to
protect our body.
What is Pain.
Anatomy
Primary afferent neurons
1. Sensory afferent neurons have a unipolar
cell body.
2. They are classified into 3 major groups
(A,B,C), according to the fiber size.
3. Group A is further sub-classified into 4
subgroups (A, A, A).
4. Sensory afferent that respond to noxious
stimulation include myelinated A, or
unmyelinated C- fiber.
5. Most A and all C fiber originate as free nerve
endings which is called NOCICEPTORS

Classification
of
Peripheral
nerve
5
1. NOCICEPTORS
What is a nociceptor?
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,
5HT etc
TRPVs ASICs TRPs P2X

capsaicin
H+
PGs
EPs
cold
warm
ATP

COX1/2
ATP
heat
Na
+
, K
+
,
Ca
2+

channels
DRG
C-fibre
Tissue damage and pain in the periphery
Mechanical?
Nociceptors;is characterized
by their response;
1. A-delta Mechanothermal nociceptors
Respond to mechanical and thermal stimuli.
display rapid conduction.
Produced first pain and well localized.
Ad fibers respond to this naciceptors.
2. C-fiber Polimodal nociceptors
Respond to mechanical, thermal and chemical.
Slow conduction.
Produced second pain and diffuse.
C fibers respond to this receptor.
Exist in many tissues, skin, muscle, pariosteum, joints, and viscera, except brain.
Characteristic of A and C-fiber
Polimodal
Nociceptor
A Fiber
Rapid Conduction
First
Pain
Secound Pain
C-Fiber
Slow Conduction
Mechano
Thermal
Nociceptors
Glu
First Pain
Secound
Pain
Glu
sP
2. PERIPHERAL SENSORY
AFFERENT FIBERS
Anatomy of peripheral sensory
nerve fibers
A
A C
Dorsal Horn
Dorsal root
ganglion
Peripheral sensory
Nerve fibers
A
A
C
Large
fibers
Small
fibers
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
Modified by AHT
Although in normal condition A fiber does not
response to noxious stimuli, but it plays a big
role in NORMAL SENSATION.
The Role of A fiber
Without A fiber, any noxious stimuli will perceive
as BURNING PAIN (TN, HZ)
A
I
IIo
IIi
III
IV
V
VI
VII
VIII
IX
X
A
WDR
A
C
heavily
myelinated
fast conducting
thinly myelinated
intermediate
conducting
unmyelinated
slow conducting
peripheral
endings
dorsal root
ganlgia
high intensity
noxious
stimuli
low
intensity
non-noxious
stimuli
SP & CGRP
INPUTS
REFLEXES
SENSATIONS
NS
Peripheral fibre systems
It is important to know that two
distinct responses to a noxious
stimulus FIRST PAIN and SECOUND PAIN
First pain: sharp and
pricking, well-localised
and brief. Responded by
mechanoreceptors ,
conveyed by Ad fiber.
Second pain: dull and
diffuse and prolonged .
Responded by polimodal
nociceptors , conveyed by
C fiber
C Fiber
A Fiber
First Pain
Secound Pain
Modified by AHT
1. TRANSDUCTION
2. CONDUCTION

Role of nociceptors
and primary afferent
neurons are:
TRANSDUCTION PROCESS
(NOCICEPTORS ACTIVATION)
Action Potential
Na
+
Ca
++
TRP
Peptides-
sP, CCK,
CGRP
Ca
++
TRP
Generator
Potential
Traumatic
Mediators-
K+, H+,
ATP,PGE
Neural
Mediators-
Epine,
Norepine
Local &
Vescular
Mediators-
Bradykinin,
Cytokines
Histamine,
5HT.
In Creased
Synthesis
Pro
Inflammatory
Cytocaines
-(IL) 1
-IL-6
Modified by AHT
R. Sinatra 2007
Noxious Soup
Tissue
Injury
TRP (Transient Receptor Potential) Ion
Channel is a Transducer molecules.
Pain Perception


Spinothalamic
tract
Peripheral
nerve
Dorsal Horn
Dorsal root
ganglion
Pain
Ascending
input
Descending
modulation
Peripheral
nociceptors
Trauma
Adapted from Gottschalk A et al. Am Fam Physician. 2001;63:1981, and Kehlet H et al. Anesth Analg. 1993;77:1049.
Conduction
Modified by AHT

Transduction
3. DORSAL HORN NEURONS
Lehmann, K. A.: From the first stimulus to pain memory. UN. Cologne, 2000
Dorsal Horn of Spinal cord
Plays a big role in pain perception
Is the first gate to control pain
Nociception (Pain) is born in DHN

21
Dorsal Horn Neurons
Is highly organized center of neurons
The place where afferent input is processed.
The place where terminal endings of primary
afferent ( first order neuron) and receiving neurons
(second order neurons) synapse.
Where interaction between excitatory and
inhibitory system.
Two types of second order nociceptive neurons are
found in DHN.
1. NS (Nociceptive-Specific Neurons )
2. WDR (Wide-Dynamic Range Neurons)


Targets of Primary Afferent Neurons in
the posterior gray (dorsal) horn
23
Transmission at DH
NS
WDR
NS : Respond exclusively to noxious stimuli
from A & C fiber.
WDR :
Respond to both noxious and innocuous
stimuli.
May receive afferent input from skin, muscle,
joint and visceral nociceptors referred pain.
Low frequency stimulation of C fiber lead to
gradually increase WDR discharge, until
continuous discharge wind up.
These responsible by NMDA receptors, while
AMPA receptors responsible for short-lasting
depolarization (brief pain).
Neurotransmitters and receptors
on Dorsal Horn
25
Modulation at DH
Primary afferent neurons may release one or more
excitatory
Amino acid (EAA) such as:
Glutamate
Aspartate, or
Peptide such as
Substance P Neurokinin A
CGRP (Calcitonin Gene-Relate Peptide)
CCK (Cholecystokinin) Somatostatin
Bombezine etc.
EAA mediated rapid short-duration depolarization of
second order neurons.
Peptides produce a delayed and long lasting
depolarization.
NEUROTRANSMITTERS
4. ASCENDING PATHWAYS
Ascending Pathways
5 ascending pathways have been recognized.
1. SPINOTHALAMIC TRACT
Discriminative pathway location of pain
2. SPINORETICULAR TRACT
Emotional aspect of pain (suffering pathway)
3. DORSAL HORN COLUMN TRACT
Transmission of visceral pain
4. SPINOMESENCEPHALIC TRACT
Behavioral response
5. SPINOHYPOTHALAMIC TRACT
Sensationl from the skin, lips & sex organs
A-Alpha Motor
Efferent
Sympathetic
Efferent
Delta Sensory
Afferent
C-Fiber Sensory
Afferent
Peripheral
Nociceptor
Spinal Cord
NSTT
PSTT
NRM Brainstem
Midbrain
Hypothalamus
and Pituitary
Cortex and
Thalamus
LC
PAG
MT VPL
SSC
FLC
Ascending
Pathaways
Descending
Pathaways
Sympathetic
Outflow
Hypothalamic-
Pituitary Outflow
SPINOTHALAMIC TRACT
Neo Spino Thalamic Tract direct to
Thalamus SSC Localizing and
discriminative information withdrawal
reflex.
Pleo Spino Thalamic Tract FLC (Frontal
Limbic Cortex) Affecting circulation,
respiration, endocrine, emotional,
behavioral responses (fear, anxiety,
helplessness, avoidance).
Response Cortical
Response Suprasegmental
Response Segmental
Response Local
- anxiety
- fear
- apprehension
- neurohumoral response
- catecholamines
- cortisol
- dll.
- muclespasm
- vasospasm
- bronchospasm
- decreased gastrointestinal
motility
-release pain substances
-inflammation
RESPONSES TO NOXIOUS STIMULI INDUCED BY AN ABDOMINAL SURGERY
5. DESCENDING MODULATING
PATHWAYS
Descending Modulating
Pathways
CEREBRAL CORTEX
THALAMUS
HYPOTHALAMUS
BRAINSTEM/ MIDBRAIN
Periaqueductal gray (PAG)
Nuclei raphe magnus
Locus ceruleus
Sub ceruleus
SPINAL CORD
Those ascending pathways is modulated by descending
modulating pathways in several higher centers;
A-Alpha Motor
Efferent
Sympathetic
Efferent
Delta Sensory
Afferent
C-Fiber Sensory
Afferent
Peripheral
Nociceptor
Spinal Cord
NSTT
PSTT
NRM Brainstem
Midbrain
Hypothalamus
and Pituitary
Cortex and
Thalamus
LC
PAG
MT VPL
SSC
FLC
Ascending
Pathaways
Descending
Pathaways
Sympathetic
Outflow
Hypothalamic-
Pituitary Outflow
SEROTONIN
NEOREPINEPHRINE
Modulation
Descending Pain Control
Cortex
Hypothalamus
Thalamus
PAG
NRM
DHN
Brain
Midbrain
Brain stem
Spinal cord
Releases
Endogenous opioids
GABA
NE
Releases
Serotonin
NE
Inhibit
WDR neurons
NS neurons
Analgesia
NO BRAIN, NO PAIN
1. MODULATION
2. TRANSMISSION

Role of DHN, is the place
where interaction between
afferent ascendern input
and descedern modulation
pain control.
Pain Perception


Spinothalamic
tract
Peripheral
nerve
Dorsal Horn
Dorsal root
ganglion
Pain
Medulation
Ascending
input
Descending
modulation
Peripheral
nociceptors
Trauma
Adapted from Gottschalk A et al. Am Fam Physician. 2001;63:1981, and Kehlet H et al. Anesth Analg. 1993;77:1049.
Conduction
Modified by AHT

Transduction
Pain
Perception
Brain
Noxious perception?
A number of theories:
1. Specificity theory by Descartes
(16 century)
2. Gate control theory by
Melzack and Wall (i965)
3. Sensitization theory by Woolf
et al (1990 an)
PAIN PERCEPTION
How pain perception is processed, still obscured, and
Where pain perceptions in the brain still unclear.
Limbic Cortex
Sensory Cortex
Thalamus
SS
SS
Pain was
faithfully
transmitted
from
periphery to
brain
1. Specificity theory
Descartes
(17
th
Century)
Modified by AHT
2.GATE CONTROL THEORY by MELZACK and Wall
Ascending Action
System
Large
fibers
Central
Control
Descending
Modulation
Small
fibers
Dorsal Horn Gate
The Gate control theory of pain processing. T = Second-order transmission cell; SG = substantia
gelatinosa cell.
Modified by AHT
3.Sensitization theory by Woolf
After the injury sensitization in the periphery
and centrally is occurred. (Hyperalgesia and
allodynia).
Pain perception is the net process starting
from:
Nociceptor activation
Neural conduction
Spinal transmission
Noxious modulation
Limbic & frontal cortical perception


So, there are three
possibilities how do
we feel pain.
Noxious stimulus with Pain
Pain
CNS
Nociception exp. normal situation
Nociception with Pain
Inhibition

Excitation
Modulation
Pain
CNS
Nociception

Nociception without pain
Inhibition

Excitation
Example:
Stress Induced Analgesia
X
Modulation
Noxious stimulus without Pain
Pain
CNS
Nociception

Pain without nociception
Inhibition

Excitation
Example: Phantom Pain
Neurophatic Pain
X
Modulation
Pain without noxious stimulus

6. Peripheral Sensitization

Activation of neciceptor
HT Hist.
PGE
2
PGI
2
LTB
4
BK NOR
Primary afferent nerve
Nociceptive stimulation
Axon reflex
vessel
Platelet
Tissue
cell
Mast
cell
Membrane
phospholopid
Tissue damage
Kininogen
Nocicepto
r
Redness
Swelling
Pain
Fever
H
+
K
+
H
+
serotoin platelets ++
activate
histamine mast cell +
activate
leukotrienes arachidonic acid-damaged cell

sensitize
Chemical intermediaries in nociceptive transduction
Pain: Howard L. Fields p.32
Primary Hyperalgesia
Cell injury
Kinins
H+
K
Prostaglandin
Bradikynin
NO
Kinins
Vasculature
Neuropeptides
Primary Afferent Neurones
Nociceptors
Cannabioids
Opioids
Adenosine
Cytokines
Neurotrophins
Histamine
5HT
Immuno Cells
Prostaglandins
Sympathetic Efferent Neurones

7. Central Sensitization


NMDA RECEPTOR / CHANNEL
IS BLOCKED BY Mg ion
Gly NMDA AMPA
PCP Zn
Mg
Na
Ca
K
Na
K
NKr
PKC
Dickenson, 1994
3 conditions are needed to release Mg blockade.
NMDA is binding by Glu, Gly and Long depolarisation
Gly NMDA AMPA
PCP Zn
Na
Ca
K
Na
K
NKr
PKC
SP
DEPOLARIZATION
Mg
Glu
Glu
Dickenson, 1994
When NMDA channel is open large of
Ca and Na influx into the cell
Gly NMDA AMPA
PCP Zn
Na
Ca
K
Na
K
NKr
PKC
SP
DEPOLARIZATION
Mg
Glu
Glu
Ca
Increased excitability
Long term changes
Cell death Dickenson, 1994
Central sensitization Processing in Spinal Cord
Inhibitory
Interneuron
Nociceptor
Terminal ending
NMDA Receptor: Requires voltage
dependent priming for activation -
mRNA synthesis, and
upregulation of inducible
enzymes/ protein
Second Messenger
Formation, (cAMP, PKA)
Post Synaptic Membrane of
the Spinal Sensory Neuron
NE
MU
Glu
SP
Glu
Glu
MU
Glu
Na+
AMPA
Receptor
Kainate
Receptor
Fast Prime
Slow Prime
NK-1
Receptor
NMDA
Receptor
Glu
Mg++
SP
SP
SP
Ca++
Nerve fibers

1220

512

36

25

3

0.41

0.31.3

70120

7080

1580

1230

315

0.52

0.72.3

d.r.

S

temperature pain
motor
spindle fiber
sympatheic preganglionic
sympathetic postganglionic
pain
myelin
+
+

diameter
funtion
nerve fiber
A
B
C

proprioceptive
Tactile sense
pressure
velocity
PERIPHERAL
ACTIVITY
CENTRAL
SENSITIZATION
Decreased
threshold to
peripheral
stimuli
Increased
spontaneous
activity
Expansion of
receptive
field
Hyperalgesia
Allodynia
Tissue damage
Nerve damage
Spontaneous
pain
Inadequate postoperative
pain management
May produce long term
synapse potentiating in
term of Central sensitization .
62
Consequence of Prolonged
Central sensitization
Under treatment of postoperative pain
Central sensitization
Pain disease
Collapse of the body's pain defenses
Sandkhler, J.: Preventing Pain Memory. MMW 2002; Special edition 2
VISCERAL PAIN
1. Neurophytiological thinking about pain in
general has been dominated by
Sherrington's approach.
PAIN AS PHYSICAL ADJUNCT OF A
PROTECTIVE REFLEX
IT HAS A SURVIVAL VALUE
(Sherrington 1926)
Cara pandang ini berlaku pada Sopratic Pain, tapi toh
pada Visceral Pain
Looks likely that Visceral Pain is not playing a role as
survival protection.
NATURE OF VISCERAL PAIN
1. Is the most common form of pain produced by
disease and one of the most frequent reasons
for patients to seek medial attention.
2. Mechanism of visceral pain is less well
understood than somatic pain. (visceral pain
research started 1990)
3. The more we know about mechanism of
somatic and visceral pain, the more realized
that these two processes, while heaving many
common features, also have important
differences.
4. Visceral pain is evoked by a stimulus which may
not evoke in somatic pain.
2.
5 CHARACTERISTIC OF VISCERAL PAIN
1. Is not evoked from all visceral (liver, kidneys
or lungs do not have any sensory unless
adjacent structures are also affective.
2. Is not liked to visceral injury.
3. Is referred to other location.
4. Is diffuse and poorly location.
5. Is accompanied by method and autonomic
reflex.
3.
THE DIFFERENT OF
SOMATIC AND
VISCERAL PAIN.
1. Visceral pain can not be evoked
from all visceral.
Some Visceral organs such as the liver,
kidneys or lungs do not evoked any sensory feed
back, unless adjacent structures are also
affected (e.g. cancer in these organs).
We dont know why pain can be evoked by
certain internal stimuli, such as renal or biliary
calculi.
Visceral pain is usually evoked by stimuli
that cause strong contractions of smooth
muscle or ischemic of the viscous.
2. Visceral pain is not linked to
internal injury
Some forms of injury, such as ischemic or inflammation
can evoked visceral pain however these stimuli will not always
trigger pain when applier to certain viscera.
In general visceral pain can be evoked by the following
stimuli:
1. Spasm of the smooth muscle in hollow visceral.
2. Distention of hollow visceral.
3. Ischemia.
4. Inflammatory states.
5. Chemical stimuli.
6. Traction, compression and twisting of the mesenteries.
While cutting, crushing or buring which may produce
severe pain of applied in somatic again but not in visceral
organ.
Many form of visceral pain are felt in regions
of the body other than the organ whose
stimulation cause the pain e.g.
The pain of angina is a characteristic
example.
Pain produced by cardiac ischemia will be
felt into left shoulder and arm.
3. Visceral pain can be referred to other
locations.
All form of visceral pain are poorly localized and
most are felt in are as considerably larger than
the size of the originating viscous.
It is also a common experience that as the pain
becomes more intense, somatic area in which
pain is felt becomes larger (intestinal pain is felt
vaguely over the entire abdomen).
A classical exception to the poor localization of
visceral pain is the pain of gastro-duodenal
peptic ulcer, which some patients are able to
pinpoint to epigastria with a fingertip.
4. Visceral pain is diffuse and poorly
location.
All form of pain, coetaneous and visceral, will
generate neurophysiologic response include motor
and autonomic reflex. (these response called
pseudaffective reaction by Sherrington 1906)
These response, clinically shows as muscle
contractures and spasm accompanied by tachy
cardia BP, sweating and change motility which
contribute greatly to the patients discomfort.
These pseudaffective reaction makes patients
looke more ill than they would be without them.
Walaupun reflex ini memiliki arti klinik, namun
tidak bisa menjadi alasan untuk tidak segera
memberi analgetik agar motor and autonomic
responses dapat ditekan to make patient
comfort.
5. Visceral pain is accompanied by intense
motor and autonomic reflexes.

WIDE DYNAMIC RANGE SPINAL
NEURON
Brain
NMDAr
Glutamate
(Subs P)
GABA
Glycine
Opioids
NA, 5HT
C
A
A
+
-
Glutamate
Glutamate
Inhibitory
Fibers
Wind-up

Gene induction
DECENDING CONTROL
All decending control, particularly
endogenern opioid (70%) will.
1. Inhibit pre synaptic release of algesic
neurotransmitters. (glutamate or peptide)
2. Suppression of second order neurons (WDR
and NSD at postsynaptic neurons).
What the textbooks
would have you believe
about pain
Noxious (painfull)
stimulus to the body
What PAIN is?
Dorsal homs
Opioids
NRM LC
PAG
Cortex
Opioids
Descending
Modulatory Systems
5-HT - - Enkephalin - Norepinephrine
Modified by AHT
Injury
C fiber=second pain
Afiber=first pain
Pain intensity
Time
Two distinct sensations
(dual pain sensation)
early sharp, relatively brief
pricking sensation
later dull, somewhat
prolonged sensation
Limbic Cortex
Sensory Cortex
Thalamus
Central Grey
Mid Brain
Ascending
Pathways
Spinal Cord
Motor Efferent
Noxious Fiber
Nociceptor
Trauma
Descending
Pathway
Dorsal
Horn
Adapted from Julius & Basbaum.
Nature 2001;413(6852):203
Pain Processing in Spinal Cord
Inhibitory
Interneuron
Nociceptor
Terminal ending
NMDA Receptor: Requires voltage
dependent priming for activation -
mRNA synthesis, and
upregulation of inducible
enzymes/ protein
Second Messenger
Formation, (cAMP, PKA)
Post Synaptic Membrane of
the Spinal Sensory Neuron
+
-
NE
MU
Glu
SP SP
SP
SP
Glu
Glu
MU
Na
+ Glu
Mg++
Na
+
-
Glu
Na
+
AMPA
Receptor
Kainate
Receptor
Fast Prime
Slow Prime
NK-1
Receptor
NMDA
Receptor
Modified by AHT
NOCICEPTIVE TRANSMISSION
C-fiber Dorsal Horn Neuron
Glu
( SP )
NO
AA
NMDA r
(CGRP)
Cortical structures
It has been long to divide higher neural center
in pain processing into 2 parts:
Somatosensory cortex sensory discriminative
pain
Cingulate cortex affective pain
However, this is maybe an oversimplification,
the role of cortex in PAIN PERCEPTION
remains unclear.
( Philip Siddal )
PAG
( Periaqueductal gray )
Play a big role in pain control modulation,
it may releases:
Endogenous opioids
Enkephalin
Endorphine
Dynorphine
GABA (gamma amino butiric acid)
Norepinephrine
Noxious afferent fibers
A myelinated fiber
C unmyelinated fiber
Responds to noxious stimuli
A nociception has at least 4 components

1. TRANSDUCTION
2. CONDUCTION
3. TRANSMISSION
3. MODULATION
4. PERCEPTION
ACUTE (NOCICEPTIVE)
PAIN PATHWAYS
Mechanical
Thermal
Chemical
Transduction
Conduction/
Transmission
Modulation
Transmission
Persepsion
Neuron I
Neuron II
Neuron III
Modified by AHT
1.TRANSDUCTION (NOCICEPTOR ACTIVATION)
Defines as noxious stimuli are converted into a
calcium ion-(Ca
2+
) mediated electrical
depolarization within the distal nociceptor
endings.

Note!
Ca
++
ion channels is a Generator Potential (gear)
Na+ ion channels is like accelerator (gas)
Ka+ ion channels is like breaker (rem) in
automobile.


K
+
K
+
Ca
2+
Na
+
1. Transduction

4. Transmission

2. Spike Initiation

3. Propagation (conduction)

Modified Meliala, 2006
Transduction and Conduction Process
TRANSMISSION (spinal transmission)
Refers to the transfer of noxious impulses
from primary nociceptors cells in the dorsal
horn neurons.
Ad and C fibers are the axons of unipolar
neurons that have distal projections known as
nociceptive field.
Two nociceptive fields in dorsal horn neurons;
1. Nociceptive-specific neurons (NS)
2. Wide dynamic range (WDR)
MODULATION (noxious modulation)
Refers to pain- suppressive mechanism within the
spinal cord dorsal horn neurons and at higher levels
of the brainstem and midbrain.
In the spinal cord, this intrinsic breaking
mechanism inhibits oxious transmission at the
first synapse between the primary noxious afferent
and second order WDR and NS neurons.
Thereby reducing spinothalamic relay of noxious
impulses.
Spinal modulation is mediated by spinal-inter
neurons and terminal descending inhibitory.
Pharmacologic Modalities of
acute pain management
Cyclo-oxygenase inhibitors
Non-specific COX inhibitors(classical
NSAIDs)
Selective COX-2 inhibitors, the coxibs
Acetaminophen is probably COX-3
Local anesthetics
Opioids
NMDA antagonists
Ketamine, dextromethorphan
Anti-convulsants
Gabapentin, Pregabalin
What is pain?
94
Poisons
mechanical , thermal , chemical
Tissue damage
Release of mediators
Hydrogen and potassium ions,
neurotransmitters, kinins, prostaglandins
Stimulation of nociceptors
Transmission to CNS
via afferent pathways
Pain

Tissue damage - inflammation
or nociceptive pain
Nerve damage - neuropathy
Headache/period
Central pain
Cancer pain

Co-existence

Acute
Chronic

Most accepted classification:
Nociceptive pain (Acute pain)
Neuropathic pain
mixed pain
psychologic pain
Pain Perception


Spinothalamic
tract
Peripheral
nerve
Dorsal Horn
Dorsal root
ganglion
Pain
Modulation

Transduction
Ascending
input
Descending
modulation
Peripheral
nociceptors
Trauma
Adapted from Gottschalk A et al. Am Fam Physician. 2001;63:1981, and Kehlet H et al. Anesth Analg. 1993;77:1049.
Perception
transmission
Conduction
Conduction
Modified by AHT


Spinothalamic
tract
Peripheral
nerve
Dorsal Horn



Pain
Ascending
input
Descending
modulation
Peripheral
nociceptors
Trauma
Adapted from Gottschalk A et al. Am Fam Physician. 2001;63:1981, and Kehlet H et al. Anesth Analg. 1993;77:1049.
PERCEPTION
MODULATION
CONDUCTION/
TRANSNISSION

TRANSDUCTION
OPIOID
- Systemic
- Epidural
- Subarachnoid
LOCAL ANESTHETIC
- Epidural
-Subarachnoid
-Peripheral nerve block

Steroids
LA
COX-1
COX-2

No single drug can produce optimal analgesia without adverse effect
Multimodal Analgesia
COX-2, COX-3?
Ketamin, Tramadol,
agonist
TRANSMISSION
Modified by AHT

TERIMA KASIH BANYAK

SEMOGA ADA MANFAATNYA