PATOFISIOLOGI NYERI

Dibawakan pada Blok Mekanisme Dasar Penyakit

Fakultas Kedokteran Universitas Muslim Indonesia

8 April 2021

dr. FENDY DWIMARTYONO Sp.An – KMN

Prof. Dr. Andi Husni Tanra,PhD, SpAn-KIC-KMN

BAGIAN ANESTESI, TERAPI INTENSIF DAN MANAJEMEN NYERI

UNIVERSITAS MUSLIM INDONESIA
 PEMBAHASAN MELIPUTI
1. Apa itu nyeri?
2. Mengapa nyeri harus diobati
3. Anatomi Serabut Saraf yang berhubungan dengan Nyeri
4. Proses Perjalanan Nyeri
5. Kapan seseorang merasa nyeri
6. Pembagian nyeri dari aspek neurobiologi dan aspek klinik.
Before Eva was created from
Adam’s rib, he was put into sleep

Anesthesia was the first

applied science in the world
Apa itu Nyeri?
(Pain)
Pain is a sensation that - hurt
- discomfort
- distress
- agony

Pain derived from Latin (poena)

signify “ a penalty or punishment”

Nyeri adalah perasaan

inderawi yang tidak
menyenangkan.
 KENAPA NYERI HARUS DIOBATI?
Pain relief is a basic human right!
( Menghilangkan nyeri merupakan Hak Asasi Manusia)
  penderitaan pasien.
  kepuasan pasien
  mempercepat penyembuhan   LoS   cost
  komplikasi akibat nyeri yang tidak diobati.
  produktifitas dan kualitas hidup.
  berkembangnya menjadi nyeri khronik.
Pain is the fifth vital sign (Nyeri adalah tanda vital ke 5)
 UNRELIEVED PAIN CAN LEAD TO...

Insomnia Anxiety Depression

Anorexia Immobility
 APAKAH ORANG INI
MERASA NYERI?
• Ada Rangsang kuat
• Ada Kerusakan jaringan
• Tapi wajahnya tidak
memperlihatkan kalau
dia nyeri.
• Tidak mungkin orang ini
mau melakukannya
kalau dia nyeri.
• Bagaimana
Ini adalah upacara ritual agama …. menerangkannya?
Kenapa dia tidak nyeri?,
karena otaknya berkata
Ini adalah ibadah jadi tidak nyeri
PAIN IS ALWAYS REAL, NO MATTER
WHAT IS CAUSING I
 PAIN DEFENITION
Menurut IASP (International Association for Study of Pain) 1979

Unpleasant sensory and emotional experience;

• associated with actual tissue damage,
• or potential tissue damage,
• or described in terms of such damage.
 PAIN IS UNPLEASANT SENSORY AND EMOTIONAL
EXPERIENCE;
- associated with actual tissue damage,
- or potential tissue damage
- or described in term of such damage

Actual tissue damage Potential tissue damage

(Adanya jaringan rusak yg nyata) (Berpotensi merusak jaringan)
Pain is unpleasant sensory and emotional
experience;
- associated with tissue damage,
- Or potential tissue damage,
- or described in terms of such
damage

LBP

Post herpetic Neuralgia Low Back Pain

• beyond the healing period
• no more tissue damage Chronic Pain
• Longer than 3-6 months
 Emosional
(takut, Physical
menangis)
Normal Situation
(lokalisasi)
Limbic
Pain is unpleasant sensory System Cortex
and
emotional experience.
So, pain has two dimentions Thalamus
(physical and
psychological).

Midbrain
Projection
To PGA
Noxious
stimulus
Spinoreticular Brainstem
tract Reticular
formation
Dorsal horn
Nociceptors Of spinal cord

A fiber
C fiber
Spinothalamic
Cell body in tract
DRG

Modify by
AHT
 ANATOMY OF PERIPHERAL
SENSORY NERVE FIBERS

A

Modified by AHT
C A
 Two Primary sensory afferents
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
 Nerve fibers
diameter velocity
nerve fiber funtion myelin
（μ） （ｍ / ｓ）
proprioceptive
α motor 12〜20 70〜120
Tactile sense
A β pressure 5〜12 70〜80 +

γ spindle fiber 3〜6 15〜80

δ Pain, temperature 2〜5 12〜30
sympatheic +
B preganglionic
＜ 3 3〜15
d.r. pain 0.4〜1 0.5〜2
C sympathetic －
S 0.3〜1.3 0.7〜2.3
postganglionic
 BAGAN PERJALANAN NYERI

1.Transduction 3.Modulation
5.Perception
2.Conduction
action potensial
4.Transmission
Mechanical

Thermal
Neuron I Neuron II Neuron III
Chemical

Nociceptors Thalamus Cerebral Cortex

DHN of SC

Modified by AHT
Mekanisme nyeri nosiseptif
• Antara suatu stimulus kuat (Noxious Stimuli) sampai
dirasakannya persepsi nyeri, terdapat serangkaian proses yang
jelas yaitu;
1.TRANSDUCTION (TRANSDUKSI)
2.CONDUCTION (KONDUKSI)
3.TRANSMISSION (TRANSMISI)
4.MODULATION (MODULASI)
5.PERCEPTION (PERSEPSI)
 5.Persepsion

Neuron III

1.Transduction

Mechanical 2.Conduction
4.Transmission
Action potential
3.Modulation
Neuron II
Thermal

Neuron I
Chemical

Nociceptors
Modified by AHT
 1. TRANSDUKSI (TRANSDUCTION)
• Proses Transduksi adalah proses dimana
suatu stimulus kuat (noxious Stimulus)yg
diterimah oleh nosiseptor (reseptor nyeri),
diubah menjadi suatu aktivitas listrik, dkenal
sbg action potential.
TRANSDUCTION

TRAUMA (Noxious Stimuli)

Overall effect is increased -Mechanical
Nociceptor activation -Thermal
-Chemical

Mediators
-Prostaglandins - Bradykinin
-Leukotrienes - Serotonin
-Substance P - Hydroxyacids
-Histamine - Reactive oxygen species
 2.KONDUKSI (CONDUCTION)
• Proses konduksi adalah penghantaran dan
pembesaran aksi potensial tadi dari perifer sampai
ke kornu posterior medulla spinalis.
 cortex

thalamus Descending
Inhibition,
Periaqueductal done by 3
Grey matter substances

Transmission
 Endorphin
 Noradrenalin
 Serotonin

Modulation

Spinal cord

Conduction

Peripheral sensory nerve

20th century
 3. MODULASI NYERI
• Modulasi adalah perubahan suatu
rangsangan pada level medula spinalis .
• Modulasi pada umumnya menekan suatu
rangsang kuat (meng-inhibisi) menjadi
lemah, tapi dapat juga meningkatkan
(meng-eksitasi) suatu rangsang lemah
menjadi kuat.

Modulasi Inilah yang menyebabkan

mengapa suatu rangsangan yang sama
dapat dirasakan berbeda orang per-orang.
Itulah sebabnya nyeri sangat subyekti
bagi setiap orang.
 Descending
Cortex
Modulatory Systems

Three descending inhibitor hormones

PAG
Opioids 1. Encephalin
2. Noradrenalin
3. Serotonin
NRM LC

Serotonin - - Encephalin - Norepinephrine

Opioids Dorsal horns

Modified by AHT
 The role of
modulation
Pain modulation can be
triggered by the meaning of
injury

Injury for merit

Motivation to win
Motivation to win
 4. TRANSMISI (TRANSMISSION)
• Transmisi adalah perpindahan impuls dari aferent I (first order neuron) ke
aferent II (second order neuron).
• Transmisi inilah yang menentukan apakah suatu impuls diteruskan ke otak
atau tidak.
• Hal itu sangat ditentukan oleh kekuatan proses modulasi.
 cortex

thalamus Descending
Inhibition,
Periaqueductal done by 3
Grey matter substances

Transmission
 Endorphin
 Noradrenalin
 Serotonin

Modulation

Spinal cord

Conduction

Peripheral sensory nerve

20th century
 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
1. Specificity theory by
Descartes (16 century)
SS
Limbic
SS
Cortex
Sensory
Cortex
Thalamu
s
3. Gate control theory by
Melzack and Wall (i965)
4. Sensitization theory by
Woolf et al (1990 an)

Modified by AHT
1. Specificity theory
Descartes
(17th Century)

Pain was
faithfully
transmitted
from
periphery to
brain
Modified by AHT
Intensitas nyeri
berbanding lurus
dengan kerusakan
Jaringan.
 The Meaning of injury
Henry
Beecher

Prof. Hyodo
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
3.SENSITIZATION THEORY BY WOOLF ET
Is the net process starting from:
• Nociceptor activation
• Neural conduction
• Spinal transmission
• Noxious modulation
• Limbic & frontal – cortical
perception
• Spinal & supra spinal response.
After the injury is occurred sensitization
in the periphery and centrally.
(Hyperalgesia and allodynia)
 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

Modified by AHT
Primary hyperalgesia

Secondary
hyperalgesia
 Clinical Features of
Postoperative Pain
Primary
Hyperalgesia
• HYPERALGESIA Inflammed

ALLODYNIA
area
• Non-Inflammed
area

Secondary
Hyperalgesia

X
CLINICAL PAIN
Vanished Chronic pain
(PATHOPHYSIOLOGICAL after healing after surgery
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 Neurobiology :
- Nociceptive pain
- Inflammatory pain
- Pathological pain
 Neuropathic pain
 Dysfunctional pin
 FROM NEUROBIOLOGICAL
PERSPECTIVE PAIN CAN BE DIVIDED
INTO 3 TYPES
PAIN

Nociceptive Inflammatory Pathological

Pain Pain Pain
 Neurophatic Pain
 Dysfunctional Pain
Woolf CJ. What is this thing called pain? J Clin Invest 2010; 120(11): 3742-3744
 1. Nociceptive Pain

• Pain that is detected by nociceptors, due to noxious stimuli.

Nociceptive pain (noxious from Latin nocere to harm)
• Due to potential tissue damage (Noxious Stimuli) .
• To protect further damage.
• Protective pain.
• Early-warning physiological protective system.
• E.g. touching something too hot, cold or sharp
• Also called physiological pain  withdrawal reflex.
WITHDRAWAL REFLEX
• Pentingnya nyeri
nosiseptif dalam
kehidupan
manusia sebagai
alat proteksi dapat
kita bayangkan
dengan melihat
penderta ini.
Hidupnya tidak
bisa panjang
karena tidak bisa
merasa nyeri.

Congenital insensitivity to pain

( chennelopathy)
 2. Inflammatory Pain

• Pain due to tissue damage and infiltration of immune

cells.
• Pain due to inflammation
• Adaptive and protective pain
• To promote repairing by causing pain hypersensitivity until
healing occurs.
• Pain is one of the cardinal features of inflammatory.
Tissue damage
SETIAP KERUSAKAN JARINGAN SELALU DIIKUTI
DENGAN PROSES INFLAMASI
1
Painful stimulus
Prostaglandins
meningkatkan
sensitizasi jaringan 
Pain-sensitive tissue nyeri.

Prostaglandin 2
1 Blood
Substance P
Mast cell vessel Bradykinin
Histamine
vasodilatasi
kemerahan dan panas.
Bradykinin
Substance P
2
3 3
Histamine memicu
Nociceptor terbentuknya degranulasi oleh
sel mast  pembengkakan

Sensitizasi perifer
 INFLAMMATION PAIN
Pain may occur
without
noxious stimuli

Clinical Signs:
• Calor (heat)
• Rubor (redness)
• Tumor (swelling)
• Dolor (pain)
• Functio laesa (loss of function)
Bimolecular changes
in inflammation
 Five
Cardinal
Signs of
Inflammatio
n
HEAT REDNESS SWELLING PAIN LOSS OF FUNCTION
 PROTECTIVE PAIN
Pain
1. Nociceptive pain Autonomic response
Withdrawal reflex
Nociceptor
Sensory neuron
Noxious stimuli Adaptive, high-threshold pain
 Heat Early warning system
 Cold (protective)
 Mechanical force
 Chemical irritants
Spinal cord
2.Inflammatory pain Spontaneous pain
Inflammation Pain hypersensitivity
Peripheral  Macrophage
Inflammation Mast cell Adaptive, low-threshold pain
Positive  Neutrophil Tenderness promotes repair
symptoms  Granulocyte (protective)
Tissue damage

Modified by AHT
 3. Pathological Pain

• Maladaptive pain and non protective pain

• This is not a symptom or protective pain but a
disease state.

Due to damage of No damage of the

nervus system NS

Neuropathic Pain Dysfunctional Pain

• Panthom pain • Fibromyalgia
• Herpetic neuralgia • IBS (Intractable Bowel
• Trigemenial Syndrome)
neuralgia • Tension Headache
 3. NYERI NEUROPATIK
. Nyeri neuropatik;
Adalah nyeri yang terjadi akibat adanya
kerusakan pada saraf, baik saraf perifer
atau saraf sentral. Jadi nyeri akibat
terjadinya disfungsi dari saraf baik perifer
maupun sentral.
Spontaneous pain
Pain hypersensitivity
Peripheral - Allodinia - Hyperalgesia
Nerve damage
Neuropathic pain
Neural lesion
Positive and negative Injury
symptoms Stroke
Abnormal Maladaptive, low-threshold pain
Central processing Disease of the nervous system

Modified by
AHT
Tanpa nosisepsi ada nyeri
(Pain without nociception)
PAIN

Inhibition
CNS Modulation
Excitation
(sangat kuat)
X
NOCICEPTION Contoh: Nyeri Phantom
Nyeri Neuropatik (TN,PHN)
 CONTOH KLASIK DARI NYERI
NEUROPATIK

1. Phantom limb pain (nyeri

pantom, nyeri setan)
2. Post Herpetic Neuralgia
3. Trigeminal neuralgia
 PHANTOM PAIN

Phantom Pain phanto

m pain
 key distinctions
• phantom pain
• phantom sensation
• stump pain
• telescoping movement
• variable onset

telescoping
 3 Sensations can be felt
1. Phantom pain
2. Phantom sensation
3. Stump pain

stump pain
phantom pain
If not pain  Phantom sensation

WRAMC Feb1, 2005

 PHANTOM LIMB PAIN IS A ‘PAIN
MEMORY’!

• In 57% of subjects with phantom pain,

this resembled preamputation pain.
• “… somatosensory inputs of sufficient
intensity and duration can produce long-
lasting changes in central neural
structures”
Katz&Melzack, Pain 1990;43:319
POST HERPETIC NEURALGIA
 DAPAT DISIMPULKAN:
• Nyeri dapat terjadi tanpa adanya stimulus kuat (noxious Stimulus)atau
kerusakan jaringan yang nyata.
• Bahkan nyeri bisa dirasakan pada organ yang sudah tidak ada:
 amputasi kaki/ tangan
(Phantom Pain/ Phantom Sensation)
 NYERI NEUROPATIK
• Tidak ada gejala inflamasi, penyembuhan sudah usai,
tidak ada lagi jaringan rusak. jadi obatnya bukan obat
analgesik anti inflamasi (NSAID at AINS).
Pengobatannya adalah;
Obat-obatan adjuvant ( obat- obat yg bukan
analgesik tapi mampu menghilangkan nyeri.).
1. anti depresan
2. anti konvulsan
3. gabapentinoid
- Gabapentine
- Pregabaline
4.ketamin
6. dexamethasone
•Pembagian Nyeri dari aspek klinis
DARI ASPEK KLINIS NYERI DIBAGI ATAS;
1. Nyeri Nosiseptif  Nyeri Akut
 Nyeri Somatik (organ soma meliputi; kulit,
otot, sendi, tulang dll)
 Nyeri Viseral (organ visera meliputi: Jantung,
Paru, hati, ginjal, gaster, pancreas dll)
2. Nyeri Neuropatik  Nyeri Kronik
Akibat adanya kerusakan atau lesi dari saraf
 Nyeri Nosiseptif
Nyeri Somatik
• Nyeri konstan
• Tajam
• Lokalisasinya jelas
• Sakit kalau
digerakkan
Contohnya
 Nyeri tulang karena
metastase.
 Kerusakan jaringan
lunak
 Nyeri sendi
 Nyeri Nosiseptif
Nyeri viseral
• Nyeri konstan
• Terasa kram
• Lokalisasinya tdk jelas
• Kadang ada nyeri rifer

Contohnya
– Karsinoma pangkreas
– Hepatoma, setelah
kapsulnya meregang.
– Obstruksi usus
(kolorektal)
 Analogi
NYERI NOSISEPTIF

Api
NYERI INFLAMASI

Air Hangat

?
NYERI PATOLOGIS

Tanpa rangsangan
San Diego, USA