Patofisiologi Nyeri

Esdras Ardi Pramudita

20 November 2012

Universitas Kristen Duta Wacana Yogyakarta

Latar Belakang

NYERI

masalah medis yang sering ditemui (80%). Bahkan tidak jarang menjadi keluhan utama yang membuat pasien datang menemui dokter 9 dari 10 orang di Amerika secara reguler mengalami nyeri. Setiap tahunnya, 25 juta orang di Amerika mengalami nyeri akut karena trauma ataupun pembedahan dan 50 juta orang mengalami nyeri kronik.
Sources: The Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) Gallup Survey June 1999

Latar Belakang
43% orang dewasa di US melaporkan bahwa nyeri mengganggu aktifitas harian 55% orang dewasa di US merasakan nyeri setiap harinya

Menurunkan kualitas hidup

Permasalahan ekonomi

Th 1995, kerugian USD 3 milyar, krn hilangnya 20 juta jam kerja Disabilitas yang menurunkan jam kerja seseorang

Latar Belakang

Stimulus

Nyeri

Penyakit

Gejala Mekanisme proteksi (thdp rangsangan yang dpt mencederai) Memicu respon terhadap stres (penarikan, melarikan diri atau immobilisasi bagian tubuh)

Definisi

Nyeri adalah pengalaman sensorik dan emosional yang tidak menyenangkan akibat kerusakan jaringan, baik aktual maupun potensial atau yang digambarkan dalam bentuk kerusakan tersebut
(IASP, 2000).

Pain is perfect misery, the worst of evils, and excessive, overturns all patience.
John Milton

Somatic Sense

Protopatik

Nyeri Suhu

Somatic Sense
Propioseptif
Raba Tekanan Vibrasi Posisi Diskriminasi

Sensory Modality

Figure 10-3: Two-point discrimination

Sensory Modality

Figure 10-6: Lateral inhibition

Fisiologi Nyeri

Terdapat empat proses:

Transduksi
Transmisi Modulasi Persepsi
Illustration of the pain pathway in Ren Descartes' Traite de l'homme (Treatise of Man) 1664. The long fiber running from the foot to the cavity in the head is pulled by the heat and releases a fluid that makes the muscles contract.

Nociceptor
Nosiseptor saraf aferen primer untuk menerima dan menyalurkan rangsangan nyeri. Reseptor yg peka terhadap rangsangan mekanis, suhu, listrik, kimiawi yg menimbulkan nyeri. Terletak di jaringan subcutis, otot rangka, dan sendi

Reseptor nyeri di visera tidak terdapat di parenchym organ internal, tetapi dipermukaan peritonium, membran pleura, dura mater, dan dinding pembuluh darah.

Klasifikasi Nosiseptor

Peripheral free nerve endings are nociceptors, where most nociceptors are either myelinated A-fibres or unmyelinated C-fibres. Thermal pain is mediated by both thin myelinated A- and unmyelinated Cfibres
Meyer et al. 1994

Klasifikasi Nosiseptor

Sensitasi perifer

Tipe Reseptor Sensorik

Simple receptors Complex neural Special senses Chemoreceptors Mechanoreceptors Thermoreceptors Photoreceptors

Tipe Reseptor Sensorik

Reseptor
Free nerve ending Vater-Pacini corpuscles Ruffini corpuscles Merkel receptors Meisaner's corpuscles

Raba, Tekanan, Vibrasi

Nyeri

Free nerve ending

Suhu

Free nerve ending Bulb of Krause Rufini corpuscel

Raba

Figure 10-11: Touch-pressure receptors

Proses Fisiologik
Transduksi
proses rangsangan yang menganggu sehingga menimbulkan aktivitas listrik di reseptor nyeri proses penyaluran impuls nyeri dari tempat transduksi melewati saraf perifer sampai ke terminal di medula spinalis dan jaringan neuron2 pemancar yg naik dari medula spinalis ke otak Aktivitas saraf melalui jalur2 saraf desendens dari otak mempengaruhi transmisi nyeri setinggi medula spinalis (melibatkan faktor2 kimiawi yg menimbulkan/ meningkatkan aktifitas di reseptor nyeri aferen primer pengalaman subyektif nyeri yg bagaimanapun juga dihasilkan oleh aktivitas transmisi nyeri oleh saraf

Transmisi

Modulasi

Persepsi

Transduksi
Start free nerve endings (nociceptors) of C fibres and

A-delta fibres of primary afferent neurones respond to noxious stimuli. Nociceptors are exposed to noxious stimuli when tissue damage and inflammation occurs as a result of, for example, trauma, surgery, inflammation, infection, and ischemia.

Noxious stimuli
pressure, swelling, abscess, incision, tumour growth

Mechanical

Thermal

burn, scald
prostaglandin bradykinin serotonin substance P potassium histamine

Chemical

excitatory neurotransmitter, toxic substance, ischaemia, infection

NORMAL IMPULSE TRANSMISSION

Impulses reach terminals of presynaptic neuron

Presynaptic neuron

Substance P

Glutamate

NMDA receptor is blocked by Mg2+

Synaptic cleft

Postsynaptic neuron

NK-1

NMDA receptor

AMPA receptor

NORMAL IMPULSE TRANSMISSION

Glutamate is released into synaptic cleft

Presynaptic neuron

Substance P

Glutamate

Synaptic cleft

NMDA receptor remains blocked by Mg2+

NMDA receptor

Postsynaptic neuron

NK-1

AMPA receptor

NORMAL IMPULSE TRANSMISSION

Glutamate binds to AMPA receptor and impulse is transmitted to postsynaptic neuron

Presynaptic neuron

Substance P

Glutamate

Synaptic cleft

NMDA receptor remains blocked by Mg2+

Postsynaptic neuron

NK-1

AMPA receptor

DEVELOPMENT OF CENTRAL SENSITIZATION

Injury or trauma causes increased nerve activity

Presynaptic neuron

Substance P

Glutamate

NMDA receptor is blocked by Mg2+

Synaptic cleft

Postsynaptic neuron

NK-1

NMDA receptor

AMPA receptor

DEVELOPMENT OF CENTRAL SENSITIZATION

Substance P and excessive levels of glutamate are released into the synaptic cleft
Presynaptic neuron

Substance P

Glutamate

NMDA receptor is blocked by Mg2+

Synaptic cleft

Postsynaptic neuron

NK-1

NMDA receptor

AMPA receptor

DEVELOPMENT OF CENTRAL SENSITIZATION

Substance P binds to NK-1 receptors, causing NMDA receptors to release Mg2+ ions

Presynaptic neuron

Substance P

Glutamate

Synaptic cleft

Postsynaptic neuron

NK-1

NMDA receptor

AMPA receptor

DEVELOPMENT OF CENTRAL SENSITIZATION

Glutamate molecules can now bind to AMPA and NMDA receptors

Presynaptic neuron

Substance P

Glutamate

Synaptic cleft

Postsynaptic neuron

AMPA receptor

DEVELOPMENT OF CENTRAL SENSITIZATION

Increased impulses transmitted to postsynaptic neuron

Presynaptic neuron

Substance P

Glutamate

Synaptic cleft

Postsynaptic neuron

Transmisi

Transduction site

Nociceptor fibre

Med-Spinalis kornu dorsalis

Brainstem

Thalamus, Korteks

Neuro transmiter

adenosine triphosphate; glutamate; calcitonin gene-related peptide; bradykinin; nitrous oxide; substance P

Modulasi

The modulation of pain involves changing or inhibiting

transmission of pain impulses in the spinal cord.

The multiple, complex pathways involved in the modulation of pain are referred to as the descending modulatory pain pathways (DMPP) and these can lead to either an increase in the transmission of pain impulses (excitatory) or a decrease in transmission (inhibition).

Neurotransmiter pada Modulasi

endogenous opioids (enkephalins and endorphins); serotonin (5-HT); norepinephirine (noradrenalin); gamma-aminobutyric acid (GABA); neurotensin; acetylcholine; oxytocin.

Jalur Sensorik

Persepsi
Perception of pain is the end result of the neuronal activity of pain transmission and where pain becomes a conscious multidimensional experience. The multidimensional experience of pain has affectivemotivational, sensory-discriminative, emotional and behavioural components.

JALUR NYERI
PERSEPSI NYERI

MODULASI TRANSMISI

TRANSDUKSI

Gate Control Theory of Pain

Pain input to the spinal cord:

-Projecting neurons in lamina I receive A-delta and C fibers info.

-Neurons in lamina II receive input from C fibers and relay it to other laminae. -Projecting neurons in lamina V (wide-dynamic range neurons) receive A-delta, C and Abeta (low threshold mechanoceptors) fibers information. How is pain info sent to the brain: hypotheses pain is signaled by lamina I and V neurons acting together. If lamina I cells are not active, the info about type and location of a stimulus provided by lamina V neurons is interpreted as innocuous. If lamina I cells are active then it is pain.
Thus: lamina V cells details about the stimulus, and lamina I cells whether it is painful or not -A-delta and C fibers release glutamate and peptides on dorsal horn neurons. -Substance P (SP) is co-released with glutamate and enhances and prolongs the actions of glutamate. -Glutamate action is confined to nearby neurons but SP can diffuse and affect other populations of neurons because there is no specific reuptake.

Kortek sensorik

Kortek sensorik

Kortek sensorik

General Properties of Sensory Systems

Figure 10-4: Sensory pathways

Duus, 1996

Duus, 1996

Gate Channel theory

Figure 13-8 - Overview

Klasifikasi
Akut OnsetDurasi
Mengikuti kerusakan jaringan krn trauma Durasi terbatas Intensitas berangsur berkurang Rasa tidak nyaman >3 bulan

Kronis

Nyeri

Fungsional/ psikogenik
Somatik

Patofisiologi

Nosiseptif inflamatorik
Neuropatik

Viseral Sentral Perifer

Nyeri
Fungsional/psikogenik

Nyeri akibat abnormalitas sistem saraf pusat berupa peningkatan sensitivitas thd berbagai stimuli dahulu dikenal dgn nyeri psikogenik

(Meliala et al 2000).

Nyeri Fungsional
Spontaneous Pain Pain Hypersensitivity Brain

Normal Peripheral Tissue and Nerves

Abnormal Central Processing

Meliala,2005

Nyeri
Nociceptive dan inflamatorik

Nyeri Nosiseptif - stimulasi singkat, tdk timbul kerusakan jaringan Nyeri Inflamatorik - Stimulasi kuat,kerusakan/ lesi jaringan atau proses inflamasi - Dapat bersifat spontan atau dibangunkan - Berguna utk proses penyembuhan - Melibatkan inflamasi perifer dan mediator inflamasi pada timbulnya rasa nyeri
(Meliala et al 2000).

Nyeri
Nociceptive dan inflamatory
Somatik Terlokalisir dan terbatas pada dermatom Karakteristik: tajam, crushing, tearing Nociceptive dan inflamatory

Rasa tidak nyaman krn iritasi peritoneum (peritonitis) Obstruksi usus atau uretra, apendiksitis Viseral

Nyeri sering dijalarkan ke dermatom Referred pain

Nyeri Nosiseptif
Pengalaman sensorik muncul saat neuron perifer sensorik spesifik
merespon stimulus yang noxious

Nyeri terlokalisir pada tempat trauma --- karakteristik: throbbing, aching

or stiffness

Dibatasi oleh waktu dan membaik saat terjadi penyebuhan jaringan

(bone fractures, burns and bruises)

Can also be chronic (e.g. osteoarthritis)

Responds to conventional analgesics

Meliala,2005

Nyeri Nosiseptif
Noxius Pheripheral Stimuli Pain Autonomic Response Witdrawal Reflex Brain

Heat
Cold Intense Mechanical Force

Nociceptor sensory neuron

Heat

Cold

Spinal cord
Meliala,2005

NYERI INFLAMASI
Inflamasi

Otak

Saraf penghantar

Kerusakan jaringan

Sumsum tulang belakang

TISSUE DAMAGE INFLAMATION SENSITITATION

Si-Na+
R-NE Anger Fear Anxiety Depression

SSA
ECT. DISC.

MI

NOS
PG B 5HT Adenosin

ACTIvATION

DORSAL COLUMN DESCENDING INHIBITION

BRAIN PAIN NO PAIN

EXAMPLE OF CHRONIC NOCICEPTIVE PAIN: OSTEOARTHRITIS OF THE KNEE

Perceived pain

Ascending input

Descending modulation

Tissue damage

Spinal cord

Peripheral nerve

Meliala,2005

Activation of local nociceptors

Nyeri
Neuropatik
Nyeri yang ditimbulkan karena adanya lesi sistem saraf perifer atau sentral Karakteristik: tertembak, elektrik shock, terbakar, kadang disertai dengan kesemutan atau kebas Lokasi nyeri mungkin tidak sama dengan lokasi trauma, nyeri muncul sesuai teritori neurologis dari struktur yang terkena ( saraf, radiks, medula spinalis, otak ) Almost always a chronic condition (e.g. postherpetic neuralgia, poststroke pain) Responds poorly to conventional analgesics

(Meliala et al 2000).

Nyeri Neuropatik
Spontaneous Pain Pain Hypersensitivity

Brain

Peripheral Nerve Damage

Spinal cord Injury

Meliala,2005

Burning, feeling like the feet are on fire

Freezing, like the feet are on ice, although they feel warm to touch

Stabbing, like sharp knives

Modified by Meliala 2006

Lancinating, like electric shocks

Pendekatan Terapi
Beydoun, 2002

BRAIN
Descending Inhibitors NE/5HT Opiate receptors Peripheral Sensitization

TCAs SSRIs SNRIs Tramadol Opiates

Central Sensitization
Ca++ : Pregabalin, GBP,OXC,LTG,LVT NMDA : Ketamine, TPM Dextromethorphan Methadone Others Capsaicin NSAIDs Cox inhibitors Levodopa

PNS
Na+ CBZ OXC PHT SPINAL TCA TPM LTG Mexiletine Lidocaine

CORD

Modified by MELIALA 2006

ANALGESIC MEDICATIONS INFLAMATORY PAIN

PRIMARY ANALGESICS Acetminophen Prostaglandin synthesis inhibitors Salicylates Traditonal NSAIDs COX-2-selective NSAIDs (coxibs) Tramadol Opioids Traditional Mixed ADJUVANT MEDICATIONS Antidepressants Anticonvulsants Local anesthetics Muscle Relaxant Miscellaneous agents

Nyeri Kronik: Intervensi

(McQuay & Moore, 1999)

Metode Terapi
Analgesik Blok Transmisi Saraf Ireversibel Operasi Destruksi saraf Stimulator Akupunktur Hipnosis Psikologi Alternatif

Analgesik - NSAID - Parasetamol opioid Ajuvan analgesik Antidepressan Antikonvulsan Muscle Relaxant Lain-lain

Reversibel Anestesi lokal steroid opioid

The WHO Analgesic Ladder

WHO Step III

Very severe

Hydromorphone Morphine Oxycodone Fentanyl Buprenorphine Tramadol Tilidine Codein Dextropropoxyphene NSAIDs COX II inhibitors

Severe

Pain intensitiy

WHO Step II

Moderate

WHO Step I

Mild

Acetylsalicylic acid Acetaminophene

Langford, 2002; Proceeding of the Grnenthal symposium

Drugs

Referensi

Wallace MS & Staats PS, 2005, Pain Medicine and Management, Mc Graw Hill, USA Basbaum A & Bushnell MC, 2009, Science of Pain, Elsevier, United Kingdom Bone I & Lindsay KW, 2004, Neurology and Neurosurgery Ilustrated, Churchil Livingstone, London Baehr M & Frotscher M, 2005, Duus Topical Diagnosis in Neurology, New York Meliala L, 2006, Manajemen Nyeri Lengkap, Yogyakarta