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Clinical Mentoring

Nyeri kronik
Dr Darma Imran Sp.S
Departememen Neurologi RSCM - FKUI

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Kasus 1
Seorang pria 49 tahun dengan keluhan nyeri pada
kepala, leher lengan bawah dan pinggang yang telah
berlangsung berulang dalam beberapa tahun
Pemeriksaan klinis neurologi dan ortopedik : dalam
batas normal
Pada pemeriksaan laboratorium dan pemeriksaan
radiologi : dalam batas normal
Apa yang harus kita jelaskan pada pasien ini ?

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Kasus 1
Apa yang akan kita sampaikan pada pasien ini ?
1. Keluhan nyeri ini tidak ada kelainan, ini hanya
perasaan pasien saja
2. Keluhan ini merupakan penyakit psikosomatik
3. Akan dilakukan pemeriksaan lain yg lebih canggih
untuk mencari sumber nyeri
4. Proses Central sensitization - FM

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The Normal Pain Processing Pathway
4. The descending tract carries
3. A signal is sent via
the ascending tract
Pain modulating impulses back to
to the brain, and Perceived the dorsal horn
perceived as pain

2. Impulses from afferents


depolarize dorsal horn
neurons, then, extracellular
Ca2+ diffuse into neurons
causing the release of Pain
Associated Neurotransmitters
Glutamate and Substance P

Glutamate
1. Stimulus sensed by
the peripheral nerve
Substance P
(ie, skin)

1. Staud R and Rodriguez ME. Nat Clin Pract Rheumatol. 2006;2:90-98.


2. Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1984.
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Central Sensitization: A Theory for
Neurological Pain Amplification in FM
Central sensitization is believed to be an underlying cause of the
amplified pain perception that results from dysfunction in the CNS1
May explain hallmark features of generalized heightened pain sensitivity2
Hyperalgesia Amplified response to painful stimuli
Allodynia - Pain resulting from normal stimuli
Theory of central sensitization is supported by:
Increased levels of pain neurotransmitters3,4
Glutamate
Substance P
fMRI data demonstrates low intensity stimuli in patients with FM
comparable to high intensity stimuli in controls5

fMRI = functional magnetic resonance imaging


1. Staud R and Rodriguez ME. Nat Clin Pract Rheumatol. 2006;2:90-98.
2. Williams DA and Clauw DJ. J Pain. 2009;10(8):777-791.
3. Sarchielli P, et al. J Pain. 2007;8:737-745.
4. Vaery H, et al. Pain. 1988;32:21-26.
5. Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343. 5
Central Sensitization Produces Abnormal
Pain Signaling
After nerve injury, increased input to the dorsal
Perceived pain horn can induce central sensitization

Nerve dysfunction
Ascending Descending
input modulation

Nociceptive afferent fiber


Induction of central sensitization
Perceived pain
(hyperalgesia/allodynia)
Increased release of pain neurotransmitters
glutamate and substance P
Minimal
stimuli
Pain
amplification

Increased pain perception


1. Adapted from Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1984.
2. Woolf CJ. Ann Intern Med. 2004;140:441-451. 6
FM: An Amplified Pain Response

10 Pain in FM
Normal pain
Subjective pain intensity

8 response
Hyperalgesia Pain
amplification
(when a pinprick causes an response
6 intense stabbing sensation)

4 Allodynia
(hugs that feel painful)

0
Stimulus intensity
Adapted from Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1986.
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fMRI Study Supports the Amplification of
Normal Pain Response in Patients With FM
14

12
Pain intensity

10

0
1.5 2.5 3.5 4.5
Red: Activation at low intensity stimulus in patients with FM
Stimulus intensity (kg/cm2)

Patients with FM experienced high Green: Activated only at high intensity stimulus in controls
pain with low grade stimuli
Yellow: Area of overlap (ie, area activated at high
FM (n=16) intensity stimuli in control patients was activated by low
Subjective pain control intensity stimuli in patients with FM)
(n=16)
Stimulus pressure control

fMRI = functional magnetic resonance imaging


Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343. 8
Patients With FM Have Elevated Pain
Neurotransmitter Substance P in Their CSF
In 3 separate clinical studies, substance P, a pain
neurotransmitter, was elevated in FM patients1-3

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Substance P concentration

P<0.001 P<0.001
FM patients
40 42.8 43 Healthy control subjects
(fmoles/mL)

30
P<0.03
20
19.26
16.3 17
10 12.83

0
*1 *2 *3
Russell 1994 Russell 1995 Bradley
n=32 n=24 n=14
n=30 n=24 n=10

CSF = cerebrospinal fluid


*CSF sample collected via lumbar puncture in FM and healthy controls and SP levels assessed by radioimmunoassay
fmoles/mL = femtomole/mL = 10-15 mole/mL

1. Russell IJ, et al. Arthritis Rheum. 1994;37:1593-1601.


2. Russell IJ, et al. Myopain 1995: Abstracts from the 3rd World Congress on Myofascial Pain and Fibromyalgia; July 30 - August 3, 1995; San Antonio, TX.
3. Bradley LA, et al. Arthritis Rheum. 1996;suppl 9:212. Abstract 1109. 9
Patients With FM Have Elevated Pain
Neurotransmitter Glutamate in Their CSF
CSF Levels of Glutamate
2.5 Sarchielli et al measured
CSF level of glutamate (g/mL)

P<0.003 FM patient CSF levels of glutamate in


2.0 Control 20 FM patients and 20
age-matched controls
1.5
Significantly higher levels
1.0
of glutamate were found in
FM patients compared
0.5 with controls

0
FM patient Control

CSF = cerebrospinal fluid


Sarchielli P, et al. J Pain. 2007;8:737-745. 10
FM Pathophysiology: Summary
Central sensitization is a leading theory of FM
pathophysiology1
Elevated pain neurotransmitters in CSF of patients with
FM2-4
Several studies showed elevated levels of glutamate and
substance P
Elevated levels suggest that this may contribute to pain
amplification

fMRI data supports FM as a disorder of central pain


amplification5
Areas activated by high intensity stimuli in control patients were
activated by low intensity stimuli in patients with FM

CSF = cerebrospinal fluid


fMRI = functional magnetic resonance imaging 3. Bradley LA, et al. Arthritis Rheum. 1996;suppl 9:212. Abstract 1109.
1. Staud R and Rodriguez ME. Nat Clin Pract Rheum. 2006;2:90-98. 4. Sarchielli P, et al. J Pain. 2007;8:737-745.
2. Russell IJ, et al. Arthritis Rheum. 1994;37:1593-1601. 5. Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343. 11
Clinical Features of FM
Chronic Widespread Pain1,2
CORE criteria of FM
Pain is in all 4 quadrants of the body 3 months
Patient descriptors of pain include:4
Aching, exhausting, nagging, and hurting

Tenderness2
Sensitivity to pressure stimuli
Hugs, handshakes are painful
Tender point exam given to assess tenderness
Hallmark features of FM4
Hyperalgesia
Allodynia

Other Symptoms2,3,5
Fatigue
Pain-related conditions/symptoms
Chronic headaches/migraines, IBC, IC, TMJ, PMS
Subjective morning stiffness
Neurologic symptoms
Other Nondermatomal paresthesias
Symptoms Subjective numbness, tingling in extremities
Sleep disturbance
Non-restorative sleep, RLS

1. Leavitt F, et al. Arthritis Rheum. 1986;29:775-781.


2. Wolfe F, et al. Arthritis Rheum. 1995;38:19-28. 4. Staud R. Arthritis Res Ther. 2006;8(3):208-214.
3. Roizenblatt S, et al. Arthritis Rheum. 2001;44:222-230. 5. Harding SM. Am J Med Sci. 1998;315:367-376.
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Widespread Pain and Tenderness
are the Defining Features of FM
In patients with FM, pain involves more areas
than other chronic pain conditions
* Chronic Pain Controls
98
100 FM patients
*
* 85
* 79
80
72
69
% of patients

60
51
46

40

24
20

0
Widespread pain Thoracic pain Lumbar pain Cervical pain
*P<0.001
Wolfe F, et al. Arthritis Rheum. 1990;33:160-172. 13
Patients With FM Present With
a Global Pain Disorder
While the ACR classification
criteria focuses on 18 points,
patients do not usually speak
of tender points1
This is a pain drawinga
patient colors all areas of the
body in which they feel pain2
The diagram shows that the
pain of FM is widespread1

ACR = American College of Rheumatology Back Front


1. Wolfe F, et al. Arthritis Rheum. 1990:33:160-172. Adapted from pain drawing provided courtesy of L Bateman.
2. Silverman SL and Martin SA. In: Wallace DJ, Clauws DJ, eds. Fibromyalgia & Other Central Pain
Syndromes. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2005:309-319. 14
Manual Tender Point Survey* for the
Diagnosis of FM
TRAPEZIUS
LOW CERVICAL Upper border of trapezius,
Anterior aspects of C5, C7 midportion
OCCIPUT
intertransverse spaces At nuchal muscle
insertion

FOREHEAD
SUPRASPINATUS
SECOND RIB SPACE
about 3 cm lateral to sternal At attachment to medial
border border of scapula

ELBOW RIGHT FOREARM


Muscle attachments to
Lateral Epicondyle
GLUTEAL
Upper outer quadrant of
gluteal muscles
KNEE
Medial fat pad of knee GREATER
proximal to joint line LEFT TROCHANTER
THUMB Muscle attachments just
posterior to GT

Manual Tender Points Survey:


Presence of 11 tender points on palpation to a maximum of 4 kg Control Points
of pressure (just enough to blanch examiners thumbnail) Tender Points
*Based on 1990 ACR FM Criteria
1. Adapted from Chakrabarty S and Zoorob R. Am Fam Physician. 2007;76(2);247-254. 15
Kasus 1

Seorang pria berusia 36 tahun jatuh dari


atap rumah, saat memperbaiki antena TV
Pasien mengeluhkan nyeri hebat di
pinggang bawah-bokong, disertai dengan
nyeri tekan pada bokong. Selain itu pasien
juga merasakan bokongnya terasa baal.
Nyeri apakah yg dialami pasien ini ?
A. Nyeri akut
B. Nyeri kronik
C. Nyeri nosiseptif
D. Nyeri neuropatik
E. Nyeri campuran
Karakter nyeri : deskripsi keluhan nyeri

Nyeri tajam (sharp pain)


Nyeri ditusuk (stabbing pain)
Nyeri tumpul (dull pain)
Nyeri berdenyut (throbbing pain)
Identifikasi istilah yg digunakan oleh berbagai bahasa di
Indonesia untuk melukiskan nyeri
Cekot-cekot ?
Mules
Panas
Sakit
Pendekatan thdp
pasien dgn masalah nyeri

1. Lokasi
2. Onset dan durasi
3. Karakter nyeri intensitas nyeri
4. Faktor yg memperberat dan meringankan, akibat nyeri pd aktifitas
pasien
5. Tentukan gejala-tanda penyerta
6. Tentukan sindrom nyeri dan patofisiologinya
7. Tentukan diagnosis dan penyebab nyeri
8. Rencanakan pemeriksaan lain untuk menunjang diagnosis sementara
9. Atasi kegawat daruratan yang ada
10. Tentukan strategi pengobatan secara holistik
Penanganan Nyeri
Non-farmakologik
Information, Reassurance and Identification of Trigger Factors
Psychological Treatments
Relaxation Training
Electromyography Biofeedback
CognitiveBehavioural Therapy
Physical Therapy

Terapi farmakologik
Kerja obat anti nyeri
Bekerja pd tempat cedera dgn mengurangi
reaksi inflamasi : dengan menghambat kerja
enzim cyclo-oxygenase (COX). Contoh
:NSAID seperti aspirin, ibuprofen dan asam
mefenamat.
Merubah konduksi saraf : menghambat
potensial aksi dengan cara menghambat
channel natrium. Obat anastesi lokal
Modifikasi transmisi pd ganglion dorsalis :
golongan opioid dan agonisnya, obat
antiepileptik
Mempengaruhi komponen sentral dari
jaras sensorik : antidepresan, antiepileptik,
opioid, relaksan otot
Kasus 3
Seorang wanita berusia 50 thn
Mengeluh nyeri hebat pd pada rahang atas kanan yang
berlangsung sangat singkat namun sering berulang
dalam 4 bulan terakhir.
Apa yg dialami oleh pasien ini ?
Nyeri neuropatik
Nyeri nosiseptif
Nyeri neuralgia trigeminal
Nyeri neuralgia glosofaringeal
lanjut Kasus 3
Obat apa yg dapat diberikan utk mengurangi keluhan
pasien ini ?
a) Asam mefenamat
b) Parasetamol
c) Ibuprofen
d) Karbamazepin

Apa efek samping obat tsb ?


Kasus 4

Pria berusia 30 tahun


Nyeri hebat pada pinggang yang menjalar ke tungkai kiri
hingga ibu jari kaki sejak 3 hari yg lalu.
6 bulan yll pasien telah menjalani operasi untuk keluhan
yg sama karena saraf kejepit di pinggang.

Tentukan pilihan obat yang akan digunakan


a) Ibuprofen
b) Gabapentin
c) Morfin
d) Neurorestorasi modulasi nyeri di otak
Kasus 5

Seorang wanita 30 thn


Nyeri kepala berulang sejak 5 hr yll
data apa lagi yg ingin anda
dapatkan ?
Lanjut .. Kasus 5
Nyeri berulang dialami sejak 3-5 thn yll
Durasi nyeri ??
Nyeri datang beberapa jam terutama disiang hari dan berkurang
dimalam hari.
Tidak ada penglihatan ganda, namun pasien tidak kuat melihat sinar
terang dan juga suara yg bising
Pasien juga mengeluhkan mual dan tidak pergi ke kantor akibat nyeri
kepala yg terjadi
Letak nyeri tu pd kepala sisi kiri, berdenyut
Tanda vitaldalam batas normal
PF Neurologi : dalam batas normal
Lanjut . Kasus 5
1. Apakah ada tanda sakit kepala yg berbahaya
2. Apakah termasuk sakit kepala primer ?
a) Migren ?
b) Tension type headache ?
Chronic pain
"Chronic pain really is a disease of the central nervous
system," . "As such, it is a disease that affects the
sensory, emotional, motivational, cognitive and
modulatory pathways.
The way we approach patients in pain may need to be
revised.
Borsook et al 2011
Kesimpulan
Fibromyalgia sering kali ditemukan bersama dengan berbagai
kelainan kronik lainnnya yang berhubungan dengan central
sensitization
Kriteria fibromyalgia
Nyeri luas 3 bulan
Nyeri di 4 kuadran and aksial skeleton
tender points > 11
Perlu dibedakan apakah nyeri akut atau nyeri kronik
Masalah nyeri nosiseptif atau nyeri neuropatik atau nyeri campuran.
Tatalaksana nyeri secara non-farmakologik dan farmakologik.
Aspek Central sensitization dipertimbangkan dlm setiap kasus nyeri

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