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 3. A signal is sent via the ascending tract to the brain, and perceived as pain
Pain Perceived
4. The descending tract carries modulating impulses back to the dorsal horn
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 (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.
Substance P
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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. Vaerøy H, et al. Pain. 1988;32:21-26. 5. Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.
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Central Sensitization Produces Abnormal Pain Signaling Perceived pain
Ascending input
After nerve injury, increased input to the dorsal horn can induce central sensitization Nerve dysfunction
Descending 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.
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FM: An Amplified Pain Response
Subjective pain intensity
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Pain in FM Normal pain response
8 Hyperalgesia 6
(when a pinprick causes an intense stabbing sensation)
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Allodynia
Pain amplification response
(hugs that feel painful)
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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
Pain intensity
12 10
8 6 4 2 0 1.5
2.5
Stimulus intensity
3.5
4.5
(kg/cm2)
Patients with FM experienced high pain with low grade stimuli FM (n=16) Subjective pain control Stimulus pressure control fMRI = functional magnetic resonance imaging Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.
(n=16)
Red: Activation at low intensity stimulus in patients with FM Green: Activated only at high intensity stimulus in controls
Yellow: Area of overlap (ie, area activated at high intensity stimuli in control patients was activated by low intensity stimuli in patients with FM)
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Patients With FM Have Elevated Pain Neurotransmitter Substance P in Their CSF
Substance P concentration (fmoles/mL)†
In 3 separate clinical studies, substance P, a pain neurotransmitter, was elevated in FM patients1-3 50 40
P<0.001
P<0.001
42.8
43
FM patients Healthy control subjects
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P<0.03 20 10
19.26
17
16.3
12.83
0 Russell 1994
*1
*2
*3
Russell 1995
Bradley
n=32
n=24
n=14
n=30
n=24
n=10
CSF = cerebrospinal fluid 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. *CSF
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Patients With FM Have Elevated Pain Neurotransmitter Glutamate in Their CSF CSF level of glutamate (µg/mL)
CSF Levels of Glutamate 2.5 P<0.003
FM patient Control
2.0 1.5
Sarchielli et al measured CSF levels of glutamate in 20 FM patients and 20 age-matched controls Significantly higher levels of glutamate were found in FM patients compared with controls
1.0 0.5 0 FM patient
CSF = cerebrospinal fluid Sarchielli P, et al. J Pain. 2007;8:737-745.
Control
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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 1. Staud R and Rodriguez ME. Nat Clin Pract Rheum. 2006;2:90-98. 2. Russell IJ, et al. Arthritis Rheum. 1994;37:1593-1601.
3. Bradley LA, et al. Arthritis Rheum. 1996;suppl 9:212. Abstract 1109. 4. Sarchielli P, et al. J Pain. 2007;8:737-745. 5. Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.
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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
Other Symptoms
• Neurologic symptoms • Nondermatomal paresthesias • 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. 3. Roizenblatt S, et al. Arthritis Rheum. 2001;44:222-230.
4. Staud R. Arthritis Res Ther. 2006;8(3):208-214. 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 FM patients
98
100
*
85
*
*
80
72
69
% of patients
79
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.
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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 drawing—a 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 1. Wolfe F, et al. Arthritis Rheum. 1990:33:160-172.
Back
Front
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.
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Manual Tender Point Survey* for the Diagnosis of FM LOW CERVICAL – Anterior aspects of C5, C7 intertransverse spaces
TRAPEZIUS – Upper border of trapezius, midportion
OCCIPUT – At nuchal muscle insertion
FOREHEAD SUPRASPINATUS –
SECOND RIB SPACE –
At attachment to medial border of scapula
about 3 cm lateral to sternal border
ELBOW –
RIGHT FOREARM
Muscle attachments to Lateral Epicondyle
GLUTEAL – Upper outer quadrant of gluteal muscles
KNEE – Medial fat pad of knee proximal to joint line
LEFT THUMB
Manual Tender Points Survey: • Presence of 11 tender points on palpation to a maximum of 4 kg of pressure (just enough to blanch examiners thumbnail) *Based on 1990 ACR FM Criteria 1. Adapted from Chakrabarty S and Zoorob R. Am Fam Physician. 2007;76(2);247-254.
GREATER TROCHANTER – Muscle attachments just posterior to GT
Control Points Tender Points 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
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Onset dan durasi
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Karakter nyeri – intensitas nyeri
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Faktor yg memperberat dan meringankan, akibat nyeri pd aktifitas pasien
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Tentukan gejala-tanda penyerta
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Tentukan sindrom nyeri dan patofisiologinya
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Tentukan diagnosis dan penyebab nyeri
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Rencanakan pemeriksaan lain untuk menunjang diagnosis sementara
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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 Cognitive–Behavioural 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
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Modifikasi transmisi pd ganglion dorsalis : golongan opioid dan agonisnya, obat antiepileptik
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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) b) c) d)
Asam mefenamat Parasetamol Ibuprofen 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) b)
Migren ? 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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