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Management Of Different Types Of Pain KRT Lucas Meliala Guru Besar Luar Biasa Bagian Ilmu

Management Of Different Types Of Pain

KRT Lucas Meliala

Guru Besar Luar Biasa Bagian Ilmu Penyakit Saraf Fakultas Kedokteran Universitas Gadjah Mada, Yogyakarta

Symposium Clinical Update Yogyakarta, Januari 2011

Curriculum Vitae Pendidikan : Lulus Dokter tahun 1969, Nama : : : : : :

Curriculum Vitae

Pendidikan :

Lulus Dokter tahun 1969,

Nama

:

:

:

:

:

:

Prof. dr. KRT. Lucas Meliala, SpKJ, SpS(K).

alumnus FK-UGM

Tempat/tanggal lahir

Membang Muda (Sumut),

Lulus Spesialis Saraf & Jiwa tahun 1974

Alamat

22 September 1941 Jl. Nagan Lor 70, Jogjakarta

Pekerjaan

:

alumnus FK-UI, FK-UGM, FK Unair Staf Fakultas Kedokteran UGM

Telepon

(0274) 450758

bagian IP Saraf sejak tahun 1968 sampai sekarang

Fax.

(0274) 374052

Organisasi :

1999-2007 :

Mobile

0815 687 0584

Ketua Pokdi Nyeri Perdossi

E-mail

: lucasmeliala@yahoo.com

Anggota IASP, ENS Ketua Governing board IPS

Definisi Nyeri

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

Meliala et al., 2002, Pokdi Nyeri Perdossi

Klasifikasi Nyeri

Nyeri

Adaptif

Klasifikasi Nyeri Nyeri Adaptif Maladaptif Nosiseptif Inflamasi Neuropatik Fungsional NOCICEPTIVE PAIN Noxius Pheripheral
Klasifikasi Nyeri Nyeri Adaptif Maladaptif Nosiseptif Inflamasi Neuropatik Fungsional NOCICEPTIVE PAIN Noxius Pheripheral

Maladaptif

Klasifikasi Nyeri Nyeri Adaptif Maladaptif Nosiseptif Inflamasi Neuropatik Fungsional NOCICEPTIVE PAIN Noxius Pheripheral
Klasifikasi Nyeri Nyeri Adaptif Maladaptif Nosiseptif Inflamasi Neuropatik Fungsional NOCICEPTIVE PAIN Noxius Pheripheral

Nosiseptif

Inflamasi

Neuropatik

Fungsional

NOCICEPTIVE PAIN

Noxius Pheripheral Stimuli Heat Pain Autonomic Response Witdrawal Reflex Cold Brain Intense Mechanical
Noxius Pheripheral Stimuli
Heat
Pain
Autonomic Response
Witdrawal Reflex
Cold
Brain
Intense
Mechanical
Nociceptor
Force
sensory neuron
Heat
Spinal cord
Cold
Inflammation
INFLAMANTORY PAIN
Spontaneous Pain
Pain Hypersensitivity
Macrophage
Reduced Threshold
: Aliodyna
Mast Cell
Increased Response : Hyperalgesia
Neutrophil
Brain
Granulocyte
Nociceptor
Tissue Damage
sensory neuron
Spinal cord

NEUROPATHIC PAIN Spontaneous Pain Pain Hypersensitivity

Peripheral Nerve Damage Spinal cord Injury

Peripheral Nerve

Damage

Spinal cord Injury

Brain

FUNCTIONAL PAIN

Spontaneous Pain Pain Hypersensitivity NOCICPTOR Brain NOCICPTOR Normal Peripheral Tissue and Nerves NOCICPTOR
Spontaneous Pain
Pain Hypersensitivity
NOCICPTOR
Brain
NOCICPTOR
Normal Peripheral
Tissue and Nerves
NOCICPTOR
Abnormal Central
Processing

PAIN – SERIES OF EVENTS

PERCEPTION

PAIN
PAIN
PAIN – SERIES OF EVENTS PERCEPTION PAIN MODULATION CONDUCTION TRANSMISSION “Rasa sakit adalah hak istimewa kita”

MODULATION

CONDUCTION

– SERIES OF EVENTS PERCEPTION PAIN MODULATION CONDUCTION TRANSMISSION “Rasa sakit adalah hak istimewa kita”
– SERIES OF EVENTS PERCEPTION PAIN MODULATION CONDUCTION TRANSMISSION “Rasa sakit adalah hak istimewa kita”

TRANSMISSION

SERIES OF EVENTS PERCEPTION PAIN MODULATION CONDUCTION TRANSMISSION “Rasa sakit adalah hak istimewa kita” TRANSDUCTION

“Rasa sakit adalah hak istimewa kita”

TRANSDUCTION

Nyeri Inflamasi

• Nyeri akibat kerusakan jaringan atau proses inflamasi

• Dapat bersifat spontan atau dibangunkan

• Berguna untuk mempercepat penyembuhan

Meliala, 2004

Heat Cold Intense Mechanical Force Heat Cold NOCICEPTIVE PAIN Pain Autonomic Response Witdrawal Reflex Brain

Heat

Cold

Intense

Mechanical

Force

Heat

Cold

NOCICEPTIVE PAIN

Pain Autonomic Response Witdrawal Reflex Brain Nociceptor sensory neuron Spinal cord
Pain
Autonomic Response
Witdrawal Reflex
Brain
Nociceptor sensory neuron
Spinal cord

Noxius Pheripheral Stimuli

Modifikasi Meliala, 2005

PRESENTATION ACROSS PAIN STATES VARIES

Neuropathic Pain Pain initiated or caused by a primary lesion or dysfunction in the nervous
Neuropathic Pain
Pain initiated or caused by a
primary lesion or dysfunction
in the nervous system
(either peripheral or
central nervous system) 1
Mixed Pain
Pain with
neuropathic and
nociceptive
components
Nociceptive Pain
Pain caused by injury to
body tissues
(musculoskeletal,
cutaneous or visceral) 2

Examples

Peripheral

Postherpetic neuralgia

Trigeminal neuralgia

Diabetic peripheral neuropathy

Postsurgical neuropathy

Posttraumatic neuropathy Central

Poststroke pain Common descriptors 2

Burning

Tingling

Hypersensitivity to touch or cold

Examples

Low back pain with radiculopathy

Cervical radiculopathy

Cancer pain

Carpal tunnel syndrome

Examples

Pain due to inflammation

Limb pain after a fracture

Joint pain in osteoarthritis

Postoperative visceral pain

Common descriptors 2

Aching

Sharp

Throbbing

1. International Association for the Study of Pain. IASP Pain Terminology.

HEAT

PRESSURE

PEGELBRAINPERIHPANAS

HEAT PRESSURE PEGEL BRAIN PERIH PANAS CHEMICAL Modifikasi Meliala, 2003
CHEMICAL
CHEMICAL

Modifikasi Meliala, 2003

NOCICEPTIVE TRANSDUCTION

Capsaicin

Na V 1.8/1.9 Na +
Na V 1.8/1.9
Na +

H +

Heat

TRANSDUCTION Capsaicin Na V 1.8/1.9 Na + H + Heat Heat Heat H + Pinch Cold

Heat

TRANSDUCTION Capsaicin Na V 1.8/1.9 Na + H + Heat Heat Heat H + Pinch Cold
TRANSDUCTION Capsaicin Na V 1.8/1.9 Na + H + Heat Heat Heat H + Pinch Cold

Heat

H +

Pinch

Cold

ATP

Nociceptor Peripheral Terminal

PAIN

EXAMPLE OF CHRONIC NOCICEPTIVE PAIN:

OSTEOARTHRITIS OF THE KNEE

OF CHRONIC NOCICEPTIVE PAIN: OSTEOARTHRITIS OF THE KNEE Normal joint Osteoarthritis Inflammation as bones rub

Normal joint

Osteoarthritis

PAIN: OSTEOARTHRITIS OF THE KNEE Normal joint Osteoarthritis Inflammation as bones rub together Synovial fluid Synovial
PAIN: OSTEOARTHRITIS OF THE KNEE Normal joint Osteoarthritis Inflammation as bones rub together Synovial fluid Synovial
PAIN: OSTEOARTHRITIS OF THE KNEE Normal joint Osteoarthritis Inflammation as bones rub together Synovial fluid Synovial
PAIN: OSTEOARTHRITIS OF THE KNEE Normal joint Osteoarthritis Inflammation as bones rub together Synovial fluid Synovial

Inflammation as bones rub together

Synovial

fluid

Synovial

Inflammation as bones rub together Synovial fluid Synovial membrane Joint capsule Cartilage Thinned cartilage

membrane

Inflammation as bones rub together Synovial fluid Synovial membrane Joint capsule Cartilage Thinned cartilage

Joint

capsule

Cartilage

Thinned

cartilage

Nyeri Neuropatik

Nyeri yang disebabkan oleh lesi atau disfungsi pada sistem saraf

Meliala, 2004

“Berbuatlah dan cintailah tanpa memperhitungkan kebahagiaanmu sendiri, dan engkau akan berbahagia sepanjang waktu”

WHAT IS NEUROPATHIC PAIN?

• Pain initiated or caused by a primary lesion or dysfunction in the peripheral or central nervous system

• Pain often described as shooting, electric shock-like, burning – commonly associated with tingling or numbness

• The painful region may not necessarily be the same as the site of injury. Pain occurs in the neurological territory of the affected structure (nerve, root, spinal cord, brain)

• Almost always a chronic condition (e.g. postherpetic neuralgia, poststroke pain)

• Responds poorly to conventional analgesics

NEUROPATHIC PAIN

NEUROPATHIC PAIN Modifikasi Meliala, 2005 Spontaneous Pain Pain Hypersensitivity Brain Peripheral Nerve Damage Spinal
NEUROPATHIC PAIN Modifikasi Meliala, 2005 Spontaneous Pain Pain Hypersensitivity Brain Peripheral Nerve Damage Spinal

Modifikasi Meliala, 2005

Spontaneous Pain Pain Hypersensitivity

Brain Peripheral Nerve Damage
Brain
Peripheral Nerve
Damage

Spinal cord Injury

Ectopic Discharges

Nerve lesion induces hyperactivity due to changes in ion channel function

Perceived pain Nerve lesion Descending Ascending modulation input Nociceptive afferent fiber
Perceived pain
Nerve lesion
Descending
Ascending
modulation
input
Nociceptive afferent fiber
pain Nerve lesion Descending Ascending modulation input Nociceptive afferent fiber Ectopic discharges Spinal cord
Ectopic discharges
Ectopic discharges

Spinal cord

Central sensitization
Central sensitization
After nerve injury, increased input to the dorsal horn can induce central sensitization Perceived pain
After nerve injury, increased input to the dorsal horn can induce central
sensitization
Perceived pain
Nerve lesion
Descending
Ascending
modulation
input
Nociceptive afferent fiber
Perceived pain
(allodynia)
Abnormal discharges induce central sensitization
Tactile
Descending
Ascending
stimuli
modulation
input
Intact tactile fiber

Pathophysiological Mechanisms Of Neuropathic Pain

Aδ or Aβ fibre

Mechanisms Of Neuropathic Pain A δ or A β fibre Spinal cord dorsal horn C-fibre Skin

Spinal cord dorsal horn

C-fibre Skin C-fibre Α2-δ subunit
C-fibre
Skin
C-fibre
Α2-δ subunit
Skin
Skin
Skin

Skin

Skin
Opioid receptor NMDA receptor NE/5HT receptor GABA receptor α-adrenoceptor A δ or A β fibre
Opioid receptor NMDA receptor NE/5HT receptor GABA receptor α-adrenoceptor A δ or A β fibre
Opioid receptor NMDA receptor NE/5HT receptor GABA receptor α-adrenoceptor A δ or A β fibre

Opioid receptor NMDA receptor NE/5HT receptor GABA receptor

α-adrenoceptor

Aδ or Aβ fibre

TRPV1 receptor AMPA/KA receptor Chemokine receptor Cytokine receptor Sodium channel Calcium Channel (Α2-δ subunit)

Baron et al., 2010 Lancet Neurology 2010;9:807-19

receptor Sodium channel Calcium Channel (Α2- δ subunit) Baron et al., 2010 Lancet Neurology 2010;9:807-19
receptor Sodium channel Calcium Channel (Α2- δ subunit) Baron et al., 2010 Lancet Neurology 2010;9:807-19

Cytokine receptor AMPA/KA receptor

Neurology 2010;9:807-19 Cytokine receptor AMPA/KA receptor C-fibre C-fibre Chemokine receptor Modifikasi Meliala, 2010

C-fibre

Neurology 2010;9:807-19 Cytokine receptor AMPA/KA receptor C-fibre C-fibre Chemokine receptor Modifikasi Meliala, 2010
Neurology 2010;9:807-19 Cytokine receptor AMPA/KA receptor C-fibre C-fibre Chemokine receptor Modifikasi Meliala, 2010

C-fibre

Chemokine receptor

Modifikasi Meliala, 2010

EXAMPLE OF NEUROPATHIC PAIN:

ULNAR NERVE LESION FOLLOWING BONE FRACTURE

EXAMPLE OF NEUROPATHIC PAIN: ULNAR NERVE LESION FOLLOWING BONE FRACTURE Ulnar nerve
EXAMPLE OF NEUROPATHIC PAIN: ULNAR NERVE LESION FOLLOWING BONE FRACTURE Ulnar nerve
EXAMPLE OF NEUROPATHIC PAIN: ULNAR NERVE LESION FOLLOWING BONE FRACTURE Ulnar nerve

Ulnar nerve

EXAMPLE OF NEUROPATHIC PAIN:

ULNAR NERVE LESION FOLLOWING BONE FRACTURE

NEUROPATHIC PAIN: ULNAR NERVE LESION FOLLOWING BONE FRACTURE Trauma leading to nerve lesion Ascending Descending input

Trauma

leading

to nerve

lesion

Ascending Descending input modulation
Ascending
Descending
input
modulation
Spinal cord
Spinal cord

Perceived pain

Lesion
Lesion

Impulses generated within ulnar nerve

Perceived pain Lesion Impulses generated within ulnar nerve Peripheral nociceptors “Gedung-gedung makin tinggi namun

Peripheral

nociceptors

“Gedung-gedung makin tinggi namun sumbu amarah kita makin pendek”

NEUROPATHIC PAIN PREVALENCE RANGES FROM 6.0-7.7% IN EUROPE

10 9 8 7.7% 7.5% 7 6.4% 6.0% 6 5 4 3 2 1 0
10
9
8
7.7%
7.5%
7
6.4%
6.0%
6
5
4
3
2
1
0
% of patients

UK

France

Germany

Spain

Modified Meliala, 2007

Patients with axial back pain with a neuropathic component included in the survey Data on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey

FUNCTIONAL PAIN

FUNCTIONAL PAIN Spontaneous Pain Pain Hypersensitivity Brain Abnormal Central Processing Normal Peripheral Tissue and
FUNCTIONAL PAIN Spontaneous Pain Pain Hypersensitivity Brain Abnormal Central Processing Normal Peripheral Tissue and

Spontaneous Pain Pain Hypersensitivity

Brain

FUNCTIONAL PAIN Spontaneous Pain Pain Hypersensitivity Brain Abnormal Central Processing Normal Peripheral Tissue and
FUNCTIONAL PAIN Spontaneous Pain Pain Hypersensitivity Brain Abnormal Central Processing Normal Peripheral Tissue and

Abnormal Central Processing

PAIN Spontaneous Pain Pain Hypersensitivity Brain Abnormal Central Processing Normal Peripheral Tissue and Nerves
PAIN Spontaneous Pain Pain Hypersensitivity Brain Abnormal Central Processing Normal Peripheral Tissue and Nerves

Normal Peripheral Tissue and Nerves

Nyeri Fungsional

• Nyeri akibat abnormalitas sistem saraf pusat, berupa peningkatan sensitivitas terhadap berbagai stimuli

• Dahulu dikenal dengan nyeri psikogenik

Woolf, 2004, Meliala, 2004

PENYAKIT, KESAKITAN, ATAU KEDUANYA

BERU

PENYAKIT, KESAKITAN, ATAU KEDUANYA BERU Penyakit tanpa kesakitan Ulkus (luka) Penyakit dan kesakitan SAKIT T a

Penyakit

tanpa

kesakitan

KESAKITAN, ATAU KEDUANYA BERU Penyakit tanpa kesakitan Ulkus (luka) Penyakit dan kesakitan SAKIT T a n

Ulkus (luka)

ATAU KEDUANYA BERU Penyakit tanpa kesakitan Ulkus (luka) Penyakit dan kesakitan SAKIT T a n p
ATAU KEDUANYA BERU Penyakit tanpa kesakitan Ulkus (luka) Penyakit dan kesakitan SAKIT T a n p

Penyakit dan kesakitan

tanpa kesakitan Ulkus (luka) Penyakit dan kesakitan SAKIT T a n p a U l k
tanpa kesakitan Ulkus (luka) Penyakit dan kesakitan SAKIT T a n p a U l k

SAKIT

Tanpa Ulkus ( tidak luka)

SAKIT T a n p a U l k u s ( tidak luka) Nyeri perut
SAKIT T a n p a U l k u s ( tidak luka) Nyeri perut

Nyeri perut fungsional yang kronik

Kesakitan

tanpa

penyakit

A M E SAKIT
A M E
SAKIT

Somatic symptoms that might be considered in reaching a diagnosis of fibromyalgia

Muscle pain/weakness

Fatigue/tiredness

Cognitive problems

Headache

Abdominal pain/cramps

Numbness/tingling

Dizziness

Insomnia

Depression

Constipation

Nausea

Nervousness

Chest pain

Fever

Diarrhoea

Dry mouth

Itching

Wheezing

Raynaud’s phenomenon

Hives/welts

Ringing in ears

Vomiting

Heartburn

Oral ulcers

Seizures

Dry eyes

Loss of appetite

Rash

Sun sensitivity

Hearing difficulties

Easily bruised

Hair loss

Frequent urination

Painful urination

Bladder spasms

Loss of taste

Change in taste

Blurred vision

Shortness of breath

Wolfe et al. Arthritis Care Res 2010;62:600-610

ID Pain Questionnaire

1. Did the pain feel like pins and needles ?

Yes (+1 point)Questionnaire 1. Did the pain feel like pins and needles ? No (0 points) 2. Did

1. Did the pain feel like pins and needles ? Yes (+1 point) No (0 points)

No (0 points)

2. Did the pain feel hot/burning ?

Yes (+1 point)(+1 point) No (0 points) 2. Did the pain feel hot/burning ? No (0 points) 3.

No (0 points)points) 2. Did the pain feel hot/burning ? Yes (+1 point) 3. Did the pain feel

3. Did the pain feel numb ? Yes (+1 point)

4. Did the pain feel like electrical shocks ?

(+1 point) 4. Did the pain feel like electrical shocks ? No (0 points) Yes (+1
(+1 point) 4. Did the pain feel like electrical shocks ? No (0 points) Yes (+1

No (0 points)

4. Did the pain feel like electrical shocks ? No (0 points) Yes (+1 point) No

Yes (+1 point)

feel like electrical shocks ? No (0 points) Yes (+1 point) No (0 points) 5. Is

No (0 points)

5. Is the pain made worse with the touch of clothing or bedsheets ?

pain made worse with the touch of clothing or bedsheets ? Yes (+1 point) No (0

Yes (+1 point)

with the touch of clothing or bedsheets ? Yes (+1 point) No (0 points) 6. Is

No (0 points)

6. Is the pain limited to your joints ?

clothing or bedsheets ? Yes (+1 point) No (0 points) 6. Is the pain limited to

Yes (-1 point)

clothing or bedsheets ? Yes (+1 point) No (0 points) 6. Is the pain limited to

No (0 points)

ID Pain Score Card

-1

Neuropathic pain not likely

0

Neuropathic pain less likely

1

Neuropathic pain less likely

2

Consider neuropathic pain

3

Consider neuropathic pain

4

Strongly consider neuropathic pain

5

Strongly consider neuropathic pain

Minimum total score = -1 Maximum total score = 5

Burning, feeling like the feet are on fire Freezing, like the feet are on ice,

Burning, feeling like the feet are on fire

Burning, feeling like the feet are on fire Freezing, like the feet are on ice, although

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

like the feet are on ice, although they feel warm to touch Stabbing, like sharp knives

Stabbing, like sharp knives

Modified by Meliala 2006

Lancinating, like electric shocks

The task of a doctor:

TO CURE IS SOMETIMES

TO TREAT IS OFTEN

TO COMFORT IS ALWAYS

A. Pare (1598)

PENGERTIAN MODEL NYERI

Terapi kognitif Restorasi fungsional

Opioid Tramadol Oxcarbazepine Gabapentin Eperisone HCL Paracetamo OAINS

BYERS AND BONICA, 2001 MODIFIKASI PENULIS

PERILAKU NYERI

(PAIN BEHAVIOUR)

PENDERITAAN

(SUFFERING)

NYERI

(PAIN)

NOSISEPSI

(NOCICEPTION)

BIOPSIKOSOSIAL

(BIOPSYCHOSOCIAL)

“Rasa senang dan rasa sakit adalah kembar”

“Rasa senang dan rasa sakit adalah kembar” • Antidepresan • Psikotropika • Relaksasi •
“Rasa senang dan rasa sakit adalah kembar” • Antidepresan • Psikotropika • Relaksasi •

Antidepresan

Psikotropika

Relaksasi

Spiritual

Diklofenak Etodolac Dexketoprofen Celecoxib Modalitas fisik

MECHANISTIC APPROACH TO TREATMENT OF NeP

Beydoun, 2002

PNS

BRAIN

TCAs

Duloxetin

SSRIs

SNRIs

Tramadol

Opiates

2002 PNS BRAIN TCAs Duloxetin SSRIs SNRIs Tramadol Opiates Descending Inhibitors NE/5HT Opiate receptors Peripheral

Descending Inhibitors

NE/5HT

Opiate receptors

Peripheral

Sensitization Na+ CBZ OXC PHT TCA TPM LTG Mexiletine Lidocaine
Sensitization
Na+
CBZ
OXC
PHT
TCA
TPM
LTG
Mexiletine
Lidocaine
Na+ CBZ OXC PHT TCA TPM LTG Mexiletine Lidocaine SPINAL CORD Central Sensitization Ca++ : Lyrica,

SPINAL CORD

Central Sensitization

Ca++ : Lyrica, GBP,OXC,LTG,LVT NMDA : Ketamine, TPM Dextromethorphan Methadone

Others Capsaicin NSAIDs Cox inhibitors Levodopa

Modified by MELIALA, 2006

“Sukacita yang besar selalu didahului oleh penderitaan yang hebat”

MECHANISTIC APPROACH TO TREATMENT

BRAIN

PNS
PNS

Ectopic Discharge

SPINAL CORD

“Pengetahuan makin berlimpah, namun kemampuan kita untuk menilai makin tumpul”

Descending

Inhibition

Central Sensitization

Beydoun, 2002 Modified by MELIALA 2006

Pengobatan Nyeri Neuropatik Saat ini

• Ditujukan untuk mengurangi kepekaan neuron di sistema nervorum perifer dan sentral dengan memodulasi aktivitas saluran ion (GBP, PGB, CBZ)

• Meningkatkan mekanisme inhibisi endogen (TCA, Duloxetine, opioid, Tramadol) dan hasilnya belum memuaskan

• Mengapa?????

Watkins & Maier, 2002; Scholz & Woolf, 2007

EFNS guidelines for the treatment of painful polyneuropathy

• Drugs with established efficacy include PREGABALIN, gabapentin, TCAs, SNRIs,, strong opioids and tramadol

Recommendations:

First line therapy

PREGABALIN/gabapentin or TCAs/SNRIs (evidence level A)

Second line therapy

Opioids and lamotrigine (evidence level B)

Lack of or weak efficacy

SSRIs, capsaicin, mexiletine, oxcarbazepine and topiramate (evidence level A)

Low strength evidence or safety concerns

Carbamazepine and valproate

EFNS: European Federation of Neurological Societies

OXCARBAZEPINE IN NEUROPATHIC PAIN :

PROSPECTIVE OPEN-LABEL TRIAL

Royal M et all, AAPM 17 th Annual Meeting Feb 2001

% 50

patients

40

30

20

10

0

t h Annual Meeting Feb 2001 % 50 patients 40 30 20 10 0 Excellent (>70%)
t h Annual Meeting Feb 2001 % 50 patients 40 30 20 10 0 Excellent (>70%)
t h Annual Meeting Feb 2001 % 50 patients 40 30 20 10 0 Excellent (>70%)
t h Annual Meeting Feb 2001 % 50 patients 40 30 20 10 0 Excellent (>70%)

Excellent

(>70%)

Good

(51-70%)

Fair

(20-50%)

Poor

(<20%)

Patients’ subjective respone

% of Participants

100%

80%

60%

40%

20%

0%

Antineuralgic of Choice: Peripheral Sensitization (n=207)

61% 23% 18% 7% OXC/CBZ TPM TA Other
61%
23%
18%
7%
OXC/CBZ
TPM
TA
Other

OXC=Oxcarbazepine; CBZ=Carbamazepine;TPM= Topiramate; TCA=Tricyclic Antidepressant; Other=Phenytoin,lamaotrigin,Mexiletine, Lidocaine

R. Harden et al.The Journal of Pain, Vol.3 Nr.2 Suppl.1April 2002

OXCARBAZEPIN ADVANTAGE IN NEUROPATIC PAIN

• No monitoring of hematologic parameters required

• Fewer drug-drug interaction

• No autoinduction of metabolisme

• Comparable efficacy

• Twice-daily schedule.

• Therapeutic effect maybe detected in 24-48 hours

Trileptal usage by indication cumulative since launch

Psychiatric

Seizure

37% 40%
37%
40%

Pain

23%

USA, Scott-Levin PDDA; June 2001

Multidisciplinary approach to management

Strike a balance between pharmacological and non- pharmacological approaches

Initial symptom of pain, fatigue, etc • Disordered sensory processing • Neuroendocrine disturbances
Initial symptom of pain, fatigue, etc
• Disordered sensory processing
• Neuroendocrine disturbances
Functional consequences of symptoms • Distress • Decreased activity • Isolation • Poor sleep •
Functional consequences of symptoms
• Distress
• Decreased activity
• Isolation
• Poor sleep
• Increased appetite
• Maladaptive illness behaviors
Pharmacological therapies to improve symptoms
Pharmacological therapies to improve symptoms
Pharmacological therapies to improve symptoms

Pharmacological therapies to improve symptoms

Pharmacological therapies to improve symptoms
Pharmacological therapies to improve symptoms
Nonpharmacological therapies to address dysfunction
Nonpharmacological therapies to address dysfunction
Nonpharmacological therapies to address dysfunction

Nonpharmacological therapies to address dysfunction

Nonpharmacological therapies to address dysfunction
Nonpharmacological therapies to address dysfunction

Dadabhoy D, Clauw DJ. Nat Clin Pract Rheumatol 2006;2:364-372.

Management of fibromyalgia:

Recommended treatment approach

Multidisciplinary therapy individualized to patients’ symptoms and presentation is recommended

A combination of nonpharmacological and pharmacological therapies may benefit most patients

Nonpharmacological
Nonpharmacological

Aerobic exercise

Cognitive behavioral therapy

Patient education

Strength training

Acupuncture*

Biofeedback*

Balneotherapy*

Hypnotherapy*

*Limited evidence for efficacy exists

Pharmacological

Analgesics*

Analgesic antiepileptics

Antidepressants

Other

Mease P. J Rheumatol 2005;32:6-21; Carville et al, [published online ahead of print July 20, 2007] Ann Rheum Dis Doi:10.1136/ard.2007.071522; Goldenberg et al, JAMA 2004;292:2388-2395; Clauw et al, Best Pract Res Clin Rheumatol 2003;17:685-701; Arnold et al, Arthritis Rheum 2007;56:1336-1344

Treatments used by primary care physicians

• Amitriptyline

• Milnacipran

• Fluoxetine

• Nortriptyline

• Pregabalin

• Tramadol

• Moclobemide

• Cyclobenzaprine

• Duloxetine

• Zolpidem

Moclobemide • Cyclobenzaprine • Duloxetine • Zolpidem Garcia-Campayo et al. Arthritis Res Ther 2008;10:1-15.

Garcia-Campayo et al. Arthritis Res Ther 2008;10:1-15.

SNRI = selective norepinephrine reuptake inhibitor. Please see Full Prescribing Information and Medication Guide available at at this presentation. Cymbalta ® , Savella TM , and LYRICA ® are the trademarks of Lilly LLC, Forest Pharmaceuticals Inc, and Pfizer Inc, respectively.

METHYCOBAL

An active form of cobalamin

Participates in transmethylation

Improves synthesis of proteins, nucleic acids and phospholipids which are needed in the repair of damaged nerves.

BENEFITS ALL TYPES OF PERIPHERAL NEUROPATHIES

SEGMENTAL DEMYELINATION e.g :

Diabetic neuropathy Alcoholic neuropathy Uremic neuropathy Guillain-Barre syndrome

WALLERIAN DEGENERATION e.g :

Spondylosis deformans Hernia of intervartebral disc Carpal tunnel syndrome Facial palsy Glaucomatous optic atrophy

AXONAL DEGENERATION e.g :

Drug-induced neuropathies [Vincristine, isonicotinic acid hydrazide (INH), etc] Herpes zoster

Modified MELIALA, 2006

Muscle

Nerve cell Myelin sheath A x o n
Nerve cell Myelin sheath A x o n

Nerve cell

Myelin sheath

Axon

Nerve cell Myelin sheath A x o n
Modified MELIALA, 2006 Muscle Nerve cell Myelin sheath A x o n Direction of degeneration Direction
Modified MELIALA, 2006 Muscle Nerve cell Myelin sheath A x o n Direction of degeneration Direction
Modified MELIALA, 2006 Muscle Nerve cell Myelin sheath A x o n Direction of degeneration Direction

Direction of degeneration

Modified MELIALA, 2006 Muscle Nerve cell Myelin sheath A x o n Direction of degeneration Direction
Modified MELIALA, 2006 Muscle Nerve cell Myelin sheath A x o n Direction of degeneration Direction
Modified MELIALA, 2006 Muscle Nerve cell Myelin sheath A x o n Direction of degeneration Direction
Direction of degeneration
Direction of degeneration

METHYCOBAL’S EFFECT ON ECTOPIC FIRING OF DORSAL ROOT GANGLION (DOG MODEL)

EFFECT ON ECTOPIC FIRING OF DORSAL ROOT GANGLION (DOG MODEL) Atsuta et.al Methycobal Forum 1993; 101-103

Atsuta et.al Methycobal Forum 1993; 101-103

Methycobal was added to the CSF solution (to make a concentration of 50 μg.ml) bathing the dorsal root ganglia During anoxia-induced ectopic firing. The firing was suppressed and the frequency (spike/sec.) dropped significantly after the addition of Methycobal

Metilkobalamin: Kesimpulan

• Metilkobalamin adalah bentuk aktif Vit B12, siap digunakan tubuh dalam reaksi metilasi homosistein membentuk metionin

• Reaksi metilasi berperan pada pembentukan DNA, protein yang penting untuk saraf, pembentukan mielin dan transpor aksonal

• Metilkobalamin berperan pada regenerasi saraf yang mengalami kerusakan, misalnya pada, nyeri neuropatik, neuralgia nervus kranialis, peripheral nerve injury, vertigo dan tinitus dengan mengurangi ectopic discharge

Kesimpulan

• Metilkobalamin berperan pada penurunan kadar homosistein mengurangi kerusakan saraf akibat terbentuknya reactive oxygen species

• Berperan pada proteksi neuron SSP akibat glutamate-induced neurotoxicity proteksi neuron pada stroke, cedera serebral, Alzheimer, Parkinson, Hipoglikemia dan Status epileptikus

• Secara umum sediaan oral maupun injeksi cukup aman dengan kejadian efek samping yang kecil

ANALGESIC MEDICATIONS ON INFLAMATORY PAIN

PRIMARY ANALGESICS

• Acetaminophen

• 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

Clinical Experience

• NSAID dipergunakan > 40 th sampai sekarang masih terbaik

• Khusus : Nyeri dengan inflamasi

Dionne et al, 2010 In Mogill J (Ed) Pain 2010, Clinical Pharmacology et Nonsteroidal Antiinflammatory Drugs, 217-223

Analgetik Yang Paling Sering Digunakan

Nama Obat Aspirin Kalium Diklofenak Natrium diklofenak Ibuprofen Indometasin Ketoprofen Asam mefenamat Naproxen Piroksikam Tenoksikam Meloksikam Celecoxib Nimesulfid Ketolorak Asetaminofen Tramadol

Dosis

 

Jadwal

325-1000 mg 50-200 mg

4-6 jam sekali

8

jam sekali

50

mg

8

jam sekali

200-800 mg

4-8 jam sekali

25-50 mg

8-12 jam sekali 6-12 jam sekali

25-75 mg

250

mg

6

jam sekali

250-500 mg

12

jam sekali

10-20 mg

12-24 jam sekali

20-40 mg

24

jam sekali

75

mg

24

jam sekali

100

mg

12

jam sekali

100

mg

12

jam sekali

10-30 mg

4-6 jam sekali

500

mg

6-8 jam sekali 8 jam sekali

50-100 mg

Mekanisme Proteksi Nyeri

Mekanisme Proteksi Nyeri spasme otot Descending influences C Spinothalamic Joint receptor (nociceptor) tract II-IV B

spasme otot

Descending influences C Spinothalamic Joint receptor (nociceptor) tract II-IV B III-IV Joint dysfunction or pain
Descending influences
C
Spinothalamic
Joint receptor (nociceptor)
tract
II-IV
B
III-IV
Joint dysfunction
or pain
I I
Ia
α α
Nociceptor
γ γ
α-Motoaxon
A Muscle pain
NONOPAINPAINPAIN
γ-Motoaxon
Muscle spindle

Eperison

Eperisone HCl (Myonal ®)

• Golongan antispasmodik, banyak dipakai nuntuk efek muscle relaxant

• Insidensi sedasi kecil, dibanding obat lain yang segolongan

– Mempermudah aplikasi klinis, untuk pasien yang membutuhkan terapi tanpa mempengaruhi alertness

• Efek samping yang timbul biasanya jarang terjadi

SITES OF ACTION OF EPERISONE IN THE VICIOUS CYCLE OF HYPERTONIA

OF ACTION OF EPERISONE IN THE VICIOUS CYCLE OF HYPERTONIA Relaxes hypertonia Contraction of Muscles EPERISONE

Relaxes hypertonia

Contraction of Muscles

Contraction of Muscles

EPERISONE HCL Ischemia Ischemia Ischemia
EPERISONE HCL
Ischemia
Ischemia
Ischemia
Improves circulation Pain Stimuli

Improves circulation

Pain Stimuli

Contraction of Muscles EPERISONE HCL Ischemia Ischemia Ischemia Improves circulation Pain Stimuli Pain Pain Pain
Contraction of Muscles EPERISONE HCL Ischemia Ischemia Ischemia Improves circulation Pain Stimuli Pain Pain Pain
Contraction of Muscles EPERISONE HCL Ischemia Ischemia Ischemia Improves circulation Pain Stimuli Pain Pain Pain

Pain

Contraction of Muscles EPERISONE HCL Ischemia Ischemia Ischemia Improves circulation Pain Stimuli Pain Pain Pain
Contraction of Muscles EPERISONE HCL Ischemia Ischemia Ischemia Improves circulation Pain Stimuli Pain Pain Pain
Contraction of Muscles EPERISONE HCL Ischemia Ischemia Ischemia Improves circulation Pain Stimuli Pain Pain Pain

Pain Pain

Contraction of Muscles EPERISONE HCL Ischemia Ischemia Ischemia Improves circulation Pain Stimuli Pain Pain Pain
Contraction of Muscles EPERISONE HCL Ischemia Ischemia Ischemia Improves circulation Pain Stimuli Pain Pain Pain

Inhibit pain reflex

Ischemia Improves circulation Pain Stimuli Pain Pain Pain Inhibit pain reflex Modifikasi Meliala, 2005
Modifikasi Meliala, 2005
Modifikasi Meliala, 2005

IMPROVEMENT RATES WITH EPERISONE

68.9 Stiffness
68.9
Stiffness
66.4 Rigidity
66.4
Rigidity
77.5 77.5 Dizziness Headache 65.4 Tinnitus Cervical Pain 71.9 80.7 Stiff Shoulders 71.5 Lumbago Difficulty
77.5
77.5
Dizziness
Headache
65.4
Tinnitus
Cervical Pain
71.9
80.7
Stiff Shoulders
71.5
Lumbago
Difficulty in Going Up
and Down Stairs
55.2
53.9

Difficulty in Walking

Modifikasi Meliala, 2005
Modifikasi Meliala, 2005

Myonal: Kesimpulan

• Relaksasi otot skelet yang mengalami hipertonus

• Memperbaiki aliran darah intramuskuler

• Mengurangi sensitivitas muscle spindle melalui neuron motorik

• Vasodilatasi dan augmentasi aliran darah

• Aksi analgesik dan inhibisi refleks nyeri di medula spinalis

Simpulan

Pemahaman mekanisme nyeri sangat bermanfaat dalam penatalaksanaan nyeri

SEMOGA TIDAK NYERI SALAM

SEMOGA TIDAK NYERI SALAM