RIWAYAT HIDUP

Nama : Dr. SURYADI, Sp.S, Msi.Med

Alamat : Borobudur Utara Raya no. 14 Semarang
Telp. 085290921168
Riw. Pendidikan :
 Fakultas Kedokteran UNDIP Semarang Th.1991
 Spesialis Ilmu Penyakit Saraf FK UNDIP Semarang Th.2004
 Magister Ilmu Biomedik FK UNDIP Semarang Th.2004
Riw. Pekerjaan :
Th.1991 -1992 : Dokter Lepas Pantai BPPKA Pertamina, Jakarta
Th.1993 -1996 : Dokter Puskesmas Kalijaga, Lombok Timur,NTB
Th.2005 - 2010 : Dokter Spesialis Saraf RSAD. Bhakti W. Tamtama, Semarang
Th.2006 - 2007 : Dokter Spesialis Saraf RS. Tebet, RS. JMC Jakarta
Th.2009 - sekarang : Dokter Spesialis Saraf RSUP Dr. Kariadi Semarang
Th. 2010 Fellowship on Pain Management. Daradia The Pain Clinic. Kolkata India
Th. 2012 Speaker “Lower Limb Region” in Workshop International Pain Management, Update in Clinical and Neuroscience. Semarang
Th. 2014 Pembicara “Role of Glial Cell in Pain Mechanism” Pertemuan Ilmiah Regional XXVI PERDOSSI. Yogyakarta
Th 2016 Interventional Pain Management Course. Pain and Spine Centre. New Delhi India
Th 2016 – sekarang : Ketua Tim Nyeri RSUP Dr Kariadi Semarang
 IX E D
M
Management of Neuropathic Pain
Dr SURYADI

RSUP Dr. Kariadi/ FK UNDIP Semarang

2
 DEFINISI NYERI
International Association for Study of Pain (IASP)

Pengalaman sensorik dan emosional yang tidak

E D
menyenangkan akibat kerusakan jaringan, baik aktual

IX
maupun potensial, atau yang digambarkan dalam bentuk

M
kerusakan tersebut
Pain is the 5th vital sign initially promoted by the
American Pain Society (APS) referred to more aware of pain
syndromes & treatment also → serious management & screening
the unrelieved pain mechanism
James Campbell, MD
Presidential Address, American Pain Society
November 11, 1996
 Challenge In Managing Neuropathic Pain

• Suboptimal management :
• Complex Pathophysiology and symptomatology
• Resistant to many medication / multiple mechanisms
• Presence of comorbid condition (Sleep disorder, anxiety & depression) (relay by
thalamus and reach higher cortical aspects : Anterior cingulate cortex, Insular cortex, Prefrontal
cortex, Primary and secondary somatosensory, Nucleus accumbens, Amygdala)
• Adverse effects associated the effective medications
 Pain Classification

Duration1 Location2 Severity3 Pathophysiology4,5

Acute Head Mild Nociceptive

Chronic
Low back Moderate Neuropathic

Central
Etc. Severe sensitization/
dysfunctional

1. McMahon SB, Koltzenburg M. In: McMahon SB, Koltzenburg M (eds). Wall and Melzack’s Textbook of Pain. 5th ed. Elsevier; London, UK: 2006;
2. Loeser D et al (eds). Bonica’s Management of Pain. 3rd ed. Lippincott Williams & Wilkins; Hagerstown, MD: 2001;
3. Hanley MA et al. J Pain 2006; 7(2):129-33; 4. Jensen TS et al. Pain 2011; 152(10):2204-5; 5. Woolf CJ. Pain 2011; 152(3 Suppl):S2-15.
 Nociceptive Pain
Somatic Visceral

Trauma

Musculoskeletal injury Ischemic, e.g., myocardial Abdominal colic

infarction

Post-operative pain

Burn pain
Infection, e.g.,
pharyngitis
Dysmenorrhea
Fishman SM et al (eds). Bonica’s Management of Pain. 4th ed. Lippincott, Williams and Wilkins; Philadelphia, PA: 2010.
 Neuropathic Pain

Post-stroke pain Postherpetic neuralgia

Diabetic peripheral neuropathy

Common descriptors
Shooting
Electric shock-like
Burning
Tingling
Numbness Chronic post-surgical pain
Lumbar radicular pain

1. Baron R et al. Lancet Neurol 2010; 9(8):807-19.

 Universe of Pain

Central sensitization/
dysfunctional pain

Multiple pain
Nociceptive pain
mechanisms
Neuropathic pain
- Somatic may coexist - Peripheral
- Visceral (mixed pain) - Central

Freynhagen R, Baron R. Curr Pain Headache Rep 2009; 13(3):185-90; Jensen TS et al. Pain 2011; 152(10):2204-5;
Julius D et al. In: McMahon SB, Koltzenburg M (eds). Wall and Melzack’s Textbook of Pain. 5th ed. Elsevier; London, UK: 2006;
Ross E. Expert Opin Pharmacother 2001; 2(1):1529-30; Webster LR. Am J Manag Care 2008; 14(5 Suppl 1):S116-22; Woolf CJ. Pain 2011; 152(3 Suppl):S2-15.
 How Neuropathic Pain Happened

• Excitation Inhibition Imbalance

• Altered Sensory Processing & Spinal Mechanism
• Changes in Descending Control Mechanism
• Ectopic Activity in Primary Afferent Fibers
• Neuroimmune Interactions
• And so many other biological processes not yet
understood.We try to answer ‘how to better manage it’ by trying to find the
solution to each patho-mechanism..
 PAIN
Criteria of Diagnosis
History : 1,2
1) pain with a distinct neuroanatomical distribution
Possible NP 2) a medical history that suggests a lesion or disease
of the nervous system

Examination: 1,2,3
3) a confirmatory test to demonstrate
Probable NP neuroanatomical distribution

Diagnostic Test : 1,2,3,4 4) a confirmatory test to demonstrate a lesion or

disease of the nervous system
Definite NP
Medicinenews, 2018 ; Treede et al., 2008
Goals in the Treatment of Neuropathic Pain

2nd goals

1st goal:

Sleep
>50% Mood
pain relief*
… but be
realistic!

Function Quality
of life

*Note: pain reduction of 30–50% can be expected with maximal doses in most patients
Argoff CE et al. Mayo Clin Proc 2006; 81(Suppl 4):S12-25; Lindsay TJ et al. Am Fam Physician 2010; 82(2):151-8.
 Analgesics Affect Different Parts
of the Pain Pathway
α2δ ligands
Pain
Antidepressants
nsNSAIDs/coxibs
Opioids
Ascending
input Descending
modulation
Local anesthetics
Dorsal
horn α2δ ligands
Antidepressants
nsNSAIDs/coxibs
Dorsal root Opioids
ganglion
Spinothalamic Local anesthetics
tract Antidepressants
Peripheral
Peripheral nociceptors
nerve Local anesthetics
nsNSAIDs/coxibs
Trauma

Coxib = COX-2 inhibitor; nsNSAID = non-specific non-steroidal anti-inflammatory drug

Adapted from: Gottschalk A et al. Am Fam Physician 2001; 63(10):1979-84; Verdu B et al. Drugs 2008; 68(18):2611-32.
Comprehensive Algorithm For The Management Of Neuropathic Pain
Assessment

Initiate Treatment
and Refer if Indicated

Treatment Multidicplinary Team

• Step 1
• Step 2
• Step 3
• Step 4
• Step 5
• Step 6
A Comprehensive Algorithm for Management of Neuropathic Pain , Bates et al, Pain Medicine, 20, 2019
Comprehensive Algorithm For The Management Of Neuropathic Pain
Assessment Hystory & Examination

1. Type Of Pain • HADRS, BPI Uncertain Dx of NP or

Initiate Treatment (DN4, ID pain, • Epworth Sleepiness Further Investigation
SteP, LANSS, Scale
and Refer if Indicated Pain Detect) • SF-36
required

2. Pain Intensity
(VAS, NPS, WB)
3. Comorbidity/SE
Treatment (CV, Renal, GIT,
• Step 1 Resp.)
• Step 2 4. Pain Generator
• Step 3
• Step 4 Neuropathic Pain • Mood (anxiety- Refer for Further
• Step 5 (NP) Depression) Invest.
• Sleep
• Step 6 • Functional Deficits
A Comprehensive Algorithm for Management of Neuropathic Pain , Bates et al, Pain Medicine, 20, 2019
 Neuropathic Pain Screening Tools
LANSS DN4 NPQ painDETECT ID Pain

Symptoms
Pricking, tingling, pins and needles x x x x X
Electric shocks of shooting X x x x x
Hot or burning X x x x x
Numbness x x x x
PainBurning
evoked by light touching
Tingling X
Shooting Electricx shock-like x Numbness x
Painful cold or freezing pain x X
Clinical examination
Brush allodynia X X
Raised soft touch threshold X
Pain pin prick threshold X X
DN4 = Douleur Neuropathique en 4 Questions (DN4) questionnaire;
LANSS = Leeds Assessment of Neuropathic Symptoms and Signs; NPQ = Neuropathic Pain Questionnaire
Bennett MI et al. Pain 2007; 127(3):199-203; Haanpää M et al. Pain 2011; 152(1):14-27.
Comprehensive Algorithm For The Management Of Neuropathic Pain
Assessment

Initiate Treatment
and Refer if Indicated

Treatment Refer for Further

Invest.
• Step 1
• Step 2
• Step 3
• Step 4
• Step 5
• Step 6
A Comprehensive Algorithm for Management of Neuropathic Pain , Bates et al, Pain Medicine, 20, 2019
 Treatment

Non Pharmacology Pharmacology Interventional PM

Pure Analgetics NSAIDs Adjuvant Analgetics Opioid Anestetic

PCT
Metampiron Anti- Vitamins?
Convulsant

Anti- Steroids
Ns NSAIDs Coxib Deppresant Opioid Atypical Opioid
Comprehensive Algorithm For The Management Of Neuropathic Pain
Assessment Neuropathic Pain
(NP)

Initiate Treatment
and Refer if Indicated

Step 1: TCA’’s SNRI’s Gabapentinoids Topical

1st Line 4-6 week Trial (Focal)

A Comprehensive Algorithm for Management of Neuropathic Pain , Bates et al, Pain Medicine, 20, 2019
 Recommendation for first- and second-line treatment
Pain First-line Level of Second-line Level of
Condition evidence evidence

Painful Periphe- PGB A Lamotrigine B

ral Neuropathy Gabapentin A SNRI A
TCA A Tramadol A
Opioids A

Postherpetic PGB A Capsaicin topical B

Neuralgia Gabapentin A Tramadol B
TCA A Opioid A
Lidocain topical B Valproate B

Trigeminal Oxcarbazepine B Surgery B

Neuralgia Carbamazepine A

Central Pain PGB (in SCI) B Lamotrigine (in stroke) B

Gabapentin (in SCI) B Cannabinoids (in MS) B
Amitriptylin (in stroke) B Opioids (in multiple etiology) C
 Prescribing Recommendations for First-Line Medications
Medication Starting dose Titration Max. dosage Trial duration
α2δ ligands
Gabapentin 100–300 mg at ↑ by 100–300 mg 3600 mg/day 3–8 weeks + 2 weeks
bedtime or tid tid every 1–7 days at max. dose
PGB 50 mg tid or 75 mg bid ↑ to 300 mg/d 600 mg/day 4 weeks
after 3–7 days,
then by 150 mg/d
every 3–7 days
Anticonvulsant antidepressant, Topical
Duloxetine 30 mg qd ↑ to 60 mg qd 60 mg bid 4 weeks
after 1 week
Venlafaxine 37.5 mg qd ↑ by 75 mg e 225 mg/day 4–6 weeks
ach week
TCAs 25 mg at bedtime ↑ by 25 mg/day 150 mg/day 6–8 weeks, with
(desipramine every 3–7 days ≥2 weeks at max.
nortriptyline tolerated dosage
Topical Max. 3 5% patches/day None needed Max. 3 patches/d 3 weeks
lidocaine for 12 h max. for 12–18 h max.

SNRI = serotonin-norepinephrine reuptake inhibitor; TCA = tricyclic antidepressant; Dworkin RH et al. Mayo Clin Proc 2010; 85(3 Suppl):S3-14.
 Pregabalin Demonstrated Greater Neuropathic Pain Reduction
In People Previously Treated With Gabapentin

Patients switching from gabapentin to Pregabalin also demonstrated fewer adverse effects and
improvement in QOL.
Toth C. Pain Med. 2010;11(3):456-65
 How to start Pregabalin

150 mg at
50 mg at night
night, 75 mg at
for 2 days
morning

75 mg at night
150 mg BID
for 2 days

75 mg BID ( at Continue meds

night and for 1 to 2
morning months
 Adverse Effects of a2d Ligands
System Adverse effects
Digestive system Dry mouth
CNS Dizziness, somnolence

Other Asthenia, headache, peripheral

edema, weight gain

α2δ ligands include gabapentin and pregabalin

CNS = central nervous system
Attal N, Finnerup NB. Pain Clinical Updates 2010; 18(9):1-8.
 Adverse Effects of Antidepressants
System TCAs SNRIs

Constipation, dry mouth, Constipation, diarrhea,

Digestive system urinary retention dry mouth, nausea,
reduced appetite
Cognitive disorders,
CNS dizziness, drowsiness, Dizziness, somnolence
sedation

Cardiovascular Orthostatic hypotension, Hypertension

palpitations

Blurred vision, falls, gait Elevated liver enzymes,

Other disturbance, sweating elevated plasma glucose,
sweating

CNS = central nervous system; TCA = tricyclic antidepressant; SNRI = serotonin-norepinephrine reuptake inhibitor
Attal N, Finnerup NB. Pain Clinical Updates 2010; 18(9):1-8.
Comprehensive Algorithm For The Management Of Neuropathic Pain
Assessment Neuropathic Pain
(NP)

Initiate Treatment
and Refer if Indicated

Step 1: 1st Line TCA’’s SNRI’s Gabapentinoids Topical

4-6 week Trial (Focal)

Inadequate Respons/
Exacerbation

Step 2: 2nd Line Combination 1st Tramadol

4-6 week Trial Line Therapy

A Comprehensive Algorithm for Management of Neuropathic Pain , Bates et al, Pain Medicine, 20, 2019
Comprehensive Algorithm For The Management Of Neuropathic Pain
Step 1: 1st Line TCA’’s SNRI’s Gabapentinoids Topical (Focal)
4-6 week Trial
Inadequate Respons/
Exacerbation

Step 2: 2nd Line Combination 1st Line Tramadol

4-6 week Trial Therapy

Specialistic/ Referal

Step 3: 3rd Line SSRI’s/ Interventional

Inadequate Respons Anticonvulsant/ Therapies
NMDA’s Antagonist
A Comprehensive Algorithm for Management of Neuropathic Pain , Bates et al, Pain Medicine, 20, 2019
 DOSIS DAN FREKUENSI PEMBERIAN ADJUVAN ANALGETIK :

Nama Obat Dosis Oral Jadual Pemberian

Pregabalin 150-600 mg/hari 2 kali sehari
Gabapentin 300-1500 mg/hari 2-4 kali sehari
Okskarbasepin 900-1800 mg/hari 2-4 kali sehari
Carbamazepin 100-1000 mg/hari 2-4 kali sehari
Lamotrigin 150-500 mg/hari 2 kali sehari
Fenitoin 100-300 mg/hari 1-3 kali sehari
Topiramat 25-200 mg/hari 2 kali sehari
Asam valproat 150-1000 mg/hari 3 kali sehari
Catatan: Dosis obat perlu dipertimbangkan toleransi individual
Comprehensive Algorithm For The Management Of Neuropathic Pain
Step 2: 2nd Line Combination 1st Line Tramadol
4-6 week Trial Therapy

Specialistic/ Referal

Step 3: 3rd Line SSRI’s/ Anticonvulsant/ Interventional

Inadequate Respons NMDA’s Antagonist Therapies

Step 4: 4th Line Neuromodulation

Inadequate Respons (RF, SCS,
VAS >= 5/10, 6 mo
of NP

A Comprehensive Algorithm for Management of Neuropathic Pain , Bates et al, Pain Medicine, 20, 2019
Comprehensive Algorithm For The Management Of Neuropathic Pain
Step 4: 4th Line Inadequate Respons Neuromodulation (RF,
VAS >= 5/10, 6 mo of NP SCS,

Step 5: 5th Line Inadequate Respons Low Dose Opioid

4-6 week trial, Regular 3 mo review

Step 6: 4th Line Inadequate Respons Targeted Drug Delivery

Recommend > 50 Morfin Equivalent
Dose (MED)
Strongly Recommend > 90 MED

A Comprehensive Algorithm for Management of Neuropathic Pain , Bates et al, Pain Medicine, 20, 2019
 Multimodal Treatment of Pain Based on
Biopsychosocial Approach

Lifestyle management

Sleep hygiene Stress management

Interventional pain
Physical therapy Pharmacotherapy management

Occupational therapy

Education
Complementary therapies Biofeedback

Gatchel RJ et al. Psychol Bull 2007; 133(4):581-624; Institute of Medicine. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research.; National Academies Press; Washington, DC: 2011; Mayo Foundation for Medical
Education and Research. Comprehensive Pain Rehabilitation Center Program Guide. Mayo Clinic; Rochester, MN: 2006.