Clinical Practice in Management

of Pain
KRT. Lucas Meliala

Professor
Department of Neurology
Faculty of Medicine Gadjah Mada University Yogyakarta
Curriculum Vitae
Nama : Prof. Dr. KRT. Lucas Meliala, SpKJ, SpS(K) Pendidikan : Lulus Dokter tahun 1969,
Tempat/tanggal lahir : Membang Muda (Sumut), 22 September 1941 alumnus FK-UGM
Alamat : Jl. Nagan Lor 70, Jogjakarta Lulus Spesialis Saraf & Jiwa tahun 1974
Telepon : (0274) 450758 alumnus FK-UI, FK-UGM, FK Unair
Fax. : (0274) 374052 Pekerjaan : Staf Fakultas Kedokteran UGM
Mobile : 0815 687 0584 bagian IP Saraf dan Jiwa sejak
E-mail : lucasmeliala@yahoo.com tahun 1968 sampai sekarang
Organisasi : 1999-sekarang : Ketua Pokdi Nyeri Perdossi
Anggota IASP, ENS
Ketua Governing board IPS
 Disease Symptoms

Symptoms is major reason for patient to seek

medical help

BUT

Many of the somatic symptoms that they with

such as pain, weakness, and fatique remain
unexplain by identiviable disease even after
extensive medical assessment
 Disease Symptoms

Most functional somatic symptoms are

transient

BUT

Sizeable minority became persistent

 Disease Symptoms

Almost any symptoms can occurs in the

absence of disease but some, such as fatique
and subjuctive bloating, are more likely to be
functional than others.
Three year incidence of 10 common presenting symptoms and
proportion of symptoms with a suspected organic cause in US
primary care
10
Organic Cause
8
3 year incidence (5)

Mayou & Farmer, 2002

 Pain Definition

Pain is a series of neuronal processes that

involve the peripheral nerves, spinal cord, and
brain.

Rahman & Dickenson, 2008

 Classification of Pain

PAIN RECEPTORS STATUS OF

PAIN TYPE SYMPTOMS
INVOLVED NERVOUS SYSTEM

Peripheral
Somatic Ussualy well
nociceptive and Undamaged
localized
somatic sensory
efferent nerves
Poorly localized,
Visceral nociceptive
Visceral deep aching,
and efferent nerves Undamaged
cramping

Damaged due to
Neuropathic None Burning sensation
injury or disease
 Acute vs Chronic Pain

ACUTE PAIN Symptoms

CHRONIC PAIN Disease

Sign : Symptoms :
Scowled Anxiety
Abnormal posture Depression
Doctor shopping Sleep disorders
Etc Anger, etc
 The Task of A Doctor

TO CURE IS SOMETIMES
TO TREAT IS OFTEN
TO COMFORT IS ALWAYS

A. Pare (1598)
 Understanding Pain Model

Cognitive Therapy PAIN BEHAVIOUR

Fungtional restoration
Antidepressant
SUFFERING Psycotropics
Relaxation
Opioid PAIN Spiritual healing
Tramadol
Oxcarbazepine Indo.farnesil
Gabapentin Etodolac
Eperisone HCL NOCICEPTION Dexketoprofen
Paracetamo Celecoxib
OAINS Diclofenac
Physical modality

BIOPSYCHOSOCIAL
BYERS AND BONICA, 2001
Author s Modification
Achieve Pain control
Earlier is better
 Treatment

Paracetamol should be used for the first line analgesic

agent due to its favourable side effect and safety profile
Non selective NSAID and COX-2 inhibitors were
developed with the goal of delivering pain relief with
caution on cardiovascular and or cardiorenal risk
The additional of weak opioids is recommended when
greater analgesia desired

Schnitzer, 2006
 Analgesic Medications
PRIMARY ANALGESICS
Acetaminophen
Prostaglandin synthesis inhibitors
Salicylates
Traditonal NSAIDs (Diclofenac)
COX-2-selective NSAIDs (Coxibs)
Tramadol
Opioids
Traditional
Mixed

ADJUVANT MEDICATIONS
Antidepressants
Anticonvulsants
Local anesthetics
Miscellaneous agents (Neurotrophic vitamins)
 The WHO Analgesic Ladder
Very severe Hydromorphone
WHO
Step III
Morphine
Oxycodone
Severe Fentanyl
Buprenorphine
Pain intensitiy

Tramadol
Tilidine

Drugs
WHO Codein
Step II Moderate Dextropropoxyphene
NSAIDs
COX II inhibitors

Acetylsalicylic acid
WHO
Step I Mild Acetaminophene

Langford, 2002; Proceeding of the Grnenthal symposium

 Acute and Severe Pain

Recommended Significant Toxicity

Initial Dosing
Significant Sedation

Pain/Analgesia Threshold

Some Analgesia

Traditional
Initial Dosing No Analgesia

Analgesic dosing ladder

 17

Case Study 1
 18
Mr Chan: Patient Details &
Initial Presentation
54-year-old male taxi driver
15-year history of back pain radiating to the left leg, and
surgery for a herniated disc
The lumbar pain decreased after surgery but the pain in the
leg persisted and was described as severe burning,
cramping and shooting (7/10 on the numerical rating scale)
and was associated with intense tingling and numbness
Co-morbid symptoms included:
Major sleep disturbance
Increasing feelings of isolation and depression
Long duration of sick leave
 19

Mr Chan: Previous Medical History

The patient had a previous history of chronic back pain
and surgery
Back pain initially described as dull, heavy pressure

Then the patient experienced tingling and

numbness in the left leg and foot associated with
intense pain in the left buttock and thigh; sometimes
described as an excruciating electric shock-like and
burning sensation
Reduced sensitivity to light touch (tactile
hypoesthesia) over the side of the left leg and foot
A herniated disc in the L5S1 space was confirmed
by magnetic resonance imaging (MRI) and the
patient underwent surgery
Post-surgery, the patient experienced a significant
reduction in lumbar pain
However, there was limited reduction in radicular
pain, which increased progressively
 20

Mr Chan: Previous Pain Treatment and

Outcome
Regular oral NSAID therapy initially provided satisfactory relief of
lumbar pain, but the duration of effect shortened over time
Diclofenac alone (150 mg daily), paracetamol (3 g daily) and
tramadol (150 mg daily) proved ineffective
Oxycodone (40 mg daily) induced a significant reduction in
lumbar pain but only a slight improvement in radicular burning
pain
Opioid treatment was discontinued because of adverse events,
including nausea, constipation and somnolence
 21

Mr Chan: Physical examination

Lasgue sign (straight leg raise) positive at ~30

Sensory loss to touch (hypoesthesia) on the lateral aspect
of the left foot
Diminished Achilles reflex, left foot
 22

Point For Discussion

Based only on the clinical history and physical examination

what would be the most probable diagnosis?
What are the elements that support your diagnosis?
What other elements or exams/tests do you need to
confirm the diagnosis?
 23

Mr Chan: Diagnosis

The patient has lumbar radiculopathy

The diagnosis was based on:
History of disc herniation with lumbar pain and surgery (which failed to
relieve the pain)
Verbal descriptors and sensory changes suggesting nerve involvement
Topographical distribution of pain and sensory changes (L5/S1)
Pain refractory to conventional analgesics
Other exams
MRI did not show recurrence of disc herniation
Somatosensory evoked potentials were normal
Electromyography showed denervation in the L5 territory
 24

Keys toTake Away

Up to 10% of adults suffer from low back pain, and a

neuropathic component may be present in up to 37% of these
patients1-2
A simple, stepwise approach to diagnosis may help
differentiate between neuropathic and nociceptive pain3-6;
patients with low back pain should be screened for a
neuropathic component
Several evidence-based treatment guidelines propose similar
approaches to pharmacological management of the
neuropathic component of low back pain7-9

1. Freburger JK et al. Arch Intern Med 2009;169:251-258; 2. Freynhagen R, et al. Curr Med Res Opin 2006;22:1911-1920;
3. Haanp ML et al. Am J Medicine 2009;122(10 Suppl):S13-S21; 4. Baron R, Tlle TR. Curr Opin Support Palliat Care 2008;2:1-8;
5. Jensen TS et al. Eur J Pharmacol 2001;429:1-11; 6. Gilron I et al. Can Med Assoc J 2006;175:265-275; 7. Attal N et al. Eur J Neurol 2010;17:1113-e88;
8. Dworkin RH et al. Mayo Clin Proc 2010;85(3 Suppl):S3-14; 9. Moulin DE et al. Pain Res Manag 2007;12:13-21.
 25

Low Back Pain Is A Burden To

Many Individuals

Up to 10% of adults may suffer from low back pain1

Across Asia, low back pain is a very common
condition:
China: 64% (1-year prevalence rate in a rural population)2
Philippines: 21% (point prevalence rate from a national sample)3
Thailand: 28.5%49% (point prevalence rates)4-5

1. Freburger JK, et al. Arch Intern Med 2009; 169:251-258; 2. Barrero LH, et al. Spine (Phila PA 1976) 2006;31:2728-2734; 3. Lu H, Javier F. Phil J Int Med
2011;49:61-69; 4. Tomita S, et al. Industrial Health 2010;48:283-291; 5. Taechasubamorn P, et al. J Med Assoc Thai 2011;94:616-621.
 Comparison in US, Europe & Australia

US1:
2nd most common ailment in US after headache
US$ 50 billions spent on low back pain
Most common cause of job-related disability & leading contributor to
missed work
Europe2:
Major health & socioeconomic problem throughout Europe
Lifetime prevalence: estimated 59 90%
One-year incidence: 5% of population
Australia3:
1 in 4 adults seeks care in a 6-month period
0.22% of Gross Domestic Product (GDP) & 1.65% of health
expenditure (1991)
1. National Institute of Neurological Disorders & Stroke. http://www.ninds.nih.gov/disorders/backpain/detail_backpain.htm. 2009
2. Hermans V. Research on work-related low back disorders. Institute for Occupational Safety and Health, Brussels. 2000
3. Kent PM, Keating JL. Chiropractic & Osteopathy 2005;13:13
Prevalence and Incidence Disability and Lost Working
Days
Northen Central Java in 1991: Sweden (Peter, 2001)
Male : 18,2% 1980 : 7 milllion working days
Female : 13,6% 1987 : 28 million working days

Jakarta and Semarang

5,4% - 5,8% (Wirawan, 1991)
Inggris
1992 : 33 million working days
(Nachemson, 1992)
Jogjakarta (RS Sardjito) 1999 : 100 million working days
5,5%-8,9% (Jayson 1999)

14 province (teaching hospital)

May 2002
4,57% (Pokdi Nyeri Perdossi,
2002)
 28
Low Back Pain Negatively Affects Quality of
Life

Low back pain is the leading cause of

disability and the highest cost for
workers compensation in industrialized
countries1
Up to 50% of the working population
suffers from back pain every year, with
many experiencing functional limitation2
Patients with chronic pain will often have
sleep difficulties, and may experience
depression and anxiety3

1. Tomita S, et al. Industrial Health 2010;48:283-291; 2. Patel AT, Ogle AA. Am Fam Physician 2000;61:1779-1786; 3.
Nicholson B, Verma S. Pain Med 2004;5:S9-S27.
 29

What Happened in Low Back Pain?

Freynhagen R, Baron R. Curr Pain Headache Rep 2009;13:185-90.

 30
Low Back Pain is Often
a MIXED Pain1-4

Mixed Pain Nociceptive Pain

Neuropathic Pain
Pain caused by a lesion or disease Pain with Pain that arises from actual or
of the neuropathic and threatened damage to non-neural
somatosensory nervous system5 nociceptive tissue and is due to the activation of
components nociceptors5

Examples Examples Examples

Postherpetic neuralgia Low back pain Pain due to inflammation
Trigeminal neuralgia Postsurgical pain Limb pain after a fracture
Painful diabetic neuropathy Cancer pain Joint pain in osteoarthritis
Central poststroke pain Carpal tunnel syndrome Postoperative visceral pain
Common descriptors6 Common descriptors6
Burning Aching
Tingling Sharp
Hypersensitivity to touch or cold Throbbing

1. Morlion B. Curr Med Res Opin 2011;27:11-33; 2. Freynhagen R, Baron R. Curr Pain Headache Rep 2009;13:185-190; 3. Khoromi S, et al. Pain 2007;130:66-75; 4. Siddall PJ,
et al. Neurology 2006;67:1792-1800; 5. International Association for the Study of Pain. IASP Pain Terminology; 6. Raja et al. in Wall PD, Melzack R (Eds). Textbook of
Pain. 4th Ed. 1999;11-57.
 31
Example of a Mixed Pain: Herniated Disc Causing
Low Back Pain and Lumbar Radicular Pain

Freynhagen R, Baron R. Curr Pain Headache Rep 2009;13:185-90.

 32
Example of a Mixed Pain: Herniated Disc Causing
Low Back Pain and Lumbar Radicular Pain
Activation of peripheral nociceptors cause of
nociceptive pain component1
Disc herniation

Lumbar
vertebra

Compression and inflammation of nerve root cause of

neuropathic pain component2

1. Brisby H. J Bone Joint Surg Am 2006;88(Suppl 2):68-71; 2. Freynhagen R, Baron R. Curr Pain
Headache Rep 2009;13:185-90.
 33
Example of a Mixed Pain: Herniated Disc Causing
Low Back Pain and Lumbar Radicular Pain
Constant ache, throbbing Shooting, burning
pain in the low back2 pain in the foot3
Patient presents
with both types
of pain

Lesion

Activation
of local Ectopic discharges
nociceptors1 from nerve
root lesion2

1. Brisby H. J Bone Joint Surg Am 2006;88(Suppl 2):68-71; 2. McMahon SB and Koltzenburg M. Wall and Melzacks
Textbook of Pain. 5th ed. London: Elsevier; 2006; pp. 910, 1032; 3. Freynhagen R, Baron R. Curr Pain Headache Rep
2009;13:185-90.
 34
Consider a Neuropathic Component
in Low Back Pain
Neuropathic back pain may have
many clinical causes, including
radiculopathy, spinal stenosis
and trauma3
Chronic low back pain may have
a neuropathic component in
more than one third (37%) of
patients4

Excessive release of
neurotransmitters2

Neuropathic symptoms in chronic low back pain may include4:

Positive sensory symptoms, eg, tingling or burning pain
Negative sensory symptoms, eg, numbness
1. Kavoussi R. Eur Neuropsychopharmacol 2006;16(Suppl 2):S128-33; 2. Baron R. Nat Clin Pract Neurol 2006;2:95-106;
3. Audette JF, et al. Curr Pain Headache Rep 2005;9:168-77; 4. Freynhagen R, et al. Curr Med Res Opin 2006;22:1911-20.
 Disc Finding in Normal Subjects
AGE 70
100% 100 100

90% AGE 42
DISC CRACKS

A 80%
75
B 70%
AGE 28 X-RAY DJD
N 60% 60
O
50% AGE 35 AGE 60
R
40% AGE 23 40
M
DISCOGRAM 34 CT/MRI-HERNIA
A 30% 30
25 OIL MYELOGRAPHY
L 20% AGE 30
15 AGE 51
10%
AGE 15
0%
0 10 20 30 40 50 60 70
AGE IN YEARS

Find your age on the age in years line then look up the chance
of findings being present before your symptoms begin
Case Study 2
 Case Study 2

Pasien has been diagnosed migraine with aura,

What is the recommended treatment in this case?
A. Avoid predisposition factors

B. Exercise to reduce phycological stress

C. Sumatriptan

D. Ergotics

E. NSAIDs
 Consider a Diagnosis of Migraine

Patients with recurrent severe disabling headaches

associated with nausea and sensitivity to light, and with a
normal neurological examination (C).
 Things Have Not Been Met In Management of
Migraine

70% patients are not satisfied with current treatment for migraine

Long onset of actions 87

Limited indication (not for all pain) 84
Inffective 84
Recurrent migraine 71
More side effects 35

0 50 100
Percentage
 Strategies for Migraine Treatment

British Association for the Study of Headache, 2010,

Guidelines for All Healthcare Professionals in the Diagnosis and Management of Migraine
 Principles of Acute Treatment

Treat EARLY and SHORTLY (2 to 3 days per

week)
Use correct TYPE, DOSE and FORMULATION
Advantages
May prevent disability
May reduce headache recurrence
Decrease number of tablets used per attack
May prevent sensitization and allodynia
Disadvantages
May lead to over treatment
 Acute Therapy for Migraine
(Pharmacology)

Abortive Preventive
(symptomatic) (prophylactic)

Nonspecific Specific

Pain-free response at 2 hours (IHS,2010)

Clinical Practice Guideline for the Diagnosis and Management of Migraine, IEHP, November 2010
 Five step treatment ladder
in Acute Migraine
Step 1: Oral Analgesics Antiemetic
Step 2: Parenteral/Rectal Analgesic Antiemetic
Step 3: Triptans or Ergotamine (Specific)
Step 4: Combinations (Steps 1+3, followed by Steps 2+3)
Step 5: Emergency treatment

British Association for the Study of Headache, 2010,

Guidelines for All Healthcare Professionals in the Diagnosis and Management of Migraine
 Recommendation of
Acute Migraine Treatment

US Headache Consortium BASH/EFNS/AAFP/ACP-ASIM

Recommendation Recommendation
NSAIDs or combination NSAIDs or Oral analgesics
Antiemetic
Migraine Specific agent in If failed: Migraine Specific
severe migraine or respond agent
poorly to NSAIDs or
combination Aspirin
Acetaminophen Caffeine
 Acute Management of Migraine

Paracetamol Opiate based and mixed

analgesics should be avoided.
NSAIDs orally /rectally/im
Anti-emetic /prokinetics
orally/rectally /im/ buccal mucosa
Combinations-eg migraleve/
Specific anti-migraine
therapy- triptans
 Analgesics with Evidence of Efficacy (BASH, 2010; EFNS, 2009)
(A: Establish, B: probable, C: Posible)
Substance Dose LoR Comment
Acetylsalicylic acid 1000 mg (oral or iv) A Gastrointestinal side effects,
(ASA) risk of bleeding
Diclofenac 50 100 mg A Gastrointestinal side effects,
risk of bleeding
Ibuprofen 200 800 A Side effects as for ASA

Naproxen 500 1000 mg A Side effects as for ASA

Paracetamol 1000 mg (oral or Supp) A Ctn. liver and kidney failure

ASA + paracetamol + 250 mg + A ASA and paracetamol
caffeine 200 250 mg + 50 mg
Metamizol 1000 mg (oral or iv) B Agranulocytosis, Hypotension

Phenazon 1000 mg (oral) B See paracetamol

Tolfenamic acid 200 mg (oral) B Side effects as for ASA

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