Seminar neuropathic pain in daily practice

1. Neuropathic Pain
in Daily Practice
Jimbaran resto, 28 Agustus 2013
Teddy Wijatmiko ,dr.Sp.S
RSUD. Dr. Wahidin Sudirohusodo
Kota Mojokerto
1

2. 10.8%
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3. Classification of Pain
6/15/13 PPRP 3

4. NOCICEPTIVE AND NEUROPATHIC PAIN MAY
CO-EXIST IN LOW BACK PAIN CONDITIONS
Neuropathic pain componentNociceptive pain component
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5. Peripheral neuropathic pain
Arch Pain 2011
 Prolonged LBP 37 %
 Diabetes 26%
 Herper zoster 8%
 Post mastectomy ~30-40%
 Trigeminal neuralgia incidence 27/100.000
person-yr
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6. Central neuropathic pain
Arch Pain 2011
 Stroke 8 %
 Multiple sclerosis 28%
 Spinal cord injury 67%
 Phantom limb pain incidence 1/100.000
person-yr
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7. Recognition of neuropathic pain may be
challenging for many clinicians
Proportion of physicians finding it difficult to recognize
neuropathic pain
0 10 20 30 40 50 60 70
2010 4030 500 60 70
GP
Oncologist
Rheumatologist
HIV specialist
Neurologist
Endocrinologist
Pain specialist
Areaofexpertise
Percentage of physicians
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8. Pain
 Unpleasant sensory
and emotional
experience
-Associated with
actual or potential
tissue damage
-or described in
terms of such
damage
International Association for the Study of Pain
(1986)
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9. Pain Pathway
Netter Neurology 2012
6/15/13 PPRP 9

10. Physiology of Pain Perception
• Transduction
• Transmission
• Modulation
• Perception
Injury
Descending
Pathway
Peripheral
Nerve
Dorsal
Root
Ganglion
C-Fiber
A-beta Fiber
A-delta Fiber
Ascending
Pathways
Dorsal
Horn
Brain
Spinal Cord
Adapted with permission from WebMD Scientific American® Medicine.10
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11. Neuropathic pain mechanisms
Netter 2012
6/15/13 PPRP 11

12. I
II
III/IV/V
Nerve
injury
Nerve
injury
Dorsal horn
Normal termination pattern
C-fiber terminal atrophy
A-fiber sprouting
Interneuron degeneration
Pain hypersensibility - persistent Doubell et al, 1999
C-fibre
A -fibre
Aberrant connection with facilitated transmission
Structural Reorganization
I
II
III/IV/V
Modifikasi Meliala, 2003
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13. Adapted from Julius & Basbaum.
Nature 2001;413(6852):203
Pain Patho physiology
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14. Sensitization
Primary
• Tissue level
Secondary
• CNS Level
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Result in:
-↓ treshold activation after injury
-↑respons to noxious stimuli
-↑ spontaneus activity
Aguggia 2003

15. Peripheral sensitization
Core Topic in Pain 2006
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16. Central sensitization
Core Topic in Pain 2006
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17. Inhibitory Substance within DH
Core Topic in Pain,2006
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18. Gate Control Theory
Melzack and Wall 1960
Core Topic in Pain,2006
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19. Supra spinal modulation Core Topic in Pain,2006
Diagram illustrating a major descending painmodulatingpathway. Regions of the frontal lobe (F), hypothalamus(H) and amygdala (A)
project to the PAG in themidbrain. The PAG controls the transmission of nociceptiveinformation in the rostroventral medulla (RVM), DH
via relaysin the RVM and dorsolateral pontine tegmentum (DLPT). :nociceptive activation; : inhibitory (anti-nociceptive) activity
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20. What is Neuropathic pain?
 Definition:
Pain arising as a direct consequence of a lesion or disease
affecting the somatosensory system
 Characterized by:
Pain often described as shooting, electric shock-like or burning.
The painful region may not necessarily be the same as the site
of injury.
Almost always a chronic condition (e.g. postherpetic neuralgia,
poststroke pain)
Responds poorly to conventional analgesics
Example: PHN, DPN,
CPSP
6/15/13 PPRP 20

21. PERBEDAAN SECARA UMUM
NYERI NOSISEPTIK DAN NYERI NEUROPATIK :
NYERI NOSISEPTIK NYERI NEUROPATIK
- Terlokalisasi pada tempat
cedera.
- Sensasi sesuai stimulus, misalnya
jika terbakar akan terasa panas, jika
tertusuk pisau maka lesi seperti
ditikam dan lain-lain.
- Akut, mempunyai batas waktu. Nyeri
menghilang setelah cedera sembuh.
- Memiliki fungsi protektif
- Nyeri di bagian distal dari lesi atau
disfungsi saraf.
- Sensasi tidak selalu sesuai stimulus,
rasa panas, berdenyut, ngilu, kaku.
- Kronis, persisten setelah cedera
menyembuh.
- Tidak memiliki fungsi protektif
Konsensus Nasional Diagnostik & Penatalaksanaan Nyeri Neuropatik 2011
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22. Low back pain, diabetic neuropathy, & post herpetic
neuralgia are the most common type of pain with NeP
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23. Neuropathic Pain
Signs and Symptoms
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24. Your Patients may be suffering NeP if they
have following characteristic
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25. Diagnosing
Neuropathic Pain
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26. The 3L Approach to Diagnosis
LISTEN
LOCATE LOOK
Nervous system
lesion / dysfunction
Sensory abnormalities,
pattern recognition
Patient verbal descriptors,
Q & A
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27. Examples of Tools Used in the Diagnosis
and Assessment of Neuropathic Pain
Diagnostic aids
– ID Pain Screening
– Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Scale1
– DN4 Pain Questionnaire2
– Neuropathic Pain Questionnaire (also available in short-form)3
– Neuropathic Pain Scale4
Pain intensity and characteristics
– Numerical Pain Scale / Faces Pain Rating Scale9,10
– Pain Visual Analog Scale5
– Pain Likert Scale
– McGill Pain Questionnaire6
• Short-form McGill Pain Questionnaire derived
– Neuropathic Pain Symptom Inventory7
– Brief Pain Inventory (BPI)8
1. Bennett. Pain. 2001;92:147-57; 2. Bouhassira et al. DN4; 3. Backonja and Krause Clin J Pain. 2003;19:315-6;
4. Galer and Jensen. Neurology.1997;48:332-8;5. Huskisson. Lancet. 1974;2:1127-31; 6. Melzack and Togerson.
Anesthesiology. 1971;34:50-59; 7. Bouhassira et al. Pain. 2004;108:248-57;
8. Cleeland. Ann Acad Med Singapore. 1994;23(2):129-38
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28. ✔
✔
✔
✔
✔
✔ Score = 3
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ID Pain
Screening
test

29. Select the number that best describes your neuropathic pain
during the past 24 hours. (Circle one number only)
0 1 2 3 4 5 6 7 8 9 10
No
pain
Worst
possible
pain
 Pain Diary (primary efficacy parameter)
 Sleep Diary
0 1 2 3 4 5 6 7 8 9 10
None Unable
to sleep
Select the number that best describes how your pain interfered with your sleep
during the past 24 hours. (Circle one number only)
Efficacy Assessments:
Daily Pain and Sleep Interference Diaries
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30. Management of Neuropathic Pain
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31. Stepwise Pharmacology
Management Neuropathic Pain
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• Step 1
Assess pain and establish the diagnosis of NP
Establish and treat the cause of NP
Identify relevant comorbidities (e.g., cardiac, renal, or
hepatic disease, depression, gait instability)
Explain the diagnosis and treatment plan to the
patient, and establish realistic expectations
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32. 6/15/13 PPRP
Step 2
Initiate therapy of the disease causing NP, if applicable
Initiate symptom treatment
Evaluate patient for nonpharmacologic treatment
Step 3
Reassess pain and health-related QoL frequently
 If substantial pain relief (e.g., average pain reduced to NRS 3/10)
and tolerable side effects, continue treatment.
 If partial pain relief add 1 of the other first-line medications
If no or inadequate pain relief switch to an alternative first-line
medication
Step 4
If trials of first-line medications alone and in combination
fail, consider second-line medications or referral to a pain
specialist or multidisciplinary pain center
O’Connor and Dworkin Guidelines for Treatment of Neuropathic Pain 2009 33

33. The Inter-Relationship Between
Pain, Sleep, and Anxiety / Depression
Nicholson and Verma. Pain Med. 2004;5 (suppl. 1):S9-S27; Arsenault. Canadian J Diagnosis 2010; Meyer-Rosberg K. Eur J Pain. 2001
Pain
Sleep
Disturbances
90%
Anxiety &
Depression
45%
Functional
impairment
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34. PENATALAKSANAAN NYERI
NEUROPATIK
Konsensus Nasional Diagnostik & Penatalaksanaan Nyeri
Neuropatik, Pokdi Nyeri PERDOSSI, 2011
Meningkatkan kualitas hidup pasien dengan melakukan
pendekatan secara holistik, berupa pengobatan terhadap
pain triad, yaitu nyeri, gangguan tidur dan gangguan mood
( ansietas, depresi dan obsesi konvulsi ) yang dilakukan oleh tim
multidisiplin.
Tujuan :
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35. Analgesic for Neuropathic Pain
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First Line (TCA, SSNRi, Calcium Channel
α2-δLigands (Gabapentinand Pregabalin)
Topical Lidocain
Second Line : Opioid analgesic, Tramadol
Third line : bupropion, citalopram, and
parox- etine,
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36. EFNS recommendation 2010
6/15/13 PPRP 37
Diabetic NP Duloxetin,Gabapentin, pregabalin,
TCA, venlavaxine
PHN Gabapentin, pregabalin,
TCA, lidocain plester
TN Carbamazepin, oxcarbazepine
Central pain Gabapentin, pregabalin,
TCA

37. Tricyclic antidepressants (TCAs)
• 40-60% effiacy for partial relief (NNT~ 2.5-3)
• Starts 10-25 mg/d and ↑ 10-25 mg each w
best effect 50-150 mg/d
• Mechanism : NE & 5 HT reuptake blockade
• Anticholinergic effects
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38. Selective Serotonin-Norepinephrine
Reuptake Inhibitors (SNRIs)
Duloxetine
• NNT~ 4-5(~7 for SSRI)
• Start & efficacius @ 60
mg/d
• Antidepressant & anxiolityc
• Favorable side effect profile
• Limited long term data
Venlavaxine
• NNT~ 4-5
• Start37,5 mg/d
• Increase by 37,5 mg weekly
• Effective @ 150-225 mg/d
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39. Pregabalin
NNT~ 3.5-4.5
• Despite advance in research and clinical trial,
a considerable number of individuals do not
get relief
• NNT~3-5 for most drugs
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40. Non-Pharmacological Treatment
• Should be considered whenever appropriate 1
• Complementary to drug therapy ,Include2
Physiotherapy
Acupunture
Transcutaneus electrical nerve stimulation
(TENS)
1.Gilron, Can Med Assoc J, 2006;175;265-275
2. Bennet MI, Pain Clinical Update, 2010; 18 :1-6
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41. Provelyn ® Pregabalin
The Advance Treatment
for Pain Triad
in Neuropathic Pain
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42. INDICATIONS
• Approved by BPOM
– Peripheral neuropathic pain
– Central neuropathic pain
– Epilepsy
– Generalized Anxiety Disorder (GAD)
– Fibromyalgia
1. BPOM Approval 2008.
2. FDA Approval 2007.
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43. *Does not affect Ca++ influx in normal neurons
Pregabalin Modulates Hyperexcited Neurons
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44. The Difference
Pregabalin is different molecule from gabapentin1
Pregabalin is rapidly absorbed 1  fast pain relief 4,5
Pregabalin plasma concentration is proportional to dose (high
bioavailability)1more predictable pharmacokinetics
6ease to use in clinical practice6
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References: 1. Bockbrader HN et al. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet 2010; 49: 661–69. 2. Provelyn
Product Information. 3. Nepatic Product Information. 4. Lesser H et al. Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial. Neurology 2004; 63:
2105. 5. Dworkin RH et al. Pregabalin in the treatment of postherpetic neuralgia: A randomized, placebo-controlled trial. Neurology 2003; 60: 1274–83. 6. Ben-Menachem E. Pregabalin
pharmacology and its relevance to clinical practice. Epilepsia 2004; 45 Suppl 6: 13–18.
Pregabalin Gabapentin

45. The Difference
Pregabalin has predictable, linear pharmacokinetics
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Steady state minimum plasma drugs concentration
Bockbrader HN et al. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin
Pharmacokinet 2010; 49: 661–69

46. Most Frequent Adverse Events‡ and Discontinuations
in Peripheral Neuropathic Pain Studies (% of Patients)
Placebo (n=764) Pregabalin (n=1556)
Incidence
Discontinue
d
Incidence
Discontinue
d
Dizziness 6.4 0.3 21.7* 3.1
Somnolence 3.8 0.1 13.8* 2.6
Peripheral edema 1.8 0.1 9.5* 0.8
Infection 4.8 0.1 6.2 0.1
Dry mouth 1.8 0.1 5.9* 0.3
* P<0.05 all pregabalin vs. placebo
‡ Those occurring in ≥5% of pregabalin-treated patients and with higher frequency with pregabalin
than placebo
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47. Overall assesment by physicians and
patients of the tolerability of pregabalin
Physicians
95 %very good or good
Patients
95%very satisfied or
satisfied
Mallison R et al, MMW Forschr Med 2007;149;46
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48. Pregabalin, Pain , Sleep and Mood
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After 12 weeks, significant improvements in
pain, associated symptoms of anxiety, depression and
sleep disturbances, general health; and level of disability

49. Recommended treatments for
peripheral neuropathic pain
1. Attal N et al. Eur J Neurol 2010;17:1113-e88.
2. Dworkin RH et al. Mayo Clin Proc 2010;85(3Suppl):S3-14.
3. Moulin DE et al. Pain Res Manag 2007;12:13-21.
*Guidelines did not distinguish between peripheral and central neuropathic pain.
§For focal neuropathy, such as postherpetic neuralgia.
TCAs, tricyclic antidepressants; ER, extended release; SNRIs, serotonin-norepinephrine reuptake inhibitors.
Venlafaxine is not approved for the treatment of neuropathic pain.
Guideline 1st line recommendations 2nd line recommendations
The European Federation of
Neurological Societies
(EFNS)1
Pregabalin, gabapentin, TCAs,
duloxetine, venlafaxine ER,
lidocaine§
Tramadol, opioids, capsaicin§
The International Association
for the Study of Pain (IASP)*2
Pregabalin, gabapentin, TCAs,
duloxetine, venlafaxine, lidocaine
(topical)
Opioid analgesics, tramadol
The Canadian Pain Society
(CPS)*3
Pregabalin, TCAs, gabapentin SNRIs, lidocaine (topical)
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50. Recommended treatments for
central neuropathic pain
1. Attal N et al. Eur J Neurol 2010;17:1113-e88.
2. Dworkin RH et al. Mayo Clin Proc 2010;85(3Suppl):S3-14.
3. Moulin DE et al. Pain Res Manag 2007;12:13-21.
*Guidelines did not distinguish between peripheral and central neuropathic pain.
TCAs, tricyclic antidepressants; ER, extended release; SNRIs, serotonin-
norepinephrine reuptake inhibitors.
Venlafaxine is not approved for the treatment of neuropathic pain.
Guideline 1st line recommendations 2nd line recommendations
The European Federation of
Neurological Societies
(EFNS)1
Pregabalin, gabapentin, TCAs Lamotrigine, tramadol, opioids,
cannabinoids
The International Association
for the Study of Pain (IASP)*2
Pregabalin, gabapentin, TCAs,
duloxetine, venlafaxine, lidocaine
(topical)
Opioid analgesics, tramadol
The Canadian Pain Society
(CPS)*3
Pregabalin, TCAs, gabapentin SNRIs, lidocaine (topical)
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51. Conclusion
• NeuP is pain arising as a direct
consequence of a lesion or disease
affecting the somatosensory system
• 5 Characteristics of NeuP: Electric shocks,
Painful cold, Pins & needles, Burning,
Itching.
• Approach for NeuP with Pain Triad
• Pregabalin (Provelyn ®) recommended
treatment for peripheral & central NeuP
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52. Maturnuwun
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