Dr Teddy Wijatmiko Sp.S neuropathic pain

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Seminar neuropathic pain in daily practice

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Dr Teddy Wijatmiko Sp.S neuropathic pain

  1. 1. Neuropathic Pain in Daily Practice Jimbaran resto, 28 Agustus 2013 Teddy Wijatmiko ,dr.Sp.S RSUD. Dr. Wahidin Sudirohusodo Kota Mojokerto 1
  2. 2. 10.8% 9/1/2013 2
  3. 3. Classification of Pain 6/15/13 PPRP 3
  4. 4. NOCICEPTIVE AND NEUROPATHIC PAIN MAY CO-EXIST IN LOW BACK PAIN CONDITIONS Neuropathic pain componentNociceptive pain component 9/1/2013 4
  5. 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 6/15/13 5
  6. 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 6/15/13 6
  7. 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 9/1/2013 7
  8. 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) 9/1/2013 8
  9. 9. Pain Pathway Netter Neurology 2012 6/15/13 PPRP 9
  10. 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 9/1/2013 10
  11. 11. Neuropathic pain mechanisms Netter 2012 6/15/13 PPRP 11
  12. 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 9/1/2013 12
  13. 13. Adapted from Julius & Basbaum. Nature 2001;413(6852):203 Pain Patho physiology 9/1/2013 13
  14. 14. Sensitization Primary • Tissue level Secondary • CNS Level 6/15/13 14 Result in: -↓ treshold activation after injury -↑respons to noxious stimuli -↑ spontaneus activity Aguggia 2003
  15. 15. Peripheral sensitization Core Topic in Pain 2006 6/15/13 15
  16. 16. Central sensitization Core Topic in Pain 2006 6/15/13 16
  17. 17. Inhibitory Substance within DH Core Topic in Pain,2006 6/15/13 17
  18. 18. Gate Control Theory Melzack and Wall 1960 Core Topic in Pain,2006 6/15/13 18
  19. 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 6/15/13 19
  20. 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. 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 6/15/13 21
  22. 22. Low back pain, diabetic neuropathy, & post herpetic neuralgia are the most common type of pain with NeP 6/15/13 22
  23. 23. Neuropathic Pain Signs and Symptoms 6/15/13 23
  24. 24. Your Patients may be suffering NeP if they have following characteristic 6/15/13 24
  25. 25. Diagnosing Neuropathic Pain 6/15/13 26
  26. 26. The 3L Approach to Diagnosis LISTEN LOCATE LOOK Nervous system lesion / dysfunction Sensory abnormalities, pattern recognition Patient verbal descriptors, Q & A 6/15/13 27
  27. 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 6/15/13 28
  28. 28. ✔ ✔ ✔ ✔ ✔ ✔ Score = 3 6/15/13 PPRP 29 ID Pain Screening test
  29. 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 309/1/2013
  30. 30. Management of Neuropathic Pain 6/15/13 31
  31. 31. Stepwise Pharmacology Management Neuropathic Pain 6/15/13 • 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 32
  32. 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. 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 6/15/13 34
  34. 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 : 6/15/13 35
  35. 35. Analgesic for Neuropathic Pain 6/15/13 First Line (TCA, SSNRi, Calcium Channel α2-δLigands (Gabapentinand Pregabalin) Topical Lidocain Second Line : Opioid analgesic, Tramadol Third line : bupropion, citalopram, and parox- etine, 36
  36. 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. 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 6/15/13 38
  38. 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 6/15/13 39
  39. 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 6/15/13 40
  40. 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 6/15/13 41
  41. 41. Provelyn ® Pregabalin The Advance Treatment for Pain Triad in Neuropathic Pain 6/15/13 42
  42. 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. 6/15/13 43
  43. 43. *Does not affect Ca++ influx in normal neurons Pregabalin Modulates Hyperexcited Neurons 6/15/13 44
  44. 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 6/15/13 45 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. 45. The Difference Pregabalin has predictable, linear pharmacokinetics 6/15/13 46 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. 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 6/15/13 47
  47. 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 6/15/13 48
  48. 48. Pregabalin, Pain , Sleep and Mood 6/15/13 49 After 12 weeks, significant improvements in pain, associated symptoms of anxiety, depression and sleep disturbances, general health; and level of disability
  49. 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) 6/15/13 50
  50. 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) 6/15/13 51
  51. 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 6/15/13 52
  52. 52. Maturnuwun 6/15/13 53

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