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Neuropathic Pain :   Strategies to Improve Clinical              OutcomeBrought to you by :    One is the most independent...
Common conditions                     associated with                    neuropathic painDiabetes             Peripheral n...
Neuropathic pain• Not a single entity or diagnosis• Represents a variety of syndromes      • Painful diabetic neuropathy  ...
Neuropathic pain:                                       Pathogenesis• Altered alpha-2 delta subunit expression of calcium ...
Diagnostic pointersDistinguishing the type of pain through clinical  history• Neuropathic pain: Often worse at night• Musc...
Diagnosis based on the                    typical characteristics of                        neuropathic pain• The presence...
Clues from the examination                    of the patient reporting                       neuropathic pain• Neurologica...
Two Most Important                      Neuropathies• Post herpetic neuralgia• Diabetic neuropathy related pain
Post-herpetic Neuralgia• Varicella-zoster virus is a re-emerging  infection  Acute pain that accompanies Herpes zoster  us...
Herpes zoster• Approximately 50% of individuals reaching  90 years of age will have had HZ• In approximately 6% of the pat...
Risk Factors for PHN• Old age• Female gender• Presence of a prodrome• Severe rash                          Neurology. 2004...
Startling Facts of Treatment                           of PHN• Lidocaine patch 5% gives relief of pain and tactile  allody...
Acyclovir treatment• Treatment of herpes zoster with 800 mg/d  of oral acyclovir within 72 hours of rash  onset may reduce...
Diabetic Neuropathy  • The prevalence : 7.5% in newly diagnosed    diabetics when the definition is restricted    to sympt...
Diabetic Neuropathy•   Distal symmetric polyneuropathy•   Longest nerves are affected first•   The earliest manifestations...
Recent advances in                       diagnosis of neuropathy•   Corneal confocal microscopy•   Laser Doppler flowmetry...
Neuropathic Pain:                              Approach to Treatment• Diagnosis• Treat underlying condition/Symptomatic  t...
Site of action of drugs used                                for neuropathic pain                           BRAIN          ...
Site of action of drugs used                                for neuropathic pain                           BRAIN          ...
Management of neuropathic                             painPatient diagnosed with neuropathicpainStart treatment with the f...
Pregabalin• A new neuromodulator for neuropathic  pain.• An alpha 2-delta ligand• A structural analogue of GABA• Analgesic...
Pregabalin: Mechanism of                                action       • Acts as a ligand of the alpha2- delta         subun...
Site of action of Pregabalin                      Nerve injuryAltered alpha (2) delta subunit expression in spinal cord   ...
Pregabalin and Gabapentin• Pregabalin is a more effective analogue of  gabapentin• Pregabalin has a higher potency at the ...
Pregabalin                                    Pharmacokinetics• Absorption: Almost 100%• PPB: None• Metabolism: Not metabo...
Dose of Pregabalin• Initial dose : 75 mg bd or 50 mg tds• Can be increased to 300 mg/day in 1 week• Can be increased to a ...
Side Effects  Pregabalin is usually well tolerated  • CNS: dizziness and drowsiness  • General: Weight gain in the elderly...
Side Effects  Pregabalin is usually well tolerated  • CNS: dizziness and drowsiness  • General: Weight gain in the elderly...
Pregabalin vs Gabapentin            • Greater affinity for the alpha 2 subunit of              calcium channels : Effectiv...
Clinical Experience with                        Pregabalin in Neuropathic                                   PainPregabalin...
Pregabalin in Diabetic                                                                                 Neuropathic Pain   ...
Clinician’s and Patient’s                                                       rating of Pregabalin                      ...
Pregabalin Effects on                           Health Related Quality of                                  Life (QoL)• Sig...
PREGABALIN: Salient                                 Effects in Neuropathic Pain          • Rapid and sustained analgesic a...
CONCLUSIONSuccessful therapy of neuropathic pain basedon :• Accurate diagnosis• Right choice of drugs• Ability to maintain...
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Neuropathic pain strategies to improve clinical outcome

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Neuropathic pain strategies to improve clinical outcome

  1. 1. Neuropathic Pain : Strategies to Improve Clinical OutcomeBrought to you by : One is the most independent, unconventional and individualistic of all numbers
  2. 2. Common conditions associated with neuropathic painDiabetes Peripheral neuropathy Mononeuropathy RadiculopathyHerpes zoster Radiculopathy (dermatome)Spine surgery RadiculopathyHIV infection or Peripheral neuropathyAIDS Mononeuropathy Radiculopathy MyelopathyAlcoholism with Peripheral neuropathyneuropathy MononeuropathyAmputation Neuroma Phantom limb
  3. 3. Neuropathic pain• Not a single entity or diagnosis• Represents a variety of syndromes • Painful diabetic neuropathy • Trigeminal neuralgia • Post-herpetic neuralgia• Improved understanding of the basic mechanisms Whatever the Mind can conceive and Believe, the mind can Achieve Napoleon Hill
  4. 4. Neuropathic pain: Pathogenesis• Altered alpha-2 delta subunit expression of calcium channels• Central sensitization NMDA receptor activation• Peripheral sensitization: formation of ectopic impulsesNew treatment options modulate these mechanisms. e.g. Pregabalin •Ann Pharmacother. 2005 Dec;39(12):2029-37. Epub 2005 Nov 15. •Psychopharmacology (Berl). 2005 Dec;183(2):133-43. Epub 2005 Nov 9 .
  5. 5. Diagnostic pointersDistinguishing the type of pain through clinical history• Neuropathic pain: Often worse at night• Muscular pain: Usually worse during the day when activity is increased• Inflammatory pain: Worse first thing in the morning and during activity
  6. 6. Diagnosis based on the typical characteristics of neuropathic pain• The presence of certain accompanying conditions (e.g. diabetes, HIV or herpes zoster infection, multiple sclerosis)• Pain described as shooting, stabbing, lancinating, burning, or searing• Pain worse at night• Pain following anatomic nerve distribution• Pain in a numb or insensate site
  7. 7. Clues from the examination of the patient reporting neuropathic pain• Neurological deficit in the distribution of pain• Anesthesia dolorosa• Presence of allodynia• A swollen limb that is redder and also cooler than the contralateral limb, a neurogenic process (rather than inflammation)
  8. 8. Two Most Important Neuropathies• Post herpetic neuralgia• Diabetic neuropathy related pain
  9. 9. Post-herpetic Neuralgia• Varicella-zoster virus is a re-emerging infection Acute pain that accompanies Herpes zoster usually subsides spontaneously, but in 10% of patients the pain persists and intensifies• The incidence of Post-herpetic neuralgia increases up to 50% amongst elderly patients Acta Chir Iugosl. 2004;51(4):53-7.
  10. 10. Herpes zoster• Approximately 50% of individuals reaching 90 years of age will have had HZ• In approximately 6% of the patients, a second attack may occur (usually several decades after the first) Expert Opin Pharmacother. 2004 Mar;5(3):551-9.
  11. 11. Risk Factors for PHN• Old age• Female gender• Presence of a prodrome• Severe rash Neurology. 2004 May 11;62(9):1545-51. Science is below the mind; Spirituality is beyond the mind
  12. 12. Startling Facts of Treatment of PHN• Lidocaine patch 5% gives relief of pain and tactile allodynia• Corticosteroids give neither reliable protection from appearance of postherpetic neuralgia, nor shorten its duration???• Pre-emptive treatment with low-dose tricyclics (ami- or nor-triptyline 10-25 mg nocte) from the time of diagnosis of acute shingles reduces the incidence of postherpetic neuralgia by about 50% Drugs. 2004;64(9):937-47. When they tell you to grow up, they mean stop growing
  13. 13. Acyclovir treatment• Treatment of herpes zoster with 800 mg/d of oral acyclovir within 72 hours of rash onset may reduce the incidence of residual pain at 6 months by 46% in immunocompetent adults Arch Intern Med. 1997 Apr 28;157(8):909-12. Of a burning and unremitting character - F.W.PAVY
  14. 14. Diabetic Neuropathy • The prevalence : 7.5% in newly diagnosed diabetics when the definition is restricted to symptomatic subjects who have abnormalities on neurological examination • The prevalence increases with the duration of diabetes, so that 25 years after the initial diagnosis of diabetes, the prevalence is 50%Three is the most playful of all numbers and also creative, inspirationaland motivating
  15. 15. Diabetic Neuropathy• Distal symmetric polyneuropathy• Longest nerves are affected first• The earliest manifestations may be primarily small- fiber• As the disease progresses, symptoms begin in the fingertips and eventually affect the thorax and abdomen; it always advances proximally• Nocturnal exacerbation of neuropathic symptoms (NENS) Diabet Med. 2005 Dec;22(12):1763-5 Postgrad Med J. 2006 Feb;82(964):95-100 “Men of Genius Admired: Men of Wealth envied women of power feared but only women of character are trusted” A- Friedman
  16. 16. Recent advances in diagnosis of neuropathy• Corneal confocal microscopy• Laser Doppler flowmetry Invest Ophthalmol Vis Sci. 2004 Feb;45(2):418-22. Invest Ophthalmol Vis Sci. 2000 Sep;41(10):2915-21 Take time to think; it is the source of power Take time to read; it is the foundation of wisdom Take time to work; it is the price of
  17. 17. Neuropathic Pain: Approach to Treatment• Diagnosis• Treat underlying condition/Symptomatic treatment• Reduce pain• Improve physical function• Reduce psychological distress• Improve QoLNine is the most humanitarian of all numbers. It is effort and sacrifice withoutthe need for reward.
  18. 18. Site of action of drugs used for neuropathic pain BRAIN Descending Modulation Anticonvulsants C Opioids N Tricyclic Antidepressant / Selective nor epinephrine S reuptake inhibitor Central Sensitization Anticonvulsants SPINAL Opioids PNS CORD NMDA – ReceptorPeripheral AntagonistsSensitization Tricyclic Antidepressant / Anticonvulsants Selective nor epinephrine Opioids reuptake inhibitor Topical Analgesics Local anesthetics Tricyclic Antidepressant “By Nature All Men/ Women are alike but by Education widely different” - Chinese
  19. 19. Site of action of drugs used for neuropathic pain BRAIN Descending Modulation Anticonvulsants C Opioids N Tricyclic Antidepressant / Selective nor epinephrine S reuptake inhibitor Central Sensitization Anticonvulsants SPINAL Opioids PNS CORD NMDA – ReceptorPeripheral AntagonistsSensitization Tricyclic Antidepressant / Anticonvulsants Selective nor epinephrine Opioids reuptake inhibitor Topical Analgesics Local anesthetics Tricyclic Antidepressant “By Nature All Men/ Women are alike but by Education widely different” - Chinese
  20. 20. Management of neuropathic painPatient diagnosed with neuropathicpainStart treatment with the first line drugsIn case of no response after 3 monthsDrugs from a second drug class may betried Try combination therapy“Serious, sincere, systematic study surely secures supremesuccess”
  21. 21. Pregabalin• A new neuromodulator for neuropathic pain.• An alpha 2-delta ligand• A structural analogue of GABA• Analgesic, anxiolytic and anticonvulsant activity “The Truth is fear and immorality are two of the greatest inhibitors of Performance to progress”
  22. 22. Pregabalin: Mechanism of action • Acts as a ligand of the alpha2- delta subunit of calcium channels. • Decreased calcium entry into nerve endings • Less glutamate released from nerve endings Relief of neuropathic painIt is not your position that makes you happy or unhappy it is your disposition
  23. 23. Site of action of Pregabalin Nerve injuryAltered alpha (2) delta subunit expression in spinal cord and dorsal root ganglia Site of action of Pregabalin Neuropathic pain processing As one is common to all numbers, it is often seen as the origin of all things
  24. 24. Pregabalin and Gabapentin• Pregabalin is a more effective analogue of gabapentin• Pregabalin has a higher potency at the alpha 2 delta subunit of calcium channelsTwo symbolizes partnership implying that accomplishments are best through coordination.
  25. 25. Pregabalin Pharmacokinetics• Absorption: Almost 100%• PPB: None• Metabolism: Not metabolized in the liver• Excretion: Urine• Half-life: 6 hours• Clinical Implications: Effective at lower dose No drug interactionsHate screeches, fear squeals; conceits trumpets but love sings lullabies
  26. 26. Dose of Pregabalin• Initial dose : 75 mg bd or 50 mg tds• Can be increased to 300 mg/day in 1 week• Can be increased to a maximum dose of 300 mg bd or 200 mg tds after 2-4 weeks if required A good teacher is a perpetual learner
  27. 27. Side Effects Pregabalin is usually well tolerated • CNS: dizziness and drowsiness • General: Weight gain in the elderlyThree can be seen in the divisions of a human in mind, body and spirit
  28. 28. Side Effects Pregabalin is usually well tolerated • CNS: dizziness and drowsiness • General: Weight gain in the elderlyThree can be seen in the divisions of a human in mind, body and spirit
  29. 29. Pregabalin vs Gabapentin • Greater affinity for the alpha 2 subunit of calcium channels : Effective at lower doses • Better oral bioavailability: Effective at lower doses • More potent than gabapentin: Effective at lower doses • No pharmacokinetic variability : Lesser chances of inter -individual variability • Favorable pharmacokinetics: No drug interactions • Greater therapeutic index: Lesser ADR“Motivation is the Spark that lights the Fire of Knowledge and fuels the engine of Accomplishment
  30. 30. Clinical Experience with Pregabalin in Neuropathic PainPregabalin in Post-herpetic neuralgia(PHN)• Significant dose-proportional pain relief• Rapid and sustained pain relief• Reduced interference with sleep• Improves QoL• Well tolerated Curr Med Res Opin. 2006 Feb;22(2):375-84.Learn to adapt, adjust and accommodateLearn to give, not to take and learn to serve not to rule
  31. 31. Pregabalin in Diabetic Neuropathic Pain 50%% Patients with 50% reduction of pain scores from baseline 45% 40% 39% 35% 30% 25% 20% 15% 15% 10% 5% 0% Pregabalin Placebo In all of us, even in good men, there is a wild - beast nature which peers out in sleep
  32. 32. Clinician’s and Patient’s rating of Pregabalin 90% 85% 80% 73% 70% %Patients reporting improvement 60% 47% 50% 45% 40% 30% 20% 10% 0% Pregabalin Placebo“Knowledge can be communicated but not Wisdom” - Hermann Hesse
  33. 33. Pregabalin Effects on Health Related Quality of Life (QoL)• Significantly reduced weekly mean sleep interference scores• Improvement in the mental health domain• Body pain and vitality domains were improved in the 300 mg/day group• Decreased sleep interference and significant improvements in health related QoL (Quality of Life) measures Pain. 2004 May;109(1-2):26-35.At twenty the will rules At thirty the intellect At forty the Judgment
  34. 34. PREGABALIN: Salient Effects in Neuropathic Pain • Rapid and sustained analgesic action • Significantly improves slow-wave sleep • Reduces neuropathic pain of post herpetic neuralgia and diabetic neuropathy • Improves health related QoL (Quality of Life) • Well tolerated • Has a low discontinuation rateFour is reliable, punctual, systematic and dependable, doing what it says it will do.
  35. 35. CONCLUSIONSuccessful therapy of neuropathic pain basedon :• Accurate diagnosis• Right choice of drugs• Ability to maintain the QoL of the patient Time and Words cannot be recalled - Fuller
  36. 36. THANK YOU

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