diabetic neuropathy

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  • This slide illustrates the concept that many different underlying causes of neuropathic pain may express as different spontaneous and stimulus-evoked pain symptoms via different pathophysiological mechanisms. The key talking points on this slide are as follows: There are many possible causes of neuropathic pain. Neuropathic pain is commonly classified according to the etiological nature of the damage to the nervous system or the anatomical distribution of the pain, although the relationship between etiology, mechanisms, and symptoms/signs is highly complex. For instance, the pain caused by diverse diseases may originate through common mechanisms also one mechanism could be responsible for many different symptoms conversely, the same symptom in 2 patients may be caused by different mechanisms furthermore, more than one mechanism can operate in a single patient, and the pattern of mechanisms and symptoms within a single patient may change with time. No pain pathophysiological mechanism is an inevitable consequence of a particular disease process. Studies are needed to further define pathophysiological mechanisms of neuropathic pain. Reference Woolf and Mannion. Lancet 1999;353:1959-64 Additional key words: pathophysiology
  • This slide describes the type of pain associated with the two broad categories of neuropathic pain signs and symptoms: spontaneous (also termed stimulus-independent) and stimulus-evoked symptoms. The key talking points on this slide are as follows: Spontaneous pain is the most frequent symptom in all painful neuropathies and presents with a burning quality, localized superficially, or electric shock-like pain for several seconds. Dysesthesias are abnormal sensations that are unpleasant, and include shooting, lancinating (piercing/stabbing) or burning pains. Paresthesias are abnormal sensations that are not unpleasant, such as tingling. Symptoms of stimulus-evoked pain can be described according to the nature of the provoking stimulus, i.e. whether it is usually pain-free and innocuous, or painful and noxious. Allodynia is a painful response to a stimulus that is not normally painful. Hyperalgesia is a heightened response to a stimulus that would normally evoke pain. Hyperpathia is a painful syndrome characterized by an abnormally delayed painful reaction to a stimulus, especially a repetitive stimulus. References Baron. Clin J Pain. 2000;16:S12-S20. Merskey H et al. (Eds) In: Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 1994:209-212.
  • diabetic neuropathy

    1. 1. Management of Painful Neuropathy
    2. 2. Neuropathic PainPain initiated or caused by aprimary lesion or dysfunctionin the nervous systemClassification of Chronic PainInternational Association for the Study ofPain, 1994
    3. 3. Mechanisms of Neuropathic Pain
    4. 4. Development of Neuropathic Pain Syndrome Neuropathic pain Symptoms Spontaneous pain Stimulus-evoked pain Pathophysiology Mechanisms Metabolic Traumatic Ischemic Toxic Etiology Hereditary Infectious Compression Immune-related Nerve damageWoolf and Mannion. Lancet 1999;353:1959-64
    5. 5. Signs and Symptoms of Neuropathic PainSign/Symptom Description (example)Spontaneous symptoms Persistent burning, intermittent shock-like or – Spontaneous pain1 lancinating pain Abnormal unpleasant sensations – Dysesthesias2 e.g. shooting, lancinating, burning – Parasthesias2 Abnormal, not unpleasant sensations e.g. tinglingStimulus-evokedsymptoms Painful response to a non-painful stimulus – Allodynia2 e.g. warmth, pressure, stroking Heightened response to painful stimulus e.g. pinprick, – Hyperalgesia2 cold, heat – Hyperpathia2 Delayed, explosive response to any painful stimulus 1.Baron. Clin J Pain. 2000;16:S12-S20. 2. Merskey H et al. (Eds) In: Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 1994:209-212.
    6. 6. Nociceptive vs. Neuropathic Pain
    7. 7. Types of Neuropathic Pain•Peripheral Neuropathy •Central NeuropathyDue to anatomical, chemical or Due to pathophysiologicalbiochemical changes to peripheralnerves changes in the brain or spinal chord i.e. the primaryExamples include: lesion is in the CNS•diabetic neuropathy•sciatica, Examples include:•post-surgery•Fibromyalgia •phantom limb pain•post-herpetic neuralgia, •Pain following stroke•trigeminal neuralgia, •multiple sclerosis•compression by a tumour•radiation therapy•Chemotherapy (e.g. vincristine)•pain in HIV infections
    8. 8. Most Common Neuropathic Painful Conditions1. Radiculopathy – Cervical Radiculopathy: Restricted motion in neck; pain in neck and arms – Lumbosacral Radiculopathy: Commonly, low back pain and sciatica2. Fibromyalgia3. Post traumatic nerve compression4. Post herpetic neuralgia5. Diabetic peripheral neuropathy6. Trigeminal neuralgia7. Phantom limb pain8. Pain following stroke9. Multiple sclerosis
    9. 9. Current Treatment Options• Tricyclic Antidepressants (e.g. Imipramine)• Conventional Anticonvulsants (e.g. Carbamazepine)• Opioid Analgesics• Gabapentin• Mecobalamin• Pregabalin
    10. 10. Tricyclic Antidepressants Adverse Effects • blurred visionTricyclic (Tertiary Amines) • cognitive changes• Amitriptyline• Doxepin • constipation• Clomipramine • dry mouth• Imipramine • orthostatic hypotensionTricyclic (SecondaryAmines) • Sedation• Desipramine • sexual• Nortriptyline dysfunction• Protriptyline • tachycardia • urinary retention
    11. 11. Conventional AnticonvulsantsCarbamazepine• Diabetic neuropathy Adverse Effects• Postherpetic neuralgia• CRPS type I and II •Dizziness• Trigeminal neuralgia •Drowsiness •Mental slowingClonazepam• Phantom pain •Drug interactions •DiplopiaPhenytoin •Nausea & vomiting• Diabetic neuropathy• Trigeminal neuralgia •Agranulocytosis •Aplastic anemiaValproic Acid •Possibility of• Trigeminal neuralgia• Occipital neuralgia activating latent psychosis
    12. 12. Opiod Analgesics• Constipation• Nausea• Somnolence• Dizziness• Pruritus• Vomiting• Sweating• Frequency of AEs ≥10% of patients.
    13. 13. Gabapentin• Gabapentin, alpha -2-delta subunit voltage-gated calcium-channel antagonist• Dose titration required to achieve optimal level• Optimal dosage 1800mg/day in PHN
    14. 14. GabapentinAdverse Events* GabapentinDizziness 17.1%Somnolence 19.3%Peripheral Edema 1.7%Ataxia 12.5%Weight Gain 2.9% *Gabapentin Product Monograph
    15. 15. Gabapentin GabapentinMechanism of Action Selectively bind to the alpha2-delta subunit of Ca+ channelPharmacokinetic profile Non-linear (plasma concentration increases dispropotionately to dose)Oral bioavailability 60% 900mg 47% 1200mg 34% 2400mg 33% 3600mgDosing TIDTime to Effective dose > 9days (titrate to effective dose of 1800mg/d) *Gabapentin Product Monograph
    16. 16. Healthy Neuron Happy Life
    17. 17. Analog of GABA, binds to alpha 2 delta subunit of voltagegated calcium channels.
    18. 18. • Novel evidence suggest that regulation of…• Glutamate.• Substance P & Noradrenalin.• Results is relief from neuro - pathic pain syndrome.
    19. 19. Partial Onset SeizuresDiabetic Peripheral Neuropathy Post Herpetic Neuralgia Fibromyalgia
    20. 20. Comparative Pharmacokinetics Pregabalin GabapentinFDA Approved DPN, Fibromyalgia, PHN, PHN, EpilepsyIndications Partial SeizuresMechanism of Selectively bind to the alpha2- Selectively bind to the alpha2-deltaAction delta subunit of Ca+ channel subunit of Ca+ channelPharmacokinetic Linear (plasma concentration is Non-linear (plasma concentrationprofile dose proportionate) increases disproportionately to dose)Oral bioavailability > 90% all doses 60% 900mg 47% 1200mg 34% 2400mg 33% 3600mgDosing BID TIDTime to Effective 1 day (effective starting dose > 9days (titrate to effective dose ofdose of 150mg/day) 1800mg/d)
    21. 21. Clinically Evidence•The efficacy of Gablin (pregabalin) for the management ofneuropathic pain associated with DM•4 double-blind, fixed-dose, placebo controlled, multi-centerstudies with twice a day (BID) and 3 times a day (TID) dosing•Studies DPN1, DPN2, DPN3 and DPN4 enrolled a total of 1124patients with type 1 or 2 diabetes mellitus with painful distal symmetrical sensorimotor polyneuropathy for1 to 5 years
    22. 22. Clinically Proven Efficacy45403530 Pregabalin 600mg25 39%201510 Placebo 15% 5 0 Reduction in Pain Symptoms
    23. 23. Clinically Proven Efficacy60504030 Pregabalin Pregabalin 600mg 300mg 48%20 46%10 Placebo 18% 0
    24. 24. Clinically Proven Efficacy45403530 Pregabalin 300mg25 40%201510 Placebo 5 15% 0
    25. 25. Clinically Proven Efficacy5045403530 Pregabalin25 300/600mg 46%20 Placebo15 30%10 5 0
    26. 26. Clinically Proven Efficacy In DPN 90 80 70 Pregabalin 600mg Pregabalin 60 80% 300mg 74% Pregabalin 50 150mg 65% Placebo 40 54% 30 20 10 0 Meta-analysis of 7 clinical trials Total number of patients 1510 (557 placebo, 953 Pregabalin)
    27. 27. Fibromyalgia 30 25> 50% pain reduction 20 Gablin 450mg 15 29% 10 Placebo 13% 5 0 Crofford Lj. RowbothamMC. et.al Arthritis Rheum 2005 52:1264-1273
    28. 28. Spinal Cord Injury “The literature data suggest that Gablin (Pregabalin) is more efficacious thanGabapentin in many important variables for Neuropathic pain in Spinal Cord Injury” Eur J Clin Pharmacol. 2008 Jul 8
    29. 29. Comparative Adverse Event ProfileAdverse Events* Pregabalin GabapentinDizziness 10.7 17.1%Somnolence 8.3 19.3%Peripheral 0.0 1.7%EdemaAtaxia 7.1 12.5%Weight Gain 1.2 2.9% *Gabapentin & Pregabalin Product Monograph
    30. 30. FDA APPROVED DOSAGE SCHEDULE• … Initial Dose in …• … Diabetic Peripheral Neuropathy• … Post Herpetic Neuralgia• … Partial Onset of Seizures• … Fibromyalgia• … Is 75mg Twice daily• … Maximum daily recommended dose is … 600mg per day.
    31. 31. Recommended DosageDosing Parameter Low Back Pain Sciatica Spinal Cord Injury Initial Daily 75mg 2 times 75mg 2 times daily 75mg 2 times daily daily (150mg/day) (150mg/day) Dosage (150mg/day)Maximum Daily Dosage 600mg/day 600mg/day 600mg/day
    32. 32. Wishing You A Healthy Life

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