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NEUROPATHIC PAIN   Dr.S.Anjaneyulu   PG neurology
Neuropathic Pain <ul><li>Pain initiated or caused by a primary lesion or dysfunction in the nervous system </li></ul><ul><...
Pathophysiology of pain perception <ul><li>Transduction </li></ul><ul><li>Transmission </li></ul><ul><li>Modulation </li><...
Symptoms and Signs <ul><li>Spontaneous vs stimulus evoked  </li></ul><ul><li>Burning, constant, throbbing vs jabbing, stab...
Fellow travelers <ul><li>Sleep </li></ul><ul><li>Mood </li></ul><ul><li>Recreation  </li></ul><ul><li>Anxiety </li></ul><u...
Neuropathic Pain vs Muscle Pain
Likely causes of neuropathy according to speed of onset Acute onset Inflammatory Immunological Toxic Vascular Subacute ons...
Etiologies of Neuropathic Pain Low  back Diabetes PHN Cancer Others
Goals of Neuropathic  Pain Management Treat/prevent recurrence of pain-causing condition Reduce pain Improve physical/psyc...
Neuropathic Pain:  Approach to Treatment Diagnosis Treat underlying condition/symptomatic treatment Reduce Pain Prevention...
Common Peripheral Neuropathies <ul><li>Postherpetic neuralgia (commonly lower trunk) </li></ul><ul><li>Complex regional pa...
Common Central Neuropathies <ul><li>Compression myelopathy from spinal stenosis (radiating arm, fingers, lower back, radia...
Risk Continuum of Pain Therapy Level of Risk Most invasive Least invasive Interventional  techniques Oral  medications Top...
Neuropathic Pain: Nonpharmacologic Treatment Options <ul><li>Cognitive-behavioral strategies </li></ul><ul><ul><li>Meditat...
Topical vs Transdermal  Delivery Systems Topical (eg, lidocaine patch 5%) Transdermal (eg, fentanyl patch) <ul><li>Periphe...
Neuropathic Pain: First-Line Pharmacologic Treatments <ul><li>Gabapentin </li></ul><ul><li>Lidocaine patch 5% </li></ul><u...
Pharmacological Treatments *: FDA approved in various neuropathic pain diseas +: FDA approved for use in severe chrnic pain
APPROACHES TO THE MANAGEMENT  OF NEUROPATHIC PAIN <ul><li>Monotherapy Combinations Additional Measures </li></ul><ul><li>F...
APPROACHES TO THE MANAGEMENT  OF NEUROPATHIC PAIN Monotherapy  Combinations Additional Measures B. Second-line Capsaicin P...
APPROACHES TO THE MANAGEMENT  OF NEUROPATHIC PAIN Monotherapy  Combinations C. Third-line Alternative opioids Ketamine plu...
Peripheral neuropathic pain ALGORITHM FOR SEQUENCE OF DIFFERENT DRUG TREATMENTS IN PERIPHERAL NEUROPATHIC PAIN  Lidocaine ...
Algorithm for the management of neuropathic pain Consider nonpharmacologic treatments (e.g. physiotherapy, psychological i...
Algorithm for the management of neuropathic pain If postherpetic neuralgia or focal neuropathy, initiate topical lidocaine...
Algorithm for the management of neuropathic pain Initiate first-line drug monotherapy (Pregabalin or Gabapentin  OR  TCA  ...
Algorithm for the management of neuropathic pain Switch  to alternate first-line drug monotherapy (TCA or SNRI  OR  Gabape...
Algorithm for the management of neuropathic pain Initiate monotherapy with Tramadol or Oxycodone Ineffective or not tolera...
Algorithm for the management of neuropathic pain Refer patient to pain specialty clinic for consideration of third-line dr...
Topical Agents: Proposed MOA <ul><li>Lidocaine Patch 5% </li></ul><ul><ul><li>Acts by blocking sodium channels thereby red...
Topical Agents: Lidocaine <ul><li>Lidocaine </li></ul><ul><ul><li>Advantages: </li></ul></ul><ul><ul><ul><li>Approved for ...
Opioids: Proposed MOA <ul><li>Opioids </li></ul><ul><ul><li>Modulates the perception of pain via  µ opioid receptor </li><...
OPIOID ACTIVITY AT RECEPTOR SITES Mu Kappa Delta NOP NMDA Serotonergic Noradrenergic Morphine + Oxycodone + + Fentanyl ++ ...
Opioids <ul><li>Advantages: </li></ul><ul><ul><li>Several double-blind studies demonstrated oxycodone, morphine, and metha...
Antidepressants: Proposed MOA <ul><li>TCAs </li></ul><ul><ul><li>Inhbition of serotonin and nor-epinephrine reuptake </li>...
TCAs <ul><li>Advantages </li></ul><ul><ul><li>Well documented efficacy in treatment of PHN and DPN. </li></ul></ul><ul><ul...
SSRIs & SNRIs <ul><li>Advantages: </li></ul><ul><ul><li>selective and are better tolerated than TCAs, with fewer associate...
Anticonvulsants: Proposed MOA <ul><li>Oxcarbazepine </li></ul><ul><ul><li>Modulation of high voltage activated calcium cha...
Anticonvulsants <ul><li>Disadvantage: </li></ul><ul><ul><li>Phenytoin: low safety profile </li></ul></ul><ul><ul><li>Exten...
Gabapentin <ul><li>Advantages </li></ul><ul><ul><li>Approved for treatment of PHN </li></ul></ul><ul><ul><li>does not requ...
Drugs in Neuropathic Pain Drug Category Type of Neuropathic Pain Daily Dosage Antidepressants Amitryptyline PHN, DPNP 10-1...
Drugs in Neuropathic Pain Anticonvulsants Gabapentin PHN, DPNP 1800-3600 mg Carbamazapine Trigeminal Neuralgia 400-800 mg ...
Neuropathic Pain:  Emerging Treatments  Class/Drug Under Investigation <ul><li>Bisphosphonate </li></ul><ul><li>Pamidronat...
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Neuropathic Pain

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Neuropathic Pain

  1. 1. NEUROPATHIC PAIN Dr.S.Anjaneyulu PG neurology
  2. 2. Neuropathic Pain <ul><li>Pain initiated or caused by a primary lesion or dysfunction in the nervous system </li></ul><ul><li>Two types </li></ul><ul><li>Peripheral Neuropathic pain : Lesion in Peripheral Nervous system </li></ul><ul><li>Central Neuropathic pain : Lesion in Central Nervous system </li></ul>
  3. 3. Pathophysiology of pain perception <ul><li>Transduction </li></ul><ul><li>Transmission </li></ul><ul><li>Modulation </li></ul><ul><li>Perception </li></ul><ul><li>Interpretation </li></ul><ul><li>Behavior </li></ul>
  4. 4. Symptoms and Signs <ul><li>Spontaneous vs stimulus evoked </li></ul><ul><li>Burning, constant, throbbing vs jabbing, stabbing </li></ul><ul><li>Mild, moderate, severe </li></ul><ul><li>Distribution may not along classical neuroanatomical lines </li></ul><ul><li>Associated with </li></ul><ul><li>analgesia </li></ul><ul><li>hyperalgesia </li></ul><ul><li>allodynia </li></ul>
  5. 5. Fellow travelers <ul><li>Sleep </li></ul><ul><li>Mood </li></ul><ul><li>Recreation </li></ul><ul><li>Anxiety </li></ul><ul><li>Sex </li></ul><ul><li>Work </li></ul><ul><li>“ QOL and function” </li></ul>
  6. 6. Neuropathic Pain vs Muscle Pain
  7. 7. Likely causes of neuropathy according to speed of onset Acute onset Inflammatory Immunological Toxic Vascular Subacute onset over weeks or months Toxic Nutritional Systemic disease Chronic onset over many years Hereditary Metabolic disease
  8. 8. Etiologies of Neuropathic Pain Low back Diabetes PHN Cancer Others
  9. 9. Goals of Neuropathic Pain Management Treat/prevent recurrence of pain-causing condition Reduce pain Improve physical/psychologic function Improve quality of life
  10. 10. Neuropathic Pain: Approach to Treatment Diagnosis Treat underlying condition/symptomatic treatment Reduce Pain Prevention (if applicable) Reduce psychological distress Improve physical functioning Improve overall quality of life
  11. 11. Common Peripheral Neuropathies <ul><li>Postherpetic neuralgia (commonly lower trunk) </li></ul><ul><li>Complex regional pain syndrome (arms and legs) </li></ul><ul><li>Mechanical neuropathies (commonly upper extremities) </li></ul><ul><ul><li>Entrapment neuropathies </li></ul></ul><ul><ul><li>Nerve compressions </li></ul></ul><ul><li>HIV-related sensory neuropathy (feet and ankles) </li></ul><ul><li>Idiopathic sensory neuropathy (distal/proximal) </li></ul><ul><li>Phantom limb </li></ul><ul><li>Posttraumatic neuralgias </li></ul><ul><li>Trigeminal neuralgia (facial) </li></ul><ul><li>Cancer-chemotherapy–induced neuropathies (hands and feet) </li></ul><ul><li>Painful diabetic neuropathy (hands and feet) </li></ul>
  12. 12. Common Central Neuropathies <ul><li>Compression myelopathy from spinal stenosis (radiating arm, fingers, lower back, radiating leg) </li></ul><ul><li>HIV myelopathy </li></ul><ul><li>Pain related to multiple sclerosis and Parkinson’s disease </li></ul><ul><li>Postischemic and postradiation myelopathy </li></ul><ul><li>Poststroke pain (face, arm, leg, or trunk on side of stroke) </li></ul>
  13. 13. Risk Continuum of Pain Therapy Level of Risk Most invasive Least invasive Interventional techniques Oral medications Topical medications Psychologic/ physical approaches Injections
  14. 14. Neuropathic Pain: Nonpharmacologic Treatment Options <ul><li>Cognitive-behavioral strategies </li></ul><ul><ul><li>Meditation </li></ul></ul><ul><ul><li>Imagery </li></ul></ul><ul><ul><li>Biofeedback </li></ul></ul><ul><ul><li>Relaxation therapy </li></ul></ul><ul><li>Physical rehabilitation </li></ul><ul><li>Acupuncture </li></ul><ul><li>Transcutaneous electrical nerve stimulation </li></ul>
  15. 15. Topical vs Transdermal Delivery Systems Topical (eg, lidocaine patch 5%) Transdermal (eg, fentanyl patch) <ul><li>Peripheral tissue activity </li></ul><ul><li>Applied directly over painful site </li></ul><ul><li>Insignificant serum levels </li></ul><ul><li>Systemic side effects unlikely </li></ul><ul><li>Systemic activity </li></ul><ul><li>Applied away from painful site </li></ul><ul><li>Serum levels necessary </li></ul><ul><li>Possible systemic side effects </li></ul>
  16. 16. Neuropathic Pain: First-Line Pharmacologic Treatments <ul><li>Gabapentin </li></ul><ul><li>Lidocaine patch 5% </li></ul><ul><li>Opioid analgesics </li></ul><ul><li>Tramadol </li></ul><ul><li>Tricyclic antidepressants </li></ul><ul><li>Recently approved agents </li></ul><ul><ul><li>Duloxetine </li></ul></ul><ul><ul><li>Pregabalin </li></ul></ul>
  17. 17. Pharmacological Treatments *: FDA approved in various neuropathic pain diseas +: FDA approved for use in severe chrnic pain
  18. 18. APPROACHES TO THE MANAGEMENT OF NEUROPATHIC PAIN <ul><li>Monotherapy Combinations Additional Measures </li></ul><ul><li>First-line TCA Low-dose TCA+ AE Paracetamol </li></ul><ul><li>e.g.amitriptyline TENS </li></ul><ul><li>Anti-epileptic (AE), Acupuncture </li></ul><ul><li> Pregabalin/Gabapentin Physiotherapy </li></ul><ul><li> Occupational therapy </li></ul>
  19. 19. APPROACHES TO THE MANAGEMENT OF NEUROPATHIC PAIN Monotherapy Combinations Additional Measures B. Second-line Capsaicin Physiotherapy Lidocaine patch Occupational therapy Tizanidine Paracetamol Clonidine TENS Baclofen Acupuncture Alternative antidepressant (e.g. duloxetine) Opioid tramadol, morphine, oxycodone Opioid with TCA or AE
  20. 20. APPROACHES TO THE MANAGEMENT OF NEUROPATHIC PAIN Monotherapy Combinations C. Third-line Alternative opioids Ketamine plus opioid Ketamine Intrathecal drug delivery Neuromodulation Additional Measures : Paracetamol, TENS, Acupuncture,Physiotherapy, Occupational therapy plus Psychological support
  21. 21. Peripheral neuropathic pain ALGORITHM FOR SEQUENCE OF DIFFERENT DRUG TREATMENTS IN PERIPHERAL NEUROPATHIC PAIN Lidocaine patch NO Post-herpetic neuralgia and focal neuropathy Pregabalin/ Gabapentin Tramadol, oxycodone TCA (SNRI) TCA (SNRI) Pregabalin/ Gabapentin YES YES NO YES NO TCA contraindication TCA contraindication
  22. 22. Algorithm for the management of neuropathic pain Consider nonpharmacologic treatments (e.g. physiotherapy, psychological interventions) and, in some cases, early referral for nerve blocks to facilitate rehabilitation (e.g., complex regional pain syndrome) First Step
  23. 23. Algorithm for the management of neuropathic pain If postherpetic neuralgia or focal neuropathy, initiate topical lidocaine treatment Ineffective, partial response or other diagnosis Second Step
  24. 24. Algorithm for the management of neuropathic pain Initiate first-line drug monotherapy (Pregabalin or Gabapentin OR TCA OR SNRI) Third Step
  25. 25. Algorithm for the management of neuropathic pain Switch to alternate first-line drug monotherapy (TCA or SNRI OR Gabapentin or Pregabalin) Ineffective or not tolerated/ TCA contraindication Partial treatment response Consider adding alternate first-line drug (TCA or SNRI OR gabapentin or pregabalin) Fourth Step
  26. 26. Algorithm for the management of neuropathic pain Initiate monotherapy with Tramadol or Oxycodone Ineffective or not tolerated Partial treatment response Consider adding Tramadol or Oxycodone Fifth Step
  27. 27. Algorithm for the management of neuropathic pain Refer patient to pain specialty clinic for consideration of third-line drugs, interventional treatments and pain rehabilitation programs Ineffective or not tolerated Sixth Step
  28. 28. Topical Agents: Proposed MOA <ul><li>Lidocaine Patch 5% </li></ul><ul><ul><li>Acts by blocking sodium channels thereby reducing ectopic nerve impulses </li></ul></ul><ul><li>Capsaicin </li></ul><ul><ul><li>Acts via depletion of substance P and activity at the vanilloid receptor </li></ul></ul>
  29. 29. Topical Agents: Lidocaine <ul><li>Lidocaine </li></ul><ul><ul><li>Advantages: </li></ul></ul><ul><ul><ul><li>Approved for the treatment of PHN (sufficient data available for its efficacy in PHN) </li></ul></ul></ul><ul><ul><ul><li>Minimal risk of drug interactions or systemic adverse effects. </li></ul></ul></ul><ul><ul><li>Disadvantages </li></ul></ul><ul><ul><ul><ul><li>Currently approved dose of 12-hour on/12-hour off was found to be insufficient for some patients. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Not approved for DPNP </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Adverse effects: Skin erythema, rash </li></ul></ul></ul></ul>
  30. 30. Opioids: Proposed MOA <ul><li>Opioids </li></ul><ul><ul><li>Modulates the perception of pain via µ opioid receptor </li></ul></ul><ul><li>Tramadol </li></ul><ul><ul><li>Acts through both µ opioid receptors and inhibits the uptake of nor-epinephrine </li></ul></ul><ul><ul><li> </li></ul></ul>
  31. 31. OPIOID ACTIVITY AT RECEPTOR SITES Mu Kappa Delta NOP NMDA Serotonergic Noradrenergic Morphine + Oxycodone + + Fentanyl ++ Tramadol + + + Methadone + - Buprenorphine (+) - - Diamorphine + + = full agonist (+) = partial agonist - = antagonist
  32. 32. Opioids <ul><li>Advantages: </li></ul><ul><ul><li>Several double-blind studies demonstrated oxycodone, morphine, and methadone efficacy in PHN, DPN </li></ul></ul><ul><ul><li>In clinical studies patients preferred treatment with opioids over TCA </li></ul></ul><ul><li>Disadvantages: </li></ul><ul><ul><li>Very high rates of side effects most important being euphoria and constipation </li></ul></ul><ul><ul><li>Abuse liability or chances of addiction </li></ul></ul>
  33. 33. Antidepressants: Proposed MOA <ul><li>TCAs </li></ul><ul><ul><li>Inhbition of serotonin and nor-epinephrine reuptake </li></ul></ul><ul><li>SSRIs & SNRIs </li></ul><ul><ul><li>Inhbition of serotonin and nor-epinephrine reuptake </li></ul></ul>
  34. 34. TCAs <ul><li>Advantages </li></ul><ul><ul><li>Well documented efficacy in treatment of PHN and DPN. </li></ul></ul><ul><ul><li>Recommended as first-line agents for all neuropathic pain by many practitioners </li></ul></ul><ul><li>Disadvantages </li></ul><ul><ul><li>Unacceptable side effects like </li></ul></ul><ul><ul><ul><li>Anticholinergic effects: Dry mouth, constipation, blurred vision, urinary retention, dizziness, tachycardia, memory impairment </li></ul></ul></ul><ul><ul><ul><li>Sedation </li></ul></ul></ul><ul><ul><ul><li>Alpha-1-adrenergic effects: Orthostatic hypotension / syncope </li></ul></ul></ul><ul><ul><ul><li>Cardiac conduction delays/heart block: Arrhythmias, Q-T prolongation </li></ul></ul></ul><ul><ul><ul><li>Other side effects: Weight gain, excessive perspiration, sexual dysfunction </li></ul></ul></ul>
  35. 35. SSRIs & SNRIs <ul><li>Advantages: </li></ul><ul><ul><li>selective and are better tolerated than TCAs, with fewer associated side effects and toxicities. </li></ul></ul><ul><li>Disadvantages: </li></ul><ul><ul><li>Except Duloxetine which is a SNRI all the other agents in this group are believed to be less efficacious in the treatment of neuropathic pain and are not regarded as first-line agents </li></ul></ul><ul><ul><li>Citalopram and paroxetine have shown some benefit in the management of DPNP but have no efficacy in the PHN patients </li></ul></ul><ul><ul><li>Though the SNRI duloxetine has recently received FDA approval for use in DPNP it has poor efficacy in the treatment of PHN </li></ul></ul>
  36. 36. Anticonvulsants: Proposed MOA <ul><li>Oxcarbazepine </li></ul><ul><ul><li>Modulation of high voltage activated calcium channels </li></ul></ul><ul><ul><li>Blockade of voltage gated sodium channels </li></ul></ul><ul><li>Valproate, Lamotrigine, Topiramate </li></ul><ul><ul><li>Blockade of voltage gated sodium channels </li></ul></ul><ul><li>Gabapentin, Pregabalin </li></ul><ul><ul><li>Modulates voltage gated calcium channels by binding to α 2-  subunit of presynaptic neurons </li></ul></ul>
  37. 37. Anticonvulsants <ul><li>Disadvantage: </li></ul><ul><ul><li>Phenytoin: low safety profile </li></ul></ul><ul><ul><li>Extensive adverse effect profile </li></ul></ul><ul><ul><li>Lamotrigine: Stevens–Johnson syndrome </li></ul></ul>
  38. 38. Gabapentin <ul><li>Advantages </li></ul><ul><ul><li>Approved for treatment of PHN </li></ul></ul><ul><ul><li>does not require blood monitoring </li></ul></ul><ul><li>Disadvantages </li></ul><ul><ul><li>Side effects like drowsiness, somnolence, and generalized fatigue </li></ul></ul><ul><ul><li>Due to low potency the dose requirement for gabapentin is high nearly 900-1800mg </li></ul></ul>
  39. 39. Drugs in Neuropathic Pain Drug Category Type of Neuropathic Pain Daily Dosage Antidepressants Amitryptyline PHN, DPNP 10-140mg Nortryptyline PHN 10-160mg Desipramine DPNP 111 mg (avg) Citalopram DPNP 40 mg Paroxetine DPNP 40mg Bupropion DPNP, PHN 150-300mg Duloxetine DPNP 60mg Venlafaxine DPNP 150-225 mg Methadone Various neuropathic pain 10-20 mg
  40. 40. Drugs in Neuropathic Pain Anticonvulsants Gabapentin PHN, DPNP 1800-3600 mg Carbamazapine Trigeminal Neuralgia 400-800 mg Local Application Lidocaine patch, 5% PHN 3 patches/12hrs Opioids CR oxycodone PHN, DPNP 60-120mg CR morphine PHN 22 mg Tramadol DPNP 400 mg
  41. 41. Neuropathic Pain: Emerging Treatments Class/Drug Under Investigation <ul><li>Bisphosphonate </li></ul><ul><li>Pamidronate </li></ul>Phase III trials for the management of malignant bone pain <ul><li>Novel Analgesic </li></ul><ul><li>Bicifiadine </li></ul><ul><li>Ziconotide (Conus snail venom peptide) </li></ul>Under clinical investigation for chronic low back pain (LBP) In clinical development for chronic LBP and cancer, neuropathic, and postoperative pain <ul><li>NMDA-Receptor Antagonist </li></ul><ul><li>Memantine </li></ul>Currently being studied for neuropathic pain syndromes(approved for treatment of Alzheimer’s disease) Cannabinoid-Receptor Agonist Under investigation for cancer, neuropathic, and postoperative pain (UK); neuropathic pain (Canada)
  42. 42. THANK YOU

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