Your SlideShare is downloading. ×
0
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Neuropathic pain revised 2010
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Neuropathic pain revised 2010

3,324

Published on

0 Comments
10 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
3,324
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
0
Comments
0
Likes
10
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Treating Neuropathic Pain Joseph A. Cardinale, MD Assistant Professor Division of Pain Management Department of Anesthesiology August 31, 2010
  • 2. Causes of Neuropathic Pain <ul><li>• Diabetes </li></ul><ul><li>• HIV </li></ul><ul><li>• Multiple sclerosis </li></ul><ul><li>• Herpes zoster </li></ul><ul><li>• Neoplasia </li></ul><ul><li>• Vitamin deficiencies </li></ul><ul><li>• Traumatic </li></ul><ul><li>Spinal Cord injury </li></ul><ul><li>Tissue damage </li></ul><ul><li>Nerve damage </li></ul><ul><li>Loss of limb </li></ul><ul><li>Stroke </li></ul><ul><li>Vasculitis </li></ul><ul><li>Medications </li></ul><ul><li>– Amiodarone </li></ul><ul><li>– Cisplatinum </li></ul><ul><li>– Isoniazid </li></ul><ul><li>– Metronidazole </li></ul><ul><li>– Nitrofurantoin </li></ul><ul><li>– NRTIs (ddI, d4T, ddC) </li></ul><ul><li>– Phenytoin </li></ul><ul><li>– Vinca alkaloids </li></ul><ul><li>• Heavy metals </li></ul><ul><li>Arsenic, Lead, </li></ul><ul><li>Mercury, Thallium </li></ul><ul><li>• Alcohol </li></ul>
  • 3. Neuropathic Pain Conditions <ul><li>Diabetic neuropathy </li></ul><ul><li>Post-herpetic </li></ul><ul><li>neuralgia </li></ul><ul><li>Pain associated with </li></ul><ul><li>strokes </li></ul><ul><li>Trigeminal neuralgia </li></ul><ul><li>Complex Regional </li></ul><ul><li>Pain Syndrome </li></ul><ul><li>(CRPS) </li></ul><ul><li>• Stump / Phantom limb </li></ul>
  • 4. Neuropathic Pain Symptoms <ul><li>Onset of pain delayed after injury </li></ul><ul><li>Can be constant or intermittent </li></ul><ul><li>(even paroxysmal) </li></ul><ul><li>Pain described as: </li></ul><ul><li>– Electric shock </li></ul><ul><li>– Burning </li></ul><ul><li>– Aching </li></ul><ul><li>– Tingling, needles and pins </li></ul><ul><li>- Lancinating </li></ul>
  • 5. Neuropathic Pain Symptoms <ul><li>Nonsensory neurological &musculoskeletal signs </li></ul><ul><li>– Weakness </li></ul><ul><li>– Tremor </li></ul><ul><li>– Dystonia </li></ul><ul><li>– Spasticity </li></ul><ul><li>– decreased ROM </li></ul><ul><li>– muscle spasms </li></ul>
  • 6. Cardinal Symptoms of Neuropathic Pain <ul><li>• Hyperalgesia </li></ul><ul><li>– exaggerated painful response to a </li></ul><ul><li>normally noxious stimuli </li></ul><ul><li>• Allodynia (Mechanical & Thermal) </li></ul><ul><li>– painful response to a normally nonnoxious </li></ul><ul><li>stimulus (light touch or </li></ul><ul><li>temperature) </li></ul>
  • 7. Two Types of Peripheral Pain Neurons <ul><li>• A-delta fibers </li></ul><ul><li>– Thick, myelinated, fast conducting </li></ul><ul><li>– Mediate the feeling of initial fast, sharp, </li></ul><ul><li>highly localized pain. </li></ul><ul><li>• C fibers </li></ul><ul><li>– Thin, unmyelinated, slow-conducting </li></ul><ul><li>– Mediate slow, dull, more diffuse, often </li></ul><ul><li>burning pain </li></ul>
  • 8. Pathophysiology of Neuropathic Pain <ul><li>Peripheral </li></ul><ul><li>– Following a peripheral nerve injury, </li></ul><ul><li>abnormal accumulation of Na+ </li></ul><ul><li>channels at nociceptor & DRG </li></ul>
  • 9. Pathophysiology of Neuropathic Pain <ul><li>Peripheral </li></ul><ul><li>Altered expression & increased </li></ul><ul><li>distribution of Na+ channels leads to: </li></ul><ul><li>• Lowering of nociceptor depolarization </li></ul><ul><li>threshold = Ectopic discharges </li></ul><ul><li>• Phenomenon known as “peripheral </li></ul><ul><li>sensitization” </li></ul>
  • 10. Pathophysiology of Neuropathic Pain <ul><li>Central Sensitization </li></ul><ul><li>Wind-up’ phenomenon </li></ul>
  • 11. Pathophysiology of Neuropathic Pain <ul><li>Central Sensitization </li></ul><ul><li>– Up-regulation of NMDA receptors </li></ul><ul><li>– increased Intracellular Ca++ </li></ul><ul><li>• decreased threshold of spinal horn neurons </li></ul><ul><li>• increased magnitude & duration of response to stimuli </li></ul><ul><li>– Induction of early gene expression </li></ul><ul><li>(plasticity and pain “memory”) </li></ul>
  • 12. Pathophysiology of Neuropathic Pain
  • 13. <ul><li>Neuroplasticity” </li></ul><ul><li>• Sprouting of A δ fibers from deep </li></ul><ul><li>laminae to synapse in Lamina I & II of </li></ul><ul><li>dorsal horn (C fiber termination) </li></ul><ul><li>• Partially responsible for allodynia </li></ul>
  • 14. Pathophysiology of Neuropathic Pain <ul><li>Central </li></ul><ul><li>– Loss of central descending inhibition </li></ul><ul><li>– Down-regulation of endogenous opioids </li></ul><ul><li>• Down-regulation of NE & 5-HT </li></ul><ul><li>• Decreased production of GABA </li></ul>
  • 15. Drugs Management for Neuropathic Pain <ul><li>• Antidepressants </li></ul><ul><li>• Antiepileptics </li></ul><ul><li>• NMDA receptor antagonists </li></ul><ul><li>• Topical agents / Local anesthetics </li></ul><ul><li>• Opioids and NSAIDs </li></ul><ul><li>• Autonomic Drugs </li></ul><ul><li>• GABA receptor agonists </li></ul>
  • 16. Antidepressants <ul><li>• Tricyclics </li></ul><ul><li>• SSRIs </li></ul><ul><li>• SNRIs </li></ul><ul><li>• In general, antidepressants seem to be </li></ul><ul><li>most effective on continuous burning </li></ul><ul><li>pain </li></ul>
  • 17. Tricyclic Antidepressants <ul><li>– Neuropathic pain (PHN, DN, etc) </li></ul><ul><li>– Evidence of efficacy exists for </li></ul><ul><li>amitriptyline, imipramine,desipramine </li></ul><ul><li>and clomipramine </li></ul><ul><li>• Overall efficacy – </li></ul><ul><li>– Modest (30% have 50% pain reduction) </li></ul><ul><li>• Pain generally responds more quickly than </li></ul><ul><li>depression (i.e., three-to-ten days, versus </li></ul><ul><li>four - six weeks). </li></ul>
  • 18. Tricyclic Antidepressants <ul><li>Mechanism: </li></ul><ul><li>Unknown </li></ul><ul><li>• Block reuptake of NE and 5HT </li></ul><ul><li>• Neuromodulatory effect on opioid systems </li></ul><ul><li>• NMDA receptor antagonism. </li></ul><ul><li>• Blockade of voltage gated Na channels </li></ul>
  • 19. Tricyclic Antidepressants <ul><li>• Added benefit </li></ul><ul><li>– Improved mood </li></ul><ul><li>– Sleep disorders common with </li></ul><ul><li>chronic pain syndromes </li></ul><ul><li>• Doses </li></ul><ul><li>– Generally lower (10 – 50%) than </li></ul><ul><li>antidepressant dose </li></ul>
  • 20. Tricyclic Antidepressants <ul><li>• Adverse effects </li></ul><ul><li>– Cardiac conduction irregularities </li></ul><ul><li>– Anticholinergic effects </li></ul><ul><li>– Sedation </li></ul><ul><li>– Orthostatic hypotension </li></ul><ul><li>– Weight gain </li></ul>
  • 21. SSRIs <ul><li>• Less consistent effects </li></ul><ul><li>• Fluoxetine shown to decrease pain </li></ul><ul><li>secondary to diabetic neuropathy, but </li></ul><ul><li>only in depressed patients </li></ul><ul><li>• Paroxetine was shown comparable to </li></ul><ul><li>imipramine for relieving diabetic </li></ul><ul><li>neuropathy pain, independent of mood </li></ul><ul><li>• In one study citalopram was more </li></ul><ul><li>effective than placebo for decreasing </li></ul><ul><li>diabetic neuropathic pain </li></ul>
  • 22. Duloxetine <ul><li>First drug specifically approved for Diabetic Peripheral Neuropathy </li></ul><ul><li>• Serotonin / Norepinephrine Reuptake </li></ul><ul><li>inhibitor (SNRI) </li></ul><ul><li>• A balanced and potent inhibitor of </li></ul><ul><li>serotonin and norepinephrine </li></ul><ul><li>reuptake in CNS </li></ul>
  • 23. Duloxetine <ul><li>Benefits vs TCAs </li></ul><ul><li>– No AntiACh, no cardiotoxicity </li></ul><ul><li>• Potential Drug Interactions </li></ul><ul><li>– Metabolized by both CYP2D6 & 1A2 </li></ul><ul><li>• Efficacy may be reduced by CYP1A2 </li></ul><ul><li>inducers </li></ul>
  • 24. Antiepileptic Drugs <ul><li>• Similarities in the pathophysiology </li></ul><ul><li>observed in some epilepsy models and </li></ul><ul><li>in neuropathic pain models provides a </li></ul><ul><li>rationale for the use of anticonvulsants </li></ul><ul><li>in the management of neuropathic pain </li></ul><ul><li>• In general, anticonvulsants may work </li></ul><ul><li>best on sudden, lancinating, &quot;shock-like&quot; </li></ul><ul><li>pains that appear to involve large </li></ul><ul><li>numbers of peripheral nerves improperly </li></ul><ul><li>firing together </li></ul>
  • 25. Antiepileptic Drugs Sodium-Channel Modulators <ul><li>Peripheral nerve injury -- abnormal </li></ul><ul><li>accumulation of Na+ channels within </li></ul><ul><li>nociceptors & dorsal root ganglia </li></ul><ul><li>• Na + channel blocking actions: </li></ul><ul><li>– Carbamazepine </li></ul><ul><li>– Phenytoin </li></ul><ul><li>– Topiramate </li></ul><ul><li>– Lamotrigine </li></ul><ul><li>• Also blocks glutamate </li></ul>
  • 26. Antiepileptic Drugs Sodium-Channel Modulators <ul><li>Side effects / Interactions </li></ul><ul><li>– Phenytoin and carbamazepine </li></ul><ul><li>• Cytochrome P450 inducers </li></ul><ul><li>• Rash </li></ul><ul><li>• Blood dyscrasias </li></ul><ul><li>– Lamotrigine – rash </li></ul><ul><li>– Topiramate – cognitive/memory issues </li></ul>
  • 27. Antiepileptic Drugs Calcium Channel Effects <ul><li>• Lamotrigine </li></ul><ul><li>• Topiramate </li></ul><ul><li>• Gabapentin </li></ul><ul><li>• Pregabalin </li></ul><ul><li>• Levetiracetam </li></ul>
  • 28. Antiepileptic Drugs Gabapentin & Pregabalin <ul><li>– Bind to a subunit of a voltage-dependent </li></ul><ul><li>Ca++ channel in spinal cord at termination </li></ul><ul><li>of nociceptors </li></ul><ul><li>– May modulate GABA activity </li></ul><ul><li>– Approved for DPN and PHN </li></ul><ul><li>• Used off-label for many more pain conditions </li></ul><ul><li>– Relatively well tolerated / easy to use </li></ul><ul><li>• No binding to plasma proteins </li></ul><ul><li>• No hepatic metabolism </li></ul><ul><li>• Side effects = Sedation, dizziness, drug </li></ul><ul><li>mouth, peripheral edema </li></ul>
  • 29. NMDA receptor antagonists <ul><li>• Glutamate released by primary afferent </li></ul><ul><li>nerves – wind-up, central sensitization </li></ul><ul><li>• Blockade of NMDA (glutamate) </li></ul><ul><li>receptors </li></ul><ul><li>– Dextromethorphan </li></ul><ul><li>– Ketamine </li></ul><ul><li>– Methadone </li></ul><ul><li>– Amitriptyline </li></ul>
  • 30. NMDA receptor antagonists <ul><li>• Ketamine </li></ul><ul><li>• behavioral disturbances such as learning </li></ul><ul><li>and memory impairments, sensorimotor </li></ul><ul><li>disturbances, stereotypical behavior and </li></ul><ul><li>hyperactivity </li></ul><ul><li>– Available as compounded topical gel </li></ul><ul><li>• May be effective if neuropathy is localized </li></ul><ul><li>• Dextromethorphan </li></ul><ul><li>– requires high doses (>250 mg) </li></ul><ul><li>– Variable benefits/ side effects due to genetic </li></ul><ul><li>polymorphism </li></ul>
  • 31. Analgesics <ul><li>• Generally not first-line agents for </li></ul><ul><li>treating neuropathic pain </li></ul><ul><li>• Relief of neuropathic pain with </li></ul><ul><li>nonsteroidal anti-inflammatory </li></ul><ul><li>drugs (NSAIDs) is variable. </li></ul><ul><li>• Opioid treatment of neuropathic </li></ul><ul><li>pain has been controversial over </li></ul><ul><li>the past 10–15 years. </li></ul>
  • 32. Opioid Analgesics <ul><li>• Neuropathic pain may be less </li></ul><ul><li>responsive to opioids than other types of </li></ul><ul><li>pain, and often requires the addition of </li></ul><ul><li>other agents </li></ul><ul><li>• Natural and semi-synthetics have limited </li></ul><ul><li>or no benefit </li></ul><ul><li>– Codeine/Morphine have limited effect </li></ul><ul><li>– Oxycodone may help some </li></ul><ul><li>• Synthetics like methadone and tramadol </li></ul><ul><li>may have better activity due to </li></ul><ul><li>secondary mechanisms </li></ul>
  • 33. Opioid Analgesics
  • 34. Methadone <ul><li>• Methadone is a racemic mix </li></ul><ul><li>– levo isomer is a mu-agonist opioid </li></ul><ul><li>– Dextro isomer acts as an NMDA </li></ul><ul><li>receptor antagonist </li></ul><ul><li>– The NMDA mechanism likely plays an </li></ul><ul><li>important role in the prevention of </li></ul><ul><li>opioid tolerance, potentiation of opioid </li></ul><ul><li>effects, and efficacy for neuropathic </li></ul><ul><li>pain syndromes </li></ul>
  • 35. Tramadol <ul><li>• A mu-opioid receptor agonist and a </li></ul><ul><li>weak inhibitor of norepinephrine and </li></ul><ul><li>serotonin reuptake. </li></ul><ul><li>• Studies have demonstrated benefit on </li></ul><ul><li>paresthesia, allodynia, and touch evoked </li></ul><ul><li>pain </li></ul><ul><li>• Can be combined with other drugs </li></ul><ul><li>• Low risk for abuse </li></ul>
  • 36. Topicals - Capsaicin <ul><li>• Neurotoxin found in hot peppers </li></ul><ul><li>• Selective for C-fiber nociceptors and </li></ul><ul><li>heat receptors </li></ul><ul><li>• Depletes substance P and selectively </li></ul><ul><li>blocks (low concentrations) or destroys </li></ul><ul><li>(high concentrations) nociceptive </li></ul><ul><li>sensory afferents </li></ul>
  • 37. Topicals - Capsaicin <ul><li>• Compliance may be a problem </li></ul><ul><li>• Needs to be applied 4-5 times a day for </li></ul><ul><li>several weeks </li></ul>
  • 38. Topicals - Lidocaine Patch <ul><li>• 5% lidocaine in a non-woven polyester </li></ul><ul><li>patch </li></ul><ul><li>• Approved for postherpetic neuralgia </li></ul>
  • 39. Topicals - Lidocaine Patch <ul><li>• Can apply up to 3 patches daily </li></ul><ul><li>– Directly over site </li></ul><ul><li>– 12 hrs on, 12 hrs off (FDA-approved) </li></ul><ul><li>• Systemic side effects unlikely </li></ul><ul><li>– Most common side effect: application site </li></ul><ul><li>sensitivity </li></ul><ul><li>– Clinically insignificant serum lidocaine </li></ul><ul><li>levels </li></ul><ul><li>• Mechanical barrier may decrease </li></ul><ul><li>allodynia </li></ul>
  • 40. Other possibilities for treating neuropathic pain <ul><li>• Lidocaine / melixitene </li></ul><ul><li>• NSAIDs </li></ul><ul><li>• Autonomic drugs </li></ul><ul><li>– Alpha1 blockers, alpha2 agonists </li></ul><ul><li>• Baclofen </li></ul><ul><li>• Benzodiazepines </li></ul><ul><li>• Muscle relaxants </li></ul><ul><li>• Botox </li></ul><ul><li>• Compounded combinations </li></ul>
  • 41. Summary <ul><li>• Neuropathic pain is a chronic condition </li></ul><ul><li>that can have substantial morbidity </li></ul><ul><li>• Available drugs to treat neuropathic pain </li></ul><ul><li>have incomplete efficacy and dose-limiting </li></ul><ul><li>adverse effects </li></ul><ul><li>• Patient variability may require many </li></ul><ul><li>different dosages, titration and schedules </li></ul><ul><li>• Polypharmacy is common and potential </li></ul><ul><li>interactions can complicate therapy. </li></ul>
  • 42. Article Discussion

×