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A Case Study in Neuropathic Pain

A Case Study in Neuropathic Pain. June 3, 2009 Palliative Care Team Drs. St. Godard, Loiselle, Hohl and Pilkey. Objectives. By the end of the hour the learner will be able to: Define neuropathic pain List at least 2 types of Pain receptors

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A Case Study in Neuropathic Pain

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  1. A Case Study in Neuropathic Pain June 3, 2009 Palliative Care Team Drs. St. Godard, Loiselle, Hohl and Pilkey

  2. Objectives • By the end of the hour the learner will be able to: • Define neuropathic pain • List at least 2 types of Pain receptors • List at least 4 different types of adjuvant pain medications • List the mechanisms of action, benefits, and side-effects of these 4 medications • List 2 new/different adjuvant pain medications

  3. Talk Outline • Case Study – Dr. Ted St. Godard & Dr. Joel Loiselle • Pathophysiology of Neuropathic Pain – Dr. Jana Pilkey • Adjuvant Medications – Dr. Chris Hohl • What’s new/different in Neuropathic Pain – Dr. Jana Pilkey

  4. History • Ms. G. D. • 55 y.o with breast cancer • Mets to bone • Pain to left arm

  5. History • 2 week hx of worsening pain • Mid back – dull ache, Pressure • Burning to L hand and arm • Since 1997 • brachial plexus neuropathy • “Pins and needles” • “Like dipped in acid” • Morphine for 4 weeks not helping

  6. Cancer History • Breast cancer dx 1997 • Lumpectomy, tamoxifen x 2 yrs • Mastectomy 1999 and LN dissection • Oophorectomy 1999 • Multiple courses of chemo • 2008- mets to c-spine, ribs, sternum. • Sept 2008 – Rx to spine • Phx: PUD

  7. Physical Exam & Investigations • Temp 37.2 • Hr 100 • Rr 18 • Sao2 – 90% on RA • BP 150/88 • Lab work normal throughout

  8. Course in Hospital • Admission orders: • Methadone 5mg bid • Dex 10mg bid • Pariet 20mg po od • Dilaudid 8 mg subcut q4h and q1prn • Fentanyl 50 per IPP

  9. Course in Hospital • Dec 30 • Myoclonus noticed – hydrated • Rotated to fentanyl patch • Methadone increased • Jan 14 • CT head – mets to R cerebellum and R frontal lobe • Pain better- on methadone 40 bid, dex 8 bid • Starts 12 rdtx to whole brain

  10. Course in Hospital • Jan 27 Pain Crisis • Severe excruciating burning pain • From neck to top of R shoulder • Crying, screaming • BT HM ineffective • Slept with 5mg versed • Methadone increased • Ketamine added 2.5 mg subcut tid • Pregabalin added 50mg bid • Lidocaine 2% gel to shoulder qid prn

  11. Potentially useful Peripheral Nerve Block in this Case Interscalene block -Performed at root level -“Single shot” -only lasts 12 h. -Catheter techniques difficult to maintain (displacement). -Disease extent limits anesthetic flow. -Risk of bleeding /epidural hematoma is prohibitive in this case.

  12. Neuraxial (Intraspinal) blocks Epidural: • comparable to bilateral peripheral nerve block • catheter outside dura • would be placed at C7/T1 Intrathecal = Spinal • catheter enters CSF in lumbar cistern • can be guided to high thoracic level as required for upper limb pain

  13. Contraindications to Neuraxial Analgesia in this Case • Extent of Disease involving C-spine: • Risk of epidural hematoma if needle at C7-T1. • Poor CSF flow impedes spread of analgesics • Brain Metastasis: • Posterior Fossa- increased risk of “coning” • Relative contraindication • Remember coagulopathy (Plt <100; INR >1.3) and need for ongoing anticoagulation are contraindications.

  14. Course in Hospital • Consult to Dr J. Loiselle • Nerve-block or epidural too risky given fragility of spine and cerebellar mets • Jan 28 • Pain continues • On Methadone 60mg bid • Starts fentanyl 50mcg/hr IV • HM stopped – twitching • Ketamine 5 mg subcut tid

  15. Course in Hospital • Jan 28 • Family concerned about sedation on fentanyl • Jan 29 • RR 7 - fentanyl stopped, Pain again severe • Fentanyl IV not restarted at family request • Ativan started • Jan 30 – Mini Case conference • Ketamine IV @ 2.5mg/hr • Gabapentin being lowered

  16. Course in Hospital • Jan 31-Feb 5 – good pain control • Feb 6 – weepy and tired, pain with movement • Feb 9 – increase in ketamine IV 3.52mg/hr • Feb 13 – increase in ketamine IV 6mg/hr • Feb 17 – decrease po intake – deteriorating – ketamine 7.5mg/hr

  17. Course in Hospital • Feb 19 – pt wishes she could sleep until death • – tired of trying to “hold the pain in” • Feb 23 – unresponsive • Feb 26 – prognosis hrs to days/ discussed sedation • Feb 28 – difficulty maintaining sedation • Mar 4 – died sedated and comfortable

  18. What is Neuropathic Pain? • Pain initiated or caused by a primary lesion or dysfunction in the nervous system • Characterized by : • Burning, Tingling, Electric ,Shooting Pain

  19. Pain Receptors • A delta • Mechanical sensation eg. Cut, prick • C fibres • Diffuse, respond to many stimuli • Burning sensation • Sleeping receptors • Active in injured tissue only • Acquire mechanical sensitivity (Almeida 2004)

  20. Nociceptors • Damaged tissue releases: • Serotonin, Substance P, Bradykinin, Prostaglandin • Involved in acute & chronic pain • Influenced by endorphins

  21. Sensitization • Can be a tissue level (primary) or • At CNS level (secondary) • Results in: • threshold of activation after injury • intensity of a response to a noxious stimulus • emergence of spontaneous activity (Aguggia 2003)

  22. Sensitization • Primary sensitization • Sympathetic activity and Inflammatory Mediators • (Chong 2003) • Secondary sensitization • CNS changes in spinal cord and brain • NMDA receptors activated • “Wind-up” = increased amplitude and frequency summation in neurons after prolonged stimulation • (Chong 2003) • Blocked by NMDA antagonists, anti-inflammatories • (McHugh 2000)

  23. The Dorsal Root Ganglion

  24. Tricyclic Antidepressants (TCAs) • 40-60% efficacy for partial relief (NNT~2.5-3) • Start 10-25 mg/d and  10-25mg each week • Best effects: 50-150 mg/day • Mechanism: • NE & 5HT reuptake blockade • +/- NMDA antagonism, • +/- Na channel blockade • Anticholinergic effects • Secondary amine better tolerated

  25. Selective Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) Venlafaxine • Start 37.5 mg/day • Increase by 37.5 mg weekly • Effective @ 150-225 mg/d • Lower doses – results inconsistent • Short vs XR preps Duloxetine • NNT ~4-5 (~7 for SSRI) • Start & efficacious @ 60mg/day • Antidepressant & anxiolytic • Favorable side effect profile • Limited long term data

  26. ά2-δ Ligands (Gabapentinoids) • Bind to ά2-δ subunit of voltage gated Ca channels •  glutamate, NE, substance P release • NNT ~3.5-4.5 Gabapentin • Few drug interactions • Dizziness & sleepiness • Exacerbate cognitive impairment • Start 100-300mg TID • Titrate to 1800-3600 mg/d • Peak effect in >2 weeks Pregabalin • No drug interactions • Similar side effects to gaba • Start 50-150mg divided Q8-12H • Titrate 50-150mg/day weekly • Goal 300-600 mg/d in 1-2 weeks • Peak effect in 2 weeks

  27. Opioids • 20-30% pain reduction, NNT ~2.5 • Provides rapid relief • Rapid titration • No ceiling effect • Multiple forms & delivery methods • More side effects than 1st line treatments • Risk of misuse and abuse (5%)

  28. Methadone • μ-receptor agonist + NMDA antagonist • Very long half-life, variable in individuals • Slow titration: • start 2.5mg TID • Increase 50-100% every 48-72 hours • ~5:1 to ~30:1 morphine equivalency (depending on dose) • Little literature support, ++ practical support

  29. NMDA Antagonists Ketamine • Start 2.5-5mg PO TID • Titrate by 50-100% dose to 1-2 mg/kg/day • Start IV infusion @ 0.05-0.1mg/kg/hr • IV bolus @ 0.1-0.2 mg/kg/dose over 20 minutes • No NNT data • Poor performance in studies, good efficacy in practice • Topical or gargle preparations possible • *opioid sparing effects

  30. Other/New Things to Try IV Lidocaine And po Mexilitine Cochrane Review 2005 • Good quality evidence in neuropathic pain • Both decrease VAS by 11 on 1-100 scale • 47% of people in trials had a 30% decrease in pain • (22% in placebo) • 35% had Side –effects • Numbness, dizziness, fatigue, metallic taste • Authors conclude similar efficacy to other adjuvants and good safety profile

  31. Other/New Things to Try • Capsaicin – High dose patch in PHN (640mcg/cm2) • 1 – 60 min application • Lasts up to 12 weeks • Mean decrease in pain score of 29.6% • Side-effects – Pain and erythema at site • (Backonja – Lancet Neurology, 2008) • Cannabis – Sativex - Neuropathic pain with Allodynia • Improvements of 1.43 on 10 point VAS • Good safety profile – SE include GI upset & drowsiness • (Nurmikko – Pain 2007)

  32. Other/New Things to Try • Intrathecal Ziconotide • N-type Ca Channel blocker (NCCB) • Median dose 6.48mcg/day • Improved VASPI scores in 53.1% • Decreased opioid usage in 9% • Very expensive • Side Effects: • Memory loss, dizziness, nystagmus, somnolence, gait, CK rise (Pommer - J Pain Symptom – 2009)

  33. A Comparison of Adjuvants

  34. Summary/Objectives • By the end of the hour the learner will be able to: • Define neuropathic pain • List at least 2 types of Pain receptors • List at least 4 different types of adjuvant pain medications • List the mechanisms of action, benefits, and side-effects of these 4 medications • List 2 new/different adjuvant pain medications

  35. Recommended References • Cruccum, G. Treatment of painful neuropathy. Current Opions in Neurology. 2007; 20; 531-535. • Dworkin, R. et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007; 132; 237-251. • Gilron, I. et al. Neuropathic pain: a practical guide for the clinician. CMAJ. 2006; 175(3); 265-275.

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