Neuropathic pain

1. Neuropathic pain 1. Mechanism 2. Characteristic 3. Diagnosis 4. Treatment

2. Neuropathic pain Mechanism of pain: caused by cancer • nerve compression - nerve root compression caused by a collapsed vertebra total tumor mass = neoplasm + surrounding inflammation • nerve infiltration by cancer • nerve injury

3. Neuropathic pain Mechanism of pain: caused by treatment • postoperative (neurotomy) • phantom limb pain, post-mastectomy pain • radiotherapy (fibrosis) e.g. Brachial plexopathy • chemotherapy - peripheral neuropathy (wincristine, cisplatine, taxol)

4. Neuropathic pain Mechanism of pain: • post-herpetic neuralgia • diabetic neuropathy • post-stroke pain • uraemic neuropathy

5. Neuropathic pain Pain characteristic: • superficial burning pain • spontaneous stabbing/shooting pain • boring and radiating pain • allodynia - pain caused by a stimulus which does not normally provoke pain • hyperalgesia- an increased response to a stimulus which is normally painful

6. Neuropathic pain Diagnosis: • history • clinical examination • neurological examination • MRI / CT

7. Neuropathic pain Treatment: I. Adiuvant analgesics II. Corticosteroids III. Analgesics (opioids) IV. Neurolysis, spinal analgesia

8. Neuropathic pain Corticosteroids (reduces total tumor mass) e.g. Dexamethason 16-24mg at the begining and then reduse dose Antidepressants - tricyclic antidepressants (amitriptyline, desipramine, doxepin, imipramine, clomipramine) SSRI (paroxetine, citalopram, fluoxetine)

9. Neuropathic pain • Amitriptyline is effective in migraine and other types of headache, chronic low back pain, post-herpetic neuralgia, fibromialgia, painful diabetic polyneuropathy, central pain, cancer pain. • Superficial burning pain, allodynia = tricyclic antidepressants • 10-25mg nocte at the begining; max 75mg • relief may not occur for 4-5 days, for effect you have to wait even 1-2 weeks

10. Neuropathic pain • Anticonvulsants - carbamazepine, gabapentin, valproate, oxcarbazepine, lamotrigine • spontaneous stabbing/shooting pain • carbamazepine 200-1600mg; effect after 10-14 days • adverse effects! • gabapentin - 300-3600mg; effect after one week

11. Neuropathic pain Other drugs: • oral local anasthetics - mexiletine 450-600mg ; lignocaine infusions • NMDA receptor antagonists - dextromethorphan, ketamine (in subanaesthetic doses), bupivacaine, methadon • muscle relaxants - Baclofen 10-15mg >>75-100mg • topical agents - capsaicin, lignocaine patch, EMLA • benzodiazepines and neuroleptics • spinal analgesia - epidural and intrathecal routes.

12. A 4-step analgesic ladder used either alone or in conjunction with the WHO 3-step ladder

13. Bone pain 1. Mechanism 2. Pain characteristic 3. Diagnosis 4. Treatment

14. Bone pain Mechanism: • metastases - breast, prostate, thyroid, kidney, lung, colon • cancer infiltration of the bone • pathologic fracture

15. Bone pain Pain characteristic: - continuous, aching and localized pain - is exacerbated by movements and sneezing - may be unifocal multifocal generalized

16. Bone metastases Symptoms: • pain (75%) • neurological symptoms • pathologic fracture • hypercalcaemia • bone marrow failure

17. Bone pain Diagnosis: • history • clinical examination • rtg • scintigram • MRI / CT

18. Bone pain Treatment: • surgery - bone stabilisation, tumor excision • radiation therapy - is usually considered when bone pain is focal and poorly controlled with an opioid • chemotherapy (chemosensitive tumors) • hormonotherapy (hormonosensitive tumors - breast, prostate)

19. Bone pain • Radiopharmaceuticals that are absorbed at areas of high bone turnover - strontium-89, rhenium-186, samarium-153 • strontium is only potentially effective in treatment of pain due to osteoblastic bone lessions or lession with an osteoblastic component e.g. prostate cancer metastases • strontium - initial clinical response occurs in 7-21 days - the usual duration of benefit is 3-6 months

20. Bone pain • Non-steroidal anti-inflammatory drugs (NSAID) • opioids • corticosteroids • bisphosphonates (clodronate, pamidronate) • calcitonin • neurolysis, spinal analgesia

21. Bone pain • Bisphosphonates - inhibit osteoclast activity and reduce bone resorption -provide analgesia and decrease the use of analgesics • clodronate: - intravenous dose 600mg weekly - oral dose - 1600mg daily • pamidronate: - intravenous dose 60-90mg every 3-4 weeks - is safe in patients with impaired renal function - adverse effect: occasional hypocalcaemia, nausea

22. Bone pain • Calcitonin: mechanism of action is unclear - increase endorphin levels in the central nervous system - interact with the serotonergic system - anti-inflammatory action - direct effect on osteoclasts • calcitonin - subcutaneous - relatively low dose at the begining, then gradually increased to 200 IU - intranasal- 200 IU in one nostril; alternating nostril everyday

23. Spinal cord compression • Neurological emergency • 3-5% of patients with advanced cancer • 40% is associated with cancers of the breast, lung, prostate • others are associated with: renal cell cancer, lymphoma, myeloma, melanoma, sarcoma, colorectal cancer • very rarely spinal cord syndromes are due to epidural or cord metastases

24. Spinal cord compression • Mechanism of compression: - metastatic spread to vertebral body or pedicle - 85% - tumor extension through intervertebral foramina - 10% - intramedullary primary - 4% - haematogenous dissemination - epidural space - 1%

25. Spinal cord compression • Clinical presentation: pain (>90%) - pain of long duration which suddenly changes -pain is aggravated by lying down - pain may occur spontaneously - radicular pains are often exacerbated by neck flexion or straight leg raising, by coughing, sneezing or straining - funicular pain is less sharp, has a more diffuse distribution and is sometimes described as a cold unpleasant sensation

26. Spinal cord compression • Clinical presentation: - weakness > 75% - paraesthesiae - sensory loss (>50%) starting in the feet and moving proximally (is helpful in defining the level of the compression) - sphincter dysfunction >40% loss of sphincter function is a bad prognostic sign

27. Spinal cord compression • Diagnosis: - history - clinical examination - neurological examination - rtg - shows vertebral metastasis / collapse - MRI is the investigation of choice - CT with myelography may be helpful if MRI is not available

28. Spinal cord compression • Treatment: - high-dose steroids and radiation should be offered to all patients. Steroids can reduce pain and preserve neurological function; initial dosage - 100mg i.v.bolus (usually 24-50mg) followed orally halving of the dose every third day until the end of radiation

29. Spinal cord compression • Treatment: - surgery is only occasionally indicated - solitary vertebral metastasis - neurological symptoms and signs progress despite radiotherapy and high dose dexamethason - vertebral body resection with anterior spinal stabilization is generally the operation of choice

30. Corticosteroids in palliative care Special indications (Dexamethason 2x8mg 10-14 days): • superior vena cava syndrome • lymphadenopathy • lymphangitis carcinomatosa • obstruction of a hollow viscus (e.g. Bowel, ureter) • postradiation inflamatory • pericarditis exudative • hypercalcaemia • hormonal therapy

31. Corticosteroids in palliative care • Neuropathic pain • bone pain • neuropathic pain from infiltration or compression of neural structures • increased intracranial pressure • arthralgia • neuromyopathy

32. Corticosteroids in palliative care Other indications: • anorexia • cachexia • difficulty with breathing • nausea, vomiting • fever