Neuropathic Pain Causes, Mechanisms and Treatment of Neuropathic Pain Presented At Primed, QE2 Conference Centre, Westminster, London to National Audience of Primary Care Doctors 5th November 2009

1. Neuropathic Pain Dr. Christopher A. Jenner MB BS, FRCA Consultant in Pain Medicine, Imperial Healthcare NHS Trust Medical Director London Pain Consultants and Spinal Healthcare 5th November 2009 VXXXX Date of preparation October 2009

2. Agenda Definition Neuropathic v. nociceptive Physiology Epidemiology Diagnosis Management options www.londonpainconsultants.com

3. Definitions (1) Pain. ‘An unpleasant sensory and emotional experience which we primarily associate with tissue damage or describe in terms of tissue damage, or both.’ (IASP 2001) www.londonpainconsultants.com

4. Definitions (2) Time-course: • acute • chronic www.londonpainconsultants.com

5. Definitions (3) Type: • nociceptive • neuropathic www.londonpainconsultants.com

6. Nociceptive Pain www.londonpainconsultants.com

12. Neuropathic Pain www.londonpainconsultants.com

15. Pain Physiology www.londonpainconsultants.com

17. Noxious Stimulus

18. Pain Physiology (boring) www.londonpainconsultants.com

20. Noxious Stimulus

21. Impulse Transmission

22. Afferent sensory fibres

23. Spinal cord

24. Dorsal Horn

25. Synapse

26. Ca and Glutamate

27. Synaptic Cleft

28. Post Synaptic

29. Nociceptive Neuron

30. Pain perception

31. Brain

32. Neuropathic Pain

33. Aetiology of NP I N V I T E D A M P C

34. Aetiology of NP Infection Neoplasia Vascular Iatrogenic Trauma Endocrine Drugs Autoimmune Metabolic Psychiatric Congenital

35. Neuropathic pain : Classification Peripheral Neuropathies (e.g. diabetes, alcohol) Post-operative nerve injuries Herpes zoster Trigeminal neuralgia Amputations Plexus avulsions Spinal cord Spinal injury MS Tumour Arachnoiditis Syrinx Brain Stroke MS Tumour Epilepsy Syrinx Jensen T. 2007

36. Neuropathic pain syndromes Peripheral Chemotherapy-induced neuropathy Complex regional pain syndrome HIV sensory neuropathy Neuropathy secondary to tumour infiltration Painful diabetic neuropathy Phantom limb pain Postherpetic neuralgia Postmastectomy pain Trigeminal neuralgia Central Central post-stroke pain Multiple sclerosis pain Parkinson disease pain Spinal cord injury pain Dworkin R.H. A overview of Neuropathic pain: Syndromes, Symptoms, Signs and several Mechanisms Clin J Pain (2002) 18:343-349

37. Epidemiology of Neuropathic Pain The Neuropathy Trust

39. Over 30% neuropathy prevalence in diabetes

40. Predicted by 2010 ~ 1 million diabetes sufferers with neuropathy

41. Up to 70% neuropathy patients experience painThe Neuropathy Trust

43. 1 in 7 experience post-thoracotomy neuralgia

44. 1 in 8 experience severe post herniorraphy pain

45. 1 in 33 experience phantom tooth pain after extractionMacrae WA. Chronic pain after surgery BJA 87 (2001) 88-98

46. How Common is Neuropathic Pain in Primary Care? Epidemiology of conditions (per 100,000 person yrs) Post Herpetic Neuralgia = 40 ↓ Trigeminal Neuralgia = 27 Phantom Limb Pain = 1 ↓ Painful Diabetic Neuropathy = 15 ↑ Hall G. et al. Epidemiology and treatment of neuropathic pain: The UK primary care perspective. Pain 2006; 122: 156–162

47. Clinical features of Neuropathic Pain

48. History Pain description- burning/ shooting/ stabbing/ electric shock/ lancinating/ severe/ constant….. Local hypersensitivity- allodynia/ hyperalgesia/ dysaesthesia Dysfunction

50. Allodynia (mechanical, thermal & punctate)

51. Skin changes (autonomic activity)

52. Sensory disturbances

53. Cold

54. Pin

55. Vibration

58. Neurop. Pain Questionnaire Krause, 2003

59. DN4 Bouhassira, 2005

60. ID Pain Portenoy, 2006

61. Pain Detect Freynhagen, 2006Diagnostic & Screening Tools

62. LANSS Questionnaire

63. Items Common to all Screening Tools Bennett et. al. Using screening tools to identify neuropathic pain Pain 127 (2007) 199–203

64. Pharmacological Treatment • WHO analgesic ladder (abridged) • + tramadol • + opioids- buprenorphine TDD/ oxycontin/ fentanyl TDD (New: sufentanyl TDD/ product X) www.londonpainconsultants.com

65. Pharmacological treatment of Neuropathic Pain www.londonpainconsultants.com

66. Neuropathic Pain Management Antidepressants Amitryptilline Anticonvulsants - Gabapentin/ Pregabalin/ Carbamazepine/ Valproate Opioids Local Anaesthetics/Analgesics Lidocaine/ EMLA www.londonpainconsultants.com

67. NMDA antagonists Sympatholytics GABA –ergics Capsaicin www.londonpainconsultants.com

68. Future Agents for Neuropathic Pain Ziconotide (sea snail, conus magnus) P2X3- (purine) receptor antagonists (ATP) (knockout mice) Epibatidine (Equadorian poison dart frog) Morphine and ketamine Regular gabapentin www.londonpainconsultants.com

71. Lidocaine plaster v. Pregabalin in PHNBaron et al., 2009: Study overview and design * according to SmPC Baron et al., (2009) CMRO. 25: 1663-1676.

72. Baron et al., 2009: Results – PHN NRS-3 response rate after 4 weeks, Per protocol (PP) Baron et al., (2009) CMRO. 25: 1663-1676.

73. Baron et al., 2009: Results – PHN Subject-based adverse event (AE) evaluation, Safety population * p = 0.0020 * * p = 0.0001 Baron et al., (2009) CMRO. 25: 1663-1676.

74. Physical and Alternative Treatments

75. Physical and Alternative Treatments Graded desensitisation Mirror box therapy Rehabilitation

76. Psychologically based therapy

77. Pain Management Psychological CBT Operant Conditioning Psychoanalysis Relaxation Biofeedback • Psychiatric www.londonpainconsultants.com

78. Pain Management Programmes Medication • Goals (SMART- specific/ measured/ agreed/ realistic/ timed) • Coping • Contingency • Pacing • Education • Pain Behaviours • Reinforcementwww.londonpainconsultants.com

79. Advanced Pain Management Techniques www.londonpainconsultants.com

80. Nerve Stimulation

81. Nerve Stimulation (2)

82. Intrathecal Pumps

83. The Future? Demographics Healthcare advances ↑ Patient expectations and involvement www.londonpainconsultants.com

84. Summary Incidence of NP increasing Nociceptive v neuropathic Management of NP in primary care When to refer www.londonpainconsultants.com

85. Summary Very common (1 in 7 UK) Time course- acute n chronic Nociceptive and neuropathic Multiple treatment modalities www.londonpainconsultants.com

86. Case reports/ Blogs/ Links/ Appointments dr.jenner@satellitesec.co.uk 0845 045 0250 www.londonpainconsultants.com

87. Any Questions