1. Neuropathic Pain - Diagnosis Mechanism and Management Dr AmitVerma M.D, D.N.B, P.D.C.C, F.I.P.P CONSULTANT ANAESTHESIOLOGIST DR BALWANT SINGH’S HOSPITAL 1

3. CASE 1 • 55 yr. , Female • Presented with pain in back of chest for 5 yrs • No h/o HZ, DM, Trauma, Loss of weight • Quality - burning • Intensity 5 - 6 / 10 • Tried NSAIDs multiple times

4. CASE 2 • 75 yrs, Female • Feels Depressed due to Pain in chest • Severe lancinating pain with increased sensitivity • H/O very painful rash in the same distribution 5 months back • Rash subsided but pain didnt

5. CASE 3 • 35 yr., female patient with severe headache. • Diagnosed as a case of migraine • Wincing in pain , ℅ jolts of pain while combing her hair • On Migraine prophylaxis

6. CASE 4 • 45 yr. Old Male on a hot summer day with a wool shawl draped around his shoulder and right arm • ℅ Pain in the right hand following closed reduction of wrist fracture • Right arm was cold and sometimes sweaty • Severe pain on cutting nail • Visited three physician who referred her to a psychiatrist with the diagnosis of Conversion disorder

7. Pain • Poena - penalty / punishment • Start of Pain Clinics • Insight into the Etiopathogenesis • Fifth vital Sign 2

8. Classification ( IASP) • Region • System • Acute Vs Chronic • Mild / Moderate / Severe • Nociceptive / Inflammatory/ Neuropathic ( Clifford J Woolf ) 3

9. Definition • IASP defines Pain as • an unpleasant sensory or emotional experience which we primarily associate with tissue damage or describe in terms of such damage , or both • Neuropathic Pain as - • Pain initiated or caused by a primary lesion or dysfunction of the peripheral or central nervous system 4

10. Neuropathic Pain - Difficulties • No Consensus on Definition • Pain Perception is subjective • Rarely One Diagnostic Test • Lack Of Specificity in Diagnosis • Signs & Symptoms Change Over Time • Patients not believed 5

11. Components of Neuropathic Pain • Pain • Lancinating/burning/pricking/stabbing • No ongoing tissue damage • Delay in onset after nerve injury • Spontaneous paroxysmal electric shock sensation 13

12. ALLODYNIA HYPERALGESIA PAIN INCREASED PAIN PAINFUL STIMULUS Low Intensity Stimulation Innocuous sensation Abnormal Sensations

13. Negative sensory signs • Pain with numbness • Presence of neurologic deficit 14

14. Descriptions of Neuropathic Pain • “I feel as though someone has pulled the skin off my left arm and is then constantly rubbing salt into the wound.” • “I feel as though my leg is on fire. My skin feels burnt, and it is as though someone is taking a claw and tearing into my skin 24 hours a day.” • “I feel as though someone has taken a hot poker knife and is jabbing it deep into my right eye. If I could pull my eye out, only to remove the sensation, I would gladly do so.” 15

15. Neuropathic Pain Syndromes • Peripheral Nervous System ( focal and multifocal lesions ) • Peripheral Nervous System ( Generalized polyneuropathies ) • Central Nervous System Lesions • Complex Neuropathic Disorders

16. Peripheral Nervous System (focal and multifocal lesions) • Trigeminal neuralgia • Post herpetic neuralgia • Diabetic Mono neuropathy • Entrapment Syndrome • Ischemic Neuropathy • Phantom Limb • Post Traumatic Neuralgia 7

17. Peripheral Nervous System Generalized Polyneuropathies • Metabolic - DM, Amyloid • Toxic - Alcohol, taxanes • Infective - HIV • Autoimmune - GBS • Hereditary - Fabry’s Disease • Malignancy 8

18. Central Nervous System Lesions • Spinal Cord Injury • Prolapsed Disc • Stroke • Multiple Sclerosis • Parkinson’s Disease • Surgical Lesions 9

19. Complex Neuropathic Disorders • Complex Regional Pain Syndrome I • Complex Regional Pain Syndrome II 10

20. MECHANISM OF NEUROPATHIC PAIN 16

22. Ascending Pain Pathway 17 17

23. Descending Pain Pathway 18 18

24. Peripheral nerve fibers Sympathetic Fibers • Spinal Cord anatomical reorganization • Dorsal Horn Denervation Sensitivity • Molecular Changes Spinal Cord Cerebral Reorganization Molecular Changes Brain • Ectopic Discharge • Collateral Sprouting • Nociceptive sensitization Ephaptic Crosstalk 19

25. Ectopic Discharges • Increase in the level of spontaneous firing in the injured neurons as well as their uninjured neighbor neuron • Result of alteration in the expression of Sodium channels

26. Ephaptic Conduction • Cross excitation among the neurons having spontaneous firing capacity leading to amplification of depolarization • Important in association of Sympathetic system

27. Collateral Sprouting • Primary afferent neuron injury leads to sprouting of collateral fibers from sensory axon in their attempt to regenerate • These sprouts are sensitive to low threshold stimulus

28. SNS AND PNS COUPLING • DUE TO ENHANCED SENSITIVITY TO CATECHOLAMINES LEADING TO PAIN PERCEPTION

29. Nociceptive Sensitization • Increase in Bradykinin binding sites within DRG following axotomy leading hyperalgesia

30. Central & Spinal Cord 20

31. CENTRAL MECHANIMS • Spinal Cord reorganization • Spinal Cord hyper excitability ( central sensitization ) • Cerebral Reorganization

32. DIAGNOSIS OF NEUROPATHIC PAIN 21

34. Healing begins with the History • Clinical description and history taking are the best mechanism to diagnose Neuropathic Pain • Identify • Painful symptom • Altered sensation • History } All matching neuroanatomical or dermatomal pattern 22

35. Screening Methods • Leeds Assessment of Neuropathic Symptoms and Signs ( LANSS ) scale • Sens / Spec - 83 / 87 % • Pain DETECT questionnaire • Neuropathic Pain Questionaire • Neuropathic Pain Scale 23

36. 24 24

37. Bedside Examination • Identify the altered sensation in painful area ( compare with non painful area ) • Dysesthesia (Allodynia, Hypoalgesia, Hyperalgesia ) • Inability to distinguish warm and cold objects 25

38. Pain & Functional Brain Imaging( F.B.I ) • Positron Emission Tomography • Functional MRI • Both Measure energy consumption in activated brain regions • FBI has mapped the brain neuromatrix ( area of brain that processes pain response ) 26

39. Functional Brain Imaging • Neuromatrix - • 1o & 20 somatosensory cortex ( mediate sensory discriminative features of pain ) • Anterior cingulate gyrus cortex and insula ( mediate affective motivational component of pain • Pre frontal cortex - mediate cognitive aspects of pain • Thalamus - gateway between cortex and brainstem • Increased regional blood flow of neuromatrix in Neuropathic Pain

41. REDUCE PAIN Approach To Treatment DIAGNOSIS TREAT UNDERLYING CONDITION PREVENTION IMPROVE PHYSICAL FUNCTION IMPROVE QUALITY OF LIFE REDUCE PSYCHOLOGICAL DISTRESS

42. Management • Mx of ectopic activity / Ephaptic Conduction • Na+ Channel Blockers - • Phenytoin • Lignocaine • Oxcarbazepine • Gabapentin 33

43. Reducing Central Sensitization • NMDA receptor antagonist • Ketamine • Amitryptyline • Methadone • Gabapentin, Pregabalin 34

44. Improving Descending Control • Local Inhibitory controls • GABA - B agonist - Baclofen • Opioids - Oxycodone, tramadol • Descending inhibition form brain • Clonidine • TCA 35

45. Sympathetically Mediated Pain • Sympathetic Plexus Block • Stellate ganglion • Lumbar Sympathetic chain block • Central Neuraxial Block • Epidural infusions of adjuvants and local anesthetics • Intrathecal infusions - opioids / baclofen 36

46. Somatic / Sensory Nerve Block • Brachial Plexus Block • Para - vertebral Block • Lateral Cutaneous Nerve of Thigh Block • Intercostal Nerve Block 37

48. Interventional Strategies • Diagnostic • Break in cycle of Pain • Should be Imm. Followed by active physiotherapy • Epidural, Trans Foraminal , Facet Blocks • Spinal Cord Stimulation 38

49. Complementary Therapies • Acupuncture • Nutritional Counseling • Massage Therapy • Mirror Therapy 39

50. Pharmacotherapy • Carbamazepine • Dose – 100 mg BD - 1000 mg / day • S/I – Dizziness, Ataxia, N/V, S.J Syndrome, TCP • C/I – Liver Dysfunction, B.M suppresion 40