Pain Physiology. Presented At St Thomases Hospital for trainee Anaesthetists as part of their FRCA (Fellow of the Royal College of Anaesthetists) examination preparations. 2nd March 2007

1. Pain Physiology Dr. Christopher A. Jenner Consultant in Pain Medicine and Anaesthesia, SMH 2 nd March 2007

2. What can u say?

3. Its very complicated !!!

8. FRCA requirements

14. Techniques for answering MCQ’s

15. A. Knowledge

22. B. Techniques

26. Category Hit rate for answering correctly Certain 80-100% Fairly certain 60-80% Probably 50-60% No clue 50%!

31. Definitions

34. Overview to Pain Pathways

36. Cue the CD-ROM !

38. Nociceptors

41. Unimodal

42. Unimodal- Mechanical

44. Unimodal- Thermal

45. Thermal- Noxious heat/ cold Noxious cold CMR1 TRPM8 Noxious heat VR1 TRPV1

46. Unimodal- Chemical

47. Chemical Receptor Ligand PTX3 ATP B2 Bradykinin EP2 PGE2 ASIC H+ TTX-R (predominate) Na+

50. Polymodal nociceptors

52. Tissue Injury

53. Tissue injury causes the release of various inflammatory and pain mediators resulting in peripheral sensitisation

54. Pain Response Mediators

55. Pain Response Mediators Released from Mediator Damaged endothelial cells and platelets ATP, ACh, serotonin, PG E2 Damaged vessels Bradykinin

56. Inflammatory Response Mediators

57. Inflammatory Response Mediators Released from Mediator Mast cells Histamine Sub P, CGRP trigger mast cell degranulation Blood cells Cytokines, Complement factors C3a, C5a, serotonin, PAF, NCF, LK, fibrinopeptides

58. Actions of Inflammatory Mediators

60. Outcome on pain pathways?

63. Pain Transmission

66. Properties of Ad and C fibres (rote learning!)

67. C Ad Ab Myelination No Yes Yes Diameter 0.4-1.2 mcm 2-5 mcm Conduction velocity 0.5-2 m/s 12-30 m/s Normal sensation Slow pain Diffuse, dull Fast pain Sharp, localised, reflex withdrawal Pathological sensation Hyperalgesia Allodynia

68. C Ad Ab Threshold high high low Main Transmitters peptides EAA EAA Main receptors activated NK1,2 (neurokinin) NMDA AMPA mGlu AMPA Lamina 1,2,5 1,2,5 3,4 Target sc neurones NS (nociceptor specific) WDR LT WDR

69. Note about Ad and C fibres

71. Synapses

72. Activity of Synapses

77. Spinal Cord

79. Dorsal Horn

84. Anatomy of the spinal cord

85. Anatomy of the spinal cord

86. Rexed’s laminae

87. Rexed’s laminae I,II Most nociceptors terminate in superficial layers via Ad and C III, IV Tactile afferents synapse V Some A  project into deeper layers. V Nociceptive and tactile afferents converge (directly or via inter-neurones) V,VI Inter-neurones mainly regulate flow of nocicpetive info

88. Summary of the Spinal Cord

90. Anyone been to …

96. … healthy eating…

98. … leads to…

100. Second Order Neurones

104. NMDA Receptors

105. NMDA Receptors

106. Ascending Spinal Pathways

107. Tract Information STT Spinothalamic tract Temp, Pain, Touch, Visceral Mediates and separates discriminative (fast) and affective (slow) aspects into different regions of the tract Anterior STT- simple touch Lateral STT- pain and temperature VPL, VPM, PO nuclei- conscious perception of pain SRT Spinoreticular tract To reticular formation- arousal-emotional pain. Slow pain SMT SPT

109. Details of the tracts

110. Direct (fast) Indirect (slow) Tract Lateral STT Lateral STT SRT Origin I, IV, V I, IV, V (+VII,VIII) Somatotopic organisation Yes No

111. Direct (fast) Indirect (slow) Body representation Contralateral Bilateral Synapse in RF No Yes Sub-cortical targets None Hypothalamus Limbic system Autonomic centres

112. Direct (fast) Indirect (slow) Thalamic nucleus VPL Intra-laminar nuclei Other midline nuclei Cortical location Parietal lobe Cingulate gyrus Role Discriminative pain (quality, intensity, location) Affective-arousal component of pain Other functions Temperature Touch

116. Ascending Spinal Pathways

120. Pain Modulation

125. Pain and Cannabinoids

130. Descending Inhibitory Pathways

135. Gate Control Theory

139. Gate theory

141. Neurotransmitters

147. The Brain

150. Neuropathic Pain

152. More definitions

153. Term Definition Allodynia Pain due to a stimulus which does not normally provoke pain Analgesia Absence of pain in response to stimulation which would normally be painful Central Pain Pain initiated or caused by a primary lesion or dysfunction in the CNS

154. Dysaesthesia An unpleasant abnormal sensation, whether spontaneous or provoked Hyperalgesia An increased response to a stimulus which is normally painful

155. Hyperaesthesia Increased sensitivity to stimulation, excluding the special senses Hyperpathia A painful syndrome characterised by an abnormally painful reaction to a stimulus, especially a repetitive stimulus, as well as an increased threshold Hypoalgesia Diminished pain in response to a normally painful stimulus Neuralgia Pain in the distribution of a nerve or nerves Neuritis Inflammation of a nerve or nerves

156. Neuropathic Pain Pain initiated or caused by a primary lesion or dysfunction in the nervous system Neuropathy A disturbance of function or pathological change in a nerve: in one nerve, momoneuropathy; in several nerves, momoneuritis multiplex; if diffuse and bilateral, polyneuropathy Pain threshold The least experience of pain which a subject can recognise

157. Pain tolerance level The greatest level of pain which a subject is prepared to tolerate Paraesthesia An abnormal sensation, whether spontaneous or eveoked

158. Causes of Neuropathic Pain?

160. Pathophysiology of Neuropathic Pain

167. Wind-up

172. Allodynia and Hyperalgesia

174. NMDA Receptor

179. RCT evidence of effect of drugs on evoked pain Drug Effect on Tramadol Mechanical allodynia TCA Mechanical allodynia Gabapentin Cold allodynia Opioids Skin hypersensitivity IV lidocaine Mechanical allodynia Topical lidocaine Mechanical and thermal hyperalgesia

180. Clinical Confusion

182. … please visit…

183. www.frca.co.uk