Lecture 13 - Pain and Analgesia 1 PDF

Pain, nociception and analgesia Chris Bailey [email protected]  Lecture summary Pain and nociception Detection of noxious stimuli Transmission of noxious information to spinal cord and brain Sensitization and modulation of nociceptors Transmission at spinal leve...

Pain, nociception and analgesia Chris Bailey [email protected]  Lecture summary Pain and nociception Detection of noxious stimuli Transmission of noxious information to spinal cord and brain Sensitization and modulation of nociceptors Transmission at spinal level Regulation of nociception Opioid analgesia NSAIDS analgesia Other analgesics  Definitions Pain the subjective conscious appreciation of a stimulus that is causing, or threatening to cause, tissue damage. Nociception the physical process of detection and transmission of damaging or potentially damaging (noxious) stimuli Nociceptors Structures which detect noxious stimuli Algesia the induction of a condition leading to nociception and pain Analgesia reduction or prevention of either nociception or pain without loss of consciousness Pain (nociceptive) fibres  Two types of nociceptor polymodal nociceptors high intensity mechanical thermal (> 45oC, 60oC)  Nociception Noxious stimulus Skin/viscera Primary transduction Channel opening Sensory receptor Secondary transduction Change in membrane voltage Depolarization and action potential generation Primary afferent axon Transmitter release Second order neurone Spinal cord response  Signal detection in nociceptors ASIC Acid sensing ion channel H+ Free nerve ending P2X3 Purinergic receptor ATP Mechanical stimulation Na+ Primary afferent axon Na+ Depolarization/excitation Na+ Na+/Ca++ VGNa Action potential firing Voltage gated sodium channel Mechanical stimulation VR-1/TRPV-1 Vanilloid 1 Capsaicin H+ heat  Nociception Noxious stimulus Skin/viscera Primary transduction Channel opening Sensory receptor Secondary transduction Change in membrane voltage Depolarization and action potential generation Primary afferent axon Transmitter release Second order neurone Spinal cord response Is nociception just exaggerated sensory (ie. touch) transmission? They conduct at slower velocities Nociceptors have different thresholds of activation They have different sites of projection into the spinal cord They elicit different physiological responses in dorsal horn neurones Information ascends in different pathways  Somatosensory afferent fibres Is nociception exaggerated somatosensory transmission? No - ‘pain fibres’ conduct at slower velocities  Pain (nociceptive) fibres Fast pain Slow pain Sharp, pricking Burning, aching, throbbing Well-tolerated Poorly tolerated Is nociception just exaggerated sensory transmission? They conduct at slower velocities Nociceptors have different thresholds of activation They have different sites of projection into the spinal cord They elicit different physiological responses in dorsal horn neurones Information ascends in different pathways Discriminating thermoreceptors v thermal nociceptors Is nociception exaggerated somatosensory transmission? No - nociceptors have different thresholds of activation  Activation profiles Thermoreceptors v thermal nociceptors 6 cold receptor warm receptor Axonal firing frequency (Hz) cold pain heat pain 4 2 10 20 30 40 50 60 Skin temperature (oC)  Graded potentials in nociceptors heat applied Nociception and sensory (touch) perception are different They conduct at slower velocities Nociceptors have different thresholds of activation They have different sites of projection into the spinal cord They elicit different physiological responses in dorsal horn neurones Information ascends in different pathways  Nociception Noxious stimulus Skin/viscera Primary transduction Channel opening Sensory receptor Secondary transduction Change in membrane voltage Depolarization and action potential generation Primary afferent axon Transmitter release Second order neurone Spinal cord response  Somatosensory transmission DORSAL White matter Grey matter Dorsal root Dorsal root ganglion Dorsal root ganglion cell Peripheral receptor Ventral Afferent VENTRAL root fibre  substantia gelatinosa Spinal projection sites I dorsal II funiculus III Dorsal horn IV V X VI lateral VII funiculus IX IX ventral horn VIII IX ventral IX nociceptive A fibre funiculus neurones I C fibre II III IV wide dynamic range neurone V VI Ascending pain pathways (spinomesencephalic tract) (spinoreticular tract) Spinothalamic tract Sensory and nociceptive pathways  Referred Pain oesophagus heart right prostate skin viscera anterolateral tract projection neurone  Altered detection of pain Hyperalgesia Increased response to a noxious stimulus Allodynia Painful responses to a non-noxious stimulus Possible sites Increased sensitivity of peripheral nociceptors Increased transmission in spinal cord  Altered detection of pain Hyperalgesia Increased response to a noxious stimulus Allodynia Painful responses to a non-noxious stimulus Possible sites Increased sensitivity of peripheral nociceptors Increased transmission in spinal cord  mast cell Nociceptor sensitization Skin substance P histamine H+ bradykinin damage or prostaglandin inflammatio NGF n K+ ATP substance P blood vessel  Modulation of nociception TrkA nerve growth factor (NGF) Potassium channels Prostanoid receptor prostaglandins K+ + + + + VGNa + + Inhibitory Opioid/cannabinoid receptor + VR-1 Morphine/anandamide BK2 H1 bradykinin histamine  Altered detection of pain Hyperalgesia Increased response to a noxious stimulus Allodynia Painful responses to a non-noxious stimulus Possible sites Increased sensitivity of peripheral nociceptors (peripheral sensitization) Increased transmission in spinal cord (central sensitization)  Itch Afferent input is via Aδ and C fibres from free nerve endings Inflammation, particularly histamine, can cause it BUT………… Analgesics don’t inhibit itch To cure an itch, you scratch it (mechanical, almost nociceptive stimulation) Strong central component  Lecture summary Pain and nociception Detection of noxious stimuli Transmission of noxious information to spinal cord and brain Sensitization and modulation of nociceptors Transmission at spinal level Regulation of nociception Opioid analgesia NSAIDS analgesia Other analgesics