The Principles of Neural Science 4th-edition Chapter 24 The Perception of Pain sshi@brn.dis.titech.ac.jp http://www.brn.dis.titech.ac.jp/~sshi/ 22.Nov. 2002 nociception pricing, nociception burning, aching, stinging abstraction soreness somatic sensation nociceptive neuropathic 2 Nociceptive pains soft tissu inflammation nociceptors arthritis noxious insults Neurpathic pains -1-
A Polymodal mociceptors sympathetic dystorophy postherpetic neuralgia syndromes 1.0m/s C Figure24-1A shingles,herpes zoster 3 Phantom limb pain nociceptors traumatic surgical Chapter 20 Anesthesia fiest pain dlorosa 2 second pain Figure24-1B dorsal root nerves A polymodal C Noxious Insults Activate Nociceptors A thermal mechanical polymodal Thermal nociceptors 5 45 5-30m/s A Mechanical nociceptors B First Second 2 First pain 5-30m/s A Figure24-1 Filds 1987-2-
Second pain C viscera Silent nociceptors A A C silent C nociceptor 2 secondary hyperalgesia central sensitization 2 The dorsal column-medial lemniscal system A A nociceptors free norve ending free sensory ending A capsaicin Capsaicin Vaniloid Capsaicin reflexive shakin A C touch-pressure nociceptors allogynia blood pressure cuff 30 hyperalgesia 2 systolic pressure anoxia A allogynia -3-
A C 5 A 4 rheumatoid arthritis 5 3 2 allogynia Fields 1987 hyperalgesia afferent neuron dosal horn Nociceptive Afferent Fibers Terminate on anatomical Neurons in the Dorsal Horn of the Spinal dosal horn Cord lamina 1 substantia gelatinosa lamina 2 A C nociceptive 1 lamina 1 afferent fivers spinalcord dosal horn dosal nociceptive-specific neurons horn cytological 6 Figure24-2 wide-dynamic-range neurons Figure24-2 spinal 2 substantia cord dosal horn gelatinosa interneurons 1 lamina 1 A 3 4 laminae3,4 substantia C 2 lamina 2 gelatinosa ventral A interneurons 5 lamina 5 monosynaptic mechanoreceptors ropographically A 5 letina 5 brain stem thalamus -4-
wide-dynamic-range neurons horn1 A A projection neurons monosynaptic Figure24-2 C 1 C Fields 1987 higher centers 5 visceral structures somatic visceral 5 nociceptive input referrend pain referrend pain visceral structures 6 lamina 6 myocardial infarction dosal horn 7 8 single projection neuron 2 7 2 Figure24-3 Figure24-3 brain stem reticular formation 7 referrend pain referrend pain dosal horn 7 A myocardial infarction Nociceptiv Afferent Fiber Use Glutamate angina and Neuropeptides As Neurotransmitters referrend pain Teodori,Galletti 1962 B dosal horn referrend pain dosal -5-
central sensory nerve endings B C A C P substance P electron-dense immunoreaction glutamate glutamate dense-core vesicles S.P.Hunt. dosal horn AMPA C fast synaptic potential P substance P Capter 12 afferent fibers double-labeled 2 lamina 2 slow excitatory postsynaptic potentials dosal axoplasm horn P substance P granular electron-translucent vesicles synaptic vesicles LGV dense-core vesicles A.Rustioni. Figures 24-4,24-5 Figure 24-4 spinal cord dosal horn substantia gelatinosa lamina 2 A P substance P dosal horn electronmicrographs antisera 2 Figure 24-5 dosal horn A dosal horn D B enkephalin C P 2 synaptic vesicles A B S.P.Hunt. electron-translucent C Psubstance P synaptic vesicles immunoreactivity dense-core vesicles H.J.Ralston,III D -6-
-opioid enkephalins Hyperalgesia Has Both Peripheral and Central Origins P substance P Changes in Noceceptor Sensitivity Underlie P Primary Hyperalgesia substance P C sensitization postsynaptic desensitization Figure24-6 neurons P substance P Figure24-6 2 nociceptors 1 glutamate 2 hyperalgesia Rajaetal1984 A A D postsynaptic neurons A,B,C 53 30 hyperalgesia dosal horn hyperalgesia hyperalgesia dosal horn B 7-7-
axon reflex chemical mediators sensitization nociceptors vasodilation bradykinin:9 nociceptors sensitization prostaglandins: ;, nociceptors bradykinin 9 sensitization, nociceptors histamine P substance P:P,, prostaglandins CGRPcalcitoningene related peptide ; P substance, P mast cells, degranulation histamine: leukotriene P eicosanoid, plasma extravasation CGRP acetylcholine, bradykinin serotonin ; Table24-1 Lembeck,Gamse, P substance P P, ATP ACh, Table 24-1 nociceptors nociceptors histamine arachiconic acid metabolite polymodal Figure24-7 nociceptors cyclooxygenase Figure24-7 1982,Fields 1987 E 2-8-
; substance P nonpeptide antagonists aspirin nonsteroidal anti-inflammatory analgesics The Hyperexcitability of Dorsal Horn Neurons Underlies Centrally Mediated A C Hyperalgesia 2 C Chapter4,5 "wind-up" chemical mediators glutamate C P substance P NMDA calcitonin gene-related peptides2 NMDA wind-up vasodilation long-term potentiation long-term changes histamine hippocampus hyperalgesia,, long-term changes P substance P Chapter 63 NMDA, peripheral blood vessels central plasma sensitization extravasation postcapillary sensitization venules neurogenic ifnlamation long-term changes C P -9-
dosal horn spinothalamic tract c-fos spinal cord transcription early genes factors, lamina1,5,7 Figure24-8 upregulation: dosal spinal cord horn 3 spinothalamic tract phantom limb pain: spinal cord general anesthesia contralateral anterolateral white matter spinal cord general thalamus anesthesiacentral sensitization spinothalamic tract cordotomy: central sensitization spinal cord Nociceptive Information Is Transmitted Figure 24-8 side spinoreticular tract lamina 7,8 anterolateral quadrant From the Spinal Cord to the Thalamus and thalamus reticular Cerebral Cortex Along Five Ascending formation spinothalamic Pathways tract spinoreticular 5 tract midline spinomesencephalic tract lamina 1,5 5 anterolateral spinothalamic, quadrant mesencephalic spinoreticular, reticular formation spinomesencephalic, cervicothalamic periaqueductal gray matter, spinohypothalamic 5 spinoparabrachial tract parabrachial nuclei -10-
parabrachial nuclei thalamus nuclei amygdala, limbic system lateral medial, Chapter 50 spinomesencephalic tract thalamus latetal nuclear group ventoposterior medial nucleus, ventoposterior lateral lateral funiculus nucleus posteriot nucleus anterolateral spinothalamic quadrant tract lamina 1,5 cordotomy: cervicothalamic tract 2 lateral thalamus white matter lateral cervical nucleus lateral cervical nucleuslamina 3,4 spinothalamic tract cervicothalamic central pain midline brain stem medial ventoposterolateral lemniscus infarct thalamus ventroposterior lateral thalamic Dejerine-Roussysyndorome posteromedial lamina 3,4 dorsal columns dysesthesia medulla cuneate nuclei thalamus gracile nuclei spinohypothalamic thalamus tractlamina 1,5,8 angina Thalamic Nuclei Relay Afferent Information thalamus pectoris anesthesiologist heart to the Cerebral Cortex attack Box 24-1 -11-
thermocouple thalamus medial nuclear group central lateral nucleus intralaminar complex lamina 7,8 spinothalamic tract 2 1 paleospinothalamic tract reticular formation disinhibition spinoreticulothalamic tract Figure 24-9B nuclei primates neospinothalamic tract thalamocortical nociceptors basal ganglia PET Box 24-1 Thunberg 's grill 1896 Thunberg Figure 24-9C 'illusion Figure 24-9A Figure 24-9A Thunberg's illusion stroke 20 14cm central 92.5% pain syncrome 1cm 15 3mm Figure 24-9B anteror cingulate cortex anterior cengulate cortex peltier 1cm 2 3-12-
Chapter 50 insular cortex thalamus nuclei insular cortex cool insular cortex asymbolia for pain morphine insular cortex Figure 24-C anterior cingulate insula Pain Can Be Controlled by Central The Cerbral Cortex Contributes to the Mechanisms ProcessingofPain thalamus somatosensory cortex The Balance of Activity in Nociceptive and PET 2 Nonnociceptive Primary Afferent Fibers cingulate gyrus insular cortex Can Modulate Pain: The Gate Control Theory Box 24-1 cingulate gyrus limbic system -13-
Figure 24-10 1960 gate control theory Figure 24-10 dosal horn 4 1 C lamina 5 2 lamina 1 A A 3 A C 4 1 2 A 4 lamina 2 3 lamina5 4 2 A C lamina 5 1 lamina 2 A projection neurons close open Direct Electrical Stimulation of the Brain Produces Analgesia TENS dorsal column TENS periaqueductal gray region 3 third ventricle cerebral aqueduct gray mutter dorsalcolumns analgesia A stimulation-produced analgesia analgesia analgesia -14-
periaqueductal gray periaqueductal gray matter raphe magnus matter nuclei withdrawal reflexes raphe magnus dorsolateral funiculus dosal horn lamina 1,5 medulla pons noradrenergic cells groups dosal horn Figure 24-10 periaqueductal gray matter dosal horn rostroventral medulla Opiate-Induced Analgesia Involves the Same raphe magnus nucleus Pathways as Stimulation-Produced midline Analgesia nuclei lamina 1,2,5 Figure 24-11 rostroventral medulla morphine codeine dosal horn dosal horn noradrenergic locus seruleus medulla pons nuclei morphine dosal horn lamina 1,5 periaqueductal gray region dosal horn opiate antagonist naloxone periaqueductal gray region Figure 24-11 nuclei -15-
tolerance morphine addiction morphine Figure 24-13 tolerance dosal horn opioids G A dosal horn opioids tolerance enkephalin opioids brain stem Stress Induces Analgesia Through Both Opioid and Nonopioid Mechanisms B glutamate C Ca2+ analgesia analgesia naloxone Tolerance and AddictiontoOpioidsAreDistinct Phenomena naloxone morphine 2 tolerance analgesia addiction morphine -16-
1 Daid Livingstone An Overall View 1 2 brain stem 3 analgesia Allan I. Basbaum Thomas M.Jessell -17-
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