SOMATOSENSORY SYSTEMS AND PAIN
A 21 year old man presented with a stab wound of the right side of the neck (Panel A). Neurological examination revealed right hemiplegia and complete right-sided loss of twopoint discrimination, proprioceptive and vibratory sensation below the level of C5. On the left side, the patient had a loss of pain and temperature sensation below the level of C7.
FEATURES OF THE BROWN SEQUARD SYNDROME: Ipsilateral loss of two point discrimation, conscious joint position sense, vibration sense Contralateral loss of pain and temperature Ipsilateral paralysis (with increased deep tendon reflexes)
Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract
MEDIAL-LEMNISCAL ANTEROLATERAL Dorsal columns Fast Neurons: place specific (topographic) Spinothalamic-spinoreticular Slow Neurons: larger receptive fields (Aδ vs C fiber pain) modality specific multimodal (parallel-labeled line) (highly convergent, except for periphery) Test: Test: two-point pain and temperature joint position sense vibration sensibility
SPECIFICITY IN THE SOMATOSENSORY PATHWAY IT BEGINS IN THE PERIPHERY
HAIRY SKIN HAIRLESS (GLABROUS) SKIN
Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract
REPRESENTATION OF THE BODY SURFACE IN THE POSTCENTRAL GYRUS
Magnification Factor
TWO-POINT DISCRIMINATION THRESHOLDS
REPRESENTATION OF THE BODY SURFACE IN THE POSTCENTRAL GYRUS How many maps?
Central sulcus CYTOARCHITECTURE OF THE POSTCENTRAL GYRUS
MULTIPLE MAPS IN THE POSTCENTRAL GYRUS AREA 3b OWL MONKEY AREA 1
VIBRISSA-INDUCED GLUCOSE UTILIZATION IN RAT SOMATOSENSORY CORTEX ONE VIBRISSA----ONE CORTICAL COLUMN
USE IT OR LOSE IT BRAILLE AMPUTATION
PAIN
PAIN IS A SUBJECTIVE EXPERIENCE: It is not a stimulus MAJOR FEATURES OF THE PAIN EXPERIENCE: Sensory discriminative Affective (emotional) Cognitive MEASUREMENT OF PAIN: A BIG PROBLEM
Worst pain ever Visual Analogue Scale (VAS) No pain
O U C H E R S C A L E
DESCARTES
Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract
DESCARTES
ANTEROLATERAL CORDOTOMY (SPINOTHALAMIC TRACTOTOMY)
NEUROSURGICAL PROCEDURES THAT HAVE BEEN USED TO TREAT PAIN
NOCICEPTIVE (TISSUE INJURY) PAIN: (Associated with inflammation) Aches and sprains Back pain Arthritis Temporomandibular joint pain (TMD) Cancer Headache (migraine)
Nociceptive Pain: Tissue Injury/Inflammation
NEUROPATHIC (NERVE INJURY) PAIN: Reflex sympathetic dystrophy (RSD); causalgia Trigeminal Neuralgia Post-herpetic neuralgia Anesthesia Dolorosa Phantom Limb Pain Cancer
Neuropathic Pain: Nerve Injury (RSD)
Neuropathic Pain: Post-Herpetic Neuralgia
Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract ----IS NOT A PAIN TRACT
So where does specificity break down?
Peripheral nerves contain small and large diameter primary afferent fibers
Large myelinated Aβ Small myelinated Aδ Unmyelinated C Peripheral nerve fibers
Myelinated A delta and unmyelinated C fibers only respond to noxious stimulation
But in the setting of tissue injury the small diameter fibers respond to innocuous stimulation: NON-PAINFUL STIMULI NOW HURT!
Tissue Injury Arachidonic acid Cyclooxygenase Prostaglandins C FIBER THRESHOLD LOWERED ALLODYNIA PERIPHERAL SENSITIZATION
NSAIDS Aspirin Ibuprofen Naprosyn (Alleve) Cox-2 inhibitors
Large myelinated afferents (Aβ) do not respond to noxious stimulation
But activity of large diameter fibers can reduce the pain that results from activity in small diameter primary afferent fibers. SHAKE YOUR HAND; IT HURTS LESS!
Organization of the Dorsal Horn Laminar organization
Organization of the Dorsal Horn Somatic-visceral convergence: Referred Pain
REFERRED PAIN
Organization of the Dorsal Horn CENTRAL SENSITIZATION
Central sensitization: Tissue Damage Nerve Injury
Central sensitization:
CENTRAL SENSITIZATION Pain responsive neurons can now be activated by non-noxious stimuli (allodynia) Receptive field size of dorsal horn neuron increases Spontaneous activity increases
Mechanisms of Central Sensitization C-fiber input NMDA Mg ++ NK-1 AMPA WDR cell
Mechanisms of Central Sensitization Presynaptic: Increased transmitter release Ca 2+ MOR C-fiber input Gabapentin (α2δ) Ziconatide (N) Morphine Prostaglandin (EP receptor) COX inhibitors
Mechanisms of Central Sensitization Presynaptic: Increased transmitter release Ca 2+ MOR C-fiber input Prostaglandin (EP receptor) NMDA AMPA Postsynaptic: increased response to transmitter strengthening of synaptic efficacy Mg ++ ALTERATION IN SECOND MESSENGERS PHOSPHORYLATION OF RECEPTORS AND ION CHANNELS WDR cell INCREASED EXCITABILITY AND SYNAPTIC EFFICACY
Mechanisms of Central Sensitization: Descending influences Facilitation Inhibition (SNRI) 5-HT and NE Glutamate GABA (Anticonvuslants) Glycine
Microglia Quiescent glia Ipsi Contra Nerve injury Activated glia
Organization of the Dorsal Horn Ascending pathways
Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract
Dimensions of Pain Perception Sensory-Discriminative Stimulus features: Location, Modality, Intensity Affective-Motivational How unpleasant or upsetting is the pain? What will I do about the pain?
Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract
Nociceptive neurons in lateral, medial and posterior thalamus
Somatosensory cortex
Pain activates sensory cortex S1 S2
Somatosensory cortex Anterior cingulate cortex Insular cortex
Pain activates limbic cortex ACC IC
Pain affect without pain sensation in patient with postcentral lesion (Ploner et al. 1999)
Where pain activity in the brain is evoked depends on. what part of the body was stimulated.
Esophageal distension vs noxious thermal heat Insular Cortex QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture. Motor Cortex Anterior Cingulate Cortex Strigo, I. A. Bushnell, M. C. Alert
It depends on. who was stimulated.
QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture. Male Female From Casey et al
It depends on. the psychological state of the subject when he/she was stimulated.
It depends on. how much attention is paid to the stimulus.
Pain evokes more brain activity when attending to pain Attention to pain Attention to tones Bushnell et al. 1999
It depends on. how much pain you expect to experience.
Expectancy can alter pain Pain Warm Warm (expect pain) (expect pain) (expect warm) Sawamoto et al. 2000
It depends on. the meaning (and emotional content) of the stimulus.
What can we conclude.. There is no pain area in the brain. Rather, a matrix of activity in loci related to cognitive, affective and sensorydiscriminative components underlies the overall pain experience.
What can we conclude...that you cannot predict and must never assume that you know the magnitude and quality of pain that people experience.
PAIN CONTROL
PAIN CONTROL PROCEDURES Aspirin and other NSAIDS (ibuprofen; COX-2 inhibitors) Transcutaneous electrical nerve stimulation (TENS) Deep brain stimulation (DBS) Morphine and other opioids Placebo Acupuncture Stress/other psychological mechanisms Hypnosis
DEEP BRAIN STIMULATION
DEEP BRAIN STIMULATION MODULATION NALOXONE OPIATES + Periaqueductal Gray Nucleus Raphe Magnus Dorsal horn
ENDORPHINS Enkephalin Dynorphin β Endorphin Opioid Receptors NALOXONE
PAG stimulation evokes the MODULATION release of endorphins to initiate descending inhibition and pain OPIATES control NALOXONE is the key to this interpretation. DEEP BRAIN STIMULATION Periaqueductal Gray (PAG) Nucleus Raphe Magnus (NRM) Dorsal horn
ENDORPHINS Enkephalin Dynorphin β Endorphin Endogenous Opioid Receptors Exogenous Morphine and other opiates
SIDE EFFECTS MODULATION OPIATES SYSTEMIC MORPHINE OPIATE ANALGESIA Periaqueductal Gray Nucleus Raphe Magnus Dorsal horn GUT (CONSTIPATION)
OPIATE ANALGESIA MODULATION OPIATES EPIDURAL MORPHINE Periaqueductal Gray Nucleus Raphe Magnus Dorsal horn
MORPHINE
PAIN CONTROL PROCEDURES Aspirin and other NSAIDS (ibuprofen) Transcutaneous electrical nerve stimulation (TENS) Deep brain stimulation (DBS) Morphine and other opioids Placebo Acupuncture Stress/other psychological mechanisms Hypnosis
S1 ACC Under Hypnosis Rainville et al HIGH Unpleasantness LOW