pain modulation and the thalamus 3/6

pain (nociception)

sharp pain (cutting)

dull pain (diffuse, burning)

sharp pain (cutting)

noxious stimuli that may be tissue damaging sources of energy (internal or external)

dull pain (diffuse, burning)

noxious stimuli following tissue damage (inflammation)

nociceptors are found in

skin, muscle, joint, connective tissue , viscera

types of nociceptors

myelinated A-delta fibers (fast pain)

unmyelinated C fibers (slow, burning pain)

pain is a

complex sensory and emotional experience

two phase of pain perception

discriminative: fast pain, well localized, sharp and pricking sensation

affective: slow pain, diffuse, dull burning pain

spinal fast pain pathway

neospinothalamic system

discrimination and localization

first order neuron synapses on lamina I marginal nucleus

axon decussates through ventral white commissure, ascends in spinothalamic tract

axons synapse on VPL in lateral thalamus

axons travel to primary somatosensory cortex for localization, discrimination, intensity perception

spinal slow pain pathways

paleospinothalamic and spinoreticulothalamic systems

phylogenetically older

affective/motivational/emotional/arousal aspects of pain

collaterals to medullary reticular formation—from massive reticulothalamic system which projects nociceptive impulses to medial thalamus then to many areas of cerebral cortex

where do the neospinothalamic, spinoreticulothalamic and paleospinothalamic tracts ascend?

anterolateral quadrant/system/region

paleospinothalamic and spinoreticulothalamic tracts

cell bodies in spinal cord

axons travel toward thalamus, but first synapse and give off collaterals in spinal cord and brainstem (causes diffuse effect of slow pain)

go to different thalamic nuclei and then different cortical regions (causes responses in various systems to pain, ex. emotional)

slow pain pathway steps

c fibers synapse in lamina II/V

crosses ventral white commissure

ascends in anterolateral system/quadrant

collaterals enter reticular formation as info ascends brainstem to medial thalamus

medial thalamus projects to part of cortex associated w emotion (cingulate gyrus) and others

fast pain second order neuron

marginal nucleus lamina 1

slow pain second order neuron

spinal projection neurons→proper sensory nucleus (lamina 5)→axons cross at ventral white commissure→ascend in the anterolateral system (intermingled with spinothalamic tract)

slow pain vs fast pain

response to tissue damage vs acute pain

slow pain pathway first order neurons

unipolar neurons (C fiber) in dorsal root ganglion→project centrally through lateral portion/division of dorsal root/rootlets→funneled into Lissauer’s tract (dorsolateral fasciculus, DLF)→synapse in lamina 2 (substantia gelatinosa)

slow pain pathway third order neuron

medial thalamus:

intralaminar thalamic nuclei (centromedian)

medial dorsal nuclei

anterior nuclei

project to anterior cingulate cortex (ACC) and orbitofrontal cortex and insula

insula

integrates sensory, affective, and cognitive components for autonomic responses to pain, pain related learning and memory

anterior cingulate cortex (ACC) and orbitofrontal cortex

transmits and processes pain related information and emotional responses, connects with and contributes to activity of centers responsible for modulating (descending) nociception (such as periaqueductal gray or PAG)

asymbolia for pain

patients with lesions of the insular cortex can recognize fast pain, but have no emotional responses

how does the PAG modulate descending pain pathways

ACC and orbitofrontal cortex have connections to PAG→descend and inhibit activity of pain pathways

medial dorsal nucleus

thalamocortical axons project to the limbic system for affective responses to pain (anguish, depression, fear, anger)

intralaminar thalamic nuclei

centromedian

thalamocortical axons project to widespread areas of cerebral cortex for arousal and attention

slow pain pathways share similarities with

spinothalamic pathway in the spinal cord—1st neuron cell bodies in DRG, 2nd neuron axons cross in ventral white commissure & ascend in anterolateral quadrant

slow pain pathways form

a multisynaptic reticulothalamic pathway

slow pain pathways give off terminals to

medulla (nucleus raphe magnus)

pons (locus coeruleus)

midbrain (periaqueductal gray)

hypothalamus (periventricular gray)

amygdala

reticular formation

influences voluntary movements

regulates visceral activity via the ANS

participates in the conduction and modulation of slow pain

associated with diffuse modulating systems

regulates activity of the cerebral cortex and consciousness

exogenous pain modulation

via large cutaneous primary afferent nerve fiber (A-alpha and A-beta) connections in the substantia gelatinosa (lamina II)

endogenous pain modulation

via activity of periaqueducteal gray, periventricular gray, nucleus raphe magnus, and dorsal horn neurons in substantia gelatinosa (also involved in other pain modulation, same mechanism from different area)

endogenous pain modulation pathway

analgesia centers (periventricular and periaqueductal gray) send descending fibers, impact nucleus raphe magnus, send descending pathway to dorsal horn→excites inhibitory interneurons in substantia gelatinosa (lamina II)→inhibit 2nd order pain neurons

exogenous pain modulation pathway

A-alpha and A-beta fibers give off collaterals (remainder ascends in spinal touch pathway), which excite substantia gelatinosa (lamina II) inhibitory interneurons, which inhibit 2nd order pain neurons that project to spinothalamic tract (spinal pain sensory pathway)

gate theory of melzack and wall

selective activation of large (A-beta) fibers to manage chronic pain

transcutaneous electrical nerve stimulation (TENS)

intractable pain treatments

aka pain that doesn’t go away

pharmacological approaches—NSAIDs, opioids

electrical stimulation

ablative surgeries—cut the nerve

thalamus

gateway to the cerebral cortex

relay for motor information—basal ganglia (VA) and cerebellum(VL)

relay for sensory information—almost all sensory, cerebellar, BG, limbic pathways have neuronal relays in these nuclei; spinal pathways (VPL) and cranial pathways (VPM)

processes and refines information sent to cerebral cortex

receive, process, sort, send info back and forth between lobes of brain (arousal)

diencephalon parts

epithalamus (pineal gland)

subthalamus

hypothalamus

thalamus

thalamic borders

medially: 3rd ventricle

laterally: internal capsule

superiorly: lateral ventricle

3 regions of each thalamus

medial, anterior, lateral

divided by internal medullary lamina

fast pain thalamic nucleus

ventral posterior nucleus in lateral thalamus (spinal→VPL, cranial→VPM)

slow pain thalamic nucleus

medial thalamus—intralaminar, medial dorsal, anterior nuclei

cerebellum thalamic nucleus

ventral lateral (VL)

basal ganglia thalamic nucleus

ventral anterior (VA)

auditory pathway thalamic nucleus

medial genicualte nucleus (MGN)

visual pathway thalamic nucleus

lateral genicualte nucleus (LGN)

PI: which statement correctly summarizes exogenous inhibition of pain?

1. flow of ascending pain info is modified by stimulation of low-threshold mechanoreceptors

2. flow of ascending pain info is modified by stimuli from cortical centers

3. flow of ascending pain info is modified by stimuli from brainstem centered

4. descending inputs from pain centers indirectly modify the activity of dorsal horn projection neurons by acting on local circuit neurons

5. descending inputs from pain centers directly modify the activity of dorsal horn projection neurons

1

PI: which thalamic nucleus contributes to the affective aspect of pain?

1. ventral posterolateral

2. ventral posteromedial

3. ventral anterior

4. ventral lateral

5. medial dorsal

5

note to self

make separate flash cards for thalamic nuclei and where they project to—medial dorsal projects to ACC & orbitofrontal cortex

PI: in an experiment, subjects are given a selective A-delta fiber blocker and then exposed to a strong heat stimulus. which curve best represents the expected perception of pain by the subjects?

1. A

2. B

3. C

4. D

5. E

1

PI: in a neuroscience experiment examining the effect of hypnosis on pain perception subjects were first poked in the hand with a sharp probe and asked to rate the pain on a 1 (no pain) to 5 (intense pain) scale. researchers noted how much pressure it took to elicit pain at both a level 2 and a level 4. subjects were then hypnotized and scanned using fMRI. during fMRI evaluation, subjects were poked with the sharp probe with enough pressure to elicit level 2 pain. without changing the intensity of the pressure, researchers then persuaded subjects that the pressure was increasing during the fMRI measurements. in what brain region would you expect to see increases in activity in the hypotized subjects?

1. cerebellum

2. somatosensory cortex

3. ventral posterolateral nucleus of the thalamus

4. anterior cingulate gyrus

5. no region would change in activity

4

PI: logan has been managing chronic pain in his leg and back from bike accident injuries for over a year. his doctor has suggested that they stimulate his brain in an attempt to relieve some of the pain. stimulation of which region would be most likely to produce relief?

1. periaqueductal gray

2. somatosensory cortex

3. medial geniculate nucleus

4. ventral posterior medial nucleus of the thalamus

5. superior colliculus

1