Somatosensory and Pain - Kenyon Flashcards
What is the general function of primary afferent neurons?
Encode mechanical, chemical, or thermal stimulus into a receptor or generator potential
Are generator and action potentials the same
NO
Describe a generator potential?
small, graded, and NOT CONDUCTED.
Generator potential is equivalent to what type of post-synaptic event?
EPSP
Where are the cell bodies of PANs?
in the DRG
Are there synapses in the DRG?
Normally speaking, NO
Are there IPSPs or EPSPs in the DRG?
No, all electrical activity passes right through it
“A” fibers have a (large/small) diameter and conduct (fast/slow)
large, fast
C fibers are (large/small) diameter and conduct (fast/slow)
small, slow
C and A-delta conduct what signals?
Pain and temperature
which fiber type is the fastest and what type of signal does it carry?
A-beta; TVP
what are the slowest fibers?
C and A-delta
Does the fast/slow differentiation have any impact on actual ability to conduct?
NO
Do specialized receptors of PAN’s adapt to stimuli?
Some adapt quickly, some slowly, some not at all. Theyre the goldilocks bears of neuroscience.
In two-pt. discrimination, what happens as you move the points farther apart?
AP frequency from the central receptive field lowers while frequency increases in the lateral receptive fields
Describe the pathway taken for TVP and Pain and Temp from the body and back of head?
PAN’s to DRG to dorsal roots to dorsal column to medial lemniscus
Describe the path for TVP, pain, and temp, form the the face and teeth?
PAN’s to trigeminal ganglion
When axons enter the spinal cord, what types of events utilize the pathway that synapse in Rexed Layer 3 of the cord?
spinal reflexes: knee jerk, somato-somatic, viscero-somatic
When axons enter the spinal cord and branch without synapsing, what do these form?
The dorsal columns of he spinal cord
Lower limbs form what tract?
medial gracile tract
Upper limbs, trunk and neck form what tract?
lateral cuneate tract
With respect to dorsal column somatotopy, what body structures will be more lateral? More medial?
lateral: occiput and neck
medial: lower limb and trunk
Will we see facial innervation in the the somatotopy of the dorsal column?
No, that stuff goes through the trigeminal!
What is the effect on TVP of lesions in the dorsal column? what does this tell us about TVP fibers?
There is PARTIAL loss of TVP; dorsal columns are NOT the only pathway for TVP
Axons from the dorsal columns synapse with second order neurons in which nuclei?
gracile nucleus
cuneate nucleus
Is the information at the gracile and cuneate nuclei simply relayed or is it processed?
it is processed
The (blank) tract is the pathway in which axons go ventral and corss over to form the medial lemniscus
Internal Arcuate tract
Axons from the lower body end up (ventral/dorsal)
ventral
Fibers from the gracile or cuneate tracts synapse in the (blank or blank) nuclei
Gracile or cuneate nuclei
The gracile and cuneate nuclei are in which brain layer?
Caudal medulla
The internal arcuate tract connects the gracile and cuneate nuclei to the (blank)
medial lemniscus
Axons in the medial lemniscus synapse with third order neurons where?
Ventral Posterior Lateral nucleus of the thalamus
The VPL nucleus of the thalamus sends its fibers to what cortical structure and to which gyrus?
Post central gyrus of the primary sensory cortex
does the VP complex have all peripheral somatic sensory fibers?
yes!
Fibers from the trigeminal ganglion first enter at what brain level?
PONS
trigeminal fibers synapse at what nucleus in the Pons?
principal nucleus of trigeminal complex
Do fibers from the trigeminal travel on the medial or lateral lemniscus?
medial
Where does the crossing over ocurr in the trigeminal pathway?
After synapsing in the principal nucleus and meeting up with the medial lemniscus
Where does the crossing over occur in the somatosensory pathway?
In the caudal medulla, after synapsing in the gracile or cuneate nuclei and becoming the medal leminscus
Fibers in the trigeminal lemniscus synapse where in the brain proper?
VPM of the thalamus
Trigeminal fibers in the VPM travel to what cortical structure?
pimary somatic sensory cortex
With regard to the sensory cortex somatotopy, are structures of the face more medial or lateral?
lateral
what structures are most medial on cortical somatotopy?
Trunk, leg, feet, toes
the Ant. cerebral artery supplies what somatotopic structures?
tunk, leg, foot, and genitals
the middle cerebral artery suppplies what somatotopic structures?
arms, hands, face, tongue
Does the posterior cerebral artery supply any somatotopic structures?
noooooope
Is there anything coming out of the primary sensory cortex?
YES, DESCENDING branches going to the secondary sensory cortex
From the SII, to what brain structures do fibers go? What are their functions?
Limbic structures, amygdala, and hippocampus.
Involved in inhibitory pathways blocking out proprioception (not always aware of your shoes/socks), as well as tactile sensation and learning memory
Are there more ascending or descending axons?
Descending!
effective analgesic therapy increases the (blank) of life for pts with pain
quality
What three classes of drugs help with neuropathic pain?
- COX 2 inhibitors
- opioid analgesics
- adjuvant analgesics
What fraction of pts actually get adequate neuropathic pain relief from current treatments?
1/3
When processing pain in the sensory-discriminative model, in what nucleus do pain fibers synapse?
Ventral posterior (VP) nucleus
After hitting the VP, where does pain go for the sensory-discriminatory model?
Somatosensory cortex (SI, SII)
In the affective-motivational model, what are the two cortical areas that are acivated?
Anterior cingulate cortex and insular cortex
From what nuclei do you travel to reach the ant. cingulate cortex and the insular cortex?
midline thalamic nucleus
lesions in what thalamic nuclei cause complete loss of contralateral pain and temp?
ventromedial nucleus
What are the two ways of measuring pain?
Self-reporting or fMRI
Nociceptors have their cell bodies where?
in the DRG
the goal of pain management is to manipulate, aka (blank), nociceptors to control the first stage of pain generation
KILLLLLL
Capsaicin receptors are part of the (blank) receptor family
TRPV1
(Pre/post)ganglionic sympathetic neurons will synapse in the (blank) following injury
post, DRG
Synapse of sympathetic fibers in the DRG will cause (blank)
pain
Nociceptors have a (higher/lower) threshold than thermoreceptors
higher!! First something feels good and warm before it burns!
Stimulation of (hi/low) threshold mechano/thermoreceptors is non painful
low
stimulation of high threshold (thermoreceptor/nociceptors) is painful
nociceptor
What is the order of conduction speed from fastest to slowest of c, A-delta, and TVP fibers?
TVP>A-delta>C
do A-delta fibers carry first or second pain?
first pain
T/F: C-fibers carry second pain
T
Besides pain, what two other stimuli do A-delta fibers carry?
mechano and mechanothermal
Can C-fibers carry several sorts of painful stimuli?
Yes, this is called polymodal
Is conduction rate the event that causes difference between first and second pain?
Nope
What is the general reason for difference in first and second pain?
Fibers are going to different areas of the brain
What three types of stimuli can excite nociceptors?
- mechanical
- thermal
- chemical (pH)
what class of ion channels are involved in pain and temp info?
TRP channels
What three stimuli open capsaicin channels?
- heat
- low pH
- capsaicin
T/F: the capsaicin channel is selective for Ca
F! It is NONSELECTIVE
T/F: capsaicin channels are regulated by intracellular Ca and enzymes
T
does capsaicin bind to the receptor outside of the plasma membrane or within the cytosol?
On the cytosolic side
Does the capsaicin receptor produce a generator potential or an AP?
generator potential
What ion that TRPV1 lets into the cell causes autoregulation of the channel?
Ca, of course
What receptor is involved in the itch response?
TRPA1
is TRPA1 metabotropic or ionotropic?
metabotropic
Binding different intracellular (blanks) will differentiate between pain and itch
GPCRs
Pain and temperature afferents synapse in the (blank)
dorsal horn
Axons from the secondary neurons cross and form the (blank) tract to the thalamus
anterolateral tract (spinothalamic)
lesion of the dorsal column will result in what specific defieciency beyond partial TVP loss?
loss of ability to detect direction and speed of stimulus
TVP and pain are (same/opposite) sides below the medulla
OPPOSITE
TVP and pain are on (same/opposite) sides above the medulla
SAME
TVP crosses over to the same as pain at what brain level?
caudal medulla
What tract does TVP travel on to reach the medial lemniscus to decussate?
the internal arcuate tract
At their entrances to the CNS, do both TVP and pain come up ipsilaterally?
NO; TVP ispalateral, pain contralateral
Pain travels through what spinal tract?
The spinalreticular tract within the anterolateral system
A lesion of one side of the spinal cord will result in reduced TVP on the (blank) side and reduced pain and temperature sensation on the (blank) side.
ispilateral, contralateral
When pain and temp come in from the face, what direction (up/down) do they first travel in the CNS?
Descend
Trigeminal pain and temp decussate onto the (blank) tract
trigeminothalamic tract
to what brain level does the trigeminal dive down to for pain and temp?
Enters at mid-pons, dives down to middle medulla
Between the mid pons and middle medulla pain and temp from BOTH sides of the face are on (blank) side(s) of the brainstem.
BOTH SIDES OF BRAINSTEM!
Sensory discriminative pathway mediates what three things?
- location
- intensity
- quality of noxious stim
Affective-motivational pathway mediates what three sensations?
- unpleasantness
- anxiety
- fear associated with pain
Sensory discriminative is in what part of the brain
somatosensory cortex
Affective-motivational pathway is associated with what parts of the brain? (6)
Amgydala Hypothalamus Periaqueductal grey Reticular Formation Cingulate Cortex Insula
It’s scary to sit down int the P-CHAIR (pain chair!)
Besides making you feel like absolute dog shit while you throw a pity-party for your pain, what actual useful thing can the affective-motivational pathway do?
it can dampen down those debby downer thoughts!
Projections to the reticular formation are in what brain structure?
Middle medulla
Affective-motivational pathway synapses at what nucleus and at what level?
Parabrachial nucleus in the mid pons
Fromt he affect-motivate path, Projections to these two structures come off at mid-pons
amygdala
hypothalamus
What nucleus does the A-M pathway synapse in at the thalamus/
Intralaminar nuclei
What two terminal brain structures does the A-M pathway go to?
insula and cingulate cortex
Referred pain is (visceral/somatic) pain
visceral
T/F: A lesion of the dorsal column could alleviate cancer pain
T; cancer is visceral pain
What pathway does visceral/referred pain follow?
medial lemniscus, surprisingly
Where does referred pain synapse in the thalamus
VP nucleus
What terminal brain structure does referred pain go to? is this part of the A-M or S-D pathway?
insular cortex; A-M
What is hyperalgesia?
Increases sensitivity to a painful stimulus
What is allodynia?
Nonpainful simtuli now causes pain
Hyperalgesia and allodynia arise from both (blank and blank) mechanisms
peripheral and central
Sensitivity of nociceptors can be adjusted in the (blank)
periphery
An “inflammatory soup” of substances is released following (blank)
injury
What is result of releasing this inflammatory soup?
Sensitization of nociceptors
What chemicals are released during injury that sensitize the nociceptor?
ATP prostaglandins Histamine Bradykynin 5-HT H Substance P nerve growth factor CGRP
Peripheral sensitization acts on a (positive/negative) feedback system
Positive
T/F: Nociceptive neurons themselves can release sensitizing compounds
T
COX inhibitors reduce pain by inhibiting sythesis of:
prostaglandins
What is windup?
progressive increase in response by a dorsal horn neuron due to repetitive stimulation
In central sensitization, cytokines promote transcription of (blank) that make prostaglandins that increase neuronal activity
COX-2
COX 2 inhibitors work on (blank) peripherally and (blank) centrally
DRG peripherally, spinal cord neurons centrally
damage to the pain pathways results in what kind of pain?
neuropathic
T/F: The perception and response to a painful stimulus is determined solely by the magnitude of the stimulus or activity in the primary afferent nociceptor.
F: IT IS NOT SOLEY DETERMINED
Descending pathways activate neurons in the (blank) of the midbrain
periaqueductual grey
A-M descending pathway is controlled at what 4 structures?
- Amygdala
- Hypothalamus
- midbrain periaqueductal grey
- Medullary reticular formation
What are the nuclei that the periquedecutal grey project to? (4)
- parabrachial nucleus
- dorsal raphe nucleus
- locus coeruleus
- medullary reticular formation
Where is the parabrachial nucleus?
junction of midbrain and pons
Where is the dorsal raphe nucleus?
Medulla
Where is the locus coeruleus/
PONS
Where is the medullary reticular formation?
medulla
In the (blank) horn of the spinal cord, activity in the descending pathways inhibits nociceptive activity
dorsal
What neurotransmitters are used for inhibition of pain?
Serotonin
Enkephalins
Activation of GPCRs coupled with inactivation of Ca channels modulates pain how?
inhibits it
how does inactivation of Ca channels inhibit pain?
Inhibition of Ca influx prevents neurotransmitter release
What types of nuerons release enkephalins/
interneurons
Activation of low-threshold mechanoreceptors can also (blank) nociceptive activity.
inhibit
Where are the opioid receptors?
Periaqueductal grey and spinal cord
Is there a real neurochemical basis of the placebo effect?
YES
What drug blocks the placebo effect?
naloxone
Newborns exposed to repeated heel lances have increased
hyperalgesia and conditioning to painful stimuli