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pain pathway
Neuroanatomy Pain Pathway
164
Anatomy
Graduate
03/14/2012

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Term
does pain arise from excessive stimulation of mechanoreceptors
Definition
no
Term
what receives and conveys painful sensory signals to the CNS
Definition
dedicated receptors and pathways
Term
what is the name of receptors that receive pain signals
Definition
nociceptors
Term
why does it make good sense to have a separate system for the detection of pain and mechanical stimulation
Definition
don't want to confuse pain with squeezing, for example
Term
what are the 2 classifications of receptors based on morphology
Definition
encapsulated, free nerve endings
Term
what do encapsulated receptors detect
Definition
mechanical stimuli
Term
what do free nerve endings detect
Definition
pain and temperature stimuil
Term
are free nerve endings myelinated
Definition
no, or else they're very lightly myelinated
Term
are free nerve endings big
Definition
no
Term
are free nerve endings fast
Definition
no
Term
what are nociceptors
Definition
unspecialized free nerve endings that intitiate the sensation of pain
Term
what sensations do nociceptors carry
Definition
pain and temperature
Term
do nociceptor axons conduct quickly or slowly
Definition
slowly
Term
what are the 2 categories of nociceptors
Definition
a delta, c fiber
Term
what determines which category a nociceptor falls into
Definition
axon properties
Term
what are the axon properties of a delta nociceptors (myelinated? Conduction speed? Diameter? What kind of stimuli it responds to?)
Definition
lightly myelinated. 20 m/s. medium diameter. responds to dangerously intense stimuli
Term
what are the axon properties of c fiber nociceptors (myelinated? Conduction speed? Diameter? What kind of stimuli it responds to?)
Definition
unmyelinated. 2 m/s. small diameter. Responds to innocuous temperature, itch
Term
what is the faster pain pathway
Definition
a delta
Term
what is the slower pain pathway
Definition
c fiber
Term
what is the pathway of initial pain
Definition
a delta
Term
what is the pathway of chronic pain
Definition
c fiber
Term
If I were to take a little electrode and put electrical impulses in an A beta fiber, would it convey pain?
Definition
no
Term
if I were to take a little electrode and put electrical impulses in an A delta fiber, would it convey pain?
Definition
yes
Term
how do we know that a Beta fibers don't convey pain
Definition
experimental evidence: direct electrical stimulation at any intensity/frequency does not produce pain in A beta fibers, but stimulation of A delta and C fibers does produce pain
Term
what do mechanothermal nociceptors detect
Definition
potentially harmful thermal stimuli
Term
what do non-nociceptive thermoreceptors detect
Definition
innocuous, non-harmful warm and cold temperatures
Term
describe the firing rate of non-nociceptive thermoreceptors as a temperature gets hotter and hotter
Definition
the firing rate of non-nociceptive themoreceptors stays about the same as at lower temperatures
Term
describe the firing rate of mechanothermal nociceptors as a temperature gets hotter and hotter
Definition
mechanothermal nociceptor axons increase their firing rate as temperature gets dangerously hot
Term
are the receptive fields of all pain and temperature sensitve neurons large or small
Definition
large
Term
why are the receptive fields of pain and temperature sensitive neurons large
Definition
the detection of pain is far more important than the exact location
Term
what do we call the specific receptors associated with nociceptive afferent nerve endings
Definition
vanilloid receptors
Term
what is another term for vanilloid receptors
Definition
VR-1
Term
in what types of fibers are VR-1 receptors found
Definition
A delta and C fibers
Term
what makes VR 1 a transmembrane receptor
Definition
it has a channel/central pore in the middle
Term
what activates VR-1 receptors
Definition
heat: temp greater than 45C
Term
what happens when VR 1 receptors are activated and opened
Definition
the channel allows an influx of sodium and calcium ions which generate action potentials in the nociceptive axon
Term
how does capsacin affect VR 1 receptors
Definition
capsaicin is cell-permeant. It can bind to the intracellular part of the receptor causing the receptor to open
Term
what 2 things activate VR-1 receptors
Definition
heat, capsaicin
Term
what happens when capsaicin is applied to the skin
Definition
produces a burning pain and elicits hyperalgesia to thermal and mechanical stimuli
Term
what is hyperalgesia
Definition
increased sensitivity to pain
Term
what is capzasin
Definition
.75% capsaicin. Helps desensitize nerve endings to treat arthritis and neuritis.
Term
why is the area surrounding an injury (cut or bruise) so painful
Definition
because damaged tissues release substances that change responsiveness of nociceptors
Term
what local substances are released following injury y damaged tissues
Definition
prostaglandins, histamine, ATP, bradykinins, substance p
Term
what is inflammatory soup
Definition
term to describe the release of prostaglandins, histamine, ATP, bradykinins, and substance P following tissue damage
Term
what is substance P
Definition
large molecule neurotransmitter
Term
what is peripheral sensitization
Definition
the change in responsiveness of nociceptors caused by the inflammatory soup following injury
Term
how do released prostaglandins change the responsiveness of nociceptors following injury
Definition
released prostaglandins reduce the threshold of depolarization required to generate action potentials in nociceptive neurons, thereby increasing neuronal activity
Term
how does bradykinin change the responsiveness of nociceptors following injury
Definition
increases the activity of VR-1 receptors
Term
how does substance P change the responsiveness of nociceptors following injury
Definition
causes mast cells to release histamine, which causes vasodilation
Term
what releases substance P following tissue damage
Definition
sensory afferents
Term
once you get inflammatory soup and you've reduced the threshold by which an action potential can get fired in a nerve ending, what is the result of a littl ebit of pressure
Definition
a little bit of pressure is enough to fire action potential in pain fibers
Term
what is the purpose of inflammatory soup
Definition
protect injured tissue, promotes healing, guards against infection
Term
how does inflammatory soup promote healing
Definition
increases blood flow
Term
how does inflammatory soup guard against infection
Definition
recruits WBCs
Term
how do anti-inflammatory agents like aspirin reduce pain
Definition
by inhibiting cyclooxygenase
Term
what is cyclooxygenase
Definition
an enzyme important in the biosynthesis of prostaglandins
Term
what happens if you don’t' form prostaglandins
Definition
you don't supercharge the sensory nerves so you decrease the pain
Term
where does aspirin work
Definition
at the site of injury
Term
where do opiates work
Definition
in the CNS
Term
what happens in hyperalgesia
Definition
stimuli that don't usually cause pain are perceived as painful
Term
what causes hyperalgesia
Definition
peripheral sensitization of afferent receptors
Term
how does hyperalgesia change as tissues heal
Definition
the sensitization of peripheral nerves typically declines and pain thresholds return to preinjury levels
Term
what can happen with hyperalgesia in someone with diabetes, stroke, MS
Definition
sensitization can persist
Term
what is neuropathic pain
Definition
persistent sensitization/hyperalgesia. A chronic painful condition that is difficult to treat
Term
what are central pain pathways
Definition
pathways that convey information concerning potentially noxious stimuli to the brain
Term
what are the 2 components of central pain pathways
Definition
sensory discriminative component, affective-motivational component
Term
what does the sensory discriminative component of the central pain pathway do
Definition
signals the location and intensity of a noxious stimulus
Term
what does the affective-motivational component of the central pain pathway do
Definition
signals the unpleasant quality of the experience
Term
what pathways does the sensory discriminative component of the central pain pathway depend on
Definition
depends on pathways that target the traditional somatosensory complex
Term
what pathways does the affective motivational component of the central pain pathway depend on
Definition
depends on cortical and brainstem pathways that go to other areas of the brain (not the traditional somatosensory complex)
Term
what is the spinothalamic tract
Definition
a pathway responsible for the discriminative component of pain
Term
how do pain and temperature reach the primary sensory cortex
Definition
through the spinothalamic tract
Term
how many neurons in the spinothalamic tract
Definition
3
Term
what do we call the neurons in the spinothalamic tract
Definition
1st order, 2nd order, 3rd order neurons
Term
what is the spinothalamic tract sometimes called
Definition
anterolateral system
Term
what does the spinothalamic pathway convey
Definition
conveys pain and temperature stimuli from the body
Term
why is the spinothalamic pathway sometimes called the anterolaterarl system
Definition
because it rises up in the anterolateral part of the spinal cord
Term
aside from pain and temperature, the spinothalamic tract can carry crude sensations of what?
Definition
touch
Term
if you lose your mechanosensory pathway, could you still feel a little bit of touch?
Definition
yes, from the pain pathway
Term
where are the cell bodies of the 1st order neurons of the spinothalamic trat located
Definition
dorsal root ganglion
Term
where are the peripheral processes of the 1st order neurons of the spinothalamic tract
Definition
their peripheral processes end in free nerve ending nociceptors
Term
where are the central processes of 1st order neurons of the spinothalamic tract
Definition
their central processes enter the dorsal horn of the spinal cord
Term
where do 1st order neurons synapse on 2nd order neurons of the spinothalamic tract
Definition
dorsal horn of the spinal cord
Term
in the spinothalamic tract, what do 2nd order neurons do after being synapsed on by 1st order neurons in the dorsal horn of the spinal cord
Definition
cross the midline and ascend the spinal cord via the spinothalamic tract
Term
what order neurons cross in the spinothalamic tract
Definition
2nd order neurons
Term
in the spinothalamic tract, where do 2nd order neurons carrying pain sensation from the body synapse on 3rd order neurons
Definition
within the ventral posterior lateral nucleus of the thalamus
Term
in the spinothalamic tract, where do 3rd order neurons project to
Definition
3rd order neurons project to the somatosensory cortex via the internal capsule
Term
what do the 3rd order neurons of the spinothalmaic tract travel on to get to the somatosensory cortex?
Definition
internal capsule
Term
through what path do sensory neurons in the DRG enter the spinal cord
Definition
trhough the dorsal root
Term
what are the 2 divisions through which sensory neurons enter the dorsal root
Definition
lateral division, medial division
Term
what axons enter the dorsal root through its lateral division
Definition
a delta and C axons carrying pain and temperature information
Term
what axons enter the dorsal root through its medial division
Definition
Abeta and groups 1, 2 carrying mechanosensory information
Term
what do centrally projecting nociceptive axons do when they reach the dorsal horn?
Definition
they branch into ascending and descending collaterals called Lissauer's Tract
Term
what is the area that pain/temperature snsory nerves are in as soon as they get to the cord from the dorsal root
Definition
Lissauer's Tract
Term
what do pain/temp axons do before penetrating the gray matter of the dorsal horn
Definition
they run up and down the spinal cord for 1-2 segments
Term
in what regions of the spinal cord do spinothalamic tract 1st order neurons synapse?
Definition
Rexed's Laminae: Laminae I-V
Term
is Lissauer's tract associated with nociception or with mechanical reception?
Definition
nociception
Term
If you touch a candle with your index finger, where will that sensory information penetrate the spinal cord
Definition
C5-T1. (first enters dorsal root at C7, then takes Lissauer's Tract up or down 1 or 2 segments)
Term
What are Rexed's Laminae
Definition
nerve cell layers in the spinal cord. 10 descriptive divisions of the gray matter.
Term
what is Rexed Lamina I called
Definition
marginal zone
Term
what is Rexed Lamina II called
Definition
substantia gelatinosa
Term
what are Rexed's Laminae III-V referred to as
Definition
nucleus propius
Term
what part of Rexed's Laminae do C fibers project to
Definition
lamina 1 and 2
Term
what part of Rexed's Laminae do A delta fibers project to
Definition
lamina 1 and 5
Term
what do 2nd order neurons from lamina 1&5 do after being synapsed on by 1st order neurons
Definition
cross the cord and ascend in the spinothalamic tract
Term
describe how there are modality sensitive neurons in Rexed's Laminae
Definition
modality sensitive neurons exist in Rexed's Laminae that convey noxious and innocuous sensory information to the spinothalamic pathway.
Term
what are some types of modality sensitive neurons in Rexed Laminae
Definition
neurons sensitive to: sharp/dull/burning pain; innocuous warm and cold temps; itch; lactic acid
Term
how do 1st order neurons of the spinothalamic tract enter the spinal cord
Definition
through Lissauer's tract
Term
in spinothalamic tract, where are the 2nd order neurons that 1st order neurons synapse on
Definition
Rexed's Laminae: Laminae I-V
Term
what are the names of the Rexed's Laminae where 2nd order neurons of spinothalamic tract are synapsed on by 1st order neurons
Definition
marginal zone, substantia gelatinosa, nucleus propius
Term
which order neurons in spinothalamic tract cross over
Definition
2nd order neurons
Term
what is the destination of 2nd order neurons traveling on the spinothalamic tract
Definition
VPL of thalamus
Term
what do 2nd order neurons of spinothalamic tract do in VPL of thalamus
Definition
synapse on 3rd order neurons
Term
what do 3rd order neurons of spinothalamic tract do
Definition
project to somatic sensory cortex via internal capsule
Term
is the spinothalamic tract the sensory discriminative component or the affective-motivational component of central pain pathways to the CNS
Definition
discriminative component
Term
what mediates the affective-motivational aspect of pain
Definition
several projections arising from the spinothalamic pathway to several other cortical and brainstem regions
Term
what are the cortical and brainstem regions that receive nociceptive information that signal the unpleasant quality of pain from the spinothalamic pathway
Definition
reticular formation, parabrachial nucleus, intralaminar nuclei of the thalamus
Term
where is the parabrachial nucleus
Definition
in the pons
Term
what happens to nociception information that is projected from the spinothalamic tract to the parabrachial nucleus of the pons
Definition
it is projected to the hypothalamus and amygdala
Term
what are the hypothalamus and amygdala important for
Definition
emotion
Term
along with the hypothalamus and amygdala, where else does the parabrachial nucleus project nociception information
Definition
periaqueductal gray matter of the midbrain
Term
what is the periaqueductal gray matter of the midbrain important for
Definition
monitoring descending pain pathways to limit how much pain info can come up to our brain
Term
what happens to nociception information that is projected from the spinothalamic tract to the laminar nuclei of the thalamus
Definition
it is distributed to the frontal lobe, insula, and cingulate cortex
Term
what are the frontal lobe, insula, and cingulate cortex all involved with
Definition
emotion
Term
Here are the bottom lines concerning central pain pathways
Definition
1. Full experience of pain involves the cooperative action of extensive network of brain regions. 2. These pathways and regions are only beginning to be understood. 3. The prominent role of these networks in pain perception is evident by the fact that ablation of the sensory cortex does not eliminate chronic pain
Term
how do we know that multiple networks are involved in pain perception
Definition
ablation of the sensory cortex does not eliminate chronic pain
Term
what is brown-sequard syndrome
Definition
clinical presentation following spinal cord hemisection injury
Term
what does spinal cord hemisection result in
Definition
loss of ipsilateral mechanosensory, loss of contralateral pain and temperature sensation
Term
what carries pain and temperature information to the CNS from the face
Definition
trigeminothalamic tract
Term
how many neurons in the trigeminothalamic tract
Definition
3
Term
which order neurons in trigeminothalamic tract cross over
Definition
2nd order neurons
Term
where are the cell bodies of the 1st order neurons of the trigeminothalamic tract located
Definition
trigeminal ganglion
Term
where do the 1st order neurons of the trigeminothalamic tract project centrally
Definition
into the spinal nucleus of trigeminal in the medulla
Term
in the trigeminothalamic tract, where do 1st order neurons first enter the brainstem
Definition
pons. They then descend to the medulla
Term
in the trigeminothalamic tract, where do 1st order neurons synapse on second order neurons
Definition
spinal nucleus of trigeminal in the medulla
Term
in the trigeminothalamic tract, where do 2nd order neurons cross the midline
Definition
in the medulla
Term
in the trigeminothalamic tract, how do 2nd order neurons ascend
Definition
through the trigeminothalamic tract
Term
in the trigeminothalamic tract, where do 2nd order neurons synapse on 3rd order neurons
Definition
ventral posterior medial nucleus of the thalamus
Term
in the trigeminothalamic tract, what do 3rd order neurons do after being synapsed on by 2nd order neurons
Definition
project from the VPM to the somatic sensory cortex via the internal capsule
Term
in the trigeminothalamic tract, how do 3rd order neurons go from the thalamus to the somatic sensory corte
Definition
internal capsule
Term
does damage to the somatic sensory cortex or internal capsule affect pain and temperature sensation from ipsilateral or contralateral face
Definition
contralateral
Term
does the VPM or VPL receive nociceptive axons from body and limbs?
Definition
VPL
Term
does the VPM or VPL receive nociceptive axons from face?
Definition
VPM
Term
how do soldiers and battle or extreme athletes experience little to no pain despite physiologic demands?
Definition
our CNS has the ability to modulate how much pain can come in
Term
what experiments helped show that the CNS can modulate pain
Definition
electrical stimulation of periaqueductal gray matter produced pain relief
Term
how does the stimulation of periaqueductal gray matter produce pain relief
Definition
by activating descending pain-modulating pathways
Term
what 5 places in the brain have descending modulatory systems
Definition
somatosensory cortex, hypothalamus, periaqueductal gray matter, raphe nuclei, other nuceli in the rostral medulla
Term
where do descending pain modulating pathways project to
Definition
to neurons in the dorsal horn of the spinal cord and/or to the spinal trigeminal nucleus
Term
what do the descending pain modulating systems modulate once they have reached the dorsal horn of the spinal cord and/or the spinal trigeminal nucleus
Definition
they modulate the transmission of incoming/ascending pain signals
Term
where do serotonin neruons originate
Definition
raphe nucleus
Term
what do the descending pain modulating systems use to modulate pain
Definition
neurotransmitters
Term
what types of neurotransmitters do the descending pain modulating systems use to modulate pain
Definition
acetylcholine, norepinephrine, and opioids
Term
what do the neurotransmitters released by the descending pain modulating systems do
Definition
inhibit or facilitate incoming nociceptive information
Term
overall, what is the function of the descending pain modulating systems
Definition
balance the efficacy of nociceptive transmission
Term
are there more descending pathways to limit pain or are there more axons that bring pain signals in?
Definition
more descnding pathways to limit pain than axons that bring pain signals in
Term
what is the gate theory of pain
Definition
local interactions between mechanoreceptive afferents and neural circuits in the dorsal horn can help modulate incoming nociceptive stimuli
Term
what exactly happens in gate theory to modulate incoming nociceptive stimuli
Definition
mechanosensory Abeta axon terminals activate local circuit interneurons that inhibit incoming nociceptive stimuli
Term
when does morphine produce analgesia
Definition
when applied to regions associated with descending pain modulating pathways
Term
when were endogenous opioids discovered
Definition
1960s
Term
where are endogenous opioids
Definition
in the pain modulatory pathways
Term
what do endogenous opioids modulate
Definition
nociceptive afferents
Term
wherever we have descending pain modulating pathways, what goes with them
Definition
endogenous opiods
Term
do endogenous opioids work centrally or peripherall
Definition
in the CNS
Term
how do endogenous opioids modulate pain transmission
Definition
local circuit interneurons in the dorsal horn synapse with axon terminals of nociceptive afferents, which are also synapsing with 2nd order neurons. The interneurons release endogenous opioids to modulate the activity of the ascending 2nd order neuron. interneurons are also targets of descending pain modulating pathways.
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