Chapter 9: Chronic pain Flashcards
where does peripheral pain originate
outside the CNS
what happens when peripheral pain becomes chronic
it causes changes in CNS pain mechanisms that enhance/perpetuate the original pain
what are 3 pain conditions that start centrally
depression
anxiety
fibromyalgia
nociceptive pain pathway
series of neurons that begins with noxious stimuli and ends with the perception of pain
location of nociceptive pain pathway
starts in the periphery, enters the spinal cord, and projects to the brain
which neurons detect sensory input
primary afferent neurons
location of nociceptive pathways neuronal cell bodies
dorsal root ganglion along the spinal column
are primary afferent neurons peripheral or central
peripheral
three types of nociceptive pain pathways to the spinal cord
AB
C
Aẟ
what does the AB nociceptive pain pathway to the spinal cord detect
detects small movements, light touch, hair movement, and vibrations
C nociceptive pain pathway to the spinal cord
bare nerve endings that are only activated by noxious, mechanical, thermal, or chemical stimuli
Aẟ nociceptive pain pathways to the spinal cord
somewhere in between AB and C pathways. Senses noxious and subnoxious stimuli
what causes pain input
activation of primary afferent neurons
transduction of the nociceptive pain pathway to the spinal cord
how does transduction of pain signals begin
specialized membrane proteins along the peripheral projections of afferent neurons detect a stimulus and generate a voltage change
how is the action potential that moves along the neurons to the spinal cord generated
strong pain stimulus lowers the voltage membrane enough to activate VSSCs and trigger the action potential
how can you reduce/stop nociceptive impulse flow from primary afferent neurons into the CNS
block VSSCs with a local anesthetic
what type of neuron makes up the nociceptive pain pathways from the spine to the brain
dorsal horn neurons
function of dorsal horn neurons
receive input from primary afferent neurons and project to higher centers
location of nociceptive pain pathway from spinal cord to the brain
located entirely in the CNS
3 classes of dorsal horn neurons
-receive input
-interneurons
-project up
location of sensory/discriminatory nociceptive pain pathway from the spine to the brain
-thalamocortical pathway
-dorsal horn neurons ascend to spinothalamic tract
-thalamic neurons project to primary somatosensory cortex
which pain pathway is thought to convey the precise location of the stimulus and its intensity
thalamocortical nociceptive pain pathway from the spinal to the brain
emotional/motivational nociceptive pain pathway from spine to brain
-limbic pathway
-dorsal horn neurons ascend to the brainstem nuclei in the spinobulbar tract and then project to the thalamus and limbic regions
what is thought to be the purpose of the limbic nociceptive pathway from the spine to the brain
convey affective component that painful stimuli evokes
the combination of what two pathways results in the subjective feeling of pain
thalamocortical and limbic nociceptive pain pathways from the spine to the brain
definition of neuropathic pain
pain from damage to or dysfunction of any part of the PNS/CNS
transduction/conduction of peripheral afferent neurons in neuropathic pain states
can be hijacked so that nociceptive signaling is maintained in the absence of noxious stimuli
peripheral sensitization in neuropathic pain
neuronal damage by disease/trauma can alter electrical activity of neurons, allow cross-talk between neurons, and initiate inflammatory processes
peripheral mechanisms in neuropathic pain
-hijacked transduction/conduction in peripheral afferent neurons
-peripheral sensitization
central mechanisms in neuropathic pain
-phosphorylation of key membrane receptors/channels
-segmental central sensitization
-suprasegmental central sensitization
how does phosphorylation of key membrane receptors/channels in the dorsal horn increase synaptic efficiency
-trips a “master switch” opening the gate to the pain pathway and turning on central sensitization
what is central sensitization
perception of pain is created/amplified in the absence of pain input from the periphery
what causes segmental central sensitization
when plastic changes occur in the dorsal horn
plasticity in segmental central sensitization
activity- or use-dependent because it requires constant firing of the pain pathway in the dorsal horn
consequences of constant pain input
-exaggerated/prolonged response to noxious stimuli
-painful response to normally innocuous stimuli
suprasegmental central sensitization
plastic changes that take place in brain sites within the nociceptive pain pathway in the presence of a known peripheral cause or in the absence of a trigger (especially in the thalamus or cortex)
2 ways to accomplish suprasegmental central sensitization
-peripherally activated
-pain that originates w/o peripheral input
peripherally activated suprasegmental central sensitization
the brain “learns” from the experience of pain and decides to keep it going, enhance it, and make it permanent
conditions hypothesized to be caused by suprasegmental central sensitization (originating in the brain without evidence of peripheral pain)
fibromyalgia
physical pain sx of depression and anxiety (especially PTSD)
what type of disorder is pain with and without emotional symptoms
without - neurological
with - psychiatric
pain in fibromyalgia is linked to..
malfunctioning thalamus
physical fatigue in fibromyalgia linked to dysfunction of..
striatum and spinal cord
fibro-fog and mental fatigue linked to what malfunctioning brain circuits
PFC (especially DLPFC)
fatigue, low energy, and lack of interest in fibromyalgia may be d/t malfunctioning of what brain circuit
PFC but may also be r/t nucleus accumbens
malfunctioning brain circuit in fibromyalgia that causes disturbances in sleep/appetite
hypothalamus
malfunctioning brain areas responsible for the depressed mood of fibromyalgia
amygdala and orbital frontal index
malfunctioning area of the brain causing anxiety symptoms in fibromyalgia
amygdala
what are the main non=pain sx of fibro
fatigue
anxiety
depression
sleep disturbance
concentration problems
chronic pain may result in gray matter loss in which areas of the brain
DLPFC
thalamus
temporal cortex
periaqueductal gray
site of origin and regulation of much of the descending inhibition that projects down the spinal cord to the dorsal horn
main functions of the periaqueductal gray
-integrates input from nociceptive pain pathways and limbic structures (amygdala, limbic cortex)
-sends output to brainstem nuclei and rostroventromedial medulla to drive descending inhibitory pathways
u-opioid receptors in which areas are targets for opioid analgesics
spinal
periaqueductal gray
where does the descending spinal norepinephrine pathway originate and what does it do
-locus coeruleus
-descending NE neurons inhibit neurotransmitter release from primary afferents
where does the serotonergic descending spinal pathway originate
in the nucleus raphe magnus of the rostroventromedial medulla
how does 5HT inhibit primary afferent terminals in the descending spinal serotonergic pathway
by indirectly influencing ion channels to hyperpolarize the nerve terminal and inhibit nociceptive neurotransmitter release via postsynaptic 5HT1B and 5HT1D G-protein coupled receptors
what other pathway is serotonin a major neurotransmitter for
descending facilitation pathways to the spinal cord
what pain syndromes are SNRIs approved for
fibromyalgia
diabetic peripheral neuropathy
what does descending inhibition of the spinal serotonergic pathway accomplish
active at rest to mask perception of irrelevant nociceptive input like peristalsis and joint movement
what physiologica mechanism causes pain when there is no trauma
descending inhibition of the spinal serotonergic pathway is not working correctly to filter out irrelevant nociceptive input so you experience pain from input that is usually ignored
how do SNRIs work to treat pain
enhance the descending inhibition of the spinal serotonergic pathway so that innocuous stimuli can once again be ignored
when is descending inhibition of the spinal serotonergic pathway activated
during severe injury and in dangerous situations
what happens when descending inhibition of the spinal serotonergic pathway is activated
-release of endogenous opioid peptides, serotonin, and norepinephrine
-reduces release of nociceptive neurotransmitters in the dorsal horn
-reduces transmission of nociceptive impulses up the spinal cord to the brain
what happens when central sensitization occurs at the spinal or segmental levels
likely linked to neurotransmitters released there
what happens when central sensitization occurs at the suprasegmental level in the thalamus and cortex
likely linked to the release of mostly glutamate
what hypothetically happens in states of central sensitization
there is excessive and uneccessary ongoing nociceptive activity causing neuropathic pain
what does blocking VSCCs with ligands do
inhibits release of neurotransmitters in the dorsal horn, thalamus, and cortex to treat neuropathic pain
what are ligands used for in fibromyalgia
reduce anxiety
improve slow-wave sleep disorder
how do SNRIs work to treat fibromyalgia
reduces depression/anxiety
treats fatigue and cognitive sx
how do SNRIs decrease fibro fog
increasing dopamine in the DLPFC
what are some other strategies for decreasing fibro fog besides SNRIs
modafinil/armodafinil
NDRIs (Wellbutrin)
stimulants
2nd line treatments for fibromyalgia
-sedating drugs for depression (mirtazapine, TCAs)
-tricyclic muscle relaxant cyclobenzaprine
-sleep aids
