Quiz #1: Pain (6) Flashcards
What is nociception?
physiological process involved in the transduction of a noxious stimulus (one strong enough to signify tissue damage) and the conduction of impulses from the periphery to the cortex
What is pain?
Unpleasant sensory/emotional experience associated with actual/potential tissue damage
Pain vs nociception?
Nociception = neural process of encoding harmful stimuli
Pain = the subjective experience of that encoding (perception
What are nociceptors?
sensory receptors involved in pain
subset of peripheral sensory organs that respond to noxious stimuli
What are the categories of pain?
- physiological pain
- clinical (inflammatory) pain
- persistent (neuropathic) pain
What is the four parts of the nociceptor process?
- transduction
- conduction
- spinal processing
- perception
What is clinical (inflammatory) pain?
not as easily localized as physiological pain
awareness of injured area (healing and protected from reinjury)
guarding behaviors
Why is physiological pain?
sharp + easily localized
site of injury is known
“Fast pain” / “slow pain”
What is persistent (neuropathic) pain?
maladaptive (not providing adequate or appropriate adjustment to the environment or situation)
leads to behaviors that diminish quality of life
difficult to localize
What are the two types of physiological pain?
- fast pain - sharp/well-localized
- slow pain - aching or throbbing/poorly localized
How are nociceptors activated?
transduction of tissue damage into an action potential
peripheral nociceptive nerve terminal
Ca2+ channels
What is the main difference between the two types of physiological pain?
carried by different nerve fibers
fast pain - Aδ fibers (myelinated)
slow pain - C fibers (unmyelinated)
What are the types of Ca2+ channels involved in the transduction of noxious stimuli?
- Vanilloid receptor (VR1) - transduction of noxious heat
(aka capsaicin receptors or transient receptor potential vanilloid TRPV1) - Purinergic receptor (P2X2) - senses a localized increase in ATP (Bc cell contains a lot of ATP, if dies, releases it, ATP binds to purinergic receptors, produces glutamate)
What are Na+ channels in nociceptor activation?
Acid sensing ion channel (ASIC)
sensitive to the increase in H+ (aka decrease in pH)
What does the influx of calcium do the the cell?
depolarize it
release NT: glutamate
go to Aδ fibers or C fibers to show there is injury
TRUE OR FALSE
Regardless of how or which calcium channels are activated, glutamate will always be released.
TRUE
What does the influx of Na+ ions do to the cell?
depolarize it
release NT: glutamate
go to Aδ fibers or C fibers to show there is injury
What is bradykinin?
activates signaling pathways inside the cell
activates 2:
- PKC (protein kinase C)
- PKA (protein kinase A)
What do PKA and PKC do?
increase intracellular Ca2+
–> will lead to eventual released of calcium ions
What does changes/mechanical deformation of the plasma membrane do?
mechanical receptors
any time there is change in plasma membrane, will cause the release of glutamate as well
What are nociceptors found in teeth?
- Aδ fibers (thermoreceptors/mechanoreceptors)
- C fibers (polumodal chemoreceptors like H+/ATP/Bradykinin/others)
Why does the tooth hurt with heat/cold?
Activated TRPV1 –> release calcium ions –> release of glutamate –> PAIN
What is the hydrodynamic mechanism?
Thought of why mechanical changes causes pain in the tooth
odontoblasts sit in fluid-filled tubules
if those fluids move inside those tubules, odontoblasts respond, then PAIN
mechanoreceptors (changes in cell membrane due to movement of fluid)
What happens at the spinal cord?
NT is glutamate
signal from Aδ fibers/C fibers: synapse at projection neuron
release glutamate
glutamate activates AMPA receptors
What are the limits of the hydrodynamic mechanism?
does not explain why hot/cold causes tooth pain as well
What happens after glutamate is released?
nociceptor activated –> glutamate released –> pain is being transferred along the fiber –> gets to spinal cord
Whether coming from Aδ fibers or C fibers, will synapse at what?
projection neurons
What is substance P?
Substance released under certain circumstances from C fibers
more for clinical pain
What are AMPA receptors?
ligand gated Na+/K+ channels
ligand = glutamate
Na+ moves INTO projection neuron
K+ moves OUT of projection neuron
Where does the spinal cord send the signal to afterwards?
To the CNS brain
for most of body, goes to the spinal cord (spinal nerves = impulses sent to dorsal horn of the spinal cord)
for facial region, goes to the trigeminal system
What is the interneuron in the gate control theory of pain?
- innervates the projection neurons
- has some control in whether the projection neuron is activated or not
- large fiber is STIMULATORY to interneuron
- small fiber is INHIBITORY to interneuron
- interneuron INHIBITS the projection neuron
How to differentiate between touch and pain?
Gate control theory of pain
What are the two types of small fibers?
- Aδ fibers
- C fibers
What is the difference between visceral and somatic pain?
visceral:
- thorax/pelvic/abdomen
- larger receptive field
- harder to localize
- Ex. heart attack
somatic:
- periphery (arms/legs)
- smaller receptive field
- easier to localize
What is the pathway for small fibers?
Aδ fibers or C fibers –> activate projection neuron –> pain
What are large fibers?
Touch fibers (just pressure)
how we know we are being touched
What is the gate control theory of pain?
Theory of how we differentiate between touch and pain
introduces interneuron
The small fibers are ____________ (inhibitory/stimulatory) to the interneuron.
INHIBITORY
Which fiber synapse with the interneuron?
BOTH
the small AND large fibers
The large fiber is ____________ (inhibitory/stimulatory) to the interneuron.
STIMULATORY
TRUE OR FALSE
the large fiber activates the projection neurons
FALSE
the SMALL fibers (Aδ fibers or C fibers) activate the projection neurons
The interneuron is _________ (inhibitory/stimulatory) to the projection neuron.
INHIBITORY
What is the gate control theory of pain pathway for JUST touch sensation?
large fiber activated –> stimulates interneuron –> interneuron inhibits projection neuron –> NO PAIN
*just feel pressure without pain
What is the gate control theory of pain pathway for a PAINFUL touch sensation?
small fiber activated –> interneuron inhibited –> projection neuron is NOT inhibited by interneuron –> projection neuron is activated –> PAIN
What happens when CNS inhibits the pain (what is it/pathway)?
- pain is NOT felt as much
- interneuron is called inhibitory interneuron (ININ)
- neurotransmitter is released –> activates ININ –> inhibits the projection neuron to reduce pain signal
Once CNS processes that there is pain, what happens?
Descending CNS pathway
Controlling pain (pain is good, allows you to control your limitations or what you can or can not do)
What does an inhibitory interneuron (ININ) do?
reduces the pain sensation
What happens when CNS facilitates the pain (what is it/pathway)?
- when CNS enhances the pain
- interneuron is called excitatory interneuron (EXIN)
- neurotransmitter is released –> activates EXIN –> activate the projection neuron
What are opiod receptors?
Sensitive to endogenous opioids
What are endogenous opiods?
released from NT
classified as endorphins, enkephalins, or dynorphins
come from same precursor molecule: proopiomelanocortin
bind to opiod receptors
pain killers mimic these endogenous opioids
What are the classifications of opioid receptors?
- mu
- delta
- kappa
** expressed in different parts of spinal cord **
What is the general pathway of opioid receptors?
Endogenous receptors bind to opioid receptors –> inhibit the pathway of pain –> no pain
What is primary hyperalgesia?
- enhancement of normal pain pathways
- alr painful stimuli becomes MORE painful
- more sensitive to same amount of protons
- Ex. calcium flux becomes MORE calcium flux
What is hyperalgesia?
- stimuli that causes CLINICAL pain
- SAME stimuli at SAME strength cause MORE pain
- Ex. inflamed gums - normal probing does not cause too much pain but probing on inflamed gums will cause a lot of pain
What is allodynia?
- stimuli that DOES NOT cause pain all the sudden the SAME stimuli CAUSES PAIN
- Ex. getting a sunburn and a warm shower - usually warm shower feels good but sunburn causes warm shower to hurt a lot
What are the types of voltage gated Na+ channels?
- tetrodotoxin sensitive (TTX-S)
- in presence of TTX, will be inhibited
- no signal with TTX
- TTX = no action potential = no pain sensation
- tetrodotoxin resistant (TTX-R)
- signal still occurs in TTX presence
What is a NMDA receptor?
at projection neuron, glutamate is released –> activate AMPA
HOWEVER
when have INFLAMMATION, substance P is also released with glutamate from C fiber
substance P activates NMDA by removing Mg2+
sensitive to glutamate (same level of glutamate now activates AMPA and NMDA)
means more sodium flux = more pain from SAME AMOUNT of stimuli
Why is there still pain when TTX is injected into patient?
Patient has mixture of TTX-S and TTX-R Na+ channels
TTX-S are inhibited by TTX (therefore no pain)
TTX-R are NOT inhibited by TTX (therefore still have pain)
HARD TIME NUMBING PATIENT DUE TO THE RESISTANCE NA+ CHANNELS = PAIN
What is wind-up?
situation where stimuli does not normally cause pain
however, continuously give this stimuli
eventually, builds up and more and more pain is felt
each stimuli builds off each other (even if you keep stimuli at the same level)
based off of FREQUENCY of the stimuli rather than the force of the stimuli
Ex. hand slapping game (first few is okay but starts to hurt more and more)
What does substance P do?
increase IP3 –> increase Ca2+ –> removes Mg2+ from NMDA receptor
causes the same amount of stimuli to create MORE pain
