Pain Flashcards
where does pain transmission and processing occur
Peripheral - at site of injury
Central - spinal dorsal horn; midbrain and cortex
Pathway of pain transmission
nociceptor -> DRG -> spinal cord -> processed -> relayed to brain
What are nociceptive fibers
nerve fibers located in skin and deep tissue that detect pain (not called pain until brain registers it as pain)
Two types of nociceptive fibers
A-delta and C-fibers
A-delta fibers
myelinated, fast conducting, involved in 1st pain sensation
C-fibers
non-myelinated, slower conducting, involved in 2nd/continuous pain sensation
Do A-delta and C-fibers go to the brain?
NO. Only located in periphery. Cell bodies located in DRG
Pain travels through _____ and causes the release of _____ in the _______
- nociceptive fibers
- neurotransmitters
- spinal cord
Primary neurotransmitters released into the spinal cord upon activation of nociceptive fibers
Glutamate and Substance P
What does NT release activate
projection neurons of spinal cord
Is glutamate excitatory or inhibitory
excitatory
Main neuronal pathway involved in nociceptive transmission from spinal cord to brain
spinothalamic pathway
where do projection neurons from spinal cord send information
to the brain
Pathway of pain processing in the brain
Ascending pathway: signal goes to primary somatic sensory cortex -> homunculous, lets the brain know where pain is coming from –> projection neurons stimulate specific parts of the brain.
what is the primary sensory cortex involved in
awareness of pain
what is the amygdala involved in
affective components of pain (emotional aspect)
what part of the brain is constantly activated in chronic pain
the amydala
the descending pain pathway is also known as the
bulbospinal pathway
The descending patheway consists of several synaptic connections where in brain (2)
midbrain and brainstem
prominent NT of descending pathway (2)
NE and 5HT
What is the mechanism by which you can inhibit pain
descending pathway
where are NT and 5HT released
spinal cord
descending pathway
cell bodies in brain release NE and 5HT into spinal cord –> make synaptic connection with interneuron –> interneuron synapses with projection neuron and releases NE and enkephalin –> this inhibits projection neuron –> stops pain transmission
NT with inhibitory effect
NE, 5HT, Enkephalin
Nociception
physiological perception of pain
hyperalgesia
enhanced sensitivity to painful stimuli
allodynia
enhanced sensitivity to non-painful stimuli
What causes peripheral sensitization
A-delta and C-fibers
What causes central sensitization
neurons in spinal cord
peripheral sensitization pathway
- tissue damage
- prostaglandins (PG) and bradykinin )BK) released
- this stimulates release of substance P from local fibers –> causes MORE release of PG, BK, histamine, 5HT, etc.
- Leads to sensitization of nociceptive fibers: sensitized fibers transmit more intense messages to spinal cord; fire multiple AP; can contribute to primary hyperalgesia
central sensitization pathway
- projection neurons sensitized when large amts of glutamate and substance P constantly released.
- sensitization of neurons in the spinal dorsal horn magnify pain signal to brain
what receptors are believed to play a role in central sensitization
NMDA
Can you have central sensitization without first having peripheral sensitization
No
What lasts longer: central or peripheral sensitization
central
does central sensitization always occur?
No - depends on severity of injury
Primary and secondary hyperalgesia are due to central sensitization
True
What is neurokinin receptor 1 (NK1r)
player in central sensitization
activated by substance P
What do interneurons release
Enkephalin and NE
Describe the tissue inflammation pathway
Injury -> PLA2 activation leads to increase in AA -> COX and AA released -> increases PG release -> increases PG -> terminal sensitization and pro-inflammation
What to block to treat pain
block enzymes that convert AA to PG –> COX 1 and 2
Does COX 1 or 2 have minimal constitutive activity
COX 2
Inhibitors of Cox 1 and 2
Acetylsalacylic Acid (Aspirin) Ibuprofen (Advil) Naproxen (Aleve) Ketoprofen Indomethacin Ketorolac (Toradol) Meloxicam (Mobic)
NSAIDs with LOW potency and FAST elimination
Acetylsalacylic Acid (Aspirin) Ibuprofen
NSAIDs with INTERMEDIATE potency and INTERMEDIATE elimination
Naproxen (Aleve)
NSAIDs with HIGH potency and FAST elimination
Ketoprofen
Indomethacin
Ketorolac
NSAIDs with HIGH potency and SLOW elimination
Meloxicam
Which NSAID is most selective for COX 2
Meloxicam
Selective COX-2 inhibitors
Celecoxib (Celebrex)
Valdecoxib (Bextra) -> off market
Rofecoxib (Vioxx) -> off market
COX 1 and 2 inhibitors SE profile
Lung: can exacerbate asthma sx (esp aspirin)
Stomach: can induce ulcers and stomach bleeds (mainly COX1 property)
Platelets: inhibits platelet aggregation (good for pt at risk for clots)
Anti-coagulant properties -> can be good or bad
Selective Cox 2 inhibitors SE profile
just as effective as COX1/2 inhibitors in reducing pain
reduced risk of ulcers and modest decrease in stomach bleeds
no effect on platelet aggregation
no long term use risk
Para-aetylaminopenol
Acetaminophen (Tylenol)
Is Tylenol an NSAID
NO! It is an analgesic/antipyertic
What does acetominophen increase?
endogenous NT
What can disable acetominophens anti-inflammatory properties
peroxidases
