Lecture 8 Flashcards
what are the 4 neurotrophins?
- NGF
- Brain derived neurotrophic factor (BDNF)
- N 4/5
- N 3
- These neurotrophins bind to one of 3 receptors (Trk A B or C)
how does NGF work? (increasing pain)
- In periphery: causes peripheral sensitization
- In Dorsal root ganglion: can increase substance P, CGRP, Na channels, bradykinin receptors
- In CNS: cause central sensitization
explain the biology of inflammation (simpler terms)
- inflammation is body’s response to wound
- Wounds cause bacteria to enter body
- Inflammation is how our immune system recognizes where to act
when immune system is activated, what does it bring in?
brings in macrophages, mast cells, platelets
why do histamine, serotonin, prostaglandin, ATP, etc hurt when they’re injected?
hurts when injected because they activate nociceptors
what are algogens?
- things that activate nociceptors
- Algogens released during inflammation are known as “inflammatory soup”
what are the important ions channels in the inflammatory soup?
- TTX - resistant sodium channels
- TRPV1
These ion channels cause neuron firing
what can change the number of receptors?
gene regulation
The firing of a nociceptor is dependent on:
amount of excitatory/inhibitory receptors
function of aspirin
Aspirin interferes with algogens of inflammatory soup
- works entirely in the periphery
how was aspirin discovered?
Aspirin arose from discovery that willow tree bark helps w pain
** willow bark tree is hard on stomach
difference between aspirin (ASA) and salicylic acid
ASA has same effects of salicylic acid but isn’t as hard on the stomach
what is COX?
COX: cyclooxygenase
- Turn arachidonic acid into PGH2
explain PGE2 and EP receptors
- PGE2 binds to a type of receptor called EPs
- EP receptors are found in brain, kidney, vascular smooth muscle cells, platelets, mast cells, nociceptors
how do NSAIDs work? (and what do they stop)
NSAIDs work by blocking production of PGE2 because NSAIDs are inhibitors of COX1 and COX2
- NSAIDs stop pain and inflammation but have many side effects and have ceiling effects
which inhibitors are more COX 1 / COX 2 specific?
COX1: naproxen, ibuprofen
COX2: rofecoxib, celecoxib
explain coxib controversy
- latest data suggest that coxibs may not actually reduce risk of serious GI events over standard NSAIDs
- Merck execs didn’t want to fund a study to test vioxx (associated with heart problems)
how does chemical transduction work?
conversion of energy in environment or molecule environment into neural firing
what are TRP channels?
TRP channels are expressed by sensory fibres (not all nociceptors, but they are all primary afferents)
- Sensory fibres express molecules and allow us to know what temperature our skin is
- Evolutionarily, we have TRP channels for temperature
* plants evolve ability to activate these TRP channels
which TRP channel is most activated with cold?
TRPA1
which TRP channel is most activated when skin temp reaches level of painfully hot?
TRPV1
what is capsaicin?
makes chili pepper hot
- topical cream (TRPV1 helps with pain)
what is resiniferatoxin?
lab drug
what is anandimide?
endogenous cannabis