lecture 15 Flashcards
Opioids inhib _ pathways and activate _ pathways
GABA receptors
inhib ascending pathways
activate descending pain relief pathways
a delta fibers
_ Adelta - low mechanical threshold
high heat threshold
Type 1 a delta
_ a delta - low heat threshold
- high mechanical
Type 2
A delta fibers
Type 1 _ stimuli
Type 2 _
Type 1 mechanical stimuli
Type 2 - heat
type A and C fibers are polymodal meaning
sense heat and mechanical stimmuli
C- dull burning poorly localized
Adelta - sharp
how does nociceptor signaling work
molecular sense of various stimuli
local depolarization and produces AP
mechanosensitive senors have been around a long time _ billion years
3.8 billion
_ mechano receptor
this is what we are causing pain because of these receptors
TRPV1
inflammation and nociceptive pain - related
how
Inflammation is why we have pain
That’s why we like anti-inflamm inside of opiods
cells release PG, substance P, TNFa ILs interacting with receptors and facilitate the transmission of pain signals
tissue injury can lead to sensitization of the pain response
how
inflammation makes it hurt more
Hyperalgesia - if someone is injury even a little touch can hurt it
Allodynia - something that doesn’t cause pain causes pain for some reason
a single neuron might receive multiple different APs but whether this happens is afftected by things like _ _ _
number and types of postsynaptic rececptors
synchrony and frequency of incoming signals - could be additive
pre or post synaptic
hyperpolarization diminishes Ca++ influx and NT release
depolarization enhances Ca++ influx and NT release
pre
pre or post
hyperpolarization diminished opening of Na channels and reinitiation
depolarisation enhances opening of Na channels and reinitiation of APs
post
4 endogenous opioids
Pro-opiomelanocortin peptides
pro-enkephalin peptides
prodynorphin
endomorphones
all have different receptors
beta endorphin - binds to mu receptor
3 important opioid receptors
Mu, kappa, delta
the are all _ receptors
g protein coupled
widely distrubted in CNS
activate G alpha -inhib
_ is the natural agonist of the mu receptor
beta-endorphin
met-enkephalin and leu-enkephalin are the natural agonists of the _ opioid receptor
delta
dynorphin A, B and alpha/beta neo-endorphin are agonist of the _ opioid receptor
kappa
how do opioids work?
g protein coupled alphainhib receptors
Galpha inhib and G beta and Ggamma
they dont act as blockers
they make it more difficult to send synapses
Galpha Inhib - inhib of adenylate cyclase, reduced cAMP, reduce PKA, reduction of Ca++ entry from voltage sensitive Ca++ channels
GbetaGgamma - potassium channel - hyperpolarize - make K get outside easier
opioids
postsynaptically, hyperpolarization will diminish _
presynatically, Ca is required to NT release and inhib of the Ca channel and hyperpolarization will each diminish Ca entry, thus will inhib synaptic transmission by _
postsynaptically - hyperpolarization diminish generation of AP
presynaptically - inhibit transmission by reducing NT release
which receptors are not located in the midbrain
delta - might be new target to eliminate constipation/death
3 forms of Mu receptors, _ and _ are physio important
found in periaqueductal gray region, superficial dorsal horn of spinal cord. - MAINLY PRESYNATPIC
majority of analgesic drugs act at Mu
mu 1 and mu 2 important
are endogenous opioids were attenuating responses to pain
not sure but when give antagonist
it does not seem to modify base-line pain responses
sites of action of opioids
_ of ascending pathway of pain inhibition
inhibit the ascending pathway to the brain - inhib excitatory NT release
