Exam 3 - Lecture 2 Flashcards
Where do pain signals cross over?
AWC; At the level of the cord immediately, before ascending up anterolateral/spinothalamic pathway
Characteristics of fast pain
Detailed localization, lateral pathway, Glutamate NT’s, “fast”, through A-delta fibers, nociceptors/free nerve endings
Connects pain sensor to next order ascending neuron
Glutamate NT
Glutamate is very _____ to be released, bind, and _________.
Fast; fire an action potential.
Everything about glutamate is
Fast
Fast pain gets transmitted to _________ as regular sensor signals
the same part of the brain in parietal
Characteristics of slow pain
Anterior spinothalamic tract, not all of it makes it to past thalamus, poor localization, C-fibers, thermoreceptors/heat, also uses glutamate NT’s
Paleospinothalamic tract
anterior spinothalamic/slow pain
Neospinothalamic tract
Fast pain/lateral spinothalamic tract
Neo means
new
Fast pain passes through _______ with __________
Ventrobasal complex; DCML sensory information
NT also used by slow pain pathways
CGRP: Calcitonin G-related peptide
Main NT for slow pain pathway
Substance P
How does glutamate act different in the slow pain pathway?
Its slower for some reason.
Why does slow pain have poor localization?
Less dense receptors and because not much of the pain signal actually makes it to the parietal lobe
Slow pain ascends up which pathway?
Anterior spinothalamic tract
Somatosensory areas
part of the brain that allows us to localize where pain is coming from.
Where do slow pain signals often terminate?
Brain stem or thalamus
Slow pain can impact ________ areas of brain.
Emotional.
Chronic pain can mess with your head and make you more emotional.
Emotional centers of brain are typically near diencephalon so thats why slow pain being terminated there can affect ______
Emotion
Ventrobasal complex
DCML and fast pain run through here in thalamus
Reticular formation
swath of tissue in top of brain stem where slow pain signals end up terminating
Extrapyramidal tracts
Vestibulospinal
Olivospinal: just know it exists lol
Reticulospinal
Rubrospinal
-All are CNS outputs to spinal cord
Vestibulospinal
eye fixation, muscle formation, maintain balance, descending motor pathway
Reticulospinal
maintenance of muscle tone, we have a small amount of tone at all times in our muscles.
Rubrospinal
Used by cerebellum; modulation of voluntary movement
Descending pain suppression system
Inhibitory in nature, usually activated in response to pain. Helps take the edge off for pain.
DIC
Descending inhibitory complex (pain suppression)
Primary/initial neuron of DIC
Periventricular nuclei (near 3rd ventricle) or periaqueductal gray (near cerebral aqueduct)
-Send APs towards targets further down brainstem/spinal cord
What do periventricular or periaqueductal gray neurons release when excited?
Enkephalins
2nd order neuron
Serotonergic neuron: releases serotonin
Name for serotonin
5-HT
Where is enkephalin released by 3rd order neuron?
In the dorsal horn of cord
Serotonin acts on ______
3rd neuron in DIC.
3rd order neuron is (size?)__________. What does it secrete?
Very small; enkephalin
In the cord, enkephalin is a _________ NT.
Inhibitory
Enkephalin receptors are located
on the pain sensing neuron/nociceptor, binds to it and shuts down pain sensor outside and in spinal cord.
1st order ascending pain neuron
pain receptor neuron outside spinal cord
2nd order ascending pain neuron
pain receptor relaying signal in spinal cord
Enkephalin is a ________ analog.
Morphine
Opiate receptors are actually _______.
Enkephalin receptors
Enkephalin receptors could also be thought of our bodies __________.
Endogenous opiates receptors.
Specific place in middle of pons with first synapse in DIC
Raphe magnus nucleus, aka RMN
If we were to implant electrodes into periventricular nuclei or periaqueductal gray areas, it would
Generate an inhibitory pain signal that could reduce perceived pain.
DIC is a system that could be a target for
stimulating this pathway with drugs to inhibit pain and dull perception of brain.
Enkephalin is released by enkephalin neuron on both _____________ and ___________.
Pre and post synaptic of nociceptor
Meditation/inner wellness can control
Pain and develop a high pain tolerance, by utilizing the DIC.
What are you injecting into patients in spinal cord
enkephalin receptors essentially.
DIC can affect both:
slow and fast pain
Chronic pain can _______ glutamate NTs
upregulate
Chronic pain is a mix of an increase in _________ and a decrease in _________.
Glutamate NTs; enkephalin receptors
Physical damage such as crush/cuts/acid to a nociceptor will cause it to
depolarize and feed that information into cord as painful
Lactic acid can be _________
painful
What ions with a high concentration can cause increased pain signals?
Potassium/Protons
Elevated K+ are going to do what more than normal healthy people?
Complain about pain more because they are truly more sensitive to pain than a normal person.
Serotonins nature in the cord vs in the periphery
It is painful when outside the cord in the periphery but it is inhibitory for pain inside the cord.
Prostaglandins role in pain in the periphery
Not directly painful, but they augment the pain sensation for anything thats painful. Increase pain without activating action potentials.
7 examples of things in the periphery that can increase interpretation of pain
K+, H+, 5-HT, Ach, bradykinins, prostaglandins, and histamines.
In DIC, increased serotonin results in
More pain inhibition, can treat chronic pain.
SSRI’s role in chronic pain management
Increases serotonin in spinal cord by inhibiting reuptake of serotonin, resulting in less perceived pain.
drugs examples: paxil and prozac.
Tricyclic antidepressants
Also known as TCA’s: help treat chronic pain with increased serotonin, tend to cause drowsiness and helps people with chronic pain go to sleep.
2nd order neuron in DIC
Serotonin
3rd order neuron in DIC
Enkephalin
Old antidepressant drugs that went out of favor, but are now useful for chronic pain
TCA’s due to crappy/problematic side effects like drowsiness, but the drowsiness is beneficial for sleep in chronic pain patients.
why can’t people with chronic pain sleep well?
Overactive brain from receiving pain signals.
Sensory receptors that run parallel to nociceptors to the spinal cord
Pressure receptors
Lateral inhibition
Pain signals run parallel to pressure signals to spinal cord, and activating those pressure sensors can inhibit the pain signals. Thats why we grab the body part that hurts, and why acupuncture works.
neurons next to each other can _____________ but its not fully understood how
Talk to eachother and shut down their neighbors, such with lateral inhibition.
Where does the pain get inhibited by lateral inhibition?
In the dorsal horn of the cord
Glutamate
Primary neurotransmitters with fast pain, excitatory in nature.
Nociceptor uses ______ as the neurotransmitter to excite the second order neuron in the ascending pathway
Glutamate
1st order neuron in pain sensor
actually sensing the pain in the periphery
Neurotransmitter in 1st order neuron that gets released to excite 2nd order neuron
Glutamate
How does glutamate get released from nociceptor?
Ca++ influx into cell, vesicles fuse to cell wall and dump glutamate into synapse
Primary glutamate receptor of fast pain system
AMPA-r
What type of channel are AMPA-r?
Ligand gated Ion channels
How does the AMPA-r open?
Glutamate binds to AMPA-r on second order neuron, which opens up a sodium channel for sodium to flood into and excite the second order neuron to generate an action potential.
NDMA-r - what’s the neurotransmitter for it and is it faster or slower than AMPA-r?
Glutamate receptor attached to ion channel, but takes longer than AMPA-r to work.
Whats the ion current in NDMA-r?
Calcium channels, thats why its slower.
Which of the second order neuron receptors have larger channels?
NDMA-r because its calcium
In order to actually open NDMA-r, they need 2 things:
Glutamate binding, and the neuron needs to be depolarized.
Why does NDMA-r require depolarization before the channels actually open?
Intracellular Mg++ is bound to inside of receptor channel, clogging the channel.
Once the inside of the cell becomes positive, the magnesium moves out of the way and allows calcium to flood in.
What causes the depolarization of this second order neuron?
AMPA-r allowing sodium in, or “anything” that would depolarize the neuron.
AMPA-r and NDMA-r receptors being on the same synapse allows for
more information to go through the neurons
At birth, do we have NDMA-r?
Not alot, but as we grow and mature, they get plugged into the cell walls of the nervous system.
What is the main receptor of pain transmission?
AMPA-r
What can block NDMA-r?
Ethanol, lead poisoning, ketamine, nitrous, tramadol
Why dont drunk people feel alot of pain?
Inhibition of NDMA-r
What happens if you eat paint chips off the wall in a old house?
Lead intoxication, leads to inhibition of NDMA-r
Ketamine
A dissociative, makes people unaware of what’s going on but doesn’t put them to sleep. It works by inhibiting NDMA-r through taking out calcium portion of the pathway, thus affecting perception of pain. Does not affect AMPA-r.
What drug is a terrible drug mentioned during NDMA-r? What is it classified as? But how is it supposed to help with pain?
Tramadol. It inhibits NDMA-r but not very well. It’s classified as a narcotic.
Decent SSRI, and inhibits NDMA-r. Still does not inhibit AMPA-r.
What gas inhibits NDMA-r
Nitrous
Who is tramadol best for?
Elderly patients, who are super sensitive to opiates.
What drug should not be used for after surgery but it is?
Tramadol
What can increase the amount of AMPA and NDMA-r?
Chronic pain, leading to increased sensitivity.
Other glutamate receptors not much discussed and how does it work? The ionotropic one!
Kanate, it inhibits GABA activity in the brain.
Three types of ionotropic glutamate receptors
Kanate, NDMA, AMPA
Separate category of glutamate receptors we are not discussing
Metabotropic (GPCRs), involved in signal transduction pathways in nervous system. Just be aware thats the second class of glutamate receptors.
Main class of glutamate receptors
Ionotropic
Is the calcium channel in first order nociceptor also a p-type channel?
No, but it is voltage gated.
