Lecture 17 Flashcards Preview

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Flashcards in Lecture 17 Deck (17):
1

Describe the pain pathway from the spinal cord up.

SPINO-RETICULAR TRACT
DRG
Dorsal gray matter
Cross to contralateral side
Synapse @ pons
Into thalamus
Post central gyrus

2

Aside from the post-central gyrus, where else would you expect to find morphine receptors?

Periaqueductal gray matter (spino-mesencephalic pathway)
Limbic system (affective component of pain)

3

What is the endogenous form of morphine?

Enkephalins

4

What 5 areas of the brain do you find enkephalin and opiate receptors?

Substantia gelatinosa
Periaqueductal gray
Hypothalamus
Globus pallidus
Amygdala

5

What is the enkephalin precursor?

Pre-pro-enkephalin
Different tissues have different processing enzymes to get tissue specific splicing products (ex: ant vs post pituitary)
Therefore, multiple final versions of opiod peptides - each has its own receptor

6

How is enkephalin made?

@ neuron soma
Ribosomes --> golgi --> vesicles with processing enzymes
Get processed as move down the axon
Stored or released at the nerve terminal

7

Describe general opioid receptors.

3 families: mu, kappa, delta (depending on which splice product)
7 transmem domains
G protein mechanism
Inhibit adenylate cyclase - ↓cAMP

8

What is the mechanism by which enkephalin-containing neurons work?

Release enkephalins onto excitatory neurons
↓Ca2+ influx - harder to reach threshold
Decreases excitatory NT release
Ex: if the excitatory neuron is a pain neuron, opioids will decrease the release of pain stimulating NTs

9

Talk about the similarities and differences between mu, kappa, and delta opioid receptor function.

All underlie/contribute to analgesia = inability to feel pain
- Mu contributes most
Kappa - level of spinal cord

10

Why do opioids have addiction parallels?

Chronic exposure to opioids --> ↑# receptors
Aka need more opiates to get same response
Also explains the withdrawl you get with sudden removal

11

Do enkephalins have a long or short shelf life? How could this be targeted for treatment?

SHORT!
Degraded by proteases
- Neprilysin
- Aminopeptidase
If you inhibit these, you get longer life of enkephalins in the synapse - new approach for analgesia

12

What is one important difference between morphine and enkephalins?

Enkephalins can be localized to specific structures and pain pathways - better treatment

13

What is substance P?

Excitatory NT for pain

14

Where are substance P receptors? What changes do you see if the incoming neuron is cut?

Skin --> DRG --> dorsal horn
Lesion: ↑SP receptors
Leads to hypersensitivity aka HUGE pain

15

What is the relationship between substance P and opioids?

Enkephalin interneurons can fire onto substance P pain neurons to change transmission to the thalamus

16

Compare/contrast classical vs peptide NTs.

Classic - synthesized at terminal, ready supply at the terminal in part due to reuptake methods
Peptide - make at soma ribosomes, more complex synthesis and transport, no reuptake

17

If both classic and peptide NTs exist at the same synapse, how can one be released alone?

Depends on the speed of depolarization spikes:
- Slower = more specific, only release classic NT
- Faster = release everything
- Middle range will be a mix of the 2