Flashcards in Lecture 17 Deck (17):
Describe the pain pathway from the spinal cord up.
Dorsal gray matter
Cross to contralateral side
Synapse @ pons
Post central gyrus
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)
What is the endogenous form of morphine?
What 5 areas of the brain do you find enkephalin and opiate receptors?
What is the enkephalin precursor?
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
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
Describe general opioid receptors.
3 families: mu, kappa, delta (depending on which splice product)
7 transmem domains
G protein mechanism
Inhibit adenylate cyclase - ↓cAMP
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
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
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
Do enkephalins have a long or short shelf life? How could this be targeted for treatment?
Degraded by proteases
If you inhibit these, you get longer life of enkephalins in the synapse - new approach for analgesia
What is one important difference between morphine and enkephalins?
Enkephalins can be localized to specific structures and pain pathways - better treatment
What is substance P?
Excitatory NT for pain
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
What is the relationship between substance P and opioids?
Enkephalin interneurons can fire onto substance P pain neurons to change transmission to the thalamus
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