Pain System 2 Flashcards
(38 cards)
What does damaged tissue or inflammation release?
NGF, bradykinin, serotonin, ATP, histamine, prostaglandins, H+, K+, cytokines (IL6 and IL1beta, TNFalpha)
(inflammatory soup)
Describe how the chemical sensitization of nociceptors occurs.
- damaged tissue or inflammation releases inflammatory soup
- inflammatory soup sensitizes the nociceptor
- nociceptor releases CGRP and Substance P
- vasodilation occurs
“backwards release” (ask someone to explain)
What are TRP channels?
variety of ligand gated ion channels activated at different temperatures
What kind of neurons can TRPV1 be found on? What are they activated by? At what temperature are they activated?
- on small nociceptive neurons
- activated by: capsaicin, moderate thermal stimuli, H+ ions
- temperature: 43 degrees celcius
Which channels do chili peppers activate?
TRPV1
What kind of neurons can TRPV2 be found on? What are they activated by (temperature) ?
- on A-delta cells (to lamina I)
- activated by intense noxious heat >52 degree celcius
At what temperature are TRPM8 receptors activated? What are they activated by?
- cold/cool temperatures –> 8-22 degree celcius
- activated by menthol and icilin
Which substance increases sensitivity of all TRP channels?
bradykinin
label the diagram on slide 7.
flare, mechanical hyperalgesia
When inflammatory factors are release at an injury, an area of ____________________ develops around the original injury.
hyperalgesia
excitation of which type of pain fiber causes release of substance P and CGRP? Where are they released from?
- C-fiber
- released from sensory nerve endings
What are the effects of the release of substance P and CGRP?
- excite other C-fibers
- axon reflex
- vasodilation (redness)
- extravasation of plasma proteins (add to inflammatory soup)
- oedema (swelling)
- migraine pain
Provide an overview on how neurogenic inflammation can cause sensitization of sensory nerve fibers.
DETAILS:
- prostaglandin sensitizes TRP channels via PKA –> phosphorylate Na+ channel –> TRP channel open at lower temperature threshold –> generate more APs
- bradykinin sensitizes TRP channels –> reduce threshold for activation –> increased output to a given stimulus
OVERVIEW:
1. CGRP and substance P stimulate mast cell
2. mast cell release histamine
3. bradykinin and prostaglandin sensitize the axon
4. axon further releases CGRP and substance P to stimulate blood vessel
If pain signals tissue damage, why do we have endogenous analgesic mechanisms? What substance play a role in the analgesia?
- central mechanisms that suppress pain have a significant survival value
- endogenous opioids (enkephalin, dynorphin, endorphin, endomorphin) dampen pain signals
Where are pain signals modified in the descending top down inhibitory pain path?
- PAG
- RVM
What mechanism hold the descending analgesic pathways in check so that we can feel pain?
tonic GABAergic inhibition in RVM and PAG
draw the descending analgesic pathway from amygdala to spinal opioid INs.
slide 12
What is the prototypical substance for analgesia
opioids
What are the 3 endogenous opioids? What are the 3 pro-hormones?
- endogenous opioids: endorphin, dynorphin, enkephalin
- pro-hormones: POMC, prodynorphin, proenkephalin
What are the 3 MAIN endogenous opioid receptor types?
mu, kappa, delta
What were the initial opioid receptor types identified?
mu, kappa, sigma
Which opioid receptor type is bound by enkephalins? endorphins?
- delta bound by enkephalins
- epsilon bound by endorphins
What is the mechanism of action of opioid receptors?
- GPCR
- inhibit adenylyl cyclase
- open K+ channels
- hyperpolarization
Which opioid receptor is most widely expressed?
mu opioid receptors
