Nociception/Pain Flashcards
What are nociceptors?
cells that respond to pain
Pain signals are carried by (same/separate) cells and pathways from mechanosensory signals (touch)
separate
The cells that mediate pain + temp terminate in what?
free nerve endings
What is congenital insensitivity to pain?
-Individuals with this disorder cannot feel pain but can feel normal touch
What is the cause of congenital insensitivity to pain?
-Due to a mutation in a Na+ channel that is specific to nociceptors
What are the 2 types of nerve fibers that detect pain and what kind of pain?
Alpha delta = sharp pain (first)
C fibers = slow dull pain (second)
do Aalpha and Abeta nerve fibers carry pain information?
no
Which afferents are the slowest for pain nerve fibers?
skinniest afferents are the slowest
What are the 3 molecules of temperature and pain?
- TRPV1- noxious heat/pain and chili peppers (capsaicin)
- TRPM8- cold and menthol
- TRPA1-pain and wasabi/mustard, carbonation
What was the experimental method for isolating the TRPV1 or capsaicin receptor?
Used cloning:
- isolated total mRNA from DRG
- introduced to tissue culture that don’t normally respond to capsaicin
- measured influx of calcium with intracellular calcium imaging
What can an isolated single mRNA generate?
-response to capsaicin (calcium ion channel) and determine receptor amino acid sequence
What is the TRPV1 receptor opened by?
This receptor is opened by heat, capsaicin, and acidification
What does knocking out TRPV1 do?
causes inability to taste chili peppers and less sensitive to hot temperatures
What happens with a knockout of TRPA1? (experiment)
- injecting formalin into the paw of a mouse
- measuring the time spent licking the paw,
- see that with knockout all phases of the pain response are decreased.
What happens during a kKO of TRPA1?
elimination of pain
What else does TRPA1 also respond to?
carbonation, CO2
What happens in an inflammatory reaction?
- Inflammatory mediators (NGF) up regulates TRPV1 activity causing channels to open at lower temperature
- cells fire at lower temp
What are inflammatory mediator cells?
NGF
What is the result/example of an inflammatory reaction?
warm shower feels hot
Where do nociceptors synapse?
- in spinal cord
- same level that they enter
How are afferent nociceptor fibers organized?
-cross midline, ascened through anteriolateral tract
What do we mean by saying that pain has descending control?
Descending fibers synapse on pain afferents and block incoming pain signals
How was the Gate Theory of Pain discovered?
In WWII, Henry Beecher noticed wounded soldiers reported little pain
What is the conclusion from the Gate Theory?
-concluded perception of pain depends on context
How is the placebo effect related to the Gate Theory?
central mecahnisms that “gate” pain
What is an example of the placebo effect?
75% of patients reported relief from post op pain by saline injection, relief was blocked by opiate receptor naloxone
How do opiates work with the gate theory of pain?
-Opiates bind to opiate receptors on nociceptor + dorsal horn cells inhibit activity
Endogenous ligands are _______
peptide NTs
What are new targets for pain relief?
-TRPV1, TRPA1, Na+ channels
