Nociception/Pain

Question 1

What are nociceptors?

Answer 1

cells that respond to pain

Question 2

Pain signals are carried by (same/separate) cells and pathways from mechanosensory signals (touch)

Answer 2

separate

Question 3

The cells that mediate pain + temp terminate in what?

Answer 3

free nerve endings

Question 4

What is congenital insensitivity to pain?

Answer 4

-Individuals with this disorder cannot feel pain but can feel normal touch

Question 5

What is the cause of congenital insensitivity to pain?

Answer 5

-Due to a mutation in a Na+ channel that is specific to nociceptors

Question 6

What are the 2 types of nerve fibers that detect pain and what kind of pain?

Answer 6

Alpha delta = sharp pain (first)

C fibers = slow dull pain (second)

Question 7

do Aalpha and Abeta nerve fibers carry pain information?

Answer 7

no

Question 8

Which afferents are the slowest for pain nerve fibers?

Answer 8

skinniest afferents are the slowest

Question 9

What are the 3 molecules of temperature and pain?

Answer 9

1. TRPV1- noxious heat/pain and chili peppers (capsaicin)
2. TRPM8- cold and menthol
3. TRPA1-pain and wasabi/mustard, carbonation

Question 10

What was the experimental method for isolating the TRPV1 or capsaicin receptor?

Answer 10

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

Question 11

What can an isolated single mRNA generate?

Answer 11

-response to capsaicin (calcium ion channel) and determine receptor amino acid sequence

Question 12

What is the TRPV1 receptor opened by?

Answer 12

This receptor is opened by heat, capsaicin, and acidification

Question 13

What does knocking out TRPV1 do?

Answer 13

causes inability to taste chili peppers and less sensitive to hot temperatures

Question 14

What happens with a knockout of TRPA1? (experiment)

Answer 14

• 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.

Question 15

What happens during a kKO of TRPA1?

Answer 15

elimination of pain

Question 16

What else does TRPA1 also respond to?

Answer 16

carbonation, CO2

Question 17

What happens in an inflammatory reaction?

Answer 17

• Inflammatory mediators (NGF) up regulates TRPV1 activity causing channels to open at lower temperature
• cells fire at lower temp

Question 18

What are inflammatory mediator cells?

Answer 18

NGF

Question 19

What is the result/example of an inflammatory reaction?

Answer 19

warm shower feels hot

Question 20

Where do nociceptors synapse?

Answer 20

• in spinal cord

- same level that they enter

Question 21

How are afferent nociceptor fibers organized?

Answer 21

-cross midline, ascened through anteriolateral tract

Question 22

What do we mean by saying that pain has descending control?

Answer 22

Descending fibers synapse on pain afferents and block incoming pain signals

Question 23

How was the Gate Theory of Pain discovered?

Answer 23

In WWII, Henry Beecher noticed wounded soldiers reported little pain

Question 24

What is the conclusion from the Gate Theory?

Answer 24

-concluded perception of pain depends on context

Question 25

How is the placebo effect related to the Gate Theory?

Answer 25

central mecahnisms that “gate” pain

Question 26

What is an example of the placebo effect?

Answer 26

75% of patients reported relief from post op pain by saline injection, relief was blocked by opiate receptor naloxone

Question 27

How do opiates work with the gate theory of pain?

Answer 27

-Opiates bind to opiate receptors on nociceptor + dorsal horn cells inhibit activity

Question 28

Endogenous ligands are _______

Answer 28

peptide NTs

Question 29

What are new targets for pain relief?

Answer 29

-TRPV1, TRPA1, Na+ channels