Kenyon: Pain

Question 1

Do monkeys or rodents experience pain in the same way that humans do?

Answer 1

No

Question 2

A special class of primary afferent neurons with their cell bodies in the dorsal root ganglia

Answer 2

nociceptors

Question 3

Which nociceptive fibers conduct relatively slowly? Why?

Answer 3

C and A-gamma fibers; small diameter axons, small diameter cell bodies

Question 4

Normally there are no synapses in the DRG. What can happen when there is injury to post-ganglionic sympathetics?

Answer 4

these neurons will synapse with sensory neurons and cause pain :(

Question 5

Which has a higher threshold, thermoreceptors or nociceptors?

Answer 5

nociceptors!

Ex: something feels hot, then too hot, then OUCH pain!

Question 6

Stimulation of (blank) mechanoreceptors, thermoreceptors, etc. results in a non-painful sensation. It might be intense but not painful.
Stimulation of (blank) nociceptors results in pain

Answer 6

low threshold; high threshold

Question 7

What’s this?

Conduct APs faster than C fibers but slower than TVP neurons

Answer 7

A-delta fibers

Question 8

A-delta fibers are involved in which type of pain?

Answer 8

first pain

Question 9

What’s this?

Slow unmyelinated fibers

Answer 9

C fibers

Question 10

C fibers are involved in which type of pain?

Answer 10

second pain, polymodal (several kinds of painful stimuli)

Question 11

What’s this?

Relatively fast A-delta fibers mediate a sharp pain

Answer 11

first pain

Question 12

What’s this?

Relatively slow C fibers mediate a delayed, longer lasting pain

Answer 12

second pain

Question 13

What is the capsaicin receptor?

Answer 13

TRPV1

Question 14

What’s this?

A family of ion channels that have a variety of functions including temp and pain sensation

Answer 14

TRP channels

Question 15

nonselective cation channels opened by heat, low pH, and capsaicin (the hot in hot peppers).

Answer 15

capsaicin receptors

Question 16

What happens to mice without TRPV1?

Answer 16

they have reduced sensitivity to noxious stimuli

**TRPV1 channels are a target for pain therapy

Question 17

TRP channels are tightly (blank)

Answer 17

regulated

Question 18

Where do pain and temperature afferents synapse?

Answer 18

dorsal horn neurons

Question 19

Axons from the secondary neurons cross and form the (blank) to the thalamus

Answer 19

anterolateral tract

Question 20

TVP and pain/temperature are on opposite sides (blank) the medulla, and are on the same side (blank) the medulla

Answer 20

below; above

Question 21

A lesion in one side of the spinal cord will result in reduced TVP on the (blank) side and reduced pain and temperature sensation on the (blank) side.

Answer 21

same side; opposite side

Question 22

How to pain and temperature from the face enter the brainstem?

Answer 22

from the trigeminal nerve

Question 23

What happens to the axons of the face before they cross over to form the trigeminothalamic tract?

Answer 23

they descend

Question 24

Between the mid-pons and the middle medulla, pain and temperature from (blank) sides of the face are on (blank) sides of the brainstem

Answer 24

both; both

Question 25

In the brain, we separate two aspects of pain sensation. What are they?

Answer 25

1. sensory-discriminative pathway, which mediates location, intensity, and quality of the noxious stimulation 2. affective-motivational pathway which mediates unpleasantness, anxiety, fear associated with pain

Question 26

Which part of the brain is associated with the sensory-discriminative pathway?

Answer 26

somatosensory cortex

Question 27

What part of the brain is associated with the affective-motivational pathway?

Answer 27

amygdala, hypothal, periaqueductal gray anterior cingulate cortex insular cortex reticular formation

Question 28

What's this? | mediates location, intensity, and quality of noxious stimulation

Answer 28

sensory-discriminative pathway

Question 29

What's this? | mediates unpleasantness, anxiety, fear associated with pain

Answer 29

affective-motivational pathway

Question 30

Areas important in the affective-motivational pathway?

Answer 30

``` anterior cingulate cortex insular cortex reticular formation amygdala hypothalamus periaqueductal gray ```

Question 31

Is the affective-motivational pathway associated with the primary sensory cortex?

Answer 31

No!

Question 32

Some dorsal horn neurons receive input from visceral and cutaneous nociceptors. What can this cause?

Answer 32

referred pain

Question 33

In which pathway are there projections to the insula?

Answer 33

affective-motivational pathway

Question 34

Ablation of the dorsal column pathway for visceral pain can reduce pain associated with (blank)

Answer 34

visceral cancers of abdomen and pelvis

Question 35

increased sensitivity to a painful stimulus.

Answer 35

hyperalgesia

Question 36

previously nonpainful stimuli now cause pain

Answer 36

allodynia

Question 37

Hyperalgesia and allodynia can arise by (blank) and by (blank) mechanisms

Answer 37

peripheral; central

Question 38

What's this? The sensitivity of nociceptors can be adjusted in the periphery. An “inflammatory soup” of substances is released following injury. The endings of nociceptors respond by becoming more sensitive.

Answer 38

peripheral sensitization

Question 39

What are sensitizing compounds involved in peripheral sensitization?

Answer 39

``` protons arachidonic acid bradykinin histamine seratonin prostaglandins ATP adenosine nerve growth factor CGRP substance P ```

Question 40

T/F: Nociceptive neurons themselves can release sensitizing compounds

Answer 40

True...Yipes!

Question 41

Prostaglandins are potent sensitizers. What can inhibit them?

Answer 41

COX inhibitors ex: aspirin

Question 42

What's this? Changes in Spinal cord and higher centers can increase pain sensation. For example, following injury light touch will activate dorsal horn neurons that receive nociceptive input (allodynia).

Answer 42

central sensitization

Question 43

What are two transcription independent mechanisms of central sensitization?

Answer 43

“Windup” | Ca2+ influx via NMDAR and Ca2+ channels.

Question 44

Progressive increase in response by a dorsal horn neuron to repetitive stimulation.

Answer 44

windup

Question 45

What's this? | Cytokines promote transcription of COX-2 that makes prostaglandins that increase neuronal activity.

Answer 45

trx dependent mechanism of central sensitization

Question 46

Damage to the pain pathways can result in the sensation of pain after the injury has healed. What kind of pain is this?

Answer 46

neuropathic pain

Question 47

Where is pain sensation regulated?

Answer 47

several locations, including the brainstem and spinal cord

Question 48

Discuss the descending control of pain perception starting at the somatic sensory cortex and going to the dorsal horn of the spinal cord.

Answer 48

somatic sensory cortex --> amygdala and hypothalamus --> midbrain periaqueductal gray --> parabrachial nucleus, medullary reticular formation, locus coeruleus, raphe nuclei --> dorsal horm of spinal cord

Question 49

What happens when pain signals finally reach the dorsal horn of the spinal cord?

Answer 49

activity in the descending pathways inhibits nociceptive activity

Question 50

In the dorsal horn of the spinal cord, several neurotransmitters are important in inhibiting nociceptive activity. How do they do this? What neurotransmitters can you think of?

Answer 50

they activate GPCRs coupled to the inhibition of voltage-gated Ca++ channels; this will decrease the release of neurotransmitter from the C fibers

Question 51

What can Raphe nuclei do?

Answer 51

essentially, they can shut down the generation of the pain signal

Question 52

Activation of (blank) can also inhibit nociceptive activity.

Answer 52

low-threshold mechanoreceptors **esp if mom activates them

Question 53

Activation of (blank) receptors in the periaqueductal gray and in the spinal cord can reduce pain. How are these activated?

Answer 53

opioid; exogenous or endogenous opioids

Question 54

Note that reduction of pain by a placebo can be blocked by (blank), a competitive antagonist of opiate receptors. The implication is that the placebo causes the release of (blank).

Answer 54

naloxone; endorphins

Question 55

What are these? New neurotransmitters and receptors Gene silencing (siRNA) Identification and killing of nociceptors

Answer 55

new approaches to the management of pain