Nociception

Question 1

The first synapse for vibratory neurons is ___________.

Answer 1

the caudal medulla

Question 2

The first synapse for pain neurons is ____________.

Answer 2

the posteromarginal nucleus in the dorsal horn of the spinal cord

Question 3

For the warm/cold receptors that are not painful, which are myelinated?

Answer 3

Alpha-delta (cool): lightly myelinated

C (warm): unmyelinated

Question 4

Warm receptors increase their firing rate in response to ____________.

Answer 4

increases in temperature

Question 5

Cool receptors increase their firing rate in response to ______________.

Answer 5

decreases in temperature

Question 6

There are 10x as many __________ receptors as ________ receptors.

Answer 6

cool; warm

Question 7

What is nociception?

Answer 7

Sense of pain

Question 8

What molecule does the P2X receptor sense?

Answer 8

ATP – this is important because it acts as a sensor of cytolysis

Question 9

Differentiate activators and sensitizers.

Answer 9

Activators bring a neuron to threshold and sensitizers make it easier for a neuron to get to threshold.

Question 10

Some activators and sensitizers include _____________.

Answer 10

Activators: bradykinin, 5HT

Sensitizers: substance P, prostaglandins

Question 11

Describe the triple response.

Answer 11

After an injury, you get (1) a red center and (2) an edematous wheal (from bradykinin released from tissue damage) as well as (3) a flare of pinkness around the edema due to C fibers releasing substance P.

Question 12

Bradykinin is a _____________.

Answer 12

vasodilator and inducer of vascular permeability

Question 13

What are flares around wounds?

Answer 13

Pink areas that radiate outward

Question 14

What are the qualitative differences between first pain and second pain?

Answer 14

First: tolerable, well-localized
Second: horrible, not well-localized, aching/throbbing

Question 15

__________ and __________ are products of sensitization.

Answer 15

Hyperalgesia and allodynia

Question 16

NMDA receptors can functionally become AMPA receptors by __________.

Answer 16

phosphorylation (which is accomplished by neurokinase I)

Question 17

What causes hyperalgesia after a surgery?

Answer 17

Phosphorylation of the NMDA receptors

Question 18

What neurotransmitter activates the inhibitory interneuron?

Answer 18

Enkephalin

Question 19

Activation of inhibitory interneurons does what to the pre- and postsynaptic neurons?

Answer 19

Pre: blocks calcium channels (which thence makes the neuron release fewer vesicles!)

Post: opens potassium channels, which hyperpolarizes the membrane (making the neuron require more vesicle to become activated)

Question 20

Stimulation of the ____________ leads to widespread analgesia.

Answer 20

periacqueductal gray

Question 21

Enkephalin is an ______________.

Answer 21

endogenous opiate

Question 22

What is tabes dorsalis?

Answer 22

A condition of dorsal column degeneration (that is, degeneration of A-beta axons)

Question 23

TENS stands for ___________.

Answer 23

transcutaneous electrical nerve stimulation

Question 24

The main mechanism of systemic opiates is _______________.

Answer 24

activation of the periacqueductal gray area – there are “lots of” opiate receptors in the PAG – leading to widespread analgesia

Question 25

What is the principle of giving opiates in the spine (either epidural or intrathecal [which is subarachnoid])?

Answer 25

The inhibitory interneurons are in the spine; thus, giving opiates here leads to activation of the inhibitory neurons while avoiding the systemic side effects.

Question 26

The cannabinoid receptors have been shown to interact with two systems: ________________.

Answer 26

1) opiate system 2) immune system: - decreasing proinflammatory cytokines - increasing anti-inflammatory cytokines

Question 27

Fascinatingly, the placebo effect has been shown to be blocked by _____________.

Answer 27

naloxone; this is taken as evidence that the placebo effect relies on endogenous opiates (i.e., the frontal cortex – most likely – has a connection to the periacqueductal gray matter)

Question 28

Define neuropathic pain.

Answer 28

(n.) a state in which one experiences debilitating pain in the absence of external stimuli

Question 29

There are two rare disorders that lead to extreme pain states. What are they and what causes the disorder?

Answer 29

Primary erythralgia (PE) and paroxysmal extreme pain disorder (PEPD) Both are due to gain-of-function mutations in sodium channels, making them hyperactive.

Question 30

True or false: a child who bites their lips or tongue to the point of mutilation likely has a condition caused by a gain-of-function mutation.

Answer 30

False This is a classic sign of CID (congenital ionchannelopathy disorder) – a syndrome in which a loss-of-function mutation in pain-sensing sodium channels leads to decreased ability to sense pain.

Question 31

What temperature ranges are encompassed by "cool" and "warm" receptors?

Answer 31

Cool: 10 - 37 Warm: 30 - 48

Question 32

While warm and cool receptors are best at detecting changes in temperature, they can also ____________.

Answer 32

detect absolute temperature (with cool receptors firing more frequently at lower temperatures)

Question 33

Cool receptors are found on ________ fibers, while warm receptors are found on _______ fibers.

Answer 33

A-delta; C

Question 34

We've previously learned that the spinothalamic tract synapses on the VPL in the thalamus. To what other sites does the anterolateral system synapse?

Answer 34

The reticular formation (which thence goes to the hypothalamus) in the brainstem and the mesencephalon (aka midbrain, aka periacqueductal gray matter)

Question 35

The cingulate gyrus also activates in response to painful stimuli and is thought to play a role in the _________ response to pain.

Answer 35

emotional (because the cingulate gyrus is part of the limbic system)

Question 36

Where do painful sensations in the face/head synapse?

Answer 36

In the spinal trigeminal nucleus

Question 37

On which axons do hot (greater than 43 degrees C) stimuli travel?

Answer 37

A-delta (think of Dairy queen: Cool treats, Hot eats)

Question 38

Noxiously cold stimuli travel on ________ fibers.

Answer 38

C

Question 39

Intense pressure stimuli travel on _________ fibers.

Answer 39

A-delta

Question 40

What kind of fibers are polymodal fibers? What information do they transduce?

Answer 40

C fibers; mechanical and chemical pain (chemical pain includes moieties like capsaicin and acid)

Question 41

VR-1 is activated by ______________.

Answer 41

heat and capsaicin

Question 42

True or false: C fibers conduct faster than A-delta.

Answer 42

False (A-delta are myelinated and conduct faster)

Question 43

What is the fiber basis of the first-localized-then-diffuse pain?

Answer 43

A-delta are finely localized and arrive first, then C fibers – which are diffusely spread – arrive later

Question 44

The first fibers to be blocked by anoxia are _____________.

Answer 44

the more metabolically active A-beta and A-delta

Question 45

Bradykinin is produced by cleavage of ___________.

Answer 45

kininogen

Question 46

What is the cellular basis of referred pain?

Answer 46

Visceral-organ-pain neurons synapse on the same dorsal-horn neurons as external pain, and thus internal pain manifests as diffuse, C-fiber-like pain from a limb or external feature.

Question 47

The primary neurotransmitter used at the first synapse (in the dorsal horn) is __________, which activates these channels:

Answer 47

glutamate; AMPA and NMDA

Question 48

What is the receptor mechanism of substance P?

Answer 48

It binds to the neurokinin 1 receptor and causes potassium channels to close, thus depolarizing the cell. This allows glutamate to activate NMDA channels.

Question 49

Why does CNS substance P lead to long-term sensitization?

Answer 49

Because it is not efficiently removed from the extracellular environment

Question 50

Inhibitory interneurons stem from ______ fibers.

Answer 50

A-beta

Question 51

What is the pathophysiology of tabes dorsalis?

Answer 51

Advanced syphilis leads to the destruction of A-beta fibers and consequent hyperalgesia

Question 52

True or false: stimulation of top-down analgesia leads to action potentials in the nucleus raphe magnus in the medulla.

Answer 52

True! This is the pathway of the periacqueductal gray matter

Question 53

Neurons from the nucleus raphe magnus are activated by ___________ and synapse on __________ that use enkephalin.

Answer 53

serotonin; inhibitory interneurons

Question 54

Why are opiates sometimes given intrathecally?

Answer 54

Because they block transmission of pain signals in the spinal cord without systemic effects

Question 55

What is the dominant theory behind the stress-induced analgesia phenomenon?

Answer 55

That the limbic system (cingulate gyrus) stimulates the PAG

Question 56

When C fibers are killed and A-beta afferents sprout to make new connections, __________ results.

Answer 56

allodynia