Chapter 12b - Pain

Question 1

What are nociceptors?

Answer 1

Nociceptors are free, branching, unmyelinated nerve endings that signal that body tissue is being damaged or is at risk of being damaged.

Question 2

How do nociceptor pathways relate to mechanoreceptor pathways?

Answer 2

The information from nociceptors takes a different path and produces different sensations. Selective activation of nociceptors can lead to conscious experience of pain.

Question 3

How do nociception and pain relate to each other?

Answer 3

Nociception: Sensory process that provides signals that trigger pain.

Pain: The feeling or perception of irritating, sore, stinging, aching, throbbing, miserable, or unbearable sensations arising from a part of the body.

Question 4

What kind of stimuli can activate nociceptors?

Answer 4

E.g., strong mechanical stimulation, extremes in temperature, oxygen deprivation, and exposure to certain chemicals.

The membranes of nociceptors contain ion channels that are activated by these types of stimuli.

Question 5

What kind of mechanisms can activate nociceptors when cells are damaged?

Answer 5

• Damaged cells can release substances, such as proteases, ATP and K+, that cause ion channels on nociceptor membranes to open
• Proteases can break down an abundant extracellular peptide, kininogen, to form bradykinin, that binds to specific receptor molecules that actrivate ionic conductances in some nociceptors
• ATP causes nociceptors to depolarize by binding directly to ATP-gated ion channels
  Elevation of extracellular [K+] directly depolarizes neuronal membranes

Question 6

What kind of mechanisms can activate nociceptors when tissue is burned?

Answer 6

Heat-sensitive ion channels in nociceptors open at a temperatore of 43ºC, which causes pain.

The sensation of warmth (37ºC - 43ºC) and scalding (43ºC+) are mediated by separate neural mechanisms.

Question 7

What causes the excruciating dull ache associated with very hard exercise?

Answer 7

1) When tissue oxygen levels do not meet oxygen demand, anaerobic metabolism is used to generate ATP.
2) As consequence of anaerobic metabolism, lactic acid is released.
3) Buildup of lactic acid leads to an excess of H+ in the extracellular fluid.
4) The H+ ions activate H+-gated ion channels on nociceptors.

Question 8

What causes the pain associated with bee stings?

Answer 8

1) The skin and connective tissue contain mast cells, a component of the immune system.
2) Mast cells can be activated by exposure to foreign substances (e.g., bee venom)
3) The mast cells release histamine
4) Histamine binds to specific cell surface receptors on nociceptors and causes membrane depolarization
5) Histamine also causes blood capillaries to become leaky, which leads to swelling and redness at the site of injury
[6) Antihistamines can reduce the pain and the swelling]

Question 9

What are the 4 types of nociceptors?

Answer 9

1) Polymodal nociceptors: Majority of nociceptors. These respond to mechanical, thermal, and chemical stimuli.
2) Mechanical nociceptors: Show selective responses to strong pressure
3) Thermal nociceptors: Show selective responses to burning heat or extreme cold
4) Chemical nociceptors: Show selective responses to histamine and other chemicals

Question 10

Where are nociceptors located?

Answer 10

They are present in most body tissues, including skin, bone, muscle, most internal organs, blood vessels, and heart.

Notably absent in the brain itself, except for the meninges.

Question 11

Where does the transduction of painful stimuli occur?

Answer 11

In the free nerve endings of unmyelinated C fibers and lightly myelinated Aδ fibers.

Question 12

What is hyperalgesia and where does it occur?

Answer 12

A reduced threshold for pain, an increased intensity of painful stimuli, or even spontaneous pain.

Primary hyperalgesia occurs within the area of damaged tissue, secondary hyperalgesia in the tissues surrounding a damaged area.

Question 13

What is inflammation?

Answer 13

When skin is damaged, a variety of substances (inflammatory soup) are released. This includes certain neurotransmitters, peptides, lipids, proteases, neurotrophins, cytokines, and chemokines, and other substances.

Together, they can trigger inflammation, which is a natural response of the body’s tissues as they attempt to eliminate injury and stimulate the healing process.

Question 14

What are prostaglandins?

Answer 14

Chemicals generated by the enzymatic breakdown of lipid membrane. They greatly increase the sensitivity of nociceptors to other stimuli, even though they do not elicit overt pain.

Question 15

What is substance P?

Answer 15

A peptide synthesized by the nociceptors themselves. Activation of one branch of a nociceptor axon can lead to the secretion of substance P by the other branches of that axon in the neighboring skin.

Substance P causes vasodilation (swelling of blood capillaries) and the release of histamine from mast cells.

One cause of secondary hyperalgesia.

Question 16

What is a CNS cause for hyperalgesia?

Answer 16

The cross-talk between the touch and pain pathways in the spinal cord.

Question 17

How do itch and pain relate to each other?

Answer 17

• Both are mediated by thin sensory axons, although they seem to be different axons.
• Both can be triggered by various types of stimuli, including chemicals and touch.
• Some pain regulating drugs and compounds can also trigger itch.
• Some signaling molecules transduce both sensations.
• They interact: pain can suppress itch.

Question 18

What are first pain and second pain?

Answer 18

Aδ and C fibers bring information to CNS at different rates because of conduction velocity differences. Skin nociceptors, therefore, produce two different perceptions of pain: sharp first pain, and duller long lasting second pain.

First pain is caused by the activation of Aδ fibers, second pain is caused by activation of C fibers.

Question 19

What is the zone of Lissauer?

Answer 19

A region of the spinal cord where the Aδ and C fibers travel through, before synapsing on cells in the outer part of the dorsal horn in the substantia gelatinosa region.

Question 20

What are the primary afferents of the pain system?

Answer 20

Aδ and C fibers.

Question 21

What is referred pain?

Answer 21

A phenomenon where a visceral nociceptor activation is perceived as a cutaneous sensation.

Classic example: Angina, where heart fails to receive sufficient oxygen, is localized to the upper chest wall and the left arm.

Question 22

What are some of the main differences between the touch and pain pathways?

Answer 22

1) Nerve endings: Touch pathway is characterized by specialized structures in the skin, the pain pathway has only free nerve endings.
2) Diameter of axons: Touch pathway is swift, using fat, myelinated Aβ fibers; pain pathway is slow, using thin, lightly myelinated Aδ fibers and unmyelinated C fibers.
3) Connections in the spinal cord: Branches of the Aβ axons terminate in the deep dorsal horn; Aδ and C fibers branch, run within the zone of Lissauer, terminate within the substantia gelatinosa.

Question 23

What is the spinothalamic pain pathway?

Answer 23

The pathway in the body from the spinal cord to the brain, transferring information about pain and temperature.

Question 24

Describe the 6 parts of the spinothalamic pathway for PAIN.

Answer 24

1) Small dorsal root axon Aδ, C
2) Dorsal column
3) Lateral spinothalamic tract
4) Medulla
5) Thalamus (intralaminar and VP nuclei)
6) Primary somatosensory cortex S1

Question 25

What are the 7 parts of the dorsal column-medial lemniscal pathway for TOUCH?

Answer 25

1) Dorsal root axon Aα, Aβ, Aδ
2) Dorsal column
3) Dorsal colum nuclei
4) Medulla
5) Medial lemniscus
6) Thalamus
7) Cerebral cortex

Question 26

What are the 3 parts of the trigeminal pain pathway?

Answer 26

1) Spinal trigeminal nucleus of the brain stem
2) Trigeminal lemniscus
3) Thalamus

Question 27

What is afferent regulation of pain?

Answer 27

Pain evoked by activity can be reduced by simultaneous activity in low-threshold mechanoreceptors (Aβ fibers).

Question 28

What is descending regulation of pains?

Answer 28

Strong emotion, stress, or stoic determination can powerfully suppress feelings of pain.

Question 29

What is the periventricular and periaqueductal gray matter (PAG)?

Answer 29

A zone of neurons that is implicated in pain suppression. Electrical stimulation of the PAG can cause profound analgesia (pain suppression).

Question 30

What are opioids?

Answer 30

Opium, its active narcotic ingredients, and their analogues (e.g., morphine, codeine, heroin), and other drugs with similar actions.

Question 31

How do opioids affect pain?

Answer 31

They produce profound analgesia when taken systemically. They bind tightly and specifically to several types of opioid receptors in the brain.

Question 32

What are endorphins?

Answer 32

Endogenous morphine-like substances. They are relatively small proteins, or peptides.

Question 33

How do endorphins affect pain?

Answer 33

Extensive systems of endorphin-containing neurons in the spinal cord and brai nstem prevent the passage of nociceptive signals through the dorsal horn and into higher levels of the brain where the perception of pain is generated.