L17: The Medial Pain System & Limbic-Motor Interactions

Question 1

Explain the differences btw nociception & pain.

Answer 1

nociception = “sensation” -process that is associated with a noxious stimulus

pain = “conscious,” “emotional” -subjective experience associated w/ noxious stimuli

Question 2

List the 5 main functions of medial pain system

Answer 2

a. limbic & autonomic activation (indirect ALS)
b. learning & anticipation (connections with amygdala & thalamus)
c. nocifensive behavior (medial premotor areas)
d. empathy (lateral nociceptive & medial pain systems )
e. inhibition (activate PAG & ACC)

Question 3

In neuroanatomy, we learned about the anterolateral system carrying protopathic sensations (pain, temp, crude touch). The anterolateral system actually has 3 pathways, which are?

Answer 3

1 - direct anterolateral pathway –> pain, temperature, simple tactile sensations

2 - Indirect anterolateral pathways –> limbic, autonomic, endocrine & activation of pain inhibitory circuits

3 - posterior medial pathways –> visceral nociceptive info & conveys T, pain, irritation, chemical changes & stretch from visceral organs.

Question 4

List the 3 main ascending spinal pain systems and the tracts that are associated with them.

Answer 4

1 - direct anterolateral pathway: neospinothalamic tract

2 - indirect anterolateral pathways:

a. paleospinothalamic tract
b. spinoreticular tract
c. spinomesencephalic tract

3. posterior medial pathway
   
   • *these receptors have poor localization, thus the phenomenon of referred pain

Question 5

What kind of surgery can be performed for chronic, debilitating, intractable visceral pain?

Answer 5

myelotomy/cordotomy of the posterior midline.

Question 6

The major pt regarding the indirect ascending pain pathways (paleospinothalamic, spinomesencephalic, spinoreticular) is their connections support limbic/ANS activation, which is the 1st major function of medial pain system. Where are some of their projections and what impt 6 structures do they innervate?

Answer 6

-projections to RF, LC, midline & intralaminar thalamic nuclei (MITN) & PAG innervate:
1. nucleus ambiguous (breathing & HR)
2. gigantocellular RF that projects to sympathetic IML
3. parabrachial nucleus
4. PVN of hypothalamus
5. amygdala
6 -ACC

Question 7

What is the 1st major function of medial pain system?

Answer 7

Limbic/ANS activation, which is achieved by the indirect ascending pain pathways.

Question 8

Reticular formation is found thru out brainstem. What are the 4 impt nuclei of RF?

Answer 8

• raphe nucleus (5-HT)
• Locus Coerulus (NE)
• parabrachial area
• nucleus gigantocellularis

Question 9

Mesencephalic & rostral pontine RF vs caudal pontine & medullary RF have different functions.

Answer 9

Midbrain & rostral pons –> modulating forebrain activity

Caudal pons & medulla –> premotor coordination of lower somatic & visceral motor neuronal pools

Question 10

RF & PAG regulate ANS via projections to which 3 nuclei?

Answer 10

• nucleus tractus solitarus
• Dorsal motor nucleus of vagus
• IML

**will modify autonomic functions (HR, BP, etc) in response to pain

Question 11

An expt was conducted where a noxious stimulus was applied to hand. Patient was asked to “rate the unpleasantness” (the feeling of pain) and then to “attend to the location” (nociceptions). What did the results conclude about if pain and nociception are activating the same or different regions of the brain?

Answer 11

When asked to rate “unpleasantness,” the ACC & PAG (medial system) was activated.

When asked to attend to the location of the noxious stimulus, the MCC & thalamus are activated (lateral system).

Question 12

What structures are involved in the medial and lateral systems and state whether pain or nociception is involved?

Answer 12

Medial System = ACC + PAG –> feeling of pain

Lateral System = MCC + thalamus –> nociception

Question 13

The 2nd major function of the medial pain system is anticipation/learning. What is it?

Answer 13

Anticipation/learning is a form of associative learning in which a sound is associated with inflicting pain. Once, the person hears the sound, the brain is anticipating the pain stimulus. This depends on connections with amygdala & thalamus.

Question 14

The 3rd major function of the medial pain system is nocifensive behavior. Which areas in the brain initiate nocifensive behavior?

Answer 14

medial premotor areas (SMA-supplementary motor areas & Cingulate motor areas) when activated will prime motor system to initiate nocifensive behaviors.

Question 15

So far we’ve mentioned limbic/ANS activation, anticipation/learning, and nocifensive behavior as important functions of medial pain system. Another is pain empathy. Explain what this will activate.

Answer 15

seeing pain inflicted on others will activate many lateral nociceptive & medial pain systems & can evoke similar emotions.

Question 16

What is the last resort treatment for debilitating chronic pain? After the procedure, what can the patient feel?

Answer 16

Anterior cingulotomy is a last resort treatment for debilitating chronic pain. Patient will still feel the pain, but doesn’t care about it because will abolish nocifensive behavior & many limbic/autonomic responses.

Question 17

1. Limbic/ANS activation
2. anticipation/learning
3. Nocifensive behavior
4. pain empathy
   What is the last major function of the medial pain system that we talked about in class?

Answer 17

5. pain inhibition

- it is experimentally shown that stimulating medial area near motor cortex will relieve pain, and activate PAG & ACC.

Question 18

Experimentally, what do you expect when you give opiate placebo analgesia?

Answer 18

effective placebo effect activating the ACC

Question 19

Can medial pain system modify subjective experience of pain?

Answer 19

Yes, there are many functions of medial pain system that can modify subjective experience of pain (limbic/ANS activation, anticipation/learning, nocifensive behavior, pain empathy, pain inhibition)

Question 20

What is mental-stress-induced analgesia (SIA)?

Answer 20

relies on medial pain system & descending pathways, involves opiod & non-opiod mechanisms.

for ex: Pt while given noxious stimuli & asked to perform mental math (mental stress) will have increased pain tolerance.

Question 21

What occurs during central pain sensitization to chronic nociceptive input?

*Central sensitization is a condition of the nervous system that is associated with the development and maintenance of chronic pain. When central sensitization occurs, the nervous system goes through a process called “wind-up” and gets regulated in a persistent state of high reactivity.

Answer 21

• Glial cells mobilize and release calcium, glutamate and pro-inflammatory molecules
• Magnesium blockade of the NMDA receptor is released and second messenger systems enabled
• The LC becomes hyperactive, and initiates stress-related activation of other brain regions
• Subjects can begin to report the perception of pain in the absence of tissue injury