Regulation of Pain

Question 1

For homeostatic control of pain, what circuit & what nucleus are used?

Answer 1

spino-parabrachial-amygdala circuit projects pain to parabrachial nucleus in RF

Question 2

Where does the parabrachial nucleus in RF project to?

Answer 2

amygdala
PAG
hypothalamus & ventrolateral medulla
sympathetic activation

Question 3

In relation to homeostatic control of pain, what is the amygdala for?

Answer 3

emotional-affective aspects of pain: anxiety, fear conditioning, antinociception, & autonomic adjustments

Question 4

In relation to homeostatic control of pain, what is the periaqueductal gray (PAG) for?

Answer 4

defense responses & pain regulation

Question 5

In relation to homeostatic control of pain, what is teh hypothalamus & venterolateral medulla for?

Answer 5

autonomic homeostatic adjustment

Question 6

In relation to homeostatic control of pain, what is sympathetic activation for?

Answer 6

diversion of blood to vital organs, increased HR, BP & RR, glycogenolysis in liver & muscles, gluconeogenesis from a.a.s

Question 7

Where does the PAG receive input from (directly & indirectly)? What is it involved in?

Answer 7

directly from ascending spinothalamic pathways
indirectly from parabrachial nucleus
involved in defense responses & supraspinal pain regulation

Question 8

Defense responses produced by the PAG are regulated by what 5 brain structures?

Answer 8

cingulate, insula, amygdala, hypothalamus & PFC

Question 9

In the PAG, what are the two zones that produce emotional coping? Which one is for active coping and which one is for passive coping?

Answer 9

Ventrolateral zone: passive emotional coping

Lateral zone: active emotional coping

Question 10

What are the defining characteristics of the venterolateral zone? aka how will you act and what do opioids cause?

Answer 10

quiescence, immobility, fright/hyporeactivity
disengagement, withdrawal, inhibition of sympathetic activity
long lasting opioid mediated analgesia

Question 11

What are the two divisions of the lateral zone and what kind of behavior does each produce? What are the general characteristics in terms of ANS activation and opioid effects?

Answer 11

rostral: confrontational zone
caudal: defensive behavior
excitation of sympathetic system
short-lasting non-opioid mediated analgesia

Question 12

Homeostatic maintenance of physiologically acceptable pain is determined by what?
What is the pathway?
What is the central figure in the pain modulation/regulation pathway?

Answer 12

activity & sensitivity of ascending & descending pain pathways
cingulate cortex –> hypothalamus –> PAG –> reticular nuclei –> dorsal horn
PAG is central figure: responsible for stress-induced hypoalgesia

Question 13

What pathway provides negative feedback on the spinal cord?

Answer 13

descending pathways: somatosensory, cingulate, insula, PFCs regulate amygdala, hypothalamus & PAG
PAG projects to raphe & A5,7 RF nuclei
A5,7 & raphe regulate synpase b/w sensory & spinothalamic neurons

Question 14

What kind of cells make up the raphe? What are the characteristics of each?

Answer 14

serotonergic cells: stress-mediated, tonic inhibition of pain transmission
non-serotonergic cells: regulation of immediate pain, alerting & arousal; ON cells= pain transmission; OFF cells= inhibit pain via opioid mechanisms

Question 15

What neurotransmitter comes from A5, A7? What are they for?

Answer 15

NE

inhibit pain transmission via alpha2 receptors

Question 16

Opioids and cannabinoids do what so as to inhibit pain (what is their mechanism)?

Answer 16

opioid & cannabinoid action in midbrain & medulla inhibit pain by upregulating medullary raphe OFF cells

Question 17

What two agonists work to help down regulate pain perception? Via what neurotransmitter?

Answer 17

tricyclic antidepressants & NE reuptake inhibitors enhance antinociceptive effects of opioids by increasing spinal NE

Question 18

Descending ______ and _____ pathways stimulate dorsal horn _______ interneurons to inhibit spinothalamic neurons

Answer 18

serotonin; NE; opioid

Question 19

What do opioid interneurons in the dorsal horn do?

Answer 19

inhibit synaptic transmission b/w pain afferent & spinothalamic neurons
decrease substance P release
down regulate substance P neurokinin-1 receptors

Question 20

How do opiates work?

Answer 20

agonists of opioids

stimulate opioid receptors in hypothalamus, PAG & dorsal horn

Question 21

What is the gate control theory?

Answer 21

• C fibers excite pain projection neurons: directly or by inhibiting enkephalin inhibitory interneurons
• Aalpha & Abeta inhibit C pain axons by stimulating enkephalin
• pain= descending pain control pathways inhibits Cs via presynaptic inhibition

Question 22

What makes up the reappraisal-emotional matrix?

Answer 22

cingulate & insular cortex

-convergence of somatosensory, association cortex & ascending spinal pathways

Question 23

Emotional-affective modulation of pain cognition is provided by interaction b/w what structure and what cortex?

Answer 23

amygdala & PFC

Question 24

What does anticipating pain include and lead to? What is the placebo effect?

Answer 24

anticipation: cingluate & insula coordinate somatosensory features w/PFC to determine long term implications of pain; could cause anxiety
placebo: anticipated reduction of pain reinforces descending pain control from anterior cingulate, insula & dlPFC