Week 3 - The Medial Pain System and Limbic-Motor Interactions

Question 1

between pain and nociception, which is sensory-discriminative, and which is affective-motivational?

Answer 1

pain = affective-motivational (subjective emotion)
nociception = sensory-discriminative (sensation)

Question 2

what are the 5 main functions of the medial pain system?

Answer 2

1. limbic and autonomic activation
2. learning and anticipation
3. nocifensive behavior (pain avoidance)
4. empathy
5. inhibition

Question 3

what are the 3 main ascending spinal pain systems, what they mediate/control, and their components?

Answer 3

1. direct anterior lateral pathway - pain, temperature, simple tactile sensation
   - neospinothalamic tract
2. indirect anterior lateral pathway - limbic, autonomic, endocrine, motor components of pain, activation of pain-inhibiting circuits
   - paleospinothalamic
   - spinoreticular
   - spinomesencephalic
3. posterior medial pathways - temperature, pain, irritation, chemical changes, and stretch from visceral organs

Question 4

what is the neospinothalamic tract part of? where is it found and where do its axons go?

Answer 4

direct anterior lateral pathway

• neurons are found mainly in nucleus proprius in laminae IV to VI of dorsal horn
• axons cross and ascend in lateral funiculus, synapsing on VPL thalamic nucleus, which projects to primary somatosensory cortex in postcentral gyrus

Question 5

what is the paleospinothalamic tract part of?

Answer 5

indirect anterior lateral pathway

• axons ascend bilaterally in ventrolateral spinal, synapse in reticular formation (RF) of brainstem, and midline and intralaminar thalamic nuclei (MITN)
• these nuclei project mainly to limbic cortical and subcortical regions, particularly anterior cingulate and insular cortex

Question 6

what is the spinoreticular tract part of? where is it found and where do its axons go?

Answer 6

indirect anterior lateral pathway

• axons from these cells ascend bilaterally, and terminate at 2 different levels of the RF
• -caudal RF: sends recurrent projection back to IML cell column (segmental nociceptive arc regulating sympathetic NS)
• -rostral RF and LC: innervate PVN of hypothalamus and MITN

Question 7

indirect anterior lateral pathway

• where are its neurons of origin?
• where do its axons ascend?

Answer 7

originate in dorsal horn and intermediate gray matter
-axons ascend bilaterally, with poor somatotopic organization, and make multiple synapses in brain stem and midbrain areas that access limbic and autonomic systems

Question 8

what is the spinomesencephalic tract part of? where is it found and where do its axons go?

Answer 8

indirect anterior lateral pathways

• axons from dorsal horn and intermediate gray ascend to midbrain and PAG
• some visceral info is contained in pathway, creating important clinical implications

Question 9

how do PAG neurons regulate ANS?

Answer 9

transmit ascending info to amygdala via parabrachial nucleus (PB) and send descending projections to inhibit pain sensation

Question 10

what does the posterior medial pathway do and go?

Answer 10

visceral nociceptive info arises in gut to convey signals from visceral organs

• receptors are widely scattered (poor localization) and initial afferents run w/in autonomic nerves (esp. vagus and sympathetic)
• reaches telencephalon via projections from lamina X neurons that synapse in gracile nucleus, then project to VPL and central lateral of thalamus, then to insula and anterior cingulate cortex, respectively
• this is important for referred pain

Question 11

how does “referred pain” come about clinically?

Answer 11

visceral nociceptive input being perceived as cutaneous pain from segmentally related dermatomes due to “cross-wiring”
-because not all visceral nociceptive info projects to lamina X in posteriomedial pathway; some also synapse in dorsal horn of spinoparabrachial branch of spinomesencephalic pathway

Question 12

how are nociceptive signals from the heart referred?

Answer 12

relayed through upper thoracic dorsal horn segments to parabrachial nucleus, and then to amygdala and PVN (paraventricular nucleus)

Question 13

what are myelotomy and cordotomy procedures used for?

Answer 13

for chronic intractable visceral pain
-attempting to deafferent the source of pain signal is impossible b/c of proximity of initial sensory fiber to vagus nerve or sympathetic fibers

Question 14

what are 6 structures that projections to the reticular formations, LC, MITN, and PAG innervate?

Answer 14

1. nucleus ambiguus (breathing and heart rate)
2. gigantocellular RF that projects to sympathetic IML
3. parabrachial nucleus
4. paraventricular nucleus of hypothalamus
5. amygdala
6. anterior cingulate cortex

Question 15

what does the LC integrate and give rise to?

Answer 15

integrates diverse signals and gives rise to diffuse projections throughout the brain that alert and orient it to significant events
-prime neuroendocrine and limbic systems for actions or reactions

Question 16

what does the MITN engage?

Answer 16

engages multiple cortical areas involved in pain perception and reactions to it

Question 17

what does the PAG have direct control of?

Answer 17

ANS (along with RF) via projections to NTS, DMX, and IML

• caudal pontine and medullary reticular formation –> premotor coordination of lower somatic and visceral motor neuronal pools
• mesencephalic and rostral pontien reticular formation –> modulates forebrain activity

Question 18

what is stimulated if subjects are asked to rate the unpleasantness of a noxious heat stimulus to the back of the hand?

Answer 18

strongly activate anterior ACC and PAG (medial system)

Question 19

what is stimulated if subjects are asked to attend to the location of the innocuous thermal stimulus?

Answer 19

midcingulate cortex + thalamus is activated (lateral system)

-neither ACC nor PAG is activated

Question 20

what are contingent negative variations?

Answer 20

slow negative surface potential that appears in EEG recordings several seconds after a fear inducing stimulus (such as visual cue conveying threat)
-corresponds to fear conditioning depending on connections with amygdala and thalamus

Question 21

what highlights priming of motor system to initiate nocifensive behaviors?

Answer 21

activation of the medial motor system

Question 22

what is sympathy pain? where are there major implications?

Answer 22

seeing pain inflincted on others

• activates lateral nociceptive and medial pain systems to evoke equivalent emotions
• caregivers of patients with acute/chronic pain, and psychopaths who exhibit absence of pain empathy

Question 23

what is anterior cingulotomy?

Answer 23

treatment for debilitating chronic pain (esp. in cancers)

• abolishes nocifensive and many limbic/autonomic responses, but does not alter ability to localize noxious stimulus
• can “feel” pain, but not bothered by it or care

Question 24

what do surgical lesions in ventroposterior nucleus and somatosensory cortex do?

Answer 24

impair localization of pain, but don’t reduce affective pain perceptions

Question 25

what is mental stress-induced analgesia?

Answer 25

perform rating of painful thermal stimuli to hand while being asked to perform mental arithmetic in presence of increasing levels of noise

• increased pain tolerance associated with mental and auditory stress
• decreased unpleasantness rating of painful stimuli