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BIOM30001 - Frontiers in Biomedicine > Lecture 27 - Pain & Pleasure II > Flashcards

Lecture 27 - Pain & Pleasure II Flashcards

1
Q

Describe the physiological component of emotional responses

A
  1. Emotional stimuli detected by senses
    • Eyes, ears, touch
  2. Projections to hypothalamus
  3. Projections:
    • Motor neurons
    • Autonomic nerves
      • Smooth & cardiac muscle
        • Increased blood pressure
      • Endocrine glands
        • Hormone (eg stress) release
    • Pituitary
      • Hormone release
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2
Q

Define emotion

A

*“an internal, central (ie CNS) state, which is triggered by specific stimuli, extrinsic or intrinsic to the organism *

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3
Q

How do human emotional responses differ from other species

A

Pain circuitry is conserved from flies through to humans

Humans exhibit subjective responses to emothional stimuli

  • Other animals do not do this
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4
Q

How can one tell when a human baby is experiencing pain?

A

Subtle facial expressions typical of experience of pain

Examples

  • Premature infant pain profile
    • Brow bulge
    • Eye squeeze
    • etc.
  • Open lips
  • Nasolabial furrow
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5
Q

Describe the descending pain modulation system

A
  1. Cortical areas:
    • Anterior cingulate (AC)
    • Pre-frontal cortex (PFC)
    • Insula
  2. Descending projections from
    • Rostral ventromedial medulla
    • Periaquaductal grey
  3. Release **NA **and 5-HT onto second order neuron in dorsal horn of spinal cord
    • Laminae I and II
    • NA acts on interneurons in the dorsal horn
    • 5-HT can act directly on the projection neurons (inhibition)
  4. Inhibition of second order nociceptor neuron (that projects to thalamus)
  5. Inhibition of pain
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6
Q

What are ‘narcotics’?

A

ie Opioids

“…a drug that relieves pain and induces drowsiness, stupor, or insensibility”

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7
Q

What is Opium composed of?

Where does it come from?

A
  • Morphine
  • Codeine

Naturally occuring in poppies

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8
Q

What is heroin?

A

Semi-synthetic opiate, derivate of morphine

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9
Q

Outline the various classes of opioid drugs

A

Strong

  • Diamorphine
  • Morphine
  • Fentanyl

Intermediate

  • Buprenorphine

Weak

  • Codeine

Antagonist

  • Naloxone (‘Narcan’)
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10
Q

Describe the use of opioid drugs for analgesia

A

Sites of administration:

  • PAD
  • Rexed laminae I and II
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11
Q

List the major classes of centrally acting analgesics

A
  1. Opioids
  2. NSAIDs
  3. Anti-convulsants
  4. Cannabinoids
  5. TCAs (tri-cyclic antidepressants)
  6. a2-adrenergic agonists
  7. SNRIs
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12
Q

List some endogenous opioid peptides

What is the role of endorphins?

A
  • β-endorphin
  • (Met-, Leu-) enkephalin
  • Dynorphin
  • Orphanin

These each bind different receptors and are release by neurons in different regions

Role:

  • Associated with dampening of fear through the descending pain modulatory system
  • Dynorphin and Enkephalin are released by descending neurons into the dorsal horn of the spinal cord:
    • Inhibition of pain
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13
Q

Describe the response to fear-inducing stimuli

A
  1. Fear-inducing stimulus (eg snake)
  2. Visual sensation of the snake
  3. Projections to thalamus
    1. Projections to visual cortex
    2. Projections to amygdala
      • Elicitation of defensive behaviours:
      • Projection to hypothalamus
        • Autonomic activation
          • Increased HR and BP
          • Perspiration
      • Muscle innervation
      • Projections to central grey area
        • Analgesia
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14
Q

Describe the mechanism of fear conditioning

Compare innate and learned fear responses

A

Associative learning

  • Projections from auditory cortex activated when musical tone is heard, and projections to the amygdala are strengthened when ‘pain’ stimulus is delivered at the same time
  • Now, the music tone alone activates projections form the auditory cortex to the amygdala
  • Amygdala then makes contacts with somatosensory and autonomic regions

Innate:

  • Lab rats brought up in an artifical environment have an innate fear of cats
    • Can smell the cats
  • Monkeys have innate fear of long thing things (snakes)
  • Electrical shocks incite innate fear responses

Learned:

  • Musical tones do not usually incite a fear response
  • When a music tone is experienced in conjunction with an electric shock, the mouse ‘learns’ to fear the tone when it is experienced in isolation
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15
Q

Describe the role of context in fear modulation

(Use an illustrative example)

A

Our brain has powerful systems that allow us to:

  • Learn fear towards neutral stimuli
  • Inhibit fear responses to normally fear inducing stimuli

based on the context of the stimulus

Mechanism:

  • Dampening of fear and pain responses by descending pain modulation pathways:
    • Originate in **PFC **and ACC
    • Activate PAG
    • Projections from PAG down into dorsal horn of spinal cord
    • NA and 5-HT inhibition of nociceptors

Scenarios:

  • Snake experienced in the wild
  • Snake experienced at a zoo
    • The context is processes by higher order areas in the brain
      • PFC
      • ACC
    • These interact with the ‘fear’ responses in the amygdala to attenuate fear
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16
Q

Where are the PAD and RVM located?

A

Midbrain

17
Q

Explain the concept of goal-directed behaviour

A

Goal directed behaviour:

  • Behaviour controlled by representation of a goal
  • Understanding of causal relationship between behaviour and attainment of some end
18
Q

Explain reinforcers

A

Reinforcers guide behaviour

Positive reinforcers:

  • Increase frequency of behaviour that leads to their aquisition
  • Eg
    • Ecstasy, elation, pleasure
  • Lessening of a positive reinforcer can also have a negative action

Negative reinforcers: (S-)

  • Decrease frequency of behaviour that leads to their encounter
  • Increase frequency of behaviour that leads to their avoidance
  • Eg
    • Fear, terror
  • Relief from a negative reinforcer can deliver positive reinforcement
19
Q

Describe dopamine projections in the brain

A

Dopamine diffuse modulatory system

  • Ventral tegmental area in midbrain is the most important source of dopaminergic neurons
  • These neurons project extensively around the brain to:
    • PFC
    • ACC
    • Amygdala
    • Nucleus accumbens

Dopamine basal ganglia loops:

  • Movement
  • Emotional / motivational
    • Like the loops that control activation of movement, there are also equivalent regions in the basal ganglia that are responsible for emotion and motivation
    • As with the motor loops, disturbances to this loop can result in enhancement of inhibition of behaviours
20
Q

Describe placebos and nocebos

A

Nocebo:

  • Innocuous substance administered
  • Patient expects it to be noxious

Placebo:

  • Innocuous, not analgesic
  • Patient expects it to be analgesic

Brain activity:

  • Placebo analgesic
    • Decreased activity in Cingulate gyrus, thalamus, and Insula
    • Increased activity in PFC, PAG (?) and posterior parietal cortex
    • This effect can be blocked with Naloxone
  • Nocebo:
    • Brings about genuine biological nociceptive effect
    • This can be removed with analgesics
21
Q

Outline the psychobiological model of pain

A

The follow affect the pain experience

  • Cognition
    • Attention
    • Distraction
  • Mood
    • Depression
    • Anxiety
    • Catastrophising
  • Context
    • Beliefs
    • Expectations
    • Placebos
  • Genetics
  • Chemical and structural
    • Atrophy
22
Q

Describe the diffuse modulatory systems in the brain

A

eg. 5-HT, NA modulatory systems

Few number of neurons that release 5-HT or NA that project extensively to many regions of the brain.

Have the capability of affecting many regions of the brain

23
Q

Outline the various regions of the amygdala, and what roles they perform

A
  1. Cortical region
    • Lateral amygdala
    • Basolateral amygdala
    • Involved in fear learning
  2. Central amygdala (sub-cortical)
    • Projections to brain stem, resulting in coordination of emotional responses to fear
      • Hypothalamus
        • Autonomic responses: increased heart rate, blood pressure
      • Central grey area
        • Analgesia
        • Freezing
        • Diminished social interaction
      • Basal forebrain:
        • Increased arousal
      • Paraventricular nucleus
        • Corticosteroid release
24
Q

What is the effect of fear on pain sensitivity?

A

Experiment:

  • Tail flick test in mice
    • Mouse tails put in 42° C water bath
    • Measure time it takes for mouse to remove tail
  • Performed in presence and absence of fear in mice

Results

  • Decreased pain sensitivity in mice that are experiencing fear

Explanation

  • Central amygdala projects to central grey area, which control pain
  • The activation of the amygdala during fear results in analgesia, mediated by this central grey area.
25
Q

Give an example of a situation in which there is psychological down-modulation of pain or fear responses

A

eg Encounter a snake in a cage at the zoo

  • The individual does not need to launch a fear response, as there is no real danger to the individual
  • Cortical centres (PFC, ACC) in the brain interpret the context (ie zoo, cage)
  • These higher order centres instruct the amygdala
  • Attenuation of the fear response

‘Walking wounded’

  • Context interpreted by cortical centres:
    • PFC
    • ACC
  • PFC and ACC make connections with midbrain regions:
    • PAG
    • RVM
  • PAG delivers inhibitory signals to nociceptors in the spinal cord
    • NA
    • 5-HT
  • Inhibition of pain
26
Q

Compare molecule type:

  • 5-HT
  • NA
  • Dopamine
A

5-HT: indolamine

NA: catecholamine

Dopamine: catecholamine

27
Q

Exmplain an experiment that investigated the role of dopamine in reward

A
  • Monkey receives a visual cue to pull a lever, which results in delivery of food to monkey
  • Initially, the food results in increased firing of dopaminergic neurons
    • Firing occurs when the visual cue is experienced, not when the food is received
    • The expectation of the food is the reward, not the food itself
  • After a while, there is diminished firing of the dopaminergic neurons when the food is received
  • Then, if the monkey no longer receives the food, there is inhibition of the dopaminergic neurons
28
Q

Describe an experiment that investigated motivation and morphine

A

Experiment:

  • Rat in a box with three rooms with distinct visual environments
  • The movement of the rat between these three rooms is recorded

Results

  • When there is no morphine, the rodent spends an equal amount of time in each room
  • When morphine is administered in one room, the rat spends more time in that room

Morphine self-administration

  • A rodent receives morphine/cocaine when a lever is pulled
  • The rodent quickly establish the lever pressing behaviour
  • When the dose is decreased, the rat will pull the lever at a greater rate to maintain the dose

Conclusion:

  • Morphine is not just an analgesic, but also a powerful motivator
29
Q

Describe how pain and pleasure can be thought of as opposing forces

A
  • Pleasurable stimuli, that activate the reward circuits, can lessen the experience of pain
    • and vice versa
  • If pain is inflicted during a pleasure response, the pleasure experience is diminished

BIOM30001 - Frontiers in Biomedicine (35 decks)

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