Lecture 27 - Pain & Pleasure II Flashcards Preview

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Flashcards in Lecture 27 - Pain & Pleasure II Deck (29):

Describe the physiological component of emotional responses

  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


Define emotion

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


How do human emotional responses differ from other species

Pain circuitry is conserved from flies through to humans


Humans exhibit subjective responses to emothional stimuli

  • Other animals do not do this


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

Subtle facial expressions typical of experience of pain



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


Describe the descending pain modulation system

  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



What are 'narcotics'?

ie Opioids

"...a drug that relieves pain and induces drowsiness, stupor, or insensibility"




What is Opium composed of?


Where does it come from?

  • Morphine
  • Codeine


Naturally occuring in poppies


What is heroin?

Semi-synthetic opiate, derivate of morphine


Outline the various classes of opioid drugs


  • Diamorphine
  • Morphine
  • Fentanyl


  • Buprenorphine


  • Codeine



  • Naloxone ('Narcan')


Describe the use of opioid drugs for analgesia

Sites of administration:

  • PAD
  • Rexed laminae I and II


List the major classes of centrally acting analgesics

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


List some endogenous opioid peptides


What is the role of endorphins?

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


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



  • 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


Describe the response to fear-inducing stimuli

  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


Describe the mechanism of fear conditioning

Compare innate and learned fear responses

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


  • 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


  • 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


Describe the role of context in fear modulation

(Use an illustrative example)

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



  • 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



  • 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


Where are the PAD and RVM located?



Explain the concept of goal-directed behaviour

Goal directed behaviour:

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


Explain reinforcers

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



Describe dopamine projections in the brain

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



Describe placebos and nocebos


  • Innocuous substance administered
  • Patient expects it to be noxious


  • 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


Outline the psychobiological model of pain

The follow affect the pain experience

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


Describe the diffuse modulatory systems in the brain

eg. 5-HTNA 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



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

  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


What is the effect of fear on pain sensitivity?


  • 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


  • Decreased pain sensitivity in mice that are experiencing fear


  • 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.


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

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


Compare molecule type:

  • 5-HT
  • NA
  • Dopamine

5-HT: indolamine

NA: catecholamine

Dopamine: catecholamine


Exmplain an experiment that investigated the role of dopamine in reward

  • 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


Describe an experiment that investigated motivation and morphine


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


  • 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



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


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

  • 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