Lecture 27 - Pain & Pleasure II Flashcards
Describe the physiological component of emotional responses
- Emotional stimuli detected by senses
- Eyes, ears, touch
- Projections to hypothalamus
- Projections:
- Motor neurons
- Autonomic nerves
- Smooth & cardiac muscle
- Increased blood pressure
- Endocrine glands
- Hormone (eg stress) release
- Smooth & cardiac muscle
- 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
Examples
- Premature infant pain profile
- Brow bulge
- Eye squeeze
- etc.
- Open lips
- Nasolabial furrow
Describe the descending pain modulation system
- Cortical areas:
- Anterior cingulate (AC)
- Pre-frontal cortex (PFC)
- Insula
- Descending projections from
- Rostral ventromedial medulla
- Periaquaductal grey
- 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)
- Inhibition of second order nociceptor neuron (that projects to thalamus)
- 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
Strong
- Diamorphine
- Morphine
- Fentanyl
Intermediate
- Buprenorphine
Weak
- Codeine
Antagonist
- 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
- Opioids
- NSAIDs
- Anti-convulsants
- Cannabinoids
- TCAs (tri-cyclic antidepressants)
- a2-adrenergic agonists
- 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
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
Describe the response to fear-inducing stimuli
- Fear-inducing stimulus (eg snake)
- Visual sensation of the snake
- Projections to thalamus
- Projections to visual cortex
-
Projections to amygdala
- Elicitation of defensive behaviours:
- Projection to hypothalamus
- Autonomic activation
- Increased HR and BP
- Perspiration
- Autonomic activation
- 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
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
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
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
- The context is processes by higher order areas in the brain
Where are the PAD and RVM located?
Midbrain
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
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
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-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
Outline the various regions of the amygdala, and what roles they perform
- Cortical region
- Lateral amygdala
- Basolateral amygdala
- Involved in fear learning
- 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
- Hypothalamus
- Projections to brain stem, resulting in coordination of emotional responses to fear
What is the effect of fear on pain sensitivity?
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.
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
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
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
