lecture 27: neurochemistry: pleasure and pain II

Question 1

What are emotions?

Answer 1

• trace back scientific studies of emotions to darwin
• people and animals in local environment
• aspects of our human behaviour (pleasure and so on) were linked to behavioural expression in animals
• e.g. facial expressions in domestic dog

Question 2

What are the ‘basic’ human emotions?

Answer 2

• happy
• sad
• fearful
• angry
• suprised
• disgusted
• ekman and freisen 1978
• emotions are always considered to be positive or negative

Question 3

What is the role of the hypothalamus in emotional responses?

Answer 3

• neural control of emotional responses to external stimuli
• externa; stimuli processed by sensory systems converge on emotional processing systems
• if the stimuli are emotionally salient, emotion systems such as the amygdala are activated
• outpts of the emotion processing systems to hypothalamic and brain stem regions activate effector cells that control the expression of physiological responses, including skeletomuscular action, autonomic nervous system activity, and hormonal release
• the figure shows some responses associated with fear

Question 4

What is a definition of emotions?

Answer 4

• an emotion constitutes an internal, central (as in central nervous system) state, which is triggered by specific stimli (extrinsic or intrinsic to the organism)
• humans show unique species typical behaviours and subjective feelings
• however, underlying states with certain fundamental properties are shared across emotions and across species (from humans to flies)

Question 5

How can you know when a human baby is experiencing pain?

Answer 5

• eye signs
  
  • quiet infants are not necessarily pain free
  • nurses need to look for subtle changes in an infants’ facial expressions - such as brow bulge or eye squeeze - to recognise discomfort in the youngest of patients
• orbital tightening
• nose bulge
• cheek bulge
• ear position
• whisker change

Question 6

What are commonly used methods for assessment of pain in newborns?

Answer 6

• premature infant pain profile (PIPP)
  
  • brow bulge
  • eye squeeze
  • nasolabial furrow
• neonatal facial coding scale (NFCS)
  
  • brow bulge
  • eye squeeze
  • nasolabial furrow
  • open lips
  • stretch mouth
  • lip purse
  • taut tongue
  • chin quiver
  • tongue protrusion
• neonatal infant pain scale (NIPS)
  
  • facial expression
• CRIES score
  
  • expression

Question 7

What is the descending pain modulation system?

Answer 7

• rostral ventromedial medulla (RVM; includes nucleus raphe magnus)
• serotonin neurons
• emotional systems generate subjective feelings and interact with physical effect parts of our body
• descending pathway from insula cortex, amygdala through PAG, rostral ventral medial medulla to spinal cord
• activated by pain
• RBMM → serotonin neurons

Question 8

What are the roles of serotonin and norepinephrine/epinephrine?

Answer 8

• diffuse transmitter system in the brain
• very small numbers of neurons that have extensive projections
• serotonin = 5HT
• midbrain → cerebral cortex and basal forebrain
• 5HT neurons in B2 nucleus (raphe magnus in medulla)
• project into spinal cord

noradrenaline/adrenaline

• diffuse transmitter systems
• locus coerulues → projects to almost entire cortex
• capability of activating/modulating entire brain networks from a very small number of neurons
• also have projections down into spinal cord

5HT modulates projections directly, norad. blocks interneurons

both of this interrupt the flow of pain related information through the dorsal horn so that the transmission of this information is inhibited

enkephalin

Question 9

What are opiates (‘narcotics’)?

Answer 9

• opium
• natural product containing two opiate alkaloids: morphine and codeine
• semi-synthetic opiate derivatives include heroin (diacetyl-morphine)
• many other semi- and fully synthetic opiates
• use as analgesic pain relieving drugs correlates with abuse liability

Question 10

What is the classification of opioid drugs?

Answer 10

• Traditional
  
  • strong
    
    • morphine, diamorphine, fentany
  • intermediate
    
    • partial agonists, mixed agonist-antagonists
  • weak
    
    • codeine
• functional
  
  • pure agonists (max. possible response)
    
    • morphine fentanyl
  • partial agonists (ceiling effect)
    
    • buprenorphine
  • agonist-antagonist
    
    • pentazocine, nalbuphine, butorphanol
  • mixed action
    
    • pethidine, tramadol
• note: naloxone “narcan” is a pure antagonist used to reverse opioid overdose

Question 11

What are the major classes of centrally acting analgesic drugs?

Answer 11

• opiods (morphine)
• NSAIDs
• anticonvulsants (gabapentin, pregabalin)
• cannabinoids (marijuana)
• TCAs (tricyclic antidepressants)
• alpha2-adrenergic agonists (clonidine)
• SNRIs (serotonin-noradrenaline reuptake inhibitors)

Question 12

What are the four major classes of endogenous opioid peptides?

Answer 12

• POMC
  
  • beta-endorphin (µ/delta)
  • endomorphin-1 (µ)
  • endomorphin-2 (µ)
• proenkephalin
  
  • met-enkephalin (delta)
    leu-enkephalin (delta)
• prodynorphin
  
  • dynorphin A (kappa)
  • dynorphin B (kappa)
• pro-orphanin Fq
  
  • orphanin FQ (orphan receptor)

Question 13

What is the relationship between fear and the amygdala?

Answer 13

• pathway activated by exogenous drugs
• endogenous agonists
• why are they there/
• basic emotion of fear
• function that is very tied up with amygdala
• amygdala is complex with wide variety of actions relating to emotions
• people with faulty amygdala often not able to recognise emotions in others
• respond to stimuli
• in rats → lab rat will have an innate fear of cats, respond to a smell that is unique to cats, even cat collar will initiate a set of response
• primates have an innate fear of long, thin things that resemble snakes
• if we encounter a snake
  
  • visual info from visual thalamus, identified by cortex
  • direct action pathways that will activate the amygdala
  • defensive behaviours activated rather rapidly
  • critical to survival
• emotional systems relate to fundamental survival mechanisms of humans and other animals

Question 14

What is the relationship between the amygdala and emotional responses to fear?

Answer 14

• output targets → fear or panic symptoms
• lateral hypothalamus → increased HR, BP, perspiration
• dorsal vagal nucleus → bradychardia, ulcers
• parabrachial nucleus → panting, respiratory distress
• basal forebrain → increased arousal, vigilance, attention
• nucleus reticularis pontis caudalis → increased startle response
• central gray area → freezing, diminished social interaction (analgesia)
• paraventricular nucleus → corticosteroid release
• amygdala has a cortical region (Lateral and basolateral amyg. three layers of pyramidal neurons, involved in fear learning), and a subcortical region (central amygdala has extensive outputs to brainstem regulating motor response to fear)

Question 15

What is fear conditioning?

Answer 15

• no fear responses → sound
• innate (unlearned) fear stimulus→ sound + shock
• learned fear stimulus → sound
• can learn fear responses, not just innate
• requires cortical part of amygdala

Question 16

What is fear modulation by context?

Answer 16

• snake
  
  • encounter in the woods vs exhibit at zoo
  • am I in danger or am I safe?
  • is it a snake (or a twig)?
  • is it moving (towards me)?
  • where is it? where am i?

Question 17

What is top-down psychological modulation of pain?

Answer 17

• cortical areas:
  
  • anterior cingulate (AC)
  • prefrontal (PFC)
  • insula
• midbrain:
  
  • periaqueductal gray
  • rostral ventromedial medulla
• can block pain related info at level of spinal cord

Question 18

What is pleasure vs pain?

Answer 18

• humans have been fascinated by the relationship between pain and pleasure for a long time

Question 19

What is motivation?

Answer 19

• exactly how bad do you want it
• very basic brain mechanisms that drive these processes

Question 20

What are reinforcers?

Answer 20

• goal-directed behaviour
  
  • behaviour controlled by representation of a goal or an understanding of a causal relationship between behaviour and attainment of a goal
• reinforcers
  
  • positive reinforcemnets (rewards, +S) increase the frequency of behaviour leading to their acquisition
  • negative reinforcers (punishes, -S) decrease the frequency of behaviour leading to their encounter and increase the frequency of behaviour leading to their avoidance

Question 21

What is morphine place preference?

Answer 21

• video tracking of conditioned place preference (CPP)
• time spent in 3 rooms during 30 pretest (A) and test (B) (n=14)
• path of one rat during a 30 minute pretest (C) and test (D) after 4 pairings of morphine and 4 pairings of saline in left and right rooms, respectively
• error bars represent SE for all figures

Question 22

What is drug self-administration?

Answer 22

• way of showing how morphine can motivate behaviour
• lever pressing experiment
• learns that if it presses lever if gets motivating effect of drug
• if you change dose it will change the number of times it presses the lever

Question 23

What is dopamine projection from ventral tegmental area (A10)?

Answer 23

• motivation v closely linked with diffuse modulatory system - dopamine
• chatecolamine
• precursor to noradrenaline
• neurons found mostly in midbrain
• reward neurons found in VTA
• project forward into basal forebrain → NAc and striatum (part of basal ganglia)
• prefrontal cortex and cingulate cortex and down into amygdala

Question 24

What are cortico-basal ganglia-thalamocortical circuits?

Answer 24

• motor circuit affected in parkinsons
• loss of dopamine affects normal motion patterns
• emotional equivalents
• VTA
• output areas and equivalent parts of thalamus
• cortical basal ganglia loops
• when this circuitry is damage there are enhanced or inhibited behaviours

Question 25

What kind of reward is food?

Answer 25

• primary (innate)
• trained that when it gets a visual cue, it presses a lever and then it reaches into a box to find its reward (food)
• recorded electrical activity in dopamine neurons over time
• time zero is where the visual cue is presented
• change in activity elicited by visual cue
• if the animal reaches into the box and there is food they fire more
• no food = no firing

Question 26

What changes with reward learning?

Answer 26

• neuronal activity
• dopamine release decreases over time - stops being a reward when it expects to find food
• not just coding purely the reward - unexpected reward = firing

Question 27

What is the relationship between dopamine and reward prediction

Answer 27

Question 28

What are placebo and nocebo?

Answer 28

• previous experience and learning produce positive or negative expectations or beliefs
• substituting a placebo (sugar pill) for an active treatment alters activity pain matrix activity in neuroimaging and produces genuine analgesia via endogenous pain modulation, this placebo analgesia is reduced or prevented by opioid antagonists
• expectations of pain (injection) also produce activity changes, but these correlate with nocebo hyperalgesia

Question 29

What are common substrates of pain and pleasure?

Answer 29

• the point is that there are substantial overlaps between regions that release opiouds and regions that are activated during placebo analgesia
• there’s correlation with the regions that release dopamine in the conext of placebo analgesia

Question 30

What are pain and pleasure as opponent processes?

Answer 30

• pain and pleasure systems in the brain that interect
• things that cause pleasure can have the effect of reducing pain and vice versa

Question 31

What is a psychobiological model of pain?

Answer 31

• cognition: attention, distraction, control, hypervigilance, catastrophizing, re-appraisal
• mood: depression, anxiety, catastrophizing
• context: beliefs, expectations, placebo
• genetics
• chemical and structural: atrophy and opioidergic/dopaminergic dysfunction?
• injury: peripheral and central sensitisation
• nociception