Case 2 - Pain

Question 1

What aspects does CBT address?

Answer 1

• Cognitive sources of pain
• Emotional sources of pain
• Physiological sources of pain

Question 2

What is the definition of addiction?

What are the most commonly abused drugs?

Answer 2

Compulsive engagement in rewarding stimuli, despite adverse consequences

Alcohol, opioids, and cocaine

Question 3

Define these terms:

• Drug abuse
• Drug dependence (Physical)
• Drug dependence (psychological)
• Drug sensitisation
• Tolerance

What does detoxification do to tolerance?

Answer 3

• Substance used in a manner that doesnt conform to social norms
• Adaptive state associated with withdrawal syndome on cessation of the drug
• Acquiring and using the drug becomes a strong motivator of behaviour and use.
• Escalating effect of the drug due to repeated administration at a given dose
• Dminisheing effect of the drug due to repeated dosing.

Detox removes tolerance, so the drug level must be reduced to avoid overdose

Question 4

What are the factors in DSM V which define a substance use disorder?

How many of these symptoms denote a severe substance use disorder?

Answer 4

• Tolerance
• Withdrawal symptoms
• Continuation despite negative personal consequences
• Using greater amounts, or using for a longer period than intended
• Persistent desire for the drug
• Are they stopping or reducing important activites?

6-7

Question 5

1. Which system in the brain is important for drug addiction?
2. What is the effect of drugs on this area?

Answer 5

1. Mesolimbic dopaminergic system
2. Increases DA here

Question 6

Where is the origin of the mesolimbic dopaminergic system?

Identify which number it is on the diagram?

Where does it project to?

Answer 6

Ventral tegmental area

Dashed line on number 2 pathway

Nucleus accumbens & prefrontal cortex

Question 7

What does increased drug sensitisation lead to in:

1. Nucleus accumbens

Answer 7

1. increased DA outflow from the NA

Question 8

What are the physiological effects of drug withdrawal on:

1. Nucleus accumbens

Answer 8

1. Reduction in DA outflow from NA – mediates rewarding effects

Question 9

What is the correlation between the following receptor levels and drug intake?

• Low levels of D2
• High levels of D2

Answer 9

• Low levels of D2 – pleasure in drug naive individuals
• High levels of D2 associated with unpleasant feelings

Question 10

What are the 3 types of opioid receptor?

What type of receptors are they?

Answer 10

1. Mu
2. Kappa
3. Delta

G protein coupled receptors

Question 11

Where are mu opioid receptors found?

What is the function of the mu opioid receptor?

What is the resulting effect on DA?

Answer 11

• Selectively expressed on inhibitory GABA interneurons in the VTA
• Hyperpolarise GABAergic neurons
• Leads to increased DA release, due to dis-inhibition of the neuron

Question 12

What are the levels of NT and receptor at these times:

• Normal baseline
• During drug use (Acute intake)
• Mu Opioid receptor activation
• Chronic addiction
• Withdrawal

Answer 12

• Normal production of DA & Noradrenaline
• More GABA and more DA
• Suppression of GABA and increased DA
• MOR adaptation/sensitisation & reduced GABA suppression and less DA
• Increased GABA & Little DA - no reward

Question 13

What are the risk factors of addiction?

• Genetic
• Environmental

Answer 13

• Familial or multi gene inheritance - DAergic genes which increases vulnerability
• Childhood trauma or events, stress, and availability of the drug - leads to the addiction

Question 14

1. What is the cause of sensation seeking which leads to addiciton?
2. What is the cause of self-medication which leads to addiction?

Answer 14

1. Positive reinforcement - Negative reinforcement. Drugs make them feel good - high drives drug use, feel horrible when not taking drug.
2. Negative reinforcement - Negative reinforcement. Feel bad so take drugs to stop feeling bad, need the drug to feel better to deal with initial problem

Question 15

What are the 3 methods of treating addiction?

Answer 15

1. management of withdrawal
2. harm reduction
3. maintaining abstinence

Question 16

What is an agonist?

What agonist is used for drug addiction?

How does it work?

What are the risks?

Answer 16

1. A drug that has the same effect as receptors ligand
2. Methodone
3. Acts as straight substitute for heroin, allowing for easier withdrawal of heroin
4. respiratory depression

Question 17

What is a partial agonist?

What agonist is used for drug addiction?

How does it work?

What are the risks?

Answer 17

1. A drug that acts like the ligand to the receptor, but does not have exactly the same effect
2. Buprenorphine
3. Not as strong in its effects as morphine, allows for weaning
4. Less risk of respiratory depression but less pleasurable than full agonist

Question 18

What is an antagonist?

What agonist is used for drug addiction?

How does it work?

What are the risks?

Answer 18

1. Has the opposite effect to the drug/receptor ligand
2. Naltrexone
3. Blocks mu opioid receptor - reduced DAergic activity, reducing drug cravings
4. Low adherence, but safest of all

Question 19

What are the lifestyle and behaviour changes that can also be encouraged? What is involved?

Answer 19

• Motivational interviewing - target ambivalence
• Community reinforcement - Earn tokens/money with clean urine samples
• Relapse prevention - CBT, finding a healthier alternative etc.

Question 20

• Where does the sciatic nerve originate?
• What does the sciatic nerve divide into?
• Where does the sciatic nerve divide into its 2 branches?

Identify:

• Sciatic nerve
• Common fibular nerve
• Tibial nerve

Answer 20

• L4-S3 from lumbar & saccral plexus
• Tibial nerve & Common fibular nerve
• Popliteal fossa

Question 21

Which parts of the leg generally are supplied by the:

• Common fibular nerve
• tibial nerve

Answer 21

• Anterior and lateral compartments of the leg and foot
• Posterior compartment of the leg and foot

Question 22

• What is sciatica?
• What is it caused by?

Answer 22

• Pain down the leg from the lower back
• Spinal disc herniation which presses on the lumbar or saccral nerve roots

Question 23

What is a spinal disc herniation?

Answer 23

• Nucleus pulposus bulges outwards, tearing the annulus fibrosus
• This then extrudes into the spinal canal and compresses the nerve root against the vertebrae
• Also causes inflammation of surrounding tissue

Question 24

• What are nociceptors senstive to? (x3)
• What is the function of pain?

Answer 24

• Mechanical, thermal and chemical stimuli
• Protective mechanism, causing person to react to stimulus

Question 25

What are the characteristics of the following neurons? (Body size, conduction velocity, myelinated?) 1. A alpha (A1) neurons 2. A beta (A2 neurons) 3. A delta (A3 neurons) 4. C fibers (IV neurons)

Answer 25

1. Large cell body, myelinated, fast conduction velocity 2. Large cell body, myelinated, fast conduction velocity 3. Small/Medium cell body, myelinated thinly, medium conduction velocity 4. Small cell body, un-myelinated, slow conduction velocity

Question 26

# Define the following: * Peripheral sensitisation * Central sensitisation * Hyperalgesia * Allodynia

Answer 26

* Reduction in the threshold and increase in responsiveness of peripheral nociceptors * Increased excitability of neurons in CNS, so normal stimuli leads to abnormal responses * Enhanced pain evoked by noxious stimuli * Pain evoked by non-noxious/normal stimuli

Question 27

What are the characteristics of the following types of pain: 1. Fast pain/Acute pain 2. Inflammatory pain 3. Neuropathic/Chronic pain

Answer 27

1. High threshold stimulus dependant pain. Graded response. Good pain, has protective purpose 2. Caused by active inflammation, sensitisation to pain. Low to high intensity stimuli evoked, adaptive and protective during healing process. Reversible 3. Spontaneous and evoked by low and high intensity stimuli, or none at all. Bad pain, persistent, abnormal amplification of pain.

Question 28

1. What are the 4 stages of acute pain? 2. What are nociceptors?

Answer 28

1. Transduction, Transmission, Perception, Modulation 2. Free nerve endings that are activated by noxious stimuli

Question 29

1. What inflammatory markers are released in neuropathic pain? 2. What happens to vascualar permeability? 3. Which cells are the first to inflitrate damaged tissue?

Answer 29

1. TNF alpha & Histamine 2. Increases to allow more cells through 3. Neutrophils

Question 30

1. What ion channel is altered in neuropathic pain? 2. What happens to them? 3. Where do the emotional and behavioural responses to pain arise from? 4. What neuropeptides do C fibers release?

Answer 30

1. Na+ channel 2. They are upregulated so there is increased excitability 3. Hypothalamus & limbic system 4. CGRP & Substance P

Question 31

1. What is 2 pathways transmit pain from receptors to the brain? 2. What does the spinothalamic tract transmit? 3. What does the spinoreticular tract transmit?

Answer 31

1. Spinothalamic tract & Spinoreticular tract 2. Fast acute pain 3. Slow, Chronic pain

Question 32

1. Which way do the following ascend: Ipsilaterally or contralaterally? 1. Touch sensation 1. Pain sensation

Answer 32

1. Ipsilaterally 2. Contralaterally

Question 33

1. What are the 5 fiber types in the body? 2. Which has the fastest conduction speed? 3. Which has the biggest diameter? Smallest? 4. Which fibers are not myelinated?

Answer 33

1. A alpha, A beta, A gamma, A delta, C fibers 2. A alpha 3. A alpha, C fibers 4. C fibers

Question 34

1. Which Lamina do the fibers of the Spinothalamic tract originate from? 2. What type of neurons are they? 3. Where do the fibers enter the spinal cord? 4. Where do the fibers decussate? 5. Where do they terminate?

Answer 34

1. Laminae 1 2. A delta fibers 3. Dorsal horn 4. In the spinal cord through the anterior commissure 5. Posterior nuclear group of thalamus

Question 35

1. Where do the fibers of the spinoreticular tract originate? 2. Where do they decussate? 3. Where do they terminate?

Answer 35

1. Rexeds laminae 7 & 8 2. They do not 3. Reticular area of the brainstem

Question 36

1. What does the paleospinothalamic tract convey? 2. Which neurons do they carry fibers from? 3. 2nd order neurons arise? 4. Where do they decussate? 5. Where do they terminate?

Answer 36

1. Chronic/Slow pain 2. C fibers 3. Substantia gelatinosa 4. Spinal cord, past the anterior commissure 5. Brainstem

Question 37

1. What family of receptors mediate pain? 2. Which are the important channels?

Answer 37

1. TRP channels 2. TRPV1, TRPM8, TRPA1 channels

Question 38

1. What are the pain producing chemicals? (2) 2. What do kinnins do? 3. What are examples of them? 4. What do Prostaglandins do?

Answer 38

1. Kinins, and Prostaglandins 2. Produces pain by releasing prostaglandins. They act on B2 receptors on nociceptive neurons and open the TRP channels by phosphorylation 3. Bradykinnin 4. Enhance pain producing effect of 5-HT and Bradykinnin. They sensitise nerve terminals

Question 39

1. What are the 3 types of synapses? Identify the type of synapse

Answer 39

1. Axoaxonic, dendrodenritic, somatodendritic synapses

Question 40

Identify the following parts of a neuron: * Axon * Oligodendrocyte * Soma * Dendrite * Synapse * Node of Ranvier * Myelin sheath

Answer 40

Question 41

1. What are the 2 types of synapse? 2. What is spatial summation? 3. What is temporal summation?

Answer 41

1. Electrical synapse & Chemical synapse 2. Adding together of EPSP's generated at different synapses on a dendrite 3. Adding together of EPSP's generated at the same synapse at different times

Question 42

1. What are the characteristics of an AP? (2) 2. Where does the AP start? 3. What is the rate of travel of an AP determined by? 4. In a myelinated axon where does the movement of ions happen?

Answer 42

1. All or none signal, and unidirectional 2. Axon hillock 3. Diameter of the axon 4. At the Nodes of Ranvier

Question 43

# Define the following: * Anions * Cations

Answer 43

* Negatively charged ions * Positively charged ions

Question 44

1. What is the resting membrane potential of a neuron? 2. What happens when the cell is depolarised? 3. What happens when the cell is hyperpolarised?

Answer 44

1. -70mV 2. Potential becomes more positive 3. Potential becomes more Negative

Question 45

1. What is the tendency of Na+ and K+ 2. What does the Na+/K+ pump do? 3. Does it require energy? 4. What is the level of depolarisation which starts an AP called?

Answer 45

1. Na+ leaks INWARD, and K+ leaks OUT 2. Exports 3 Na+ and Imports 2 K+ 3. Yes, ATP 4. Generator potential

Question 46

1. What happens to the neuron at rest? 2. What happens as the membrane begins to depolarise? 3. What happens when the graph starts to fall? 4. What happens in the final stage of an AP?

Answer 46

1. Na+ and K+ channels are closed 2. Rapid opening of the Na+ channels activation gate, influx of Na+ into the membrane 3. Inactivation gate on the Na+ closes & K+ channel opens so there is hyperpolarisation 4. Overshoot of hyperpolarisation and the Na+ gate is inactivated

Question 47

1. What is the absolute refractory period? 2. What is the relative refractory period? 3. How is the frequency of impulses measured? 4. What is found at each node of Ranvier?

Answer 47

1. Neuron is incapable of initiating a 2nd impulse, too many channels are still open 2. Excessive stimuli can lead to another AP 3. Hz 4. Na+ channels

Question 48

1. What is feedforward excitation or inhibition? 2. What is feedback excitation or inhibition?

Answer 48

1. Passing forward to excite more than one cell 2. Where the information is modulating back onto the cell or circuit

Question 49

1. What is a prolapsed intervertibral disc? 2. Where does it always tear? 3. What is a lumbar discetomy? 4. What is a laminotomy? 5. What is TENS?

Answer 49

1. Tear in anulus fibrosus, which allows nucleus pulposus to bulge out causes pain 2. Posterolateral direction, due to posterior longitudinal ligament 3. Removal of herniated disc materal 4. Removal of the lamina 5. Stimulation of Non-nociceptive fibers

Question 50

1. Which are is responsible for descending regulation of pain? 2. Where do the PAG axons descend down to synapse? 3. Where do they then project to?

Answer 50

1. Periaqueductal gray matter (PAG) 2. Raphe nuclei 3. Dorsal horn of the spinal column to depress nociceptive activity

Question 51

1. What is the spinoparachial tract? 2. What does it do? 3. Where does it terminate?

Answer 51

1. Originates from the dorsal horn (Lamina 1) and terminates in the lateral parabrachial region 2. Responsible for the emotional affective responses to noxious events 3. Amygdala and hypothalamus