8: Mechanism of analgesia

Question 1

Which type of analgesic drug reduces inflammatory pain by dampening down the inflammatory response?

Answer 1

NSAIDs

inhibit prostaglandin production by inhibiting COX1/2

Question 2

How do NSAIDs work?

Answer 2

Cycloxygenase inhibitors

Reduce production of prostaglandins

Question 3

Prostaglandins produce which three effects?

Answer 3

Inflammation

Pyrexia (fever)

Pain

Question 4

Name five non-selective NSAIDs.

Answer 4

Aspirin

Ibuprofen

Diclofenac

Naproxen

Indomethacin

Question 5

How can you tell that an NSAID is COX-2 specific?

Answer 5

It will be called something-coxib

Question 6

What are some side effects of NSAIDs?

Answer 6

Peptic ulceration > GI bleeding

Renal toxicity

Cardiovascular problems (COX-2 only)

Question 7

COX-2 inhibitors (-coxibs) aren’t often used because they contribute to cardiovascular disease - how?

Answer 7

Prothrombotic

increase chance of DVT > PE, stroke

Question 8

Which type of analgesic drug reduces pain by inhibiting nociceptive nerve transmission in the brainstem and posterior horn of the spinal cord?

Answer 8

Opioids

Question 9

Which type of analgesic drug reduces pain by targetting ion channels involved in nerve damage and inflammation?

Answer 9

Anti-epileptics

Question 10

Which type of analgesic drug works by inhibiting serotonin and noradrenaline reuptake?

Answer 10

Tricyclic anti-depressants

Question 11

Which ion channel is blocked by many antiepileptic drugs e.g carbamazepine?

Answer 11

Na+

Question 12

Describe the WHO analgesic ladder.

Answer 12

1. Non-opioid +/- adjuvant

2. Weak opioid +/- non-opioid +/- adjuvant

3. Strong opioid +/- non-opioid +/- adjuvant

Question 13

Is paracetamol an NSAID?

Why (not)?

Answer 13

No

NSAIDs are anti-inflammatory, anti-pyrexial and analgesic - paracetamol isn’t anti-inflammatory

Question 14

What is the difference between pain and nociception?

Answer 14

Pain is the experience of suffering

Nociception is the nervous system’s way of conveying pain signals to the brain

Question 15

What is the Gate Control Theory?

Answer 15

Pain is transmitted by SMALL FIBRE sensory nerves

Mostly everything else is transmitted by LARGE FIBRE sensory nerves

if the large fibre nerves are transmitting impulses, inhibitory interneurons stop small fibre impulses (i.e pain impulses) from going any higher

i.e if you’re bombarded with other sensory information, your perception of pain is reduced

Question 16

In the Gate Control Theory, nerve impulses from large (Aα and Aß fibres) sensory fibres activate the ___ interneurone, stopping the transmission of pain signals.

Answer 16

inhibitory interneurone

Question 17

Which types of nerve fibre are classed as large fibre sensory nerves?

Answer 17

A-alpha

A-beta

Question 18

A-alpha and A-beta fibres are involved in dampening down nociceptive signals in the Gate Control Theory.

Which senses are these fibres responsible for?

Answer 18

A-alpha = proprioception

A-beta = skin mechanoreceptors

Question 19

Which types of nerve fibre are classed as small fibre sensory nerves?

Which sensations do they control?

Answer 19

A-delta

C

Pain, temperature, itch

Question 20

Question 21

Which inhibitory neurotransmitter is involved in the Gate Control Theory?

Answer 21

GABA

Glycine

Question 22

Which excitatory neurotransmitter is involved in the Gate Control Theory?

Answer 22

Glutamate

Question 23

The Gate Control Theory is an example of (afferent / efferent) pain modulation.

Answer 23

afferent

ascending tracts, sensory

Question 24

Pain modulation descending from the brain is known as (afferent / efferent) modulation.

Answer 24

efferent

Question 25

Which area of the **brainstem** has an **analgesic effect** when stimulated? Where specifically in the brainstem is it found?

Answer 25

**Periaqueductal grey matter** **Midbrain**

Question 26

The **periaqueductal grey area** of the **midbrain** is an efferent regulator of pain. Apart from **electrical stimulation**, what activates it?

Answer 26

**Opioids**

Question 27

What is the result of **activation** of the **periaqueductal gray matter**?

Answer 27

**Nociceptive signals from the posterior horn are INHIBITED** i.e perception of pain is reduced because **Nucleus raphe magnus** and **Locus coeruleus** are activated

Question 28

What are the body's **endogenous opioids** called?

Answer 28

**Enkephalins**

Question 29

When **activated by electrical impulses** or **opioids, the periaqueductal gray area activates two other brain areas**. What are they called?

Answer 29

**Nucleus raphe magnus** **Locus coeruleus**

Question 30

Which **chemicals** are released by the **nucleus raphe magnus**? What is the end result of this chemical release?

Answer 30

**Serotonin (5-HT)** **Enkephalins** inhibition of nociceptive transmission, analgesia

Question 31

Which area of the **midbrain** is involved in **pain regulation** and can be activated by **electrical impulses** and **opioids**?

Answer 31

**Periaqueductal gray matter**

Question 32

Which neurotransmitter is released by the **locus caeruleus**? What is the end result of this release?

Answer 32

**Noradrenaline** Inhibition of nociceptive transmission, analgesia

Question 33

Which areas of the **CNS** are **affected** (either excited or inhibited) by **opioids**?

Answer 33

**Periaqueductal gray matter** in the midbrain **Nucleus raphe magnus** in the pons **Relay neurons** in the posterior horn of the spinal cord

Question 34

Which **type** of receptor do **opioids** act on?

Answer 34

**G-protein coupled receptors**

Question 35

**Opioids** inhibit a) **Ca****2+** channels b) **K+** channels found on nociceptive neurons (both pre and post-synaptic, a bit confusing). **How does this modulate pain?**

Answer 35

a) **Ca2+** responsible for excitatory neurotransmitter (glutamate) release, so blocking this channel dampens down excitation b) **K+** enters the cell to cause repolarisation and stop an action potential, so blocking this channel prolongs the AP, reducing excitation

Question 36

Which channels are blocked in response to the activation of G-protein coupled opioid receptors?

Answer 36

**Ca****2+** ## Footnote **K+**

Question 37

Which **named** opioid receptor is most important in analgesia?

Answer 37

**Mu (μ) receptor**

Question 38

**Opioids** are highly ___ if used inappropriately.

Answer 38

**addictive**

Question 39

Apart from their **addictive potential**, what are some **side effects** of opioids?

Answer 39

**Respiratory depression** \> **Apnoea** ## Footnote **Postural hypotension** **N&V, constipation** **Confusion, hallucinations**

Question 40

What are important a) respiratory b) GI c) neurological d) cardiovascular side-effects of opioids like morphine?

Answer 40

**a) Respiratory depression** **b) N&V, constipation** **c) Confusion, hallucinations** **d) Postural hypotension**

Question 41

Which **opioid receptor** does **morphine** activate?

Answer 41

**μ​ receptor**

Question 42

How does **morphine** tend to be administered for a) **acute pain** b) **chronic pain**?

Answer 42

**a) IV** **b) Oral**

Question 43

What is an **opiate antagonist** used to reverse the effects of opiates like morphine?

Answer 43

**Naloxone**

Question 44

Why must **continuous release morphine** be prescribed carefully?

Answer 44

**Can be misused** (dissolved and injected to deliver a high dose rapidly)

Question 45

What is **diamorphine** also known as?

Answer 45

**Heroin**

Question 46

What is **heroin** also known as?

Answer 46

**Diamorphine**

Question 47

Which **strong opioid** has a rapid effect when delivered intravenously and is sometimes used for severe post-op pain?

Answer 47

**Diamorphine** (heroin)

Question 48

Which **weak opioid** is only given **orally** and is converted to **morphine** by the liver?

Answer 48

**Codeine**

Question 49

**Codeine** is given **(orally / IV)**.

Answer 49

**oral** only

Question 50

Which two **strong opioids** are derivatives of codeine?

Answer 50

**Oxycodone** **Hydrocodone**

Question 51

Which **opioid** is **75-100x more potent than morphine**? What does it tend to be used for?

Answer 51

**Fentanyl** Maintenance anaesthesia during surgery

Question 52

Which **opioid** can be given for **acute pain** and is often used during **childbirth**?

Answer 52

**Pethidine**