Pain

Question 1

Define analgesia

Answer 1

Inability to feel pain, without removing all feeling or ability to move muscles

Question 2

Define analgesic

Answer 2

Drug used to achieve analgesia

Question 3

Define anaesthetic

Answer 3

Drug used to eliminate all sensation, including pain

Question 4

What is a neuromuscular blockade?

Answer 4

Also known as muscle relaxant

Works by blocking the neuromuscular junction

Question 5

What is a perineural blockade?

Answer 5

Injection to selectively block a nerve root

Question 6

What is radicular pain?

Answer 6

Pain that radiates into a lower extremity

e.g. sciatica

Question 7

What are the 5 types of sensory receptors?

Answer 7

Mechanoreceptor
Nociceptors
Chemoreceptors
Thermoreceptors
Photoreceptors

Question 8

What is the pathway of a pain signal?

Answer 8

Afferent peripheral nerve (nociceptor)
Synapses with interneuron in spinal cord in dorsal horn
Releases glutamate which binds to AMPA and NMDA receptors
Thalamus
Cortex

Question 9

What is nociceptive pain?

Answer 9

Sensation of pain in response to detection of potentially damaging stimuli

Question 10

What is neuropathic pain?

Answer 10

Pained caused by damage to the sensory nervous system

Question 11

What is pain wind-up?

Answer 11

Perceived increase in pain intensity over time when the stimulus is applied repeatedly
Caused by repeated stimulation of group C nerve fibres and priming of the NMDA receptor response

Question 12

What is Ketamine and how does it work?

Answer 12

Used as an IV anaesthetic
NMDA receptor antagonist
Leads to inhibition of CNS

Question 13

How does Nitrous Oxide work as an anaesthetic (and what is it also known by)?

Answer 13

Antagonist of NMDA, AMPA and Kainate receptors

Also known as Entonox

Question 14

What are the 4 types of receptor that opioids bind to?

Answer 14

Mu
Kappa
Delta
ORL1

Question 15

What type of receptor are opioid receptors?

Answer 15

GPCR - coupled to Gi/o

Question 16

What are the downstream effects if the Go receptor?

Answer 16

Potassium channels open
Potassium efflux
Hyperpolarisation
Less likely to reach action potential threshold

Also inactivates VOCCs, preventing neurotransmitter release

Question 17

What 5 receptors are coupled to a Gi/o protein?

Answer 17

a2-adrenoreceptors
M2 and M4 receptors
All opioid receptors 
5-HT1 receptor
GABA-b receptor

Question 18

How does the GABA-a receptor work?

Answer 18

It is a ligand-gated chloride channel
Allows chloride ion influx
Hyperpolarisation
Less likely to reach action potential threshold

Question 19

Is Glycine an excitatory or inhibitory neurotransmitter?

Answer 19

Inhibitory

Also works on ligand gated chloride channels

Question 20

What are the two types of neuromuscular blockade?

Answer 20

Depolarising

Non-depolarising

Question 21

How do depolarising neuromuscular blockades work?

Answer 21

Agonist of nAchRs
Causes persistent refractory depolarisation
Motor endplate becomes inexcitable
(Ach normally released in brief spurts and rapidly hydrolysed)

Question 22

Example of a depolarising neuromuscular blockade

• administration
• structure
• how is it broken down

Answer 22

Succinylcholine

• Administered by IV
• Looks like two Ach joined together
• Broken down by plasma cholinesterase

Question 23

How do non-depolarising neuromuscular blockades work?

Answer 23

They are competitive reversible antagonists of nAchRs

Question 24

How does botox work?

Answer 24

Botox targets proteins in the SNARE complex

Prevents exocytosis of Ach

Question 25

How does Neostigmine work?

Answer 25

Inhibits acetylcholine esterase Prevents breakdown of Ach Used to treat Alzheimers and Parkinson's

Question 26

How is Ach recycled?

Answer 26

Acetylcholine esterase breaks it down into acetate and choline Choline reuptaken into presynaptic membrane by cotransportation with sodium ions Choline + Acteyl Coa makes more Ach Repackaged into vesicles

Question 27

What 3 things can anticonvulsant drugs be used to treat?

Answer 27

Seizures Mood disorders/stabilisers Neuropathic pain

Question 28

How do anticonvulsant drugs work?

Answer 28

Block sodium channels Block calcium channels Enhance GABA function

Question 29

By what 3 ways can GABA neurotransmission be enhanced?

Answer 29

Positive allosteric modulation of GABA-a receptors e.g. by benzodiazepines Inhibition of GABA transaminase (preventing GABA breakdown) Inhibition of the GAT1 reuptake transporter

Question 30

Example of a drug that inhibits sodium channels

Answer 30

Carbamazepine | Specifically Na1.8 channels

Question 31

Examples of 2 drugs that inhibits calcium channels | How do they work?

Answer 31

Gabapentin and Pregabalin Block t-type calcium channels Also prevent insertion of calcium channels into the membrane Reduce expression of a2-delta subunits in calcium channels

Question 32

How does neuropathic pain after injury arise?

Answer 32

Injury causes inflammation Release of inflammatory mediators Inflammatory mediates upregulate a-adrenoreceptors on the sensory nerve and upregulate NMDA receptors on the spinal cord synapse Lowers nerve activation threshold

Question 33

What is a nociceptor?

Answer 33

Sensory neuron that responds to potentially damaging stimuli Detection of noxious stimuli transduced into electrical energy

Question 34

What are the two types of nociceptor axon?

Answer 34

A-delta fiber axons | C fiber axons

Question 35

What is the difference between A-delta fiber axons and C fiber axons?

Answer 35

A-delta fiber axons are myelinated and cause feeling of sharp pain. Action potentials are initiated through specific TRP channels C fiber axons are non myelinated and cause feeling of dull, prolonged pain. They are polymodal - response to a range of stimuli

Question 36

How do thermoTRP channels work?

Answer 36

Ion channel, opens in response to extreme heat | The TRPV1 channel opens in response to 42 degrees, also vanilloids present in chilli

Question 37

What is hyperalgesia?

Answer 37

Increased sensitivity to pain, usually caused by inflammatory mediators

Question 38

What are A-beta fibers?

Answer 38

Detect non-noxious, mechanical stimuli

Question 39

What are 3 possible causes of phantom pain?

Answer 39

1. Neuroma (tumour on a nerve sheath cell), causing abnormal firing of action potentials 2. Degeneration of C fiber axons due to injury. A fibers branch into same lamina, so A fiber input becomes reported as noxious stimuli 3. Cortical remapping following amputation