6.0 Pharmacology of Pain Flashcards

Question 1

Q

Define pain:

Answer

A

Unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage

Question 2

Q

Define nociception:

Answer

A

The neural processes of encoding noxious stimuli

Question 3

Q

What are the nociceptive fibres?

Answer

A

Aδ (thin myelin) C (no myelin)

Question 4

Q

Where are cell bodies of nociceptors found?

Answer

A

1) Dorsal root ganglia 2) Trigeminal ganglia (head and neck)

Question 5

Q

What is the structure of the nociceptive fibre axon terminals?

Answer

A

Free endings (do not have specialised endings)

Question 6

Q

What are the steps for nociceptive transmission from nociceptive receptor to post-synaptic neuron:

Answer

A

1) Many ion channel can be activated in peripheral nerve → receptor potential 2) If receptor potential is great enough → Voltage-gated sodium channels (NaVs) open 3) Action potential propagates along the presynaptic nerve towards the spinal cord 4) AP opens voltage gated calcium channels (CaVs) in end terminals 5) Influx of Ca²⁺ → neurotransmitter release onto post-synaptic neuron in spinal cord

Question 7

Q

What are the ion channels that are stimulated by the following noxious stimuli: 1) Noxious heat 2) Noxious cold 3) Protons 4) ATP 5) Mechanical stimuli

Answer

A

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Question 8

Q

At what temperature do heat sensitive nociceptive neurons activate? (What temperature is pain reported?)

Question 9

Q

Define sensitisation:

Answer

A

A characteristic of nociceptors. When a stimulus is large enough to cause damage, subsequent stimuli generate a larger response. Can cause hyperalgesia or allodynia

Question 10

Q

Define hyperalgesia:

Answer

A

Stimuli that usually cause pain, now cause more pain

Question 11

Q

Define allodynia:

Answer

A

Previously innocuous stimuli now cause pain

Question 12

Q

What are examples of external stimuli and internal factors that nociceptors can directly respond to:

Answer

A

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Question 13

Q

Give examples of agents that are purely sensitising agents: (i.e. they do not directly excite nociceptive nerve terminals, only enhance response to excitatory agents)

Answer

A

1) Prostaglandins 2) Nerve growth factor (NGF)

Question 14

Q

Give examples of agents that both excite and sensitize nociceptiors:

Answer

A

1) Bradykinin 2) ATP 3) H⁺

Question 15

Q

What agents, released from nerves, induce neurogenic inflammation?

Answer

A

1) Calcitonin gene-related peptide (CGRP) Indirect effect 2) Substance P (SP) Direct effect (cause mast cell degranulation)

Question 16

Q

What is the mechanism by which PGE2 sensitises nociceptors?

Answer

A

1) PGE₂ binds to EP₄ receptor (upregulated in inflammation) 2) Gs coupled → ↑ cAMP → + PKA → phosphorylation of sodium channels 3) This phosphorylation means that the sodium channel has a lower threshold for AP firing

Question 17

Q

Define neuropathic pain:

Answer

A

Peripheral nerve damage can cause pain that outlasts initial nerve injury (sometime permanent). Following changes in periphery, it is likely that nociceptive processing at the spinal cord and higher centres are likely involved in disease progression. Examples: 1) Phantom limb 2) Diabetic neuropathy 3) Trigeminal neuopathy 4) Post-herpetic neuropathy

Question 18

Q

Mechanism of action of most NSAIDs:

Answer

A

1) Enter COX via hydrophobic channel 2) H-bond with Arg 120 3) This prevents arachidonic acid to enter catalytic site Reversible

Question 19

Q

Mechanism of action of Aspirin:

Answer

A

1) Enters active site 2) Acetylates Serine 530 3) This prevents arachidonic acid to enter catalytic site Irreversible

Question 20

Q

Mechanism for COX-2 selectivity:

Answer

A

COX-2 has a larger hydrophobic channel thus, COX-2 selective drugs have a large sulphur side group. This prevents them from entering the hydrophobic channel of COX-1

Question 21

Q

What activates COX-2 to increase its expression during inflammation?

Question 22

Q

Effect of NSAIDs on periphery:

Answer

A

NSAIDs work mainly via peripheral action: COX inhibition ⟶ ↓ PGE₂ ⟶ ↓ nociceptor sensitisation and less pain (nociceptor excitability is returned to the resting, normal state) Some PGs are also vasodilators (PGE₂ and PGI₂) ∴ NSAIDs can also help in headache (by ↓ vasodilation of cerebral vasculature)

Question 23

Q

Effect of NSAIDs centrally:

Answer

A

NSAIDs work mainly via peripheral action Smaller effect centrally PGs are thought to facilitate nociceptor neurotransmission

Question 24

Q

What is the lifespan of a platelet?

Answer

A

10 days (Effect of aspirin on platelets = 10 days)

Question 25

Q

Examples of COX-2 selective NSAIDs:

Answer

A

Celecoxib Etoricoxib Tend to end in -coxib

Question 26

Q

Side effects of NSAIDs:

Answer

A

Due to COX-1 inhibition: 1) GI bleeding 2) Bronchospasm 3) Renal insufficiency 4) Stroke/MI (because of disruption of consitutive COX-2 in CVS tissue)

Question 27

Q

Define opiods:

Answer

A

Substances that provide morphine-like effects

Question 28

Q

Give some endogenous opiods:

Answer

A

1) Endorphin 2) Endomorphin 3) Dynorphin 4) Enkephalin

Question 29

Q

What is the reversal agent for opiods?

Question 30

Q

What are the four receptors for opiates?

Answer

A

1) μ 2) κ 3) δ 4) ORL₁ All receptors are Gi/Go protein coupled

Question 31

Q

Structure of opiods:

Answer

A

1) Benzene rings 2) Free hydroxyl group on one ring 3) Nitrogen atom linked by 2 carbon atoms to another benzene ring

Question 32

Q

Mechanism of opiods at receptors:

Answer

A

All receptors are Gi/Go protein coupled βγ subunit interacts with: 1) GIRKS (inward rectifying K⁺ channels) → hyperpolarisation → less chance of AP 2) Voltage gated calcium channels → ↓ opening 3) Adenylate cyclase (AC) → ↓ activity

Question 33

Q

Mechanism of opiod induced analgesia on: 1) Periphery 2) Spinal cord 3) Supraspinally

Answer

A

Peripherally • Inhibition of AC counteracts sensitising activity of PGs Spinal cord • Dorsal horn opioids act: 1) Presynaptically on nociceptors ⟶ ↓ neurotransmitter release 2) Postsynaptically on nociceptors ⟶ ↓ dorsal horn neuron excitability Supraspinally • Opioids have roles in a number of brain areas including PAG region • Opioids may evoke the activation of endogenous inhibitory systems

Question 34

Q

Examples of opiods:

Answer

A

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Question 35

Q

List some side effects of opiods:

Answer

A

1) Respiratory depression 2) Nausea/vomiting 3) Constipation 4) Tolerance and dependence

Question 36

Q

What opoid receptor(s) is/are responsible for respiratory depression?

Answer

A

1) μ (inhibits respiratory rhythm + central chemoreceptors)

Question 37

Q

What opoid receptor(s) is/are responsible for nausea and vomitting?

Answer

A

1) μ 2) δ

Question 38

Q

What opoid receptor(s) is/are responsible for constipation?

Answer

A

1) μ 2) κ 3) δ

Question 39

Q

Mechanism of Gabapentin/pregabalin:

Answer

A

Good for neuropathic pain Mechanism = unclear Though to ↓ surface localisation of α₂δ₁ subunit of the voltage gated calcium channels. This reduces neurotransmitter release Pregabalin = better pharmacokinetics

Question 40

Q

What is Ziconotide?

Answer

A

Voltage gated calcium channel blocker Needs to be administered intrathecally

Question 41

Q

Which receptor does ketamine work on?

Answer

A

NMDA receptor

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6.0 Pharmacology of Pain Flashcards

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