Pain 2 (analgesia)

Question 1

What is stress analgesia?

Answer 1

The body’s own pain relieving pathway that occurs under extreme stress

Question 2

Describe the stress analgesia pathway?

Answer 2

1) Neurones in periventricular nuclei of hypothalamus activated
2) signals then relayed > periqueductal gray of the mesencephalon and upper pons > raphe magnus nucleus of pons > inhibitory interneurones ( in dorsal horn of spinal cord)
3) In response inhibitory interneurones release GABA and enkephalin neurotransmitters

Question 3

What is the function of GABA in analgesia?

Answer 3

• prevent signals being carried along 2nd order projection neurones by:
• opening Cl- channels on postsynaptic DHN cells, causing hyperpolarisation (reduces firing of APs in DHN)

Question 4

What is the function of enkephalins in analgesia?

Answer 4

• prevent signals being carried along 2nd order projection neurones by:
• activating opioid receptors in A(d) and C fibres and dorsal horn neurones (DHN)
• will open K+ channels on DHN (presynaptic) and inhibit Ca2+ channels on C or A(d) (postsynaptic) which stops depolarisation of DHN

Question 5

What signalling molecule mediates neurotransmission between inhibitory neurones

Answer 5

serotonin

Question 6

How can you activate natural analgesia neurotransmitters?

Answer 6

• TENS (transcutaneous electrical nerve stimulation), peripheral inhibitory pathways by releasing enkephalins
• applying pressure (rubbing wound will reduce pain as inhibitory interneurones activated by A(beta) fibres (mechanical)

Question 7

When can hot or cold treatments be useful in analgesia?

Answer 7

Hot - stiff joints or lower back pain

Cold - reduce inflammation and nociceptor activation

Question 8

How do medical analgesics generally work?

Answer 8

1) reduced nociceptor activation
2) reduced activation of ascending DHNs
3) Activating descending inhibitory pathways

Question 9

Describe MoA of opioids?

Answer 9

• inhibit transmission of pain signals in spinal cord
• to do this they activate opioid receptors
• and stimulate RMN which will then activate inhibitory interneurones to reduce DHN activation

Question 10

Describe MoA of NSAIDs?

Answer 10

• inhibit prostaglandin production by COX inhibitors

- reduces the hyperalgesia associated with inflammation

Question 11

What are the negative side effects of opioids?

Answer 11

• constipation
• nausea
• vomiting
• respiratory depression

Question 12

What are the positive side effects of opioids?

Answer 12

• Euphoria/sense of well being

- sedative

Question 13

What are the symptoms of opioid withdrawal?

Answer 13

• reduced capacity to experience pleasure
• increased anxiety
• nausea
• muscle ache
• diarrhoea
• low mood

Question 14

What do prostaglandins do?

Answer 14

• ## Cause peripheral sensitisation by increasing nociceptor sensitivity

Question 15

What do prostaglandins do?

Answer 15

• Cause peripheral sensitisation by increasing nociceptor sensitivity
• cause vasodilation, anti-coagulation and hyperalgesia

Question 16

What are the side effects of NSAIDS?

Answer 16

GI bleeding, sodium and water retention, stroke, MI

Question 17

Give examples of NSAIDS?

Answer 17

Non-selective COX inhibitors: Diclofenac, Ibuprofen and Naproxen
Selective COX-2 inhibitors: Celecoxib
COX-3 selective: Paracetemol

Question 18

Give examples of NSAIDS?

Answer 18

Non-selective COX inhibitors: Diclofenac, Ibuprofen and Naproxen
Selective COX-2 inhibitors: Celecoxib
COX-3 selective: Paracetemol (acts centrally)

Question 19

What is the MoA of local anaesthetics (LA)?

Answer 19

• block initiation and propagation of AP by pain fibres
• un-ionized LA enters cell through membrane
• ionized in the cell due to acidity
• LA closes inactivation gate of Na+ channels this prevents transmission of pain signals
• If extracellular environment becomes more acidic LA can be ionized outside cell and can only enter cell through pore (slower)

Question 20

What are the side effects of local anaesthetic?

Answer 20

Common
- Nausea 
- dizziness 
- bruising 
- redness 
- itching  
- swelling on injection site 
Less common
- drowsiness
- mental mood swings 
- vision changes
- tremor

Question 21

How do antidepressants produce analgesia?

Answer 21

• serotonin re-uptake inhibitors increase serotonin levels at inhibitory interneuron synapse and descending analgesic pathways
• increased activation of inhibitory neurones means less C and A(d) mediated pain signals are transmitted up ascending pathways