Pain : Analgesia

Question 1

What is Stress analgesia

Answer 1

A pain relieving pathway activated when the body is under extreme stress

Question 2

Explain the process of stress analgesia

Answer 2

1- Acitvated neurones in the periventricular nuclei of the hypothalamus release signals to the periaqueductal grey of the mesencephalon and upper pons
2- signals then sent to the raphe Magnus nucleus of the pons
3- Signals then reach inhibitory interneurons int he dorsal horn of the spinal cord where serotonin mediates the neurotransmission between the interneurons
4- In response GABA neurotransmitters and enkephalins are released by the inhibitory interneurons
5- GABA presents transmission from the second order neurons by opening Cl channels on the postsynaptic DHN cells – causes hyperpolarisation
= firing of AP’s in DHN is reduced since it now needs more glutamate
7- Enkephalins activate opioid receptors to reduce nociception transmission

Question 3

What are enkephalins known for

Answer 3

Being the body’s endogenous opioids ( naturally occurring )

Question 4

Where are the opioid receptors expressed

Answer 4

On presynaptic and postynaptic terminal

Question 5

How do the enkephalins reduce transmission of nociception

Answer 5

1- Inhibit DHN depolarization by opening potassium channels ( hyper polarizing membrane when potassium moves out ) = now much more glutamate is needed for depolarization
2- At presynaptic membrane inhibit opening of Ca channels, less Ca entry means less transmitter release

Question 6

How can natural analgesia be harnessed

Answer 6

1- Transcutaneous electric nerve stimulation ( TENS ) : relaxes enkephalins and thus stimulates inhibitory pathway
2- relaxation techniques to increase enkephalin and serotonin release centrally
3- Application of pressure on injury : effects body’s transmission of pain
4- Heat / Ice treatments :

Question 7

How does applying pressure ease pain

Answer 7

A beta fibres ( sensory mechxnosensitive fibres ) are activated which stimulate activation of inhibitory neurones. Results in the natural analgesic pathway

Question 8

What are the three possible effects of general analgesics

Answer 8

1- reducing nociceptor activation directly or via reduced sensitivity
2- reduced activation of ascending DHNS directly or via increased inhibitory neurone activation
3- activating descending inhibitory pathways

Question 9

What are the 3 main types of analgesics

Answer 9

1- Opioids ( morphine, codeine , pethidine )
2- NSAIDs ( aspirin, ibuprofen )
3- Local Anaesthetics( lidocaine, benzocaine )

Question 10

What is the novel treatment of analgesic

Answer 10

Anti-Anti-depressent

Question 11

How do Opioids work

Answer 11

Inhibit trasmission of pain signals at the level of the spinal cord by activating the same opioid receptors as enkephalins. Opioids activate raphe Magnus nucleus ( RMN ) neurons coming down the spinal cord to activate inhibitory interneurons.
Reduce Ca entry presynaptically & Postsynaptically causing potassium to leave cell

Question 12

When are opioids used and why is their use limited

Answer 12

1-surgical pain
2- child birth
3- terminal pain
Limited due to being very addictive

Question 13

What are the side effects of opioids

Answer 13

1- dependency ( physical and psychological need for the opioids )
2- Euphoria/ senses of well-being ( helpful in terminal pain )
3- sedative effect
4- constipation
5- Nausea/ vomiting
6- Respiratory depression
7- Withdrawal symptoms : trouble sleeping, diarrhoea, low mood, muscle ache

Question 14

How can opioids cause constipation

Answer 14

opioid receptors in the gut will oppose parasympathetic activation of contractions

Question 15

How can opioids cause nausea/vomiting

Answer 15

stimulate chemoreceptors in the medulla

Question 16

How can opioid cause respiratory depression

Answer 16

Reduce sensitivity of respiratory centre to CO2. CO2 is what makes the respiratory centre to respond to the need to breathe. Need to breathe is suppressed and patient may stop breathing

Question 17

What could be contraindication to opioids

Answer 17

Patients with breathing problems , ex: COPD

Question 18

How do NSAIDs work as analgesics

Answer 18

1- NSAIDs inhibit COX-1 & COX-2. This stops prostaglandin production
2- reduces Hyperalgesia associated with inflammation and increased nociceptor sensitivity

Question 19

What are the effects of prostaglandins

Answer 19

cause peripheral sensitization by increasing nociceptor sensitivity. Produce signs of inflammations via vasodilation.
Also have anti-coagulation and hyperalgesic effects

Question 20

Side effects of NSAIDs

Answer 20

1- COX-1 in the GI will secrete ProstaglandinE2 which works to increase mucosal secretion, bicarbonate and blood flow to protect GIT => COX-1 inhibition can cause peptic ulcers and bleeding

2- COX-1&2 in the kindey will secrete PGE & PGI2 which work to vasodilator afferent arteriole to increase GFR and increases Na and water excretion =.COX1&2 inhibition can cause Na&water retention, hypertension and AKI

3- COX2 in CVS will secrete PGI2 which work to vasodilator & inhibit platelet aggregation vessels and COX-1 will secrete TXA for vasoconstriction and platelet aggregation => COX2 inhibition can cause stroke or MI

Question 21

Which is more fatal if inhabited COX-1 or COX-2 in CVS

Answer 21

COX-2 can not be inhibited or side effects will occur

Question 22

How come aspirin is given for CVS despite side effects of NSAIDs

Answer 22

Low doses of aspirin given will only irreversibly inhibit COX-1 , COX-2 will still be working. Will work to stop TXA from being released not PGI2 , so vasodilation and inhibition of platelet aggregation will still be working.

Question 23

Give examples of non selective , Cox-1 selective, Cox2 selective and COX3 selective drugs

Answer 23

Nonselective : ibuprofen, naproxen, diclofenac
Cox1: low dose aspirin
Cox2 : Celecoxib, Rofecoxib
Cox3: Paracetamol ( centrally in Brian and spinal cord )

Question 24

How do Local anaesthetics work

Answer 24

Block initiation and propagation of action potential by pain fibres , locally to a specific part of the body.
1- un ionized LA enters cell through membrane and is ionized
2- binds to Na channels to close the inactivation gate = no new action potential can be transmitted to spinal cord since sodium can’t enter cell

Question 25

What is the difference in ionized LA and when can this happen

Answer 25

ionized LA can only enter cell via the pore of the channel which will be slower due to restricted entry. Reduces effectiveness.
If there is bacteria it can ionize LA before it gets to neurons

Question 26

Why would LA be given with a vasoconstrictor ( adrenaline )

Answer 26

Vasoconstrictor is used to stop the spread of the LA to other tissues. means it’s more effective to tissue it is applied to .

Question 27

Side effects of LA

Answer 27

Common : 
1- nausea
2- dizziness 
3- bruising, redness, itching, swelling 
Less common 
1- drowsiness 
2- mental/mood changes 
3- ringing in ears 
4- vision changes 
5- tremors 
6- numbness 
7- headaches / backaches

Question 28

Name modern local anaesthetics

Answer 28

Lidocaine , benzocaine ,

Question 29

How can anti-depressents produce analgesia

Answer 29

1- Act on reuptake mechanism of serotonin to increase the amount of serotonin sitting in synaptic cleft
2- increasing activation of neurones sensitive to serotonin in the descending analgesic pathway = increased GABA and enkephalin release via inhibitory interneurons
3- reduced nociceptive singling through the spinal cord
4- breaks psychological and physical effects of pain

Question 30

When are anti-depressants helpful in pain management

Answer 30

In chronic and neuropathic pain since it helps with psychological and physical effect of pain