Pain : Analgesia Flashcards
What is Stress analgesia
A pain relieving pathway activated when the body is under extreme stress
Explain the process of stress analgesia
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
What are enkephalins known for
Being the body’s endogenous opioids ( naturally occurring )
Where are the opioid receptors expressed
On presynaptic and postynaptic terminal
How do the enkephalins reduce transmission of nociception
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
How can natural analgesia be harnessed
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 :
How does applying pressure ease pain
A beta fibres ( sensory mechxnosensitive fibres ) are activated which stimulate activation of inhibitory neurones. Results in the natural analgesic pathway
What are the three possible effects of general analgesics
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
What are the 3 main types of analgesics
1- Opioids ( morphine, codeine , pethidine )
2- NSAIDs ( aspirin, ibuprofen )
3- Local Anaesthetics( lidocaine, benzocaine )
What is the novel treatment of analgesic
Anti-Anti-depressent
How do Opioids work
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
When are opioids used and why is their use limited
1-surgical pain
2- child birth
3- terminal pain
Limited due to being very addictive
What are the side effects of opioids
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
How can opioids cause constipation
opioid receptors in the gut will oppose parasympathetic activation of contractions
How can opioids cause nausea/vomiting
stimulate chemoreceptors in the medulla
How can opioid cause respiratory depression
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
What could be contraindication to opioids
Patients with breathing problems , ex: COPD
How do NSAIDs work as analgesics
1- NSAIDs inhibit COX-1 & COX-2. This stops prostaglandin production
2- reduces Hyperalgesia associated with inflammation and increased nociceptor sensitivity
What are the effects of prostaglandins
cause peripheral sensitization by increasing nociceptor sensitivity. Produce signs of inflammations via vasodilation.
Also have anti-coagulation and hyperalgesic effects
Side effects of NSAIDs
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
Which is more fatal if inhabited COX-1 or COX-2 in CVS
COX-2 can not be inhibited or side effects will occur
How come aspirin is given for CVS despite side effects of NSAIDs
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.
Give examples of non selective , Cox-1 selective, Cox2 selective and COX3 selective drugs
Nonselective : ibuprofen, naproxen, diclofenac
Cox1: low dose aspirin
Cox2 : Celecoxib, Rofecoxib
Cox3: Paracetamol ( centrally in Brian and spinal cord )
How do Local anaesthetics work
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
