Pain Flashcards by louisa wegbe

Pain vs Nociception ?

NOCIOCEPTION - neural encoding from actual or potential (future tissue damage ) -HARD WIRING

0 nociceptors - nerves which sense & respond to tissue damage in parts of the body.

Pain - subjective experience (unpleasant sensory & emotional experience ) of actual or potential ( future ) harm - PERCEPTION

pain is multifactorial
0 impacted by many things e.g gender , culture , anxiety , stress etc.

How well did you know this?

Not at all

Perfectly

How does the body transmit pains signal from periphery to brain ?

ASCENDING PATHWAY

signal from body (periphery) to brain

BODY ———> BRAIN (primary somatosensory cortex just posterior to central sulcus - parietal lobe ) -(ascending pathway.)

PSSC - Perceives sensation - in this case pain.

ex -

## damage to right hand hand
immune cells in damage area/ skin cells or any other damaged cells - inflamed & damage - release cytokines /inflammatory mediators
- Prostaglandins
  - Bradykinins
  - ATP
  - H+
  - Serotonin
  - Histamine
Cytokines - include prostaglandins

These chemicals stimulate Nociceptors - bind to receptors on the neurone causing depolarisation.

part2 - nociceptors further release chemicals e.g substance P , CGRP - promote inflammation - amplifying inflammatory response.

(Calcitonin gene related protein -highly potent vasodilator as well - helps protect cardiovascular system )

NOCICEPTORS under skin , ( can be in joints ) - detect noxious stimuli - immune cells etc release chemicals

2 TYPES

0 ALPHA / DELTA FIBRES
     myelinated 
    & small - 
     produce 
     fast sharp 
     pain

0 C FIBRES
Unmyelinated , smaller produce slow , poorly localised - throbbing / burning pain.

1st order neurone (nociceptor/ afferent -bringing info in) - Sensory nerve fibre respond to prostaglandins .
1st order neurone - carries
signal/ impulse to dorsal horn of spinal corn ( back of it )
1st Order neurone synapse with 2nd order within dorsal horn - relaying impulse. Substance P released by 1st order neurone to relay signal.
2nd order neurone crosses over to opposite side if spinal cord
2nd order - enters spinothalamic tract. ( from spinal cord - to Thalamus)
2nd order neurone - continues up the ascending pathway —–> up spinal cord ———–> medulla ——-> pons (medulla & pons midbrain ) —————> midbrain ———> terminates in Thalamus.
2nd order synapses with 3 order neurone in thalamus.
3 order neurone relay with part of the PSSC that correlates with injured hand. —–

(
this is on the left side of the brain - the 2nd order neurone cross over in spinal cord. )

How well did you know this?

Not at all

Perfectly

What is the descending pain pathway ?

Controls & can inhibit ascending pathway.

Neurones arise from periaqueductal grey matter —————–>
neurone synapses with neurone which produces Serotonin or Noradrenaline in nucleus Raphe magnus
Serotonergic / Noradrenergic neurone travels down to the dorsal horn of spinal cord
( where 1st and 2 order neurone of ascending pathway synapse
Serotonergic / Noradrenergic neurone - release serotonin & noradrenaline

SE/NA binds to pre - synaptic membrane ( 1st order neurone end terminal ) preventing release of substance P.

they inhibit and control communication btw them - controlling pain signals going up to brain )

In the Sustantia Gelatinosa - there is also also an interneuron (which is an opioid neurone ) with serotenergic / noradrenergic neurone synapses with - stimulates it to release - ENKEPHALIN
( endogenous opioid )

ACTION OF OPIOD

inhibit presynaptic neurone from releasing substance P by binding.
inhibits post- synaptic neurone from depolarising -stop continuation of impulse to thalamus.

periaqueductal grey matter - area of gray matter found in midbrain - surrounds cerebral aqueduct occupies column in brainstem (length - 14mm)

Nucleus Raphe magnus in medulla -

PAG - plays a role in analgesia - inhibits pain - through descending pathway

Substantia Gelatinosa - collection of cells in gray mater of dorsal horn - where 1st order & 2nd order neurones of ascending pathway synapse -

(synapse of neurones from body carrying info about pain & temp to neurones which will carry info to brain. )

How well did you know this?

Not at all

Perfectly

What is the difference btw the position of white & gray mater in brain & spinal cord ?

Spinal cord - White on the outside
0 Gray on the inside.

0 White matter contains axons of nerves

0 Gray matter - contains cell bodies.

Brain - Gray on the outside ,
0 white on the inside.

How well did you know this?

Not at all

Perfectly

Withdrawal reflex

0 Nociceptor - detect painful stimuli

Sensory neurone carries signal to dorsal horn of spinal cord.
Multiple reflex pathways activated

ACTIVATION
4. One of pathway excites motor neurone which activates flexor muscle in thigh)

INHIBITION
another pathway inhibits the motor neurone which activates extensor muscle in thigh -opposing muscle to flexor.

Another pathway crosses over to opposite side of spinal cord
0 does the opposite of the other leg (which detected pain )
- extensor muscle activated by motor neurone , flexor muscle inhibited.
(cross extension reflex )

CROSS EXTENSION REFLEX - contralateral limb - extension activated , flexion inhibited -
compensates for lack for support when ipsilateral limb withdraws from painful stimulus

happens to hold weight e.g if other leg withdrawing from something e.g fire - the other leg has to be ready to hold your weight.

How well did you know this?

Not at all

Perfectly

What is visceral pain ?

Pain originating from internal organs within :
0 Thoracic
0 Abdominal
0 Pelvic pain

visceral structures in these areas are high susceptible to :

0 Stretch /distension
0 Inflammation
0 Ischemia

Visceral pain - poorly localised - vague
( can feel like pressure , aching , deep squeeze )

How well did you know this?

Not at all

Perfectly

What is Radicular pain ?

caused by compression of nerve root (which exits out of spinal column )

0 can happen in neck ——-> radiates to shoulder blade & hand

0 happen in lower back ——–> radiate to lower back e.g sciatica

pain travels down nerve – radiating from spinal nerve root to extremity - partly or fully.

COMMON CAUSES

DISC HERINATION
- irritates nerve and compresses it.
anywhere from that point - you can get pain , tingling , numbness etc.

NOTE - RADICULOPATHY -( range of symptoms produced by pinching of nerve) - nerve does not work properly - conduction block / neuropathy .

SYMPTOMS - radiating pain.

weakness
numbness /paraesthesia
difficulty controlling muscles.radiating pain is one of its symptoms but involves other things

How well did you know this?

Not at all

Perfectly

What are the ways you can provide analgesia - mechanisms ?

Block pain pathway ( disrupt pathway which recognises pain ) e.g local anaesthetics
Inhibit amplification symptoms - NSAIDS - block COX enzymes - which trigger pain.
Boost inhibitory systems - OPOIDS / SRI - facilitate inhibitory system.

How well did you know this?

Not at all

Perfectly

Mechanism of Action of Local anaesthetics ?

numb small part of the body

BLOCKS GENERATION AND CONDUCTION OF NERVE ACTION POTIENTIAL ALONG NOCIOCEPTOR - brain does not get signal ——————————> NO PAIN.

IMPORTANAT

0 Unionised form - penetrate cell membrane - effective - can be absorbed by body
(non - polar and lipid bilayer so compatible )

0 Ionised - polar - cannot pass through membrane - ineffective - cannot be absorbed

IMPORTANT

if administer local A in a person with a lot of acid in body - it is will ionise as it is a weak base

this means that it the local A will quickly ionise and thus not be effective.

ACTS ON NOCIORECPTOR CELL MEMBRANE.

## Local A - administered -ionised form - needs to pass through aqueous extracellular phase ( is a Weak base)
LA becomes UNIOINSE-

has to be unionised - to penetrate membrane.

Ionised LA binds on sodium channels - (blocks transmembrane pore from the inside ) - prevent sodium from coming in to the neurone - prevent propagation of action potential down neurone.
( once ionised can no longer leave through membrane - stuck,)

ACTION POTIENTIAL

More NA + on outside
More K + on inside
Action potential -NA + moves in - make inside more positive = actional potential propagates.

How well did you know this?

Not at all

Perfectly

Which nerves are most & least susceptible to LA ?

0 small fibres more than large

0 Myelinated more than unmyelinated

MOST
1. Nociceptor

Sympathetic
Temp fibres
Motor fibres ( massive dose would be needed to paralyse a person )

LEAST

How well did you know this?

Not at all

Perfectly

Types of Local A ?

Lidocaine / Lignocaine - rapid onset - medium duration of action - commonly used

*- also an anti - arrithymic drug

Bupivacaine - slow onset , long duration , medium tissue penetration - used in long surgeries

(High myocardial toxicity - take care with patients with heart
conditions / failure.

PRACTICALITIES

If duration of action is too short ——- add
adrenaline* / catheter + infusion.

Unwanted blockade - as LA can affect sympathetic nerves , temp , motor fibres )

SOLUTION
0 Use low conc.

How well did you know this?

Not at all

Perfectly

What was the first Local A ?

Cocaine

How well did you know this?

Not at all

Perfectly

Mechanism of action of NSAIDS ?

Prostglandins

e2
f2

How well did you know this?

Not at all

Perfectly

How are Prostaglandins made ?

Immune cells and other cells convert phospholipids in membrane to Arachidnoic acid ——————————–> prostagladin H2 -( converted by COX 1 & 2) ———————————> Prostagladin E2 / F2

these cause fever , enhance pain & inflammation

How well did you know this?

Not at all

Perfectly

What is COX 1 & 2 ?

Function
- side effects of blocking them ?

Enzymes that covert Arachidonic acid to Prostaglandin H2 .

COX 1 - Physiological - is always active .- maintain homeostasis
especially in stomach , kidneys ,
Stomach - PGE2, PGF2 - reduce acid production.

Inhibition of COX 1 in stomach
SIDE EFFECTS 
0 Dyspepsia 
0 Nausea
0 Vomiting 
0 gastric ulceration
0 Haemorrhage

KIDNEYS
AA ——-> PGH2 ——–> PGE2 , PGI2 ( instead of PGF2)

PGE2 / I2 - Maintain renal blood flow.
- cause dilation of afferent arteriole in kidney maintain eGFR (even more important when issues in kidney - role becomes more significant)

inhibition of COX1 reduces these prostaglandins - increases risk of injury - can cause
Nephritis

NSAIDS - part of triple Whammy (drugs you do not want to be on if you have kidney issues
0 NSAIDS
0 Diuretics
0 ACE Inhibitors or angiotensin receptor blockers.

COX-2 - inflammatory
not always on - active during injury , stress , trauma

How well did you know this?

Not at all

Perfectly

What are the different types of NSAIDS ?

Study These Flashcards

Non -specific - act at both COX 1 & 2 e.`g :

   0 Iburpofen 
   0 aspirin - irrevsible & nati- platelet action
   0   Naproxen- 
   0 Diclofenac - reversible 
- highly potent
0 paracetamol ?

antipyertic , anti-analgesic , antinflammatory

inhibition of COX -1
increased acid productio , reduce production of protective mechanisms e.g mucous
associated with prolonged bleeding time.

aspirin - works mainly by inhibiting COX & platelets.

platelets produce Thromboxane A2
(Prostoglandin H2 —————–> Thromboxane A2 (catalysed by TX synthase)

if platelets are inhibited - Thromboxane A2 not produced ——-> platelet aggregation reduced —–> clotting reduced ——> blood thins.

aspirin - irreversibly inhibits COX -1 in platelets - blood thinning effect -platelets don’t have nucleus so effects persist as cant make new COX -1 enzymes

NSAIDS - with high COX -1 selectivity - have protective cardiovascular because of anti- platelet properties.

Selective - work only at COX 2

SIDE EFFECTS

normally a balance btw PGI2 & TXA2

0 PGI2 - causes vasodilation & inhibition of platelet activation. -produced mainly by COX 2

0 TXA2 - promote platelet aggregation & vasoconstriction produce mainly by COX - 1

if only COX2 inhibited - there will be more TXA2 vs PGI2 - increase in vasoconstriction & platelet aggregation ————————————————-> Increased risk of cardiovascular events e.g. stroke , myocardial infraction.

Where do corticosteroids work on the Prostaglandins synthesis pathway?

Study These Flashcards

Phospholipid ———————————————–> Arachidonic acid
( catalysed by phospholipase A2)

corticosteroids inhibit phospholipasea2 - blocking pathway.

Function of different prostaglandin ?

Study These Flashcards

PGE1 - Hyperalgesia
Renal vasodilator
Ductus arteriosus patency
Bronchodilation

PGF2a
- Bronchoconstriction

Uterine contraction ( sometimes used t terminate pregnancy )

PGI2 - prostacyclin- Hyperalgesia
vasodilation
Inhibition of platelet aggregation

TXA2 - Activation of platelet aggregation
Vasoconstriction

Where is the site of analgesia for :

Local A

NSAIDS

OPIODS.

Study These Flashcards

Local A - site of injury , peripheral nerve , spinal cord (spinal epidural )

NSAIDS - site of injury

OPOIDS - site of injury (not used as much - with opioids ), spinal epidural , brain - centrally

What are opiods ?

Study These Flashcards

Medicines - natural to synthetic

Natural - Opiates
0 Morphine - not very lipid soluble - slow onset , long duration of action.
0 Codeine - prodrug
0 Thembaine

Semi - synthetic 
  (chemically modified opiates )
      0 
      Diacetylmorphine - prodrug
     ( - mod morphine )
      0 Hydrocodone - 
        ( mod codeine )
      0 Oxycodone 
         ( mod 
          thembaine)

Sympathetic 
    0 Fentanyl - highly lipid soluble - passes easily through Blood brain barrier - has rapid onset , short duration of action ( as can leave just as fast as it came )
    0 Methodone
    0 Pethedine / 
       Meperidine

ACTION

0 mimic effects of endogenous Opiods :
1. endorphins 
2. enekaphlins
3. dynorphins
( release at brain / spinal cord ( locally ) &systemically

Opioids bind to opioid receptors 9 found in brain ,spinal cord & GI tract ) & activate them

3 types of opioid receptor 
mu -
Delta -
Kappa -
(they have special signs - look online )
THEY ARE ALL G COUPLE RECEPTORS

sedation , pain relief , anxiety reduction , euphoria etc.

Opioid administered - intravenously ( enters blood )
Opioid crosses BBB into CNS
Once in CNS - Opioid binds to opioid receptor located on pre -synaptic M of neurone in spinal cord for example.
1. prevents pre -s synaptic GABA releasing inhibitory neurone from releasing GABA (neurotransmitters - in general )( pre - synaptic inhibition )
  THIS RESULTS IN ACTIVATION OF DESCENDING PAIN PATHWAY.

HOW

binding causes part the some of the subunits of the g coupled/opiod receptor to bind & stop voltage gated CA2+ channels from opening.

CALCIUM NEEDED FOR VESICLES TO MOVE AND FUSE TO PRESYNAPTIC MEMBRANE RELEASING NEUROTRANSMITTER - ——- preventing GABA RELEASE prevents inhibition of descending pathway - DP activiated .

(GABA -inhibitory neurotransmitter - found in descending pain pathway

Descending P - inhibits & controls ascending pathway -)

2.  prevents depolarisation of post synaptic neurone (post - synaptic inhibition) OPOIDS BIND TO G COUPLED RECPTOR ON POST SM - SUBUNIT OF GCR BINDS TO VOLTAGE GATE K+ CHANNELS - OPENING IT - INFLUX OF K+ OUT OF NEURONE

So if neurotransmitter binds to NA+ channels on Post SM - sodium would enter at the same time K+ was leaving -POSITIVE CHARGE DOES NOT BUILD UP - DEPOLARISATION PREVENTED ——————————> action potential does occur.

In the case of GABA example - after descending pathway is activated :

endogenous opioids release and act on opioid receptors on pre /post SM. - causing inhibition of both 1st order & 2nd order neurone in dorsal horn of spinal cord.
PAIN CONDUCTION BLOCKED.

What are the effects of opioids ?

Study These Flashcards

Analgesia

0 Constipation

0 Sedation

0 Respiratory depression

0 Mood alteration

0 nausea -unwanted

0 vomiting - unwanted

Special case for Diamorphine / diacetyl morphine & codeine ?

Study These Flashcards

They are prodrugs (need to be broken down into active form )

Diamorphine —————————–> 6 monoacetyl morphine ————————————————–> Morphine ——————————————-> Morphine 6 Glucuronide

Codeine —————————–> Morphine ( by CP450 2D6) ————————————————-> Morphine 6 Glucuronide

in people who are ultra- metabolizers ( in terms CYP 2D6 ) & children - ultrametabolizers —– codeine rapidly metabolised - so morphine levels accumulate - toxic .- need to be careful.

THESE ARE ALL THE ACTIVE FORMS -

0 6 monoacetyl morphine

0 Morphine

0 Morphine 6 Glucuronide
(active metabolite of morphine )
- MORE POTENT THAN MORPHINE ( higher affinity for opioid receptor )
- MORE EASILY ACCUMULATES TO TOXIC LEVELS IN KIDNEY FAILURE- as it will not be cleared and levels accumulate.

What is the Analagesic Ladder ?

Study These Flashcards

Step up approach to treat chronic pain

Stength of Pain relief increased with increasing pain.

STAGE 1- Paracetamol + NSAIDS

STAGE 2 - Weak opioids -
hydrocodone
Codeine
Tramadol - prevents serotonin & NA reuptake.
(with or without non - opioid analgesics (e.g para & NSAIDS )

STAGE 3 - Strong / potent opioids -
- Morphine
-oramorph - used in severe pain (instead or morphine )(liquid morphine taken by mouth - takes effect faster than a fentanyl patch)
-Methadone
- Fentanyl
- Oxycodone
with or without non - opioid analgesics (e.g para & NSAIDS )

AT ALL OF THESE may have or may not use ADJUVANTS (co -analgesics - administration usually have indications other than pain relief. - but are still helpful e.g.
0 TCA e.g
- amytriptyline - for neuropathic pain

0 SSRI OR SNRI - ( serotonin - norephedrine reuptake inhibitors. ),

0 anticonvulsants e.g:
- pregabalin,
- gabapentin ,
0 Corticosteroids .e.g( dexamethasone)

Dexamethasone is an adjuvant analgesic; useful in reducing oedema caused by raised intra-cranial pressure, liver capsule pain and bone pain

0 bisphosphonates

Adjuvants - in some indications are used as first line treatment for specific types of pain e.g. diabetic painful neuropathy.

Points about Fentanyl ?

Study These Flashcards

Highly potent
Highly lipid soluble

Transdermal use - patch (topical )

Becoming a problem on the streets -a lot of abuse

very dangerous

What is Patient controlled analgesia ?

Patient controlled analgesia – they give themselves small doses of analgesic drug e.g morphine – they will only get a maximum amount in a 5 min period

What is : - Somatic - Visceral pain - Allodynia - Dyesthesia

NOCIOCEPTIVE PAIN - pain caused by physical or potential damage to the body. TYPES Somatic pain - generally described as musculoskeletal pain - pain originating in joints , bones (skin , muscles ) - can be either be : SUPERFICIAL - arise from nocioceptors in the skin & mucous membranes DEEP - originates from structures e.g joints , bones, muscles , tendons. PAIN DESCRIBED : - sharp , aching , throbbing , gwawing. 0 Visceral - pain originating from internal Thoracic , abdominal and pelvic organs e.g. Liver , Gut (when these structures are damaged / injured ) e.g - pelvic pain after Bladder infection - abdominal pain after IBD. PAIN DESCRIBED - Non localised - cramping pain - squeezing - pressure - aching NEUROPATHIC PAIN - damage to the Nervous systems / abnormal(not working properly ) causing pain. TYPES 0 Allodynia - non painful stimuli causing a sensation of pain (e.g brushing hair becomes painful of touching skin ) - sometimes seen in morphine toxicity. 0 Dysesthesia - Abnormal sensations e.g shocks , burning , tightening around body etc. seen in MS (multiple sclerosis )

Pain relief in renal failure ?

GFR below < 30mls/ min ( Stage 4 or 5 CKD ) - increased risk of toxic side effects with opiods due to metabolite accumulation - not being cleared by kidenys. Stage 3 - severe pain + renal failure 1st Choice - Alfentanil - undergoes hepatic metabolism , short half life , metabolites non toxic and only 1 % excreted by kidneys (limited renal clearance ) ``` Drugs to be avoided 0 NSAIDS (unless patient is already on dialysis ) 0 Morphine (however it can be used - in smaller doses and less often - as it can accumulate. ) ``` STAGE of CKD Stage 1 - > 90 mls/min Stage 2 - 89 - 61 mls/ min Stage 3 - 60 - 30mla/ min Stage 4 CKD - 29 mls - 15mls /min Stage 5 - < 15mls /min

Side effects of Opiods ?

Common - Sedation - Constipation - Nausea - Vomiting - dizziness Uncommon - Respiratory depression

Pain Flashcards

(28 cards)