Pain Flashcards
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 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
- Prostaglandins
- 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. )
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. )
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.
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.
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 )
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
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.
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.
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
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.
What was the first Local A ?
Cocaine
Mechanism of action of NSAIDS ?
Prostglandins
e2
f2
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
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
