Pain Flashcards
What are the different types of pain
Somatic, visceral, neuropathic, sympathetically maintained.
what are the different types of nociceptors
Mechanical, thermal or polymodal
What are nociceptors
Naked nerve endings
What are the types of peripheral nociceptors
a b c
A LARGEST
C smallest
pain = A and C
Ab= touch
Ad and C= nociception
what fibre is the first pain
A delta
What fibre is the second pain
C fibres
What are the 4 processes of nociception
Detection - noxious stimuli, chem mediators which then activate nociceptors, cell membranes depolarise and AP is generated
Transmission - from pain fibre to spinal cord to brainstem to thalamus to cortex to higher brain
perception - How brain perceives the signals
Modulation - How we can change the pain signals to brain
How to nociceptors become activated
Trauma causes chemical mediator release from damaged cells (ATP, bradykinin, prostaglandins, histamine, 5-HT, H+) cell membranes depolarise and AP is generated
What is bradykinin
Produced during tissue injury
Phosphorylates TRPV1- opening
causes release of prostaglandins
what receptors are involved in detecting noxious stimuli
ION CHANNELS
ASIC- high conc of protons- causes depolarisation
P2X- high conc of ATP- causes depolarisation
enough depolarisation = activation of voltage gated Na Channel
TRPV1- Non selective cation channel- capsaicin, protons, acidic pH, noxious heat, endovanilloids- causes influx of Na and Cl causing depolarisation causing AP to occur
Gprotein coupled receptors (GPCR)
B2 receptor- bradykinin - causes protein kinase C release - phosphorylates TRPV1 opening, enhances depolarisation
Prostanoid receptors - prostaglandins- stims. PKA- phosphorylates VG Na channels
Inhibitor GPCRS- stimmed by opioids, cannibinoids, noradrenaline
Nerve growth factor can effect gene expression of ion channels such as TRPV1
What is the role of prostaglandins on pain transmission
Production occurs in inflammation
PGE2 causes K+ inactivation
AND phosphorylation of trpv1
What s the role of TRPV1 receptors
Body temp regulation
What neuropeptide does c-fibre activity release into the periphery
Substance P
CGRP
What do chemical mediators do to the threshold of C fibres
REDUCE
Increases activity for a given lvl of stimulus
What does substance P do
Release of inflammatory mediators and NGF - POSITIVE feedback - increases sensitivity of neurones - sustained release = hypersensitivity of pain
Where are A delta fibres found and what do they detect
Found in skin
First pain- informative, signal of danger
What chemical mediators are released from trauma
ATP, BRADYKININ, PG, HISTAMINES, 5HT, H+
activate nociceptors
depolarise cell membrane and AP generated
What is central sensitisation
Alteration in glutaminergic NTransmission/ NMDA receptor-mediated hypersensivity
Loss of tonic inhibitory control (disinhibition)
Glial cell interactions
Microglia release signalling molecules
APT acting on P2X4 releases BDNF from microglia which alters effect of GABA on neurones
How does ketamine work
NMDA receptor blocker
What is MOR-u
an opioid receptor
Morphine is a partial agonist
B-endorpin, Met-encephalin have activity
DAMGO is a synthetic peptide
CTOP synthetic peptide antagonist
What are some noxious stimuli
DOR delta
MOR Mu
KOR Kappa
ORL1 orphan receptor
all signal via Gai/o
What is the opioid receptor signalling pathway
Opiod agonist G-protein activation
activation of Gai inhibits cAMP, Ca+, K+
Receptor phosphorylation-> arrestin recruitment-> internalisation -> recycling
What can perception of pain do
Affective-motivational, sensory-discriminative, emotional and b/h experiences
Somatosensory cortex - processes info on location and intensity
amygdala = emotive components
sites of action of opioids
spinal- to reduce transmission thru dorsal horn, pre/post synaptic
periphery- reduce nociceptor afferent firing
central- many areas and descending inhibitory pathway
