Pain

Question 1

What are the different types of pain

Answer 1

Somatic, visceral, neuropathic, sympathetically maintained.

Question 2

what are the different types of nociceptors

Answer 2

Mechanical, thermal or polymodal

Question 3

What are nociceptors

Answer 3

Naked nerve endings

Question 4

What are the types of peripheral nociceptors

Answer 4

a b c
A LARGEST
C smallest
pain = A and C
Ab= touch
Ad and C= nociception

Question 5

what fibre is the first pain

Answer 5

A delta

Question 6

What fibre is the second pain

Answer 6

C fibres

Question 7

What are the 4 processes of nociception

Answer 7

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

Question 8

How to nociceptors become activated

Answer 8

Trauma causes chemical mediator release from damaged cells (ATP, bradykinin, prostaglandins, histamine, 5-HT, H+) cell membranes depolarise and AP is generated

Question 9

What is bradykinin

Answer 9

Produced during tissue injury
Phosphorylates TRPV1- opening
causes release of prostaglandins

Question 10

what receptors are involved in detecting noxious stimuli

Answer 10

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

Question 11

What is the role of prostaglandins on pain transmission

Answer 11

Production occurs in inflammation
PGE2 causes K+ inactivation
AND phosphorylation of trpv1

Question 12

What s the role of TRPV1 receptors

Answer 12

Body temp regulation

Question 13

What neuropeptide does c-fibre activity release into the periphery

Answer 13

Substance P
CGRP

Question 14

What do chemical mediators do to the threshold of C fibres

Answer 14

REDUCE
Increases activity for a given lvl of stimulus

Question 15

What does substance P do

Answer 15

Release of inflammatory mediators and NGF - POSITIVE feedback - increases sensitivity of neurones - sustained release = hypersensitivity of pain

Question 16

Where are A delta fibres found and what do they detect

Answer 16

Found in skin
First pain- informative, signal of danger

Question 17

What chemical mediators are released from trauma

Answer 17

ATP, BRADYKININ, PG, HISTAMINES, 5HT, H+
activate nociceptors
depolarise cell membrane and AP generated

Question 18

What is central sensitisation

Answer 18

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

Question 19

How does ketamine work

Answer 19

NMDA receptor blocker

Question 20

What is MOR-u

Answer 20

an opioid receptor
Morphine is a partial agonist
B-endorpin, Met-encephalin have activity
DAMGO is a synthetic peptide
CTOP synthetic peptide antagonist

Question 21

What are some noxious stimuli

Answer 21

DOR delta
MOR Mu
KOR Kappa
ORL1 orphan receptor
all signal via Gai/o

Question 22

What is the opioid receptor signalling pathway

Answer 22

Opiod agonist G-protein activation
activation of Gai inhibits cAMP, Ca+, K+
Receptor phosphorylation-> arrestin recruitment-> internalisation -> recycling

Question 23

What can perception of pain do

Answer 23

Affective-motivational, sensory-discriminative, emotional and b/h experiences
Somatosensory cortex - processes info on location and intensity
amygdala = emotive components

Question 24

sites of action of opioids

Answer 24

spinal- to reduce transmission thru dorsal horn, pre/post synaptic
periphery- reduce nociceptor afferent firing
central- many areas and descending inhibitory pathway

Question 25

What are the causes of neuropathic pain

Answer 25

CNS: cns multiple sclerosis
peripheral nerve damage: diabetic neuropathy, shingles, surgical amputation

Question 26

How is pain modulated centrally

Answer 26

Dorsal horn cells that normally activate via nociceptors start to respond to low threshold afferents (Ab)
Hyperalgesia- inc. pain w mild stim.
Allodynia- pain from non-noxious stim.
spontaneous pain- no stim
Neuropathic pain- damage to nervous system

Question 27

How does gabapentin treat neuropathic pain

Answer 27

Binds to voltage gated Ca channel aplha2delta subunit and reduce NT release

Question 28

What is the ascending pathway

Answer 28

Nociceptive fibres, Ad or C
periphery-> spinal cord -> dorsal horn diff. laminae (layers)
Synapses with diff. neurones which go to brain and ascend via spinothalamic tracts to somatosensory cortex- USES GLUTAMATE as NT.

Question 29

What is the descending pathway

Answer 29

starts in the brain-> PAG (serotonergic) and LC (noradreneric) go down spinal cord -> changes activity of central synapse in spinal cord.
Can activate inhibitory neurones
releases endorphins to act on opioid receptors. Inhibitory GPCRs (can stop NT release or action potential, inhibits CaV channels or Activates K channels -> hyperpolarisation)