Physiology of pain 1

Question 1

what is a nociceptor?

Answer 1

a sensory neuron that responds to damage to a stimulus

Question 2

a mutation in what channel and gene causes a patient to feel no pain?

Answer 2

mutation in a sodium channel due to SCN9a gene mutation

Question 3

what type of pain is due to

i) the normal functioning of neurons in response to tissue injury?
ii) pain in response to injury/lesion in the nervous system

Answer 3

i) nociceptive
ii) neuropathic

Question 4

true or false about nociceptors

1) they are primary sensory neurons that detect pain
2) they are bipolar neurons
3) the peripheral terminal sits under the skin and conveys information through primary rami to spinal nerves

Answer 4

1) true
2) false - they are pseudo unipolar
3) true

Question 5

in the spinothalamic tract - where do first order neurons (nociceptors) synapse onto second order neurons? where do second order neurons synapse to third order neurons?

Answer 5

first order synapse to second order in the the dorsal horn of the spinal cord second order synapse to third order in the thalamus

Question 6

where are cell bodies of nociceptors found? (2 locations)

Answer 6

dorsal root or cranial nerve ganglion

Question 7

what is the myelin content, diameter, sensitivity to for i) Aa and Ab fibres ii)Ad iii) C-fibres

Answer 7

i) myelinated, large diameter and sensitive to light touch and proprioception ii) thinly myelinated, medium diameter and sensitive to light touch, temperature and nocicepion iii) unmyelinated with small diameter and sensitive to temperature and nociception

Question 8

which two afferent nerve fibres transmit pain information to the spinal cord?

Answer 8

Ad and C fibres

Question 9

where are free nerve endings for Ad and C fibres found?

Answer 9

in the tissue

Question 10

nociceptors are found in muscles, joints, viscera and the meninges true or false?

Answer 10

true

Question 11

which afferent nerve fibre is responsible for i) sharp pricking pain ii) slow dull ache or burning pain

Answer 11

i) Ad ii) C-fibres

Question 12

which afferent nerve fibres work by saltatory conduction?

Answer 12

Aa and Ab

Question 13

which type of fibres are found in

i) pacinian corpuscles
ii) meissners corpuscle
iii) merkel disks
iv) free nerve endings

Answer 13

I, ii, iii = Ab
iv = Ad and C fibres

Question 14

what fibre activation occurs at peak A, B and C

Answer 14

A = Aa and Ab

B = Ad

C = C fibres

Question 15

which pain response is the first and fastest? which fibres are responsible for this?

Which pain response is second and slower? which fibres are responsible for this?

Answer 15

first and fastest pain response is sharp pricking pain due to Ad fibres

the second slower response is dull ache due to C fibres

Question 16

name five things that nocieptors are activated in response to

Answer 16

1) pressure
2) heat
3) cold
4) chemicals
5) tissue inflammation/damage

Question 17

what is a polymodal nociceptor and what stimuli does it respond to?

Answer 17

respond to different modalities and stimuli eg C fibres

respond to temp, pressure and chemical stim

Question 18

which type of ion channels respond to pressure and where do they sit?

Answer 18

mechanically sensitive channels respond to pressure and these sit in the peripheral terminal of nociceptors

Question 19

what is the sequence of events in pressure transduction from being hit with a hammer to a signal being sent to the spinal cord?

which tract does this signal travel along?

Answer 19

1) hit by hammer
2) deformation of the membrane of the nociceptor
3) deformation causes mechanically sensitive channels to open
4) cations enter and nociceptor is depolarised
5) signals travel to the spinal cord via the SPINOTHALAMIC TRACT

Question 20

which receptors are involved in temperature transduction?

how many TMD do these receptors have?

Answer 20

TRP channels

have 6 TMD

Question 21

what is the vanilloid receptor aka?

what does it respond to?

what acts as an agonist at this receptor?

Answer 21

Vannilloid receptor aka TRPV1

responds to hot temperature

agonised by capsaicin

Question 22

what stimuli does TRPM respond to?

what is it agonsied by?

Answer 22

responds to cold

agonised by menthol

Question 23

name six agents that can activate nociceptors directly

Answer 23

ATP, H+ and 5HT, histamine, bradykinin, PG, NGF

Question 24

which receptors does ATP bind to and where are these found?

Answer 24

bind to purinergic receptors found on peripheral terminals of nociceptors

Question 25

what causes the pain pathway to be switched on in runners?

Answer 25

lactic acid build up causes H+ to bind to acid sensing ion channels

Question 26

nociceptors have lots of branches

true or false?

Answer 26

true

Question 27

what can activation of one branch of a nociceptor trigger the release of?

Answer 27

Substance P from one branch

Calcitonin gene related peptide (CGRP) from another

Question 28

what does

i) substance P
ii) CGRP

release from nociceptors cause?

what type of inflammation is this seen in?

Answer 28

substance P causes vasodilation and CGRP causes activation of mast cells

• seen in neurogenic inflammation

Question 29

how does activation of mast cells by CGRP cause neurogenic inflammation?

Answer 29

mast cells release histamine which causes inflammation

Question 30

what is the sequence of events in neurogenic inflammation from arrival of tissue damage to secondary effects such as vasodilation? what does this ultimately lead to?

Answer 30

1) arrival of tissue damage or inflammation will switch on nociceptor
2) AP will shoot up towards the spinal cord
3) AP will also pass down branch points of the nociceptor to the peripheral terminals of the branches
4) Aps arrive at periph terminal and cause release of substance P and CGRP
5) this causes vasodilation, increased blood vessel permeability and activation of mast cells

THIS ALL LEADS TO INFLAMMATION

Question 31

What can modulation of nociceptors by inflammation ultimately lead to?

Answer 31

hypersensitivity

Question 32

define

i) hyperalgesia
ii) allodynia

Answer 32

i) a noxious (painful) stimuli that produces an exaggerated response
ii) non noxious (non painful) stimili that produces a pain response

Question 33

what is peripheral pain hypersensitivity?

i) does it involve hyperalgesia, allodynia or both

Answer 33

hyperalgesia at the INJURY SITE due to activation of inflammation at the peripheral terminal of nociceptors

i) involves hyperalgesia

Question 34

what is central pain hypersensitivity?

i) does it involve hyperalgesia, allodynia or both?

Answer 34

occurs within the spinal cord (AWAY FROM INJURY SITE) and is the major mechanism in neuropathic pain

i) involves both

Question 35

what type of sensitisation is an increase in responsiveness of peripheral ends of nociceptors and is driven by tissue injury and inflammation?

Answer 35

peripheral sensitisation

Question 36

what three mediators can bind their receptors and reduce threshold of activation in peripheral sensitisation?

Answer 36

bradykinin, NGF and prostaglandins

Question 37

which channels do

i) bradykinin and NGF
ii) prostaglandins

reduce the threshold for?

Answer 37

i) TRPV1
ii) sodium channels

Question 38

name a process that can cause peripheral sensitisation

Answer 38

sunburn

Question 39

BRADYKININ & primary hyperalgesia

i) what channel does it act on?
ii) is this direct or indirect?
iii) what class of receptor does it bind and what does this lead to to cause hyperalgesia?

Answer 39

i) acts on TRPV1 channels
ii) indirectly
iii) binds GPCR which causes activation of PKC and phosphorylation of TRPV1 making it more sensitive (and fire more easily)

Question 40

what does phosphorylation of TRPV1 cause?

Answer 40

reduces its threshold for firing so it is more sensitive and fires more easily = primary hyperalgesia

Question 41

which tract is aka the pain pathway?

Answer 41

spinothalamic tract

Question 42

IN THE SPINOTHALAMIC PATHWAY

i) where do cell bodies of first order neurons sit?
ii) where do first order synapse onto second order neurons (location and name)?
iii) what is the tract of lissauer?
iv) which two molecules are released from sensory neurons (nociceptors) and excite second order neurons

Answer 42

i) in the DRG
ii) at the top of the dorsal horn in the substantia gelatinosa
iii) the collateral branches formed when axons enter the dorsal horn that ascend or descend through spinal cord segments
iv) glutamate and substance P

Question 43

IN THE SPINOTHALAMIC TRACT

i) where do second order neurons decussate?
ii) which column do they then ascend in
iii) where do they synapse onto third order neurons?

Answer 43

i) in the dorsal horn at each level
ii) anterolateral column
iii) thalamus

Question 44

why does reffered pain occur?

Answer 44

due to convergence of visceral and cutaneous nociceptors on the same second order neuron in the spinal cord

Question 45

IN THE SPINOTHALAMIC TRACT

i) where do third order neurons ascend to from the thalamus? what lobe is this located in?
ii) which componets tell you where it hurts and the type of pain?

Answer 45

i) third order neurons ascend from thalamus to the somatosensory cortex in the parietal lobe
ii) somatosensory components tell you where it hurts and what kind of pain it is

Question 46

what is the basis for the emotional component of the spinothalamic tract?

i) what happens to the pain perception of a patient with insula lesions?
ii) name two cortical regions that are activated in pain

Answer 46

third order neurons also project to the insula and cingulate cortex in the limbic system

i) patients with insula lesions know when they are injured but dont feel pain
ii) pain network can involve the limbic system and PFC

Question 47

what us stress induced analgesia?

i) who has this been sseen in?
ii) how is this acheieved?

Answer 47

stress induced analgesia is supressing pain to survive (seen in animals)

i) seen in battle victims and endurance athletes
ii) achiebed by higher cortical regions which can activate descending modulatory pathways

Question 48

what are the two important regions involved in descending regulation of pain and where are they found?

Answer 48

two important regions are

• periaqueductal grey matter found in the midbrain around the cerebral aqueduct
• rostal ventromedial medulla found in the medulla/raphe nucleus

Question 49

what are the labels A, B, C, D in the descending regulation of pain?

Answer 49

A = cortical regions eg cingulate cortex, hypothalamus and amygdala

B = PAG

C = RVM

D = the dorsal horn

Question 50

INHIBITION OF PAIN

i) what type of neurons are excited by PAG neurons?
ii) where are the cell bodies of these neurons?

Answer 50

i) serotonergic neurons
ii) cell bodies are in the RVM

Question 51

in the inhibition of pain

i) which type of neurons are excited by serotonergic neurons (with cell bodies in RVM) and what do these act on?
ii) what does this ultimately lead to?

Answer 51

i) serotonergic neurons excite inhibitory interneurons which act on second order neurons of the ST tract
ii) this causes inhibition of pain being transmitted up the spinothalamic tract

Question 52

give two examples of endogenous opioids

i) where are they found
ii) are they excitatory or inhibitory?
iii) what class of receptors do they work on?
iv) what neurons are they released from? and what effect does this have?

Answer 52

endogenous opioids = endorphins and enkephalins

i) found in the RVM, PAG and dorsal horn
ii) work on inhibitory GPCRs
iv) released from interneurons throughout the CNS which inhibits second order neurons in the spinothalamic tract