Block C - Pain

Question 1

How does pain differ from nociception?

Answer 1

Pain is mulidimensional and refers to a unique sensory and emotional response to pain. Whereas, nocieption is the neural process which encodes for noxious stimuli

Question 2

What are 4 main benefits of pain and what would happen if she didn’t have pain mechanisms?

Answer 2

1. withdrawal reflex
2. Tissue repair and healing
3. Pain learning
4. motivates seeking treatment

If we didnt have pain then indiviudals will be greatly impacted by injury, infection ,self mutaliation and in some cases succumb to early death

Question 3

True or False: All pain has a function.

Answer 3

False, there are some pain types that have no function at all

Question 4

what are the main dimensions of pain?

Answer 4

1. Intensity - pain scale, mild, moderate and severe
2. characteristics - is it sharp, dull, aching
3. Modality - heat, physical touch
4. Location - superficial or deep, focal or diffuse
5. Time - acute or chronic
6. Behaviour - how is the pain effecting behavioural response
7. Emotion

Question 5

What is the 3 broad classification of pain

Answer 5

1. nociceptive
2. inflammatory
3. pathological

Question 6

What is nociceptive pain, what are the subtypes?

Answer 6

Nociceptive pain is physical or potential damage to body tissue in response to basic modality like temperature and mechanical pressure.

The 3 subtypes include:
1. Superficial somatic
2. Deep somatic
3. Visceral pain

Question 7

For each nociceptive pain type, name effected tissue, stimuli, characteristics and localisation

Answer 7

Superficial somatic:
tissue - skin and superficial tissues
Stimuli - burns, abrasions, lacerations
Character: Sharp burning pain
Localisation: Easy to locate and well define

Deep somatic:
Tissue - bones, tendons, ligaments
Stimuli - sprains, strains and fractures
character: dull aching pain
localisation: Difficult to locate

Visceral pain:
Tissue - internal organs
stimuli - hypoxia, inflammation, ischemica, stretching
character: dull deep squeezing pain, hard to explain
localisation - diffuse and hard to localise as in most cases pain will be felt distant to the origin site

Question 8

What is the basic pathway for pain peception

Answer 8

1. noxious stimulus
2. detection by nociceptors
3. tranduction via nociceptive neurons to CNS
4. activation of motor pathway at level of spinal cord - for reflex if required
5. modulation occurring at spinal level
6. Perception - high order brain regions which facilitate multidimensional aspect of pain

Question 9

What is inflammatory pain and what are the 2 subtypes asscociated with this kind of pain

Answer 9

Pain that is associated with tissue injury and peripheral inflammation which often results in pain hypersenitivity

2 types:
Hyperalgesia: Increase pain sensitivity to a stimulus that usually evokes pain

allodynia: increased pain sensitivity to a stimulus which doesn’t usally evoke pain

Question 10

True or False: Inflammatory pain is associated with protection and repair. Justify answer.

Answer 10

True, inflammatory pain increase pain sensitivity which prevents an individual from interaction with pain stimulus which has the ability to worsen original injury.

Question 11

What is pathological pain and what the subtypes?

Answer 11

Pathological pain is similar to nocieceptive and inflammatory pain but also carries neuroimmune componants. 3 types include, phatom pain (pain in amputed limbs where nerves have been severed), neuropathic pain (pain from damaged peripheral nerves and not directly from injury site) and psychogenic pain (emotions, mental state and behaviour)

Question 12

Compare the threshold type and adaptiveness of each pain type

Answer 12

Nociceptive pain
- adaptive
- high threshold
inflammatory pain
- adaptive
-Low threshold
Pathological pain
- maladaptive
- low threshold

Question 13

Name the 3 main nociceptive stimuli

Answer 13

1. Thermal
2. chemical
3. Mechanical

Question 14

Name 5 types of nocicpetors

Answer 14

1. Mechanoreceptors
2. chemical receptors
3. mechano-thermoceptors
4. polymodel: can detect all 3 stimuli
5. slient - low threshold, only activated when injury is present

Question 15

SP and CGPR are commonly released from nociceptive fibres. How do they influence pain sensation?

Answer 15

These peptide will play a role in histamine release, vasodialation and brady kinin release which will extend, broaden and amplify pain so that it can be felt beyound the site of injury

Question 16

Explain chemical mediators and how they influence hyperalgesia and allodynia.

Answer 16

Damage cells at the injury site will release prostagladins, bradykinin and sertonin which then act on specific receptor to sensitise (hyperalgesia) and activate silent receptors (allodynia)

Question 17

What are the 2 types of afferent fibres for nociception and compare and contrast they characteristics

Answer 17

A delta and C fibres which are both thin fibres that release glutamate. A delta fibres are myelinated and so there conduction velocity is higher than C fibres. A delta fibres play a role in superfical somatic pain so that very sharp, immediate pricking pain. These fibres have small receptive field which allows for pain to be easily localised. C fibres however, are unmyelinated and this have a slower conduction velocity. Alongwith glutamate, c fbres will also release SP and thus have a sustained response. These fibres are associated with deep somatic and viseral pain and is rather hard to localise due to larger receptors fields.
both fibres will terminate in the dorsal horn by synapsing with 2 order nociceptive dorsal horn neurons

Question 18

what are the two main excitatory NT’s and what do they target

Answer 18

Glutamate which targets AMPA receptors

SP which targets NK1 receptor

Question 19

describe the withdrawal arc and how nociceptive connections facilate this.

Answer 19

nocieptive fibre so a delta and c fibre are poly synaptic and so not sonly do they synpase with upper control centres but they also synapse with one inhibitory interneuron and one excitatory neuron. These intern neurons then synapse with afferent motor neurons. So in withdrawl arc reflex. one inhibitory interneuron will inhibit the anatgonist muscle and they other will excite the agonist muscle.

Question 20

What are the 3 spinothalamic tracts of ascending pain pathway and are they specific or not specific?

Answer 20

1. Neospinothalamic - synpase only with pain specific neurons
2. paleospinothalamic - synapses with either non-specific neuron and pain specific neurons
3. arcispinothalamic ^

Question 21

What fibres correspond with each spinothalamic tract?

Answer 21

Neospinothalamic - Adelta fibres
Archispinal and paleospinal thalamic - C fibres

Question 22

Match each spinothalamic tract with type of nociceptive pain type

Answer 22

Superficial somatic - Neo, Paleo and Archispinal

Deep somatic - Paleo and archispinal

Vicersal - Paleo and Archispinal

Question 23

Breifly describe the pathway for Neospinal and paleo,archispinal tracts

Answer 23

Neospinal: A delta –> VPM –> primary somatosensory cotex

Paleo,Archispinal: C fibres –> IL –> secondary somatosensory cortex

Question 24

What is referred pain? Provide an example.

Answer 24

Referred pain is when a superficial somatic and viseceral primary afferent converge on the same 2nd order neuron in paleospinal thalamic tract and so there is perception of pain at the superficial site die to focal and small receptive fields rather than the organ.

An example of this is a myocardial infraction where by pain is felt in the arm rather than the heart

Question 25

Name 5 brain regions and there associated role in pain

Answer 25

1. Primary somatosensory cortex - perception of pain
2. Secondary somatosensory cortex - recognising and remembering pain
3. PAG - descending modulatolry control
4. Reticular formation and hypothalamus - autonomic control
5. Insular, cingulate & frontal cortices - emotional aspect

Question 26

What is the gate control theory?

Answer 26

Non painful inputs can close the gate to painful inputs to CNS. Non nociceptive neurons and nociceptive neurons project to inhibitory interneuron. Nocicpetive fibres will inhibit the interneuron while non nocicpetive neurons will excite. the relative frequencies of AP from nocicpetive and non-nocicpetive neurons will determine how open the gate is and how much pain information is passing through

Question 27

name the 2 excitatory transmitters and 2 inhibitory transmitter/receptors in pain modulation? State whether they are found post/presynaptically.

Answer 27

Excitatory:
Glutamate presynaptically to bind on AMPA post synaptically

SP presynaptically to bind to NK1R postsynaptically

Inhibitory:
Opioid receptors that sit on post synaptic neuron

Gabageric neurons from PAG will release GABA which then bind post synaptically

Descending sertonergic neurons which interaction with postsynaptic neurons will release serotonin which binds to 5HT receptors in post synaptic neuron

Question 28

Whats the different between analgesic and anaesthetic

Answer 28

analgesics act to relieve pain without loss of consciousness while anaesthetics act to inhibit response to stimulus with (general) or without (local) loss of consciousness and loss of vital functions

Question 29

How do NSAIDs work?

Answer 29

Inhibits prostagladin synthesis by inhibiting COX enzyme. Has main role in periphery but can also work at conduction and modulation level

Question 30

How does opioids work?

Answer 30

Act on as agonists on opiodergic receptors which causes block of NT release (via preventing influx of Ca). Opiods work primarily on the conduction pathway and perception in cortex

Can also effect GABAgeric neurons in PAG by dishibiting them and therefore allowing excitation of PAG neurons to release serotonin

Question 31

Step out the levels of pain perception with the local of each level

Answer 31

Transduction in the periphery

Conduction in the dorsal horn of the spinal cord

Modulation in the desending pathways

Transmission at the thalamus

Perception in the cortex

Question 32

How does local anaesthesia work?

Answer 32

Works by inhibtiong sodium voltage gated channel therefore preventing APs from arise

Question 33

Compare the difference between reflexive tests and non-reflexive tests

Answer 33

Reflexive test look at periphery and spinal cord by assessing automatic responses from pain. Whereas, non reflexive looks at higher cortical perception, desending modulation and clinical assessments of pain through behaviour responses

Question 34

For animal models, name 3 reflexive tests for thermal pain

Answer 34

1. Tail flick - apply heat onto tail and observe how often they flick tail
2. Hot plate - place animal on hot plate and observe how often they lift or lick there paw - this looks at both automatic responses but also behavioural response (paw licking is higher order)
3. Hargreaves - similar to hot plate but heat is only apply to hind legs for example - this allows for there to be a control and effected

Question 35

For animal models, name 2 reflexive tests for mechanical pain

Answer 35

1. Vonfrey - test an assortment of filaments with different flexibility/pressure but applying them to paw of animal and observe when they lift there foot - thus look at superficial pain
2. applying mechanical pressure to a muscle, joint or paw to assess deep somatic pain

Question 36

what kind of pain does von frey filaments look at

Answer 36

mechincal allodynia in neuropathic and inflmmatory pain

Question 37

What are the 2 principals you must consider when selecting an appropriate pain model

Answer 37

1. understand clinical presentation of pathology known as face validity - use this to match pathology with kind of test for example post surgical pain pathology would match with a post surgical pain model
2. behavioural measures that assess issues of that particular disease

Question 38

What does a acute post surgical pain model look like?

Answer 38

often involves incision of superficial and deep tissue then sutured up. Vonfrey filaments are then place adjacent to surgery site to assess mechanical allodynia following surgery. Another aspect this pain model looks at is guarding behaviour and how the animal guards the incision site.

Question 39

Briefly describe what a inflammatory pain model looks like.

Answer 39

Injection of irritants in skin, paw, muscle, joint or organ to replicate inflammatory disorders.

Question 40

Compare the chemicals which are used for an acute and chronic inflammatory pain model

Answer 40

For acute inflammatory pain capsaicin is injection and binding of this chemical with the TRPV1 receptor will cause local neurogenic inflammation, thermal and mechanical hyperalgesia and mechanical allodynia in surround around. Carrageen is another chemical which generate both acute and chronic inflammatory pain. This chemical replicates inflammatory pain seen in sprains, strains and myositis. Another way to assess chronic inflammatory pain is freund adjvant which generates hyperalgesia + behavioural and functional responses seen in inflammatory disorders

Question 41

Generally neuropathic pain is difficult to assess. In animal models, how is neuropathic pain replicated?

Answer 41

If looking at spinal cord then that usually involves surgically lesioning the cord, laser injury or contusion however, if looking at peripheral nerve injury then you can tie, transect and lesion nerves

Another model of neuropathic pain is chronic constriction injury which works by contricting the sciatic nerve by sutures and assessing pain

Question 42

True or False, TLR4 is associated with allodynia. Provide justification

Answer 42

True. The gene encoding for TLR4 was compared in mice with this gene and knockout mice without this gene. They found absence of allodynia in knockout mice

Question 43

What is adoptive transfer and what does it demonstrate

Answer 43

Adoptive transfer is a process whereby immune cells are taken from individual and transfer to another individual. In doing this they found that cells from high pain patients can be transfered into individuals with pain and induce high pain. This was not applicable in when trying to transfer cells from no - low pain patients

Question 44

In humans, how can mechanical pain be assessed? Just name the types and what kind of pain they assess

Answer 44

1. Von frey for superficial somatic pain
2. Cuff algometry for deep somatic pain

Question 45

How does von frey work in testing pain in humans? Would you observe different responses for hyperalgesia and allodynia?

Answer 45

In hyperalgesia you would measure pain via pin pricking pain and observe the response while in allodynia you would test multiple filaments and observe the threshold or response frequency

Question 46

How does cuff algometry work

Answer 46

You place computer control pneumatic torniquet cuff on a patient and rise pressure until the individual begins to feel pain (detection threshold) and the till they can stand pain anymore (tolerance threshold)

Question 47

In humans, how is electrical pain assessed? Describe this process.

Answer 47

Painful cutaneous electrical stimulation which works by placing electrodes on skin and increase the intensity to record pain threshold and tolerance. This directly activate nociceptive fibres and bypass nociceptors.

Question 48

In humans, how is chemical pain assessed? Just name them.

Answer 48

1. UVB inflammatory pain model
2. Capsacinin

Question 49

Describe how UVB inflammatory pain model works for assessing chemical pain

Answer 49

Hyperalgesia - Firstly you induce skin erythema by UVB irradiation and then follow up by performing thermal, pressure, and mechanical pain tests and observe differences in UVB treated and untreated

Question 50

How does capsaicin work for inflammatory pain?

Answer 50

Assess hyperalgesia and allodynia by topically applying or injecting capsaicin which binds TRPV1 and cause neurogenic inflammation - this is a good for testing analgesics.

Question 51

What’s the differance between detection threshold and pain tolerance

Answer 51

Pain detection threshold is the stimulus intensity and pain intensity at which an individual will begin to feel pain. Whereas, the stimulus tolerance threshold is the stimulus intensity/duration that a patient can no longer tolerate the pain

Question 52

what is stimulus response curve in response to normal pain, analgesics and hyperalgesia & allodynia

Answer 52

An analgesic prevent perception of pain and this the detection and tolerance threshold will be moved to the right indicating a reduced ability to detect a pain stimulus and a greater tolerance to that stimulus

Following injury where their may be hyperalgesia and allodynia, the pain detection and tolerance threshold moves to the left. This is because there is increased sensitisation to pain and so detection is much more sensitive and tolerance is weak.

Question 53

Describe the key components of the human endotoxin-capsaicin model

Answer 53

Intradermal injection of capsaicin (TRPV1) into arm with a low dose intravenous endotoxin (TLR4) 3 hours prior. Measure areas of allodynia with brush and puncate hyperalgesia using vonfrey and flare which is visual. Provides neuropathic pain model and also shows clinical evidence for TLR4 potentiation of pain

Question 54

Describe the major benefits and limitations of one- versus multi-dimensional clinical pain scales.

Answer 54

One dimensional is simple, efficient and minimally intrusive however they asses limited parts of pain experience. - Multidimensional looks at sensory, affective, temoporal, location and intensity eg. McGill pain questonaries but are time consuming and hence used less.