Pain, nociception and analgesia

Question 1

What is the definition of Pain?

Answer 1

The subjective conscious appreciation of a stimulus that is causing, or threatening to, cause tissue damage

Question 2

What is the definition of Nociception?

Answer 2

The physical process of detection and transmission of a noxious stimuli

Question 3

What are nociceptors?

Answer 3

They detect noxious stimuli

Question 4

What is the definition of analgesia?

Answer 4

Reduction or prevention of either nociception or pain (without loss of consciousness)

Question 5

What do mechanical nociceptors detect?

Answer 5

High intensity mechanical
Strong thermal (>60C)

Question 6

What do polymodal nociceptors detect?

Answer 6

High intensity mechanical
Thermal (>45C and <10C)
Chemical

Question 7

The A(delta) fiber is responsible for what sort of pain?

Answer 7

Fast pain
Sharp, pricking
Well-tolerated

Question 8

The C fiber is responsible for what sort of pain?

Answer 8

Slow pain
Burning, aching, throbbing,
Poorly tolerated

Question 9

Which fibers are myolenated? A(delta) or C?

Answer 9

A(delta)

This means they transmit signals quicker

Question 10

Which fibers have a larger diameter? A(delta) or C?

Answer 10

A(delta)

Question 11

ASIC (Acid sensing ion channels) detect what?

Answer 11

Acid (H+)

Question 12

P2X3 (Purinergic receptor) detects what?

Answer 12

ATP and Mechanical stimulation

Question 13

VGNa (Voltage gated sodium ion channel) detects what?

Answer 13

Mechanical stimulation

Question 14

VR-1/TRPV-1 (Vanilloid -1 receptor) detects what?

Answer 14

Capsaicin
H+
Heat

Question 15

Is nociception just exaggerated sensory transmission?

Answer 15

They conduct at slow velocities
Nociceptors have different thresholds of activation
They have different sites of projection into the spinal cord
They elicit different physiological responses in dorsal horn neurones
Information ascends in different pathways

Question 16

Nociceptors detect what in relation to heat?

Answer 16

Intensity

Question 17

Thermoreceptors detect what in relation to heat?

Answer 17

Presence (not intensity)

Question 18

Which neurone(s) synapse to the wide dynamic range neurone?

Answer 18

A(delta) fibre only

Question 19

Which neurone(s) synapse to nociceptive neurones

Answer 19

Both A(delta) and C fibres

Question 20

Spinothalamic pathway

Answer 20

Cerebral cortex
Thalamus
Lateral spinothalamic tract
Dorsal root axon (A(d), C)

Responsible for pain, temperature and some touch

Question 21

Dorsal column - medial lemniscal pathway

Answer 21

Cerebral cortex
Thalamus
Medial lemniscus
Dorsal column
Dorsal root axon (A(a), A(b), A(d)

Responsible for touch, vibration, two point discrimination, proprioception

Question 22

What is referred pain?

Answer 22

When two fibres synapse to the same neurone

Question 23

What is hyperalgesia?

Answer 23

Increased response to a noxious stimulus

Question 24

What is Allodynia?

Answer 24

Painful responses to non-noxious stimulus

Question 25

What is neuropathic pain?

Answer 25

Pain unrelated to peripheral nociception, sometimes called pathological pain (serves no purpose) e.g nerve damage, spinal damage, thalamic stroke

Question 26

What is an itch?

Answer 26

Afferent input is via both A(d) and C fibres from free nerve endings. Inflammation can cause it However, analgesics don't inhibit itch!

Question 27

Do analgesics inhibit itch?

Answer 27

No

Question 28

What are the differences between A(d) and C fibres PREsynaptically?

Answer 28

C fibre terminals contain more substance p (cgrp)

Question 29

What are the differences between A(d) and C fibres POSTsynaptically?

Answer 29

Both A(d) and C fibres synapse to AMPA and NMDA receptors But only C fibres synapse to NK-1 receptors

Question 30

Substance P activates what?

Answer 30

Gq GPCR (increased Na/Ca influx, decreased K efflux, increased IP3)

Question 31

TRUE/FALSE? Nociceptor transmission can undergo 'wind-up'

Answer 31

TRUE

Question 32

What chemical inhibits 'wind-up'

Answer 32

2-AP5

Question 33

A(a) and A(b) non-nociceptive mechanoceptors do what in relation to the C-fibre?

Answer 33

They inhibit the C-fibre

Question 34

What is supraspinal control of pain?

Answer 34

Brain stimulation inhibits nociceptive spinal neurones (causes pain relief)

Question 35

Describe the descending pain pathway

Answer 35

Hypothalamus PAG (Midbrain) Raphe Nuclei (Medulla) Dorsal Horn (Spinal Cord)

Question 36

Describe the action of Opioids (in terms of brain regions)

Answer 36

Excite/Increase: - PAG - Nucleus reticulas (medulla) - excites raphe nuclei Inhibit: - Dorsal horn/Spinal cord - Periphery

Question 37

What is the action of opioids in the PAG

Answer 37

Inhibit both glutamate and GABA release But glutamate is released from multiple neurones so leads to an overall increase in excitation of the raphe nuclei (medulla).

Question 38

How do opioids inhibit the dorsal horn?

Answer 38

Decrease signals from primary afferent neurone and decrease signals coming from PAG + locus coeruleus Overall decrease in excitation of second order projection neurone

Question 39

What are the endogenous opioid peptides?

Answer 39

``` B-Endorphin Enkephalins (Met and Leu) Dynorphin A(1-17) ```

Question 40

How do enkephalins work? (in terms of receptors)

Answer 40

Activate Gi GPCRs Leads to decreased Ca influx and increased K efflux Inhibits production of PKA

Question 41

U-opioid receptors target which site(s) of analgesia?

Answer 41

Supraspinal Spinal Peripheral

Question 42

K-opioid receptors target which site(s) of analgesia?

Answer 42

Spinal | Peripheral

Question 43

Delta-opioid receptors target which site(s) of analgesia?

Answer 43

Spinal

Question 44

The descending pain pathway does what?

Answer 44

Decreases nociception

Question 45

How do opiates work?

Answer 45

Act on opioid receptors | mimic endogenous opioids

Question 46

Opioid receptors activate which type of channel?

Answer 46

K (therefore inhibitory)

Question 47

Methadone binds to which opioid receptor(s)

Answer 47

U only

Question 48

What are the side effects related to U opioid receptors?

Answer 48

Euphoria Respiratory depression Constipation

Question 49

What are the side effects related to K opioid receptors?

Answer 49

Dysphoria | Diuresis

Question 50

What are the side effects related to delta opioid receptors?

Answer 50

Proconvulsant

Question 51

What effects to NSAIDs have?

Answer 51

Anti-inflammatory Anti-pyretic Analgesic All effects related to decreased prostaglandin synthesis

Question 52

``` Modulation of nociception: Prostanoid receptor (prostaglandins) ```

Answer 52

Positive effect on BK2 (Bradykinin) | Positive effect on VGNa

Question 53

Modulation of nociception: | BK2 (Bradykinin)

Answer 53

Positive effect on VR-1

Question 54

How do NSAIDs work?

Answer 54

Inhibit the prostanoid receptors, BK2 and VGNa Also inhibit COX-1 or COX-2 (which leads to decrease in prostaglandin synthesis)

Question 55

What are the disadvantages of NSAIDs

Answer 55

Multiple side effects Severe gastric irritation Kidney disorders Specific COX-2 inhibitors have less side effects

Question 56

COX-1 is found where?

Answer 56

Throughout the body (multiple uses, i.e many side effects)

Question 57

COX-2 is involved in what?

Answer 57

Just involved in the inflammatory response specifically