Pain

Question 1

What is the definition of pain?

Answer 1

An unpleasant sensory and an emotional experience associated with actual or potential tissue damage

Question 2

What is the biological importance of pain?

Answer 2

• protective function

- signalling some form of damage or dysfunction

Question 3

What are the types of pain?

Answer 3

• nociceptive (generated by some peripheral damage)
• neuropathic (generated by damage to the neural pathways transmitting pain inputs)
• psychogenic (generated by activity in the CNS regions integrating pain info)

Question 4

What are pain receptors?

Answer 4

nociceptors - free nerve endings

Question 5

What are the three different types of nociceptors?

Answer 5

• thermal
• mechanical
• polymodal (chemical inflammatory response)

Question 6

How does a nociceptive stimulus generate a signal?

Answer 6

mediated by activation of channels - TRP’s. They all have non-specific permeability (Na, K or Ca) and induce a state of depolarisation. Similar type of contribution by the ASIC’s with H+ permeability. Once the initial depolarisation occurs and reaches the threshold, the voltage gated Na channel will open and an action potential will occur.

Question 7

Which TRP’s are the most relevant to pain transmission?

Answer 7

TRP-V1 (most important), TRP-M8 and TRP-A1

Question 8

What type of neurone receives the pain info?

Answer 8

Dorsal root ganglia neurone. The nociceptors are on the axonal terminal of the DRG neutrons in the periphery, instead of the dendrites receiving the signal and carrying it to create an AP elsewhere, the AP starts in the axon and goes to the dorsal root ganglion which will transmit to the spinal cord.

Question 9

Which 2 fibres are involved in carrying the message?

Answer 9

A𝛿 fibre and C fibre

Question 10

What are the difference between the A𝛿 and C fibres?

Answer 10

A𝛿 is quicker due to fibre diameter and myelination. It carries rapid pain sensation (immediate, sharp and localised)
- uses direct sensory pathway (the 3 neurons)
C fibre is slower and carries slow pain sensation (slower, diffuse, dull)
- has a large number of interneurones and relay stations hence making it slower and lack of specificity of location (diffuse)

Question 11

What does the transmission sensory pathway for pain include?

Answer 11

3 main neurones.

1. first neurone is in the peripheral, carrying the signal through the fibre into the spinal cord
2. second neurone crosses the midline and is in the anterior part of the spinal form, forming the spinothalamic tract (STT) going up towards the thalamus.
3. third neurone starts at the thalamus, into the sensory cortex. Maintaining somatotopy.

Question 12

What is somatotopy?

Answer 12

each peripheral region (location that the sensory signal came from) is represented by a specific area in the primary sensory cortex, generating the sensory homunculus.

Question 13

What is peripheral modulation?

Answer 13

Pain felt from an injured area is reduced when the skin around the injured area is rubbed or stroked
- Gate theory

Question 14

What is descending modulation?

Answer 14

Stress analgesia - not feeling pain until stress has left

Question 15

How can marked analgesia be induced?

Answer 15

By injecting morphine in minute doses in the 3rd ventricle of the brain

Question 16

What is the Gate theory of Pain control?

Answer 16

Pain pathway usually goes down the C/ A𝛿 fibre, some will continue to the projection neurone (neurone just before the STT that will make it go to the brain) and some will go down into the interneurone and inhibit the inhibition, therefore the signal is strong. With rubbing, it initiates the mechano sensory pathway which the Aβ fibres carry the signal much quicker mainly to the projection neuron but some go to the inhibitory neuron that will inhibit the projection neuron, therefore reducing the signal making it weaker.

Question 17

Which area in the brain is the most important for processing pain information?

Answer 17

Periaqueductal Gray (PAG) area - receives info from the corticol regions

Question 18

How does descending modulation work?

Answer 18

• signal sent from PAG to the dorsal horn of the spinal cord (inbetween first and second neuron)
• either noradrenaline or serotonin will be released at the same area and activate the inhibitory interneurons that release enkephalines.
• the enkephalines then inhibit the release of the normal presynaptic neurons (glutamate) by binding to opioid receptors and reduce the full activation of the STT neurone.

Question 19

What can be used as pain control in the transduction level?

Answer 19

non-steroidal anti-inflammatory drugs
- mostly COX inhibitors (enzymes that are generating prostaglandins)
anti-histaminics
- combatting inflammation associated with peripheral
- inflammation is one of the main triggers of peripheral pain
tissue damage
local anaesthetics
- blocking and inhibiting the generation or transmission of action potentials

Question 20

What can be used as pain control in the transmission level?

Answer 20

opioids
- binding to the peripheral opioid receptors (mimicking the enkephaline response)
local anaesthetics
- blocking and inhibiting the generation or transmission of action potentials

Question 21

What can be used as pain control in the modulation level?

Answer 21

opioids
- binding to the central opioid receptors
noradrenaline agonists
- activate the descending control pathways
NMDA receptor antagonists
- blocking glutamate effects (ketamine)

Question 22

What are the most common non-steroidal anti-inflammatory drugs?

Answer 22

paracetamol, ibuprofen, aspirin

• inhibit COX2
• inhibit phospholipase A2
• reducing the conc generation of prostaglandins

Question 23

Why should you be careful when taking non-steroidal anti-inflammatory drugs?

Answer 23

They inhibit both COX enzymes which will reduce the pain. However, if they inhibit COX1 too much, the gastroprotection usually produced will also be inhibited, leading to gastrobleeding.

Question 24

What are the 3 types of opioid receptors?

Answer 24

μ, κ and δ with different effectiveness on pain transmission. Mu is the most effective

Question 25

How do opioids work?

Answer 25

Once it has bound to the receptor, there is a g-protein coupled activation. Decrease in cAMP, activation of K channel (resulting in hyperpolarisation of neurones, less excitability) and inhibition of Ca signalling.