Physiology and Pathophysiology of pain

Question 1

Describe the pain pathways

Answer 1

nociceptive fibres come in via the dorsal horn and synapse at same level. They then cross over before ascending to the brainstem then the midbrain, thalamus

from the thalamus the fibres can go to the somatosensory cortex, limbic system or cingulate cortex

Question 2

Describe step by step how we recognise and act on a painful stimulus

Answer 2

Step 1. Periphery
Detection
Transmission to spinal cord (first order neurons)

Step 2. Spinal cord
Processing
Transmission to brain (Thalamus) (second order neurons)

Step 3. Brain
Perception, learning, response

Step 4. Modulation
Descending tracts

Question 3

What is nociception?

Answer 3

The detection of tissue damage by specialized transducers connected to A-delta and C fibers

Question 4

What stimuli do the free nerve endings of A delta and C-fibres respond to? (4)

Answer 4

thermal
chemical
mechanical - pressure etc
noxious stimuli

Question 5

Where do first order neurons synapse

Answer 5

grey matter of the spinal cord of same segmental level they enter

their cell body is in the dorsal root ganglion

Question 6

which cells represent the macrophagic system in the spinal cord?

Answer 6

glial cells

Question 7

Which types of neuron receptors in the grey matter receive input from primary afferent fibres? (4)

Answer 7

Nociceptive specific - layer 1+2

Low Threshold - layer 3+4

Mechanoceptive

Wide Dynamic Range - layer 5

Question 8

Primary afferent fibre types

Answer 8

A alpha and A beta
A delta
C

Question 9

What does the lateral spinothalamic tract carry?

Answer 9

Conveys fast and slow pain and temperature

Question 10

What does the anterior spinothalamic tract carry?

Answer 10

Sensation of light touch

Question 11

What is the spinothalamic tract?

Answer 11

The major tract sending impulses to the thalamus
- nociception in particular

Their cell bodies lie mostly in Rexed lamina 2+5

Question 12

What is the thalamus’ role in nociceptive pain pathways?

Answer 12

It is the second relay station (1st being spinal cord)

within the thalamus there are nuclei - ventroposterior and medial. Both receive inputs from spinothalamic tracts

The thalamus makes connections with the limbic system and the cortex ie after it receives inputs it sends them on to these areas

Question 13

Where does pain perception occur?

Answer 13

in the somatosensory cortex

Question 14

What is the cingulate cortex? what is it’s function?

Answer 14

part of the brain situated in the medial aspect of the cerebral cortex.

It lies immediately above the corpus callosum

It is an integral part of the limbic system, which is involved with emotion formation and processing, learning, and memory.

Question 15

descending pathways travel from the brain to where?

Answer 15

descend from the cortex to the brainstem. They then descend to the dorsal horn

Question 16

Describe how Descending pathways inhibit pain pathways?

Answer 16

Periaqeductal grey matter (PAG) (lies around the cerebral aqueduct) and nucleus raphe magnus (NRM) send descending controls.

These activate inhibitory interneurones that ‘close the gate’ blocking nociceptive fibres from getting through and up to the brain.

Usually decreases pain signal.

They release noradrenaline and serotonin - modulate the ascending pain transmission.

Question 17

What is hyperalgesia?

Answer 17

Increased perception of pain or even perception of non-noxious stimuli as noxious stimuli

This happens whenever there is tissue injury and inflammation

Primary and secondary - primary = site of tissue injury, secondary = surrounding tissue

can be for any stimuli ie thermal, mechanical etc

Question 18

What is Allodynia? What change occurs in the nociceptor?

Answer 18

A form of hyperalgesia - sensitive to light touch

Change = decreased threshold for response

The electrical threshold of the nerves does not change but the range at which the thermal or mechanical stimuli become noxious is changed

Question 19

What change occurs in nociceptors in Hyperalgesia?

Answer 19

Exaggerated response to normal and supranormal stimuli

Question 20

When does spontaneous pain occur and what changes are there in the nocicpetors to cause this?

Answer 20

mainly during nerve injuries

Spontaneous activity in nerve fibres

Question 21

What is central sensitisation?

Answer 21

It is the response of second order neurons in the CNS to normal input both noxious & non-noxious

similar to peripheral sensitisation ( increased sensitivity to an afferent nerve stimuli) - main difference is C.S happens at the level of the spinal cord and acts in tandem

Question 22

What are the 3 main components of central sensitisation?

Answer 22

Wind up
classical
long term potentiation

Question 23

Wind-up part of central sensitisation

Answer 23

It’s literally winding/progressively increasing the response of neurons to the input

Involves only activated synapses - ones that are working with primary afferent input

Manifests over the course of stimuli & terminates with stimuli

mainly mediated by the neurotransmitters Substance-P and CGRP

Question 24

Classical part of central sensitisation

Answer 24

Involves opening up of new synapses in the dorsal horn (silent nociceptors)

So these new synapses start to receive input and record the nociception

Immediate onset with appropriate stimuli (if strong enough)

Can outlast the initial stimuli duration

Can cause secondary hyperalgesia, where the area surrounding the injury site is also painful and where the touch also becomes painful. Once activated, it can be maintained even by low intensity of the offending stimuli.

Question 25

Long term potentiation

Answer 25

Involves mainly the activated synapses Occurs primarily for very intense stimuli The mechanism involves both AMPA and NMDA receptor activation by glutamate.

Question 26

Acute pain: - average timescale - usual presentation

Answer 26

< 1 month Usually obvious tissue damage Increased nervous system activity Pain resolves upon healing Serves a protective function

Question 27

Chronic pain

Answer 27

>3-6 months Pain beyond expected period of healing usually has no protective function Degrades health and function

Question 28

What is a nociceptive pain?

Answer 28

A sensory experience that occurs when specific peripheral sensory neurones (nociceptors) respond to noxious stimuli Painful region is typically localised at the site of injury Time limited usually Can also be chronic e.g osteoarthritis tends to respond to conventional analgesics

Question 29

What is a neuropathic pain?

Answer 29

Pain initiated or caused by a primary lesion or dysfunction in the somato-sensory nervous system Painful region may not necessarily be at the same site of injury - pain occurs in the neurological territory of affected structure (e.g nerve, root, spinal cord, brain) almost always chronic - post stroke pain, neuralgia responds poorly to conventional analgesics

Question 30

What methods are there to block pain transduction? (4)

Answer 30

NSAIDs Ice Rest Local Anesthetic blocks

Question 31

What methods are there to block pain transmission? (3)

Answer 31

``` Nerve blocks Drugs Opioids Anticonvulsants Surgery DREZ - dorsal root entry zone Cordotomy - disables selected pain-conducting tracts in the S.C ```

Question 32

transduction vs transmission

Answer 32

transduction = production of electrical signals at the pain nerve endings transmission = propagation of those signals through the PNS

Question 33

How is perception of pain managed? (5)

Answer 33

Education Cognitive behavioural therapy Distraction Relaxation Graded motor imagery Mirror box therapy - help alleviate phantom limb pain, in which patients feel they still have a limb after having it amputated.

Question 34

Descending modulation inhibition? (3)

Answer 34

``` Placebos Drugs Opioids Antidepressants Surgery Spinal cord stimulation ```