session 4 part 2

Question 1

What is lateral inhibition?

Answer 1

prevents the overlap of receptive fields so all receptor stimuli can be distinguished
mediated by interneurones within the dorsal horn
facilitates enhanced sensory perception

Question 2

Describe the gate-control theory of pain inhibition

Answer 2

you can modulate a pain response in the dorsal horn by activating an Aβ-fibre
- Aβ-fibre – involved with innocuous mechanical stimulation (e.g. brush)
(- If you hurt yourself, you ‘rub it better’ – this assimilates Aβ-fibres -> inhibits stimulated pain fibres)

The gate control theory of pain asserts that non-painful input closes the nerve “gates” to painful input, which prevents pain sensation from traveling to the central nervous system. Therefore, stimulation by non-noxious input is able to suppress pain.

Question 3

State the central sensory structures

Answer 3

• SI: Primary somatosensory cortex (in the postcentral gyrus)
• SII: Secondary somatosensory cortex (in the parietal operculum)
• Posterior parietal cortex: spatial awareness of the body-

Question 4

What are the pathways by which sensory inputs reach to the brain? (give the corresponding sensory nerve fibres)

Answer 4

2 pathways:

1. Dorsal column system (transmitting touch and proprioception) - Aβ-fibres
2. Spinothalamic pathway (pain, temperature and crude touch) - Aδ and C fibres

Question 5

What type of stimuli does the dorsal column pathway transmit? What types of sensory fibres does this involve?

Answer 5

(touch and propiception)
innocuous mechanical stimuli (fine discriminative touch, vibration)

Aβ fibers

Question 6

Information from the upper and lower limbs are converted through which tracts?

Answer 6

• Information from the lower limbs (below T6) travel ipsilaterally along the gracile tract
• Information from the upper limbs travel ipsilaterally along the cuneate tract

Question 7

Give a brief overview of the dorsal column pathway

Answer 7

• 1st order neurones terminate in the medulla
• 2nd order neurones cross in the caudal medulla
• 2nd order neurones terminate in the thalamus
• 3rd order neurones from the VPL terminate in the somatosensory cortex

Question 8

Where do fibres in the gracile tract have their first synapse?

Answer 8

the Gracile Nucleus in the medulla

Question 9

Where do fibres in the cuneate tract have their first synapse?

Answer 9

in the Cuneate Nucleus in the medulla

Question 10

Where do 2nd order neurones decussate in the dorsal columns?

What tract does this form?

Answer 10

in the caudal medulla

forms the contralateral medial lemniscus tract

Question 11

Where do 2nd order neurones terminate in the dorsal columns?

Answer 11

in the VPL nucleus of the thalamus

Question 12

Where do 3rd order neurones from the VPL terminate in the dorsal columns?

Answer 12

terminate in the somatosensory cortex

Question 13

NOTES for the dorsal columns

Answer 13

• There is a topographic representation of the body in the VPL (lower extremities terminate more lateral)
• The size of somatotopic areas is proportional to density of sensory receptors in that body region (somatosensory homunculus)
• Pain and temperature localisation not as precise

Question 14

What type of stimuli does the spinothalamic (anterolateral) pathway transmit?

Answer 14

pain, temperature and crude touch

Question 15

What are the 2 pathways within the spinothalamic tract and which pathways ascend with which tracts?

Answer 15

lateral and anterior spinothalamic tracts

• Pain and temperature - lateral spinothalamic tract
• Crude touch - anterior spinothalamic tract

Question 16

Give a brief overview of the spinothalamic pathway

Answer 16

• 1st order neurones terminate in the dorsal horn
• 2nd order neurones terminate in the thalamus
• 3rd peer terminate in the somatosensory cortex

Question 17

Where do first order neurones terminate in the spinothalamic pathway?

Answer 17

in the dorsal horn

Primary afferent axons terminate upon entering the spinal cord

Question 18

Where do the second order neurones decussate in the spinothalamic pathway?

(in comparison, where does decussation occur in the dorsal column pathway?)

Answer 18

Second order neurons decussate immediately in the spinal cord and form the spinothalamic tract

(Dorsal column tracts decussate in the medulla)

Question 19

Where do second order neurones terminate in the spinothalamic pathway?

Answer 19

terminate in the thalamus

ventral posterior lateral nucleus of the thalamus

Question 20

What are the key differences between the dorsal column and spinothalamic tracts?

Answer 20

• Dorsal column tracts: transmit light touch, vibration and 2-point discrimination – CROSS IN BRAINSTEM
• Spinothalamic tracts: transmit pain, temperature and coarse touch – CROSS IN SPINAL CORD

Question 21

Describe the pathway tat represents the emotional aspect of pain?

Answer 21

the spino-reticular system (emotional component of pain).

Pain is transmitted through a pathway from the spinal cord to the parabrachial area (in the brainstem), and then to the limbic system.

Question 22

How can we test the integrity of ascending somatosensory pathways?

Answer 22

QUANTITATIVE SENSORY TESTING

E.g. temperature thresholds, vibration sensitivity, brush sensitivity

Question 23

Describe and explain the consequences of an anterior spinal chord lesion?

Answer 23

• Blocked anterior spinal artery -> causes ischemic damage to the anterior part of the spinal cord
• Spinothalamic tract damage causes pain and temperature loss below the level of the lesion
• normal light touch and vibration sensation due to intact dorsal columns
• If the entire spinal cord was damage, you wouldn’t have ANY SENSATION AT ALL below the level

Question 24

What is ELECTRICAL PERCEPTUAL THRESHOLDS (EPT)?

Answer 24

• Like QST but instead, electrical current is passed through the skin
• You ask the patient whether or not they can feel it – you can map the whole body through this
• If you have a spinal cord injury, you begin to lose sensation (so thresholds go up)
• Depending on where they start to lose sensation, we can determine the vertebral LEVEL of the lesion

Question 25

Define pain

Answer 25

An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage

Question 26

What are the different types of pain?

Answer 26

* Nociceptive – tissue damage, typically acute pain (e.g. skin cut) * Muscle – lactic acidosis, ischaemia (e.g. stretching, fibromyalgia) * Somatic – well-localized (e.g. inflammation, infection) * Visceral – deep, poorly localised (e.g. stomach, colon, IBS) * Referred – from an internal organ/structure (e.g. Angina) * Neuropathic – dysfunction of the nervous system

Question 27

Chronic pain manifests as _____ and _____

Answer 27

hyperalgesia | allodynia

Question 28

Define hyperalgesia

Answer 28

increased pain from a stimulus that normally provokes pain

Question 29

Define allodynia

Answer 29

pain due to a stimulus that does not normally provoke pain – e.g. brushing the skin

Question 30

What is neuropathic pain?

Answer 30

Pain caused by a lesion or disease of the somatosensory nervous system. Doesn't have to be from a certain injury, but also from disease.

Question 31

Describe how neuropathic pain presents

Answer 31

- Pain in area of neurological dysfunction (hyperalgesia and allodynia) - Typically sharp, burning, ‘electric shocks’ - Poor response to usual analgesic drugs (e.g. opiates)

Question 32

GIVE SOME EXAMPLES OF NEUROPATHIC PAIN

Answer 32

* Radicular low back pain (sciatica) * Diabetic neuropathy * Post herpetic neuralgia * Post-surgical pain * HIV-induced neuropathy * Chemotherapy induced neuropathy * Complex Regional Pain Syndrome (CRPS)

Question 33

Define sensitisation

Answer 33

increased responsiveness of nociceptive neurons to their normal input

Question 34

Define hypoalgesia

Answer 34

Diminished pain in response to a normally painful stimulus

Question 35

Define paraesthesia

Answer 35

abnormal sensation, whether spontaneous or evoked

Question 36

What is central sensitisation?

Answer 36

If you repeat a stimulus a number of times, it becomes more painful (chronic pain)

Question 37

What is synaptic plasticity?

Answer 37

the biological process by which specific patterns of synaptic activity result in changes in synaptic strength and is thought to contribute to learning and memory. Plasticity is the ability of the brain to change and adapt to new information. Synaptic plasticity is change that occurs at synapses.

Question 38

Which receptors are involved with inducing plasticities in the CNS?

Answer 38

NMDA receptors

Question 39

Describe how the mechanism of action by which synaptic plasticity can lead to central sensitisation

Answer 39

* Initiated by NMDA receptor activation * They allow a big post-synaptic depolarisation -> Ca enters the neurone * (Ca2+ mediated synaptic plasticity in dorsal horn neurones - Ca involved in activating signalling pathways) Therefore there is increased synaptic strength (efficacy) -> increased sensitivity * The inhibitory interneurons in the dorsal horn become less influential * Persistent activation of NMDA receptor can result in the development of chronic pain (e.g. arthritis)

Question 40

What is the normal actions of inhibitory neurones (that stops central sensitisation)?

Answer 40

normally prevent touch (abeta fibres) causing pain

Question 41

What will loss of inibitory neurones in the dorsal horn cause?

Answer 41

allodynia

Question 42

How does central sensitisation (chronic pain) usually present?

Answer 42

allodynia and hyperalgesia

Question 43

How is chronic pain reduced?

Answer 43

monoamines in the brainstem are released that work to inhibit spinal chord excitability

Question 44

Name the main monoamine neurotransmitters and where in the brainstem they are released from

Answer 44

- serotonin (from serotinergic nuclei) - medulla | - neuroadrenergic neurones - pons

Question 45

Describe how nociception is controlled using the PAG-RVM axis

Answer 45

- RVM contains serotonergic neurones, which project to the dorsal horn, releasing serotonin - (this will either inhibit of facilitate pain): - ----> 5-HT1a receptors - inhibitory - ----> 5-HT3 receptors - facilitatory

Question 46

Describe how nociception is controlled in the locus cereleus

Answer 46

(in the pons) - main nuclei is located in the dorsal horn - predominantly inhibitory (can be thought of as a pain-braking-mechanism) - dampens down the resins to pre-synaptic alpha-2 receptors on primary afferents and projection neurones

Question 47

Describe how opioids increase descending inhibition in an endogenous analgesic system

Answer 47

- The PAG and RVM contain high concentrations of µ opioid receptors - Endogenous opioids (enkephalin, dynorphin) enhance descending inhibition from the PAG-RVM axis - ----> in the dorsal horn by inhibiting glutamate release (i. e. INHIBITNG activation of spinothalamic neurons -> less excitation)

Question 48

Give another form of endogenous analgesia

Answer 48

Placebo-induced analgesia - PAG and RVM show activity following a placebo analgesia - The spinal cord is either inhibited or facilitated in placebo analgesia

Question 49

What descending controls are targeted for pain relief?

Answer 49

• Opioids – work in the PAG and RVM • Antidepressants treat neuropathic pain (opioids are ineffective) – TCA, SNRI, SSRI NOTE that SSRIs are not effective in neuropathic pain patients – low analgesic efficacy. TCAs and SNRIs have better efficacy • Amitriptyline (TCA) is widely prescribed for neuropathic pain due to its noradrenergic component

Question 50

Give an example of an SSRI

Answer 50

fluoxetine, citalopram NOTE that they are not effective in for treatment of neuropathic pain

Question 51

Give an example of a TCA | What is good about TCA in the target of descending control systems?

Answer 51

Amitriptyline it is widely prescribed for neuropathic pain due to its noradrenergic component

Question 52

How to antidepressant drugs (e.g. SNRIs) enhance descending noradrenergic inhibition?

Answer 52

damage to a primary afferent neurone -> increase in excitability -> central sensitisation in the spinal chord Antidepressant drug ---> NA increases in the synaptic cleft ---> binds to α2 receptors (inhibitory) ---> inhibits activity within the neurones ---> sensory input to brain is reduced ---> reduced pain.

Question 53

What is an SNRI? Give an example

Answer 53

serotonin and norepinephrine reuptake inhibitors | e.g. duloxetine