Neurology of Pain

Question 1

Define pain

Answer 1

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

Question 2

What is Congenital insensitivity to pain?

Answer 2

Condition with decreased or absent pain sensation caused by:

Na+ channel mutations, other conditions (Genetic usually)

Question 3

What is nociception?

Answer 3

The sensory process that provides the signals triggering pain

Question 4

What is chronic pain?

Answer 4

Pain that persists beyond normal healing time (> 3-6 months)

• pathological process (involving nervous system)
• may include biopsychosocial element

Question 5

Define dysaesthesia

Answer 5

Abnormal, unpleasant sensation (not pain itself)

Question 6

Define hyperalgesia

Answer 6

Increased pain response to noxious stimuli

Question 7

Define allodynia

Answer 7

pain response to non-noxious stimuli

Question 8

Define paraesthesia

Answer 8

Pain response in absence of any stumulus

- i.e. paroxysms = spontaneous shooting pains

Question 9

Define hyperathia

Answer 9

Pain threshold actually increased but increased pain response when threshold is passed

Question 10

Describe the reflex arc

Answer 10

Nociceptive fibre (afferent)

• > interneuron in substantia gelantinosa (dorsal horn)
• > motor neurone (ventral horn of spinal cord)
• > impulse travels to effector muscles

Question 11

Describe the substantia gelatinosa

Answer 11

Located in dorsal horn of spinal cord

Sends fibres up to brain via ascending pathways after receiving signal from nociceptive fibres

Send projections to anterior horn (reflex arc)

Synapse with descending pathways which modulate impulse transmission

Question 12

What are nociceptors?

Answer 12

Free nerve endings, i.e. not specialised structures

Question 13

Give examples of nociceptors

Answer 13

TRPV1 (Capsaicin receptor) = temperature receptor

Chemical receptors - inflammation receptors

Mechanical receptors - stretch receptors

Question 14

What are the main types of 1st-order nociceptive fibres?

Answer 14

A-delta fibres (type III fibres)

C fibres (type IV fibres)

Question 15

Describe A-delta fibres

Answer 15

Fast pain fibres (myelinated)

Unimodal (one type of pain = sharp,local)

e.g. muscle spindle, golgi tendon organ pain

Question 16

Describe C fibres (type IV fibres)

Answer 16

Slow pain fibres (unmyelinated)

Polymodal (distinguishable types of pain)

e.g. temp, stretch, inflammation

Question 17

What are A-beta fibres (Type II)?

Answer 17

Transmit crude touch (i.e. non-pain fibres)

• inhibit pain signals at dorsal horn
  e. g. rubbing sore area relieves pain

Question 18

Describe 2nd order nociceptive fibres?

• where they deccusate in ascending pathway
• which tract they ascend in
• where they synapse in the brain

Answer 18

Decussate at level of entry in spinal cord
Ascend in spinothalamic tract

Synapse in ventro postero-lateral nucleus of thalamus

Send projections to cerebral cortex

• insula and cingulate
• primary somatosensory cortex

Question 19

What are the insula and cingulate cortices resposnible for in the cerebrum?

Answer 19

Creating unpleasant sensation assoc. with pain

Question 20

What is the role of primary somatosensory cortex?

Answer 20

Locate painful stimuli

Question 21

What are the two descending pathways associated with pain?

Answer 21

Descending opioid/Serotinergic pathway
- nucleus raphe magnus (medulla)

Descending noradrenergic pathway
- Locus coeruleus (Pons)

Question 22

Describe the nucleus raphe magnus

Answer 22

Stimulated by opioidergic projections

Sends serotinergic projections to dorsal horns

Question 23

Describe the Locus Coerulerus

Answer 23

Sends noradrenergic projections to dorsal horns of spinal cord

Question 24

Stress induced analgesia occurs how?

Answer 24

Stress induces Amygdala to stimulate per-aqueductal grey matter which stimulates opioid release onto Nucleus Raphe Magnus => descending pathway inhibition results

Question 25

How do nociceptors become sensitised to inflammation?

Answer 25

Inflammatory mediators act on nociceptors e.g. prostaglandins, substance P, bradykinin, histamine Nociceptors also contribute to futher inflammation by release of substance P

Question 26

What are the effects of substance P?

Answer 26

Mast cell degranulation Blood vessel vasodilatation Increased Na+ channel expression in periphery Increased interneural connectivity Causes hypersensitisation

Question 27

Describe how the dorsal horn becomes hypersensitised?

Answer 27

By repeated stimulation of C-fibres => increased glutamate release by 1st order nociceptive fibres => opening of NMDA receptors => Ca2+ influx through these NMDA gates causes depolarisation of dorsal horn =? 2nd order fibres more likely to depolarise and cause hyperalgesia

Question 28

How does NO induce opioid resistance?

Answer 28

released after Ca2+ influx into post-synaptic fibres => stimulates closure of K+ channels o pre-syanptic membrane - i.e. the opposite to what opioids do (inhibit depolarisation)

Question 29

Why do we get referred pain from internal organs?

Answer 29

Since organs have 1st order nociceptive fibres only (no devoted 2nd order fibres) which means brain interprets signals as coming from skin

Question 30

How do NSAIDs work as analgesia?

Answer 30

Reduce inflammation and therfore reduce impulses from certain nociceptors

Question 31

How do local anaesthetics work as analgesia?

Answer 31

Block transmission of noxious stimulants to spinal cord

Question 32

How do opioids work as analgesia?

Answer 32

Act on descending pain pathways - upregulate nucleus raphe magnus Directly inhibit nociceptive signals at 1st order fibre-dorsal horn neuron synapse Blunts emotional aspects of pain also

Question 33

What is the difference between opiate and opioids?

Answer 33

Opioids generally refer to endogenous substances Opiates refer to exogenous substances

Question 34

Describe which endogenous opioids target which opioid receptor

Answer 34

Endorphins - mu receptor Enkephalins - delta receptor Dynorphins - kappa receptor

Question 35

What are the effects of opioids?

Answer 35

``` Analgesia Euphoria Sedation Cough suppression Constipation ``` Respiratory distress N&V Miosis

Question 36

What is neuropathic pain?

Answer 36

Pain generally caused by neuronal damage | - i.e. anatomical or functional abnormalities of pain pathways

Question 37

What are the causes of neuronal damage?

Answer 37

Neuropathies, Nerve avulsions, Cancers, Infections, Amputations MS, Cord injuries, Stroke

Question 38

What are the mechanisms behind neuropathic pain?

Answer 38

Inflammation => Na+ channel abnormalities - increased expression Increased sympathetic activity Sensitisation of dorsal horn neurones Central sensitisation and reorganisation

Question 39

Give a common example of neuropathic pain

Answer 39

Trigeminal neuralgia - usually due to compression of CN V - results in intense episodic pain

Question 40

How should neuropathic pain be treated?

Answer 40

With anticonvulsants, e.g. - carbamazepine - amitryptilline - baclofen - pregabalin/gabapentin

Question 41

What is phantom limb pain?

Answer 41

Perception of pain in a limb that is no longer there (e.g. has been amputated, congenital absence)

Question 42

What percentage of amputees does phantom pain occur in?

Answer 42

Up to 80%

Question 43

What is the best treatment for treating phantom limb pain?

Answer 43

Mirror visual feedback - mirrors used to trick brain into thinking limb is there by providing visual input suggesting it is - may provide instant relief