Physiology of pain 2

Question 1

Acute vs chronic pain length

Answer 1

Acute = < 3 months

Chronic = > or equal to 3 months

Question 2

Acute pain

• Causes
• Mechansim

Answer 2

Causes: after surgery, MSK injury, burns

Mechanism

• Inflammatory and nocireceptive due to tissue damage and inflammation
• Peripheral sensitisation

Question 3

Peripheral sensitisation in acute pain

Answer 3

Leads to hyperalgesia

Reduction in channel threshold at nociceptor ends

• TRPV1
• Na+ channels

Question 4

Lidocaine

• Type
• Mechanism

Answer 4

Local anaesthetic-

• Sodium channel blockers
• Prevent nociceptor firing

Question 5

Topical capsaicin treatment

- Mechanism + action

Answer 5

TRPV1 channel agonist
- Repeated use reduces nociceptor firing

Mechanism of action:

• ?Depletes substance P
• Causes peripheral terminals to die back

Question 6

NSAIDs

• Examples
• Mechanism of action

Answer 6

Aspirin, Ibuprofen

Reduces the inflammatory response by Inhibiting prostaglandin synthesis

• By blocking COX
• Prevents peripheral sensitisation by preventing a decrease in Na+ channel threshold

Question 7

Paracetamol/acetominophen

- Action

Answer 7

Not NSAID

Inhibits cyclooxygenase (COX) enzymes 			
- But does not reduce inflammation

• Acts on descending serotonergic pathways

Question 8

Opioids

• Examples
• Mechanism

Answer 8

Examples:

• Morphine
• Codeine
• Tramadol

Mechanism

• Agonists of the endogenous opioid system
• Brainstem = Disinhibition
• Spinal cord
• Peripheral = inhibit channels on nociceptors

Question 9

Gate control theory

Answer 9

Pain stimulated by nociceptors can be reduced by simultaneous activation of low threshold mechanoreceptors
- Modulates pain at spinal cord level

• Rubbing/ blowing pain can reduce pain sensation

A-beta fibres are stimulates near injury site

• Actives interneurones in dorsal horn [closes gated]
• Inhibits spinothalamic neurones

Question 10

Chronic pain causes

Answer 10

Inflammatory
- Persistent tissue inflammation

Neuropathic
- Injury to the NS

Question 11

Neuropathic pain peripheral mechanisms

Answer 11

Peripheral sensitisation

Spontaneous firing of nociceptors

Question 12

Spontaneous firing of nociceptors

Answer 12

Peripheral mechanism of neuropathic pain.

1. Peripheral nerve injury = accumulation of ion channels at regenerating tip of axon
2. Increased axonal firing at injury site

Question 13

Neuropathic pain central mechanisms

Answer 13

Central sensitization
– within spinal cord

Changes in activation patterns/cortical remapping
- within brain

Question 14

Central sensitization

Answer 14

Increase in the responsiveness of nociceptive neurons within the central nervous system
- Due to reduced threshold of activation for second order neurones

Question 15

Mechanism for reduced threshold activation in central sensitisation

Answer 15

Similar to LTP:

1. Constant firing of axons from the periphery (following injury )= Sustained release of glutamate
2. Prolonged depolarisation of the
   postsynaptic membrane
   = Massive influx of Ca2+ through NMDA receptors
3. Activation of kinases
   = Phosphorylation of NMDA/AMPA receptors
4. Channel protein synthesis

Question 16

Central hyperalgesia

Answer 16

After central sensitisation:

- Activation of nociceptors results in amplified spinal cord activation

Question 17

Central allodynia mechanism

+ Other central sensitisation mechanism

Answer 17

After central sensitisation:
- Non-noxious A-beta fibres sensitised 2nd order neurons [normally the synapse between the fibres are non-functional]

Other mechanisms:

• A-beta fibres form new sprouts that synapse with spinothalamic neurones
• Loss of inhibitory interneurones

Question 18

Chronic pain treatment

Answer 18

Acute pain treatments could work

Individual patient management is important

Associated symptoms should be treated:

• Depression
• Sleep disturbance
• Fatigue

Question 19

Tricyclic antidepressants

• Example
• Mechanism

Answer 19

Example: Amitriptyline

Mechanism:

• Acts on descending inhibitory pathways
• Inhibits serotonin and NADR re-uptake.

Question 20

Anticonvulsant

• Examples
• Mechanism

Answer 20

Examples:

• Gabapentin
• Carbamazepine

Mechanism:

• Reduces spinal cord excitability
• Gabapentin = blocks presynaptic voltage-gated calcium channels
• Prevents glutamate release in nociceptors
• Carbamazepine = blocks Na+ channels

Question 21

Ketamine

• Type
• Action
• Side effects

Answer 21

Anaesthetic

Mechanism

• NMDA antagonist = reduces glutamate influx
• Prevents second order neurone depolarisation

Side effects:

• Hallucinations
• Nightmares

Question 22

NICE guideline for treating neuropathic pain

Answer 22

1. Amitriptyline or pregabalin/gabapentin
2. Switch options in first step or combine the two
3. Referral to specialist pain service
   - Consider oral tramadol
   OR
   - Topical lidocaine in combination with second line treatment

Question 23

Placebo for treating chronic pain

Answer 23

Has be demonstrated to be successful for treating neuropathic pain

Due to activation of descending inhibitory pathways

Question 24

Complementary alternative therapies for treating chronic pain [5]

Answer 24

Acupuncture

Massage therapy

Homeopathy

Herbal medicine

Hypnosis