Physiology of pain 2 Flashcards Preview

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Flashcards in Physiology of pain 2 Deck (24)
1

Acute vs chronic pain length

Acute = < 3 months

Chronic = > or equal to 3 months

2

Acute pain
- Causes
- Mechansim

Causes: after surgery, MSK injury, burns

Mechanism
- Inflammatory and nocireceptive due to tissue damage and inflammation
- Peripheral sensitisation

3

Peripheral sensitisation in acute pain

Leads to hyperalgesia

Reduction in channel threshold at nociceptor ends
- TRPV1
- Na+ channels

4

Lidocaine
- Type
- Mechanism

Local anaesthetic-
- Sodium channel blockers
- Prevent nociceptor firing

5

Topical capsaicin treatment
- Mechanism + action

TRPV1 channel agonist
- Repeated use reduces nociceptor firing

Mechanism of action:
- ?Depletes substance P
- Causes peripheral terminals to die back

6

NSAIDs
- Examples
- Mechanism of action

Aspirin, Ibuprofen

Reduces the inflammatory response by Inhibiting prostaglandin synthesis
- By blocking COX
- Prevents peripheral sensitisation by preventing a decrease in Na+ channel threshold


7

Paracetamol/acetominophen
- Action

Not NSAID

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

- Acts on descending serotonergic pathways

8

Opioids
- Examples
- Mechanism

Examples:
- Morphine
- Codeine
- Tramadol

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

9

Gate control theory

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

10

Chronic pain causes

Inflammatory
- Persistent tissue inflammation

Neuropathic
- Injury to the NS

11

Neuropathic pain peripheral mechanisms

Peripheral sensitisation

Spontaneous firing of nociceptors

12

Spontaneous firing of nociceptors

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

13

Neuropathic pain central mechanisms

Central sensitization
– within spinal cord

Changes in activation patterns/cortical remapping
- within brain

14

Central sensitization

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

15

Mechanism for reduced threshold activation in central sensitisation

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

16

Central hyperalgesia

After central sensitisation:
- Activation of nociceptors results in amplified spinal cord activation

17

Central allodynia mechanism
+ Other central sensitisation mechanism

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

18

Chronic pain treatment

Acute pain treatments could work

Individual patient management is important

Associated symptoms should be treated:
- Depression
- Sleep disturbance
- Fatigue

19

Tricyclic antidepressants
- Example
- Mechanism

Example: Amitriptyline

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

20

Anticonvulsant
- Examples
- Mechanism

Examples:
- Gabapentin
- Carbamazepine

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

21

Ketamine
- Type
- Action
- Side effects

Anaesthetic

Mechanism
- NMDA antagonist = reduces glutamate influx
- Prevents second order neurone depolarisation

Side effects:
- Hallucinations
- Nightmares

22

NICE guideline for treating neuropathic pain

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

23

Placebo for treating chronic pain

Has be demonstrated to be successful for treating neuropathic pain

Due to activation of descending inhibitory pathways

24

Complementary alternative therapies for treating chronic pain [5]

Acupuncture

Massage therapy

Homeopathy

Herbal medicine

Hypnosis