Physiology of pain 2 Flashcards

1
Q

Acute pain

A

<3 months

Inflammatory (and nocioceptive)
- due to tissue injury or inflammation

e.g. following surgery, musculoskeletal injury, burn

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2
Q

Chronic pain

A

> 3 months

Affects 20-50% population

e.g. chronic back pain, cancer, carpal tunnel syndrome, arthritis, fibromyalgia, diabetes, migraine, post surgery, multiple sclerosis

Due to injury to nervous system

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3
Q

Peripheral sensitisation

A

Major mechanism of acute pain

Leads to pain hypersensitivity

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4
Q

Acute pain treatments sites of action

A

PNS (site of injury)

CNS

Both

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5
Q

Local anaesthetics

A

e. g. lidocaine, lignocaine
- topically applied to skin

Mechanism of action
- sodium channel blockers

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6
Q

Topical capsaicin treatment

A

TRPV1 channel agonist

Mechanism of action

  • depletes substance P
  • causes peripheral terminal to die back
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7
Q

Non-steroidal anti-inflammatory drugs

A

e.g. aspirin, ibuprofen

Mechanism of action

  • reduces the inflammatory response by inhibiting prostaglandin synthesis
  • prevents peripheral sensitisation

Cyclooxygenase inhibited ->
Prostaglandin synthesis reduced ->
Prevents decrease in Na+ channel threshold

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8
Q

Paracetamol/ acetominophen

A

Not NSAID

Mechanism of action

  • inhibits cyclooxygenase enzymes
  • acts on descending serotonergic pathways
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9
Q

Opioids

A

e.g. morphine, codeine, tramadol

Most effective pain relief but numerous side effects

Mechanisms of action

  • agonists of the endogenous opioid system
  • multiple sites of action (brainstem, spinal cord, peripheral)
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10
Q

Gate control theory

A

Modulation of pain at the spinal cord level

Pain evoked by nocioceptors can be reduced by simultaneous activation of low threshold mechanoreceptors

Rubbing/ blowing on the painful area can reduce the pain sensation

Stimulation of Aβ fibres in vicinity of injury activates interneurones in dorsal horn which inhibits spinothalamic neurones

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11
Q

Neuropathic pain mechanisms

A

Mechanisms are complex and involve both peripheral and central nervous systems

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12
Q

Spontaneous firing of nocioceptors

A

Following a peripheral nerve injury increase in axonal firing at the site of injury

Due to accumulation of ion channels at regenerating tip of axon

Responsible for spontaneous pain

Underlies central neuropathic pain mechanisms

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13
Q

Main peripheral mechanisms

A

Peripheral sensitisation

Spontaneous firing of nocioceptors

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14
Q

Central mechanisms

A

Central sensitisation
- with spinal cord

Changes in activation patterns/ cortical remapping
- within brain

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15
Q

Central sensitisation

A

Increase in the responsiveness of nocioceptive neurones within the CNS

Normal inputs begin to produce abnormal responses

Due to reduced threshold for activation of 2nd order neurones

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16
Q

Reduced threshold for activation

A

Constant firing of axons from the periphery (following injury)

Sustained release of glutamate

Prolonged depolarisation of the postsynaptic membrane

Massive influx of Ca2+ through NMDA receptors

Activation of kianses

Phosphorylation of NDMA/ AMPA receptors

Channel protein synthesis

Alters kinetics of channels and causes insertion of more channels

17
Q

Central hyperalgesia mechanism

A

Following central sensitisation

Activation of nocioceptors results in amplified spinal cord activation

18
Q

Central allodynia mechanism

A

Non-noxious Aβ fibres also synapse onto 2nd order spinothalamic neurones (normally non-functional)

Following central sensitisation

Non- noxious afferents activate sensitised 2nd order neurones

19
Q

Altered synaptic connections

A

Aβ fibres form new sprouts that synapse onto spinothalamic tract neurones

20
Q

Loss of inhibitory interneurones

A

e.g. GABA and glycine

21
Q

Chronic pain treatments

A

Difficult to treat

Acute pain treatments do not work

Good individual patient management is critical

Important to manage primary condition and other associated symptoms

  • depression
  • sleep disturbances
  • fatigue
22
Q

Current treatments for chronic pain

A

Drugs

  • tricyclic antidepressants
  • anticonvulsants
  • NMDA antagonists

Physiotherapy

Psychological therapies

Surgery

23
Q

Tricyclic antidepressants

A

e.g. amitriptyline

Mechanism of actions

  • unclear
  • act on descending inhibitory pathways
  • inhibits reuptake of serotonin
24
Q

Anticonvulsants

A

Pregabalin/ gabapentin, carbamazepine

Mechanism of action

  • unclear
  • act in spinal cord to reduce excitability
  • blocks calcium and sodium channels
25
Q

Pregabalin/ gabapentin

A

Do not act on GABAergic interneurones

Blocks presynaptic voltage gated Ca2+ channels

Prevents release of glutamate from nocioceptors

26
Q

NMDA antagonists

A

Ketamine

Mechanism of action

  • NMDA receptor antagonist
  • prevents depolarisation of second order neurone
  • adverse side effects
27
Q

NICE guideline neuropathic pain

A

First line
- amitriptyline or pregabalin

Second line
- switch drugs or combine

Third line
- refer to specialist pain serve and consider oral tramadol or in combination with second line consider topical lidocaine

28
Q

Placebo effect

A

Placebo analgesia has been demonstrated for the treatment of neuropathic pain

Due to activation of descending inhibitory pathways

29
Q

What’s gone wrong in chronic pain?

A

Peripheral terminals
- peripheral sensitisation

Axon
- spontaneous firing of nocioceptors

Dorsal root ganglia
- synthesis of new ion channels

Dorsal horn/ spinal cord
- central sensitisation

Brain
- changes in brain activation patterns