T2 L11 Physiology of pain

Question 1

What are some examples of acute pain

Answer 1

Following surgery
Musculoskeletal injury
Burn

Question 2

What reduces the threshold of TRPV1 channels?

Answer 2

Bradykinin

Nerve growth factor

Question 3

What reduces the threshold of sodium channels?

Answer 3

Prostaglandins

Question 4

Give examples of a local anaesthetic & its mechanism

Answer 4

Lidocaine, lignocaine

Blocks sodium channels to prevent nociceptor firing

Question 5

What is the mechanism of topical capsaicin treatment?

Answer 5

Deplete substance P

Causes peripheral nerve terminals to die back leading to calcium overload & mitochondrial dysfunction

Question 6

How do NSAIDs work?

Answer 6

Inhibit prostaglandin synthesis to reduce inflammatory response
Prevent peripheral sensitisation by inhibiting cyclooxygenase which reduces prostaglandin synthesis and prevents decrease in sodium channel threshold

Question 7

How does paracetamol work?

Answer 7

Inhibits cyclooxyrgenase enzymes

Acts on descending serotonergic pathways to increase serotonergic inhibitory pathway

Question 8

What is the mechanism of opioids?

Answer 8

Agonist of endogenous opioid system

Multiple sites of action at brainstem, spinal cord & peripherals

Question 9

What is the gate control theory?

Answer 9

Modulation of pain at spinal cord level
Pain evoked by nociceptors can be reduced by simultaneous activation of low threshold mechanoreceptors
Stimulation of AB fibres in vicinity of injury activates interneurons in dorsal horn which inhibits spinothalamic neurons

Question 10

What are some examples of chronic pain?

Answer 10

Back pain
Cancer
Carpal tunnel syndrome
Arthritis
Fibromyalgia
Diabetes
Migraine
Post-surgery
Multiple sclerosis
Trigeminal neuralgia
Phantom limb pain

Question 11

What are the symptoms of neuropathic pain?

Answer 11

Stabbing, aching, burning, electricity / shooting, spontaneous
Hypersensitivity

Question 12

What are the peripheral mechanisms of chronic pain?

Answer 12

Peripheral sensitisation
Following peripheral nerve injury there is an increase in axonal firing at injury site due to accumulation of ion channels at regenerating tip of axon
Spontaneous firing of nociceptors

Question 13

What are the central mechanisms of chronic pain?

Answer 13

Central sensitisation within spinal cord.
Increase in responsive of nociceptive neurons within central nervous system
Due to reduced threshold for activation of second order neurons

Question 14

Describe the mechanism for reduced threshold for activation

Answer 14

1) Constant firing of axons from periphery following injury
2) Sustained release of glutamate
3) Prolonged depolarisation of synaptic membrane
4) Massive influx of calcium through NMDA receptors
5) Activation of kinases
6) Phosphorylation of NMDA / AMPA receptors & channel protein synthesis

Alters kinetics of channels & causes insertion of more channels

Question 15

What types of drugs can be used to treat chronic pain?

Answer 15

Tricyclic antidepressants
Anticonvulsants
NMDA antagonists

Question 16

Give an example of a tricyclic antidepressant and its mechanism of action

Answer 16

Amitriptyline
Act on descending inhibitory pathways
Inhibits reuptake of serotonin & noradrenalin

Question 17

Give an example of an anticonvulsant & its mechanism of action

Answer 17

Pregabalin, gabapentin, carbamazepine
Act in spinal cord to reduce excitability
Blocks calcium & sodium channels
Prevent release of glutamate from nociceptors

Question 18

Give an example of an NMDA antagonist & its mechanism of action

Answer 18

Ketamine
Reduces glutamate influx to prevent depolarisation of second order neurons
Adverse side effects e.g. hallucinations & bad dreams

Question 19

What are some other treatments for chronic pain?

Answer 19

Physiotherapy - manipulation of tissues, pacing
Psychological therapies - CBT
Surgery - spinal cord stimulator

Question 20

What are the main complementary alternative therapies?

Answer 20

Acupuncture
Massage therapy
Homeopathy
Herbal medicine
Hypnosis