Pain Physiology

Question 1

What’s the mechanism of peripheral sensation?

Answer 1

After tissue injury, there is a plethora of chemical mediators of pain
-Capsaicin
ATP
- Bradykinin
- Adrenaline
- NGF

• These chemical mediators cause the up-regulation of existing receptors to pain mediators

Question 2

What are the receptor types which chemical mediators of pain bind to?

Answer 2

1. Ligand-gated channels
2. G-protein receptors
3. Tyrosine kinase receptors

Question 3

What’s the mechanism of peripheral sensation? (effectors)

Answer 3

• After the pain mediators bind to their receptors, they case the up-regulation of new Voltage-gated channels which are hyper-sensitive
• The terminal becomes hyper-excitable and will hyperpolarise easily

AMPA receptor causes increase in NMDA receptors – makes post-synaptic axon terminal hyper-acceptable and these can fire spontaneously

Question 4

What’s the descending pain regulation pathway?

Answer 4

Opiate interneurones block pain transmission at 2 sits

1. Signals from the periaqueductal gray (PAG) (an anatomic and functional interface between the forebrain and the lower brainstem) activate opiate interneurons
2. Opiate interneurons block neurotransmitter release from 1st order afferent neurons (pre-synaptically)
   2a. Inhibit 2nd order afferent neurons (post-synaptically)
3. Prevents pain signal from reaching the thalamus and then to the somatosensory cortex area

Question 5

What are the other stages in the descending pain regulation pathway?

Answer 5

1. Emotion/stress/arousal/higher functions from the Cortex/Thalamus/Hypothalamus can either excite or suppress the PAG in the midbrain
   1b. Endogenous/exogenous opioids excite the PAG
2. This can excite the Nucleus raphe Magnus in the Brainstem
3. This causes a release of serotonin in the dorsal horn which reduces 2nd order neuron firing
4. Decrease in pain transmission

Question 6

Pain relief - what do common analgesics target?

Answer 6

Prostaglandins play a key role in the generation of the inflammatory response. Their biosynthesis is significantly increased in inflamed tissue and they contribute to the development of the cardinal signs of acute inflammation

• Prostaglandins and thromboxane A2 (TXA2), collectively termed prostanoids, are formed when arachidonic acid (AA), a 20-carbon unsaturated fatty acid, is released from the plasma membrane by phospholipases (PLAs) and metabolized by the sequential actions of prostaglandin G/H synthase, or cyclooxygenase (COX)
  1. NSAIDs inhibit COX and prevent the conversion of Arachadonic acid to Prostaglandins
  1b. Possess anti-inflammatory properties

Question 7

Give an overview on how NSAIDs, local anaesthetics, Transcutaneous electrical nerve stimulation (TENS), Opioids and general anaesthetics work

Answer 7

NSAIDs - block noxious stimuli by preventing conversion of arachidonic acid to Prostaglandins

Local anaesthetics - block 1st order afferent fibres from transmitting action potentials

TENS - Stimulates Abeta fibres which close the “pain gate” in the Substansia Gelatinosa

Opioids - stimulate PAG an activate the descending inhibitory pathway

General anaesthetics - block sensory perception, memory and consciousness - patient is unconscious and unaware