Physiology and pathophysiology of pain

Question 1

Give a general outline of the pain pathway

Answer 1

• Step 1: Periphery
		○ Detection
		○ Transmission to spinal cord (first order neurons)
	• Step 2: spinal cord
		○ Processing
		○ Transmission to brain (thalamus) (second order neurons)
	• Step 3: Brain
		○ Perception, learning, response 
	• Step 4: modulation
		○ Descending tracts

Question 2

Explain the peripheral part of the pain pathway

Answer 2

-Cell body in the dorsal root ganglion
- First order neurons
- Synapse at spinal cord
- A alpha and A Beta fibres
□ Myelinated
□ Large diameter
□ Proprioception and light touch
- A delta Fibres
□ Lightly myelinated
□ Medium diameter
□ Responsible for fast pain
□ Thermal threshold:
® Type 1: 53°C
® Type 2: 43°C
- C Fibres
□ Unmyelinated
□ Small diameter
□ Innocuous temperature, itch, nociception
□ Dull pain after initial sharp pain produced by A
□ Thermal threshold: 43°C

Question 3

Explain the spinal cord part of the pain pathway

Answer 3

• Spinothalamic tract
  □ Major ascending tract for nociception
  □ The cell bodies are located in rexed lamina 1, 2 and 5
  □ 2 types of spinothalamic tracts
  ® lateral (neo): terminates in the ventroposterior thalamic nuclei (feeds to somatosensory cortex to facilitate the spatial, temporal and intensity discrimination of painful stimuli)
  ® ventral (paleo): goes to the medial thalamic nuclei (projects to cortical regions such as the anterior cingulate and insular cortex as well as other parts of the limbic system)

Question 4

What is peripheral sensitisation?

Answer 4

• Hyperalgesia
○ The leftward shift in the pain response curve when a tissue has been injured leading to an increased sensation of pain (even when you touch a cut lightly it can still be sore this is because of hyperalgesia)
- Allodynia: a form of hyperalgesia (dynamic mechanical hyperalgesia to light touch)
○ The electrical threshold of the nerves do not change but the range of which the mechanical and thermal stimuli become noxious is changed
○ Then for a given stimulus, there is an exaggerated response to both normal and supranormal stimuli
○ Occasionally spontaneous activity happens, mainly during nerve injuries and this is interpreted as spontaneous pain

Question 5

What is central sensitisation?

Answer 5

○ Similar to peripheral sensitisation the main difference being that it happens at the level of the spinal cord and acts in tandem
○ 3 main components
	- Wind-up 
	- Classical
        - Long term potentiation

Question 6

Explain The wind up component of central sensitisation

Answer 6

□ Winds up the response to the input
□ Involves only activated synapses
□ It is homosynaptic activity dependent and it progressively increases the response of the neurons
□ Manifests over the course of a stimulus and terminates with that stimulus
□ Mainly mediated by neurotransmitters substance P and CGRP

Question 7

Explain the classical component of central sensitisation

Answer 7

□ Leads to the opening up of new synapses in the dorsal horn
□ New synapses, which were silent until then, will start to receive input and record the nociception
□ There is an immediate onset if the stimulus is strong enough and can outlast the duration of the stimulus
□ NMDA receptor activation by glutamate is known to trigger a series of changes resulting in classical sensitization
□ The clinical response is secondary hyperalgesia (where the surrounding area of the damaged tissue is also painful)
□ Once activated it can be maintained even at low intensity of the offending stimuli

Question 8

Explain the long term potentiation component of central sensitisation

Answer 8

□ Involves mainly activated synapses
□ Occurs primarily for very intense stimuli
□ Mechanism involves both AMPA and NMPA receptor activation by glutamate

Question 9

What is acute pain?

Answer 9

○ <1 month
○ Physiological
○ Usually obvious tissue damage
○ Increased nervous system activity
○ Pain resolves upon healing
○ Serves a protection function
○ Nociceptive

Question 10

What is chronic pain?

Answer 10

○ ≥3-6 months
○ Pathological 
○ Presence of noxious stimuli is not essential
○ Pain beyond expected period of healing
○ Usually has no protective function 
○ Degrades health and function
○ Nociceptive neuropathic or mixed

Question 11

What is nociceptive pain?

Answer 11

○ A sensory experience that occurs when specific peripheral sensory neurons (nociceptors) respond to noxious stimuli
○ Painful region is typically localised at the site of injury- often described as throbbing, aching or stiffness
○ Usually time limited and resolved when damaged tissue heals
○ Can also be chronic (e.g. osteoarthritis)
○ Tends to respond to conventional analgesics

Question 12

What is neuropathic pain?

Answer 12

○ Pain initiated or caused by a primary lesion or disfunction in the somatosensory nervous system
○ The painful region may not necessarily be the same as the site of injury- pain occurs in the neurologic territory of the affected structure (nerve, root, spinal cord, brain)
○ Almost always chronic condition
○ Responds poorly to conventional analgesics

Question 13

What are the various management strategies of pain?

Answer 13

• Transduction
        ○ NSAIDs
	○ Ice
	○ Rest
	○ LA blocks
• Transmission
	○ Nerve blocks: surgical/ epidural anaesthesia
	○ Drugs: Opioids, anticonvulsants  
	○ Surgery: DREZ (dorsal root entry zone), cordotomy 
• Perception 
	○ Education
	○ Cognitive behavioural therapy
	○ Distraction
	○ Relaxation
	○ Graded motor imagery 
	○ Mirror box therapy
• Descending modulation
	○ Placebos
	○ Drugs: opioids, antidepressants
	○ Surgery: spinal cord stimulation