Physiology and Pathophysiology of pain Flashcards
What is pain?
- Pain is an unpleasant sensory and emotional experience which we primarily associate with tissue damage or describe in terms of such damage or both
- Final product of complex-information processing network
What is pain not?
A stimulus
Where do the 4 steps of pain processing take place?
- Periphery
- Spinal cord
- Brain
- Descending tracts
What part does the periphery play in pain processing?
- Detection
- Transmission to spinal cord (first order neurons)
What part does the spinal cord play in pain processing?
- Processing
- Transmission to brain (Thalamus) (second order neurons)
What part does the brain play in pain processing?
Perception, learning, response
What parts do the descending tracts play in pain processing?
Modulation
What is nociception?
The detection of tissue damage by specialized transducers connected to A-delta and C fibers
What are nociceptors?
Free nerve endings of A delta and C fibres
What do nociceptors respond to?
Respond to thermal, chemical, mechanical noxious stimuli
Where do the primary afferent/1st order neurons synapse?
Spinal cord
Where are the cell bodies of the primary afferent/1st order neurons?
Dorsal root ganglion
What are the 4 different types of nerve fibre?
- Aa
- AB
- A delta
- C
What fibres are myelinated?
Aa and AB
What fibres are lightly myelinated?
A delta
What fibres are unmyelinated?
C
What fibres have a large diameter?
Aa and AB
What fibres have a small diameter?
C
What fibres have a medium diameter?
A delta
What is the thermal threshold of Aa and AB fibres?
None
What is the thermal threshold of A delta fibres?
- Type 1 53C
- Type 2 43C
What is the thermal threshold of C fibres?
43C
What fibres are responsible for proprioception and light touch?
Aa and AB
What fibres are responsible for nociception (mechanical, thermal and chemical)?
- A delta
- C
What fibre are responsible for innocuous temperature and itch?
C
What does grey matter of the spinal cord represent?
Neurons (cell bodies)
What does white matter of the spinal cord represent?
Nerve tracts
What are the 3 anatomical divisions of grey matter?
Ventral, lateral and dorsal horn
What does rexed divide the grey matter based on?
Rexed divided the grey matter into 10 layers based on their cytoarchitecture
Where are the low threshold mechanoreceptive neurons located primarily?
Low Threshold mechanoreceptive neurons, located primarily in layer 3 & 4 receiving input from A beta fibres
Where are the nociceptive specific neurone located primarily?
Nociceptive specific neurons located primarily in layer 1 & 2 , receiving input from C & A delta fibres
Where are the wide dynamic range neurones primarily located?
WDR wide dynamic range neurons in layer 5 which receive mainly input from A beta but responds to both noxious and non-noxious stimuli via intereurons
What is located in the dorsal horn of the spinal cord?
- First order synapse
- Rexed lamina 2 and 5
What neurons are located in the spinal dorsal horn?
Neurons which receive the input
- Nociceptive specific
- Low Threshold Mechanoceptive
- Wide Dynamic Range
What does the anterior spinothalamic tract convey?
Sensation of simple touch
What does the lateral spinothalamic tract convey?
Fast and slow pain (pain and temperature sensations)
What is the spinothalamic tract?
Major ascending tract for nociception
Where do the spinothalamic tracts arise?
Rexed lamina 2 and 5
Where do the lateral spinothalamic tracts end?
Venteroposterior thalamic nucleus
Where do the anterior spinothalamic tracts end?
Medial thalmic nuclei
What is the second relay station?
Thalamus
What does the thalamus connect to?
- Cortex
- Limbic system
- Brainstem
Where does pain perception occur?
Pain perception occurs in somatosensory cortex
What structures are involved in imprinting a new memory?
- Amygdala
- Hippocampus
- Prefrontal cortex
- Cingulate cortex
- Insula
How do we develop a response to pain?
- The medialpart of the pain matrix composed of amygdala, hippocampus, cigulate cortex insula, prefrontal cortex all feed back and forward with brainstem centres for the affective and emotional component as well as descending control of pain.
- If there is no previous memory of insult then the structures above will imprint. This is how we develop a response to pain and know how to react
What is the periaqueductal grey?
Descending pathway from brain to dorsal horn
What type of system is the periaqueductal grey?
Noradrenergic system
What effect does the periaqueductal grey usually have in pain signals?
Usually decreases pain signal
What is hyperalgesia?
It is the leftward shift of the stimulus response curve, in other words: Increased perception of pain or even perception of non-noxious stimuli as noxious stimuli
When does hyperalggesia occur?
It happens whenever there is tissue injury and inflammation
What is primary hyperalgesia occur?
Primary hyperalgesia is hyperalgesia at the site of injury
What is secondary hyperalgesia?
Hyperalgesia in the surrounding uninjured tissue
What stimuli can hyperalgesia apply to?
Any stimuli including mechanical and thermal
What is allodynia?
A form of hyperalgesia: dynamic mechanical hyperalgesia that to light touch.
What mechanisms are involved in allodynia?
Both peripheral and central mechanisms
What changes occur in the nociceptor in allodynia?
Decreased threshold for response
What changes in nociceptor occur in hyperalgesia?
Exaggerated response to normal and supranormal stimuli
What changes in nociceptor occur in spontaneous pain?
Spontaneous activity in nerve fibres
What is central sensitisation?
It is the response of second order neurons in the CNS to normal input both noxious & non-noxious
What are the main components of central sensitisation?
- Wind up
- Classical
- Long term potentiation
What does wind up happen in?
Wind-up happens only in neurons taking part in the synapses with primary afferent input
What is wind up?
- Wind-up is literally winding up the response to the input
- . It is activity dependent; progressively increases the response of the neurons
What does wind-up manifest over?
It manifests only over a course of a stimulus and terminates with stimulus.
What neurotransmitters mediate wind up?
Substance P and CGRP
What does classical central sensitisation involve?
Involves opening up of new synapses in the dorsal horn. So the new synapses, which were silent till then, will start to receive input and record the nociception. It does occur with all stimuli but the intensity has to be strong to elicit this response.
What is heterosynaptic activity in classical central sensitisation dependent on?
Plasticity
What is the duration of classical central sensitisation?
If the intensity strong enough, it occurs immediately with the stimuli and can outlast the duration of stimuli. -NMDA receptor activation by glutamate is known to trigger a series of changes resulting in classical central sensitization.
What is the clinical result of classical central sensitisation?
clinical result is the secondary hyperalgesia, where the area surrounding the injury site is also painful and where the touch also becomes painful.
How can classical central sensitisation be maintained?
Once activated, it can be maintained even by low intensity of the offending stimuli.
What is involved in long term potentiation?
Involves mainly the activated synapses
What does long term potentiation occur primarily for?
Occurs primarily for
very intense stimuli
What conditions is suprsegmental central sensitisation involved in?
- Fibromyalgia
- Chronic widespread pain
- Painful physical symptoms of depression/anxiety
Describe the characteristics of acute pain?
- <1 month to resolution
- Physiological
- Presence of noxious stimuli
- Sevres protective function
- Usually nociceptive
Describe the characteristics of chronic pain?
- > 3-6 months to resolution
- Pathological
- Presence of noxious stimuli is not essential
- Does not serve any purpose
- Nociceptive, neuropathic or mixed
What is nociceptive pain?
A sensory experience that occurs when specific peripheral sensory neurones (nociceptors) respond to noxious stimuli
What are the characteristic of nociceptive pain?
- Painful region is typically localised at the site of injury – often described as throbbing, aching or stiffness
- Usually time limited and resolves when damaged tissue heals (e.g. bone fractures, burns and bruises)
- Can also be chronic (e.g. osteoarthritis)
- Tends to respond to conventional analgesics
What is neuropathic pain?
Pain initiated or caused by a primary lesion or dysfunction in the somato-sensory nervous system
What are the characteristics of neuropathic pain?
- The painful region may not necessarily be the same as the site of injury – pain occurs in the neurological territory of the affected structure (nerve, root, spinal cord, brain)
- Almost always a chronic condition (e.g. postherpetic neuralgia [PHN], poststroke pain)
- Responds poorly to conventional analgesics
What treatments can be targeted at the transduction portion of the pain pathway?
- NSAIDs
- ICE
- Rest
- LA blocks
What treatments can be targeted at the transmission portion of the pain pathway?
- Nerve blocks
- Drugs (Opioids, Anticonvulsants)
- Surgery (DREZ, Cordotomy)
What treatments can be targeted at the perception portion of the pain pathway?
- Education
- Cognitive behavioural therapy
- Distraction
- Relaxation
- Graded motor imagery
- Mirror box therapy
What treatments can be targeted at the descending modulation portion of the pain pathway?
- Placebos
- Drugs (opioids, antidepressants)
- Surgery (spinal cord stimulation)
What is gate control theory?
The gate control theory of pain asserts that non-painful input closes the “gates” to painful input, which prevents pain sensation from traveling to the central nervous system. Therefore, stimulation by non-noxious input is able to suppress pain
