Physiology and Pathophysiology of pain Flashcards
Describe the pain pathways
nociceptive fibres come in via the dorsal horn and synapse at same level. They then cross over before ascending to the brainstem then the midbrain, thalamus
from the thalamus the fibres can go to the somatosensory cortex, limbic system or cingulate cortex
Describe step by step how we recognise and act on a painful stimulus
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
What is nociception?
The detection of tissue damage by specialized transducers connected to A-delta and C fibers
What stimuli do the free nerve endings of A delta and C-fibres respond to? (4)
thermal
chemical
mechanical - pressure etc
noxious stimuli
Where do first order neurons synapse
grey matter of the spinal cord of same segmental level they enter
their cell body is in the dorsal root ganglion
which cells represent the macrophagic system in the spinal cord?
glial cells
Which types of neuron receptors in the grey matter receive input from primary afferent fibres? (4)
Nociceptive specific - layer 1+2
Low Threshold - layer 3+4
Mechanoceptive
Wide Dynamic Range - layer 5
Primary afferent fibre types
A alpha and A beta
A delta
C
What does the lateral spinothalamic tract carry?
Conveys fast and slow pain and temperature
What does the anterior spinothalamic tract carry?
Sensation of light touch
What is the spinothalamic tract?
The major tract sending impulses to the thalamus
- nociception in particular
Their cell bodies lie mostly in Rexed lamina 2+5
What is the thalamus’ role in nociceptive pain pathways?
It is the second relay station (1st being spinal cord)
within the thalamus there are nuclei - ventroposterior and medial. Both receive inputs from spinothalamic tracts
The thalamus makes connections with the limbic system and the cortex ie after it receives inputs it sends them on to these areas
Where does pain perception occur?
in the somatosensory cortex
What is the cingulate cortex? what is it’s function?
part of the brain situated in the medial aspect of the cerebral cortex.
It lies immediately above the corpus callosum
It is an integral part of the limbic system, which is involved with emotion formation and processing, learning, and memory.
descending pathways travel from the brain to where?
descend from the cortex to the brainstem. They then descend to the dorsal horn
Describe how Descending pathways inhibit pain pathways?
Periaqeductal grey matter (PAG) (lies around the cerebral aqueduct) and nucleus raphe magnus (NRM) send descending controls.
These activate inhibitory interneurones that ‘close the gate’ blocking nociceptive fibres from getting through and up to the brain.
Usually decreases pain signal.
They release noradrenaline and serotonin - modulate the ascending pain transmission.
What is hyperalgesia?
Increased perception of pain or even perception of non-noxious stimuli as noxious stimuli
This happens whenever there is tissue injury and inflammation
Primary and secondary - primary = site of tissue injury, secondary = surrounding tissue
can be for any stimuli ie thermal, mechanical etc
What is Allodynia? What change occurs in the nociceptor?
A form of hyperalgesia - sensitive to light touch
Change = decreased threshold for response
The electrical threshold of the nerves does not change but the range at which the thermal or mechanical stimuli become noxious is changed
What change occurs in nociceptors in Hyperalgesia?
Exaggerated response to normal and supranormal stimuli
When does spontaneous pain occur and what changes are there in the nocicpetors to cause this?
mainly during nerve injuries
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
similar to peripheral sensitisation ( increased sensitivity to an afferent nerve stimuli) - main difference is C.S happens at the level of the spinal cord and acts in tandem
What are the 3 main components of central sensitisation?
Wind up
classical
long term potentiation
Wind-up part of central sensitisation
It’s literally winding/progressively increasing the response of neurons to the input
Involves only activated synapses - ones that are working with primary afferent input
Manifests over the course of stimuli & terminates with stimuli
mainly mediated by the neurotransmitters Substance-P and CGRP
Classical part of central sensitisation
Involves opening up of new synapses in the dorsal horn (silent nociceptors)
So these new synapses start to receive input and record the nociception
Immediate onset with appropriate stimuli (if strong enough)
Can outlast the initial stimuli duration
Can cause secondary hyperalgesia, where the area surrounding the injury site is also painful and where the touch also becomes painful. Once activated, it can be maintained even by low intensity of the offending stimuli.
Long term potentiation
Involves mainly the activated synapses
Occurs primarily for
very intense stimuli
The mechanism involves both AMPA and NMDA receptor activation by glutamate.
Acute pain:
- average timescale
- usual presentation
< 1 month
Usually obvious tissue damage
Increased nervous system activity
Pain resolves upon healing
Serves a protective function
Chronic pain
> 3-6 months
Pain beyond expected period of healing
usually has no protective function
Degrades health and function
What is a nociceptive pain?
A sensory experience that occurs when specific peripheral sensory neurones (nociceptors) respond to noxious stimuli
Painful region is typically localised at the site of injury
Time limited usually
Can also be chronic e.g osteoarthritis
tends to respond to conventional analgesics
What is a neuropathic pain?
Pain initiated or caused by a primary lesion or dysfunction in the somato-sensory nervous system
Painful region may not necessarily be at the same site of injury - pain occurs in the neurological territory of affected structure (e.g nerve, root, spinal cord, brain)
almost always chronic - post stroke pain, neuralgia
responds poorly to conventional analgesics
What methods are there to block pain transduction? (4)
NSAIDs
Ice
Rest
Local Anesthetic blocks
What methods are there to block pain transmission? (3)
Nerve blocks
Drugs
Opioids
Anticonvulsants
Surgery
DREZ - dorsal root entry zone
Cordotomy - disables selected pain-conducting tracts in the S.Ctransduction vs transmission
transduction = production of electrical signals at the pain nerve endings
transmission = propagation of those signals through the PNS
How is perception of pain managed? (5)
Education
Cognitive behavioural therapy
Distraction
Relaxation
Graded motor imagery
Mirror box therapy - help alleviate phantom limb pain, in which patients feel they still have a limb after having it amputated.
Descending modulation inhibition? (3)
Placebos
Drugs
Opioids
Antidepressants
Surgery
Spinal cord stimulation
