Physiology and Pathophysiology of Pain Flashcards
Define pain
An unpleasant sensory and emotional experience which we primarily associate with tissue damage
It is not a stimulus but a final product of compact information processing network
How is tissue damage detected
By specialised transducers with nociceptors connected to A delta and C primary afferent fibres
What is the function of A delta and C primary afferent fibres
Free nerve endings that conduct pain as first order neurone from peripheral nerve to the spinal cord
how are nerve fibres classified
Based on the diameter and conduction velocity
How are A delta fibres classified
Lightly myelinated
Medium diameter
What are A delta fibres responsible for
Fast pain
First pain
Sharp pain
How are C fibres classified
Un-myelinated
Small diameter
What is the property of C fibres
Slow conductors
What is C fibres responsible for
Dull pain
What do A delta and C fibres respond to
Thermal
chemical
mechanical
Noxious stimuli
What is the pathway of the first order of neurones of A delta and C fibres
travel through peripheral nerves, through cell body in dorsal root ganglion and synapse in the spinal cord dorsal column
What are the 3 sensory neurones that receive input in the spinal cords dorsal horn
Nocioceptive specific
-receive input from C and A delta fibre
Low threshold
mechanoreceptive
-Receive input from A beta fibres
wide dynamic range -receive input from main A beta
-But respond to both noxious and non noxious stimuli via interneurones
What do the interneurones influence in the dorsal horn on the nociceptive fibres
Is where first order neurones synapse for nociceptive fibres so influence the projection of neurones and afferent input
as either inhibits or exhibits projection of neurones
When nociceptive fibres synapse in the dorsal horn and become second order neurone their axons continue as tracts, what is the major ascending tract for nociceptive fibres
Spinothalmic tract receives A delta and C fibres
What is the pathway of second order neurone noceceptive fibres
Follows spirothalmic tract and crosses over to contralateral side to either lateral or ventral spinothalmic tract then sends impulses to thalamus
What is the function of the lateral spinothalmic tracts
Conveys fast and slow pain
- pain
- temperature sensations
What is the function of the ventral spinothalmic tracts
Convey sensation of simple touch
Where does the lateral spinothalmic tract synapse in the thalamus
ventroposterior thalamic nuclei
Where does the ventral spinothalmic tract synapse in the thalamus
the medial thalamic nuclei
What is the purpose of synapsing in the thalamus
as acts as a second relay station which further connects
cortex
limbic system
brain stem
Where does pain perception occur
in the somatosensory cortex
the connection between different brain centres to perceive pain is seen as a pain matrix divided into
Lateral aspect of pain matrix
Medial aspect of pain matrix
What is the lateral aspect of the pain matrix composed of
Somatorsensory cortex
ventralposterioir nuclei of thalamus
What is the function of the lateral aspect the pain matrix
Is the sensory discriminative part of nocieoception
What is the medial aspect of the pain matrix composed of
(limbic system) amygdala hippocampus cigluate cortex insula prefrontal cortex
What is the function of the medial aspect of pain matrix
cause feedback and forward with brain stem centres, for affective emotional components as well as descending control of pain
What occurs once the lateral spinothalmic tract terminates in ventroposterior thalamic nuclei
nuceli primarily feeds into somatosensory cortex to facilitate the spatial temporal and intensity discrimination of painful stimuli
give pain perception
What occurs when the Ventral spinothalmic tract terminates in the medial thalamic nuclei
Projects to the cortical regions such as anterior cingulate and insular cortex as well as other parts of the limbic system
With the brains perception of pain, we involve learning via the limbic system
How do we know the limbic system is connected to behaviours
as behavioural state influence the firing in medial thalamus
How does the anterior cingulate in the limbic system contribute to pain
may contribute to the affective component of pain experience and modulate the autonomic and motor components of pain.
How do we respond to the pain
via a descending pathway from brain to dorsal horn through periaqueductal grey matter pathway
What is the cause peripheral sensitisation
a subjective experience to changes in nociceptors
either by decreases threshold for response, or the range as which stimuli become noxious changes giving an exaggerated response
What is three types of peripheral sensitisations
Hyperalgesia
allodynia
spontaneous pain
What occurs in hyperalgesia
an exaggerated response to normal and supernormal stimuli, resulting i increased perception of pain or even perception of non noxious stimuli as noxiou
When does hypergesia occur
Occurs when there is tissue injury and inflammation, and due to any stimulation thermal or mechanical
What are the different types o hypergesia
Primary hypergesai - is hypergesis at the site of injury
Secondary hypergesia - hyergesia to the surrounding uninjured tissue
What occurs in allodynia
is a decreased threshold for response,
due to increased response of neurone following normally non painful stimulation
What is involved in allodynia
Both peripheral and central mechanism are involved
Peripheral changed occur in the nociceptors because of inflammatory mediators and inherent changes
What occurs in spontaneous pan
spontaneous activity in nerve fibres mainly due to nerve injuries
How and where does central sensitisation occurs
Response of second order neurones in the CNS to normal input in both noxious and non noxious
Happens at the level of the spinal cord and acts as a tandem
What is the three main components in central sensitisation
Wind Up
Classical
Long tem potentiation
What occurs in wind up central sensitisation
Wind-up is literally winding up the response to the input. So the wind-up happens only in neurons taking part in the synapses with primary afferent input, progressively increasing the response of the neurones
=homosynaptic activity dependant
What is the length of wind up in central sensitisation
manifests over the course of stimuli and terminates with stimuli (activity dependant)
What mediates the mechanism of wind up
Mediated by neurotransmitters
Substance P
CGRP
What occurs in classical central sensitisation
Involves the opening of new synapses (silent nocieoceptors)
so the new synapses which were silent will receive input and record the nociceptors
= hetrosynpatic activity dependant plasticity
What triggers classical central sensitisation and how long does it last
Occur with all stimuli but the intensity has to be strong to elicit this response,
so has immediate onset with appropriate stimuli and can outlast the initial stimuli duration
once activated, can be maintained even at low levels of ongoing stimuli
What is an examples of classical central sensitisation
NMDA receptor activation by glutamate is known to trigger a series of chamges resulting in classical central sensitization
What is a clinical result of classical central sensitisation
Secondary hyperalgesia
where the area surrounding the injury site is also painful and where the touch also becomes painful
What occurs in long term potentiation central sensitisation
Involves mainly the activated synapses
Occurs primarily for very intense stimuli
the mechanism involves both AMPA and NDMA receptor activation by glutamate
Suprasegmental central sensitisation can clinically result in
Fibromyalgia
chronic wide spread pain
painful physical symptoms of depression/anxiety
Explain gat control theory on pain
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.
What opens the gate in gate control theory
The “gate” is opened by the activity of pain signals traveling up small nerve fibers
what closes the gate in gate control theory
closed by activity in larger fibers or by information coming from the brain
How do we control pain
through descending Peraqueductal grey (PAG) rosteroventromedial medulla (RVM) complex that exhibits gate theory control
What is PAG
is the primary control center for descending pain modulation. It has enkephalin-producing cells that suppress pain in a noadrengeric system
How does PAG exhibit gate control theory
The descending pathway, activates enkephalin-releasing neurons that project to the raphe nuclei in the brainstem and release serotonin
serotonin then descends to the dorsal horn of the spinal cord where it forms excitatory connections with the “inhibitory interneurons”
the activated interneurons inhibit incoming C and A-delta fibers activation of the second-order neuron that is responsible for transmitting the pain signal up the spinothalamic tract to the ventroposteriolateral nucleus (VPL) of the thalamus
The nociceptive signal was inhibited before it was able to reach the cortical areas that interpret the signal as “pain”
What is the function of the rostral ventral medulla
sends descending inhibitory and excitatory fibers to the dorsal horn spinal cord neurone
so preceding nociceptive input or inhibiting nociceptive input
Characteristics of acute pain
Physiological
presence of noxious stimuli
severe protective function
usually noceioceptive
usually obvious tissue damage
increased nervous system activity
pain resolves upon healing
characteristics of chronic pain
Pathological
presence of noxious stimuli is not essential
does not serve any purpose - usually no protective function
nociceptive, neuropathic or mixed
pain for 3- 6months of more
pain beyond period of healing
degrades health and function
Define noceioceptive pain
A sensory experience that occurs when specific peripheral sensory neurones (nociceptors) respond to noxious stimuli
Characteristics of nociceptive pain
Painful region is typically localised t the site on injury
often
described as throbbing, aching or stiffness
Usually time limited and resolves when damaged tissue heals
response to conventional analgesics
Define neuropathic pain
pain initiated or caused by a primary lesion or dysfunction in somatosensory nervous system
Define characteristics of neuropathic pain
The pain region may not necessarily be the same as the sit of injury
Mostly always a chronic condition
Poorly responds to conventional analgesics
Examples of neuropathic pain
postherpeutic neuralgia PHN
Post stroke pain
Examples of noceoceptive pain
Acute
- bone fracture
- burns
- brusises
chronic
- osteoarthritis
What does treatment of pain depend upon
Location pathway point of pain
What is the treatment If pain is due to transduction pathway
NSAIDS
ice
Rest
LA blockers
What is the treatment If pain is due to Transmission pathway
Drugs:
opiods
anticonvulsants
Surgery:
-DREZ
(creates an opening in the spine and expose the spinal cord to asses the dorsal nerve route)
- Cordotomy
(Cutting selected nerves disables pain-conducting tracts in the spinal cord, effectively blocking pain sensation)
What is the treatment If pain is due to perception pathway
Education Cognitive behavioural therapy Distraction Relaxation Grader motor imagery Mirror box therapy
What is the treatment If pain is due to descending modulation pathway
Placebos
Drugs:
opioids
antidepressants
Surgery:
cord stimulation
