Physiology + pathophysiology of pain Flashcards
What white matter tract does pain sensation ascend in
CONTRALATERAL SPINOTHALAMIC TRACT
How is pain transmitted (3 stages)
Peripheral detection
-transmitted to spinal cord via 1st order neurons to synapse in dorsal horn
Spinal cord processing
-picked up by 2nd order neurons which cross over at the same level of the spinal cord then synapses in the thalamus
Brain processing
-3rd order neuron picks up synapsed impulse and passes through IC then radiates out to the post-central gyrus
1st order neuron in the spinothalamic tract synapses in what 2 layers of the rexed lamina of the dorsal horn
2 and 5
2nd order neuron in the spinothalamic tract synapses where in the thalamus
VENTRAL POSTERIOR THALAMIC NUCLEI
Descending tracts that modulate pain begin where and end where + how do they modulate pain
Descending pathway begins from the PERIAQUEDUCTAL GREY (primary control centre for descending pain in the brainstem) and ends in the DORSAL HORN
PAG produces pain supressing cells that DECREASE PAIN SIGNAL such as noradrenaline
Define nociception
detection of tissue damage by nociceptors connected to Aδ & C fibres
Describe the nerve endings of nociceptors
FREE NERVE ENDINGS
What stimuli do nociceptors respond to
THERMAL, CHEMICAL & MECHANIAL NOXIOUS STIMULI
All receptors have noxious and non-noxious range, Aδ & C fibres respond only to which range
Noxious
Describe the size and myelination of Aδ fibres + what they transmit
Small diameter myelinated
Fast pain
Describe the size and myelination of C fibres + what they transmit
Large diameter unmyelinated
Slow dull pain
When someone pinches you, you will have a sharp pain to start with which will slowly transform into dull pain
The first and second pain are transmitted by what fibres
Aδ
C
The grey matter of the spinal cord is divided into 10 layers known as what
Rexed lamina
Low threshold mechanoreceptive neurons are located primarily in what layers of the rexed lamina, receiving input from what fibres
3 & 4
Aβ fibres
Anterior spinothalamic tract conveys what sensation
Crude touch
What is the pain matrix + what are the 2 parts of the matrix
connections between different parts of brain to perceive pain
Lateral and medial part
What does the lateral part of the pain matrix compose (2)
somatosensory cortex and ventral posteromedial nuclei of thalamus
What is hyperalgesia + what direction does hyperalgesia shift the stimulus response curve
INCREASED PERCEPTION OF PAIN/ PERCEPTION OF NON-NOXIOUS STIMULI AS NOXIOUS STIMULI
Left
When does hyperalgesia occur
When there’s tissue injury & inflammation
What is allodynia
A form of hyperalgesia
-mechanical hyperalgesia to LIGHT TOUCH
What change occurs in the nociceptor in hyperalgesia
Exaggerated response to normal stimuli
What change occurs in the nociceptor in allodynia
Decreased threshold for response
-range at which the thermal or mechanical stimuli become noxious is changed
Peripheral sensitisation involves what order neurons
1st
What is central sensitisation
response of 2nd order neurons in the CNS to normal noxious & non-noxious stimuli
3 stages of central sensitisation
Wind up
Classical
Long term potentiation
What occurs in the ‘wind up’ stage of central sensitisation
Happens only in neurons taking part in the synapses with primary afferent input.
It is activity dependent; progressively increases the response of the neurons
What occurs in the ‘classical’ stage of central sensitisation
Opening up new synapses (silent nociceptors) in the dorsal horn – GETTING HELP FROM OTHER NOCICEPTORS
If the intensity of the stimuli strong enough, it occurs immediately with the stimuli and can outlast the duration of stimuli
What occurs in the ‘long term potentiation’ stage of central sensitisation
Involves mainly activated synapses and occurs primarily for very intense stimuli.
The mechanism involves both AMPA and NMDA receptor activation by glutamate
How long does acute pain last
<1 month
Acute pain is usually physiological or pathological
Physiological
Is a noxious stimuli essential in acute or chronic pain
Acute
Does acute or chronic pain serve a protective function
Acute
Acute pain is usually nociceptive, neuropathic or mixed
Chronic pain is usually nociceptive, neuropathic or mixed
Nociceptive
Any
Name an example of acute nociceptive pain
Bone fracture
Name an example of chronic nociceptive pain
Osteoarthritis
Nociceptive pain tends to respond to what, neuropathic pain responds poorly to these
Conventional analgesia, e.g. NSAIDs, opioids, paracetamol
In neuropathic pain, the painful region may not be the same as what
Site of injury
Strategies to modulate pain at transduction stage (3)
NSAIDs
Ice
Local anaesthetic nerve block
Strategies to modulate pain at transmission stage (5)
Nerve block
Opioids
Anticonvulsants
Surgery
- dorsal root entry zone - blocking the noxious stimulus from ascending up the spinal cord to the brain by using radio waves to stop the nerve signal
- cordotomy - cutting selected nerves to disable spinothalamic tract
Strategies to modulate pain at perception stage (4)
Education
Cognitive behavioural therapy
Distraction/relaxation
Graded motor imagery – exercising brain in neuropathic pain conditions to deal with pain better
Strategies to modulate pain at descending modulation stage (3)
Opioids
Antidepressants
Surgery
-spinal cord stimulation -device delivers electric pulses to electrodes placed over the spinal cord, stimulating noradrenergic system to decrease pain
Name 5 cutaneous receptor types
Mechanoreceptors Chemoreceptors Thermoreceptors Nociceptors Proprioceptors
What do mechanoreceptors respond to changes in (3)
Pressure, stretch/deformation, vibration
What do chemoreceptors respond to changes in (3)
Arterial O2, CO2, pH
Why can’t you say nociceptors are stimulated by a painful stimulus
Because the stimulus isn’t painful until it’s perceived to be damaging/painful by the brain
What are proprioceptors
mechanoreceptors in joints and muscles that signal body/limb position
Describe the nerve endings of mechanoreceptors
Enclosed in pacinian corpuscles or meissner’s corpuscles, i.e. not free nerve endings
Sensory receptors respond to a stimulus over a specific area called what
Receptive field
What is acuity
The ability to locate a stimulus on the skin and differentiate it from another stimulus close by
What 2 things are acuity determined by
Density of innervation and size of receptive field
If you have high acuity then what does this mean in regards to locating a stimulus on the skin and discriminating 2 points
High sensitivity
Easy to tell 2 points apart
Our ability to discriminate 2 points on the skin apart depends on what 2 things
Receptive field size
Neuronal convergence
What is neuronal convergence
Multiple presynaptic neurons input on a smaller number of post-synaptic neurons, e.g. o Sensory neurons with neighbouring receptive fields exhibit neuronal convergence
Areas of skin densely innervated (sensitive areas) are characterised by what 2 things
Small receptive field
High acuity
Relatively insensitive area of skin is characterised by what 2 things
Convergence –> large secondary receptive field
Low acuity
Sensory receptors generate what kind of potential from an adequate stimulus
Receptor (generator) potential = graded potential
The size/amplitude of a receptor potential encodes what/tells us what
The intensity of the stimulus
So receptor potential is graded to stimulus intensity
Receptor potentials evokes firing of APs when…
+ what property of APs encodes intensity of stimulus
It has reached a certain amplitude
Frequency of APs
What is the adequate stimulus of mechanoreceptors and proprioceptors + how does this stimulus generate a receptor/graded potential (2)
Membrane deformation of the capsule –> activates stretch sensitive ion channels causing ion flow across the membrane –> graded potential
Is there a threshold to initiate a receptor/graded potential
No
What is the threshold potential for an AP to be fired
-55mV
What can an AP peak to
+40mV
How is an AP generated from a receptor/graded potential
Once threshold potential (-55mV) reached, AP initiated:
- change in membrane potential opens voltage gated Na+ channels, sudden +ve charge entering cell causes rapid depolarisation to +40mV
What region of a neuron is known as the trigger zone
Axon hillock
Grades potentials … to evoke an AP
summate
Receptor (graded) potentials encode stimulus intensity by what
APs encode stimulus intensity by what
Amplitude
Frequency
Name the 4 primary afferent fibre types
Aα
Aβ
Aδ
C
Describe the size and myelination of Aα fibres + what they transmit
Large + myelinated
Touch, pressure, vibration
Describe the size and myelination of Aβ fibres + what they transmit
Large + myelinated
Touch, pressure, vibration
Proprioception is mediated by which 2 afferent fibre types
Aα
Aβ
What pathway does pain and temp info travel in
Contralateral spinothalamic tract
What pathway does info about touch and limb position reach consciousness
Dorsal column
First order neurons of the dorsal column pathway synapse where
Cuneate & gracile nuclei in the medulla
Where do all primary afferent fibres ultimately terminate
Somatosensory cortex (S1)
Why/how do rapidly adapting mechanoreceptors adapt to a maintained stimulus and only signal change at the onset of stimulation (2) + give a situation where rapidly adapting mechanoreceptors are acting
Stimulus is enough to cause an above threshold generator potential, which triggers APs
But the generator potential declines rapidly and APs cease
Putting on clothes
How do slowly adapting mechanoreceptors work (2)
Stimulus is enough to cause an above threshold generator potential, which triggers APs
APs keep firing throughout stimulus and doesn’t stop firing until stimulus stops
Mechanoreceptors with pacinian corpuscles or meissner’s corpuscles are rapidly or slowly adapting
Rapidly
Mechanoreceptors with Merkel’s discs or Ruffini endings are rapidly or slowly adapting
Slowly
Are nociceptors quick or slow adapting
Slow because it is important not to ignore painful stimuli.
Describe the concept of lateral inhibition in relation to neurons (2)
Activation of one sensory input causes synaptic inhibition of its neighbouring sensory neurons
Allows precise localisation - inhibits sensory receptors on either side of the stimulus in order to increase precision/localisation and perception of the stimulus
Does all sensory info reach the brain
No, would be too much for the brain to process
Types of pain (6)
Sharp stabbing v diffuse throbbing Fast (initial) v slow (delayed) Acute v chronic Visceral Referred Phantom limb
Why can pain originating from the viscera often result in sensation being referred to a somatic structure from the same dermatomes (i.e. why do we get referred pain) (2)
Because neurons of mechanoreceptors can converge with neurons of nociceptors onto one particular neuron
Due to convergence, the brain doesn’t know where or what type of stimulus has evoked that potential
Signal transduction of nociceptors is activated by (3)
Low pH
Scolding heat
Local chemical mediators, e.g. bradykinin, histamine, prostaglandins
Noxious stimulation of the skin releases local chemical mediators such as… (3)
Bradykinin
Histamine
Prostaglandins
Function of bradykinin + function of prostaglandin
Stimulate nociceptive sensory terminals
Sensitise the sensory terminals of nociceptive fibres to bradykinin
Explain the gate control hypothesis for pain modulation (hint: inhibitory interneurons release chemicals…)
Activity in Aα/β (carry touch, pressure, vibration, stretch) fibres activates inhibitory interneurons in the spinal cord
Inhibitory interneurons release opioid peptides (endorphins) onto the 1st order neurons of the nociceptive pathway which inhibits transmitter release from the 1st order Aδ/C fibres to the 2nd order, hence “closing the gate” and stopping transmission to the 2nd order neuron so preventing damaging stimuli from reaching brain
How can pain be controlled by descending pathways in the CNS
The same inhibitory interneurons activated by Aα/β fibres are also activated by descending pathways from peri-aqueductal grey matter (PAG) and nucleus raphe magnus (NRM), hence also “closing the gate”
These descending pathways synapse with those inhibitory interneurons in the spinal cord, activating them to release opioid peptides (endorphins) onto the 1st order neurons of the nociceptive pathway
How does an analgesic such as NSAIDs prevent transmission of nociceptive info
NSAIDs inhibit cyclo-oxygenase production, the enzyme which generates prostaglandins, and therefore stop sensitisation of sensory terminals of nociceptive fibres to bradykinin
How are prostaglandins created
The enzyme, cyclo-oxygenase, converts arachidonic acid to prostaglandins
How does an analgesic such as local anaesthetic prevent transmission of nociceptive info
Block voltage gated Na+ channels that cause APs, therefore blocking all axonal transmission
How does an analgesic such as opiates prevent transmission of nociceptive info (3 ways that opiates do this)
Block transmitter release of 1st order neuron in dorsal horn by hyperpolarising nerve terminals so no AP evoked so no transmitter release
activate mu receptors which inhibit transmission across this synapse, and therefore “close the gate
activate descending pathways from the brainstem that also “close the gate” in the spinal cord
Why is an epidural anaesthetic particularly good at preventing transmission of nociceptive info
An epidural anaesthetic will have good access to the site of the synapses between the primary afferent fibres and the second order projection neurones in the superficial layers of the dorsal horn
How does TRANS CUTANEOUS ELECTRIC NERVE STIMULATION (TENS) prevent transmission of nociceptive info
activates large diameter innocuous mechanoreceptive fibres from the same body segment as the painful stimulus.
This stimulates release of endogenous opioid peptides from interneurons in the dorsal horn of the spinal cord which activates the same mu receptors and therefore inhibits synaptic transmission between the primary afferent fibres and the second order projection neurons
