Lecture Series One
Lecture One: Introduction to Pain
Allodynia: - The perception of a painful stimulus in the absence of a painful stimulus.
• Or in the presence of an anxious stimulus e.g. a feather stroked across the skin.
This can activate mechanoreceptors in the skin. These then translate this
information in the form of a neural code. Representation A. There is processing of
an external stimulus by primary afferent neurons this is translated into a neural
code
• Noxious stimuli e.g. a fire, stimulus B is represented within the primary afferent
neurons with a different code. Representation B
• The brain needs to process the two different neural codes so that it can perceive
the two different types of pain
• Stimulus A’s neural code is sent to the first gate within the pain pathway. This
gate is represented within the spinal cord.
• So the primary afferent neurons in the skin send afferent projections to the dorsal
root of the spinal cord, the neural code is then transformed from A to a and now
the neural code is represented as ‘a’ in the spinal cord
• Primary neurons within the spinal code then send the new representation/neural
code to centres higher up in the thalamus
• Representation ‘a’ is then transformed into representation ‘α’
• The original stimulus, feather, has been changed a couple of times.
• ‘α’ representation is then sent to the somatosensory cortex, this then perceives
this stimulus as percept α
• Stimulus B activates a different cohort of primary afferent neurones
• This stimulus will activate nociceptive pathways
• Stimulus B is encoded within the primary afferent neurones as representation B
• A different subset of primary afferent neurones including c-fibres and noceptive
fibres transform the neural code from B to b
• This is sent to the thalamus
• Then it is transformed from b to β
• The thalamus then sends this information to the somatosensory cortex and is
perceived as percept β
• This allows the brain to perceive a noxious stimulus
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,What happens in the spinal code when Representation A is not properly encoded by neurones within
the substantia gelatinosa within the dorsal horn of the spinal cord?
• This can cause maladaptive plasticity
• People with allodynia spinal cords translate representation A to representation A prime
• A prime looks more like representation B than representation A.
• The spinal cord will then send representation β to the thalamus
Neural Encoding
• There have been many theories about how peripheral afferent neurons that innervate the
skin encode both noxious and innocuous stimuli
• Intensity Theory: - Sufficiently strong activation of unspecialized neurons result in pain
- So it proposes that peripheral afferent neurones are largely
unspecialized and that if it is activated enough a painful stimulus will
occur but activating only a few results in an innocuous stimulus
- It is known now that this theory is incorrect as there is specialization
within the neurons
• Specificity Theory: - According to this theory high-threshold neurons respond to noxious
stimuli and it is their activation that causes pain
- AKA labelled line theory
• Combinatorial coding Theory: - According to this theory noxious stimuli activate high-
threshold
• Neurons and their activation are involved in evoking pain
- But the stimulus can also activate other PANs e.g. low-
Threshold neurons
- Because the central pathways carrying these signals interact,
Pain will depend on jointly on the HThN and LThN activation
Levels
- The nature of that joint dependence can take many forms
Diverse ways to produce pain
• A hot stimulus activates a primary afferent neuron
- The activation of nociceptors activates a second order neuron, within
the spinal cord causing the neuron in the spinothalamic tract to
synapse on a thalamocortical neuron
- This sends the information to the somatosensory cortex to the brain as
a painful stimulus
• When a cold stimulus activates primary afferent neurons
- The cold stimulus strongly activates cold responsive primary afferent
neurons
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, - (2 is strong activation)
- It also activates another set subset of primary afferent neurons which
respond to cool temperature, Innocuous
- Both stimuli are processed within the spinal cord and activate the
respective second order neurons
- The second order neurons of the spinothalamic tract are synapsed
within the thalamus
- When the cold stimulus gets to the thalamus, the strongly activated
cold responsive neurons are inhibited by the cool responsive primary
afferent neurons
- So instead of getting a cold stimulus, there is only a modest activation
of the thalamic neurons
- However, because 2-1=1 there is still a cold painful stimulus in the
brain
• When there is an innocuous cold stimulus
- The cool stimulus can weakly activate cold responsive neurons
- It also activates cool responsive neurons
- These send their signals to the second order neurons
- These then project to the thalamus
- Because the neurons were only weakly activated, there is a
cancellation effect
- The cool responsive neurons inhibit the cold responsive neurons, then
there is no signal going to the brain
- It is not perceived as pain
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