How does pain activate sensory systems?
Detection and signalling from periphery to spinal cord.
Signal integration in the dorsal horn.
Ascending pathways to the brain.
Descending modulation.
Peripheral and central mechanisms of pain facilitation.
What is pain?
An unpleasant sensory and emotional experience associated with actual or potential tissue damage.
It is a combination of sensory and affective components.
It is subjective.
Nociception is the sensory component of pain.
What are nociceptors?
Peripheral perception of pain.
Free nerve endings in skin, muscle and viscera.
Activated by intense (noxious) stimulus that is sufficient to cause tissue damage - injury, heat, cold, inflammation, pH.
Generates action potentials, the stimulus intensity is encoded through the firing rate (stronger intensity = higher rate).
What are mechanical nociceptors?
Activated by strong shearing force in skin
e.g. a cut or strong blow.
It is a sharp pain.
What are polymodal nociceptors?
Respond to many stimuli
e.g. sharp blow, damaging heat (>46 degrees), chemicals released by damaged tissue - K+, H+, histamine, prostaglandins, bradykinin.
It is a dull burning pain.
What are primary sensory neurones?
Mechanical nociceptors - A delta fibres, thin axons with some myelination.
Polymodal nociceptors - C fibres, thin axons unmyelinated.
These are primary afferent fibres.
They are all excitatory.
What is the pathway of the primary sensory neurones (primary afferent fibres)?
The cell body is in the dorsal root ganglia - outside of the spinal cord.
The cell body has two axons - one goes to the periphery.
The other axon goes into the spinal cord dorsal horn and makes synaptic contact with another neurone.
When there is stimuli sufficient to produce action potentials in the peripheral nerve ending it propagates up to the brain.
What are the different orders of primary sensory neurones?
Primary order neurones - the first neurone in the pathway, signal to second order.
Second order in the spinal cord to the brain.
Tertiary order - from the brain thalamus to other parts of the brain.
The neurones are all excitatory because they release excitatory neurotransmitter.
How does transmission of noxious information change?
The thicker the axon and the more myelinated, the faster conduction.
Delta fibres have fast transmission so sharp pain.
C fibres have slower transmission so a dull, burning pain.
See picture.
What is the pain felt when injured?
First pain - sharp pain.
This is caused by the activation of the A delta fibres, which have fast transmission.
The second pain is the dull, burning pain, due to activation of C fibres by the same stimuli, which have slower transmission.
What are the nociceptive inputs to the dorsal horn in the spinal cord?
Nociceptive inputs input to lamina I and II - the superficial dorsal horn has noxious information.
A Beta fibres input to laminar 4, which is also receiving input from A delta fibres.
The output neurones receive the signal directly from the primary afferent or indirectly via interneurones.
What are the cutaneous inputs into the dorsal horn?
Afferent input form the skin into lamina I or II.
This is topographically distributed - a specific neurone in the spinal cord inputs to a specific neurone in the sensory cortex which allows you to know where the sensory input is from.
What are the viscera inputs in to the dorsal horn?
The connection into the dorsal horn is more diffuse.
When you feel the pain, you don’t know where the input is specifically coming from.
There is a lack of topographic distribution.
e.g. in the gut don’t know specifically which part causes the pain.
What is the dorsal horn?
Local interneurones are the majority of dorsal horn neurones.
Modulates activity of projection neurones.
They are mostly inhibitory - that are spontaneously active, or are phasic stimulated by primary afferent input.
The pain signal must overcome inhibition to be sent to the brain - the gate theory, which stops sending of signals to the brain when pain shouldn’t be felt.
What is the inhibitory interneurone in the gate theory of pain?
The inhibitory interneurone is in the substantia gelatinosa, and is inhibiting the output neurone.
When activated, the output neurone sends ascending pain signals to the brain to trigger the sensation of pain.
It is usually inhibited by the inhibitory interneurone to prevent us feeling pain when we shouldn’t.
When a pain signal arrives, the gate is opened so we feel pain.
What is the non-noxious input in the gate theory?
The output neurones receive excitatory input from A beta fibres, which are activated from non-noxious stimulus.
But the output neurone is still inactive due to the inhibitory interneurone.
The A beta neurone also branches and stimulates another inhibitory interneurone to inhibit the output neurone.
So the gate is still closed.
See picture.
What happens to the neurone when there is noxious stimulus?
Stimulation of the A delta and C nociceptor fibres, which is damaging the tissues so sends action potentials.
The fibres excite the output neurone, but it is not sufficiently excited because the inhibitory interneurone gatekeeper is still active and inhibiting.
How is the inhibitory interneurone disinhibited?
The A delta and C fibres excite another inhibitory interneurone, which then inhibits the gatekeeper inhibitory interneurone.
The gate opens in response to the noxious stimulation, and the output neurone produces ascending signal to the brain to feel pain.
This is not a direct inhibitory effect on the gatekeeper neurone, because A delta and C fibres are excitatory. It is indirect through exciting another inhibitory neurone which inhibits the gatekeeper neurone.
See picture.
How is the gate closed to prevent the pain signal?
Rubbing the injured area activates the sensory nerve endings which respond to the non-noxious input via A beta fibres.
A beta afferents input in the spinal cord and activates the inhibitory interneurone, so it further inhibits the output neurone and prevents the ascending pain signal.
How could the gate control theory be used clinically?
Increased non-noxious afferent inputs through A beta fibres to spinal cord to close the gate for analgesic effect:
Transcutaneous electrical nerve stimulation (TENS).
Physical therapy.
Acupuncture.
What are the components of the ascending spinothalamic pathway?
Pain signals travel up the spinothalamic pathway.
Pain is perceived at the subcortical level.
Pain is localised at the cortical level.
The limbic system is the affective (emotional) component.
What are the descending pathways?
Feedback control - down the brainstem into the spinal cord.
The nuclei in the brainstem are rich in opioids - enkephalin, and are released to activate opioid receptors in the dorsal horn of the spinal cord to cause an inhibitory effect and close the spinal gate to have intrinsic analgesia.
Enkephalin can increases the release of 5-HT (serotonin) and noradrenaline to enhance the descending inhibitory signals.
What are analgesic drugs?
Drugs such as heroin and ketamine act on the opioid receptors to inhibit the output neurone and stop the sensation of pain.
What is normal physiological pain?
Or acute pain.
The sensation of pain felt is directly equal to the afferent input, related to the duration and intensity of the pain.
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Voltage-gated ion channels42
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Ionotropic receptors and synapses50
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Metabotropic receptors and Neuromodulation36
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Computer practical26
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Anatomy of motor systems44
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Motor control 134
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Motor control 2 - basal ganglia44
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Learning and memory33
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Pain35
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Limbic system20
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Drug dependence33
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Anxiety and depression36
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Schizophrenia29
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Neurotrauma20
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Neurodegeneration31
