Nociception Flashcards
Nociceptors
Structures which detect noxious stimuli
Pain
The subjective conscious appreciation of a stimulus that is causing, or threatening to cause, tissue damage.
Nociception
The physical process of detection and transmission of damaging or potentially damaging (noxious) stimuli
Nociceptive fibres are _ nerve endings
free
What are the two types of nociceptor?
Polymodal
Mechanical
What stimulates polymodal nociceptors?
High intensity mechanical (not just touching)
Thermal (>45 C, <10 C)
Chemical
What stimulates mechanical nocicpetors?
High intensity mechanical
Strong thermal ( > 60 C)
They have a myleinated axon
αβ vs C neurons
αβ neurones have more myelin and are associated with input, C with response
Sequence of nociception
- Noxious stimulus
- Primary transduction
- Secondary transduction
- Depolarisation and action potential generation
- Transmitter release
- Second order neuron response
Primary transduction
Channel opening
Secondary transduction
Change in membrane voltage
Signal detection in nociceptors is based on what entering the cell?
Na+
If enough enters, the cell will fire
How is acid detected?
Acid sensing ion channels respond to increased levels of protons
How is mechanical stimulation detected?
Purinergic receptors have ATP as an agonist and respond to high intensity mechanical stimuli
VGNa react to mechanical stimulation and are voltage gated ion channels
Which conducts faster, pain fibres or nociceptive?
Nociceptive fibres
They have a much larger myelin sheath
Pain and nociceptive fibres produce signals with different _ and _
Timings and intensities
Differences between nociception and sensory transmission
- They conduct at slower velocities
- Nociceptors have different thresholds of activation
- They have different sites of projection into the spinal cord
- They elicit different physiological responses in dorsal horn neurones
- Information ascends in different pathways
Discriminating thermoreceptors vs thermal nociceptors
Discriminating thermoreceptors have a different magnitude of afferent response
Nociceptors react more exponentially to temperature past a point
Dorsal column-medial lemniscal pathway
Ascending
Peripheral receptor –> afferent fibre –> dorsal root axon –> dorsal column –> medulla –> thalamus –> cerebral cortex
Touch, vibration etc
Spinothalamic tract
Ascending
Peripheral receptor –> afferent fibre –> dorsal root axon –> lateral spinothalamic tract–> medulla –> thalamus –> cerebral cortex
Other parts of the cortex tell us this is pain
Effects our mood, so we don’t do it again
Pain and temperature
Referred pain
Internal organs have fewer space specific receptors
Often times nociceptive neurones give input to neurones which gives input to a neuron that receives input from another part of the skin causing the pain to be felt there.
E.g: heartburn is caused by stomach acid burning the oesophagus
Any area where nociception has occurred is …
Sensitised
The threshold is lowered for a few days
Cause of sensitisation
Receptors respond to the “bits” that enter the intracellular space when there is damage
* K directly depolarises things by changing the equilibrium potential which makes them more likely to fire again.
* ATP acts directly on P2X3 receptors
* Substance P recruits mast cells to help the area heal, which makes blood vessels more leaky
Hyperalgesia
Increased response to a noxious stimulus
Allodynia
Painful responses to a non-noxious stimulus
Possible sites of nociception
Increased sensitivity of peripheral nociceptors
Increased transmission in the spinal cord
Modulation of nociception
- Prostaglandins don’t cause pain themselves, but sensitize bradykinins which do.
- 5-HT, histamine, ATP, K+ are released by tissue damage
- Lots of receptors react to substances that enter the extracellular space
- TrkA sensitises other receptors, makes them more likely to open and therefore for the nociceptor to depolarise the neurone.
Itch
Caused by Inflammation, particularly histamine
Afferent input is via Aδ and C fibres from free nerve endings
Analgesics don’t inhibit itch, just pain
To cure an itch, you scratch it
Strong central component
Transmission at nociceptor terminals
- Substance P activates NK1 receptors, which are G coupled (Gq type)
- PIP2 is broken down into IP3 and DAG which increase Ca2+ and PKC respectively
- Na+/Ca2+ ion channels are activated
- K+ ion channels are inhibited
“wind-up” of nociceptive transmission
Means that the more action potentials there are, the more the synapse increases in strength
Synaptic plasticity
TENS
Transcutaneous electrical nerve stimulation
Supraspinal control of pain
- Brain stimulation in animals inhibited nociceptive spinal neurons
- Similar stimulation sites reduced behavioural response to noxious stimuli
- In humans, brainstem stimulation caused pain relief
Role of opioids in analgesia
Increase activity in the periaqueductal grey
Increase activity in the nucleus reticularis
Decreases activity in the peripheral nervous system
Decreases activity in spinal cord and dorsal horn directly
