Pain System I and II Flashcards
Name two fibres which carried pain information in response to activation of nociceptors on the skin. Describe the type of pain these two fibres carried and their extent of myelination.
A-delta fibres: lightly myelinated, carried sharp, short-lasting pain
C fibres: no myelination, carries duller, long-lasting pain
Describe the pain pathway starting from peripheral nerve terminal
- Painful stimulus detected by nociceptors in peripheral nerve terminals
- This information is carried by primary afferent fibre whose cell body resides in dorsal root ganglion
- Primary afferent fibre carries information through the dorsal root in the spinal cord where central processing occurs
- Pain information carried through the ascending pathway to the brain to be perceived as pain
Describe how signal transduction occurs from the free ending of unmyelinated C fibres and lightly myelinated A-delta fibres?
- Presence of different types of POLYMODAL nociceptors which respond to different types of stimuli or a stimuli can activate a combination of it e.g. TRPV1 respond to capsaicin in hot peppers
- These receptors are ion channels. When activated, they allow the flow of ions into the terminal
- Flow of ions generate a generator potential where is a certain threshold is reached it will generate AP
- AP is transduce through the neuron into spinal cord and then brain
The dorsal horn consist of two layers: superficial and deep laminae
Where does the A-beta and C fibres innervate in these layers?
C fibres carrying pain - superficial laminae
A-beta carrying innocuous sensation - deep laminae
Name two structures of the brain stem involved in the descending pathway
Which stimulation of one of this structure results in analgesia?
- Periaqueductal gray
- Raphe nucleus
Stimulation of periaqueductal gray
Why is pain response so important? Name a condition where this pain response is diminished and explain the molecular basis and consequences
- Experiencing pain allows you to get away from the danger which could inflict injury to the tissue
- Long-lasting pain promotes recovery behaviour such as sleep, drinking water or inactivity
- Congenital analgesia: mutation in NaV 1.7 (SCN9A gene) required to amplify generator potential to spike threshold and produce AP in nociceptors of the skin
Define hyperalgesia and allodynia
Hyperalgesia: painful stimulus perceived as even more painful (exaggerated response)
Allodynia: non-painful stimulus perceived as painful
Describe what happened to the sensitivity of the nociceptors in peripheral sensitisation
- Increased nociceptor sensitisation by decrease threshold for activation and enhanced response to a given stimulus
Describe the molecular changes which result in peripheral sensitisation
- Inflammatory mediators released from damaged tissue cells and inflammatory cells
- This causes alteration of sensitivity or direct activation of nociceptor terminals
- Sensitivity occurs by modulation of transducer receptors and ion channels
- This occurred in rapid time scales - within minutes
- Long term changes in inflammatory pain response e.g. increase in NaV channel, peptides and BDNF
- Also occurs over longer time scales by altering gene expression
- Ectopic activity
Which form of sensitisation is responsible for primary (1) and secondary (2) hyperalgesia?
Primary = Peripheral sensitisation
Secondary = Central sensitisation; exaggerated pain
Describe what occurred in dorsal horn neurone following central sensitisation (not molecular basis) which causes hyperexcitability
- Increase receptive field
- Prolong response
- Spontaneous activity
Explain how Ca triggers happened in central sensitisation and how it results in hyperexcitability of neurons
- Injury causes nociceptors to be highly active
- This drives the influx of calcium through NMDA/AMPA receptors
- Metabotropic glutamate receptors triggers Ca release from intracellular storage
- Ca recruits kinase
As a result of Ca release following injury, it recruits kinases. What do these kinases do?
- Kinases phosphorylate AMPA/NMDA receptor = increase excitability
- Phosphorylate K+ channel = decrease activity = decrease K current
- Promotes the trafficking of AMPAR to synapse = increase excitatory transmission
- Kinase drives expression of TF creb -> activates expression of c-Fos -> long-lasting changes in spinal neuron -> alter long-term pain processing -> associated with chronic pain
Describe what happened in increase in excitatory control in central sensitisation
This one is due to the kinase phosphorylating AMPAR and NMDAR
- increase trafficking of AMPAR
- increase activity of AMPAR and NMDAR
- alter expression of AMPAR
Describe what happened in decrease of spinal inhibitory control in central sensitisation (3 things that occurred)
- Decrease in GABA/glycine
- Death of inhibitory neuron
- Switch of inhibitory neuron to excitatory neuron
