B. Neuronal Pain Pathway Flashcards
What is the definition of pain (IASP definition)?
Unpleasant sensory and emotional experience associated with acute or potential tissue damage or described in terms of such damage.
It is a duality as it includes both a physiological and psychological aspects.
What is the definition of nociception ?
The neural physiological process of encoding and processing noxious stimuli.
What is congenital analgesia ?
it is a genetic disorder which involved people feeling no pain.
What is the name of the system that monitors the position of limbs in space ?
Proprioreception.
During genetic analysis, what gene was inactivated and what did this gene code for? Why did this result in people not being able to recognise pain ?
SCN9A is the gene which codes for voltage-gated sodium channel Nav 1.7.
Nav1.7 is a target for pain. Inactivation of this gene would lead to loss of pain perception.
What type of mutation occurred in the SCN9A gene ?
Point mutation.
How many domains are there in voltage gated Na+ channels ?
4 domains.
Which transmembrane (S1-S6) domains sense small depolarisations/ sense voltage ?
S1-S4
Which transmembrane (S1-S6) domains make up the pore of the voltage gated Na+ channels?
S5-S6
What happened when Nav1.7 was removed from a mouse. What happened when Nav1.7 was added to a mouse?
Removal, no pain perception.
Addition, spontaneous pain which was unprovoked.
True/ false: Making an inhibitor of the Nav1.7 would therefore be a strategy to make an analgesic drug ?
True
What is the basic nociceptive pathway?
- Nociceptor neurone: Picks up harmful stimuli such as injury, pressure, temperature and pH.
- Projection neurone: leads to the brain
- Tertiary neurone: located in the brain
What is the pathway for the nociceptor?
Target tissue Peripheral nerve Dorsal root ganglion Dorsal root Spinal cord
True or false: The nociceptor is a pseudounipolar neurone with a peripheral and central axon
True
What stimuli do nociceptors detect?
Specialised to detect high threshold noxious stimuli
Heat and cold High threshold mechanical stimuli Certain chemicals (capsaicin)
What channels can detect these stimuli ?
Specific cation channels
What is the receptor for capsaicin?
TRPV1, which detects noxious heat
How many transmembrane ion channels and subunits does TRPV1 have?
6 transmembrane ion channels
4 subunits form
What ions are permeable to TRPV1?
Na+ and Ca2+
How can depolarisation occur from TRPV1?
In response to eating, the channel opens which leads to ion influx. This depolarises the membrane
What are the tetrodotoxin sensitive sodium channels ?
Nav1.1
Nav1.6
Nav1.7
What are the tetrodotoxin insensitive sodium channels?
Nav1.8
Nav1.9
What fibres are involved in nociception and what are their features?
A(gamma) fibre
- Lightly mylinated
- Medium diameter
C fibre
- Unmyelinated
- Small diameter
What fibre is involved in proprioception and light touch?
A (beta) fibre
- Myelinated
- Large diameter
