JD - Pain II Flashcards
What other names does the VR1 receptor have?
Capsaicin receptor, TRPV1
What activates the VR1 receptor?
Capsaicin (the pungent compound in chili peppers) and similar molecules
Also
- Protons
- Anandamine
- Noxious stimuli / heat
What properties does capsaicin have? (4)
It’s lipophilic (fat-soluble), colorless, odorless, and soluble in alcohol
What effect does capsaicin have on nociceptors (pain receptors)?
Initially, it activates C-fibers, causing a burning pain sensation
- However, prolonged exposure can desensitize the nociceptor, reducing pain responsiveness
What is the structure of the VR1 receptor? (4)
It includes:
- ankyrin repeats (protein-protein interaction)
- a temperature sensor
- phosphorylation sites
- a pore-forming region for ion flow
How does histamine influence pain perception?
Histamine acts on TRPV channels, increasing sensitivity and lowering the pain threshold
How does TRPV activation contribute to inflammation?
Causes the local release of substance P and CGRP which leads to intense responses in the local vasculature, increased permeability and vasodilation
Why is the TRPV channel called “polymodal”?
It can integrate responses to various noxious stimuli (heat, capsaicin, etc.)
How is capsaicin used medically?
Capsaicin cream and patches are used for neuropathic pain relief, despite initially causing pain
- This effect is thought to involve calcium-dependent desensitization of nociceptors
What are the two key excitatory neurotransmitters involved in pain perception at the spinal cord level?
Glutamate (from both A-delta and C-fibers) and substance P (from C-fibers)
What receptors are associated with pain transmission in the spinal cord dorsal horn? (3)
AMPA, NMDA, and NK-1 receptors
How does the NMDA receptor function? (3)
- NMDA activation is dependent upon glutamate/glycine binding to their respective sites AND depolarization of the neuron to remove the magnesium block
- The two events must occur together for the receptor to be activated
- Once activated this leads to an influx of calcium ions = depolarization
What is “wind-up” in pain perception?
It’s a phenomenon where repeated or prolonged stimulation of C-fibers leads to increased responsiveness of spinal cord neurons to pain signals
How do NMDA antagonists like ketamine work to reduce pain?
They block NMDA receptors, preventing calcium influx and reducing wind-up in the spinal cord
How do NK-1 antagonists like SR140333 work to reduce pain?
They block the NK-1 receptor, which is activated by substance P, thereby reducing pain transmission
