Pain, nociception and analgesia 2 Flashcards
What are the two types of primary afferent nociceptive axons?
A-delta and C fibres.
What receptors are found on the A-delta post synaptic membranes?
AMPA and NMDA.
What receptors are found on the C fibre post synaptic membranes?
AMPA, NMDA, NK-1.
What is transmission at nociceptor terminals principally mediated by?
Glutamate.
What are other substances that modify the responsiveness of nociceptors?
Substance P and CGRP (calcitonin gene related peptide).
What is substance P important in?
Pain perception and transmission - it is an 11 amino acid peptide.
What is CGRP important in?
It is a related peptide that plays a role in synaptic transmission.
What is sensitisation?
If a synapse is stimulated lots of times the response will get bigger and bigger - wind up.
What effect does an NMDA antagonist have on sensitisation?
It reduces the effect - a lot of the sensitisation is due to NMDA agonists.
What happens if a substance P antagonist is used along with an NMDA antagonist?
The number of action potentials is significantly reduced.
What is neuropathic pain?
Chronic pain that doesn’t serve any purpose. It is a result of persistent sensitivity of the synapse to the transmitters.
What effect does mechanical stimulation have on nociception transmission?
Gate control of nociceptive transmission - It inhibits nociceptive transmission. THe mechanoreceptors activate an inhibitory neuron on the nociceptive pathway, and prevent transmission to the anterolateral tract (pain pathway).
Why does rubbing something help to reduce pain?
The mechanostimulation inhibits the pain pathway.
What controls the pain transmission at spinal level?
Descending supraspinal paths - it was found that brain stimulation in animals inhibited nociceptive spinal neurons and that in humans brainstem stimulation caused pain relief.
What is the hypothalamus involved in?
Stressful output to pain.
What is the amygdala involved in?
The fearful response to pain.
What is the periaqueductal grey involved in?
It is a major station in relay that controls pain at the spinal level.
What are pain pathways important in?
The use of painkillers.
What is a key descending pain pathway?
Midbrain/periaqueductal grey to the medulla/nucleus raphe magnus and then to the spinal cord/dorsal horn.
What is the locus coeruleus involved in?
It provides the noradrenaline output pathway - it is the descending component going to the spinal cord.
What are the opioid receptors in the brain?
Mu, Delta and Kappa μ, δ, κ
What activates the opioid receptors?
A family of endogenous peptides - peptides produced in the brain.
What opioid receptors are activated the most by the endogenous peptides?
Mu and delta
What opioid receptor is involved in analgesia at all levels?
Mu.
What site of analgesia are there, involving opioid receptors?
Supraspinal, spinal and peripheral.
What do opioids in the periphery do?
They inhibit the activity of nociceptor terminals.
How do opioids inhibit nociceptor transmission at the peripheral level?
They open potassium channels which causes hyperpolarisation and they close calcium channels to reduce calcium signalling and reduce excitability.
Where are mu opioid receptors found?
In the periphery on the nociceptor terminal.
How do opioids work in the periaqueductal grey?
They inhibit GABA inhibitory neurons and inhibit excitation of inhibitory neurons. There is a decrease in GABA inhibition and an increase in excitatory output to the nucleus raphe magnus.
How do opioids act in the dorsal horn/nucleus raphe magnus ???
Opioid neurons are activated by descending inputs and directly inhibit projection neurones. They decrease release of glutamate onto projection neurons and there is an overall decrease in projection neuron output.
