Pain and analgesics second half of 2 Flashcards
Where does the nucleus reticularis paragigantocellularis project to?
Raphe nuclei
Where does the locus coeruleus project to?
Spinal cord
Where does the hypothalamic paraventricular nuclei project to?
Periaqueductal grey
Can the environment you are in affect the amount of pain you are in?
YEs
Why may your environment having an effect on how much pain you are in be beneficial?
Get injured while running away from predator–> still need to run away so pain is reduced
What effect does opioids have on nociceptive neurons?
Inhibit the free nerve endings, hyperpolarizing them and making them less likely to fire APs up pain pathway
How does the PAG act as an inhibitor of pain?
Sends input to the raphe which causes the raphe to fire inhibitory APs down the spinal cord
Which NT is used by the raphe to send inhibitory APs down the spinal cord?
Via release of 5HT
How does the locus coeruleus inhibit pain pathways in the spinal cord?
Via the release of noradrenaline
Effect of opioids on PAG?
Excitatory effect so more APs from PAG
Effect of opioids on nucleus reticularis paragigantocellularis?
Excitatory so more APs from the NRP onto the raphe nuclei
How do opioids inhibit pain?
Inhibit nociceptive neurons and the neurons in the spinal cord, and have an excitatory effect on PAG and NRP
Three different types of opioid receptor?
Mew delta and kappa
What are all of the endogenous agonists of opioid receptor?
Peptides
What is similar between the four endogenous agonists of opioid receptors?
Their first 4 AAs are the same
What are the four peptide opioid endogenous agonists?
Beta-endorphin, met-enkephalin, leu-enkephalin, dynorphin
Which endogenous opioid agonist binds well at all receptors?
beta-endorphin
Which opioid receptors are found in the brain (PAG)?
Mu
Which opioid receptors are found in the spine?
Mainly mew and delta, also kappa
Which opioid receptors are found in the nociceptive neurons?
Mu and kappa
What type of receptor are all of the opioid receptors?
GPCRs
What are the opioid receptors second messengers?
Gi/o
What does the Gi/o unit of the opioid receptor inhibit once an agonist had bound?
The conservation of adenyl cyclase to cyclic AMP
What is the effect of inhibiting the formation of cyclic AMP?
Less protein kinase A is formed
Other than AMP, what does Gi/o of opioid receptors inhibit?
Calcium channels, meaning less calcium can enter the neuron so less NTs will be released
What can the Gi/o of opioid receptors open?
Potassium channels, so more K+ leaves so neuron is hyperpolarized
How does opioid receptors cause more APs to be fired down the PAG to the raphe nucleus and thus to the spinal cord?
They inhibit the release of GABA meaning less inhibition from GABA goes to the synapse between the PAG and raphe nuclei
What is disinhibition?
Inhibiting something that is inhibitory
Net effect of disinhibition?
Excitation
What do the two branches of input from the raphe to the dorsal horn carry?
5HT to directly inhibit the synapse. The second one activates opioid interneurons neurons with enkephalins which also inhibit the synapse in the dorsal root
What is the effect of enkephalin on an action potential?
Shortens them and leads to a lower frequency due to opening K+ channels (neuron hyperpolarises more quickly
