Central Modulation of Pain

Question 1

What is the International Association for the Study of Pain’s (IASP) definition of nociception?

Answer 1

the neural mechanisms of encoding & processing harmful stimuli

Question 2

What is the International Association for the Study of Pain’s (IASP) definition of pain?

Answer 2

• an undesirable sensory and emotional experience associated w/ real tissue damage
• pain is a signal which produces a reflex and a conscious preventative response to protect the body from actual damage

Question 3

What are some conditions or situations where the level of pain experienced from an injury IS LESS than would be expected & what is this called?

Answer 3

• emotional state
• attention
• expectations
• exposure to chronic pain (repetitive stimuli)
  Called altered pain threshold/experience

Question 4

Which region in the midbrain modulates pain?

Answer 4

Periaqueductal grey matter (PAG)

Question 5

What is the order of central pain transmission modulation?

Answer 5

Question 6

What does periaqueductal grey matter do?

Answer 6

• provides info about the emotional state, amount of attention, expectation of how painful something should be
• will integrate that w/ noxious stimuli coming in
• also responsible for ID’ing threats (risk adverse area of the brain)
• computes info from a lot of different places
• this is a negative/positive feedback loop depending on the emotional state of the animal
• these synapses result in information going to the spinal relay neurons

Question 7

explain this diagram

Answer 7

• peripheral sensory neuron synapsing on a pain relay neuron in the grey matter
• sends an AP up to the brain
• green (provides inhibitory signal to this area)
• painful stimuli happens, it goes up to the brain
• if animal is really stressed or fearful, the periaqueductal grey matter can integrate & change info coming from these relay neurons

Question 8

explain this image

Answer 8

• all of our drugs are capitalizing on these pathways to reduce pain perception
• axons at the synapse release NT’s (a lot of them)
• for example: NE will bind to receptors on pre- & post-synaptic membranes; it will hyperpolarize these cells (block them from making AP and relaying info up to higher brain structures); this is what alpha-2 agonists do

Question 9

what are some examples of alpha-2 agonists?

Answer 9

• xylazine
• (dex)medetomidine

Question 10

explain this image

Answer 10

• endogenous opioids are also released from the periaqueductal grey matter (serotonin, etc.)
• they will bind to the post-synaptic cell & will inhibit that cell from making AP, then it cannot transmit pain & perception of pain is reduced
• hydromorphone, fentanyl, methadone, etc. do this
• noxious stimuli may still be coming in but the signal is not propagated
• decreased perception of that painful stimuli

Question 11

What is the periaqueductal grey matter trying to do?

Answer 11

• trying to limit the info sent to the CNS
• it is the area in the brain that is integrating & modulating pain along with all the other emotional and environmental factors that the animal is experiencing
• animal does not want to be hyperexcitable & feel more pain than is necessary
• an animal with an inflammatory condition causes hyperexcitability of this area
• but in general this matter is trying to reduce pain

Question 12

What three things are important to consider in your approach to analgesia?

Answer 12

• the drug mechanism of action
• the dose
• any pre-emptive analgesia