Pain and analgesia Flashcards
What is pain?
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
What are the two terminals of the DRG?
Primary sensory neuron
Second order neurons
What do peripheral nociceptors detect?
A noxious stimuli
Are spinal reflexes pain?
No - These simply make you move away from a certain stimuli
What is the reflex pathway?
1) Sensory receptors in skin detect a noxious stimuli
2) Sensory information goes via the afferent pathway to the dorsal root ganglia
3) The information is processed at an integrating center
4) Information goes out via the ventral root through the efferent pathway
5) Effector organs affected = response of the reflex
What is primary erythermalgia?
Pain by walking/ physical activity
What is Paroxysmal extreme pain disorder?
Pain when chewing or passing stool
What is acute pain?
Alerts the body to chemical, mechanical or thermal stimuli that has the potential to damage body tissues
Has a protective role
What is chronic pain?
Accompanies chronic inflammatory diseases eg arthritis
Neuropathic pain results from damage to nerves
Can be causes by trauma, diabetes, cancer treatment and herpetic infection
What is the total cost of pain annually to the US?
600 billion dollars (50% healthcare costs, 50% loss in productivity
What is analgesia?
The absence of pain without loosing consciousness
What are analgesias all aimed at?
The pain circuit; DRG and spinal horn neurons and pain processing parts of the brain
What are some current analgesics?
NSAIDS and opiods
List current problems with NSAIDs
Cardiovascular risk - Increases risk of thrombotic events, myocardial infarction and stroke
GI risk - bleeding, ulceration and perforation of the stomach or intestines, which can be fatal (elderly patients at greater risk)
List current problems with Opiods
Sedation - apathy and cognitive impairment
Depression of respiration - Main cause of intoxication related death in USA is from opioid overdose, Combination with alcohol is very dangerous
Inhibition of the GI tract
Addiction
What are the four classes of opioids?
Natural
Semi-synthetic
Fully synthetic
Endogenous opioid peptides
Give examples of natural opioids
Morphine, codeine and dermorphine
Give examples of semi-synthetic opioids
Heroin, hydromorphine, hydrocodone, oxycodone and oxymorphone
Give examples of fully synthetic opioids
Fentanyl, pethidine, methadone, tramadol and propoxythene
Give examples of endogenous opioid peptides
Endorphin, enkephalin, dynorphin and endomorphins
What is opium and who isolated its active ingredient?
Opium is the dried juice of the seed head in a poppy flower
Its principal active ingredient, morphine, was isolated by Frederic Serturner in 1806
What does morphine bind to?
Opioid receptors
These are GPCRs which lead to the inhibition of calcium influx
What are the three types of opioid receptors
Mu, Keppa and delta
Where are Mu opioid receptors concentrated?
At the dorsal horn area receiving input from DRG neurons
What is demamorphin?
A hepta-peptide first isolated from the skin of the South American leaf frog
It is about 30 to 40 times more potent than morphine in Mu receptors
Stable due to non-natural amino acids (hence longer acting)
What is the molecular structure of heroin?
It is morphine with an added acetate group - It is a boiled acetic acid
Why can heroin penetrate into the brain easily?
It is hydrophobic
What is fentanyl?
100 times more potent than morphine
Fast acting opioid
Used during surgery
Where are opioid peptides mainly found in the CNS?
The midbrain, brainstem and spinal cord (areas associated with pain processing
When are opioid peptides released?
During stress
Why do opioid peptides have only a short pain release?
The are quickly degraded by extracellular proteases
Met-enkaphalins prefer which receptors?
All opioid receptors
Dynorphins prefer which receptors?
Kappa opioid receptors
Endorphins prefer which receptors?
Mu-opiod receptors
Loss of function mutations cause no pain in what channel?
NaV1.7
Monoclonal antibodies against what help with lower back pain?
NGF
Why can the botulinum neurotoxin be used to treat pain?
It blocks neurotransmitter release for several months by cleaving the SNAP25 protein
What can the botulinum toxin be used to treat?
Migraines
