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what is the primary function of pain?
types of peripheral pain receptors
- polymodal receptors
what are the majority of cutaneous nociceptors?
what is the pain pathway?
nociceptor--> primary afferent--> spinal cord projection neuron--> thalamic neuron--> cortex
what is substance P?
sorta a neurotransmitter that activates pain receptors
what substances are released from damaged cells?
proteases, ATP, H+
what is released from activated immune cells?
cytokines, prostaglanidins, serotonin, histamine, H+
what is the result of activated immune cells?
does the body produce endogenous opioids?
what is endorphins?
endogenous opioid (morphine)
what does naloxone do?
it is an opioid antagonist (blocks opioid receptors)
what does endorphins do in the brain?
- analgesic characteristics of morphine in the brain
- also have behavioral effaces and neurotransmitter/neuromodulator functions
what are the different types of endogenous opioids?
- beta endorphine 31 amino acids
- dynorphin 17 amino acids
how are endorphins synthesized?
formed from pro-endorphins peptides in the cell body and transported to the nerve terminal where they are cleaved by specific proteases
what is the precursor for pro-olio-melanocortin?
- b-endorphin precursor
- what is the precursor for proenkephalin A?
- met-and leu-enkephalin precursor
what is the precursor for proenkephalin B (prodynorphin)?
dynorphin and a-neoendorphin precursor
where are opioidergic neurons concentrated in?
the ventral segmental area of the hypothalamus
where is beta-endorphin found?
in the pituitary gland
what are the post-synaptic GPCR receptors for beta-endorphins?
mu, kappa, delta (or gamma)
what are mu receptors activated by?
what is the primary action site of all opioids?
where are mu receptors located (distributed)
CNS and GI
where is the kappa receptor's analgesia produced?
activation of which receptor causes dysphoria?
what do the endorphin-containing neurons in the dorsal horns release?
what inhibits the release of substance P?
enkephalins and dynorphins
what hormone is released from a descending pathway from the locus coeruleus?
what hormone is released from a descending pathway that begins at the raphe nucleus?
What do NE and serotonin induce the release of?
opioid peptides (enkephalins and dynorphins)
what propagates the pain signal?
the release of substance P
which hormones prevent the transmission of the pain signal by inhibiting the release of substance P?
enkephalins and dynorphin
where do Alpha2 agonists work for analgesic effect?
brain and dorsal horn
where do local anesthetics work for analgesic effect?
peripheral nociceptors, peripheral nerves, dorsal horn, brain
where do opioids work for analgesic effect?
brain and the dorsal horn
what are opioid analgesics used for?
- relief from diarrhea
- cough suppression
what receptors do opioid alagesics activate?
mu and kappa
what does naloxone do?
blocks the activation of mu and kappa receptors (antagonist)
what are the secondary pharmacologic actions of opioids?
- treatment for cognition and emotion
- causes nausea and vomiting
- causes peripheral vasodilation
- increases mitosis
- pinpoint pupils
- histamine release = flushing/red eyes
- constipation b/c decreased gastric motility
- depresses respiratory system
- depress cough
- low body temp
- lowered FSH, LH, ACTH
- not hungry
what happens when you overdose on opioids?
- respiratory depression
- circulatory depression
- constricted pupils
- pulmonary edema
- decreased reflexes
how do you treat opioid overdose?
what is the mechanism for opioid tolerance?
- receptor sensitization and down regulation
- second messenger system alterations
- negative feedback suppressing antinociceptive circuits
- enhanced activity of pronociceptive circuits
what is the mechanism for creating opioid dependence?
opioids activate presynaptic opioid receptors on the GABA neurons which inhibits the release of GABA in ventral segmental area. Inhibiting GABA allows for dopaminergic neurons to fire more vigorously because GABA normally inhibits dopaminergic cells. Dopamine in the nucleus accumbens is intensely pleasurable.
what the treatment for opioid dependence?
- methadone produces a longer but less stressful withdrawal.
- clonidine is an alpha 2 agonist that can alleviate many of the symptoms of opioid withdrawal.