Lecture 8 - Pain Part 2 Flashcards
name eight inflammatory factors released by damaged/inflammed tissues
- NGF (growth factor)
- bradykinin
- serotonin (5-HT)
- ATP
- histamine
- prostaglandins
- H+, K+
- cytokines
what kinds of cytokines are released during inflammation?
interleukins (IL-6 and IL1B) and tumor necrosis factor a (TNFa)
type of cells involved in all allergic reactions
mast cells
when substance P and CGRP are activated very intensely, nociceptor fibres can:
send messages back out to the target tissues
a variety of ligand gated ion channels activated at different temperature
TRP channels
TRPV1 receptors are located on:
small nociceptive neurons
TRPV1 receptors are activated by:
- capsaicin
- moderate thermal stimuli (43 degrees)
- H+ ions (inflammed tissue becomes acidic)
TRPV2 receptors are located on:
A-delta fibers
TRPV2 receptors are activated by:
intense noxious heat (>52 degrees)
TRPM8 receptors are activated by:
- cool/cold temperatures (8-22 degrees)
- menthol
- icilin
the sensitivity of all TRP channels is increased by:
bradykinin
release of prostaglandins, interleukins, bradykinin, acid metabolites, and nerve growth factor sensitize:
nociceptors beyond the site of injury (form an area of hyperalgesia around the original site of injury)
C fibre excitation causes the release of substance P and calcitonin gene related peptide (CGRP) from:
sensory nerve endings
what are the effects of substance P and CGRP when they are released?
- excite other C fibres
- ‘axon reflex’
- vasodilation (casues redness)
- extravasation of plasma proteins
- oedema (casues swelling)
- involved in migraine pain
true or false: pain messages have a unidirectional flow
false, pain messages go in both directions (to CNS and to target tissues)
second messengers modify ion channels by:
phosphorylation
when phosphorylated, ion channels may open at:
lower voltage or remain open longer (boosts excitability/activity)
nociceptors injected with current become:
activated
go review slide 128
karabast
if pain signals tissue damage, why have endogenous analgesic mechanisms?
central mechanisms to supress pain have significant survival value
endogenous mechanisms of analgesia must have a:
high threshold of activation (or else pain would not have a survival value –> system cannot be activated all the time)
what is the role of endogenous opioids?
dampens inputs sent to the brain (short term –> activated when pain cannot be your main focus)
what are the four main types of endogenous opioids?
- enkephalins
- dynorphins
- endorphins
- endomorphins
go review slide 130
may the force be with you
descending analgesic pathways must be held in check or else:
you’d never be able to feel pain
how are descending pain pathways held in check?
by GABAergic inhibition in rostroventral medulla (RVM) and periaqueductal gray (PAG) –> must first ‘inhibit the inhibition’ to allow pain suppressing information to flow to the spinal cord
release endogenous opioids to suppress pain transmission in the dorsal horn of the spinal cord
spinal opioid interneurons
at the spinal level, descending analgesic pathways activate:
inhibitory interneurons in the dorsal spinal cord (supresses afferent flow of information getting to the brain)
the prototypical substances for analgesia
opioids
opium is obtained from exudate of _____ seed pods, and is derived from the word _____
Papaver somniferum, opos (juice)
in the 1800s, _____ was an isolated substance from opium
morphine (after Morpheus)
research into endogenous opioids determined that there are three endogenous substances:
- endorphin
- dynorphin
- enkephalin
our bodies make large polypeptides that have to be processed/cleaved to become active called:
pro-hormones
what are the three main pro-hormones for opioids:
- pro-opiomelanocortin (precursor for endorphins)
- prodynorphin
- proenkephalin
what are the five types of opioid receptors?
- mu
- kappa
- sigma
- delta (bound by enkephalins)
- epsilon (bound by endorphin)
all opioid receptors appear to be:
G-protein coupled receptors (GPCRs)
opioid receptors inhibit _____ as well as affecting many cellular processes including _____
adenylyl cyclate, ion conductance (ie: K+)
active G-alpha proteins can promote K+ conductance leading to:
hyperpolarization of the cell, inhibition of cAMP, and inhibition of Ca++ channels
what are the mu opioid receptor subtypes commonly discussed in clinical context?
- mu 1 (u1)
- mu 2 (u2)
main action of these receptors is analgesia (peripheral and spinal/supraspinal)
mu 1 (u1)
opioids acting at these receptors leads to respiratory depression, bradycardia, euphoria, and ileus (spinal/supraspinal)
mu 2 (u2)
binding to the kappa opioid receptors produces:
- analgesia
- sedation
- dysphoria
- psychomimetic effects
- inhibits ADH release (may promote diuresis)
where are kappa opioid receptors found?
peripheral and spinal/supraspinal
what is the function of delta opioid receptors?
probably modulates mu opioid receptors (activation may potentiate the effects of both mu 1 and mu 2), which may lead to analgesia and other unwanted side effects
it is thought that mu receptors and delta receptors exist as:
a complex
list nine opioids
- morphine
- fentanyl
- heroin
- methadone
- remifentanil
- sufentanil
- alfentanil
- hydromorphone
- meperidine
used as an anesthetic induction agent and possesses analgesic properties
ketamine
a phencyclidine derivative that activates the sympathetic nervous system, maintaining blood pressure and heart rate, causes bronchodilation
ketamine
ketamine produces ______ and resembles a ______ state
“dissociative anesthesia”, cataleptic
ketamine binds non-competitively to:
the phencyclidine (PCP) recignition site on NMDA receptors
what is the primary function of ketamine?
blocks NMDA receptors
what are some other functions of ketamine?
- noted to have effects on opioid receptors
- acts at monoaminergic receptors
- acts at voltage gated Na+ channels
ketamine binds at a site in the _____ to block _____
channel pore (acts similar to Mg++), conductance through the channel
what is the primary function of non-steroidal anti-inflammatory drugs (NSAIDS) and acetominophen?
block prostaglandin synthesis
the analgesic effects of NSAIDS and acetominophen depend on:
modulating peripheral and central inflammatory responses, limiting sensation
NSAIDS and acetominophen have the best effects when used:
pre- or perioperatively
list six examples of non-opioid analgesic drug classes
- salicylates (acetylsalicylic acid - ASA)
- propionic acids (ibuprofen)
- acetic acids (ketorolac)
- anthranilic acids (meclofenamate)
- phenylacetic acids (diclofenac)
- p-aminophenols (acetaminophen)
