Lecture 8 - Pain Part 2

Question 1

name eight inflammatory factors released by damaged/inflammed tissues

Answer 1

• NGF (growth factor)
• bradykinin
• serotonin (5-HT)
• ATP
• histamine
• prostaglandins
• H+, K+
• cytokines

Question 2

what kinds of cytokines are released during inflammation?

Answer 2

interleukins (IL-6 and IL1B) and tumor necrosis factor a (TNFa)

Question 3

type of cells involved in all allergic reactions

Answer 3

mast cells

Question 4

when substance P and CGRP are activated very intensely, nociceptor fibres can:

Answer 4

send messages back out to the target tissues

Question 5

a variety of ligand gated ion channels activated at different temperature

Answer 5

TRP channels

Question 6

TRPV1 receptors are located on:

Answer 6

small nociceptive neurons

Question 7

TRPV1 receptors are activated by:

Answer 7

• capsaicin
• moderate thermal stimuli (43 degrees)
• H+ ions (inflammed tissue becomes acidic)

Question 8

TRPV2 receptors are located on:

Answer 8

A-delta fibers

Question 9

TRPV2 receptors are activated by:

Answer 9

intense noxious heat (>52 degrees)

Question 10

TRPM8 receptors are activated by:

Answer 10

• cool/cold temperatures (8-22 degrees)
• menthol
• icilin

Question 11

the sensitivity of all TRP channels is increased by:

Answer 11

bradykinin

Question 12

release of prostaglandins, interleukins, bradykinin, acid metabolites, and nerve growth factor sensitize:

Answer 12

nociceptors beyond the site of injury (form an area of hyperalgesia around the original site of injury)

Question 13

C fibre excitation causes the release of substance P and calcitonin gene related peptide (CGRP) from:

Answer 13

sensory nerve endings

Question 14

what are the effects of substance P and CGRP when they are released?

Answer 14

• excite other C fibres
• ‘axon reflex’
• vasodilation (casues redness)
• extravasation of plasma proteins
• oedema (casues swelling)
• involved in migraine pain

Question 15

true or false: pain messages have a unidirectional flow

Answer 15

false, pain messages go in both directions (to CNS and to target tissues)

Question 16

second messengers modify ion channels by:

Answer 16

phosphorylation

Question 17

when phosphorylated, ion channels may open at:

Answer 17

lower voltage or remain open longer (boosts excitability/activity)

Question 18

nociceptors injected with current become:

Answer 18

activated

Question 19

go review slide 128

Answer 19

karabast

Question 20

if pain signals tissue damage, why have endogenous analgesic mechanisms?

Answer 20

central mechanisms to supress pain have significant survival value

Question 21

endogenous mechanisms of analgesia must have a:

Answer 21

high threshold of activation (or else pain would not have a survival value –> system cannot be activated all the time)

Question 22

what is the role of endogenous opioids?

Answer 22

dampens inputs sent to the brain (short term –> activated when pain cannot be your main focus)

Question 23

what are the four main types of endogenous opioids?

Answer 23

• enkephalins
• dynorphins
• endorphins
• endomorphins

Question 24

go review slide 130

Answer 24

may the force be with you

Question 25

descending analgesic pathways must be held in check or else:

Answer 25

you'd never be able to feel pain

Question 26

how are descending pain pathways held in check?

Answer 26

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

Question 27

release endogenous opioids to suppress pain transmission in the dorsal horn of the spinal cord

Answer 27

spinal opioid interneurons

Question 28

at the spinal level, descending analgesic pathways activate:

Answer 28

inhibitory interneurons in the dorsal spinal cord (supresses afferent flow of information getting to the brain)

Question 29

the prototypical substances for analgesia

Answer 29

opioids

Question 30

opium is obtained from exudate of _____ seed pods, and is derived from the word _____

Answer 30

Papaver somniferum, opos (juice)

Question 31

in the 1800s, _____ was an isolated substance from opium

Answer 31

morphine (after Morpheus)

Question 32

research into endogenous opioids determined that there are three endogenous substances:

Answer 32

- endorphin - dynorphin - enkephalin

Question 33

our bodies make large polypeptides that have to be processed/cleaved to become active called:

Answer 33

pro-hormones

Question 34

what are the three main pro-hormones for opioids:

Answer 34

- pro-opiomelanocortin (precursor for endorphins) - prodynorphin - proenkephalin

Question 35

what are the five types of opioid receptors?

Answer 35

- mu - kappa - sigma - delta (bound by enkephalins) - epsilon (bound by endorphin)

Question 36

all opioid receptors appear to be:

Answer 36

G-protein coupled receptors (GPCRs)

Question 37

opioid receptors inhibit _____ as well as affecting many cellular processes including _____

Answer 37

adenylyl cyclate, ion conductance (ie: K+)

Question 38

active G-alpha proteins can promote K+ conductance leading to:

Answer 38

hyperpolarization of the cell, inhibition of cAMP, and inhibition of Ca++ channels

Question 39

what are the mu opioid receptor subtypes commonly discussed in clinical context?

Answer 39

- mu 1 (u1) - mu 2 (u2)

Question 40

main action of these receptors is analgesia (peripheral and spinal/supraspinal)

Answer 40

mu 1 (u1)

Question 41

opioids acting at these receptors leads to respiratory depression, bradycardia, euphoria, and ileus (spinal/supraspinal)

Answer 41

mu 2 (u2)

Question 42

binding to the kappa opioid receptors produces:

Answer 42

- analgesia - sedation - dysphoria - psychomimetic effects - inhibits ADH release (may promote diuresis)

Question 43

where are kappa opioid receptors found?

Answer 43

peripheral and spinal/supraspinal

Question 44

what is the function of delta opioid receptors?

Answer 44

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

Question 45

it is thought that mu receptors and delta receptors exist as:

Answer 45

a complex

Question 46

list nine opioids

Answer 46

- morphine - fentanyl - heroin - methadone - remifentanil - sufentanil - alfentanil - hydromorphone - meperidine

Question 47

used as an anesthetic induction agent and possesses analgesic properties

Answer 47

ketamine

Question 48

a phencyclidine derivative that activates the sympathetic nervous system, maintaining blood pressure and heart rate, causes bronchodilation

Answer 48

ketamine

Question 49

ketamine produces ______ and resembles a ______ state

Answer 49

"dissociative anesthesia", cataleptic

Question 50

ketamine binds non-competitively to:

Answer 50

the phencyclidine (PCP) recignition site on NMDA receptors

Question 51

what is the primary function of ketamine?

Answer 51

blocks NMDA receptors

Question 52

what are some other functions of ketamine?

Answer 52

- noted to have effects on opioid receptors - acts at monoaminergic receptors - acts at voltage gated Na+ channels

Question 53

ketamine binds at a site in the _____ to block _____

Answer 53

channel pore (acts similar to Mg++), conductance through the channel

Question 54

what is the primary function of non-steroidal anti-inflammatory drugs (NSAIDS) and acetominophen?

Answer 54

block prostaglandin synthesis

Question 55

the analgesic effects of NSAIDS and acetominophen depend on:

Answer 55

modulating peripheral and central inflammatory responses, limiting sensation

Question 56

NSAIDS and acetominophen have the best effects when used:

Answer 56

pre- or perioperatively

Question 57

list six examples of non-opioid analgesic drug classes

Answer 57

- salicylates (acetylsalicylic acid - ASA) - propionic acids (ibuprofen) - acetic acids (ketorolac) - anthranilic acids (meclofenamate) - phenylacetic acids (diclofenac) - p-aminophenols (acetaminophen)