Neuro: General Pain Suppression

Front 1

Describe the action of capsaicin.

Back 1

1. initially cause substance P release causing burning sensation, later inhibit accumulation of substance P by depleting it, resulting in analgesic effect.

2. also stimulate vanilloid receptor typeI to induce a burning sensation.

Substance P:
NK-1 type of neurokinin
released by C fibers.

Front 2

When is substance P released?

Back 2

when there is injury
when C fiber is activated

Front 3

What type of neurotransmitter does Aδ fiber use at the synapse?

Back 3

glutamate

Front 4

Name some drugs that noncompetitively block NMDA ion channel and prevent postsynaptic response of Aδ fiber.

Back 4

Phencyclidine
Ketamine

Front 5

What type of receptor is involved in CNS sensitization to pain?

What drug could be used before extremely painful procedure to prevent the development of this sensitization?

Back 5

NMDA
Ketamine: widely used as a veterinary anesthetic for treating severe types of trauma and also after torture.

Front 6

What is the response of a nerve to physical injury?

Back 6

release substance P which then activate mast cells and endothelial cells.

Front 7

Where are opioid receptors found?

Back 7

everyplace where synapses in pain transmission occur.

Front 8

Describe the effect of the negative feedback system of pain from the PAG to the spinal cord. (2)

Back 8

1. nerve fiber synapse in NRM and release serotonine to interneuron which then releases ENK to inhibit the release of substance P and other excitatory neurotransmitters.

2. nerve fibers synapse in NRPG and release NE which either stimulate nonopioid inhibitory interneurons or activates inhibitory α2 adrenoreceptors located on spinal relay neurons.

Front 9

Inhibitory neurons that release endogenous opioids could be activated by which two pathways?

Back 9

1. negative feedback loop of pain (PAG): serotonine effect and NE effect.

2. gate control theory: non-nociceptive fibers(Aβ) activated inhibitory fibers.

Front 10

What is the mechanism of action of duloxetine? Name another drug of the same class.

Back 10

Duloxetine: block inactivation of serotonine and NE by the reuptake mechanism, thus augmenting the response to decrease the magnitude of pain (chronic).

Duloxetine and venlafaxine are both tricyclic antidepressants. Their effects similar of tramadol.

Front 11

Duloxetine can be used as analgestic agent at ___ (low/high), and as antidepressant at ___ (low/high) dose.

Back 11

As analgestic agent: low dose.
As antidepressant: 10 times higher dose.

Front 12

How does anticonvulsants work to reduce pain?

Back 12

They prolong the the inactivated state of Na+ channels to slow its firing since there are an increase in the number of Na+ channels in nerve injury.

Front 13

T/F: Gabapentine is a preferred anticonvulsant drug to treat nerve pain because it is excreted unchannged in kidney.

Back 13

T.

Front 14

What are some anticonvulsants?

Back 14

gabapentin
phenytoin
carbamazepine
clonazepam

Front 15

How does gabapentine reduce pain?

Back 15

It prolongs the inactivated state of Na+ channels to slow its firing since there are an increase in the number of Na+ channels in nerve injury.

Front 16

Which nerve fiber elicits strong affective repsonse characterized by dread, anxiety and the sense of suffering?

Back 16

C fibers

Front 17

T/F: Opioids only decrease sensory component of pain mediated by Aδ fibers.

Back 17

F. Opioids decrease both sensory and affective components of pain.

Front 18

How is severe pain most commonly treated with clinically?

Back 18

combination of opioids and Aspirin/NSAIDS.

Front 19

Name the three endogenous opioids.

Back 19

1. Enkephalins
2. β-Endorphins
3. Dynorphans

Front 20

Where are enkaphalins localized?

Back 20

interneurons

Front 21

Which endogenous opioid is a pentapeptide and has neurotransmitter-like actions and is rapidly degraded in the body?

Back 21

enkaphalin:
- rapidly degraded by enkephalinase
- localized in interneurons

Front 22

What is the difference between MET enkaphalin and LEU enkaphalin?

Back 22

Not much.
The difference lies in the last peptide component of the pentapeptides.

Front 23

Which endogenous opioids is resistance to degradation, has a hormone-like and neurotransmitter action, and is derived from proopiomelanocortin?

Back 23

β-endorphins:
- found in pituitary gland

Front 24

What is the name of the prohormone that contains the sequences for ACTH, MSH, and β lipotropin?

Back 24

proopiomelanocortin

Front 25

Which neurons release β-endorphins?

Back 25

long axoned neurons with cells bodies in the hypothalamus.

Front 26

Which endogenous opioids can be either resistant or susceptible to peptidases depending on the length of the polypeptide?

Back 26

Dynorphan:
8/9 AA: rapidly degraded by peptidases.

13/17 AA: resistant to degradation by peptidases.

Front 27

What are the actions of opioids?

Back 27

1. electrical stimulation of PAG: elicit analgesia
2. increases CSF levels of endogenous opioids.
3. inhibit substance P release.

Front 28

What is naloxone?

Back 28

pure opioid antagonist

Front 29

T/F: Opioids are the basis of gate control theory of pain.

Back 29

T.

Front 30

What is the undelying mechanism of acupuncture?

Back 30

light touch->low threshold nonnociceptive fibers-> activate inhibitory interneurons-> close gate on pain transmission.

Front 31

How does stress produce analgesic effects?

Back 31

Three mechanisms: 2 rely on different endogenous opioid systems.

Front 32

What is the role of opioids in abuse and dependence?

Back 32

Abuse: opioids inhibit GABA neurons to increase dopamine whih is crucial in the reward circuitry.

Dependence: chronic exposure to opioids decreases mu recepor coupling to G protein thus decreases the use of endogenous opioids.

Front 33

What are the three opioid receptors?

Back 33

1. mu receptor
2. kappa receptor
3. delta receptor

Front 34

Name the endogenous ligand and agonist for mu receptor.

Back 34

endogenous ligand: β-endorphin.
agonist: morphine.

Front 35

Which of the following is not an opioid receptor?
A. mu
B. kappa
C. delta
D. sigma

Back 35

D. dextromethorphan: stimulate sigma receptor and elicit suppression of cough. But higher doses eventually bind to phencyclidine receptor which inhibit NMDA ion channels.

Front 36

Which endogenous opioid bind to kappa receptors?

Back 36

dynorphans

Front 37

Why is kappa receptor not a good target for drug development?

Back 37

increases cardiac work load

Front 38

Which opioid receptor has more of the following effects:
respiratory depression
euphoria
physical dependence
miosis

Back 38

mu receptor

Front 39

Which opioid receptor has more of the following effects:
diuresis

Back 39

kappa receptor

Front 40

What are some types of pain suppressants?

Back 40

1. supstance P stimulator: caspaicin.
2. NMDA blockers: phencyclidine and ketamine
3. opioids: enkaphalin, beta-endorphin, dynorphan.
4. anticonvulsants: gabapentin, phenytoin, carbamzepine, clonazepam.
5. antidepressants: duloxetine, venlafaxine.
6. Ca channel blocker:
Ziconotide
7. loacal anesthetics