neuroimmunology of path pain

Question 1

function of astrocytes

Answer 1

connections with neuron synapses

link neurons to blood supply + form BBB

Question 2

function of mycroglia

Answer 2

macrophages of CNS
small + mobile
survey env for pathogens/damage

Question 3

functions of oligodendrocytes

Answer 3

create myelin sheaths

Question 4

3 types of glia

Answer 4

astrocytes, microglia, oligodendrocytes

Question 5

what are tri and tetra-partite pain synapses

Answer 5

tri = with astrocytes + pre/post syn cell
tetra = +microglia

Question 6

role of astrocytes in normal pain synapses

Answer 6

principal role in ion homesostasis = reg ec K and Ca which regulate excit
glutamate homeostasis (GL1, GLAST transporters)

Question 7

what happens at synapses when there are repeated pain signals

Answer 7

astrocytes decreases exp glut transporters = loss glut control = glut in synapse longer
microglia = activated => inflammatory

Question 8

how are microglia activated directly/indirectly

Answer 8

• changes in ec ions, sub P, glutamate

- central or peripheral nerve injury eg prostaglandin, atp/other damage associated molecular pattenrs

Question 9

what to microglia do in response to activation

Answer 9

release sytokines to activate other microglia, peripheral immune infiltration into CNS

Question 10

what are the mediatros of activated glial cells that act on pre and post synaptic receptors

Answer 10

cytokines, chemokines, ROS

Question 11

what is the effect of glia released mediators on glutamate releaseand glutamate transporters

Answer 11

activate presynaptic TRP cahnnels (V1, A1_ and couple IL1R1-NMDAR to increase glut release
increase ampa signalling and receptor expression

Question 12

what is the effect of glia released mediators on NMDAR activity

Answer 12

increase NMDAR activity through kinases and phosphorylation

Question 13

what is the effect of glia released mediators on inhibition

Answer 13

inhibit GABA/glycine release by inhib interneurons

prostaglandin e2 decreased inhibitory glycinergic ntsm

Question 14

what is the effect of glia released mediators on hyperpol

Answer 14

BNDF-TRKB to decrase KCC2, increase IC Cl to decrease hyperpol

Question 15

what is the effect of glia released mediators on overall sensitivity

Answer 15

increase nociceptive hypersensitiy

Question 16

what can happen when transmitters induce elevations of internal Ca in glial cells

Answer 16

cause glial cells to release glutamate, enhacning glut transmission, hypersensitivity + ectopic firing
astrocytes contact with lateral cells = spread pain sensation
increase allodynia if contact with nonnoci synapses

Question 17

describe function of TCA and SSNRI antidepressants for path pain

Answer 17

inhibit serotonin and noradreanline reuptake

enhance alpha2 adrenoreceptor noradrenergic inhibition by descending modulatory controls

Question 18

describe function na blockers and local anaesthetics for path pain

Answer 18

inhibit function of vgx Na+
reduce excit of neural membranes and nerve fibre impulse propagations
affect primary affrents

Question 19

effects of gabapentinoids

Answer 19

effect at dorsal horn to attentuate central sensitisation

- inhibit Ca ntsm release via a2d subunit, stim glut uptake by astrocytes. descending modulation?

Question 20

why is treated path pain hard

Answer 20

target neuronal components to treat pain symptoms but dont modify mechanisms of pain persistence