Nociception-pain-temp

Question 1

Structure of pain and temp axon

Answer 1

bifurcates with one receptor branch and central axon that enters CNS

both detected by sensory endings

Question 2

structure of sensory ending receptor for pain and temp axon

Answer 2

free nerve endings (but not pacinian, merkel, etc.)

afferent fibers have cell body in DRG and central axon enters cord

Question 3

pathway of pain and temp

Answer 3

1) sense in primary neuron
2) dorsal horn synapse
3) 2nd order neuron decussates at anterior commissure and ascend in spinothalamic tract
4) synapse on 3rd orde rneuron in VPL thalamus
5) project to somatosensory cortex or 2nd order neuron can also go to hypothal

Question 4

know receptors that detect temp info

2 types of temp receptors on sensory endings

which are there more of

Answer 4

1) warm receptor (30-48 degr C)
= C fibers

2) cold receptors (10-37 degrC) = Adelta fibers

MORE COOL RECEPOTRS

Question 5

know how temp receptors encode info

more sensitive to absolute temp or rate of change?

Answer 5

warm and cold receptors alter firing freq of AP in response to change in temp

more sensitive to rate of change than absolute temp

ex = cold receptor fire at steady rate then burst of rapid firing as temp dropping then slow again

Question 6

in response to painful stim what are two types of pain? what are they separated by?

Answer 6

separated by time

1st pain = pricking pain (local and well tolerated, carry by Adelta fibers (slight myelin)

2nd pain = aching, burning pain; smaller, unmyelinated C fibers; poor localize and poor tolerate

Question 7

which is better localized pricking or burning sensation

Answer 7

pinprick because Adelta fibers have smaller recepitve fields so better spatial discrim

Question 8

2 major blocking manipulations
pressure

what does this cause?
what happens with incr pressure

Answer 8

1) pressure induces anoxia (first fibers affected are metab active = Aalpha and Abeta fibers

causes loss of touch, vibration, propioception, joint movement WITHOUT PAIN
but as pressure incr, pain fibers also affected (Adelta before C) and only sense burning

as even more pressure, C fiber block and no sensory

Question 9

2 major blocking manipulations
local anesthetics

effect of 3 diff doses (low, med, high)

Answer 9

block small diameter fibers at concentration –> suppress burning pain first

higher doses block pricking pain

highest dose block touch and motor

Question 10

example of activating manipulations?

what happens if incr intensity

Answer 10

electrical stim
single, low intesnity stim can activ Aalpha and Abeta fibers –> sensation of touch and join movement without pain

higher intensity = pricking pain

higher and repetitive = burning pain

Question 11

what are afferent fibers for polymodal pain receptors

Answer 11

C fibers as afferents

have different receptors on different segments of the ending

also have diff receptors on single ending and respond to variety of stim

Question 12

VR1 receptor activated by?

where is it located?

Answer 12

activ by capsaicin but also weakly responds to acid and moderate heat (43 degrC)

found in vanilloid moiety containing compounds and on polymodal nociceptors

Question 13

ASICs respond to?

P2X responds to?

Answer 13

ASICs = acid

P2X = purines (ATP)

Question 14

chemicals that act as pain activators

define
examples

Answer 14

activators = depol nerve ending to threshold

ex = bradykinin, K+, acid, serotonin

Question 15

chemicals that act as pain sensitizers

define
examples

Answer 15

depolarizes but not to threshold and easier for activators

ex = prostaglandins, substance P, ATP, acetylcholine, serotonin

Question 16

what type of pain info is carried by C fiber affernts

Answer 16

2nd pain = burning/aching poorly localized pain that is not well tolerated

Question 17

location of first synapse in pain pathway

what NT operate here?

Answer 17

in dorsal horn of spinal column in the substantia gelatinosa = Rexed’s lamina II

major excitatory NT = glutamate

Question 18

2nd order neurons in dorsal horn of pain pathway have what receptors

Answer 18

2 receptors = AMPA and NMDA
both ionotropic

AMPA = rapid synaptic response
NMDA = simultaneous depol + glutamate 

so fast and slow response

Question 19

Difference btwn AMPA and NMDA at dorsal horn synapse

Answer 19

AMPA = rapid synaptic response

NMDA = slow excitatory potential

AMPA = require only glutamate

NMDA = require glutamate + depol to kick out Mg2+ +

Question 20

what does NMDA recepotr gate?

produces __ changes in excitatability

Answer 20

gates Ca2+ channel so incr Ca2+ influx

produces long lasting changes in excitability

Question 21

phosphorylation of NMDA by ___ does what?

Answer 21

phosphorylation by PKC and tyrosine kinase removes requirement of depol and NMDA can’t bind Mg2+

Question 22

prolonged release of glutamate at dorsal horn enables NMDA to what?

Answer 22

more easily propagate AP –> central sensitization

Question 23

NT at dorsal horn synapse
Glutamate released by?
acts on?

Answer 23

released by primary nociceptive sensory neurons at first synapse

acts on postsyn NMDA and AMPA

Question 24

NT at dorsal horn synapse
Substance P
how is it released?

what does it bind on? and effect?

Answer 24

intense stim of C fibers releases at presynap terminal

binds on NK1 receptor and causes closing of K+ channels and depol

Question 25

overall effect of substance P

Answer 25

enhancement and prolong actions of glutamate may diffuse to many dorsal horn neurons for broad central sensitization at dorsal horn for long time

Question 26

basis for peripheral sensitization | what is sensitization of nocicpetors also known as?

Answer 26

aka primary hyperalgesia because incr sensitivity to pain occurs at first site in path

Question 27

agents that sensitize nociceptors

Answer 27

1) prostaglandins 2) substance P 3) ATP 4) ACh 5) serotonin these decr threshold for activation of nociceptors

Question 28

why do sensitizing agents decr threshold for activation of nociceptors

Answer 28

when you injure yourself, you stim C pain fibers --> causes release of substance P --> sensitize nociceptors in area bigger than original wound therefold, a smaller stim needed to activate them promoting changes for better repair

Question 29

basis for central sensitization | wind-up phase

Answer 29

1) as C fibers stim, postsyn AMPA receptors stim first since only glutamate around 2) if stim persistent, both glutamate + postsyn depol activ NMDA (larger response) 3) causes wind-up = stim dependent enhancement of postsyn response of dorsal horn neuron

Question 30

basis for central sensitization | NMDA receptor phosphorylation

Answer 30

1) incr in intracellular Ca2+ 2) causes phosphorylation of NMDA by PKC and tyrosine kinase inhibiting Mg2+ binding to NMDA 3) NMDA no longer requires depol so easier open 4) P-NMDA and AMPA now both open by glutamate alone

Question 31

basis for central sensitization | effect of substance P

Answer 31

not removed by reuptake so persists and can diffuse to many dorsal horn neurons --> broad sensitization

Question 32

basis for analgesic action of aspirin

Answer 32

ASA inhib cyclooxygenase that converts arachidonic acid to prostaglandin by block synth of prostaglandin, aspirin prevents nociceptors sensitization (primary hyperalgesia)

Question 33

basis for triple response

Answer 33

triple response = central red + wheal + flare

Question 34

central red and wheal | how does it occur?

Answer 34

1) tissue damage causes local bradykinin production 2) vasodilates and produce heat and redness (central reddening) 3) incr permeability of capillary membraens --> fluid accum and swelling (edema/wheal)

Question 35

flare | how does it occur?

Answer 35

1) bradykinin activ C fiber nociceptors 2) AP propagate toward cell body of DRG and along collaterals to periphery 3) release of substance P surrounding wound site 4) mild vasodilator so pink flare CALLED "AXON REFLEX"

Question 36

location of action and effects of substance P | where is substance P released?

Answer 36

released at synapse and in periphery from C fibers

Question 37

effect of substance P on peripheral collateral how does it cause flare how does it sensitize?

Answer 37

1) mild vasodilator producing flare in triple response in response to local tissue damage 2) also sensitizes to decr threshold of nocicpetors in tissue damage sites 3) therefore, responses to noxious stim are enhanced --> behavioral changes for better healing

Question 38

effect of substance P in synapse (dorsal horn) effect of intense stim on C fibers

Answer 38

acts as sensitizer 1) intense stim of C fibers terminating in subst gelatinosa causes release of subst P 2) binds NK1 receptors and closes K+ channels --> depol 3) enhances and prolongs glutamate action on AMPA and NMDA --> incr pain sensitization 4) also diffuse to nearby neurons so broad sensitization

Question 39

PAG neurons located where? project where? the project where? what NT do they ahve?

Answer 39

found in midbrain project to medulla then project to dorsal lateral funiculus medullary neurons are 5-HT

Question 40

effect of 5-HT in spinal cord use what NT? effect on pain sensation?

Answer 40

inhib second order neurons of dorsal horn by exciting inhib interneurons they use enkephalin and blocks VG ca2+ channels presynap and open K+ channels postsynap inhib of 2nd order neuron --> decr pain sensation

Question 41

PAG neurons sensitive to?

Answer 41

sensitive to opiates exposing endogenous or exogenous opioids --> greater excitatory output --> greater inhib of 2nd order neurons in dorsal horn

Question 42

stroking or rubbing area of body experinencing pain causes ___ why?

Answer 42

decr sensation of pain because activates non-nociceptive afferent pathways (touch and A-beta fibers) activates dorsal horn interneurons that inhib synapses activated by nociceptive fibers

Question 43

selective stim of A-beta fibers causes

Answer 43

causes reduction of pain (basis of transcutaneous electrical nerve stim)

Question 44

elimination of inputs from A-beta fibers causes

Answer 44

incr pain sensation (hyperalgesia)

Question 45

define gate control theory

Answer 45

nociceptive inputs open and non-nocicpetive afferents shut gate that leads to central transmission of noxious info

Question 46

basis for placebo effect PAG receive input from? ultimate effect?

Answer 46

1) PAG receive input from limbic system and cortex 2) but expect to receive pain-releiving drug 3) incr activity in neocortex/limbic 4) PAG activated via secretion of endorphins that stim PAG excitatory output --> incr stim of inhib interneurons in dorsal horn and inhib of 2nd order neurons in dorsal horn

Question 47

placebo effect blocked by?

Answer 47

blocked by naloxone so PAG responsible

Question 48

stress induced analgesia what does it incr? result?

Answer 48

increases limbic system activity activates PAG and stim of inhib interneurons in dorsal horn results in inhib of 2nd order neurons in dorsal horn of pain pathway

Question 49

effect of naloxone on stress induced analgesia

Answer 49

naloxone blocks some but not all analgesia so stress = opioid + nonopioid mechanism

Question 50

rewiring in neuropathic pain effect on signals from primary to secondary neurons

Answer 50

1) injury causes change in concentrations of neutrophrins 2) promotes inappropriate growth of neurons 3) neurons contact inappropriate targets 4) organization awry 5) primary neurons can't be organized by stim around appropriate secondary neuron --> wrong signals from primary neurons may stim 2nd neuron

Question 51

role of GABA in neuropathic pain

Answer 51

decr GABA + decr GABA and opiate receptors causes decr inhib signals decr second order neuron excitation

Question 52

role of microglia in neuropathic pain causes release of ___

Answer 52

after injury, microglia activated (incr ATP attract microglia via purine recepotrs) release of BDNF decr expression of KCC2 (extruder of Na) alters Cl reversal potential GABA activation causes ecitation therefore, decr inhib in dorsal horn --> hyperalgesia

Question 53

3 tracts after axons ascend in anterolateral tract

Answer 53

1) VPL thalamus 2) reticular formation 3) mesencephalon

Question 54

VPL thalamus = spinothalamic tract contains what info

Answer 54

localizes the input (pain and temp)

Question 55

spinoreticular tract cotains what info

Answer 55

sends info to hypothalamus, amygdala (behavioral/emotional responses to input) (pain and temp)

Question 56

spinomesencephalic tract contains what info

Answer 56

important for descending modulatory influences of pain

Question 57

3 types of pain

Answer 57

1. Nociceptive = acute painful stimulus (flame, overinflated BP cuff, chemicals) 2. Inflammatory = injury and inflamm signals released 3. Neuropathic

Question 58

for extreme temperature extreme temp = Cold = what fibers extreme temp = warm = what fibers mechanical are primarily what fiber type polymodal fibers are all what?

Answer 58

cold = C hot = Adelta opposite of well being mechanical = adelta polymodal = C

Question 59

release of substance P requires

Answer 59

repetitive stim of c fibers

Question 60

Distinguish btwn hyperalgesia and allodynia

Answer 60

hyperalgesia = incr sensitivity to pain (flare) allodynia = non-noxious stim like touch becomes painful (sunburn then water in shower hurts rather than feel good)

Question 61

why do you have referred pain

Answer 61

a. Due to convergance of inputs from cutaneous and visceral sites but cutaneous ones dominate so therefore have referred pain

Question 62

Tabes dorsalis causes degeneration of ___ what effect

Answer 62

Abeta fibers = intolerable pain (losing Abeta because now losing endogenous way to produce analgesia)

Question 63

Electrical stim of back relieves pain how?

Answer 63

although fibers ascend and feel pain but also fibers descend and activate enkephalinergic interneuron in many segments

Question 64

Descending modulatory pathway of PAG

Answer 64

1) stim PAG 2) project to nucleus raphe magnus = medulla 3) project to dorsal horn of spinal cord (target enkephalinergic inhib interneurons)

Question 65

Types of TTX Receptors both sensitive to __

Answer 65

TTX-sensitive TTX-resistant = in sensory neurons of heart, CNS both sensitive to lidocaine