Neurobio 1&2 > Pain pathways > Flashcards

Pain pathways Flashcards

(68 cards)

Study These Flashcards
1
Q

what are some functions of pain? (5)

A
  • Lets us know when and where damage is occurring ⇒ good thing to have
  • Pain can lead to suffering ⇒ bad thing to have such as chronic pain
  • Congenital insensitivity to pain
  • Diabetes
  • Leprosy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

examples of congenital insensitivity to pain? (2)

A
  • mutations in NGF and its receptor TrkA ⇒ no pain or temperature sensing, no sweating, learning difficulties
  • No spikes happening in the nociceptors or loss of distal nociceptors (diabetes and leprosy)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Nociceptors

A

transduce pain signals via molecules and receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

free nerve endings

A

in the epidermis and mechanoreceptors have lots of specializations
- heat, acid, cold, injury, etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

where do free nerve endings depolarize?

A

at the base of the epidermal nerve fiber where it turns into an axon it turns into a spike to go towards the CNS and end up on the spinothalamic tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is the STT pathway?

A
  • the pain and temperature afferent fibers from the DRG synapse in the dorsal horn ipsilateral to the body side in question
  • synapses onto a spinothalamic tract neuron that conveys pain and temperature to the thalamus on the contralateral side up through the ventral lateral quadrant of the spinal cord
  • From the thalamus, these relay information to S1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what effects do brushing, pressure, and pinching have on the nociceptors?

A

there is gradually increasing responses of the STT neuron as the stimulus is applied
- Pressure and pinch are the nociceptive signals and they drive more of a response than the brush

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

T/F nociceptors can feel noxious information from the mechanoreceptor neurons?

A

True
- the mechanoreceptor neurons that converge onto the STT neurons that also get information from nociceptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what happens if capsaicin is injected intradermally and then you brush, put pressure on, or pinch the skin?

A

any stimulus elicits a pain response larger than the previous corresponding stimulus
- The nociceptors are being sensitized by the capsaicin and capsaicin is partially activating the nociceptors so the stimuli are able to drive that response further

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what effect does putting glutamate neurotransmitters on the nociceptors have?

A

it will activate them and those responses are also enhanced like the capsaicin responses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what do PC, RA, SA1, SA2 categories respond to or not respond to?

A

they respond to small stimuli and don’t respond at all to more intense stimuli

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

The threshold for perception of thermal pain in humans is ______ deg C

A

44-45

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what type of firing pattern do nociceptors have with intensified stimulus?

A

logarithmically (somewhat) which is characteristic of nociceptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

how sensitive are non pain coding temp receptors?

A

more sensitive than nociceptors and activate and shut off at lower temperatures
- the normal skin temperature at 32 deg C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

do nociceptors have faster or slower conduction than mechanoreceptors? what are the 2 types? speeds?

A

slower
- C fibers are about ½-2 m/s
- Adelta nociceptors are about 5-10 m/s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Stevens law

A

the pain system is exquisitely tuned to the job it is intended to perform ⇒ to protect from getting hurt
- pain perception is a positively accelerating function with an exponent >1
- nociceptors respond within narrow physical ranges so therefore they change firing pattern clearly to a relatively modest change in stimulus intensity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

T/F pain sensation becomes disproportionately intense?

A

True
- Change in temperature of skin 45-45.5 deg C is noticeable
- Change from 50-50.5 deg C produces greater change in sensation and stress

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what categories of sensation are <, = , > 1 n?

A
  • n < 1 perceived intensities of light, sound, odor
  • n ~ 1 perceived lengths of lines
  • n > 1 perceived pain intensity (self amplifying)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what are the 4 transducers of thermal stimuli?

A
  • CMH ⇒ C mechano heat
  • CMHC ⇒ C mechano heat cold
  • AMH ⇒ A mechano heat
  • AMHC ⇒ A mechano heat cold
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what TYPE of receptor are the tranducers of noxious heat?

A

all 4 of are polymodal receptors and respond to more than one kind of stimulus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

do C fibers or Adelta fibers have lower activation thresholds?

A

activation threshold for C fibers is generally lower than Adelta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

which single unit recordings are slow vs fast? What does this refer to?

A
  • Fast: CMH, AMH II
  • Slow: AMH I
    refers to how much time stimulation occurs for until the nociceptor responds
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what type of gated channels do DRG have?

A

in vitro rat dorsal root ganglion have heat gated channels activated following increase in CA2+ ⇒ you can activate them with heat, the neuron responds at 45 deg C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what are 2 transducer receptors for capsaicin?

A
  • TRPV1 ⇒ if you put capsaicin or heat on the neuron this activates the nerve fiber
    Responds to noxious chemical stimuli and noxious heat
  • TRPV2 ⇒ has a higher threshold temperature at about 54 deg C and up
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Transient receptor potential Vanniloid (TRPV)
vanniloid is a chemical class of capsaicin
26
what happens if you knockout TRPV1?
if you knockout TRPV1 you get a phenotype and dip a rats tail into varying deg C water (which is latency), then you will see there is a longer latency for knockout mice than for WT mice - drug companies wanted molecules to block this receptor to make a new analgesic but they found that this can cause hyperthermia because TRPV1 receptors are also in the brain and thermal regulation areas
27
2 markers for nociceptors cells and what they do?
- TRPV1 ⇒ thermally sensitive receptor - IB4 ⇒ lectin but is a marker for mechanical nociceptors
28
T/F neurons can be TRPV and IB4 positive or negative?
True - Exactly what's mediating the response despite some neurons lacking TRPV4 is not known at this time
29
what is special about bats?
ganglion specific splicing of TRPV1 underlies infrared sensation in vampire bats - Bats have a modified TRPV1 receptor sensitive to heat to 30 deg C when TRPV1 normally starts responding at 43 C
30
TRPV3 and TRPV4
encode for warm temperatures under 43 dg C which is the threshold for pain - they probably exist in keratinocytes and when activated by warm temperature they release ATP which activates P2X3 receptors on the thermoreceptors
31
TRPM8
m stands for menthol and these sense cooling because if the temp gets below 27 deg C we need to know
32
TRPA1
when we get below 15 deg C this is an allyl nociceptor receptor ⇒ synonymous with pain
33
Caspacin correlates with ___, camphor correlates with ___, menthol correlates with ___, cinnamaldehyde and allylisothiocyanate correlates with ___?
TRPV1, TRPV3, TRPM8, TRPA1
34
How is TRPA1 activated molecularly?
TRPA1 is activated by covalent modification of cysteines in the C terminus ⇒ activated by an endogenous aldehyde (HNE: 4-hydroxy-2-nonenal) - products of reactive oxygen species generated during tissue injury, inflammation, and oxidative stress ⇒ these can activate TRPA1 in neurons near a cell that is in trouble which initiates the sensation of pain via TRPA1
35
How do rattlesnakes detect the infrared radiation of their prey?
TRPA1 orthologues from pit bearing snakes (vipers, pythons, and boas) are the most heat sensitive vertebrate ion channels thus far identified and consistent with their role as primary transducers of infrared stimuli - They find warm blooded animals with ion channels - Their activation thresholds are 27 deg C
36
tissue acidosis during ischemia or inflammation can be as low as pH __? 30% of CMH respond to low pH via ____?
5; TRPV1
37
are pH current in sensory neurons sustained or transient?
they can be either
38
what does TRPV1 most likely mediate in regards to pH responses?
the sustained responses
39
Heteromeric ASIC channels
acid sensing channels that may underlie transient pH responses - ASIC3 has a role in cardiac ischemia
40
what molecules does tissue damage or inflammation result in the release of?
ATP, bradykinin, and tryptases that cleave protease activated receptors (PAR)
41
Protease
cuts proteins
42
PAR
where the end of the molecule is the ligand and it is held away until the elbow is cleaved by the protease which activates the receptor
43
Mediators released during tissue damage and inflammation (3)
- ATP - Bradykinin - PAR receptors
44
ATP released from damaged cells can signal through ___ and ___ receptors?
P2X and P2Y
45
bradykinin induced thermal hyperalgesia requires both ____ and ____
TRPV1; TRPA1
46
what type of receptors are physiological pain mostly coded by?
ligand gated channels ⇒ they are also gated by environmental inputs from the physical environment like temperature - all the physiological pain is coded by channels in the nociceptors
47
examples of activators and channel types for physiological pain? (5)
- Menthol activates TRPM8 - Heat and acid activate TRPV1 - Acid activates ASIC too - Mechanical and warming stimuli activate keratinocytes to release ATP which activates the P2X receptor on the nociceptor - Mechanical can also activate TRPA1
48
peripheral sensitization
when there is inflammation, infection, injury, etc. you get increased responsiveness of neurons in the pain pathway - the blood vessel has immunocytes inside of them ⇒ when there is inflammation they can come out and be in the environment near the epidermal nerve fibers and release inflammatory soup which has lots of chemicals to sensitize nociceptors
49
what is the mechanism for peripheral sensitization?
- tissue damage triggers mast cells, neutrophils, and macrophages that release the inflammatory soup - This includes 2 cytokines TNFalpha and IL1, IL6, NO, bradykinin, NGF, H+ - These act on GPCR and cytokine receptors that are not channels but communicate with intracellular signaling systems that cause things to happen
50
what type of receptors do the peripheral sensitization mechanisms typically use?
mostly through non channel receptors
51
what is the goal of peripheral sensitization?
peripheral inflammatory mediators and danger signals increase the excitability of primary afferent neurons
52
Central sensitization
neurophysiological changes that lead to increased responsiveness to normal or subthreshold input in CNS neurons of the pain pathway - neuroplasticity that happens in the spinal cord and brain
53
Synaptic plasticity
strengthening of synapses via NMDA receptor initiation (same as hippocampus) and you get the whole cascade for potentiated synapses between the nociceptor and the STT neurons as well as excitatory interneurons
54
microglia
resident immunocytes of the nervous system
55
what happens with neuro inflammation in the CNS?
microglia become activated and start releasing inflammatory soup in the CNS ⇒ probably inappropriate response but it happens
56
what does central sensitization look like in the dorsal horn? (2)
these changes include strengthening of synapses and disinhibition
57
neuropathic pain via central mechanisms of sensitization
this mechanism is the same as the peripheral mechanism - inflammatory soup comes out of microglia and feeds back to the primary afferent neuron to release transmitter release and sensitive postsynaptic neurons - Glutamate is involved
58
what does central gray stimulation do?
if you stimulate in this area then you can block pain - This stimulation activates a descending system that controls the gain of spinal cord
59
Analgesia
absence of pain ⇒ pain that was there is no longer perceived or cared about
60
Anesthesia
blocks pain signals at the spinal cord or brain to induce temporary loss of sensation
61
T/F pain can be modified by circumstance?
True
62
Examples of circumstances in which pain is altered (3)
- Life threatening situations - Some religious ceremonies - Placebo: analgesia resulting from the belief that a treatment will reduce pain
63
what is the descending system from the central gray when it is stimulated?
- The stimulation of the CG activates neurons in the rostro-ventral medial medulla (rostral midbrain to medulla in the caudal pons) - This sends inhibitory fibers to the dorsal horn of the spinal cord where they can synapse onto projection neurons/interneurons or even presynaptically on the nociceptor to inhibit transmitter release or response that the postsynaptic neuron has
64
Antidromic; Orthodromic
opposite of orthodromic or equal to a hyperpolarization; the way the spikes usually go aka depolarization
65
how do we know we are stimulating an STT neuron?
if you record a neuron in the dorsal horn of the spinal cord and stimulate in the thalamus and we see an antidromic spike come after the stimulation, then we know it is a STT neuron
66
how did the descending inhibition experiment work?
the experiment used had a stimulating electron in the thalamus and a recording electrode in the spinal cord and a stimulating electrode in the retroventral medial medulla (RVM) - Two stimulating electrodes, one recording electrode, and they find the neuron antidromically (STT) and then activate the neuron and stimulate the RVM to see if they can inhibit it
67
what happens when you stimulate in the RVM?
you see that you inhibit the firing - If you slow down the recording you can see a few hundreds of ms IPSP that hyperpolarizes and inhibits the neuron
68
end card
:) you got this
Neurobio 1&2
flashcards
Decks in class (43)
# Cards
Brainscape helps you reach your goals faster, through stronger study habits.
© 2026 Bold Learning Solutions. Terms and Conditions