Lecture 3: Pain & perception Flashcards

T.M

1
Q

Which receptor type belongs to the sensory function ‘pain & temperature?

A

(unmyelinated) free nerve endings

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2
Q

Definition of ‘noxious’ (painful):

A

Everything that has caused tissue damage or threathens to do that in the immediate future

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3
Q

A nociceptor is:

A

type of axon that selectively reacts to noxious stimuli

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4
Q

Does a nociceptor detect pain?

A

NO, pain is a concept that is encoded in the brain itself

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5
Q

What are the 2 components for pain?

A
  • Detection through the visual system
  • Psychological and cognitive aspects
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6
Q

What does the anterior cingulate cortex do?

A

The ACC is a expectation modulator: it checks what a certain action will do
(so you know if u should do it again next time or not)

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7
Q

What does pain perception depend on? + name the involved brain structures

A
  • Detection in the Thalamus & SII (second somatosensory cortex)
  • Expectation: Cingulate cortex
  • Earlier memories: Frontal cortex
  • Cognitive factors: Cingulate + frontal cortex
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8
Q

What is classical positive conditioning?

A

Positive conditioning occurs when a neutral stimlus is paired with positive/rewarding unconditioned stimulus with lead to a positive conditioned response

Vb.
- Before conditioning: Bell sound –> no salivation
- During conditioning: Bell sounds + food –> salivation (unconditioned response)
- After conditioning: bell sound –> salivation

Bell sound is neutral stimulus, food is unconditioned stimulus.
After conditiong, the bell becomes a conditioned stimulus and salivation becomes a conditioned response

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9
Q

What is classical negative conditioning?

A

Negative conditioning occurs when a unpleasant stimulus is paired with unconditioned stimulus with lead to a conditioned aversive response

Vb.
- Before conditioning: shock –> no salivation
- During conditioning: shock+ food –> salivation (unconditioned response)
- After conditioning: shock –> salivation

Shock is a negative stimulus, food is unconditioned stimulus.
After conditiong, the shock becomes a conditioned stimulus and salivation becomes a conditioned response

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10
Q

What is the diffence between nociceptor & non-nociceptor responses?

A

Nociceptors only react within a painful range.

Vb. Thermoreceptor reacts with the temperature, nociceptor only reacts from a really high/low temperature

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11
Q

How is the reaction of nociceptors determined? And what does TRPV-1 (transient receptor potential) do?

A

Determined by the receptor in the membrane.
TRPV-1 is a receptor dat reacts to heat, the reduction of the pH (H+) from tissue swelling or to tissue damage agents

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12
Q

What is the effect of capsaicin on TRPV1?

A

Capcaisin is a lipophylic that can transport through the membrane, which causes reactivity of the VR-1 receptor.
Capcaisin is a molecule that appears in peppers e.g.

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13
Q

What happens when tissue damage occurs?

A

Inflammatory reaction:
- Activated nociceptors will release:
Substance P (activates Mast cells/neutrophils –> release histamine -> attracts prostaglandines –> pain), ATP, CGRF (+ substance P affects blood vessels)
- Non-neuronal cells release:
H+, arachidonic acid, COX2, prostaglandines (PGE2), interleukines & TNF-alfa

–> All these substances protects against infections

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14
Q

What is peripheral sensitization?

A

Phenomenon where peripheral nociceptors become more responsive for stimuli from tissue injury/inflammation

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15
Q

What things are involved in peripheral sensitization?

A
  • NGF & bradykinine: potentiate activity of TRPV1 receptors
  • Prostaglandines: via GPCRs it can increase cAMP in axon. cAMP can be 2nd messenger to acitvate PKA. PKA can help with phosphorylation of TRPV1, making it more sensitive to activation.
  • Cytokines: interleukin & TNF-alfa –> can activate MAPK pathway: increae of Na+ channel activity –> less input gives more activation
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16
Q

Ways for pain reduction:

A
  • Aspirin, ibuprofen: nonsteriodal anti-inflammatory drugs –> inhibit COX2 which effects prostaglandine production
  • TNF-alfa blockade: increases pain threshold with using a neutralizing antibody. (used as autoimmune disease treatment)
17
Q

How does pain become long lasting?

A

In the post synaps of pain neurons, NMDA receptors are targeted (mainly target of C fibers). The removal of Mg2+ block –> LTP –> long lasting pain

18
Q

How does sensitization work?

A

GABA receptor are targeted. Due to high stimulus, there is a dysregulation of the K+/Cl- pump –> excess of intracellular Cl- –> GABA activates –> sensitization

19
Q

What kind noci fibers do we have and what are their characteristics?

A
  • A-lambda fibers: myelin, small receptive field, for fast sharp pain
    (first pain)
  • C-fibers: no myelin, large receptive field, for a slow burning pain, on long term can change behaviour
    (second pain)
20
Q

How are the noci fibers located through the layers of the cortex

A

C-fibers are in layer 1 + 2
A-fibers are in layer 1 + 5
Non-nociceptive AB fibers are in layer 5

NOTE: layer 1 + 5 via anterolateral tract to higher centers, in layer 5: convergence on noci & non-nociceptive afferents: referred pain (other location that location of actual injury)

21
Q

What are the pathways of the mechanoreceptive afferent and nociceptive afferents towards the cortex?

A
  • Mechanoreceptive: dorsal pathway
  • Nociceptive: anterlateral pathway
22
Q

How do receptive field differ between the first and second pain?

A

First pain has small receptive field –> sensory discrimination route
Second pain has large receptive field –> affective-motivational route via ACC

NOTE: via anterolateral pathway

23
Q

What are reaction that are non-thalamus targets of nociceptors

A
  • Reflexes –> via spinal cord interneurons: recognition is in thalamus but reaction is not
  • Reticular formation: startle reaction –> pons
24
Q

What part of the brain can control pain (non-thalamus target)? And how does it work.

A

Periaquaductal Gray via GABA and Glu neurons that go to medulla.
- GABA causes hypersensitivy, since it inhibits interneurons. This prevents inhibtion of pain neurons
- Glu causes hyposensivity, since it excites interneurons. This helps the inhibition of pain neurons.

25
How does morphine reduce GABA release in the periaquductal gray?
Morphine activates GIRK in GABAergic neuron--> K+ goes out of cell --> inhibition of adenylyl cyclase --> decreases cAMP --> hyperpolarization --> reduced GABA release --> decreased inhibition
26
What happens when there is opioid tolerance of morphine in GABAergic neuron in periaquaductal gray?
There will be an uncoupling from GIRK , cAMP will be upregulated since there is no inhibition of adenylyl cyclase. Depolarization will happen which increases GABA release
27
What types of referred pain exists?
- Hyperalgesia: increased pain after noxious stimulus by intense + long lasting painful stimulus (LTP in spinal cord) - Allodynia: pain perception with non-noxious stimuli because of interaction between AB and C-fibers by long lasting activation of the circuit. - 'Referred' pain: pain in heart bc of O2 shortage. Will feel pain in should and chest - Phantom pain: pain in amputated body parts
28
What happens to the somatosensory cortex when amputation happens?
The somatosensory cortex will reorganize itself