Lecture 3: Pain & perception

Question 1

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

Answer 1

(unmyelinated) free nerve endings

Question 2

Definition of ‘noxious’ (painful):

Answer 2

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

Question 3

A nociceptor is:

Answer 3

type of axon that selectively reacts to noxious stimuli

Question 4

Does a nociceptor detect pain?

Answer 4

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

Question 5

What are the 2 components for pain?

Answer 5

• Detection through the visual system
• Psychological and cognitive aspects

Question 6

What does the anterior cingulate cortex do?

Answer 6

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)

Question 7

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

Answer 7

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

Question 8

What is classical positive conditioning?

Answer 8

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

Question 9

What is classical negative conditioning?

Answer 9

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

Question 10

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

Answer 10

Nociceptors only react within a painful range.

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

Question 11

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

Answer 11

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

Question 12

What is the effect of capsaicin on TRPV1?

Answer 12

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.

Question 13

What happens when tissue damage occurs?

Answer 13

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

Question 14

What is peripheral sensitization?

Answer 14

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

Question 15

What things are involved in peripheral sensitization?

Answer 15

• 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

Question 16

Ways for pain reduction:

Answer 16

• 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)

Question 17

How does pain become long lasting?

Answer 17

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

Question 18

How does sensitization work?

Answer 18

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

Question 19

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

Answer 19

• 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)

Question 20

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

Answer 20

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)

Question 21

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

Answer 21

• Mechanoreceptive: dorsal pathway
• Nociceptive: anterlateral pathway

Question 22

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

Answer 22

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

NOTE: via anterolateral pathway

Question 23

What are reaction that are non-thalamus targets of nociceptors

Answer 23

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

Question 24

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

Answer 24

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.

Question 25

How does morphine reduce GABA release in the periaquductal gray?

Answer 25

Morphine activates GIRK in GABAergic neuron–> K+ goes out of cell –> inhibition of adenylyl cyclase –> decreases cAMP –> hyperpolarization –> reduced GABA release –> decreased inhibition

Question 26

What happens when there is opioid tolerance of morphine in GABAergic neuron in periaquaductal gray?

Answer 26

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

Question 27

What types of referred pain exists?

Answer 27

• 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

Question 28

What happens to the somatosensory cortex when amputation happens?

Answer 28

The somatosensory cortex will reorganize itself