Lecture 3: Pain & perception Flashcards
T.M
Which receptor type belongs to the sensory function ‘pain & temperature?
(unmyelinated) free nerve endings
Definition of ‘noxious’ (painful):
Everything that has caused tissue damage or threathens to do that in the immediate future
A nociceptor is:
type of axon that selectively reacts to noxious stimuli
Does a nociceptor detect pain?
NO, pain is a concept that is encoded in the brain itself
What are the 2 components for pain?
- Detection through the visual system
- Psychological and cognitive aspects
What does the anterior cingulate cortex do?
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)
What does pain perception depend on? + name the involved brain structures
- Detection in the Thalamus & SII (second somatosensory cortex)
- Expectation: Cingulate cortex
- Earlier memories: Frontal cortex
- Cognitive factors: Cingulate + frontal cortex
What is classical positive conditioning?
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
What is classical negative conditioning?
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
What is the diffence between nociceptor & non-nociceptor responses?
Nociceptors only react within a painful range.
Vb. Thermoreceptor reacts with the temperature, nociceptor only reacts from a really high/low temperature
How is the reaction of nociceptors determined? And what does TRPV-1 (transient receptor potential) do?
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
What is the effect of capsaicin on TRPV1?
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.
What happens when tissue damage occurs?
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
What is peripheral sensitization?
Phenomenon where peripheral nociceptors become more responsive for stimuli from tissue injury/inflammation
What things are involved in peripheral sensitization?
- 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
Ways for pain reduction:
- 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)
How does pain become long lasting?
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
How does sensitization work?
GABA receptor are targeted. Due to high stimulus, there is a dysregulation of the K+/Cl- pump –> excess of intracellular Cl- –> GABA activates –> sensitization
What kind noci fibers do we have and what are their characteristics?
- 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)
How are the noci fibers located through the layers of the cortex
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)
What are the pathways of the mechanoreceptive afferent and nociceptive afferents towards the cortex?
- Mechanoreceptive: dorsal pathway
- Nociceptive: anterlateral pathway
How do receptive field differ between the first and second pain?
First pain has small receptive field –> sensory discrimination route
Second pain has large receptive field –> affective-motivational route via ACC
NOTE: via anterolateral pathway
What are reaction that are non-thalamus targets of nociceptors
- Reflexes –> via spinal cord interneurons: recognition is in thalamus but reaction is not
- Reticular formation: startle reaction –> pons
What part of the brain can control pain (non-thalamus target)? And how does it work.
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.
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
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
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
What happens to the somatosensory cortex when amputation happens?
The somatosensory cortex will reorganize itself
