Yuste C10

Question 1

Nociception

Answer 1

The brain response to noxious stimuli, generates a painful sensation.

Question 2

Nociception vs pain

Answer 2

Two different things; Can have nociception without pain and can experience pain without nociception.

Question 3

Pain

Answer 3

Feeling of pain is an internally generated response in our spinal cord and brain to a nociceptive stimulus. It is subjective and influenced by many factors.

Question 4

Perception of pain

Answer 4

No purely painful stimuli. The variability of the perception of pain is yet another example of a principle that we have encountered: pain is not the direct expression of a sensory event but rather the product of elaborate processing by the brain of a variety of neural signals.

Question 5

Nociceptive information

Answer 5

Carried by the anterolateral pathway, which climbs via the anterolateral tract of the spinal cord level and then goes on to the thalamus, then to the cortex.

Question 6

Anterolateral pathway

Answer 6

Evolutionarily older, with thinner axons, normally not myelinated, which are therefore slower. Different channels: sharp (first) pain, burning (second) pain, hot, cold, itch, sensual touch, specific detection of lactic acid.

Question 7

Pain pathway

Answer 7

Starts in the dermis and epidermis. The receptor organs which sense noxious stimuli are the termination of the axons from the DRGs. These processes are the form of free nerve endings in the skin.

Question 8

Four major types of nociceptive stimuli

Answer 8

1. Mechanical – intense pressure
2. Temperature – hot or very cold
3. tissue injury – inflammation
4. Polymodal (silent nociception) in our viscera which respond to inflammation and chemical stimuli.

Each have different types of receptor channels, all belonging to the TRP ion channels family.

Question 9

TRP ion channels

Answer 9

Transduce noxious stimuli, K+/Na+ channels; depolarise the nerve endings and trigger APs. Their variety thought to underlie the perception of the large range of temps we can detect. They can be modulated by particular molecules (capsaicin and heat-sensing TRIPV1 channel).

Question 10

Hyperalgesia

Answer 10

Nerve fibres are involved in reactions to tissue injury. Anterolateral pathway axons, when active, can also fire their branches in the vicinity, which release compounds that trigger an inflammatory response in the nearby skin. These axons both receive inputs and also release transmitters. These substances feed on each other and the pain becomes magnified.

AKA neurogenic inflammation or flare.

Question 11

Inflammatory response

Answer 11

Local axons get activated and release slow of compounds which add to a complex mix of chemicals released from damaged cells that accumulate at the site of tissue injury.
Substance P, nerve growth factor, bradykinin, ATP, histamine, serotonin, prostaglandins, leukotrienes, acetylcholine.

Question 12

Substance P

Answer 12

Released by the nerve fibre and causes leakage of plasma to allow macrophages and immune cells to access the damaged tissue.

Question 13

CGRP

Answer 13

Released from nerve fibres and activates nociceptors and produces dilation off the peripheral blood vessels to bring more blood into the area.

Question 14

Histamine

Answer 14

Released from mast cells after tissue injury and activates polymodal nociceptors.

Question 15

ATP, serotonin, ACh

Answer 15

Released from damaged endothelial cells and platelets and act to indirectly sensitise nociceptors by triggering the release of prostaglandins and bradykinin from peripheral cells.

Question 16

Bradykinin

Answer 16

Active pain producing agent and it directly activates pain fibres and increases the synthesis of prostaglandins.

Question 17

Prostaglandins

Answer 17

Released from damaged cells by the activity of the COX enzyme.

Question 18

Parallel pathways in anterolateral system

Answer 18

A-delta fibres = larger, myelinated axons carry sharp, fast pain.
C fibers = thinner un-myelinated axons carry slower, burning pain and also itch.

If you get hit with a hammer, will feel the hit, mediated by the dorsal pathway with thick, fast axons. Then first wave of pain mediated by A-delta fibres, and finally the slower burning sensation carried by the C fibres.

Question 19

A-delta fibres

Answer 19

Synapse onto neurons in the more superficial layers of the dorsal horn.

Question 20

C fibres

Answer 20

Synapse onto neurons in the intermediate layers.

Question 21

Spinal cord

Answer 21

Has sensory dorsal horn and motor ventral horn. Info is being sent to specific spots, likely preserving the specificity of the stimulus.

Question 22

Axons of DRG neurons

Answer 22

Release both glutamate and peptides; glutamate is fast acting and peptides serve to modulate the response to glutamate and make it either stronger or longer.

Question 23

Peripheral pain properties

Answer 23

Can be learned and also controlled and modulated. If you have repeated painful stimuli, the circuitry of your spinal cord becomes potentiated. Even a small stimulus trigger will then produce a large painful response. Synapses become more efficient.

Question 24

Long-term potentiation in nociceptive pathways

Answer 24

Occurs by recruiting more NMDA receptors, which increase the influx of Ca at the synapse. Neurotrophins (NGF and BDNF) are also implicated, serving as molecular signals for the synapse to get stronger. Bind to TrKA receptors on 1º nociceptors, triggering localised post-translational changes in expression of ion channels that increase nociceptor excitability. Learning = avoid pain at all cost.

Question 25

Pain info vs touch info

Answer 25

Pain info crosses at the dorsal horn whereas touch info crosses in the medulla.

Question 26

Five major ascending anterolateral pathways

Answer 26

1. spino-thalamic 2. spino-reticular 3. spino-mesencephalic 4. spino-hypothalamic 5. cervico-thalamic All contribute to the central processing of nociceptive info and are thought to generate diff types of pain sensations.

Question 27

Spinothalamic tract

Answer 27

Most prominent tract and responsible for discriminative pain - you can identify exactly what hurts. Axons of nociceptive and thermosensitive neurons from the dorsal horn, terminating in the ventral thalamic nuclei, which then project to the primary somatosensory cortex, then to regions adjacent to the dorsal pathway. Lesioning this tract can result in a marked reduction in pain sensation on the side of the body contralateral to that of the lesion; electrical stimulation of it elicits the sensation of pain.

Question 28

Cervicothalamic tract and other tracts

Answer 28

Thought to convert the affective and emotional character of pain. Cervicothalamic tract does the same job for the nociceptive info from the head. The other tracts, terminating in the midbrain and hypothalamus, end up projecting to the amygdala and the medial thalamic nuclei, and then to the cingulate and insular cortex. = processing emotional info.

Question 29

Two main pathways in anterolateral system

Answer 29

Direct thalamocortical one, involved in sensory discriminative pain info and an indirect one, going through the midbrain, involved in the affective motivational pain.

Question 30

Referred pain

Answer 30

We have pain receptors in our viscera, like our heart or our lungs. Somatosensory cortex somehow does not have a region devoted to them. That info then gets sent our to the spinal cord and it uses the same circuitry that the spinal cord uses for the skin of the corresponding dermatome. So if this dorsal root neuron fires it could be either viscera or body region that is injured -- cannot know.

Question 31

Phantom pain

Answer 31

Partly due to the amputation, the dorsal horn neurons are more excitable and lead to spontaneous pain. Even under general anaesthesia the spinal cord experiences the surgical procedure, so amputation now includes interventions that block dorsal horn neurons to ensure they don't learn and become excitable. Phantom pain is also generated by the cortex; in fMRIs, saw that parts of the cortex are active during the pain flare, areas of the cortex that were originally devoted to the missing hand or limb are now easily triggered by all kinds of stimuli like touching the lip.

Question 32

Descending control

Answer 32

Efferent pathways that go back to the skin; flow down from the somatosensory cortex to the amygdala hypothalamus, to the midbrain and end up back in the dorsal horn of the spinal cord. Regulate the transmission of nociceptive info and employ a wealth of different NTs that can exert both facilitatory and inhibitory effects on activity in the dorsal horn, gating the incoming pain. Local interneurons in the dorsal horn are activated by the descending efferent projections and release endogenous opiates which block the activity of the dorsal neurons that receive the C fibres. Local circuits within the dorsal horn can also modulate the transmission of pain to higher centres. Rubbing your skin by. lesion to make you fell better; activate low threshold mechanoreceptors in the skin, which then synapse on inhibitory neurons in the dorsal horn, which contact the neurons receiving C fibre inputs and diminish the effect of nociceptor cells.

Question 33

Endogenous opiates

Answer 33

Endorphin, enkephalin. Synthesised by neurons in the brain and released as NTs. Open K+ channels, hyper polarise neurons or hyper polarise synaptic terminals to prevent transmitter release.