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Neuroscience > Lecture 9 - Sensation and sensory processing, pain > Flashcards

Lecture 9 - Sensation and sensory processing, pain Flashcards

1
Q

Give an overview of the organisation of the nervous system

A
  • Incoming stimulus is revieced by the sensors - sensory receptors in the PNS
  • Afferent neurons from the sensory receptors synapse onto interneurons in the integrating centres in the CNS(varies: brain - human, ganglion - squid)
  • Interneurons in the integrating centres synapse with efferent neurons which synapse onto effector organs (muscles, glands) in the PNS through output pathways to result in a response
  • feedback from PNS to the integrating centres
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2
Q

How is the basic plan of the organisation of behaviour in the nervous system variable?

A

Difference in the distribution of the integrating centre, CNS or in distributed ganglia

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3
Q

What is sensation and what does it involve?

A

Sensation involves the ability to transduce, encode, and perceive information generated by stimuli arising from both the external and internal environment

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4
Q

What are the types and examples of input stimuli of the NS?

A 
Mechanosensation
-touch, movement, imbalance, sound
Thermosensation
-temperature
Photosensation
-light
Nociception (combination of a number of sensations [mechanosensation, chemosensation, thermosensation]
-pain
Chemosensation
-taste, smell, moisture (also osmosenasation)
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5
Q

What is the anatomy of detection of incoming stimuli?

A

Have either dedicated organs or dispersed receptors

  • tuned to life strategy of an organism
    e. g.
  • mouse mixture of chemosensation and mechanosensation
  • insect mostly chemosensation
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6
Q

What are the features of TRP channels?

A
  • superfamily of ion channels
  • found across phyla
  • often have conserved role
  • six transmembrane domains (with varying regions of homology)
  • intracellular and extracellular structures change and are subject to modulation
  • characterised by a conserved TRP domain
  • permeability to cations
  • single channel can be activated by disparate mechanisms
  • critical roles in responses to all major classes of external stimuli
  • expressed in sensory neurons
  • work as heteromultimers in supramolecular complexes (channelosome)
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7
Q

What is TRPY?

A
  • found in yeast (aka not in neurons)

- required for osmotic resisitance

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8
Q

What is TRPML?

A
  • expressed globally and localised in lysosomes
  • mutations give risse to the childhood neurodegenerative disease ‘Mucopolysaccharidosis IV (MPS IV)
  • where lysosomes do not function well and ‘store’ undegraded material
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9
Q

What is a channelosome?

A

-when the intracellular and extracellular domains of TRP channels bind to other proteins to generate a complex that can be important to function

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10
Q

What can TRP channels be gated by/

A
  • many endogenous and exogeneous ligands
  • conformational change (temperature, mechanical)
  • Ca2+ status (acts as a store operated Ca2+ channel)
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11
Q

What is nociception?

A

The sensation of pain

-purely physiological

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12
Q

What is the role of nociception?

A

To alert to impending injury or to trigger appropraite protective response
-transduction of noxious stimuli (thermoceptive pain, mechanoreceptive pain, chemoreceptive pain) and the cognitive and emotional processing

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13
Q

Where is the sensory modailty of nociception located?

A

PNS
CNS
ANS

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14
Q

What are nociceptors?

A

A class of neuron (proposed by Sherrington) activated by stimuli capable of causing tissue damage.

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15
Q

What is hyperalgesia?

A

increased sensitivity to pain, usually associated with injury

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16
Q

What is the circuitry of primary sensory neurons involved in nociception in the PNS?

A

primary sensory neurons in the dorsal root ganglian project dendrites to peripheral tissue

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17
Q

What are the two types of primary sensory neurons involved in nociception in the PNS?

A

C Fibres
Aδ Fibres
(type I and II - mechanosensitive, mechanothermal)
-have morphological and physiological differeces
-both express the vanilloid receptor (VR1 or TRPV1)
-respond to rises in temperature and capsaisin and extracellular acidification

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18
Q

What are the features of Aδ fibres?

A
  • fast, compared to C fibres (20m/s)
  • two classes, mechanosensative and mechanothermal
  • express the vanilloid receptor (VR1 or TRPV1)
  • respond to rises in temperature and capsaisin and extracellular acidification
  • causes the immediate response to pain
  • lightly myelinated
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19
Q

What are the features of the C fibres?

A
  • polymodal
  • express the vanilloid receptor (VR1 or TRPV1)
  • respond to rises in temperature and capsaisin and extracellular acidification
  • major nociceptive receptor due initally to heat, then to acidification due to inflammation giving rise to longer term responses (heat has two componants, fast pain and slow pain)
  • mediate slow, burning pain
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20
Q

What are other A fibres (aside from Aδ fibres) and what are their features?

A 
Aβ (touch)
Aα (proprioception)
-large diameter (linked to high speed of conductance)
-myelinated neurons
-reponsive to non-nociceptive stimuli 
-very fast response
21
Q

What are other C fibres, not involved in the slow pain response, and what are their features?

A 
Ultra-slow histamine selective fibres
-covey itch (pruritogenesis)
Tactile C-fibres
-low threshold fibres responding to sensual touch
CT fibres found in hairy skin
C-mechano- or metabo-receptors 
-muscle cramp and fatigue
22
Q

How can nociceptors be cross modal and what does this mean?

A

e. g. -activated by multiple simuli (thermosensitive and chemosensitive)
- by expressing multiple TRPs
- but when activated perception is the same (Labelled line theory)

23
Q

What is the labelled line theory?

A

Pathways carrying sensory information are specific for one stimulus

24
Q

What is an alternative to the labelled line theory and what is this?

A

Pattern theory

  • some sensory systems (esp. taste and olfaction) integrate information across multiple primary afferents
  • some types of primary afferents are multi-modal (more than one snesation can be evoked b activation)
  • an ascending pathway can convey sensory information by altering the temporal pattern of action potentials among multiple primary afferents
  • Pattern of activation forms the basis of perception
25
Q

In what structures do the nociceptive neurons arise?

A

The dorsal root ganglion

26
Q

What is the order of response to nociceptive stimuli?

A

1-reflex withdrawal

Followed by higher order behavioural responses

27
Q

What is the capsaicin receptor?

A

TRPV1

28
Q

What is capsaicin?

A

The active ingrediant of capiscum or chilli peppers, produced by plants to prevent ingestion, a mechanism to protect seeds
-vanilloid

29
Q

What is the strength of capsaisin measured in?

A

Scoville units
e.g. jalepeno 5,000 schoville units
habernero 300,000 schoville units

30
Q

How was the TRPV1 capsaisin receptor identified and its function found?

A

-expression cloning of the receptor by Caterina (1997)
-KO mice used to identify the in vivo function of the receptor, Caterina (2000)
FOUND
-Mice lacking TRPV1 are deficient for vannilois ellicited pain, thermal sensation and tissue injury induced thermal hyperalgesia

31
Q

What can TRPV1 activity be modulated by (both inhibition and stimulation) ?

A
  • capsaisin (similar structure to anandamide but acts antagonistically to stimulate the TRPV1 channel)
  • anandamide (inhibits activity TRPV1 )
  • heat >43*C (activates)
  • camphor (activates)
  • piperine (activates)
  • garlic (activates)
32
Q

What is anandamide?

A

An endo-cannabinoid (shuts off TRP channels)

33
Q

What is the relationship between anandamide and capsaisin?

A
  • Anandamides inhibit TRPV1 receptors
  • Capsaicin has strucutral similarities and can bind to the same sites to antagonisically stimulate the channel
  • channel normally gates at >42*C
  • when capsaisin bound gates at 37*C
34
Q

Why might plants have evolved the synthesis of chemicals such as capsaisin and pipericin?

A

To subvert the function of nociceptors and protect their seeds from ingestion

35
Q

What synthetic molecules might be possible to use as an analgesic?

A

Synthetic amandamide mimics

36
Q

What ligands can a TRPV1 channel be activated and sensitised by?

A

Activated
-acidification near the outer pore region
-double knot toxin from the Earth Tiger tarantula (locks pore into open configuration)
-capsaisin (lowers the temperature of activation from 43 to 37)
Sensitised
-signal transduction mechanisms (on cytoplasmic loops) e.g. Ca2+, PKA, PLC, PIP2,

If activated by any the sensory effect is the same (pain-activation results in activation and neuronal stimulation)

37
Q

Why is the sensation of acidifcation by TRPV1 important?

A

Damage and the inflammatory soup

-long term perception of pain (hyperalgesia)

38
Q

How does injury cause longer term activation of nociceptors by sensitisation?

A

Through damage and the ‘inflammatory soup’
-injury has an initial stimulus causing an immediate response, followed by a longer term sensitisation of the injury site mediated by sensitisation of some of the same TRP channels that transduced the original response

  • Damage recruits an immune response (cells of the immune system and an inflammatory response)
  • an increase in blood flow (heat pressure)
  • acidification, reactive oxygen species
  • TRPA1 sensitive to: ROS, chemical irritants, products of tissue injury and inflammation, G-proteins activated by bradykin receptors, raised calcium (activation of TRPV1)
  • leads to a sensitized response to nociception
39
Q

What is TRPA1 involved in, activated by and sensitised by?

A

Involved in the ‘inflammatory soup’ and the longer term actvation of nociceptors by sensitisation
Activated by:
-ROS
-chemical irritants, particularly products of tissue injury and inflammation
Sensitised by:
-G proteins activated by bradykinin receptors
-raised calcium (from activation of TRPV1)

40
Q

What is TRPA1 in insects?

A

a mechanosensor
-if TRPA1 is a mechanosensor, then inflammation caused by injury will produce pressure potentially contributing to TRPA1 activation

41
Q

What is the pathway involved in nociception?

A

Afferent nociceptive fibers (first order neuron) synapse to the dorsal horn (spinal cord)

  • DH nociceptive fiber (located in the periphery) = second order neuron
  • cells in the dorsal horn are divided into physiologically distinct layers, different fiber types form synapses in different layers
  • after first order neurons synapse with specific structures in the DH the second order neurons send their information via the anterolateral system to the thalamus
  • information is then processed in the ventral posterior nucleus and sent to the cerebral cortex in the brain
42
Q

Are nociceptive neruons dynamic or stable?

A

Dynamic

-constantly changing over time

43
Q

Where can modulation of the sensory system occur?

A
  • modulation in the dorsal horn of the spinal column
  • at higher levels of communication between second order neurons
  • or can feed down through descending inhibitory pathways to affect local circuits by the modification of primary neurons (alters responses of reflex circuits)
  • Descending system alters responses of reflex circuits
44
Q

What are involved in thermosensation?

A

-non-nociceptive thermosensory neurons

45
Q

What are the features of thermosensory neurons?

A
  • rapidly conducting
  • the tuned sensitivity of TRP channels to ranges of temperatures ensures efficient detection across a range of temperatures for thermosensation
46
Q

What fibres express both TRPV1 and TRPA1 channels?

A

C-fibres in the periphery

47
Q

What is the first site of sensory integration?

A

the stratification within the dorsal horn of the spinal column

  • major input to the CNS
  • represents second order processing, immediate response and modulation of a signal
48
Q

Give an experimental example of second order structures as the site for stimulus integration

A

Coding of temp in the drosophila brain

  • Identification of TRP channels reacting to cold and warm temperature identified
  • expression patterns showed similar distribution patterns in the antennae sending projections to neighbour glomeruli
  • Glomeruli are second order structures that integrate information

Neuroscience (12 decks)

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