Nociception and Pain Flashcards
what are the classic 5 senses?
vision, hearing, touch, taste and smell
what other senses are there?
proprioception, itch, temperature, balance, visceral sensations, magnetosensation, electrosensation, pain
what is pain?
an unpleasant sensory and emotional experiences associated with actual or potential tissue damage
how is pain an evolutionary function?
- promotes survival
- want to avoid the stimuli
- requires aversion or treatment
what can happen if individuals have pain insensitivity?
- severe injuries
- leads to permanent tissue damage
what is nociception?
emotional component to pain
- pain is subjective
how is nociception different to other senses?
has both affective and emotional component
- nociception is not the same as pain
what are the 3 general nociception stimuli?
- chemical
- mechanical
- thermal
what is nociception detected by?
- nociceptors
give an overview of nociceotirs.
- dendritic free nerve endings of primary sensory neurons
- nociceptors fire action potentials in response to nociceptive stimuli
- located in tissues (different senses)
where do nociceptors send projections?
- send projection to the dorsal horn in the spinal cord
- make connections in the grey matter
where are the cell bodies located?
- mainly in the dorsal root ganglia (DRG)
- can be connections with motor neurons
what are the nociceptive fibres?
- thermal (activated by extreme temperatures)
- mechanical (activated by intense pressure to the skin)
- polymodal (activated by high intensity mechanical, chemical or thermal)
what are A fibres affected by?
mechanical and thermal
what is the structure of A delta fibres?
- small diameter
- 5-30m/s
- thinly myelinated
- slow
what are C fibres affected by?
polymodal
what is the structure of C fibres?
- small diameter
- unmyelinated
- <1m/s (very slow)
what do C and A delta fibres give rise to?
- first and second pain
- 3 classes of receptors are widely distributed and co-activated
- sharp pain = first pain (A delta)
- burning/ache = second pain (C fibres)
where are A delta and C fibres found?
the whole of the skin
apart from the webs between your fingers and the testicles
what are TRP channels?
transient receptor potential channels
what is the structure of TRP channels?
- 6 transmembrane protein with a gate
- variation in N and C termini defines physiological properties, attach to different proteins etc
- structural similarities but different TRPs mediate different functions
what is the function of TRP channels?
- in response to a stimulus it gates and allows Ca2+/Na+ through at different rations (causes a depolarisation)
what are the different stimuli of TRPs?
- conformational change (temp, mechanical, pH)
- ligand binding (endogenous and exogenous ligands)
- intracellular (Ca2+)
- an individual channel can be activated by >1 stimulus type
what is the structure of TRPV1?
- 6 transmembrane domains
- 3 anchor binding motifs (to cytoskeleton)
- phosphorylated by both protein kinase A and B
what is the vanilloid receptor?
- eg capsaicin by chilli
- chilli is somatosesory (senses heat)
what are TRPV1 channels activated by?
- temperature >43 degrees
- acidification (H+)
- allyl isothiocyanate
- capsaicin (binds to receptor and activates it at 37 degrees)
what happens in TRPV1 KO mice when treated with capsaicin?
- inject the hindleg with the capsaicin and animals will lick it
- see how long they spend licking their paw
- as you increase the dose it doesn’t change the response of the TRPV1 KO mice
how do TRPV1 KO mice respond to thermal stimuli?
- impaired response to thermal stimuli
- use a hot plate
- wild type moves off the plate much quicker than the KO mice
what is TRPV1 responsible for?
longer lasting pain
what is hyperalgesia?
- pain over time
- if peripheral tissue is damaged it can lead to increased pain sensitivity
- leads to decreased threshold of nociceptor activation
- pain can occur in the absence of sensory stimulation
what do damaged cells (tissues) release?
- complex mix of chemicals that accumulate at the site of inury
- also theres an increased blood flow and fluid pressure
what peptides can this inflammatory soup contain?
bradykinin, substance P, nerve growth factor
what molecules can this inflamatory soup contain?
atp, histamine, serotonin, prostaglandins, leukotrenes, H+
in hyperalgesia what can generate a signal?
G protein ocupled stimuli that generates a signal that will modify the signal
what does the inflammatory soup stimnulate?
TRPV1 repcetor
- much broader region/area as the molecules spread and draw blood to the area
what is nociception at different levels of the CNS?
stimulus - sensory neuron - proccesed: spinal cord (reflex), thalamus, cortex (behavioural response and subjective experience of pain)
what is the role of the antenna of flies?
- hot and cold temperature sensing neuons
- project to separate glomeruli in protocerbrum
how is hot and cold processed in flies?
- separately
- use labelled line logic for processing temperature information in the brain
what is an experiment for testing hot and cold receptors in the brains of flies?
- bathe the lies in Ca2+ dye
- stimulate the antenna with hot and cold stimuli
- 2 sets of neurons repond to hot and cold
- project on distinct but adjacent glomeri;o
- potentially act as an integration site for accurate thermosensation
