Nociceptors And Peripheral Sensitisation Flashcards
1
Q
What is the definition of pain?
A
An unpleasant sensory and emotional experience associated with actual or potential tissue damage
2
Q
What is Nociception?
A
- The neural processes of encoding and processing an actual or potential tissue-damaging event
- Nociception is sensory dimension of pain and is not necessary to experience pain
- peripheral Nociception can occur without the perception of painful sensation
3
Q
What is the Mature Organism Model (MOM) for nociception?
A
- tissue damage is the input
- scrutinised by brain
- brain experiences/beliefs analyse input
- output/response goes back to the tissue and environment
4
Q
How does the pain (nociceptive) pathway work?
A
- tissue damage
- activation of PNS through nociceptors
- transmission to brain via dorsal root ganglion
- activation of CNS at spinal cord (Spinothalamic - pain/heat or DCML - vibration/touch/joint position sense)
- input sent to thalamus in brain + cortex to identify where pain is coming from via nociceptive facilitating neurons
- output from brain via nociceptive inhibiting neurons back down the spinal cord
- modulation of pain
5
Q
What are the different types of nociceptive stimulus?
A
- temperature e.g. heat/cold
- chemical e.g. acid
- pressure e.g. hit with hammer/injection/touch
6
Q
What are the different types of (nociceptive )nerve fibres and what do they transmit?
A
- a alpha => proprioception = myelindated = diameter (d) = 13-20 = aeroplane (80-120m/s)
- a beta => touch = myelindated = d = 6-12 = racing car (35-90m/s)
- a delta => mechanical + thermal = d = 1-5 = myelinated = Tour de France (5-40m/s)
- c = (silent) mechanical + thermal + chemical = d = 0.2-1.5 = non-myelindated = walking (0.5-2m/s)
7
Q
Where does the medial pathway go through for nociception?
A
- archispinothalamic tract
- passes through medial thalamus
- to limbic system producing emotional reactions to pain
8
Q
Where does the lateral pathway go through for nociception?
A
- neospinothalamic tract
- passes through lateral thalamus
- goes to somatosensory cortex
- gives discriminating aspect of pain (location)
9
Q
What are nociceptors?
A
- travel through the dermis to the epidermis
- free nerve endings in the epidermis
10
Q
What is the receptive field of a neuron?
A
- the region that can be stimulated and affects the neuron’s response
- neurons have fixed receptive fields
11
Q
What does it mean for nociceptors to be multimodal?
A
- contain both c-fibres and a-delta fibres
- majority of nociceptors are sensitive to both mechanical and heat stimulus (CMH = C fibres or AMH = a delta fibres)
- mechanically insensitive afferents (MIAs) only become sensitive to touch when inflamed (neurogenic inflammation)
- C fibres are ‘silent’ nociceptors responding only when injured (allodynia)
12
Q
Explain first and second pain in Nociception
A
- faster relaying a-delta fibres cause 1st pain sensation
- delayed slower sensation c-fibres cause second pain
- a-fibres recover faster from fatigue than c-fibres
- tonic pressure pain due to c-fibre MIAs (mechanically insensitive afferents)
13
Q
Explain what it means for Nociceptor so to have firing thresholds
A
- nociceptors have fixed thresholds of firing, however this varies between nociceptors e.g. heat pain threshold is variable due to neurogenic inflammation
14
Q
What is neurogenic inflammation?
A
- initiation of inflammation in response to tissue damage e.g. bradykinins, histamine, serotonin, cytokines, neutrophils, mast cells
- nociceptors activated by tissue damage
- neuropeptides (substance p, CGRP) from vesicles in nerve endings are released into tissues
- neuropeptides (substance p, CGRP) act on capillaries, mast cells and smooth muscle
- cascade of events similar to acute inflammation e.g. vasodilation, oedema, heat, muscle spasm
15
Q
What happens during neurogenic inflammation at the axon?
A
- Nociceptor activated by tissue insult
- normal alkaline-phosphate inflammatory reaction initiated (healing response)
- speacialised area of axon hillock causes antidromic impulse back to periphery
- can also begin at proximal nerve terminal i.e. along the entire nerve length
- peptidergic = release of neuropeptides e.g. substance P & CGRP
16
Q
What is the normal transmission of neurogenic inflammation and how can this lead to peripheral sensitisation?
A
- injury to tissue
- area of red flare contains neuropeptides which can lead to changes in tissue caused by back dumping (retrograde transport) of substance p/CGRP
- signal sent to dorsal column up to brain -> central neuron remains unchanged
- threshold of firing lowered => increased sensitivity => caused by peripheral sensitisation
17
Q
How is this clinically relevant?
A
- misdiagnosis of cause of pain due to perceived tenderness and swelling of local tissue e.g. referred knee tenderness from hip arthritus
- referred change in tissue structure e.g. increased joint destruction in rheumatoid arthritus
- e.g. eczema, interstitial cystitis (bladder pain syndrome), fibromyalgia, inflamed spinal segments
18
Q
Describe hyperalgesia
A
- painful sensation from a normally painful stimuli i.e. noxious
19
Q
Describe allodynia
A
- painful sensation from a non-noxious stimuli i.e. innocuous
20
Q
Name the 2 types of molecular receptors
A
- gene protein coupled receptor (GPCR) - receptor in the phospholipid bilayer of cell
- ligand gated ion channel (LGIC) - channel through phospholipid bilayer of cell
21
Q
What happens to the 2 types of molecular receptors (GPCRs & LGIC) in peripheral sensitisation?
A
- gene protein coupled receptors (GPCR) lower firing threshold of ligand gated ion receptors (LGIR)
- neurotransmitter lands on GPCR and binds to receptor on outside of cell
- on inside of cell internal transduction pathways and cellular responses are activated e.g. serotonin, histamine, prostaglandin receptors
- lead to a messenger that can open or close LGIC (ion channels) letting in substances from outside the cell inside, or inside the cell outside
22
Q
How does up regulation of existing receptors contribute to sensitisation?
A
- tissue damage
- persistent activation by endogenous agonists (internal chemical agonists)
- sensitisation by inflammatory mediators
- inherited polymorphisms of signal trandsducers (inflammatory chemical cascade)
- changes in membrane excitability (GPCR + LGIC)
23
Q
What contributes to sensitisation?
A
- production of new receptors (back dumping of nociceptors)
- up regulation of new receptors
-> therefore you have an injury => results in inflammation
-> internal efferent chemical signals increase inflammatory stimulus
-> there are more nociceptors due to back dumping => increasing stimulus and further increasing inflammation => peripheral sensitisation
24
Q
What leads to hyperalgesia?
A
- sensitisation of nociceptors leads to mechanical hyperalgesia (painful sensation from a normally painful stimulus)
25
What is peripheral sensitisation?
- tissue injury causes damage to cells locally e.g. a burn
- local area becomes sensitive to both heat and touch
- area adjacent becomes sensitive to touch => mechanical hyperalgesia
- produces ‘red flare’ response due to breaches of nociceptors dumping out neuropeptides (substance P and CGDP)
26
What is the clinical relevance of peripheral sensitisation?
- tissue damage + inflammation leads to peripheral sensitisation
- firing threshold of nociceptors lowered (increased sensitivity)
- C fibres (silent nociceptors/MIAs) become activated
- acute tissue damage will be red, hot and swollen
- sensitive to both mechanical and heat stimuli = heat hyperalgesia
- e.g. sunburn leads to pain with warm water, whereas ice and cold coverings are soothing
27
What stimuli do nociceptors detect?
- a delta = mechanical + heat
- c = mechanical + heat + chemical
28
What is a free nerve ending?
- nociceptor that end in the epidermis and travel through the dermis
29
How does a free nerve ending differ from other sensory nerve endings?
- are encapsulated
- have no complex sensory structures
30
What are the main differences between nociceptors and non-noxious sensory neurons?
- non-nociceptive neurones => respond to non-noxious, low intensity, normally non-painful stimuli
- nociceptive neurones => respond to noxious, high intensity, normally painful stimuli
31
What is neurogenic inflammation and how does it come about?
- localised stimulation of the PNS
- injury to tissue
- results in inflammatory cascade e.g. bradykinins, histamine etc. which is detected by nociceptors
- nociceptors release substance P and CGDP into surrounding tissues, further increasing inflammation
- signal sent up to brain to make sense
32
What are the characteristics of nociceptive pain?
- sensitive to heat + pressure
- sharp, aching, throbbing
