Week 8 Pain and Tolerance Flashcards
(18 cards)
Pain definition and importance
“An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.”
Why is pain important:
It promotes of avoidance of situations which may decrease biological fitness
It promotes resting behaviour that either enhances recovery following injury or modifies behaviour so that further injury or death become less likely.
Pain Dectectors
Nociceptors:
- Specialized neurons
sensory neurons (specific to pain)
- free nerve endings
- synapse in spinal cord to ascending neurons to brain (withdraw from painful stimuli)
Nociocepter types
Nociceptors conduct electrical signal to spinal cord
A fibres
lightly myelinated
medium diameter
- First pain, fast and localised
C fibres
unmyelinated
small diameter
- Second pain, dull and poorly localised
A⍺ and Aβ fibres
(normal Proprioceptors)
myelinated
large diameter
Two paths of pain (to brain)
- to Somatosensory cortex via the thalamus
encode the sensory components
- sensory discrimination
- tell you “where” it hurts
- to ‘emotional’ cortex (insula and
cingulate) via the thalamus
encode the emotional components
- unpleasantness
- negative affect
Pain sensitisation processes
- Peripheral sensitisation:
Inflammatory response in and around injured tissue
Peripheral nerve endings (nociceptors) become more responsive to stimuli, lowering the threshold for pain perception
Hyperalgesia: noxious stimuli produce exaggerated pain sensation
Allodynia: non-noxious stimuli produce pain sensation (e.g. touching sun-burnt skin)
- Central sensitisation
Neuroplastic changes in the central nervous system
Neurons become more excitable and respond to stimuli that would normally not trigger a pain response
Persistent pain, nerve injury, or inflammation can lead to central sensitization
Peripheral sensitization
Inflammation, tissue damage (causes inflammatory response, releasing chemicals), and exposure to irritants can trigger peripheral sensitization
Release of ATP, H+ - affecting nicioceptor terminals
Neuropeptides - substance P and CGRP (released from nociocepter neurons) trigger:
-vasodilation,
-plasma extravasation (leakage of proteins and
fluid from capillaries)
-activation of Mast cells and neutrophils
“Inflammatory soup” - may not need to know
Histamine - causes vasodilation (mast cells)
Nerve growth factor (mast cells)
serotonin (platelets)
proteases (sensitizes nocioceptors)
COX enzymes - makes prostaglandin (contributes to inflammation, pain, and fever)
Neurotransmitters: substance P and CGRP
Cytokines
Modulation of the nocioceptor activation
Components of the inflammatory soup, Bradykinin, NGF and Prostaglandin feedback back to their own metabotropic receptors on the nocioceptor neurons
VR1 receptor (vanilloid receptor 1) is phosphorylated and threshold changes so opens at lower temperatures.
A sensory nerve specific (SNS) Na+ channel is phosphorylated so threshold voltage for firing is decreased, making the nociceptor more excitable
Nociceptors become hypersensitive to stimulation - peripheral sensitisation
Why increase pain sensitivity?
Reminds you that you have hurt yourself
Protecting injured area for recovery without further damage
Congenital disorders where people have no pain perception:
- no signals to indicate to avoid painful stimulus
- low life expectancy
Central sensitization “wind up pain”
- Nociceptor afferents release glutamate and substance P in spinal cord - activate the spinothalamic neurons
- Repetitive firing results in neuroplastic changes in the spinal cord strengthening the synapse
- so less stimulation will create a larger signal - NMDA receptor activation leads to influx of Ca2+.
Substance P activates NK1 receptor (metabotropic).
- phosphorylation of NMDA and AMPA receptors
- receptors become more responsive to glutamate
- neurons more excitable (long term potentiation) - Substance P diffuses to other synapses - so “wind up” can spread causing a generalized sensitization to painful stimuli
What you should know from part 1:
The underlying mechanisms controlling pain signals and our perception of them.
How nociceptors respond to a variety of noxious stimuli
The neuronal projections carrying information about the painful stimulus to and from the brain
Dual projection (fast and slow) to spinal cord
Dual projection onwards to forebrain
‘where’ (somatosensory cortex)
affective components (insula, cingulate and amygdala)
How and why the body modulates pain signals
Peripheral sensitization
Central sensitization
Gate Control Theory
a “gate” in the spinal cord can modulate or block pain signals from reaching the brain, influenced by both large and small nerve fibers and brain processes.
Treatment of burn patients
- Changing dressings, physiotherapy etc. very painful
- Opioid treatments but issues with dosing/tolerance etc.
- Virtual reality environment (snow world), reduced activity in pain processing areas of the brain
Patient’s pain ratings reduced by 30-50%
Reduction in time spent thinking about pain, pain intensity and in how unpleasant they found the pain.
Other internal mechanisms to decrease pain
Stress induced analgesia
(Example –soldiers escaping from danger with bullet wounds – don’t feel pain till in safety)
Adaptive response to down-regulate pain
Central mechanism triggers descending regulation of pain circuitry to inhibit pain signals arriving in the
brain
One mechanism involves the release of endogenous opioids - naloxone challenge (opioid antagonist) blocks the analgesic effect.
Descending modulation of spinal neurotransmission
somatosensory cortex via thalamus to midbrain -> medulla -> spinal cord -> dorsal horn of spinal cord ->nocioceptive neurons
Brain overrides pain signals switches them off in spinal cord
Opioids acting at inhibitory metabotropic receptors
Drugs to stop pain
Opiates - agonist of endogenous opiod system - taps into bodies own pain relief system
Capsaicin - agonist of TRP channels
Electrical stimulation
Placebo
Acupuncture
Non Opiods
Possible mechanisms leading to chronic pain
Chronic or persistent pain is pain that lasts longer than 12 weeks, or beyond the natural healing time.
Peripherally
- sensitisation of peripheral neurons
- increased activity of damaged axons and sprouting
Centrally
- hyperexcitability of central neurons
- reorganization of synaptic connectivity in spinal cord
- disinhibition - removal of tonic descending inhibitory control
Management of chronic pain
Complicated as many other associated problems that need to be treated in conjunction
e.g. primary disease
depression
sleep disturbance
fatigue
80% depressed people present at clinic with physical symptoms
Drugs for chronic pain include, tricyclic antidepressants,
anticonvulsants, NMDA antagonists, cannabinoids etc.
