Perception of Pain Flashcards
What does perception of pain depend on?
Situation
Emotion
Genetic susceptibility
Previous experience
Which parts of nociceptive nerves detect painful stimuli?
Free unspecialised nerve endings with ‘pain channels’ inserted in the membrane
What is the most common pain channel?
Transient Receptor Potential family of channels (TRP)
What are pain channels sensitive to?
O2 pH Osmolarity Valinoids (capsicum) Heat
Name 6 substances that can sensitise pain channels
Substance P Bradykinins Serotonin pH ATP NO
What s the structure of a pain channel?
6-unit transmembrane protein with a basket of regulatory complexes in the cytoplasm
What effect do extreme temperatures have on Transient Receptor Potential Vanilloid (TRPV) channels?
Allow entry of sodium and calcium causing depolarisation leading to AP
How do CGRP and substance P increase sensitivity to pain?
Recruit silent receptors which increase summation in the dorsal horn
How does histamine cause sensitisation?
Acts on blood vessels
What is the role of bradykinin in pain?
Acts on pain receptors directly and causes an increase in prostaglandins
Why does weight lifting cause muscle ache?
Tissue damage produced H+ which causes muscle ache
How do NSAIDS such as aspirin prevent pain?
Inhibit COX enzyme which is involved in the production of prostaglandin E2
Describe A-delta fibres
Myelinated
Sharp 1st pain
Detect extreme temperatures
Describe C fibres
Unmyelinated
Secondary slow pain
Burning or aching pain
Thermal and chemical stimuli
Which neurotransmitters do nociceptive fibres release?
Glutamate
Substance P
CGRP
What effect does peripheral neurotransmitter release have?
Red flare
Tenderness
What are the 3 physiological signs of pain and what is their physiological cause?
Calor (heat) - local hyperaemia
Rubor (redness) - local hyperaemia
Tumour (swelling) - plasma extravasation
Which system is the ascending pain system?
Anterolateral
Where does descending pain regulation occur?
Periaqueductal gray
What information is carried in the paleospinothalamic pathway?
Slow burning
What information is carried in the neo-spinothalamic pathway?
Fast sharp pain
Where does the neo-spinothalamic pathway terminate?
VPL of thalamus
Where does the paleo-spinothalamic pathway terminate?
DM and intralaminar nuclei of thalamus
Where does the discriminating pathway project?
Primary somatosensory cortex
Where does the undiscriminating pathway project?
Limbic system association cortices
What is the role of the spinoreticular pathway?
Motor response and ascending arousal
Describe the mechanism of wind up
When WDR fire at high frequency, they open NMDA channels
Calcium influx increases number of Na channels and blocks K channels
Resting potential closer to threshold
==> more sensitive cell (amplifies pain signal)
What is the purpose of wind up?
Priority salience
Protection from further injury
Memory
Which directly causes the variation in cell sensitivity by WDR neurones?
Intensity of C fibre stimuli
Describe pain modulation at the dorsal horn
Strong activation
- C fibres stimulate WDR neurones and inhibit the inhibitory interneuron
Weak activation (i.e. when you rub a bump)
- AB fibres activate inhibitory interneuron and WDR neurons
- Inhibitory interneuron inhibits WDR neurons which prevents sensitisation
Name an endogenous substance that can provide descending analgesia
Enkephalin
Why is the basis behind the high efficacy of opioids?
Can act simultaneously at all levels of the pain pathway via the endogenous opioid system
Name 3 classes of endogenous opioids
Endorphins
Encephalins
Dynorphins
Name 2 areas of the limbic system involved in pain
Cingulate gyrus - activated when we see others in pain
Insula - emotional, motivational and modulatory
Give examples of persistent neuropathic pain
Causalgia
Phantom limb pain
Carpel Tunnel Syndrome
Peripheral neuropathy
What is allodynia?
Painful reaction to non-noxious stimuli like light touch
What is summation?
Repeated low innocuous stimuli causing increasing intensity of response
What are dysesthesias?
Burning or shooting pain without stimulation which can sometimes be associated with thalamic syndrome
What causes central maladaption?
Increase in NMDA receptors
Descending modulation of inhibitory interneurons leading to reduced inhibition of WDR
What is central maladaption?
Long term changes in the structure of synapses in the dorsal horn of spinal cord leading to sensitisation
What is the proposed cause of headache?
Irritation of venous sinuses, meninges and capillaries
Why do you get a headache after excessive alcohol consumption?
Alcohol irritates meninges
Dehydration
Why does low CSF cause headache?
Brain settles onto the base of the skull causing deformation of dura
Describe the mechanism of referred pain
Pain signals and cutaneous signals enter spinal cord at same point
Cross talk in dorsal horn can cause signals from viscera to get picked up by ascending neurons that are mapped to the dermis
Which NT does the PAG release to modulate pain in the dorsal horn?
NA
Which NT does the PVN and raphe nucleus release?
5-HT
