Anatomy & Physiology of Pain Flashcards
Define transduction
Noxious (potentially harmful) stimuli translated into electrical activity at sensory nerve endings
Define transmission
Propagation of impulses along pain pathways
Define perception
Discrimination/affect/motivation
Define modulation
Stage 1-3 are modified (positive/negative)
What are the 4 physiological mechanisms of pain?
1) transduction
2) transmission
3) perception
4) modulation
Define pain?
unpleasant sensory and emotional experience associated with actual/potential tissue damage or described in terms of such damage
What is a cerebral construction?
Perception that usually is associated with nociceptive information
- Pain is an example of this
What are nociceptors?
Sensory neurons that transduce potentially harmful stimuli
Mainly through A-delta and C fibres
What is the difference between A-delta and C fibres?
A-delta fibres are responsible for fast pain (thermal and mechanical), sharp pricking pain,
whilst C fibres are responsible for slow pain, burning pain, autonomical effects, misery
How do nociceptors respond to stimuli?
Have receptor proteins which allow response to tissue-damaging stimuli
When are the different nociceptor receptor proteins present?
TRPV1/2 - open at high temperatures
TRPM8 - open at very low temperatures
ASIC3 - present in skeletal and cardiac muscle (detect pH change with ischaemia - acid sensing)
What is difference in the response of A-delta nociceptors and C fibre nociceptors?
A delta - recognise precise localisation of stimulus = reflex withdrawal
C fibres - peptidergic C fibres release peptides peripherally (substance P) = promote inflammatory responses/healing/thermal nociception OR peptide-poor C fibres = itch, crude touch
What are the 2 main genetic defects associated with pain?
- loss of transduction/transmission
- loss of C fibres
What genetic defect causes loss of transmission?
Loss of sodium channel subunit
Causes congenital indifference to pain
What genetic defect causes loss of C fibres?
Congenital insensitivity to pain with anhydrosis
What are causes of lack of pain fibres?
Fibres may have shortened life span
- secondary consequence of infection
- diabetes causing ischemia of fibres
What do the nociceptive fibres innervate?
C fibres directly innervate lamina I and indirectly via interneurons to lamina II and V
A-delta fibres directly innervate lamina I and V
What do laminae V projection neurons receive input from?
Convergence as direct input from A-beta fibres (touch) and C fibres (interneurons) and direct A-delta innervation
- known as wide dynamic range cells
What is the pathway of the anterior/neo spinothalamic tract?
- decussate to travel in the anterior spinothalamic tract
- innervate ventral posterior lateral (VPL) and ventral posterior medial (VPM) nuclei of the thalamus
- also innervate ventral posterior inferior nuclei of thalamus
- also innervate central lateral nuclei of the thalamus
- also innervates somatosensory thalamus
In the anterior/neo spinothalamic tract, what do the central lateral nuclei of the thalamus project to?
- To the anterior cingulate cortex -> emotion/motivation
- To the prefrontal cortex and striatum -> cognitive function and strategy
In the anterior/neo spinothalamic tract, what do the VPL and VPM nuclei of the thalamus project to?
- Project to the primary somatosensory cortex -> localisation and physical intensity of the stimulus
In the anterior/neo spinothalamic tract, what does the somatosensory thalamus of the thalamus project to?
Projects to the secondary somatosensory cortex
What is the function of the anterior/neo spinothalamic tract?
First to be involved
Discriminative aspects of pain - causing you to move affected body part away
What is the pathway of the lateral/paleo spinothalamic tract?
- mainly C fibres but some A-delta fibres innervate projection neurons in lamina I
- these decussate posterior/medial parts of the thalamus:
mediodorsal nucleus and posterior thalamus
What is the posterior thalamus made up of?
Posterior nucleus and ventral medial nucleus
In the lateral/paleo spinothalamic tract what does the mediodorsal nucleus project to?
Anterior cingulate cortex
In the lateral/paleo spinothalamic tract what does the posterior thalamus project to?
Anterior or rostral insula -> emotion, quality, autonomic integration
What is the role of the lateral/paleo spinothalamic tract?
Second involved
Punishing aspects of pain - causing you to say that hurts
What else does the lateral/paleo spinothalamic tract project to in order to produce the unpleasant character of pain?
Projects to the limbic system - subjective sensations of pain and pleasure
What is the significance of the LST collateral projections?
Stimulates general arousal and focussing attention of painful region
- as LST travels upwards projects to reticular formation, periaqueductal grey and amygdala (via pons)
What is the role of the different projections in the collateral projections?
reticular formation - arousal and alerting cortex
periaqueductal grey - descending pain modulation
amygdala - limbic activation, visceral autonomic integration
Define normal acute pain?
From nociceptor activity, sudden onset, healing resolves, fast or slow
Define fast pain
conveyed by a-delta fibres
elicits reflexive withdrawal to prevent further injury
Define slow pain
burning, lingering, emotionally charged
What are the 4 cardinal signs of inflammation?
Heat
redness
pain
swelling
What are the features of peripheral sensitisation?
- time course of pain may be prolonged
- associated with inflammation
- hyperalgesia, allodynia, spontaneous pain
- enables protection and healing
What is hyperalgesia?
Increased sensitivity to pain
What is allodynia?
Pain caused by a stimulus which doesn’t usually cause pain
What is the mechanism of peripheral sensitisation
Nociceptors have reduced activation threshold and increased responsiveness
(sodium channels change threshold, potassium channels close) via substance P and CGRP
How do prostaglandins allow peripheral sensitisation?
Sensitise C fibres by increasing numbers of other receptors and increasing number of open sodium channels
What is central sensitisation?
Prolonged nociceptor input onto dorsal horn neuron projection neurons (2nd order neurons)
- nociceptors release glutamate and peptides
When a burning hand causes tissue damage what would be the peripheral and central sensitisation that occurs?
Peripheral:
- primary thermal hyperalgesia (increased sensitivity to head induced pain)
- primary mechanical hyperalgesia (increased sensitivity to pressure pain at injury site)
Central:
- secondary mechanical hyperalgesia (increased mechanical sensitivity outside flare region)
- mechanical allodynia (increased sensitivity to light touch)
What is chronic pain?
More than 12 weeks
- nociceptive (analgesic treatment) or maladaptive (pain persisting past healing phase)
What is maladaptive pain?
Due to abnormal activity in neural system
- neuropathic (injury/dysfunction in PNS/CNS)
- dysfunctional (no known lesion/inflammation)
What treatment is there for maladaptive pain?
- often becomes debilitating
- treatment targets abnormal neural activity = anticonvulsants and anti-depressants
What are the main prostaglandins? What is their function?
Phospholipase A2 (releases arachidonic acid from cell membranes due to inflammatory mediators) COX1 and 2 use amino acids as substrates for PG synthesis
When are COX1 and 2 present?
1 normal conditions
2 during inflammation
Where does modulation occur?
At all levels
How can endogenous modulation occur?
- innocuous stimuli lessen pain (rubbing an acute injury)
- descending systems module (excite or inhibit) transmission of ascending pain signals
What does innocuous mean?
Non-harmful
What is the effect of acupuncture?
Activates alpha-delta fibres stimulating PAG-mediated diffuse noxious inhibitory controls = descending inhibition of nociception
What is the effect of transcutaneous electrical nerve stimulation?
analgesia produced by stimulating non-noxious afferents which also stimulate lamina II interneurons
What is the circuit affecting intensity of pain?
Superior parietal lobe -> insula -> amygdala path -> PAG
What is the circuit affecting unpleasantness of pain?
ACC -> PCC -> PAG
What is the mechanism of peripheral sensitisation?
Inflammatory mediator effects
Nociceptors have reduced activation threshold and increased responsiveness
- sodium channels change threshold for opening
- potassium channels close
- TRPV1 channels increase sensitivity to heat
- nociceptors become tonically active
