Draw and explain the oxygen cascade
Define and classify pain
Pain is an unpleasant sensory and emotional experience with actual or potential tissue damage
It can be classified according to its acuity or its nature:
Acute - recent onset and limited duration. Identifiable cause
Chronic - Persists beyond time of healing. No clearly identifiable cause
Nociceptive - results from stimulation of nociceptors
Neuropathic - results from dysfunction of the nervous system
Describe the pain pathway that are activated when injury occurs
- Nociceptors within the damage tissue are activated
- An action potential is generated and travels down afferent sensory neurones (Abeta, Adelta, C)
- Synapses in dorsal horn within the rexed laminae
- Interneurones (secondary neurones ) decussate the spinal cord and travel within the ascending pain pathways (spine thalamic tracts)
- The ascending tracts travel up the spinal cord and synapse within the thalamus (specifically the intralaminar nuclei and the ventral posterior nucleus)
- Tertiary neurones project into the somatosensory cortex
- Some ascending spinal pathways project directly into the reticular-activating system and then into higher centres which affect memory/emotion
- Descending fibres from the cortex/thalamus/brain stem exert an inhibitory effect on pain transmission in the dorsal horn
- An immediate polysynaptic withdrawal reflex occurs
Describe the ascending pain pathways (4x)
There are multiple ascending pathways. The most important are:
- SPINOTHALAMIC TRACT
- Anterior (light touch) and lateral (pain and temperature)
- Made of both fast and slow fibres
- FAST - travel directly in STT to brain stem & synapse in ventral posterior nucleus of thalamus before projecting into the somatosensory cortex - involved in conscious perception and memory of pain
- SLOW - synapse in the brain stems reticular formation and in intralaminar nuclei in the thalamus before projecting into hypothalamus/lambic system and autonomic centres - SPINORETICULAR TRACT
- slow fibres that terminate the reticular formation and thalamus - SPINOMESENCEPHALIC TRACT
- terminate in the midbrain and periaqueductal grey mater - DORSAL COLUMNS
- Pressure/vibration/proprioception carried by Abeta fibres
- Not involved in pain transmission
Describe the descending inhibitor pain pathways (2x)
There are 2 main descending pathways - the periaqueductal grey and the locus caeruleus
The periaqueductal grey is the main descending pathway, it gets projections from the thalamus/hypothalamus/amygdala/cortex and projects into the NUCLEUS RAPHE MAGNUS in the medulla whose fibres synapse with the substantia gelatinosa of the dorsal horn. It’s transmitters include endorphins and enkephalins (MOP opioid receptors) and serotonin
The locus caeruleus is an important brain stem nucleus projecting descending inhibitory pathways to the dorsal horn via adrenaline receptors
What are nociceptors and how are they classified?
Nociceptors are unmyelinated nerve endings that respond to thermal, mechanical and chemical stimuli
They are classified according to their sensitivity to different stimuli.
- Unimodal (thermo-mechanoreceptors) - respond to pin-prick and sudden heat
- Polymodal - respond to pressure, heat, cold, chemicals and tissue damage
How do noxious stimuli activate pain transmission?
Tissue damage leads to release of endogenous chemicals that stimulate nociceptors such as:
- bradykinin, histamine, seratonin, acetylcholine, H+ & K+
Other chemical mediators lower the threshold for excitation - eg prostaglandins, leukotrienes, substance P, neurogenic A and calcitonin gene-related peptide
Stimulation causes an influx of sodium and calcium which causes depolarisation and the generation of an action potential
This then propagates down pain pathways
What is the substantia gelatinosa?
Otherwise known as the laminae II and III in the dorsal horn
A point of significant pain modulation
What are the main neurotransmitters at the primary afferent sensory neurone?
Excitability neurotransmitters - glutamate, aspartate and substance P
What are the main neurotransmitters of the interneurones or secondary afferent neurones?
NMDA, AMPA, Neurokinin 1 and adenosine 1& 2
What are the inhibitory neurotransmitters of the pain pathways?
Enkephalins (MOP) and GABA A receptors
Describe the gate control theory of pain
The gate control theory pain is an aspect of pain modulation. It postulates that transmission from primary afferent to secondary afferent neurones is “gated” by interneurones in the substantia gelatinosa. This can be pre or post synaptic
The pain pathway - ie what opens the gate - is the C nerve fibre and substance P synapsing within the SG to secondary afferent neurones. This is aided by Adelta fibres that inhibit ENKEPALINERGIC interneurones that would otherwise post-synaptically inhibit neurotransmission
There are a number of mechanisms to inhibit pain transmission.
1. Noradrenergic & serotonergic Descending pathways (LC/NRM/PAG) activate ENKEPHALINERGIC interneurones (MOP) that inhibit post-synaptic transmission of pain pathways
2. Abeta fibres inhibit C fibre pre-synaptically via GABA receptor stimulation.
A-Beta fibres are activated by touch and pressure and explain how rubbing it better works
3. A-delta fibres also ascend to the PAG and stimulate it to, perhaps paradoxically, exert its inhibitory effect
Describe the actions of commonly used painkillers on the pain pathway:
- Paracetamol
- NSAIDs
- Opioids
- Tramadol/pethidine
- TCAs
- Anticonvulsants
- Gabapentin
- Local anaesthetic
- Ketamine
- Clonidine
- TENs machine
N
What are the different types of neurone?
There are A, B & C nerve fibres
A fibres are sub classified into A alpha, beta, gamma, delta
Tell me about A alpha neurones
A-alpha neurones
- somatic motor and proprioception
- diameter 12-20 micrometers (largest)
- conduction velocity 70-120 m/s (fastest)
Tell me about A-beta nerve fibres
A-beta
Transmit touch and pressure
Diameter 5-12 micrometers
conduction speed 50-70 m/s
Tell me about A gamma nerve fibres
A gamma
Motor fibres to muscle spindles
Diameter 3-6 micrometers
Conduction speed 30-50 m/s
Tell me about A delta nerve fibres
A delta
Pain, temperature and touch
Diameter 1-3 micrometers
conduction speed <30 m/s
Tell me about B nerve fibres
B fibres
Myelinated pre-ganglionic autonomic fibres
Diameter 1-3 micrometers
Conduction speed <15 m/s
Tell me about C nerve fibres
C fibres
Unmyelinated, post ganglionic autonomic fibres AND pain/temperature
Diameter <1 micrometer
conduction speed <2 m/s
Demonstrate the relationship between PO2, PCO2 and cerebral blood flow
Linear relationship between CBF and PCO2
Above PO2 8 there is little difference in CBF but below it there is increased CBF
Draw the lung volumes
What is the closing volume?
The volume of gas over the residual volume that remains in the lungs when the small airways begin to close
