20.2 Pain Flashcards
What is the normal function of pain?
To protect the body - by alerting about potential damage
What is the long-term function of pain?
To provide learning and behavioural changes that ensure dangerous behaviours are avoided in the future - and prolong survival
Which type of pain do A-delta fibres transmit?
Sharp ‘first’ pain
Which type of pain do C fibres transmit?
Slower, longer-lasting, burning ‘second’ pain
What do P2X channels respond to?
An increase in ATP in the tissue
What does an increase in ATP in the tissue indicate?
That there is cellular damage, as intracellular ATP is leaking out into the extracellular matrix
What does P2X receptor activation lead to influx of?
Sodium, potassium, calcium
What do TRPV1 channels respond to?
Noxious heat, vanilloids (e.g. capsaisin), low pH (protons)
What does TRPV1 channel activation mainly lead to influx of?
Calcium
What do ASIC channels respond to?
Increased proton conc
What does increased proton conc indicate?
Heartburn, ischaemia, acid placed on skin
What is the role of K+ in pain?
It directly stimulates C-fibre depolarisation through K+ channels
What is the role of Na+ in pain?
Voltage-gated Na channels activation leads to sodium influx –> triggers excitability of nociceptors
Which receptor does bradykinin activate?
B2 receptor (metabotropic)
What does bradykinin activating the B2 receptor lead to?
Gq pathway activation –> PKC activation –> ionotropic channels are phosphorylated –> HYPERalgesia
Which receptor do prostaglandins activate?
Prostanoid receptor (metabotropic)
What does prostaglandin activating the prostanoid receptor lead to?
Gs pathway –> PKA activation –> ionotropic channels are phosphorylated –> increased depolarisation of nociceptor
What is the effect of nerve growth factor (NGF) on the nociceptor?
Increases expression of ionotropic receptors on nociceptor surface - makes depolarisation more likely
Through which tract do nociceptive fibres enter the dorsal horn of the spinal cord?
Lissauer’s tract
Which Rexed laminae do the A-delta and C fibres mainly synapse in?
I and II
Some in V
Which receptors do enkephalins act on?
δ-opioid receptors
What is the intracelluar pathway stimulated by enkephalins?
Gi pathway –> reduce intracellular cAMP –> dephosphorylation of postsynaptic receptors so that second-order neurons in the pain pathway are desensitized
What is hyperalgesia?
Lowered threshold and excessive response to noxious stimuli (i.e. heightened pain).
Give an example of hyperalgesia.
Pressure sensitivity of bruised tissue
What are the two main types of pain (based on their origin)?
- Peripheral pain -> Due to activation of nociceptors in the skin or soft tissue by tissue injury.
- Neuropathic pain -> Not due to nociceptor activation, but due to damage of peripheral and/or central nerves. (Chronic pain caused by a lesion or disease to the somatosensory nervous system)
What is meant by psychological modulation of pain?
Cognitive, attentional and emotional variations can modulate pain perception and make it more or less intense
What is referred pain?
Pain perceived at a different location to the original painful stimulus
Where can cardiac pain be referred to?
Central chest, up neck, left arm, shoulder
Where can foregut pain be referred to?
Epigastric region
Where can midgut pain be referred to?
Periumbilical region
Where can hindgut pain be referred to?
Pelvic region
Give examples of some pains associated with cranial nerves.
trigeminal neuralgia and migraine
What is the main cause of trigeminal neuralgia?
Blood vessel pressing against the trigeminal nerve
What are the symptoms of trigeminal neuralgia?
Stabbing, lancinating or electrical pain sensation in the face
Can be episodic or sustained
What is migraine and what is the pathophysiology?
- A headache disorder characterized by cluster of symptoms including nausea, sensory sensitivity, aura, severe headache and vertigo.
- Pathophysiology likely involves changes in cerebrovasculature, inflammation and neural networks (including the hypothalamus, cerebral cortex and trigeminal nucleus)
- Changes in circulating 5-HT and peptides are thought to play a role.
What are the peripherally acting analgesics?
Aspirin and other NSAIDS, local anaesthetics, ibuprofen
What are some centrally-acting analgesics?
Opioids and their receptors (codeine, tramadol),
What are examples of NSAIDs?
Aspirin, ibuprofen
What is the mechanism of local anaesthetics reducing pain?
They block voltage-gated Na channels –> signals cannot propagate along the smallest nociceptive fibres
What is the mechanism of centrally-acting analgesics?
Act on on δ, κ, and (for codeine and tramadol) µ-opioid receptors
–> Gi pathway, reduction of cAMP, desphosphorylation of ionotropic receptors needed for second-order nerve stimulation
What is the mechanism of anxiolytics?
Serotonergic agonists - mimic descending supply from raphe nuclei, stimulating enkephalin release and pain inhibition
What can be used to treat migraines?
sumatriptan
What is the mechanism of sumatriptan?
5-HT inhibitor that reduces peripheral vasodilation in the head, preventing GCRP/neuropeptide release that increase sensitisation of pain fibres
