Pain Flashcards
How can you qualify pain? 5 things
What are the factors that influence pain? 7
What is nociceptive pain?
What is nociplastic pain?
What is neuroplastic pain?
What are the 5 steps of nociceptive pain?
Good (warning), bad (long-lasting), sensory (threshold/intensity), psychological (threatening), widespread effects on life e.g anxiety
Sex, age, social demographic, environment/lifestyle, patient history, attention, sleep
Pain that rises from activation of nociceptors due to actual threatened damage to non-neural tissue
Pain arising from altered nociception but no evidence of tissue damage or disease or lesion of somatosensory system (burning pain)
Pain caused by lesion or disease of somatosensory nervous system / peripheral nerve - causing excitation
- Transduction
- Transmission
- Relay
- Integration & interpretation
- Modulation
How is nociceptive pain caused in transduction?
What does the activation of TRPV1-3 receptors cause? What causes this?
What can block this receptor/pain?
What is released on activation of MDEG receptors from physical tissue damage? How can this be blocked?
What can block Na+/K+/Ca2+ channels in response to pain?
What receptor activation causes the release of prostaglandins?
How can this be blocked with drugs?
Damage to body tissues by heat, chemicals, physical damage leading to the activation of nociceptors
Release of 5-HT - heat/burning
Triptans - preventing 5-HT release & stop action potential firing to spinal cord to brain
Substance-P & CGRP (peptide) - CGRP antibodies
Lidocaine
TRPM8 - coldness
NSAIDs (ibuprofen) block COX1/2 cyclo-oxygenase which convert arachidonic acid to prostaglandins
What are NSAIDs?
How can migraines be treated?
What are the symptoms?
What else can happen in a migraine regarding pain?
Hence what do drugs against transduction actually prevent?
What are the 4 treatments against transduction?
Non-sterioidal anti-inflammaotry drugs - reduce amount of prostaglandins by blocking COX1/2 activity for less inflammation & pain
Triptans acting on 5HT1 receptors
Pain, aura, visual changes
Peripheral fibres release CGRP peptides which act on blood vessels & cause pain
Prevent neurotransmitter release by blocking the receptor or blocking the enzymes
NDAIDs, antihistamines, opioids, local anaesthetics
What is transmission?
What are the symptoms of neuropathic pain?
What do the calcium, potassium and sodium channels do?
What is the state of a nerve in neuropathic state?
What does this lead to?
When transduction has occurred and signal on nervous system pathway to the CNS - can be prevented
Numbness (pins & needles) , sensory loss, shooting/burning electric shock-like (ongoing pain), hyperalgesia (increased pain sensation), allodynia (pain response to non-painful stimuli/no noxious stimulus)
Calcium - moves into cell & causes release of NT
Potassium - moves out & stop information coming into cell
Sodium - generator/accelerator of action potential & information going in
Damage to nerve
Numbness or ectopic firing
Which sodium channels are seen on primary afferent fibres which receive a pain stimulus & signal to the spinal cord & brain?
What are the 3 different fibres involved with?
So which sodium channels on which fibres do you want to target?
What does the Nav1.7 loss of function mutation cause in populations?
What is the inherited erythromyalgia Nav1.7 mutation?
Na v1.8 & Na v1.7
C-delta = pain (unmyelinated - burn)
A-delta = pain (fast - sharp localised pain) - release glutamate
A-beta = touch
Pain fibres but not touch ones
Inability to sense pain - causes high mortality
Gain of function mutation - lower action potential threshold & enhanced responses leading to attacks of burning pain
What do alpha-2 delta ligands do to calcium channels?
What drugs then can be used to prevent pain & how do they target these calcium channels?
Why does this have no effect on GABA receptors?
What are the differences between myelinated & unmyelinated sensory neurones?
What can sequencing neurones tell you?
What would blocking TRPV1 do on an unmyelinated neurone?
Therefore, what are the main drugs used to treat pain at transmission level?
Block calcium entry into cells by binding to alpha-2-delta subunits of the calcium channel and hence prevent neurotransmitter release
Pregabalin & gabapentin - ligands that bind with high affinity to the alpha-2-delta subunits preventing calcium entry
GABA binding to GABA receptors is inhibitory - only effects excitatory receptors
Myelinated sensory neurones - touch & unmyelinated pain
Find type of receptors & proteins expressed in different sensory neurones - identify chemicals & receptors and target these
Block burning pain sensation
Anticonvulsants - pregabalin & gapapentin for calcium channels, carbamazepine & lidocaine for sodium, opioids for potassium
What is relay?
What happens here?
What is central sensitisation?
What is this mechanism dependent on?
What is it related to?
Therefore what drug can be used to treat central sensitisation?
What side effects are there?
Pain within the spinal cord
Wind-up and sensitisation of sensory neurones in the spinal cord to send signals to brain
Hypersensitisation to nociceptors causes spontaneous firing (sensitisation) even when pain is not normally felt & hence spontaneous pain (hyperalgesia)
NMDA receptors
NMDA involved in memory processing - and hence learning is same part of brain as chronic pain states
Ketamine - analgesic - inhibits NMDAR
Hijacking NMDA system so stops learning
What is modulation?
How does noradrenaline alter pain modulation?
What does serotonin do?
What is analgesia?
What does the opioidergic descending pain control system do?
Perception of pain in the brain
Activates alpha-2 adrenoceptors which reduces pain transmission by reducing release of pro-nociceptive transmitters (glutamate, substance P)
Also reduces pain transmission but can also increase - depending on the receptor
Relief of pain
Activates analgesia - can be activated regardless of a pain stimulus e.g exercise releases endorphins which activate system
How can you use integration/interpretation & perception to treat chronic pain?
What else can opioids be used for?
What is the neurotransmitter, receptor & target channel for morphine?
What is the neurotransmitter, receptor & target channel for DPDPE?
What is the neurotransmitter, receptor & target channel for U50488H?
How do they stop action potential firing?
What kind of receptors are they?
What is the problem with codeine?
Mimicking effects like endorphin release - acting on opioid receptors
Treating pain at any point along the circuit due to the number of opioid receptors
Endomorphins, Mu receptor, opens K+ channels (inhibitory)
Enkephalins, Delta receptor, opens K+ channels (inhibitory)
Dynorphin, Kappa receptor, closes Ca+ channels (inhibitory)
No Ca+ and more K+ reduces NT release (Ca2+) and reduces excitability (K+)
G-protein linked
Pharmacoginetics - needs conversion into morphine & some people don’t have the enzymes
What is the effect of opioids on pre-synaptic fibres & post-synaptic neurone?
What are the 5 side effects?
How can morphine be delivered?
To what receptors does it bind?
What is Naloxone?
What are non-opioid analgesics? 6 examples (inflammation, nerve damage, headache, extreme pain)
C-fibre & A-delta: prevents release glutamate & substance-P (closed Ca2+)
Post-synaptic: inhibition of neuronal activity by no transmission of action potential (due to high K+ outside cell)
revents glutamate release (pain signalling) to the spinal cord & brain AND action potential
- Respiratory depression & also brainstem
- Anti-tussive / coughing - brainstem
- Constipation - peripheral
- Nausea - CTZ
- Dependence - rare in patients though
Orally, injected
Mu
Antagonist of Mu receptors
- NSAIDs/COX inhibitors - inflammation
- Lignocaine & carbamazepine - Na+ channels (nerve injury)
- Gabapentin - Ca2+ channels - nerve injury
- Antidepressants - NA/5HT - nerve injury
- Triptans 0 5HT1B/D receptors - headache
- Ketamine - NMDA - chronic/extreme pain
