Pain Flashcards
Define analgesia
Inability to feel pain, without removing all feeling or ability to move muscles
Define analgesic
Drug used to achieve analgesia
Define anaesthetic
Drug used to eliminate all sensation, including pain
What is a neuromuscular blockade?
Also known as muscle relaxant
Works by blocking the neuromuscular junction
What is a perineural blockade?
Injection to selectively block a nerve root
What is radicular pain?
Pain that radiates into a lower extremity
e.g. sciatica
What are the 5 types of sensory receptors?
Mechanoreceptor Nociceptors Chemoreceptors Thermoreceptors Photoreceptors
What is the pathway of a pain signal?
Afferent peripheral nerve (nociceptor)
Synapses with interneuron in spinal cord in dorsal horn
Releases glutamate which binds to AMPA and NMDA receptors
Thalamus
Cortex
What is nociceptive pain?
Sensation of pain in response to detection of potentially damaging stimuli
What is neuropathic pain?
Pained caused by damage to the sensory nervous system
What is pain wind-up?
Perceived increase in pain intensity over time when the stimulus is applied repeatedly
Caused by repeated stimulation of group C nerve fibres and priming of the NMDA receptor response
What is Ketamine and how does it work?
Used as an IV anaesthetic
NMDA receptor antagonist
Leads to inhibition of CNS
How does Nitrous Oxide work as an anaesthetic (and what is it also known by)?
Antagonist of NMDA, AMPA and Kainate receptors
Also known as Entonox
What are the 4 types of receptor that opioids bind to?
Mu
Kappa
Delta
ORL1
What type of receptor are opioid receptors?
GPCR - coupled to Gi/o
What are the downstream effects if the Go receptor?
Potassium channels open
Potassium efflux
Hyperpolarisation
Less likely to reach action potential threshold
Also inactivates VOCCs, preventing neurotransmitter release
What 5 receptors are coupled to a Gi/o protein?
a2-adrenoreceptors M2 and M4 receptors All opioid receptors 5-HT1 receptor GABA-b receptor
How does the GABA-a receptor work?
It is a ligand-gated chloride channel
Allows chloride ion influx
Hyperpolarisation
Less likely to reach action potential threshold
Is Glycine an excitatory or inhibitory neurotransmitter?
Inhibitory
Also works on ligand gated chloride channels
What are the two types of neuromuscular blockade?
Depolarising
Non-depolarising
How do depolarising neuromuscular blockades work?
Agonist of nAchRs
Causes persistent refractory depolarisation
Motor endplate becomes inexcitable
(Ach normally released in brief spurts and rapidly hydrolysed)
Example of a depolarising neuromuscular blockade
- administration
- structure
- how is it broken down
Succinylcholine
- Administered by IV
- Looks like two Ach joined together
- Broken down by plasma cholinesterase
How do non-depolarising neuromuscular blockades work?
They are competitive reversible antagonists of nAchRs
How does botox work?
Botox targets proteins in the SNARE complex
Prevents exocytosis of Ach
How does Neostigmine work?
Inhibits acetylcholine esterase
Prevents breakdown of Ach
Used to treat Alzheimers and Parkinson’s
How is Ach recycled?
Acetylcholine esterase breaks it down into acetate and choline
Choline reuptaken into presynaptic membrane by cotransportation with sodium ions
Choline + Acteyl Coa makes more Ach
Repackaged into vesicles
What 3 things can anticonvulsant drugs be used to treat?
Seizures
Mood disorders/stabilisers
Neuropathic pain
How do anticonvulsant drugs work?
Block sodium channels
Block calcium channels
Enhance GABA function
By what 3 ways can GABA neurotransmission be enhanced?
Positive allosteric modulation of GABA-a receptors e.g. by benzodiazepines
Inhibition of GABA transaminase (preventing GABA breakdown)
Inhibition of the GAT1 reuptake transporter
Example of a drug that inhibits sodium channels
Carbamazepine
Specifically Na1.8 channels
Examples of 2 drugs that inhibits calcium channels
How do they work?
Gabapentin and Pregabalin
Block t-type calcium channels
Also prevent insertion of calcium channels into the membrane
Reduce expression of a2-delta subunits in calcium channels
How does neuropathic pain after injury arise?
Injury causes inflammation
Release of inflammatory mediators
Inflammatory mediates upregulate a-adrenoreceptors on the sensory nerve and upregulate NMDA receptors on the spinal cord synapse
Lowers nerve activation threshold
What is a nociceptor?
Sensory neuron that responds to potentially damaging stimuli
Detection of noxious stimuli transduced into electrical energy
What are the two types of nociceptor axon?
A-delta fiber axons
C fiber axons
What is the difference between A-delta fiber axons and C fiber axons?
A-delta fiber axons are myelinated and cause feeling of sharp pain. Action potentials are initiated through specific TRP channels
C fiber axons are non myelinated and cause feeling of dull, prolonged pain. They are polymodal - response to a range of stimuli
How do thermoTRP channels work?
Ion channel, opens in response to extreme heat
The TRPV1 channel opens in response to 42 degrees, also vanilloids present in chilli
What is hyperalgesia?
Increased sensitivity to pain, usually caused by inflammatory mediators
What are A-beta fibers?
Detect non-noxious, mechanical stimuli
What are 3 possible causes of phantom pain?
- Neuroma (tumour on a nerve sheath cell), causing abnormal firing of action potentials
- Degeneration of C fiber axons due to injury. A fibers branch into same lamina, so A fiber input becomes reported as noxious stimuli
- Cortical remapping following amputation
