Physiology of Pain 2 Flashcards
What is the difference between acute pain and chronic pain?
Acute pain < 3 months
Chronic pain > 3 months
What is peripheral sensitisation, and what does this cause?
The reduction in threshold for pain receptors.
Causes hyperalgesia because the cells can reach threshold more easily
What is lidocaine and how does it work?
Local anaesthetic applied to the skin that works by inhibiting Na+ channels, making depolarisation harder to occur so the nociceptors fire less.
What is topical capsaicin treatment, and how does it work?
Acts on TRPV1 channels since capsaicin is its agonist, and its repeated introduction reduces the nociceptive firing. This is because it depletes substance P, leading to Ca2+ overload which causes mitochondrial dysfunction. Peripheral terminals then die.
How do NSAIDS work?
Inhibit COX enzymes, which are required for the synthesis of prostaglandins.
This causes a reduction in the inflammatory response so peripheral sensitisation is prevented as Na+ threshold won’t be reduced.
What drug works by inhibiting COX enzymes but isn’t an NSAID, and why isn’t it considered an NSAID?
Paracetamol
Because it doesn’t reduce inflammation
What are the most effective drugs for pain relief, what are some examples, and what are some side effects of them?
Opioids (e.g. morphine, codeine and tramadol)
- Addictive
- Sedative
- Respiratory depressants
How do opioids work, and where are their sites of action?
They are agonists of the endogenous opioid system
Act on:
- Midbrain
- Spinal cord
- Periphery
What is the gate control theory, and what is an example of how it works?
A way of controlling pain at the spinal cord level. Works by simultaneous stimulation of nociceptors and low threshold A-beta fibres.
Example is rubbing the area of pain
In the gate control theory, how can the ‘gate’ be opened and closed?
Opened by the stimulation of A-beta fibres, which activates inhibitory interneurons in the dorsal horn and so inhibits the spinothalamic tract.
Closed by the stimulation of C fibres, which inhibits inhibitory interneurons and so activates the spinothalamic tract.
What is the cause of neuropathic pain, and what peripheral mechanisms can lead to it?
Injury to the nervous system
What is the cause of spontaneous firing of nociceptors, and what is an example of a cause of the injury?
The increased firing of axons at an injury site due to the accumulation of ion channels at the regenerating tip of an axon
Example is a knife wound
What is central sensitisation?
Increased responsiveness of nociceptive neurons in the CNS due to the 2nd order neurons having a reduced threshold
What is the physiological cause of reduced threshold?
1) After injury the constant firing of nociceptors leads to sustained glutamate release, causing prolonged depolarisation of postsynaptic membrane
2) This causes a large influx of Ca2+ through NMDA receptors, which then activates intracellular protein kinases
3) These protein kinases then lead to more phosphorylation and also insertion of NMDA/AMPA receptors
4) This makes it even easier for threshold to be reached = hyperalgesia
How can central sensitisation cause allodynia?
A-beta fibres also synapse onto 2nd order spinothalamic neurons which are normally non-functional. However, their reduced threshold makes it possible for them to be activated
Also, some of the A-beta fibres can form sprouts and synapse onto the spinothalamic tract.
What are some associated symptoms of chronic pain?
- Depressive mood
- Sleep disturbances
- Fatigue
What drugs can be used to treat chronic pain, and what kind of effect do they have?
- Tricyclic antidepressants (TCAs)
- Anticonvulsants
- NMDA antagonists
All have analgesic effects
What are some non-drug treatments of chronic pain?
- Physiotherapy
- Psychological therapy (e.g. cognitive behavioural therapy)
- Surgery
How do TCAs treat pain, and what is an example of one?
They stimulate descending inhibitory pathways by inhibiting the re-uptake of 5-HT and NA
Examples = Amitriptyline
What type of drugs are gabapentin/pregabalin and carbamazepine, and how do they work?
Anticonvulsants and they both work by blocking ion channels on the spinal cord in order to reduce excitability.
Gabapentin blocks Ca2+ channels (so also prevents the release of glutamate)
Carbamazepine blocks Na+ channels
What is ketamine, and how does it work?
NMDA antagonist so reduces glutmate influx, so depolarisation of 2nd order neurons is reduced
What is the main side effect of ketamine?
Hallucinations
What are the NICE guidelines for the treatment of chronic pain?
1st Line: Amitriptyline or Gabapentin
2nd Line: Switch the drugs or combine them
3rd Line: Refer to a specialist and consider opioid
How does the placebo effect help with pain?
Has an analgesic effect as it leads to the activation on descending inhibitory pathways
