Physiology Of Pain 2 Flashcards
What is the duration of acute pain?
Less than 3 months
What is the duration of chronic pain?
Longer than 3 months
What is peripheral sensitisation?
Major mechanism of acute pain
Sensitisation of peripheral nociceptors
Hyperalgesia (pain is worsened)
What does peripheral sensitisation lead to?
Leads to hyperalgesia
Reduction in threshold of TRPV1 channels by action of bradykinin and NGF
Reduction in the threshold of sodium channels by action of prostaglandins
How do local anasthetics work?
Blocks sodium channels preventing nociceptor firing
Lidocaine
- class
- MOA
Local anasthetic
- NA+ channel blockers
- prevents nociceptor firing
Topical capasacin treatment
-MOA
TRPV1 agonist
-repeated use reduces nociceptor firing
MOA-
- ?Depletes substance P
- Causes peripheral terminals to die back
NSAIDS
- e.g
- MOA
aspirin, ibuprofen
MOA-
- COX enzyme inhibited
- prostaglandin not synthesised
- so threshold of Na+ not decreased
Paracetamol/acetominophen
-MOA
Mechanism of action:
- Inhibits COXenzymes (But does not reduce inflammation)
- Acts on descending serotonergic pathways
Opiods
- examples
- mechanism
e.g morphine, codeine
Mechanism
- Agonists of the endogenous opioid system
- Multiple sites of action
1. Brainstem- disinhibition
2. Spinal cord
3. Peripheral inhibit channels on nociceptors
Gate control theory
Pain stimulated by nociceptors can be reduced by simultaneous activation of low threshold mechanoreceptors
- Modulates pain at spinal cord level
- rubbing/blowing pain can reduce pain sensitisation
- A-beta fibres are stimulated near injury site
- activates interneurones in dorsal horn [closes gate]
- inhibits spinothalamic neurones
What are the neuropathic peripheral pain mechanisms? [2]
- Peripheral sensitization
2. Spontaneous firing of nociceptors
Spontaneous firing of nociceptors
Peripheral mechanism of acute pain
- Peripheral nerve injury = accumulation of ion channels at regenerating tip of axon
- Increased axonal firing at injury site
What are the neuropathic central pain mechanisms? [2]
- Central sensitization
– within spinal cord - Changes in activation patterns/cortical remapping
– within brain
Central sensitisation
- Increase in the responsiveness of nociceptive neurons within the central nervous system
- Due to the reduced threshold for activation of 2nd order neurons
Mechanism for reduced threshold for activation in central sensitisation
Similar to LTP
1. Constant firing of axons from the periphery (following injury)=sustained release of glutamate
- prolonged depolarization of the postsynaptic membrane= massive influx of Ca2+ through NMDA receptors
- Activation of kinases = Phosphorylation of NMDA/AMPA receptors
Channel protein synthesis
Central hyperalgesia mechanism
After central sensitization:
-Activation of nociceptors results in amplified spinal cord activation
Central allodynia mechanism
Non-noxious Aβ fibres also synapse onto 2nd order spinothalamic neurons
Following central sensitization:
Non-noxious afferents activate sensitized 2nd order neurons
Chronic pain treatment
- Tricyclic antidepressants
- Anticonvulsants
- NMDA antagonists
(all have analgesic properties)
Tricyclic antidepressants
- Example
- MOA
Amitriptyline
MOA:
- Unclear
- Act on descending inhibitory pathways
- Inhibits reuptake of serotonin (and noradrenalin)
Anticonvulsants
- Examples
- MOA)
Pregabalin / gabapentin, carbamazepine
- Act in spinal cord to reduce excitability
- Blocks calcium (pregabalin/gabapentin)- prevent glutamate from nociceptors
- Blocks sodium (carbomazepine) channels
NMDA antagonists
- Example
- MOA
- Side effects
Ketamine
MOA
- reduces glutamate influx
- Prevents depolarization of second order neuron
- Adverse side effects (hallucinations/bad dreams)
NICE guidelines for treating neuropathic pain
First-line of treatment:
- Amitriptyline or pregabalin
Second-line of treatment:
- Switch drugs or combine
Third-line of treatment:
- Refer patient to a specialist pain service and consider oral tramadol (opioid) or in combination with the second-line treatment consider topical lidocaine
Placebo for treating chronic pain
- can treat analgesia
- Due to activation of descending inhibitory pathways
Complementary Alternative Therapies [5]
Acupuncture
massage therapy homeopathy
herbal medicine
hypnosis
