7.2 () Pathophysiology of pain in cancer and other terminal illnesses Flashcards
What is the source of nociceptive pain versus neuropathic pain?
Nociceptive pain - activation of sensory afferents
Neuropathic pain - damage to nerves
Which afferent sensory fibers carry nociceptive information?
Where do these fibers terminate?
A-delta (thin myelinated) and C fibers (thin unmyelinated)
Lamina I in the dorsal horn of spinal cord
Second order neurons (project to the brain) express the receptor for which neurotransmitter
Substance P (aka neurokinin 1)
What is the process in which peripheral stimuli is converted to signals carried by nerves to the CNS?
Transduction
How does gabapentin and pregabalin work
Bind to alpha-2-delta accessory subunit of calcium channel (thus reducing excessive hyperexcitability)
FS: Calcium channel blocker
NMDA receptor is blocked by what ion under normal neuronal activity?
Mg
What are 2 main types of bone - where is bone pathology largely evident
Cortical bone - dense outer layer of all bones (80% of all skeletal mass) compact hard bone
Trabecular bone - found in the epiphyseal regions of long bones, greater amount of remodelling, bone pathology is largely evident in bone of this type spongy bone
What 2 areas of bone receives the most sensory afferent fibers?
Bone marrow followed by mineralized bone
What factor released by cancer increases osteoclast activity
Parathyroid hormone related peptide (PTHrP)
What are two mechanisms cancer induce bone pain?
Peripheral mechanisms:
- Factors released in periphery (e.g. cytokines, interleukins, growth factors) which excited or sensitize nociceptive fibers
- Abnormal osteoclast activity which destroys bone and cause pain
- Structural damage to bone
Central mechanism
SS: Central - enhanced 2nd order neuron excitability.
Also higher order cognitive/emotional process can increase pain
Name 3 medications and 1 intervention to treat cancer bone pain
Opioids
Gaba
NSAIDs
Bisphosphonates
Radiation
How does bisphosphonate work?
Osteoclast inhibition (reduce activity and cause apoptosis) -> prevent bone resorption
Chemo and antiretroviral treatment damages what structure in the cell leading to increased development of pain
Mitochondria
What happens after nerve injury?
Ion channel dysregulation ->
Peripheral nerves display ectopic discharge ->
increased nociceptive signaling onto dorsal horn transmission neurons without a peripheral stimulus
Other things:
Increased substance P
Decreased inhibitory GABA interneuron
Decreased inhibitory opioid receptor
What are 2 ions involved with neuropathy and ion channel dysregulation - name medications that target these ions
Sodium - Lidocaine, Carbamazepine
Calcium - Gabapentin, pregabalin
List 4 chemical mediators of pain (also known as algogenic ligands) involved in the transduction of nociceptive stimuli
- signal stimulate first order neurons -
ATP
Adenosine
Bradykinin
Cold
Prostaglandin (key)
5-HT
Heat / capsaicin
H+
Histamine
IL-1
Nerve Growth Factor
Noradrenaline
Good YouTube video to watch
https://m.youtube.com/watch?v=uOaiaYDoUnA
Good video
https://m.youtube.com/watch?v=5c8maFAhqIc
What is the difference in pathophysiology of acute vs chronic pain
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- Acute pain = pain has overt relationship to identifiable peripheral damage or lesion.
- Chronic pains = altered neurophysiological and pharmacological substrates from the periphery to CNS, and the relationship between noxious phenomena and the level of pain experienced can become altered.
Define plasticity
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- Plasticity, the ability of the nervous system to alter in response to injury-evoked dysfunction, leads to changes in the perception of pain
(can arise with any type of pain but particularly with chronic neuropathic pains)
Explain 1 example of altered neurophysiology in chronic pain
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In some neuropathic conditions with occult sources of injury, pain may be present, or unexpectedly severe, in the absence of a peripheral process (allodynia/hyperalgesia/spont pain)
List 1 major difference in the peripheral mechanism of nociceptive vs neuropathic pain
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Neuropathic pain = prominently feature disturbances in ion channels.
(Thus, treatments aimed at the peripheral mechanisms are different for neuropathic pain vs nociceptive)
Plasticity in the CNS may lead to symptoms reflecting expanded receptive fields.
- Give 3 examples of such symptoms
- The influence of what non-somatic system must be considered as pain becomes chronic?
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- increased amplitude of response to a given stimulus (HYPERALGESIA)
- pain elicited by normally innocuous stimuli (ALLODYNIA)
- SPONTANEOUS pain in the absence of external stimuli.
- as pain persists, AFFECTIVE and EMOTIONAL responses must be considered along with the sensory aspects of the stimulus. Although the sensory and psychological aspects of pain are separable, their neural pathways are interlinked
(somatic + limbic systems converge)
List 2 mechanisms of peripheral sensitization
- Neurogenic inflammation - nerve endings release pro-inflammatory compounds themselves –> amplifies peripheral response of nociceptors
- Changes in ion channels - lowering of the nociceptive threshold in peripheral fibres and how hyperalgesia can result
- Explain central sensitization
- Describe 1 example of central sensitization - with a specific receptor
- CNS can amplify the inputs it receives and cause increased pain perception
2.
-At spinal levels, upregulation and enhancement of transmitter release via wind up phenomenon via NMDA receptor. Usually, NMDA receptors are plugged/blocked by Mg.
Prolonged afferent drive —> increased substance P —> release of magnesium –> calcium influx –> potentiation of post-synaptic response (Fig. 7.2.2.)
