Pain Flashcards
What is the sensory pathway (where does sensory information go, how does it reach the brain and cause reflexes)? (4)
- Sensory info if carried from the stimulus to the spinal chord by primary sensory neurons that live in a structure called the dorsol root ganglion
- Primary afferent fibres are the processors of primary sensory neurons, which carries the sensory info to the dorsol horn of the spinal chord
- The info then undergoes processing in the dorsol horn of the spinal chord
- This processing drives motor output to cause withdrawal reflexes and also drives ascending pathways to the brain to produce unpleasant sensations
Descending pathways come back down from the brain to the dorsol horn
Diagram in jotter
What is a primary afferent fibre?
What are the 3 types of afferent fibres and how do they differ in terms of myelination and diameter, include what type of signals each carries?
Primary afferent fibre = nerve processors that carry the signal from the skin to the spinal chord
Types:
- A beta = widest, heavily myelinated and fast. Carries non-painful signals from the skin, like touch
- A delta = smaller diameter, lightly myelinated and slower than A beta fibres. Carries pain signals
- C = smallest diameter, unmyelinated, and slower than both A beta and A delta fibres. Carries pain signals
What is a nociceptors and which 2 primary afferent fibres are nociceptors?
How do they produce different perceptions of pain?
Nociceptor = fibres which carry pain signals
A delta and C
A delta produces a sharp, quick initial pain
C produces the slower, longer lasting less intense second pain
What parts of the skin detects pain/temperature and which parts detects touch?
Pain/temperature = free nerve endings in the epidermis (upper layer)
Touch = Merkel’s disc and Meissner’s corpuscle in the dermis (lower layer)
How is an action potential produced from a pain stimulus?
A generator potential is formed, which gets stronger as the pain stimulus gets stronger.
The generator potential need to reach a certain threshold to be able to activate the action potential
(diagram in jotter)
What happens at the nociceptor-dorsal horn neuron synapse?
Action potential at the nociceptor central terminal causes glutamate and neuropeptides to be diffused across the synapse.
They bind to their glutamate and neuropeptide receptors on the dorsal horn neuron on the spinal chord to receive the signal from the nociceptor fibre
What 4 things occur during processing of signals at the dorsal horn and explain each? (include what the 2 different ascending pathways do and what 2 hormones descending pathways involve)
- Local neurons amplify/inhibit the pain signals being processed
- Output neurons carry the signals up to the brain to be perceived via 2 different ascending pathways.
One is important for location and intensity of the stimulus, the other is important for the emotional aspects of the pain - Descending pathways bring signals back down form the brain to the dorsal horn in the spinal chord. They involve monoamines such as serotonin and noradrenaline which can inhibit/activate the pain signals
- Motor output of signals travels the signals down the motor neurons to carry out a reflex response of certain signals
What is congenital analgesia, what mutation is it caused by, and what does this do?
Congenital analgesia = feeling no pain
Caused by mutation in the SCN9A gene
Leads to loss of function of the sodium channel NaV1.7
NaV1.7 is require to amplify the generator potential to action potential threshold in nociceptor terminals in the skin
How is our perception of pain modified in the brain?
Cognitive factors act on the prefrontal cortex of the brain to modulate our perception of pain by activating the descending pain modulatory system
What is hyperalgesia?
What is Allodynia?
Hyperalgesia = painful stimulus is perceived as being even more painful than it actually is
Allodynia = non-painful stimulus is perceived as being painful
What is inflammatory pain caused by?
What is neuropathic pain caused by?
Inflammatory = caused by chronic inflammatory conditions (like arthritis) or damage to tissues
Neuropathic = caused by damage to the peripheral or central nervous system (damage to nerves)
What are the 3 symptoms of chronic pain?
How can metabolic diseases like diabetes cause pain?
Hyperalgesia, Allodynia, or spontaneous pain
Metabolic diseases can cause damage to the peripheral nervous system
How are the pain pathways sensitised during inflammatory pain?
Inflammatory mediators such as serotonin are released from immune cells and damaged tissue cells to sensitise the pain pathways (serotonin will stimulate descending pain pathways from the brain)
What is CNS pain caused by? (3 conditions, just names)
How is the CNS (and PNS) made more excitable during chronic pain?
How does this lead to the 3 symptoms of chronic pain?
MS, Stroke, or spinal chord injury
Lots of molecular and cellular changes make the peripheral system much more excitable (makes the afferent fibres more excitable). More pain signals being delivered to the spinal chord causes changed in the CNS to make it more excitable as well
Excitability of the CNS leads to the pain info being “misprocessed”, leading to the 3 symptoms of chronic pain (allodynia, hyperalgesia, and spontaneous pain)
What is the peripheral nervous system made of
What is the CNS made of?
Peripheral = Primary sensory neuron + afferent fibres
CNS = spinal chord and brain
What does increasing peripheral sensitisation cause?
What does increasing central sensitisation cause?
Peripheral = decreases the threshold for action potential activation and enhances the response to a given stimulus
CNS = Leads to easier activation of motor output and increases the number of signals going up ascending pathways to the brain
What are analgesics?
What are the 2 main analgesics used to treat nervous system chronic pain, an example of each and where did they originally come from in nature?
What 2 other things are analgesics discovered from?
Analgesics = drugs that relieve pain
Opioids like morphine - Opium poppy
NSAIDs like aspirin - Willow bark
Also discovered from drugs used for other purposes such as antidepressants and anticonvulsants (anti seizure drug)
What happens when opioid receptors are activated by opioid drugs on the central terminal nociceptor (in the nociceptor-dorsal horn synapse)?
What happens when opioid receptors are activated on the spinal dorsal horn neuron?
What does this mean that opioids do overall?
Reduces neurotransmitter release (release of the neuropeptides and glutamates)
(presynaptic inhibition)
Makes the dorsal horn neuron less sensitive to pain input
(Postsynaptic inhibition)
So this means that opioids inhibit pain processing in the spinal chord by both pre and post synaptic inhibiting
Where else do opioids act on (not in the nociceptor-dorsal horn synapse) and what does this do?
Also acts on the brain, which promotes inhibition of pain signals in descending pathways from the brain
What type of pain are opioids most effective for?
What are the are the 2 limitations to using opioids? (mention the 5 side effects it causes)
Most effective for inflammatory pain (over neuropathic pain)
Limitations:
- We have opioid receptors all throughout the body, so opioids can end up causing undesirable side effects like constipation, respiratory shutdown, confusion, sedation, and lethargy (fatigue)
- Opioids can also cause addiction, tolerance, or dependence
How is inflammatory hyperalgesia promoted in inflamed skin? (2)
- In inflamed skin, the enzymes Cox1 and Cox2 are promoted which produce PGE2, so there is an increased production of PGE2 in inflamed skin
- PGE2 acts on receptors on peripheral nociceptor endings which drives intracellular signalling to promote inflammatory hyperalgesia
How do NSAIDS help reduce pain in the CNS and PNS? (include how this works in CNS pain)
NSAIDS inhibit COX1 and COX2 which produce PGE2, so this decreases the concentration of PGE2, decreasing the pain felt
PGE2 is also produced by COX1 and COX2 in the spinal chord (CNS) after injury
What are the 3 systems affected by the side effects of NSAIDs and how?
PGs (like PGE2) have protective roles in the gastrointestinal, renal and cardiovascular systems.
So since NSAIDs decrease PGs, this increases risk of things going wrong in these systems
Are noradrenaline and serotonin inhibitory or excitatory neurons involved in brain descending pathways?
What happens to these descending pathways in chronic pain?
What do antidepressants do that can help with this and what are 2 examples of antidepressants that do this?
Noradrenaline = Inhibitory
Serotonin = Excitatory/inhibitory
In chronic pain the pathways shift so that descending excitation dominates
Antidepressants act to reset the balance by promoting descending inhibition pathways
Examples = TCAs and SNRIs
