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Dti does not measure axons.

It makes a model of white matter tracts based on the characteristics os the direction of diffusion. Like so many things MRI, it's a model, and an estimate of how large bundles of axons are organized and traverse through the WM.

If you wanna learn more I bet you can find some good videos on YouTube. :)

Great question OP! I have a PhD in this topic.

TLDR:

• Drugs such as chemotherapeutic agents that damage the nervous system can enhance pain
• The term to describe this enhancement is hyperalgesia
• The processes that cause it are peripheral sensitisation and central sensitisation
• LTP, or an increase in ion-channel expression at the neuronal synapse, is one of the many mechanisms involved
• In the case of LTP, the main neurotransmitter is glutamate

Analgesics are drugs that work by reducing pain, and the opposite of this would be drugs that increase pain. The term used to describe an increased pain response is hyperalgesia.

An example of a condition that can lead to increased pain is chemotherapy-induced peripheral neuropathy (CIPN), which is caused by chemotherapeutic agents that damage the nervous system. This damage can result in peripheral sensitisation, through hyperalgesia and ectopic firing. Peripheral sensitisation occurs when the threshold for activation of high-threshold pain receptors is lowered, and their responsiveness is enhanced (hyperexcitability) when they are exposed to inflammatory mediators and damaged tissues. This can lead to central sensitisation as well, but that's a more complicated process [1].

Long-term potentiation (LTP) is one mechanism that can lead to sensitisation through increasing ion channel expression at the synapse. It occurs when the connection between neurons is strengthened due to increased firing frequency between them. Some studies have shown that ketamine, which is an NMDA antagonist that inhibits LTP, can have analgesic effects in cases of peripheral sensitisation [2]. This shows that LTP is one of the mechanisms involved in sensitisation.

P.S.

There are also surgical methods to enhance the pain response which we do in research to model disease. One example is chronic constriction of the infraorbital nerve (CCI-ION) to model trigeminal neuralgia.

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Your understanding seems more complete than mine so anybody else reading this listen to this guy. Mine is just armchair knowledge from studying my own medical issues.

They set the temperature of a scientific hotplate to the level painful but not physically damaging to lab mice, then administer a combo of whatever drug they are testing and a control/placebo to various mice, they then place said mice in said hotplate and time the pain reaction. The mice usually get used for between a week and a month then are either dissected or disposed of.

There are even studies that showed opioid antagonists like naloxone increase pain, by reducing the placebo effect in patients. So the natural endorphine system of the body does certainly play a role in placebo induced analgesia

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DTI, which has a lower resolution than other forms of MRI, supposedly maps the paths axons take in white matter and show the physical connectivity of the brain.

Are these Voxels overlapping to any extent to artificially make higher resolutions? Or is there something I'm missing.

There's a fine line between mapping where white matter is and mapping the individual connections and directions within. I'm having trouble wrapping my head around that, I know that DTI can read for diffusion resistance and thus directionality, but that would seem to require a higher resolution given the complexity of the white matter tracts.

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Interestingly treatments which cause activation of pain fibres can actually improve pain in some situations. Capsaicin (the spice compound in chillies) can be used as a topical treatment. It causes temporary activation of pain fibres followed by a more prolonged desensitisation which improves pain symptoms in neuropathic conditions such as post-herpetic neuralgia.

Capsaicin has actual physiological effects on pain receptors, but there is also what is called “gate control theory” which is the principle that when your pain receptors are activated, addition of a non-painful stimulus can overwhelm a painful stimulus and reduce pain- it’s why when you bang your knee you rub it and the pain reduces.

My issue with this explanation is that techniques like diffusion tensor imaging (a form of dMRI) can map paths taken in the white matter (ie the actually axons of neurons, and the myelin on this axons that make white matter white in the first place). Axons are very thin iirc, and while the cortex is thicker than the resolution of the MRI, how can it map things smaller than that resolution?

Do Voxels overlap?

What is this hotplate test and why do I not like it already?

Really? I took a training course on giving narcan. They said that if someone is not currently on/addicted to opioids, it should have no perceivable effect on them, so if you have suspicion someone ODed and is unresponsive, give it to them, as worst case scenario it does nothing. I now worth it could make a shock case worse. Obviously this is a niche scenario, but I wonder if that's true.

What bakes my noodle is the thought that "true location" is a bit of a Newtonian concept. When you factor in the warping of spacetime, the whole universe is a little wibbly wobbly.

It's easy to think of stars and galaxies like they're all in a fishbowl and you're watching them from the outside, but that's not how we experience the universe.

In other words, the 'where' of where something is all depends on how you plan to get there.

From the point of view of the light beam hitting your eye, the star is exactly where it appears to be. From the point of view of traveling there slower than light, your path and the star's position would only converge sometime in the future.

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When they are speaking of pain meds here they are testing responsiveness to said pain using the hotplate test with mice. While it has an analgesic property as it brings relief, it is not lessening nerve signals as the topic was about. I realize I'm using layman's terminology, but there are many plants with much better allergies and effects as far as reducing nerve signal. Such as Tylenol and aspirin, so honestly the gold standard is cone snail toxin but most people are prescribed either gabapentin or Lyrica.

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