Ian RamjohnMar 11, 2025
Holly A. Gultiano
Going down a rabbit hole of articles on capsaicin and the TRPV1 receptor the other day, I found out there's a TRPV1 antagonist that competes with capsaicin and stops its effects https://en.wikipedia.org/wiki/Capsazepine
Capsazepine - Wikipedia

Mar 11, 2025 at 3:56amWeb
Show threadHolly A. GultianoMar 11, 2025

& that the heat and pain associated receptor TRPV1 is also found in the CNS
https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2022.864828/full

"While brain TRPV1 is seemingly expressed at lower levels than the peripheral counterparts (Cavanaugh et al., 2011), its activation has been linked to different forms of synaptic plasticity and metaplasticity. Moreover, TRPV1 likely modulates anxiety, fear and panic responses in vivo (Almeida-Santos et al., 2013; Aguiar et al., 2014; Terzian et al., 2014) and also the severity of neurological and cognitive disorders, including epilepsy, depression and Alzheimer’s Disease (Chen et al., 2017; Balleza-Tapia et al., 2018; Wang et al., 2019, 2020a; Du et al., 2020)."

It's activated mechanically and by temperature, but also endogenously by anandamide https://bpspubs.onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0705467
and N-arachidonoyl-dopamine (NADA) https://www.pnas.org/doi/full/10.1073/pnas.122196999

Frontiers | Transient Receptor Potential Vanilloid 1 Function at Central Synapses in Health and Disease

The transient receptor potential vanilloid 1 (TRPV1), a ligand-gated nonselective cation channel, is well known for mediating heat and pain sensation in the ...

Frontiers
Show threadDougMerritt (log😅 = 💧log😄)Mar 11, 2025

@axoaxonic
Specific receptors in neurons seem to occur in many brain areas but with mysterious variations per region, and then they find that same receptor occurs throughout the body in non-neural cells, used differently and again mysteriously.

Same comment applies to neurotransmitters (of which I think I read that it's known that there are tenfold or more that remain undiscovered), which are first found in synaptic gaps, and later someone finds they again are used by non-neural cells for some mysterious messenger role.

Or so it seemed to me when I was doing a lot of reading a few years ago.

Show threadDougMerritt (log😅 = 💧log😄)Mar 11, 2025

@axoaxonic
Speculatively, for years I've been wondering about the vagus nerve, which has many functions and I think was evolved very early.

For instance, related: "The Polyvagal Theory is introduced to explain the different functions of the two primary medullary source nuclei of the vagus: the nucleus ambiguus (NA) and the dorsal motor nucleus (DMNX). Although vagal pathways from both nuclei terminate on the sinoatrial node, it is argued that the fibers originating in NA are uniquely responsible for respiratory sinus arrhythmia (RSA). Divergent shifts in RSA and heart rate are explained by independent actions of DMNX and NA. The theory emphasizes a phylogenetic perspective and speculates that mammalian, but not reptilian, brainstem organization is characterized by a ventral vagal complex (including NA) related to processes associated with attention, motion, emotion, and communication. Various clinical disorders, such as sudden infant death syndrome and asthma, may be related to the competition between DMNX and NA."

https://mathstodon.xyz/@axoaxonic@synapse.cafe/114141782289337740

Mathstodon

Show threadHolly A. GultianoMar 11, 2025
@dougmerritt A friend recommended that book a while back, but I didn't read it. Not sure if its purpose is to just bring attention to some neglected roles of the vagus nerve, but I move away from theories or hypotheses that hyperfocus on framing one region as the answer, when it's all an complex interacting network of networks with various hubs
Show threadDougMerritt (log😅 = 💧log😄)Mar 11, 2025

@axoaxonic
That's very sensible.

I find it interesting because I keep finding surprising things about it, but yeah, I too wouldn't want to view it as the total answer.

Show threadHolly A. GultianoMar 11, 2025
@dougmerritt It's always more complicated. I was mostly surprised that a receptor that's usually taught as being associated with mechanical damage and supraphysiological temperature is in the CNS doing something very different
Show threadDougMerritt (log😅 = 💧log😄)Mar 11, 2025
@axoaxonic
It should be in first aid kits in restaurants, similar to the rescue inhaler that has an opiate antigonist to save people who overdose.