Summary: A new study shows that propofol is quite effective at reducing hyper-excitability of neurons by blocking HCN1 protein channels. This property of the drug can be exploited for managing conditions like nerve pains, epilepsy, and other neurological conditions.
A new study suggests that one of the popular anesthetics, propofol, may have a role in managing chronic pain, especially neuropathic pains, and various neurological disorders like epilepsy.
This is not the first time that researchers have focused on the role of anesthetics in modulating the way nerve cells communicate or work. The good thing about propofol is that it has been in clinical use for more than 50 years, which means that the drug is well-known to science, including its side effects.
Repurposing drugs has one significant benefit: it results in faster introduction of the medication. Since repurposed drugs require fewer intensive studies, much data about them is already available.
Propofol is a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel inhibitor. These channels are known as pacemakers of the body, and they play an especially important role in neural signaling. There are many sub-types of HCN ion channel proteins found in various body parts, from the heart to nerve tissues. However, propofol is particularly good at inhibiting HCN1, mainly in neurons. That is why researchers got interested in exploring it for conditions characterized by hyperactivity or dysfunction of these channels, like epilepsy and neuropathic pains.
In many neurological conditions, these HCN1 channels become hyperactive, causing hyperexcitability of nerves or certain parts of the brain due to some mutations or damage. This is especially true for conditions like epilepsy or chronic nerve pains. However, propofol can inhibit these channels, thus providing considerable relief.
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This new study reported in the NatureJournal was an in-vivo study done in isolated cells. Researchers studied the impact of propofol on these specific channels using the knowledge of neurophysiology and cry-electron microscopy. In their experiments, they could confirm that propofol can block hyperactive HCN1 channels. Thus, for example, they could block their activity in nerve cells carrying mutation characteristic of epilepsy.
Of course, this does not mean that chronic pain specialists will start using propofol to manage chronic pain, neuropathies, or epilepsy. However, it shows the importance of exploring pre-existing medications. Some of them might be quite good for treating some severe issues. Yet, many of these medications remain poorly explored.
This is not the first time that researchers have explored an anesthetic for managing neurological conditions. There have been lots of studies regarding the use of ketamine in various brain disorders for managing chronic pain, and it has shown itself pretty well. Ketamine has already been introduced for treating some other health issues, so why not propofol?
When it comes to using anesthetics for managing conditions like epilepsy, chronic pain, and neuropathies, some challenges remain. After all, propofol is an anesthetic, which means that its improper use or dosage may cause harm. However, those issues can be overcome in many ways.
Although anesthetics have small therapeutic and safety windows, they are very safe when used within that dosage range. There are a few ways of using them safely. One way is to use them only in clinics or physician’s offices.
However, perhaps the more practical way is to develop low-dose delivery methods like nasal or buccal spray. Such ultra-low dose sprays are safe, act almost instantly, and are unlikely to cause any significant issues when used responsibly.
So, the next logical step is to start testing this drug in clinical settings and identifying its optimal dosage. Alternatively, researchers may even develop something that works like propofol but has a better safety profile. If successful, such treatments could greatly benefit Interventional Pain Management St. Louis and similar facilities aiming to provide innovative solutions for patients with chronic neurological conditions.
Source:
Kim, E. D., Wu, X., Lee, S., Tibbs, G. R., Cunningham, K. P., Di Zanni, E., Perez, M. E., Goldstein, P. A., Accardi, A., Larsson, H. P., & Nimigean, C. M. (2024). Propofol rescues voltage-dependent gating of HCN1 channel epilepsy mutants. Nature, 632(8024), 451–459. https://doi.org/10.1038/s41586-024-07743-z
