Neurosteroids for Anesthetics and Pain Management

  At my internship at CU Anschutz, we look at different anesthetics and how they affect the brain waves of mice. We also look at how the animal's behavior changes with anesthetics and how long it takes to regain consciousness, measured by how quickly the mouse can flip from its back to its stomach, an innate reflex inhibited with anesthesia. While I can’t talk about the work that I am specifically doing because we are working on being published, I can highlight some of the work done at the lab that is already published. 

The lab mostly works with different neurosteroids, which are steroids made in the brain, and they act on different channels to change the function of those channels. According to Joksimovic et al., 2018, one aspect of neurosteroids that the lab looks at is how they can be used as anesthetics, specifically ones like allopregnanolone, which increases the chlorine flow into neurons by increasing the activity of GABA receptors. With an increase of chlorine in the cell, being negative, the neuron is hyperpolarized, meaning that the membrane potential is decreased, making it harder to reach the threshold necessary to produce an action potential. The lab also looks at how neurosteroids can be neuroprotective, meaning that they can help damage by increasing the myelination of neurons and helping to conserve white matter that was damaged by events like traumatic brain injuries or Alzheimer's. These neurosteroids also can modulate the perception of pain by acting on calcium channels or GABA receptors, reducing the pain that the animal feels (Joksimovic et al., 2018).

With animal research, however, there is always controversy about how ethical the research is. While some people will never agree with using live animals, our lab follows strict IACUC protocol, including using as few animals as needed to get more data. The work that we are doing is also looking at how alternative anesthetics and pain regulatory molecules work, including which ones would be best to use at least on mice, which could have important effects on what anesthetics are best for humans. 

Joksimovic, S. L., Covey, D. F., Jevtovic-Todorovic, V., & Todorovic, S. M. (2018). Neurosteroids in Pain Management: A New Perspective on an Old Player. Frontiers in pharmacology, 9, 1127. https://doi.org/10.3389/fphar.2018.01127