As a dental assistant there is one aspect of my job that has always intrigued me, and that has been local anesthesia. My first post focused on cavity treatment, but this post will focus on how dental practitioners can get patients ready for tooth reconstruction. When a cavity is large enough that it starts getting close to the pulp of the tooth, the nerve tissue located inside of the pulp becomes extra sensitive. To treat a cavity, dentists must drill out all decayed tissue. So, if any drilling occurs near the pulp, even if it does not penetrate that region and stays in the dentin, the patient will have severe discomfort and pain. This discomfort and pain can be avoided by using local anesthetics such as Lidocaine and Septocaine, but how do these anesthetics work physiologically?
Believe it or not, avoiding the pain using local anesthetics uses mechanisms that we’ve already learnt in class. According to this article, there are two different hypotheses for how pain is blocked. The first hypothesis says that afferent sensory nerve activation is blocked by local anesthetics and occurs through the inhibition of conformational change of voltage-gated sodium ion channels! This makes a lot of sense, by inhibiting the sodium ion channels, the nerve would not be able to depolarize and send any signals back to the central nervous system that convey pain and discomfort. These anesthetics inhibit the sodium ion channels by attaching to a binding site that exists in the channel’s pore and then interfering with the conformational changes that occur when an action potential starts.
The second hypothesis still inhibits sodium ion channels but does not do so conformationally. In the article, the structure of sodium ion channels is discussed and says that in the tertiary and quaternary structure of the channels, there are acidic and basic amino acid side chains aligned on the edge of helices that rearrange when the channel conformationally changes. When these basic and acidic ion pairs are lined up correctly from the helices rearranging, sodium ion passage is allowed. The article proposes that local anesthetics could be binding at the helices to inhibit their rearrangement so that sodium ions are not allowed passage. This hypothesis is speculative, but it also explains why some anesthetics are longer lasting than others as smaller molecules would enter, bind to the helices and leave quicker!
Reference:
Butterworth, J. F., 4th, & Strichartz, G. R. (1990). Molecular mechanisms of local anesthesia: a review. Anesthesiology, 72(4), 711–734. https://doi.org/10.1097/00000542-199004000-00022
This is an awesome post. Anytime I get local anesthetic, I'm always asking the doctor or dentist how it works!
ReplyDeleteThat's cool that they utilize the sodium ion channels too!
What do you think would cause people to be allergic to some anesthetics? Do you think it involves the sodium ion channels too?
Since you work as a dental assistant, do you know why some dental offices don't use local anesthesia before administering the novocaine shot or when doing tooth reconstruction? I know that stuff can hurt like crazy. I feel like it would be an ethical problem and would make the experience way worse for a patient.
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