Genetic Mutation May Prevent Local Anesthesia From Working on Some People

Anesthesia makes painful surgical procedures tolerable, but what if anesthetics didn't work on you?. Wiki Commons

Imagine having to endure the dentist's drill without ever receiving anything to numb the pain. Sound like a nightmare? It's actually a terrifying reality for some rare individuals who seem to have a genetic resistance to local anesthetic, reports the BBC.

Local anesthetic resistance is a rare condition that's so poorly researched that many medical professionals refuse to acknowledge that it's even real. But for those individuals who experience it, there's no doubt. Take Lori Lemon, for instance. She has had to endure excruciating dental procedures from a young age, often at the bewilderment of dentists.

Lemon recalls one instance at the age of 7: “They started working on me and I, being obedient, I just raised my hand and let ’em know, ‘I can feel this.’” Another injection of the local anesthetic had no effect. “Finally I just kind of screamed and was in tears the whole time.”

But there are doctors who are taking this condition seriously, and a breakthrough may have finally been made, thanks in large part to Lemon and her family. Curiously, Lemon's mother and maternal half-sister also share her apparent resistance to anesthetic, a telltale sign that there's a genetic component to this condition.

Getting to the root of the problem

That's where Steven Clendenen, an anesthesiologist at the Mayo Clinic in Jacksonville, Florida, and his son Nathan, at Yale University School of Medicine, come in. Lemon first caught the attention of Clendenen as a patient; now it's a genetic analysis of the Lemon family by the Clendenens that could finally bring credibility to the idea of anesthetic resistance.

The analysis revealed a genetic defect that the anesthetic-resistant Lemons all share that relates to a specific sodium channel in the body, known as sodium 1.5. The gene itself, called SCN5A, is known to produce a protein called NaV1.5, which is a major component of this channel. The reason that's significant is because a leading theory for how local anesthetics work involves the fact that they disrupt sodium channels. These channels conduct positively charged sodium ions, and with them, the feeling of pain to nerve cells.

Sodium 1.5 channels are poorly understood, and so more research will be needed to truly get at the mechanics of what's happening in the bodies of people with SCN5A mutations like the Lemons. For now, researchers can only guess. But it's possible that the mutation could make the sodium channels more likely to remain open, which would allow pain signals to continue to flow to the brain even in the presence of local anesthetic.

There's certainly more work to be done, but for now there's hope that this little-understood condition can garner some acknowledgement, and with that acknowledgement, further study. It's a relief for people like the Lemons who have to deal with extreme levels of pain and stress just to endure a trip to the dentist.

“This is really important to get that out there,” said Clendenen. “People don’t believe [these patients] and it’s very frustrating. Even some of my colleagues that I’ve talked to say, ‘I don’t believe it’.”