- some medical researchers aim to answer: why do some patients require much higher doses of pain medication than others?
- genetic anaesthetic resistance is not limited to fair-skinned redheads and nordic celtic blondes, its all skin/eye/hair color now.
- one genetic variance relates to sodium channel 1.5 on gene SCN5A that produces a protein NaV1.5; leading theory is that local anesthetics disrupt sodium channels which conduct positively charged sodium ions, and with them, the feeling of pain to/from nerve cells aka the flow can't be blocked by anesthetic.
- 30% in Norway live with chronic pain. professor/anaesthesiologist Skorpen/Klepstad want to investigate whether there may be more people with this genetic defect among those who suffer from chronic pain. The gene error may also mean the body's natural system for pain relief is also not in order.
- my holistic dentist knew i had MTHFR and to not dose me with nitrous oxide, but most dont know/care what MTHFR is, if you told them
- important note: nitrous oxide is 'poison gas' for anyone with a B12 deficiency, MTHFR and/or COMT gene variants, chronic condition
- it kills B12 and help shut down your methylation cycle (mine already struggling) and cascade into a dozen symptoms and function areas
- nitrous oxide ruins your methylation and is not recommended for these scenarios:
- MTHFR variant
- B12 deficient
- Methylfolate deficient
- Glutathione deficient
- any chronic condition
- What to Use Instead of Nitrous Oxide?
- NuCalm - talk to your dentist about it
- Caffeine Elimination - might be good to advise patients to not drink coffee/caffeine before procedure.
- A growing body of research shows that people with red hair need larger doses of anesthesia and often are resistant to local pain blockers like Novocaine.
- MC1R gene belongs to a family of receptors that include pain receptors in the brain, as a result, a mutation in the gene appears to influence the body's sensitivity to pain
- Dr. Sessler: "The reason we studied redheads: 'redheads were difficult to anesthetize' was essentially an urban legend in the anesthesia community. This was so intriguing we went ahead and studied it: Redheads really do require more anesthesia, and by a clinically important amount."
As a dentist in private practice, I hear stories ALL the time about patients who "couldn't get numb at the dentist." Not surprisingly, many of the comments that readers post here on this site also deal with this very issue.
In response to this, I decided to compile a Top 5 list of reasons for why this happens. So here goes:
1. You have an infection
An active dental infection will usually result in the presence of pus. In most cases, the pus is acidic. Conversely, dental anesthetics (lidocaine, novcaine, etc.) function best in slightly basic environments. The end result is that the unique chemistryof the infection "deactivates" the local anesthetic, making it so that more anesthetic is needed. And in cases of severe infections, sometimes you simply cannot get the patient 100% numb.Sometimes, a patient comes in with an active infection and it can be difficult to get them completely numb. This is obviously very frustrating for both the dentist and the patient. Why does this happen?
2. You moved during the injection
Let's face it – some injections – but not all – hurt! And it just so happens that the one that hurts the most is the one that requires the most patient cooperation. I speak from experience having done this well over ten thousand times.
We have to sink this needle deep into the tissue. If you move, it is easy to miss the target. Paper clip is for scale.
For lower back teeth, we nearly always need to do a nerve block. This is where we have to go deep through muscle and other tissue and deposit the local anesthesia near the nerve. We can't actually see the nerve – we have to use various anatomical landmarks to guide us to the area.
If you move suddenly, the needle will also move. Most often, it will have moved away from the nerve! So we then end up depositing the anesthetic farther away from the nerve than we would like. What happens next? You don't get numb. Fortunately, if we have to administer a second injection, it will rarely hurt, and then we can place it spot on.
On rare occasions – and this has never happened to me nor most dentists – you can move so much that the needle can actually break!
3. I am not using epinephrine
I've blogged about this before. Epinephrine is added to dental local anesthetics because it enhances the numbness. How does it do this? Epinephrine acts as a vasoconstrictor and reduces blood flow in the area of the injection. The end result is that the local anesthetic stays around much longer and gives a more profound feeling of numbness.
Marcaine with epinephrine. The epinephrine will allow for a more profound level of local anesthesia
In certain circumstances, we use a local anesthetic that does not contain epinephrine. Why? Patients with certain cardiac conditions or who take certain medications are best served with one that does not contain it. Others have experienced a mild adverse reaction (some mistakenly think they are allergic to epinephrine) and prefer we don't use it. A small fraction of patients are allergic to the sulfite preservative so we can't use it in those cases either.
If we can't use epinephrine, there is a chance you won't feel numb enough. Or we'll have to re-inject multiple times.
4. You're wired differently
The human body is incredibly variable. People are double jointed. Remember the kid in grade school who could move his ears? Why is Usain Bolt faster then any other human? You get the picture.
Do you think your nerves look like the drawing below?
Nerves going to lower teeth. Each person is different! Image courtesy wikipedia commons.
If you answered yes, then you're probably wrong!
Most people have what I might call "standard anatomy." This means that the nerves going to your teeth are where you might expect them to be located. But just like Usain Bolt and the kid from fifth grade who could move his ears, some patients have extreme variability with the nerves going to their teeth. We see this most frequently with lower molars.
Some people may have up to 4 nerves going to their lower molar teeth. This can mean 4 different injections to get them numb! This doesn't mean your dentist is incompetent – it means you're wired differently. So if that happens to you, just think about Usain Bolt and the kid from fifth grade who could move his ears.
5. You have red hair
Joan from Mad Men would have difficulty getting numb!
I've blogged about this on two separate occasions – here and here.
But to summarize, people with red hair have a built in resistance to local anesthetics. This means that more local anesthetic is required to achieve profound numbness in those people with red hair. The reason behind this is complex, but the genetics for red hair also confers resistance to local anesthetic.
I can say definitively that from personal experience, redheads nearly always require more local anesthetic. All of my red haired patients are aware of this – and we joke about it each and every visit!
In my recent post titled 5 Reasons You Can't Get Numb at the Dentist, I laid out five reasons why this phenomenon occurs. This was based on years of experience as well as my own research.
In writing that post, it became clear that there were more than five reasons to explain the "I couldn't get numb" occurrence. So here are five more reasons why some patients experience this difficulty.
6. You have a Hot Tooth
Hot Teeth are tough to get numb!
If you are in severe pain in a specific tooth, it can be much more challenging to get you numb. This phenomenon, known by dentists as a hot tooth, produces these challenges in a different way than having an infection (infection was Reason #1 in the the first post on this subject.)
So why does this happen? There are two major reasons. When the nerve of a tooth becomes inflamed (such as from a large cavity), the nerve actually changes and becomes more excitable. Stated another way, the nerves are much more easily stimulated, and thus way more local anesthetic is needed.
The other reason is that the cavity can also cause the nerve to develop even more "receptors." While the specific details are not that important for this summary, it basically means that there are more nerves that need to be taken out by the local anesthetic.
The end result in these cases is that it can take several injections to get a hot tooth numb. And in rare cases, sometimes antibiotics and two days off are needed for the tooth to calm down enough to be properly anesthetized!
7. Your metabolism
The term metabolism is technically inaccurate. But it is the best term to describe that in some individuals, your vascular system removes the local anesthetic from the area of the tooth nerve much more quickly than in other individuals. This results in you being adequately numb for only a short period of time, or simply not being numb enough at all. In either case, you end up feeling pain during the dental procedure.
Modern dental anesthetics are primarily metabolized in the liver. So any dentist who says you are metabolizing the local anesthetic too quickly is technically incorrect. But that will be addressed in another blog post.
8. I just used expired local anesthetic!
Box and carpule of lidocaine. Yes, it can expire!
I can personally vouch that this has never happened to me. My assistants and I check the expiration date of each and every cartridge before injection. However, local anesthetic can and will expire. The average shelf life of local anesthetic is 12 to 18 months.
What happens if it expires? I really don't know – but like any expired medication, it will likely begin to break down and result in a decrease in efficacy.
9. I missed
In many cases, in order to achieve adequate numbness, a dentist has to do a nerve block.
Ultrasound guided nerve block. Courtesy wikipedia.
Nerve blocks are not unique to dentistry. The photo to the left shows a femoral nerve block being performed by an anesthesiologist. In this case, the anesthesiologist is using an ultrasound to help guide the needle. This is done because inserting the needle and guiding it to the nerve is difficult.
Dentists do not have the luxury of using an ultrasound. Nor is it practical. For many nerve blocks, we have to insert a needle one and a half inches deep and rely on several anatomic indicators to help guide us.
Ted Williams was the last baseball hitter to hit above .400. That means 60% of the time, he didn't get a hit. Most dentists have a batting average of around .900 for nerve blocks. So that means, just like Ted Williams, we sometime swing and miss! So we have to inject again. And sometimes again. It's part of doing nerve blocks… you don't always hit a home run on the first at bat.
10. You're Nervous
It is not a surprise that many people hate coming to the dentist. That it is a fact. Many people get very nervous coming to the dentist. That is a fact as well.
Dentistry is not a walk on the beach for most!
There is very little research to support my observation (and similar observations of other dentists) that patients who are very nervous tend to be more difficult to get numb.
Over the years, I've developed many theories for this. Many patients will forget to breathe and/or hold their breath. They may also clench their jaw muscles. Any of these will change the blood chemistry in a way that makes the local anesthetic less effective (similar to the blood chemistry changes I outlined in Point 1).
Since I do IV and Oral sedation dentistry, I've observed that patients who are sedated are much more easily numbed. This also suggests that nervousness and anxiety can make you more likely to experience pain.
The end result is that a nervous patient = a patient who may be difficult to get numb.
An eleventh and important reason – Ehlers Danlos – has its own post here.
[long list of personal horror story comments follows from which must can be learned if you can stomach it]
wolf max
just had lower molar #30 extracted, 3+ years after extracting the matching #19 molar on other side, both due to hairline crack slowly growing downward (likely from normal bite on hard objects mixed into food 5+ years earlier). both were excruciating, while all soft tissues were numb, i felt every millimeter of root bone moving through jawbone - tooth #30 was a 3 hr ordeal. one dds suggested some have super sensitive nerve endings inside the tooth/roots that just can't get numbed.
- nitrous oxide ruins your methylation and is not recommended these scenario:
- MTHFR variant
- B12 deficient
- Methylfolate deficient
- Glutathione deficient
- any chronic condition
- What to Use Instead of Nitrous Oxide?
- NuCalm (see below)
- Caffeine Elimination (see below)
I just kind of screamed and was in tears the whole time – Lori Lemon
I sat through the entire heart catheterisation and felt every bit. That is no place a patient wants to be – Lori Lemon
[long list of personal horror story comments follows from which must can be learned if you can stomach it]
[long list of personal horror story comments follows from which must can be learned if you can stomach it]
Around 50,000 Norwegians have a genetic variation that means they need a significantly higher dose of painkillers than the average person. Hundreds of people in Norway are completely unresponsive to opioids, such as morphine. (Illustrative photo: Colourbox)
For the first time, researchers have documented that about one in every hundred Norwegians needs a double dose of pain medication to get the same effect as other people.
About 50,000 people need a significantly higher dose than normal. And about a hundred people in Norway are completely resistant to opioids such as morphine.
Significant for cancer patients
The findings are of great importance for patients when they are operated on, or for individuals who are in severe pain – such as cancer patients.
A few years ago, Pål Klepstad, a professor at NTNU and an anaesthesiologist at St. Olav's Hospital in Trondheim, received a call from a physician colleague in western Norway. What started out as a routine operation subsequently turned out to solve a riddle among doctors and researchers:
Why do some patients require much higher doses of pain medication than others?
Doctor kept increasing the dose – with no effect
The patient, who was to be operated on for a hernia, had received the standard dose of a powerful painkiller, remifentanil, but it had no effect. So the doctor increased the dose. And increased it again. And again. Eventually, the patient had received 60 times the usual dose. But still he felt no effect. The doctor was amazed and called Klepstad in Trondheim.
Klepstad contacted fellow professor Frank Skorpen at NTNU's Department of Laboratory Medicine, Children's and Women's Health. Together they decided to investigate. They obtained permission from the patient to examine his genes via a blood test. Skorpen first tested for the most common genetic variants that might be suspected of influencing how pain medications work, but found no clues as to why the drug had no effect.
Special gene mutations
Enter NTNU PhD candidate Anne Heidi Skogholt, who was researching the gene that determines how opioids bind to the brain. When the researchers then analysed the patient's blood sample more extensively, they understood why the patient didn't react to 60 times the normal dose of morphine.
The patient had a special gene mutation, which had been described in the literature only once before – in a person in the United States.
What does it mean to have a gene defect like this?
We all have 46 chromosomes, arranged in 23 pairs. We inherit one chromosome set from each of our parents. Two of these chromosomes, X and Y, determine our sex. The patient who was resistant to morphine had the same mutation on both chromosomes in the same pair. The error causes the body's normal response to opioid pain killers, such as remifentanil, morphine, methadone and fentanyl, not to work. The opioids bind normally in the brain, but the signal isn't sent on to stop the pain.
This triggered Skorpen's curiosity: how many people in the Norwegian population might have this genetic error?
Could be suspected of using drugs
Skorpen obtained permission to check 600 healthy blood donors at St. Olav's Hospital, whose data Professor Ola Dale had collected as part of a related research project. Skorpen was able to document that approximately one person out of a hundred had this genetic defect on one chromosome in one pair.
This means that these people would probably need a double dose of opioid pain medication to achieve the same effect as people without this error. Skorpen and Klepstad further examined over 2,000 cancer patients, and calculated that one person in 40,000 will have this hereditary syndrome on both chromosomes in the same pair. These are the individuals who are completely insensitive to opioids.
"Many of the patients who need a double dose could easily be misunderstood by doctors. They might try to alter their prescriptions to get the effect they need, and be suspected of wanting to get high. It's important to emphasize that some patients actually need more painkillers to get the help they need," says Klepstad.
Totally different treatment
For patients who are resistant to opioids, doctors need to adjust the treatment, whether the patient is undergoing surgery or has intense pain due to cancer. One solution may be an epidural pump or anaesthesia.
"It's a simple matter to test whether someone has this genetic defect that leads to reduced efficacy or insensitivity to opioids," says Skorpen.
"But this is new information, and this test isn't routinely run in hospitals," Klepstad adds.
The body's natural pain relief
Thirty per cent of people in Norway report that they live with chronic pain. Skorpen and Klepstad now want to investigate whether there may be more people with this genetic defect among those who suffer from chronic pain. The gene error may also mean that the body's natural system for pain relief is not up to snuff, either. Skorpen and Klepstad will start their investigation with data from Norway's longitudinal HUNT study.
For the record: The patient who received 60 times the normal dose of remifentanil was not harmed by it. When the body does not respond to the drug, nothing happens, and the body excretes this medication relatively quickly.
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