People who can’t go numb from local anesthetic

The people who can’t go numb at the dentist’s – BBC – Jan 1, 2017

I have had problems with local anesthetics, but not dental. I’d love to hear from other people who don’t experience the full effect of anesthetics.

Some people are resistant to local anaesthetic, meaning they must endure dental and medical procedures without such pain relief. And we’re only beginning to understand why.

To Lori Lemon, the doctors all seemed flabbergasted. She had come in to the Mayo Clinic in Jacksonville, Florida, to have a lipoma – a growth of soft fatty tissue under the skin – removed from her elbow. She needed to have the area around the lump numbed for the procedure, but that was proving inexplicably difficult.

All the ways and all the different medications that they had at their disposal – none of them worked,” she says.  

She’d had this problem, local anaesthetic resistance, for as long as she could remember. The first time she remembers it coming up was decades ago at the dentists

He found a handful of stories scattered in the medical literature concerning strange cases where patients claimed local anaesthetic had no effect on them.

Alan Hakim and his colleagues at University College Hospital in London were some of the first scientists to bring these cases to light.

Hakim was helping to run a clinic for people with Ehlers-Danlos Syndrome (EDS), a group of very rare genetic diseases characterised by defects in connective tissue, leading to joint hypermobility, skin that bruises easily and fatigue

But Hakim found that some of these patients reported resistance to local anaesthesia. Instead of going numb, they were having to endure the pain. “It became obvious to us that it was a question we should ask every patient we see in the clinic,” recalls Hakim, who co-authored a short report about the findings in 2005.

One hypothesis is that their tissue is slightly different from non-EDS patients and that might affect how the anaesthetic is absorbed.

Local anaesthetics work by disrupting sodium channels.

These channels conduct positively charged sodium ions – and with them the feeling of pain – to nerve cells.

But there are still some questions over the nuts and bolts of this process.

Filling in the details of that mechanism might explain why some patients find certain drugs – say, articaine instead of lidocaine – work better than others.

One theory proposed for the heightened efficacy of articaine, for example, is that it is more soluble in fat (lipids) and therefore diffuses better through each nerve’s membrane.

It’s also possible that the patients’ nerves may be in slightly different places from the norm, with some evidence that dentists can overcome the problems by changing the location of the injection.

Sometimes local anaesthetic is injected into the tissue under the skin, known as infiltration, and sometimes it is injected into or next to a nerve, what’s called a nerve block.

Hakim says the work done by him and his colleagues has raised awareness among doctors and dentists that local anaesthetic resistance is a genuine problem.

But many today have never heard of it and are sceptical, when first told, that it even exists.

This goes along with the skepticism about pain in general. Because there is no proof, they have to rely on the patient’s word, and they seem more concerned about being fooled by a few than denying pain relief to many.

Some of her patients have told her that their doctor or dentist simply won’t believe them when they say “local anaesthetic doesn’t work on me”.

“I think until there’s that level of proof about it, it’s going to be very difficult to get doctors to accept it,” she says.

‘Missense mutation’

But there’s something else surprising about Lemon’s case: she has never been diagnosed with EDS. Could there be other reasons for her resistance to the anaesthetics?

They asked other members of Lemon’s family whether they experienced the same issue. It turned out that her mother and maternal half-sister shared the apparent resistance, though it wasn’t so pronounced, and yet her father did not.

The next step was to analyse the family members’ genomes. When Clendenen and his colleagues did this, they discovered a genetic defect relating to a specific sodium channel in the body, known as sodium 1.5.

The affected gene, called SCN5A, produces a protein called NaV1.5, which is a major component of this channel.

The type of mutation in question is known as a “missense” mutation, which means that one of the amino acids in the protein is different in people with this genetic quirk.

As a result, the functionality of the protein can be affected. A similar mutation means that people with sickle-cell anaemia, for example, have abnormal haemoglobin – the protein designed to carry oxygen in their blood

A chemical test, however, quickly showed that sodium 1.5 channels were present in peripheral nerves, so a genetic defect related to those channels could – in theory – inhibit anaesthetics in such areas of the body.

It’s not clear what difference is caused by having this mutation, but it could make the sodium channels more likely to remain open, allowing signals to flow to the brain, despite the application of local anaesthetic.

The anaesthetic usually inhibits the flow of sodium and therefore stops a pain signal being delivered from the nerve.

For those who have had to strain through invasive procedures at the doctor’s surgery without pain-relief, or undergo general anaesthetic just to have relatively routine dental work done, there might be fresh hope on the horizon.

“This is really important to get that out there,” says 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’.

Because of my problem with local anesthetics, I’ve become very apprehensive about medical procedures. Among people with EDS, this is not uncommon, but I didn’t know that earlier in life and suffered a few terribly painful procedures.

I wrote about this in KevinMD: When impossible pain is, in fact, possible

After they inject their “foolproof” local anesthetic, what doctor would believe my complaint of pain when they know I can’t feel anything?

I’d love to hear from others who have had such issues…

I also posted articles that show a link with hypermobility, the genetic basis for this, and my own experience:

• Local anesthetic failure in joint hypermobility syndrome
• Cause and genetics of local anesthetic resistance
• When Doctors Say My Pain Is Impossible…