Strong painkillers not working? Why it could be down to your genes...

I’ve never had to give anyone ne as much sedative as that at before,’ the anaesthetist st remarked as I came round from m my knee replacement surgery ry last October. ‘I used almost a whole bottle. You kept pt moving so I had to keep giving you more.’ e.’

Although I hadn’t been sufficiently tly conscious to feel discomfort, he’d clearly rly thought I was at risk of experiencing pain. in.

Heavily sedated, numb from the waist ist down and immensely relieved this longdreaded ngnk operation was over, I didn’t think much about it at the time.

The sedation was given after my spinal nal injection, similar to an epidural and nd commonly used for knee replacements.

I knew what to expect from my previous us knee replacement in 2021. I frequently had ad to ask for more Oramorph (oral morphine), e), post-op — and it didn’t help much.

This time, it had even less effect. ct. The vile-tasting liquid made me feel sick, ck, and the day after my second operation, ,I took it at least 12 times, but it had barely ely any impact.

I was concerned about the quantity I was as taking, but my nurses said the amount I’d had was fine, though probably more than an many people take.

I was in such pain when discharged two wo days after surgery, that one of the doctors ors prescribed me morphine in tablet form to take home for five days.

Stronger than Oramorph, it blunted the he pain, but made me feel so sick. I barely ate for two weeks, losing 11 lb. Friends who ho know of my ongoing weight battle said: id: ‘Oh well ... every cloud.’ But I’d rather have ve kept the weight on than feel so awful.

Over the next month or so, due to all the morphine, I became chronically constipated, had brain fog and life was miserable. At night, after I’d reached my daily morphine limit, the pain brought me to tears.

When my five-day supply ran out, I felt anxious, miserable and couldn’t sleep. A nurse friend said I was withdrawing from morphine. I turned to ibuprofen and paracetamol, but despite sticking to the daily dose, it upset my stomach so badly I suffered debilitating diarrhoea for a week, so my GP advised me to stop. In agony, I barely slept for four weeks.

T HREE months later, much improved, I called a specialist to discover if my experience with poor pain relief was common.

Apparently, it is, explains Dr vivek Mehta, a consultant in pain medicine at Barts Health NHS Trust in London: ‘Some patients are missing an enzyme, CYP2D6, that affects the body’s ability to metabolise pain relief drugs, including some opioids.’

There are private tests available for the missing enzyme. Whether you have this enzyme is genetic. ‘Its absence affects 7-10 per cent of the caucasian population,’ says Professor roger Knaggs, president- elect of The British Pain Society. He says a separate enzyme can affect how morphine specifically is metabolised — problems with this are less common.

Some people may have the CYP2D6 enzyme, but ‘ it’s too weak to do the job’, says Dr Mehta. But the picture is complicated, explains Professor Knaggs, with ‘ at least 200 different genes implicated in how we perceive pain. There is often no single answer as to why people react differently to certain analgesics.’ Another factor is that in some people the opioid receptors — proteins that are dotted throughout nerve cells in the brain, spinal cord, gut and elsewhere — become damaged. These receptors stop the electrical pulses that generate the sensation of pain from travelling through our nerve cells to the brain via the spinal cord.

Opioids attach to these receptors, blocking pain messages. Other people may have fewer such receptors, says Professor Knaggs, adding that environmental factors — such as car fumes — could also damage these receptors. So too could age, weight, sex, liver and kidney function, smoking and alcohol.

While the exact cause isn’t clear, Dr Mehta says it’s important for both you and your doctor to be aware if you have a resistance to pain medication, so that you can be prescribed correctly.

Discovering this can be a distressing process of trial and error, as former laywer Anna McKay, 67, discovered.

Anna, from London, developed ‘a terror of the dentist’ as a child, as injections to numb her mouth ahead of fillings never worked. Believing the pain was ‘just normal’, she spent her 20s avoiding the dentist as she was ‘too frightened of the pain’.

Anna also tried over-the-counter painkillers including paracetamol and ibuprofen for dental pain, with limited success.

‘My firm belief is that pain medication doesn’t work for me,’ she says — a view reinforced by the fact she gave birth to both of her sons without effective pain relief.

After an epidural for her first labour ‘did nothing’, she didn’t bother with pain relief for the second, convinced that ‘pain was normal and drugs didn’t work’.

When it comes to dental pain, resistance to the effect of local anaesthetics such as lidocaine could be due to a genetic defect relating to sodium channels, according to a 2005 study at University College London.

Sodium channels conduct sodium molecules through our nerve cells — the mechanism by which the pain sensation is transmitted. The local anaesthetic usually disables this process: but in people with the genetic defect, the channels remain open, so the pain message is delivered.

Our emotional state can also play an important role, says Dr Dev Srivastava, a consultant in anaesthesia and pain pa medicine at raigmore Hospital Hospital, in Inverness. ‘If someone is fee feeling angry or anxious, they will feel f more pain, which can make it seem as if the painkillers aren’t working. w It is an under-recognised p problem.’

He says such pat patients are usually ally offered a ‘bouq bouquet of psychological logical therapies’ in including cognitive tive behavioural the therapy (CBT) .

Painkiller or analg analgesic resistance is very much a new a area of interest now being examin examined under the umbrella of pharm pharmacogenomics — the study of how genetics can affect a patient’s reaction re to medicine icine by identify identifying relevant genetic variants that th impact how they metabolise pa particular drugs.

A 2019 paper by NH NHS Health england’s land’s Genome ed education programme gramme says: ‘Pha Pharmacogenetics has enormous pote potential to enable more accurate prescribing for better treatment and less waste.’

MEANWHILE, for patients, knowing the problem actually exists can be an important start. Mother-of-two Maddy Alexander-Grout, 39, from Southampton, has suffered from analgesic resistance for years, trying numerous forms of relief but none worked.

‘The morphine [Oramorph] I was given for my first labour made me feel sick and spaced out, but the pain was the same,’ she says.

For her second labour three years later, she asked for an epidural — ‘that didn’t work either. Both births were excruciating’.

Maddy realised she had a problem with resistance to anaesthetic when she needed three injections at the dentist just to have a filling five years ago. ‘It got me thinking about how no anaesthetic or pain relief ever works on me.’

When I explained to Dr Srivastava about my needing extra sedation during surgery, he suggested it was because I was anxious. I’m not convinced as I wasn’t aware of feeling particularly anxious.

‘How emotions can impact on the effectiveness of analgesics is also something we need to know more about,’ he said.

‘What we do know is that everyone is different. Some people need less, others need more. It depends on how sensitive you are to it. And of course on your genetics.’