Strong painkillers barely worked for me during my agonising knee surgery

I’ve never had to give anyone so much sedative,’ the anesthesiologist remarked when I recovered from my knee replacement surgery last October.

“I used almost a whole bottle. You kept moving, so I had to give you more and more.’

Although I hadn’t been conscious enough to feel discomfort, he clearly thought I was at risk of experiencing pain.

Heavily sedated, numb from the waist down, and immensely relieved that this long-dreaded surgery was over, I didn’t think much of it at the time.

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

I knew what to expect from my previous knee replacement in 2021. I often had to ask for more Oramorph (oral morphine) after surgery – and it didn’t help much.

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

I was concerned about the amount I was taking, but my nurses said the amount I had was fine, although probably more than many people take.

When I was discharged from the hospital two days after surgery, I was in so much pain that one of the doctors prescribed me morphine in tablet form to take home for five days.

Stronger than Oramorph, it eased the pain, but made me feel so nauseous. I barely ate for two weeks and lost 11 pounds. Friends who knew about my ongoing weight struggle said, “Oh well… every cloud.” But I would rather have kept my weight than feel so horrible.

Over the course of the next month or so, all the morphine left me chronically constipated, had brain fog, and life was miserable. At night, after I hit 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 coming off morphine. I turned to ibuprofen and paracetamol, but despite sticking to the daily dose, my stomach was so upset I had debilitating diarrhea for a week, so my GP advised me to stop. In agony, I barely slept for four weeks.

Three months later, much improved, I called a specialist to find out if my experience of poor pain relief was common.

Apparently so, explains Dr Vivek Mehta, a pain medicine consultant at Barts Health NHS Trust in London: ‘Some patients lack an enzyme, CYP2D6, which affects the body’s ability to metabolise painkillers, including some opioids.’

Private tests are available for the missing enzyme. Whether you have this enzyme is hereditary. “Its absence affects 7-10 per cent of the white population,” said Professor Roger Knaggs, president-elect of The British Pain Society. He says a separate enzyme may affect how specifically morphine is metabolized – problems with this are less common. Some people may have the CYP2D6 enzyme, but “it’s too weak to do the job,” Dr. Mehta says. But the picture is complicated, explains Professor Knaggs, with ‘at least 200 different genes involved in how we perceive pain. There is often no clear answer to why people respond differently to certain painkillers.’

Another factor is that in some people, the opioid receptors — proteins that are distributed throughout nerve cells in the brain, spinal cord, gut, and elsewhere — become damaged. These receptors prevent the electrical pulses that generate the sensation of pain from passing through our nerve cells to the brain through the spinal cord.

Opioids attach to these receptors and block pain messages.

Other people may have fewer such receptors, says Professor Knaggs, adding that environmental factors – such as car fumes – can also damage these receptors. This also applies to age, weight, gender, 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 resistance to pain medication so you can be prescribed correctly.

Discovering this can be a disturbing process of trial and error, as former attorney Anna McKay, 67, found out.

Anna, from London, developed ‘a fear of the dentist’ as a child because injections to numb her mouth before fillings never worked. Believing the pain was “just normal,” she spent her 20s avoiding the dentist because she was “too afraid of the pain.”

Anna also tried over-the-counter pain relievers, including acetaminophen and ibuprofen, for toothaches, with limited success.

“I’m a firm believer that pain meds don’t work for me,” she says — a view reinforced by the fact that she gave birth to both of her sons without effective pain relief.

After an epidural for her first delivery “did nothing,” she took no pain relief for the second, convinced that “pain was normal and meds weren’t working.”

When it comes to toothaches, resistance to the effect of local anesthetics such as lidocaine may be due to a genetic defect involving 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 anesthetic usually shuts down this process: but in people with the genetic defect, the channels remain open so that the pain message is delivered.

Our emotional state can also play an important role, says Dr Dev Srivastava, a consultant in anesthesia and pain medicine at Raigmore Hospital in Inverness. “If someone is angry or anxious, they will feel more pain, which can make it seem that the painkillers are not working. It’s an undervalued problem.’

He says such patients are usually offered a “bouquet of psychological therapies,” including cognitive behavioral therapy (CBT).

Resistance to analgesics or analgesics is a new area of ​​interest now being explored under the umbrella of pharmacogenomics – the study of how genetics can influence a patient’s response to drugs by identifying relevant genetic variants that influence how they metabolize certain drugs.

A 2019 paper from NHS Health England’s Genome Education program says: ‘Pharmacogenetics has enormous potential to enable more accurate prescribing for better treatment and less waste.’

Meanwhile, knowing that the problem really exists can be an important start for patients. Mother of two Maddy Alexander-Grout, 39, from Southampton, has suffered from painkiller resistance for years and has tried countless forms of relief but none have worked.

‘The morphine [Oramorph] I got it before my first delivery, which left me feeling nauseated and distant, but the pain was the same,” she says.

For her second delivery three years later, she asked for an epidural – “that didn’t work either.” Both deliveries were unbearable.

Maddy realized she had a problem with anesthesia resistance when she needed three injections at the dentist to get a filling five years ago. “It got me thinking about how no anesthesia or pain relief ever works for me.”

When I explained to Dr. Srivastava that I needed extra anesthesia during the surgery, he suggested that it was because I was anxious. I’m not convinced because I wasn’t aware of the fact that I felt particularly anxious.

“How emotions can influence 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.’