During my excruciating knee surgery, strong painkillers scarcely worked for me. Do you have genes that prevent medicine from working? 2023

During my knee replacement surgery last October, the anesthesiologist said, “I’ve never had to give someone that much sedative.”

‘Almost the whole bottle. I gave you extra since you continued moving.

He feared I may feel pain even if I wasn’t conscious.

I was heavily drugged, numb from the waist down, and pleased this long-dreaded procedure was completed.

My spinal injection—similar to an epidural and used for knee replacements—provided drowsiness.

My 2021 knee replacement was familiar. Post-op, I regularly requested additional Oramorph (oral morphine), but it didn’t help.

Even little effect this time. The vile-tasting liquid made me nauseous, and I took it at least 12 times the day following my second surgery, but it had no effect.

My nurses assured me that the amount I was taking was fine, albeit certainly more than most people.

Two days after surgery, one doctor recommended me morphine tablets to take home for five days since I was in so much agony.

It relieved pain more than Oramorph but made me queasy. During two weeks, I rarely ate, shedding 11 lb. My weight-fighting friends remarked, “Oh well… every cloud.” I’d rather have retained the weight than felt so miserable.

Morphine caused severe constipation, cognitive fog, and misery throughout the next month. After my daily morphine limit, the discomfort made me cry at night.

I panicked and couldn’t sleep when my five-day supply ran out. Morphine withdrawal, according to a nursing friend. I took ibuprofen and paracetamol everyday, but it hurt my stomach so terribly. My Physician urged me to cease after a week of terrible diarrhoea. Four weeks of misery kept me awake.

Three months later, significantly improved, I phoned a doctor to see whether my inadequate pain relief was usual.

According to London pain medicine consultant Dr. Vivek Mehta: Some people lack the enzyme CYP2D6, which inhibits the body’s capacity to metabolize painkillers, especially opioids.

Missing enzyme tests are confidential. This enzyme is inherited. Professor Roger Knaggs, president-elect of The British Pain Society, claims that 7-10% of Caucasians lack it. He adds a different enzyme can change how morphine is metabolized—this is rare. Dr. Mehta says CYP2D6 is “too weak to do the job” in some people. Professor Knaggs says ‘at least 200 different genes implicated in how we perceive pain’ complicates the picture. Why people react differently to analgesics is largely unknown.

Opioid receptors—proteins found in nerve cells in the brain, spinal cord, gut, and elsewhere—can also be damaged. These receptors block pain-causing electrical pulses from reaching the brain via the spinal cord.

Opioids inhibit pain signals at these receptors.

Professor Knaggs believes some people have fewer such receptors, and environmental factors like automobile fumes can harm them. Age, weight, sex, liver and renal function, smoking, and drinking might too.

Dr. Mehta advises patients and doctors to be mindful of pain medication resistance, even if the cause is unknown.

Former lawyer Anna McKay, 67, learned this the hard way.

As a kid, Londoner Anna had “a phobia of the dentist” since injections to numb her mouth before fillings failed. She avoided the dentist throughout her 20s, believing the pain was “simply normal.”

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