Morphine may not be as effective for some women

Experiments in rats may have revealed why some painkilling drugs are less effective in women compared with men.

US researchers found brain differences affecting the potency of opioids such as morphine.

The Journal of Neuroscience study also found drug effectiveness varied during the rats’ menstrual cycles.

Another expert said it showed the growing importance of tailoring pain relief to match the individual needs of the patient.

Morphine remains one of the most widely used drugs to alleviate severe persistent pain and doctors have noticed that it frequently does not work as well in women.

However, the study from Georgia State University claims to be the first to pinpoint the reason why.

It looked closely at a tiny area of the brain called the periaqueductal grey area (PAG), which is important in the way that pain signals are interpreted.

Many neurons in this region have, on their surface, “receptors” designed to receive and lock onto the molecules found in opioid drugs.

These “mu-opioid receptors”, when locked onto an opioid drug, send a message telling the brain to stop responding to pain signals, reducing the sensation of pain.

The Georgia State team found that, in the rat brain, females had a lower level of mu-opioid receptors in this part of the brain, suggesting that the potential potency of morphine is much reduced.

Additional tests suggested that the response to morphine varied depending on which part of the menstrual cycle the female rat was in.

Better treatment

Professor Anne Murphy, who led the research, said: “It is increasingly clear that morphine is significantly less potent in women compared with men - until now, the mechanism driving the phenomenon was unknown.

“Additional research with the inclusion of female subjects needs to be devoted to determining a more potent treatment for persistent pain in women.”

Professor Karen Berkley, from Florida State University, described the research as “important” and called for more attention to be paid to make sure that women received adequate pain relief.

“What this research is trying to do is understand the hormonal influences on pain in women.

“Clinicians are becoming far more aware of this issue, certainly more than they were five or six years ago.”

Human trials, already under way, would need to be concluded to confirm the results of this study, she said.

However, researchers from Northwestern University’s Feinberg School of Medicine believe the symptoms — pain and an urgent need to frequently urinate — are actually being provoked by a surprise perpetrator. Applying their recent animal study to humans, the scientists believe the colon, irritated by the spicy food, is to blame.

Their idea opens up new treatment possibilities for “painful bladder syndrome,” or interstitial cystitis, a condition that primarily affects women (only 10 percent of sufferers are men.) During a flare up, the pelvic pain is so intense some women administer anesthetic lidocaine directly into their bladders via a catheter to get relief. Patients typically also feel an urgent need to urinate up to 50 times a day and are afraid to leave their homes in case they can’t find a bathroom.

“This disease has a devastating effect on people’s lives,” said David Klumpp, principal investigator and assistant professor of urology at the Feinberg School. “It affects people’s relationships with family and friends.” Klumpp said some women who suffer from this become so depressed, they attempt suicide.

Klumpp worked with Charles Rudick, a postdoctoral fellow at the Feinberg School, on the paper, which was published in the September issue of Nature Clinical Practice Urology.

The Northwestern researchers believe the colon’s central role in the pain is caused by the wiring of pelvic organ nerves. Nerves from this region — the bladder, colon and prostate — are bunched together like telephone wires and plug into the same region of the spinal cord near the tailbone.

People with interstitial cystitis have bladder nerves that are constantly transmitting pain signals to the spinal cord: a steady beep, beep, beep.

But when the colon is irritated by pepperoni pizza or another type of food, colon nerves also send a pain signal to the same area on the spinal chord. This new signal is the tipping point. It ratchets up the pain message to a chorus of BEEPEEPBEEPBEEP!

“It was known that there was cross talk between organs, but until now no one had applied the idea to how pain signals affect this real world disease, how the convergence of these two information streams could make these bladder symptoms worse,” said Klumpp, who also is an assistant professor of microbiology-immunology at the Feinberg School.

The new model suggests the bladder pain can be treated rectally with an anesthetic in a suppository or gel. Another possibility is an anesthetic patch applied to pelvic skin. Studies in back pain show anesthetic patches applied to the skin can reduce back pain, Klumpp said.

“We imagine a similar kind of patch might be used to relieve pelvic pain, which might be the best solution of all,” he noted.

Klumpp’s concept is based on a 2007 study in which he showed that delivering red pepper into the colon of a mouse with pre-existing pelvic pain caused the pain to worsen. When he then delivered lidocaine into the mouse colon, “it knocked down pain just as effectively as if we put it in the bladder,” Klumpp said.

“We likened it to what happens to humans,” Klumpp noted. “Pepperoni pizza does nothing to most people other than heartburn, but when you give it to a person with an inflamed bladder, that will cause their symptoms to flare because the nerves from the bladder and bowel are converging on the same part of the spinal cord.”

Ben once pulled a tooth out without feeling any pain

Like any other toddler, Ben Whittaker has had his fair share of bumps and bruises. The difference is he doesn’t feel any pain.

The 17-month-old from Royston, Yorkshire, is only the 33rd person ever to be diagnosed with the condition.

When Ben fractured his heel bone, he ran around as if nothing was wrong, and he shed no tears after pulling out a tooth.

His parents, Wayne and Joanne, say they cannot let him out of their sight.

The couple first noticed that Ben was different to other toddlers when he was nine months old. He took a hot chip from his father’s plate and blistered three fingers - without showing any signs of distress.

The health visitor suggested there may be something unusual about the way Ben dealt with pain.

The toddler then broke his heel bone while he was playing at home.

When he was taken to hospital for treatment, doctors saw Ben running around despite having a plaster cast on his foot.

Wayne Whittaker told the BBC News Website the doctors had said Ben would have been “in agony” if he had been an adult.

‘It makes things difficult’

After a series of tests at Sheffield Children’s Hospital, Ben was diagnosed as having congenital indifference to pain, an incredibly rare condition.

Experts have suggested it could be caused by the failure of a substance called betaendorphin, which occurs naturally in the body and modulates pain sensations.

Mr Whittaker said: “It was a case of putting two and two together. He didn’t cry when he banged his head, and he didn’t cry when he had his inoculations.

“He may feel no pain at all, or he may feel pain differently to other children. We won’t know until he can communicate.”

He said the condition was becoming more of a problem as Ben got older.

“When he was a baby, it didn’t really affect him. But when he started to crawl, and now he can walk and run, it does. He keeps banging his head, but it doesn’t bother him.”

Ben is healthy in all other ways, and has a toddler’s natural curiosity - meaning he is at the stage where he is keen to climb and explore.

Mr Whittaker said the couple were terrified Ben would put his hand into the fire or burn himself on the radiator - but not feel anything.

The couple have another child, Katie, who is three months old, and Wayne said it could be difficult for his wife Joanne to keep an eye on Ben.

Mr Whittaker added: “It obviously makes things difficult. But you just can’t let him out of your sight.”

Doctors have told them there is nothing they can do to alleviate Ben’s condition, and it is something he will have to live with. They have been warned it is possible Katie will also be affected.