The difference between a child who laughs off skinned knees and one who cries at the smallest pinch could be in their DNA. Subtle changes to a certain gene seem to determine how sensitive people are to pain, according to new research.

In the past 5 years, researchers have discovered that three rare but serious pain disorders are caused by mutations in a gene called SCN9A. In nerve cells that relay painful sensations in the body's tissues to the central nervous system, SCN9A encodes instructions for sodium channels that help the cells fire. In two of the disorders, people carry faulty versions of the gene and suffer crippling pain because their sodium channels open too easily or can't close. In the third disorder, which leaves patients unable to feel pain at all, SCN9A produces a protein that can't function.

"We wondered if more common, apparently harmless [changes] in the gene might give rise to an altered degree of pain threshold," says Geoffrey Woods, a medical geneticist at Cambridge University in the U.K., who discovered the genetic reason for this third disorder. So he and his colleagues examined differences in SCN9A in 578 patients with osteoarthritis. Controlling for the severity of the condition, they checked whether the patients' pain level was related to any one of 27 subtle genetic variations, known as single-nucleotide polymorphisms (SNPs), in SCN9A.

One SNP, found in 10% of the subjects, caused the greatest increase in reported pain between those who had it and those who didn't. The team then looked for the SNP and compared it to reported pain in four other groups: 195 Finnish people with sciatica; 100 Danish amputees, some of whom experienced phantom limb pain, or pain in the limbs they had lost; 179 people who had had a lumbar disk removed to treat lower back pain; and 200 people with pancreatitis. Sciatica patients and amputees who reported more pain were more likely to have the SNP. The researchers also saw a positive trend, though not a statistically significant one, among the lower-back-pain patients and pancreatitis patients. But when the groups were combined, the statistical link between having the rare SNP and feeling more pain was impressively strong. When the team applied heat stimuli to 186 healthy women, they found that those with the rare version were more likely to have lower pain thresholds. It was as if the normal subjects had taken an ibuprofen, but the subjects with the rare SNP hadn't, Woods says. His team reports the results online today in the Proceedings of the National Academy of Sciences.

Woods's group also sought to determine how the SNP was causing more pain. When they placed the altered SCN9A gene in kidney cells, which serve as blank slates because they don't have this sodium channel, they found that the cells grew sodium channels that were "slightly less efficient" at squeezing shut after they had let sodium in and triggered the neuron, Woods says.

Woods warns that this effect is so subtle that it might not be directly due to the SNP. But the results do seem to show that sensitivity to pain is hard-wired. "Some people are stoic and some aren't. ...Maybe there's a plausible biological reason for that difference," Woods says.

In the groups Woods studied, between 15% and 18% of patients had one copy of this variant, while 2% to 3% had two copies of the variant, making them even more sensitive to pain. Meanwhile, about 20% of adults develop chronic pain, a statistic that's been "very difficult to link with the severity of injury and the severity of ongoing damage," says MacDonald Christie, a neuroscientist at the University of Sydney in Australia. This genetic variation "could go part of the way to explaining why some people have much more serious chronic pain than others."

Even as the Union Health Ministry is planning to bring out a legislation to break the cash-or-gift-for-prescription nexus between doctors and the pharmaceutical industry, the Medical Council of India (MCI) is going ahead to decide the nature and quantum of punishment to be imposed on doctors caught accepting considerations in cash or kind from pharma companies.

MCI chairman Dr Ketan Desai said that this would now be thrashed out in the MCI general body meeting on March 12 and 13.

Not that the doctors bodies have been too eager about it. On the face of it, it took three years and many reminders from the MCI to all medical associations, even to notify this regulation in the official gazette a few months ago.

"MCI had approached all national medical associations in India, including those of physicians, nephrologists and gynaecologists and cardiologists, in an attempt to come up with this new regulation. We had started this process in 2007. We sent no less than four official reminders to these associations, none of them responded," said the MCI chief.

A seven-valent pneumococcal conjugate vaccine can protect adults with HIV against recurrent pneumococcal infection, according to research published in the March 4 issue of the New England Journal of Medicine.

Neil French, Ph.D., of the Malawi-Liverpool-Wellcome Trust Clinical Research Programme in Blantyre, Malawi, and colleagues analyzed data from 496 patients, aged 15 years and older, who had recovered from invasive pneumococcal disease. Most (88 percent) were HIV-positive. Subjects were given two doses of vaccine four weeks apart or placebo. The main end point was another episode of pneumococcal disease caused by a vaccine serotype or serotype 6A.

The researchers found that all episodes of disease were in individuals with HIV. Twenty-four patients developed episodes of pneumococcal disease caused by vaccine serotypes or the 6A serotype. Of these, 19 occurred in the placebo group and five occurred in the vaccine group, for a vaccine efficacy of 74 percent. Deaths weren't statistically different in the vaccine and placebo group (73 and 63, respectively).

"We have shown that HIV-infected adults can have a clinically relevant response to a pneumococcal conjugate vaccine, leading to protection against a common and serious co-infection. The ability of a conjugate vaccine to generate protective responses in patients with a low CD4+ count is of particular note and merits further study to elucidate the immune mechanisms involved and how such mechanisms may be used to produce other vaccines for this population," the authors write.

In an experiment, laboratory mice consumed low-fat diets that were identical except that they contained either soluble or insoluble fibre. After six weeks on the diet, the animals had distinctly different responses when the scientists induced illness by introducing a substance (lipopolysaccharide) that causes the body to mimic a bacterial infection.

"Two hours after lipopolysaccharide injection, the mice fed soluble fibre were only half as sick as the other group, and they recovered 50 per cent sooner. And the differences between the groups continued to be pronounced all the way out to 24 hours," said Christina Sherry, who worked on the study.

The new University of Illinois study touts the benefits of soluble fibre. It reduces the inflammation associated with obesity-related diseases and strengthens the immune system.

"Soluble fibre changes the personality of immune cells - they go from being pro-inflammatory, angry cells to anti-inflammatory, healing cells that help us recover faster from infection," said Gregory Freund, a professor in the University of Illinois' College of Medicine. This happens because soluble fibre causes increased production of an anti-inflammatory protein called interleukin-4, he said.

Now Freund has a new question: Could soluble fibre offset some of the negative effects of a high-fat diet, essentially immunizing obese persons against the harmful effects of fat?

Scientists have long known that obesity is linked to inflammatory conditions, such as diabetes and heart disease.

Yet, in a recent study, the University of Illinois scientists demonstrated that fat tissue produces hormones that appear to compensate for this inflammation. "There are significant anti-inflammatory components in fat tissue and, if they were strategically unleashed, they could potentially protect obese people from further inflammatory insults, such as a heart attack or stroke. In obese animals, you can see the body compensating in an effort to protect itself," he said.

Not all fat is bad, the researcher noted. The Mediterranean diet, which receives high marks for its health benefits, includes such foods as olive oil; salmon, tuna, sardines, and trout, which contain important omega-3 and -6 fatty acids; and plant sources of fat, such as flaxseed.

"Now we'd like to find a way to keep some of the anti-inflammatory, positive effects that develop over time with a high-fat diet while reducing that diet;s negative effects, such as high blood glucose and high triglycerides. It's possible that supplementing a high-fat diet with soluble fibre could do that, even delaying the onset of diabetes," he said.

This study is one of the first to provide two valuable lessons, said Sherry. The first, already noted, is that soluble fibre has direct anti-inflammatory effects and builds up the immune system. The second is that the amount of soluble fibre necessary to achieve these health benefits is a reasonable, not a pharmacological, amount, according to a University of Illinois press release.

Scientists have developed a gene test which predicts how well chemotherapy will work in cancer patients.

Starting with 829 genes in breast cancer cells, the team whittled down the possibilities to six genes which had an impact on whether a drug worked.

They then showed that these genes could be used to predict the effectiveness of a drug called paclitaxel in patients.

It is hoped the approach, reported in The Lancet Oncology, can be replicated for other cancers and treatments.

The international project, including researchers from Cancer Research UK's London Research Institute, opens the way for breast cancer treatment to be targeted to those who will benefit the most.

To find which genes, if missing or faulty, could prevent the drug from working, they deleted them one by one from cancer cells in the laboratory.

They eventually highlighted the six genes which if absent or not working prevent paclitaxel from properly killing breast cancer cells.

Spare treatment

More than 45,500 women are diagnosed with breast cancer in the UK each year - and it is estimated that around 15% of these women will be prescribed paclitaxel.

The researchers estimate they could potentially spare half of the patients currently receiving this drug from treatment which would not be effective.

Study leader, Dr Charles Swanton, head of translational cancer therapeutics at the Institute, said one of the great challenges in cancer medicine is determining which patients will benefit from particular cancer drugs, which are in themselves toxic and carry severe side effects.

"Our research shows it is now possible to rapidly pinpoint genes which prevent cancer cells from being destroyed by anti-cancer drugs and use these same genes to predict which patients will benefit from specific types of treatment."

Further studies will now be done to see if the technique can be developed into a simple diagnostic test to be given to patients to help inform doctors about whether or not to prescribe paclitaxel.

He said the challenge will be to apply these methods to other drugs in cancer medicine.

"These could include treatments that are currently deemed too expensive to fund on the NHS - however, in the future, treating only the patients that will benefit from certain treatments will save the NHS money in the long term."

Dr Lesley Walker, Cancer Research UK's director of cancer information, said: "New techniques such as these can enable drugs to be tailored to individual patients, and this could potentially improve cancer survival in the long term.