ISLAMABAD – A new study has described how a cell therapy might one day be used not only to quell some common types of persistent and difficult-to-treat pain, but also to cure the conditions that give rise to them.
UCSF scientists, working with mice, focused on treating chronic pain that arises from nerve injury-so-called neuropathic pain.
In their study, the scientists transplanted immature embryonic nerve cells that arise in the brain during development and used them to make up for a loss of function of specific neurons in the spinal cord that normally dampen pain signals.
A small fraction of the transplanted cells survived and matured into functioning neurons. The cells integrated into the nerve circuitry of the spinal cord, forming synapses and signalling pathways with neighbouring neurons.
As a result, pain hypersensitivity associated with nerve injury was almost completely eliminated, the researchers found, without evidence of movement disturbances that are common side effects of the currently favoured drug treatment.
“Now we are working toward the possibility of potential treatments that might eliminate the source of neuropathic pain, and that may be much more effective than drugs that aim only to treat symptomatically the pain that results from chronic, painful conditions,” said the senior author of the study, Allan Basbaum, PhD, chair of the Department of Anatomy at UCSF.
Those who suffer from chronic pain often get little relief, even from powerful narcotic painkillers, according to Basbaum. Gabapentin, an anticonvulsant first used to treat epilepsy, now is regarded as the most effective treatment for neuropathic pain. However, it is effective for only roughly 30 percent of patients, and even in those people it only provides about 30 percent relief of the pain, he said.
The explanation for neuropathic pain, research showed, is that following injury neurons may be lost, or central nervous system circuitry may change, in ways that are maladaptive, compromising signals that normally help dampen pain. These changes contribute to a state of hyper-excitability, enhancing the transmission of pain messages to the brain and causing normally innocuous stimuli to become painful.
The inhibitory neurons that are damaged in the spinal cord to cause pain hypersensitivity release a molecule that normally transmits inhibitory signals - the neurotransmitter GABA. A loss of GABA inhibition also is implicated in epilepsy and may play a role in Parkinson’s disease. Gabapentin does not mimic GABA, but it helps to compensate for the loss of inhibition that GABA normally would provide.
Basbaum”s UCSF colleagues, including study co-authors Arturo Alvarez-Buylla, PhD, and Arnold Kriegstein, MD, PhD, along with Scott Baraban, PhD, had already been experimenting with transplanting immature neurons that make GABA, using the transplanted neurons to bolster inhibitory signals in mouse models to prevent epileptic seizures and to combat a Parkinson”s-like disease.
However, in those experiments the cells - which originate in a region of the forebrain known as the medial ganglionic eminence - were transplanted within the brain itself, which is their normal home.
Upon hearing about the research, Basbaum became interested in transplanting the same cells into the spinal cord as a potential treatment for the loss of GABA-driven inhibition in neuropathic pain. Success was by no means assured, as cells normally do not survive outside their natural environments within such a complex organism.
Another co-author of the Neuron study, UCSF researcher John Rubenstein, PhD, has made major progress in identifying molecules that can be manipulated to lead an embryonic stem cell to go through developmental stages that cause it to acquire the properties of GABA neurons that derive from the medial ganglionic eminence.
According to Kriegstein, who directs the Eli and Edythe Broad Centre of Regeneration Medicine and Stem Cell Research at UCSF, “This research is at a very early stage, and we’re a long way from thinking about it in human trials, but we do have a method of making cells that are like these inhibitory neurons, starting with human embryonic stem cells.”
As a step toward eventual therapies, the UCSF team plans to graft fatal human cells from the medial ganglionic eminence, or cells derived from human embryonic stem cells, into a rodent model of neuropathic pain, to see if the human cells also will alleviate neuropathic chronic pain. The study was recently published in Neuron.
Calcium pills raise heart attack risk
Taking calcium supplements can push up the risk of a heart attack, and could do more harm than good, warn researchers.
People take calcium supplements as they are recommended for strengthening bones against osteoporosis. But, according to the study, the supplements can no longer be seen as a low-cost panacea against thinning bones, Daily Mail reported Thursday.
Instead, the scientists suggest, people should eat more calcium-rich foods like milk, cheese and green, leafy vegetables. Researchers looked at records for 24,000 people in Germany aged 35 to 64 taking part in a nutrition research project in the 1990s. Their diet was analysed and they were asked if they had taken vitamin or mineral supplements in the previous month.
The volunteers were tracked for 11 years, during which there were 354 heart attacks, 260 strokes and 267 associated deaths, the Mail said.
Those taking any supplements, including calcium, were found to be 86 percent more likely to have a heart attack than those who did not take any. But the risk for those taking only calcium was even higher.
Ian Reid and Mark Bolland, of the University of Auckland, New Zealand, said people should be discouraged from taking the boosters.
Babies born by caesarean more likely to be obese
Babies born by caesarean section are more likely to become obese children than those delivered naturally. Researchers said the obesity epidemic could be driven in part by rising rates of surgical deliveries. The rate of caesareans in England is almost 25 percent, which totals around 155,000 a year, Daily Mail reported.
The operation can be life-saving for mother and baby but about seven percent of National Health Service (NHS) surgical births occur for no medical reason.
Researchers from Boston Children’s Hospital, US, examined 1,225 mother-and-child pairs over three years, weighing them and measuring the babies’ body fat. One in four of the deliveries was by caesarean.
After taking into account obesity in the mother and other factors, they found almost 16 percent of children delivered by caesarean were obese by the age of three compared with 7.5 percent born naturally.