Tag Archives: nerve cell

How nerve cells reach their niche.

Developmental biology, the study of the processes through which organisms grow and develop, is an area of biomedical research where modal organisms – ranging from the slime mold Dictyostelium  discoideum to the chicken – play a crucial role, and one that has been honoured with several  Nobel Prizes in recent years.  For example, the 1995 prize for “discoveries concerning the genetic control of early embryonic development” was awarded for studies of the fruit fly  Drosophila melanogaster , and the  2002 prize for “discoveries concerning ‘genetic regulation of organ development and programmed cell death”, was awarded for research undertaken with the nematode worm Caenorhabditis elegans, while the 2007 prize for  “discoveries of “principles for introducing specific gene modifications in mice by the use of embryonic stem cells”” depended on studies of stem cells in the developing mouse embryo undertaken by Martin Evans.

Today on the Neurophilosophy blog Mo Costandi has another great example of how our knowledge of developmental biology is being advanced through animal research. In a post entitled “Astrocytes build blood vessel scaffolds for long distance neuron migrations” he discusses how a research team led by Dr Armen Saghatelyan  used  Green Fluorescent Protein labeling and genetic modification to track the processes that control the migration of nerve cells to their correct location in the developing mouse brain.

It’s fascinating work, and you can read about it on the Neurophilosophy blog here.



So what does this basic research in developmental biology mean to medicine?

Scientists have known for some time that the brain has a limited ability to repair itself following injury, for example after a stroke, and more recent studies have identified a critical role for adult neuronal precursor cells in this recovery.  But the process by these adult neuronal precursor cells migrate to the site of injury and integrate into the damaged brain circuitry is very inefficient, with only a small number of cells reaching the correct location, so scientists are working on a variety of approaches to boost the brain’s ability to repair itself.

One approach to doing this is the use of exogenous stem cells, such as the human embryonic stem cell derived neuronal precursor cells developed by the UK-based company ReNeuron that entered clinical trials for stroke in 2011.

Another avenue being pursued by several research groups around the world is to improve the efficiency with which the endogenous neuronal precursor cells migrate to and repair damaged regions of the brain. In order to develop therapies that improve endogenous brain repair scientists first need to understand the processes that drive – and limit – neuronal precursor production, migration and integration in the developing and adult brain, so that they can modify and enhance those processes to safely  optimize repair.  The work of Dr Saghatelyan and his colleagues has provided medical science with another important piece of a puzzle that when solved will benefit many thousands of stroke victims around the world.

Paul Browne

From the bench and the bedside; how animal research is taming Multiple Sclerosis

Multiple sclerosis (MS) is one of the most common diseases of the central nervous system – the brain and spinal cord – affecting about one person in every thousand in the USA. It is an inflammatory condition, where the immune system attacks the myelin sheath that surrounds the axons of nerve cells. Myelin is a fatty material that insulates nerves, acting much like the covering of an electric wire and allowing the nerve to transmit its impulses rapidly. It is the speed and efficiency with which these impulses are conducted that permits smooth, rapid and co-ordinated movements to be performed with little conscious effort. Loss of myelin interrupts these impulses, and the nerve cells themselves are also damaged and eventually die. 

The consequences for people with MS can be devastating, and MS is associated with a wide variety of symptoms, including muscle weakness, spasms, ataxia, problems with speech and vision, acute and chronic pain, and fatigue.  MS is a very variable disorder, and the rate at which it progresses varies considerably from one patient to another, but a defining characteristic of it is the lesions that are visible by MRI where the myelin has come under attack. The relapses, attacks of worsening neurological function that are often found in MS, are closely associated appearance of new lesions in the CNS, although not all new lesions cause a relapse.

Until about 20 years ago there were no treatments available that could prevent relapses or slow the progression of MS – known as disease modifying treatments – but thanks to the efforts of scientists working around the word this situation has begun to change.   A number of effective disease modifying treatments are now available, the most recent to receive FDA approval is Fingolimod (known as FTY720 during its development), a drug whose immunosuppressant properties in reducing transplant rejection and as a treatment for MS were evaluated in a range of animal models during its development.

These drugs may soon be joined by another. A couple of years ago I wrote about the crucial role of studies in mice, rats, and dogs in the development of a new disease modifying treatment called Laquinimod, which safely -though relatively modestly conpared to other new therapies – reduced the number of relapses, while slowing progression of disability more that current disease modifying drugs in a Phase III clinical trial. This is good news, and one more step towards turning MS form being an incurable disease to being a manageable disease.

One reason I say manageable rather than curable is that while these treatments are effective in reducing the number of relapses for many patients they do not work for all patients and all forms of MS (particularly for primary progressive MS), and can sometimes have serious side effects that prevent patients from continuing treatment. That is why scientists are continuing to study the biological mechanisms in MS, a disease whose origin is still not fully understood, though clinical and animal research indicates that both genetic and environmental factors play a role, their ultimate goal is to develop treatments that can stop relapses altogether.

Another reason for not referring to disease modifying treatments as “cures” is that they do not directly repair the damaged myelin sheath at the lesions. Spontaneous repair of the damaged myelin sheath in MS lesions does happen and plays an important role in limiting neurological damage, but until now the molecular basis of myelin regeneration by cells called oligodentrocytes, in the central nervous system (CNS) has been poorly understood. The Guardian reports on how scientists at the University of Cambridge have discovered how to promote remyelination in MS lesions by activating a population of stem cells in the CNS called oligodentrocyte precursor cells (1).

The team led by Professor Robin Franklin generated a comprehensive transcriptional profile of 22,000 genes during the separate stages of spontaneous remyelination that follow focal toxin-induced demyelination in the rat CNS, and found that the level of retinoid acid receptor RXR-gamma expression was increased during remyelination. Cells of the oligodendrocyte lineage expressed RXR-gamma in rat tissues that were undergoing remyelination, in both active lesions and in older remyelinated  lesions. By examining post-mortem brain samples from MS patients, they were able to show that RXR-gamma expression was also elevated in oligodendrocyte precursor cells at the active lesion sites, supporting a general role for RXR-gamma in remyelination. Interesting as these findings were they did not demonstrate that RXR-gamma is actually required for remyelination, so they next performed studies to determine whether blocking the function of RXR-gamma would prevent remyelination.

Rats are crucial to many areas of MS research. Image courtesy of Understanding Animal Research.

Knockdown of RXR-gamma by RNA interference or RXR-specific antagonists severely inhibited the differentiation of oligodendrocyte precursor cells into mature oligodendrocytes in culture. In mice that lacked RXR-gamma, adult oligodendrocyte precursor cells efficiently repopulated lesions after demyelination, but showed delayed differentiation into mature oligodendrocytes. The next question was whether increasing the activity of RXR-gamma would speed up remyelination. Administration of the RXR agonist 9-cis-retinoic acid to demyelinated mouse cerebellar slice cultures and then to aged rats in vivo after focal demyelination caused an increase in remyelinated axons. Focal toxin-induced demyelination was used to produce the lesions, rather than an immunity mediated model of demyelination such as experimental autoimmune encephalomyelitis, in order to determine that the increased remyelination was due to promotion of oligodendrocyte differentiation rather than to the anti-inflammatory effects of 9-cis retinoic acid.

The results indicate that RXR-gamma plays an important role in endogenous oligodendrocyte precursor cell differentiation and remyelination, and might be a pharmacological target for regenerative therapy in MS. The discovery that 9-cis-retinoic acid, a compound already in limited clinical use, can be used to stimulate myelin regeneration raises the possibility that within the next decade treatments that repair the neurological damage in MS will begin to enter clinical trials.

For people with MS these scientific and clinical advances are a great source of hope for a better future.

Paul Browne

1)      Huang J.K. et al. “Retinoid X receptor gamma signalling accelerates CNS remyelination” Nature Neuroscience Published Online 05 December 2010 DOI: 10.1038/nn.2702

Of mice and mTOR: Can damaged spinal cords be taught to repair themselves?

There’s an interesting story on the BBC website about new research on nerve cell regeneration after spinal cord damage in mice, work undertaken by a team led by Dr. Zhigang He of the F.M. Kirby Neurobiology Center at Children’s Hospital Boston.

Nerve regeneration in mice requires mTOR. Image courtesy of Understanding Animal Research.

Those of you who follow developments on the field of spinal cord repair may find this story familiar. The study published online in Nature Neuroscience this week (1) follows up on work by the same team published two years ago (2) which examined whether regeneration of the optic nerve of mice could be promoted by using an adenovirus-based vector to locally delete several genes known to suppress cell growth. They found that knocking out gene named PTEN in the optic nerve encouraged regeneration of nerve cells following damage. PTEN inhibits the activity of the enzyme mTOR which is an important promoter of cell growth and survival, so removing PTEN increases mTOR activity and promotes regrowth of damaged nerve tissue. In agreement with this that found that mTOR levels are high in nerve cells of the central nervous system (CNS) in mice seven days after birth, when nerve cells are still naturally capable of regeneration and repair, but far lower two months later when such nerve regeneration is no longer observed. mTOR is a key regulator of cell growth throughout the body, and it’s activity is highly conserved throughout the evolutionary tree.

The latest study demonstrates that nerve regeneration through activation of the mTOR pathway does not only happen at the optic nerve but can also be induced in other parts of the CNS, with obvious implications for repairing spinal cord damage.

As the BBC report points out this is still quite preliminary work; the study demonstrated that the regenerated nervous tissue had all the features of normal nervous tissue, including the ability to form synapses that are needed to transmit signals from one nerve cell to another, but they have yet to show that it improves the function of the damaged nerve tissue. Other factors will need to be used alongside PTEN inhibition to encourage the regenerating cells to form a bridge across the damaged section of the spinal cord. The authors point out several promising approaches to achieving this are currently under development, for example growth factors that guide the growth of regenerating nerve cells to the correct location.

The PTEN knock-out approach used in these two studies, while useful in laboratory studies, is not suitable for the clinic because its effects are permanent. It should, however, be possible to develop a drug, perhaps using RNAi or Morphilinos, to temporarily turn off PTEN activity at the site of injury and promote nerve regeneration. Whatever approach is used it will be important to be able to target the increase in mTOR activity to the site of injury. mTOR is involved in the regulation of cell growth throughout the body and indiscriminate activation of it might have adverse consequences, after all several drugs are under development that turn off mTOR activity in cancer cells.

All in all it is an interesting piece of work, even if it only goes part of the way towards developing a therapy that can repair damaged spinal cords and prevent paralysis. This is an exciting time for research on treating paralysis, with a variety of techniques under development. These range from transplantation of stem cells such as Olfactory ensheathing cells or embryonic stem cells, to the development of robotic limbs controlled through brain-machine interfaces. Such a variety of approaches is entirely justified by the complexity of the problem that needs to be solved, not every technology will be appropriate for every patient, and furthermore it is likely that the regeneration-promoting technique described in this week’s report may help to increase the effectiveness of stem cell transplants.

It’s just another example of how important animal research is to progress in one of today’s most exciting areas of medicine.

Paul Browne

1)      Liu K. et al. “PTEN deletion enhances the regenerative ability of adult corticospinal neurons” Nature Neuroscience, published online 8 August 2010; doi:10.1038/nn.2603

2)      Park K.K. et al. “Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway.”  Science, Volume 322(5903), Pages 963-966 (2008) doi:10.1126/science.1161566

Finding animal research in medical news

One of the things that often strikes me when reading about medical advances or clinical trials is how variable the reporting of basic and applied research, including animal research, that underpins the clinical research is.  In some cases it is discussed in some depth, but far too often it is either skimmed over or not mentioned at all.  This is a shame since it makes it more difficult for readers to make the connection between what is happening in the clinic and animal research that may have begun years earlier. A few stories in the news this week illustrate this variability very nicely.

I’ll start with an excellent report by Miriam Falco on CNN entitled “Stem cell treatment goes from lab to operating room” which describes a clinical trial of fetal stem cells in the treatment of Amylotrophic Lateral Sclerosis (Lou Gehrig’s disease), a progressive neurodegenerative disease affecting the motor neurons that leads to severe muscle weakness and eventually death as the muscles that control breathing fail.  As the CNN report points out research on rats was vital to the identification of the correct type of cells for this transplant, and Dr. Eva Feldman demonstrated that injecting fetal stem cells into rats with ALS preserved the large motor neurons and muscle strength.

Lead researcher Dr. Eva Feldman, a neurologist at the University of Michigan, designed the trial just four years ago. After a lot of animal testing, her team determined that using fetal nerve stems rather than human embryonic or adult stem cells (such as bone marrow stem cells) was most effective, she says.

Stem cells have the ability to turn into different cells in the body. However, human embryonic stem cells, which come from 4- or 5-day-old embryos, also been found to sometimes turn into cancer cells. Fetal stem cells, such as those used in this trial, are a few weeks older and have already taken on a specific identity — in this case nerve cells.

Feldman says the fetal stem cells used in this trial did not become any of the unwanted cell types. “That’s very, very important,” she says.

Basic animal research showed the potential of this therapy, but applied research also played an important part in making this clinical trial possible. Through studies on pigs Dr. Nicholas Boulis developed an apparatus that allows the stem cells to be injected at precise locations in the spine, and then practice the technique before attempting to use it on a human patient.

Animal testing also proved very useful when it came to figuring out how to actually inject the stem cells. Emory University’s neurosurgeon Dr. Nicholas Boulis invented the device that holds the needle that injects the stem cells. The goal is to inject the cells without injuring the spine and causing even more paralysis. He practiced on 100 pigs before attempting the procedure on a human.

Our second report is from the LA Times, and in an article entitled “A personal fight against a lethal childhood illness reports on the work being done at the Centre for Duchenne Muscular Dystrophy at UCLA. It’s a nice report which shows how passionate scientists like Stan Nelson and Carrie Miceli are about finding effective treatments and cures for serious diseases.  While the report does refer to  experimental therapies such as exon-skipping and gene therapy it unfortunately does not discuss them or the research that led to their development in any depth.

Exon skipping is a particularly innovative approach to treating some cases of Duchenne Muscular Dystrophy (DMD) where the disease is due to a mutation in the dystrophin  gene that stops translation from messenger RNA prematurely and prevents the production of the protein  dystrophin. In exon-skippping a molecule known as an antisense oligonucleotide or morpholino acts to remove the portion of mRNA that contains the mutation and allows the translational machinery of the cell to read through and produce a working dystrophin protein.  As I discussed in an article last year research in mice and dogs has been crucial to the development and refinement of exon-skipping and early versions of this therapy have already had promising results in clinical trials undertaken at  Great Ormond Street Hospital in London and Royal Victoria Infirmary in Newcastle.  Gene therapy, where the faulty dystrophin gene is replaced by a working version, is also being developed, though it has not yet entered human clinical trials. A recent review (1) available to read for free at PubMed Central discusses the progress that has been made in recent years, the challenges that remain before DMD can be cured, and the vital role played by animal models  in overcoming these challenges. The review also covers stem cell therapy for DMD, another exciting approach to treating the disease that we have discussed previously.

The final news item is a BBC report on a successful clinical trial of stem cells to treat Multiple Sclerosis, this time using stem cells isolated from a patient’s own bone marrow. Multiple Sclerosis (MS) is an autoimmune disorder where the patient’s immune system turns on the myelin sheath that insulates the axons of nerve cells, leading to a range of often serious neurological problems.  At present few effective treatments have been approved for MS, and several are currently being evaluated in clinical trials.  While the improvements seen in the clinical trial were modest they do hold promise for longer and lager trials that are now being planned, and I suspect that as with other therapies the key might be to start treatment early to prevent damage as well as allowing damage to be repaired.

The symptoms of Multiple Sclerosis. Image courtesy of Mikael Häggström

The trial at Frenchay Hospital in Bristol built on years of careful animal research, including research conducted by Professor Neil Scolding who lead this clinical trial.  Interestingly the research, conducted in mice with experimental allergic encephalomyelitis that reproduces many of the features seen in autoimmune diseases that attack the myelin sheath, showed that rather than replacing the damaged cells that produce the myelin sheath or nerve cells the injected stem cells protected the myelin sheath and nerve cells by turning down the pathogenic immune response responsible for damaging the myelin sheath (2,3). This was important since it meant that it was not necessary to inject the stem cells directly into the site of the MS lesion, rather the cells could be as (if not more) effective if injected into the bloodstream so that migrate to tissues such as the lymph nodes where they can interact with cells of the immune system.  This discovery paved the way for the clinical trial reported by the BBC.

There’s a lot of stories in the news that are relevant to animal research, the trouble is that it’s not always easy to see the connection. At Speaking of Research we believe that the onus is on scientists to make sure that when they talk to reporters they give the full picture of what their research involves, and what earlier studies it depended on. Only then can the public really begin to appreciate just how important animal research is to continued medical progress.

Paul Browne

1)      Wang Z. et al. “Gene Therapy in Large Animal Models of Muscular Dystrophy” ILAR J. Volume 50(2), Pages 187-198 (2009). PMCID: PMC2765825

2)      Matysiak M. et al “Stem cells ameliorate EAE via an indoleamine 2,3-dioxygenase (IDO) mechanism” J Neuroimmunol. Volume 193(1-2), Pages 12-23 (2008) DOI:10.1016/j.jneuroim.2007.07.025

3)      Gordon D . et al “Human mesenchymal stem cells abrogate experimental allergic encephalomyelitis after intraperitoneal injection, and with sparse CNS infiltration.” Neurosci Lett. Volume 448(1), Pages 71-73 (2008) DOI:10.1016/j.neulet.2008.10.040

A Noble cause: Protecting babies brains with Xenon

Back in October I wrote about how animal research has enabled the development of brain cooling as a treatment to reduce brain damage in babies who had suffered oxygen starvation during birth. This is a problem that affects tens of thousands of babies every year, and frequently results in death or long-term disability. Brain cooling is already beginning to have an impact in the clinic, but a recent report on the BBC website shows how scientists are already improving on it by adding the inhalation of the gas xenon to the therapy .  The first clinical trial on a baby born at St Michael’s Hospital in Bristol was a success and more trials are now planned, an achievement that rests on a decade of research in rats and pigs.

Riley Joyce, the first baby to receive the new treatment. Image courtesy of the University of Bristol.

Xenon is a rare gas which is best known for its use in street lamps, but it has also recently been approved as an anaesthetic  and lacks many of the side effects associated with more commonly used anaesthetics such as nitrous oxide .  A decade ago researchers at Imperial College London (ICL) became interested in the potential of xenon to protect the nervous system after in vitro studies showed that it blocks a cell surface receptor  – the NMDA receptor – whose activation can lead to the death of nerve cells. It was however not clear if xenon would have neuroprotective effects in vivo, since many other molecules that antagonize the NMDA receptor also have neurotoxic effects that cancel out the benefits of blocking it.

To resolve this question the ICL scientists studied whether the neurotoxic effects of injecting a chemical that binds and activates the NMDA receptor on the brains of rats could be blocked by inhalation of xenon.  Their results demonstrated that xenon had a far better neuroprotective effect than other NMDA receptor blockers such as nitrous oxide and ketamine (1), and prompted several other scientists to begin animal studies evaluating whether xenon could be used to prevent brain damage after oxygen starvation.

One of those scientists is Professor Marianne Thoresen , whose work on brain cooling I discussed earlier. Her team at the University of Bristol performed a series of studies of the effect of combining hypothermia with xenon treatment in a newborn rat model of ischemia followed by hypoxia that recreates the effects of oxygen starvation in human babies (2,3). They observed that not only did the addition of xenon therapy double the effectiveness of hypothermia in preventing brain injury, but also that these benefits were still clear when rats had reached adulthood. This was studied through analysis of brain tissues and by using tests that examined the rats ability to manipulate food pellets in a puzzle were used to measure fine motor dexterity. The combination of the two therapies were found to be additive, Xenon therapy without cooling was far less effective, especially in the long term.

This was not the end of Bristol team’s work, Xenon is a rare and expensive gas and xenon therapy in newborn humans would require treatment for several hours. Designing a respirator that could deliver xenon with minimal waste was a key goal for the group if this therapy was to enter widespread use in hospitals.  Led by Dr. John Dingley they designed a closed-circuit xenon delivery system which optimises gas delivery so that the patient receives a sufficient dose while minimizing xenon consumption, and demonstrated that it worked safely and efficiently for 16 hours in a newborn pig model of ischemia and hypoxia (4).  With solid evidence from studies in rats for the benefits of combining cooling and xenon therapy, and the development of an effective delivery system for Xenon in pigs, the Bristol team were ready to begin human trials.

By coincidence the National Geographic Channel aired a program last night entitled Genius Hog which examined the contribution that pigs make to medical research – a brilliant beast indeed!

Paul Browne

1)      Ma D. et al. “Neuroprotective and neurotoxic properties of the `inert’ gas, xenon” British Journal of Anaesthesia Volume 89(5), Pages 739-746 (2002) PubMed: 12170064

2)      Dingley J et al. “Xenon provides short-term neuroprotection in neonatal rats when administered after hypoxia–ischemia. “ Stroke Volume 37, Pages 501–506 (2006) DOI:10.1161/01.STR.0000198867.31134.ac

3)      Thoresen M et al. “Cooling combined with immediate or delayed xenon inhalation provides equivalent long-term neuroprotection after neonatal hypoxia-ischemia”  J Cereb Blood Flow Metab. Volume 29(4), Pages 707-714 (2009) DOI: 10.1038/jcbfm.2008.163

4)      Chakkarapani E. Et al. “A closed-circuit neonatal xenon delivery system: a technical and practical neuroprotection feasibility study in newborn pigs.” Anesth Analg. Volume 109(2), Pages 451-460 (2009) DOI: 10.1213/ane.0b013e3181aa9550

Understanding migraines: The blind leading the…err…rats

Chances are that you have either suffered from migraine yourself or have a family member or close friend who have, after all about 1 in 8 of us will suffer from migraine at some stage in our lifetime, and some sufferers experience repeated debilitating episodes over many years . While headache on one side of the brain is typical other symptoms such as nausea are very common, indeed in some migraine victims nausea is the primary symptom of the disorder.  Through a combination of studies in animals and clinical research using techniques such as fMRI and PET scans scientists have learned a lot in recent years about what happens before and during migraine episodes but we do not yet fully understand what ultimately causes the attacks, and debate rages over the relative importance of some mechanisms originating deep in brain regions such as the hypothalamus and others that start in membranes that surround the brain, (1,2).  Current treatments can help prevent migraine, reduce suffering and hasten recovery they do not work for all patients, and a better understanding of what exactly is happening before and during a migraine attack will aid the development of really effective treatments and preventative measures.  A study published in Nature Neuroscience combines clinical research with studies of rats to provide clues about a key characteristic of migraines that has until now remained unexplained, the exacerbation of the pain experienced by sufferers by light (3).

The team, lead by Rami Burnstein of Beth Israel Deaconess Medical Centre in Boston, decided to concentrate of the role of a particular subset of nerve cells in the retina known as intrinsically photosensitive retinal ganglion cells (ipRGCs) which they knew from previous mouse research to be involved in eye functions that are not image forming, such as setting the biological clock to the day night cycle.  The ipRGCs are stimulated by light both indirectly via the rods and cones and directly through a pigment called melanopsin that they themselves contain.  In order to discover if the ipRCGs are important to light sensitivity in migraine they performed a very neat clinical study involving 20 blind patients who also suffered from migraine. Six of these patients lacked any light perception due to removal of their eyes or damage to the optic nerve, while in the remaining 14 the damage to the eyes was less total, affecting the rods and cones but not ipRGCs, so that while they were unable to see images they could detect light. The results were clear, blue and grey light made the headaches of those who retained light sensitivity worse, while having no effect on the six blind individuals who lacked light perception.

Determining that the ipRGCs are involved in the exacerbation of migraine headaches by light is of course only part of the story, and Professor Burnstein’s team next turned to tracing the nerve pathways that are responsible for the increased pain, knowledge that might help to develop new treatments.  This they could not do in human subjects because the available imaging techniques do not have the precision to determine the connections between individual neurons.  In a series of studies they injected labels including Green Fluorescent Protein into particular areas of the eyes and brain, and in some cases even individual nerve cells, of anesthetized rats with and followed the path of the neurons.  They were also able to use tiny electrodes to record the effect of light on the firing of individual nerves in the brain, something that cannot yet be done in human subjects. An exciting observation was that the ipRCGs connected to cells in a region of the brain known as the posterior thalamus, itself part of the trigeminovascular pathway that is strongly implicated in migraine headache through transmission of nerve signals from the irritated outer brain membranes to the deep brain. When they examined the electrical activity of these cells they discovered that the majority of the cells within the posterior thalamus that are involved in mediating migraine pain are also light sensitive.  Finally they demonstrated that the light-sensitive pain-mediating neurons of the posterior hypothalamus connect to nerve cells in several regions of the somatosensory region of the cortex, an intriguing discovery since abnormalities in this region have previously been seen in migraine patients. This discovery is likely to encourage scientists to study the role of the somatosensory cortex in migraine in more detail.

So how important is this study? Well it’s unlikely that this discovery will lead to any treatment breakthrough in the immediate future, though the discovery that grey light can exacerbate migraine headache is new and may help patients to avoid it.  Despite a perhaps natural tendency for the news media to look for “breakthroughs” the majority of scientific papers published are like this one, providing valuable new insights into biology that contribute to our overall understanding of how biological systems work and happens when they go awry but not indicating an easy fix.  I’ve no doubt that this and many similar basic science studies will contribute to better treatments for migraine in the future, but perhaps not tomorrow!


Paul Browne

1)      Olesen J. et al “Origin of pain in migraine:evidence for peripheral sensitization” The Lancet Neurology Volume 8, Issue 7, Pages 679-690 (2009) doi:10.1016/S1474-4422(09)70090-0

2)      Alstadhaug K.B.  “Migraine and the hypothalamus” Cephalalgia Volume 29, Issue 8, Pages 809-817 doi: 10.1111/j.1468-2982.2008.01814.x

3)      Noseda R. et al. “A neural mechanism for exacerbation of headache by light” Nature neuroscience Advance Publication Online 10 January 2010 doi: 10.1038/nn.2475