A novel painkiller, which selectively targets nociceptors therefore preventing the impairment of movement, touch and awareness that is associated with current anesthetics, has been developed by researchers from Harvard Medical School (MA, USA) and Massachusetts General Hospital (MA, USA).
“Current nerve blocks cause paralysis and total numbness. This new strategy could profoundly change pain treatment in the perioperative setting,” Clifford Woolf, coauthor of the paper commented.
The painkiller combines capsaicin, an extract from chilies, with a drug called QX-314. QX-314 is unable to cross cell membranes, however, once it has entered a cell it is able to block electrical activity. Capsaicin acts by opening TRPV1 channels, which are only present on nociceptors. Thus, combined administration of these two ingredients selectively opens pain-sensing neurons and blocks their activity.
Published in the 4th October issue of Nature, the novel painkiller was tested both in vitro and in vivo with impressive results. Firstly, the researchers administered capsaicin and QX-314 to petri dishes containing nociceptors or other neurons and measured their responses; excitation was blocked only in the nociceptors and not in the other neurons.
Following on from this, rats were injected with a combination of QX-314 and capsaicin near to their sciatic nerves. Those injected with the ‘painkiller’ tolerated much more heat than usual when placed on an uncomfortable heat source. In addition to this, five of the six rats that were injected continued to show normal movement and behavior. The capsaicin/QX-314 combination took 30 mins to take effect and lasted several hours.
Bruce Bean, coauthor of the study commented, “We’ve introduced a local anesthetic selectively into specific populations of neurons. Now we can block the activity of pain-sensing neurons without disrupting other kinds of neurons that control movements or non-painful sensations.”
The authors are hopeful that this research may revolutionize pain therapy, with Woolf commenting, “Eventually this method could completely transform surgical and postsurgical analgesia, allowing patients to remain fully alert without experiencing pain or paralysis. In fact, the possibilities seem endless. I could even imagine using this method to treat itch, as itch-sensitive neurons fall into the same group as pain-sensing ones.”
Source: Binshtok AM, Bean BP, Woolf CJ. Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers. Nature 449(7162), 607–610 (2007).
Antibody repairs myelin in mouse model of multiple sclerosis
A group of researchers at the Mayo Clinic Rochester (MN, USA) have reported successful remyelination in a mouse model of multiple sclerosis (MS).
Presented at the American Neurological Association 132nd Annual Meeting on October 9, the study used a human antibody to re-grow myelin in a mouse model of chronic progressive human MS. Each mouse received a single dose of the antibody and their disease severity was judged by assessing their level of activity, especially at night when they are most active.
Only 25 µg/kg of the antibody was required to trigger remyelination in the mice. This is equivalent to 2 mg for the average adult. However, the level of myelin repair plateaued after 5 weeks.
“The repair of chronic spinal cord injury is seldom modeled in laboratory studies, but it is an important reality for the treatment of humans. The concept of using natural human antibodies to treat disease of this kind has not yet been tested in humans, but these research findings are very promising,” Moses Rodriguez, coauthor of the study and Neurologist from the Mayo Clinic explained.
The group is continuing their studies in animal models but hope that, in the future, the antibody treatment may reach clinical trials. Indeed, they have already performed a toxicology study in mice and found that administration of 4000-times the minimal therapeutic dose of the antibody is still not toxic.
Arthur Warrington, coauthor of the study commented, “The findings could eventually lead to new treatments that could limit permanent disability.”
Although only in its early stages, other scientists in the field are also positive about the potential benefits of this research. Laura Bell, of the MS Society, commented, “Myelin repair is an exciting avenue of research that holds a lot of promise as an MS treatment. This is an exciting study but it is early days – we’ll be keen to see how it works in people with MS.”
Sources: Poster Presentation T-109. A recombinant human IgM promotes myelin repair after a single very low dose. Presented at American Neurological Association 132nd Annual Meeting. Washington, DC, USA, 7–10 October 2007
Mayo Clinic News Release. Antibody leads to repair of myelin sheath in lab study of multiple sclerosis and related disorders, mayo clinic study shows www.mayoclinic.org/news2007-rst/4294.html
Cell phones and cancerous brain cells: what’s the link?
Just a few months ago, the Mobile Telecommunications and Health Research (MTHR) program released a report in which cell phones were not “found to be associated with any biological or adverse health effects.” However, a recent study has now demonstrated that long-term cell phone use causes a significantly increased risk of developing brain cancer.
Confirming Lawrie Challis, Chairman of the MTHR’s concerns that “there is still a need for more research, especially to check that no effects emerge from longer term phone use from adults and from use by children,” the current research has demonstrated that regular and long-term use of cell phones may double the risk of developing a malignant tumor and this risk may be greater in children.
Published in the journal Occupational and Environmental Medicine, researchers from Sweden analyzed the results of 11 studies from around the globe that investigated the effects of cell phone use. Almost all of the studies demonstrated an increased risk of cancer, especially on the side of the brain to which the cell phones were held.
It was found that regular cell phone use for more than 10 years increased the risk of developing acoustic neuromas by 20% and malignant gliomas by 30%.
The authors stressed particular concern regarding children, as Lennart Hardell, coauthor of the study and Professor at the University Hospital in Orebro, Sweden, explained, “Children should be discouraged from using mobiles because their thinner skulls and developing nervous systems make them especially vulnerable. Adults should exercise caution.”
Sources: Mobile Telecommunications & Health Research Programme Press Release. Report on mobile phone research published. http://www.mthr.org.uk/press/p7/p7_2007.htm
Hardell L, Carlberg M, Söderqvist F, Mild KH, Morgan LL. Long-term use of cellular phones and brain tumours: increased risk associated with use for ≥10 years. Occup. Environ. Med. 64(9), 626–632 (2007).
Act quickly on stroke warning signs
Rapid treatment of transient ischemic attacks (TIAs), often considered a warning sign of stroke, cuts the risk of a subsequent stroke by approximately 80%, according to two recent studies published in The Lancet and Lancet Neurology.
It is currently estimated that there is an approximate 10% risk of suffering from a major stroke within 1 month of a TIA. The current studies impressively demonstrate that this risk may be dramatically reduced by early treatment.
Writing in The Lancet, Peter Rothwell and colleagues, from the University of Oxford (Oxford, UK), reported the results of their Exelon in Parkinson’s Disease Dementia Study (EXPRESS). From April 2002 to September 2004, 310 TIA patients were referred by their doctors to the hospital, resulting in an average 3-day wait for assessment, and an average 20-day wait to receive drug treatment. From October 2004 to March 2007 patients were told to visit a stroke clinic immediately and were assessed and treated within 1 day of the TIA. It was found that the risk of a subsequent stroke decreased from 10.3 to only 2.1% when TIA sufferers received early treatment.
Similarly, in a French study, published in Lancet Neurology, it was found that the 90-day stroke rate following a TIA was slashed from the predicted rate of 5.96 to 1.24% when patients visited a 24 h TIA clinic.
Joe Korner, of The Stroke Association (London, UK), commented, “This research is of the utmost importance. It clearly shows that thousands of people could be saved from life-shattering strokes every year simply by making sure that everyone who has a TIA or minor stroke gets currently available treatment quickly.”
Stroke can cause severe impairment of motor function or even paralysis. According to the American Stroke Association, approximately 700,000 people each year in the USA suffer a new or recurrent stroke. Currently, there are approximately 5.5 million stroke survivors in the USA, many of whom have permanent stroke-related disabilities. Clearly, early intervention following a TIA could not only vastly reduce the number of people suffering from stroke related disabilities, not to mention reducing the number of fatalities caused by stroke, but also save millions in treatment costs, as Peter Rothwell poined out, “The financial implication is these clinics will pay for themselves. The strokes we’ll prevent would cost a lot more than the service to prevent them. We’ve shown we could prevent 10,000 strokes in the UK, costing £200m to the NHS. It’s one of those rare situations where doing something very simple and pretty cheap will make a big difference.”
Sources: Rothwell PM, Giles MF, Chandratheva A et al. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. The Lancet (2007) (Epub ahead of print);
Lavallée PC, Meseguer E, Abboud H et al. A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects. Lancet Neurology (2007) (Epub ahead of print).
Common antidepressant treatment considerably increases risk of gastrointestinal bleeding
Recent results from a meta-analysis of data from over 150,000 patients have shown that commonly used antidepressant drugs (selective serotonin reuptake inhibitors [SSRIs]) substantially increase a patient’s risk of gastrointestinal (GI) bleeding.
SSRIs have shown an association with bleeding in the upper GI tract (i.e., the esophagus, stomach or upper part of the small intestine). The study, conducted by researchers from Wake Forest University School of Medicine (NC, USA) and colleagues from the University of East Anglia (Norwich, UK), was aimed at determining the risk of GI bleeding with SSRIs administered alone or with concomitant NSAIDs. Previously, a connection had been observed but the characteristics and scale of the risk, as well as the possibility of interactions with anti-inflammatory medication, remained uncertain.
SSRIs are prescribed mainly for the treatment of clinical depression and are the most widely used type of antidepressant in many countries. Other indications for this class of drugs include anxiety disorders, such as panic disorders, obsessive–compulsive disorder and chronic pain. There are many known side effects of the drugs, including drowsiness, headache, changes in appetite, tremors, nausea, vomiting and diarrhea.
The authors used PubMed, Science Citation index and trial registries to find data on SSRIs, NSAIDs and upper GI tract bleeding. Pooling data from four observational studies involving 153,000 patients, they were able to evaluate the incidence of upper GI hemorrhage. A random effects meta-analysis of the data found SSRI use and GI bleeding to be associated, with an odds ratio (OR) of 2.36 (95% confidence interval [CI]: 1.44–3.25; p = 0.0006). When patients also receiving NSAIDs were considered, the OR increased to 6.33 (95% CI: 3.40–11.8; p < 0.00001). Over 100 spontaneous case reports from pharmacovigilance databases were also analyzed. These data revealed that upper GI bleeding occurred at a median of 25 weeks after initiation of SSRIs.
Sonal Singh (Wake Forest University School of Medicine), one of the study authors, commented, “Clinicians who prescribe these medications should be aware of the potential risk and may need to consider alternatives … In addition, regulatory authorities should consider revising existing package inserts to highlight the magnitude of the risk.”
Although this potentially serious side effect may appear to be of more concern in elderly depressed patients, as they are more likely to be administered NSAIDs concurrently with an antidepressant medication, the results demonstrate that this is by no means the only group affected. Of the 101 spontaneous reports of bleeding included in the study, 38% of cases occurred in patients younger than 60 years of age. “While the risk to an individual may increase by only a small amount, the impact to the general population is likely to be substantial because of the large numbers of people who use these drugs,” commented Singh.
This recent study did not distinguish between specific SSRIs but investigated the class as a whole. Previous research has suggested that certain drugs are more frequently associated with GI bleeding than others. The authors recommend that future research into this important area addresses the question of whether certain drugs or combinations of drugs are more likely to cause upper GI hemorrhage.
Source: Loke YK, Trivedi AN, Singh S. Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. Aliment. Pharmacol. Ther. (2007) (Epub ahead of print).
About the news in brief
If you have newsworthy information, please contact: Lucy Tipton, Commissioning Editor, Expert Review of Neurotherapeutics, Future Drugs Ltd, 2 Albert Place, Unitec House, London N3 1QB, UK [email protected]