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The researchers, working with mice, focused on treating chronicpain that arises from nerve injury -- so-called neuropathic pain. In their study, published in the May 24, 2012 issue of Neuron , the scientists transplanted immature embryonic nerve cells thatarise in the brain during development and used them to make up fora loss of function of specific neurons in the spinal cord thatnormally dampen pain signals. A small fraction of the transplanted cells survived and maturedinto functioning neurons. The cells integrated into the nervecircuitry of the spinal cord, forming synapses and signalingpathways with neighboring neurons. As a result, pain hypersensitivity associated with nerve injury wasalmost completely eliminated, the researchers found, withoutevidence of movement disturbances that are common side effects ofthe currently favored drug treatment. "Now we are working toward the possibility of potentialtreatments that might eliminate the source of neuropathic pain, andthat may be much more effective than drugs that aim only to treatsymptomatically the pain that results from chronic, painfulconditions," said the senior author of the study, AllanBasbaum, PhD, chair of the Department of Anatomy at UCSF. Although pain and hypersensitivity after injury usually resolve, insome cases they outlast the injury, creating the condition ofchronic pain. Many types of chronic pain are induced by stimulithat are essentially harmless -- such as light touch -- but thatare perceived as painful, according to Basbaum. Chronic pain due to this type of hypersensitivity is often adebilitating medical condition. Many people suffer from chronicneuropathic pain after a bout of shingles, years or decades afterthe virus that causes chicken pox has been vanquished. Chronic painis not merely prolonged acute pain, Basbaum said. Those who suffer from chronic pain often get little relief, evenfrom powerful narcotic painkillers, according to Basbaum.Gabapentin, an anticonvulsant first used to treat epilepsy, now isregarded 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 reliefof the pain, he said. The explanation for neuropathic pain, research shows, is thatfollowing injury neurons may be lost, or central nervous systemcircuitry may change, in ways that are maladaptive, compromisingsignals that normally help dampen pain. These changes contribute toa state of hyper-excitability, enhancing the transmission of painmessages to the brain and causing normally innocuous stimuli tobecome painful. The inhibitory neurons that are damaged in the spinal cord to causepain hypersensitivity release a molecule that normally transmitsinhibitory signals -- the neurotransmitter GABA. A loss of GABAinhibition also is implicated in epilepsy and may play a role inParkinson's disease. Gabapentin does not mimic GABA, but it helpsto compensate for the loss of inhibition that GABA normally wouldprovide. Basbaum's UCSF colleagues, including study co-authors ArturoAlvarez-Buylla, PhD, and Arnold Kriegstein, MD, PhD, along withScott Baraban, PhD, had already been experimenting withtransplanting immature neurons that make GABA, using thetransplanted neurons to bolster inhibitory signals in mouse modelsto prevent epileptic seizures and to combat a Parkinson's-likedisease. However, in those experiments the cells -- which originate in aregion of the forebrain known as the medial ganglionic eminence --were transplanted within the brain itself, which is their normalhome. Upon hearing about the research, Basbaum became interested intransplanting the same cells into the spinal cord as a potentialtreatment for the loss of GABA-driven inhibition in neuropathicpain. Success was by no means assured, as cells normally do notsurvive outside their natural environments within such a complexorganism. Another co-author of the Neuron study, UCSF researcher JohnRubenstein, PhD, has made major progress in identifying moleculesthat can be manipulated to lead an embryonic stem cell to gothrough developmental stages that cause it to acquire theproperties of GABA neurons that derive from the medial ganglioniceminence. According to Kriegstein, who directs the Eli and Edythe BroadCenter of Regeneration Medicine and Stem Cell Research at UCSF,"This research is at a very early stage, and we're a long wayfrom thinking about it in human trials, but we do have a method ofmaking cells that are like these inhibitory neurons, starting withhuman embryonic stem cells." As a step toward eventual therapies, the UCSF team plans to graftfetal human cells from the medial ganglionic eminence, or cellsderived from human embryonic stem cells, into a rodent model ofneuropathic pain, to see if the human cells also will alleviateneuropathic chronic pain. "Unlike drugs, the transplanted cells can have very focusedeffects, depending on where they are transplanted," Kriegsteinsaid. According to Alvarez-Buylla, a leading scientist among thoseworking to define the potentialities of various cells in thedeveloping brain at different stages, "One of the amazingproperties of these cells from the medial ganglionic eminence istheir unprecedented migratory capacity, which enables them tonavigate through multiple terrains within the central nervoussystem, and to then become functionally integrated with othercells. Those properties have proved useful in other places where wehave transplanted them, and now in the spinal cord." Joao Braz, PhD, an assistant research scientist, and RezaSharif-Naieni, PhD, a postdoctoral fellow, both working in theBasbaum laboratory, carried out the bulk of the experimentspublished in Neuron. The authors have a patent pending on thetreatment outlined in the study. The study was funded by the National Institutes of Health, theAssociation for the Study of Pain and the Canadian Institutes ofHealth Research. I am an expert from pulverisermachine.com, while we provides the quality product, such as Centrifugal Screener , Vibrating Sieve, Food Grinding Machine,and more.
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