Researchers at the University of California San Francisco may have found a potential future treatment that uses cell therapy to not only help with relief of chronic and difficult-to-treat pain, but also to cure the conditions that cause the pain.
Using mice, the UCSF researches focused on neuropathic pain, the type of chronic pain that arises from nerve injury. The study, which can be found in the May 24, 2012 issue of Neuron, explains how researchers transplanted immature embryonic nerve cells that were taken from the brain during development, placing them in the spinal cord region.
A small percentage of the cells survived being transplanted and developed into functioning neurons. The surviving cells integrated into the circuitry of the spinal cord and formed signaling pathways with neighboring neurons. In other words, they bridged the gap left after injury, eliminating pain and hypersensitivity.
Currently, sufferers of chronic pain and hypersensitivity, such as patients that have had shingles, rely on narcotic pain relievers. Gabapentin, an anticonvulsant originally used to treat epilepsy, is the most commonly prescribed drug for sufferers of chronic pain. Unfortunately, only 30 percent of patients that try the medication find relief, and those that do find relief claim it only provides reduces the pain by about 30 percent. Side effects are common with many of the commercially available pain killers as well.
“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.
Research shows that neuropathic pain is caused by neurons that are lost or circuitry that is changed in ways that compromise the signals that help relieve pain. The changes cause hyper-excitability, which enhance the pain messages that are sent to the brain, making the brain perceive more pain that is actually present.
The damaged inhibitory neurons release a molecule that normally transmits inhibitory signals, known as the GABA neurotransmitter. The loss of GABA inhibition is blamed in epilepsy and may play a part in Parkinson’s disease as well. Previously, researches had experimented with transplanting immature neurons that make GABA, but in earlier experiments they were placed in the brain. Basbaum decided to try placing these cells into the spinal cord as a potential treatment for the loss of GABA-driven inhibition in neuropathic pain. Success was not a guarantee, as these cells usually do not survive outside of the brain, their natural home, in complex organisms.
According to Kriegstein, who directs the Eli and Edythe Broad Center 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.”
“One of the amazing properties of these cells from the medial ganglionic eminence is their unprecedented migratory capacity, which enables them to navigate through multiple terrains within the central nervous system, and to then become functionally integrated with other cells,” remarked Alvarez-Buylla, a leading scientist working to define the potentials of various cells in the developing brain and various stages. “Those properties have proved useful in other places where we have transplanted them, and now in the spinal cord.”
The authors of the study, Joao Braz, PhD and Reza Sharif-Naieni, PhD, have a patent pending on the treatment from the study.