Dr. Allan Basbaum is professor and chairman of the Department of Anatomy at the University of California San Francisco. A neurobiologist, he is recognized worldwide for his work in understanding the mechanisms that contribute to the development of chronic pain, particularly the neuropathic pains produced by nerve injury, a condition that he considers a disease of the nervous system.
With the incredible support of The Facial Pain Research Foundation’s seed grant to my laboratory, we have made tremendous progress in our development of a novel therapeutic approach to treat chronic pain, including trigeminal neuralgia. Perhaps the best evidence for the value of the contribution of the gift from The Facial Pain Research Foundation is that our preliminary findings led to successful application for longer term funding from the NIH. Our approach involves preclinical studies in which we transplant in the mouse, precursors of inhibitory cells from the embryonic brain. Our approach is directed at the underlying etiology of the persistent pain, namely loss of interneuron-derived GABAergic inhibitory controls. Our objective is to restore permanently the inhibitory controls that are lost in these persistent pain conditions. In this respect, we consider trigeminal neuralgia and other neuropathic pain conditions as manifestations of diseases of the nervous system, rather than symptoms of some other condition. Our objective is therefore curative; we aim to treat the disease using this transplantation approach. Most recently, we demonstrated that this transplantation approach is remarkably effective in both chronic pain conditions produced by traumatic nerve damage as well following treatment with chemotherapeutic drugs.
Our studies have also provided the most convincing evidence that these transplants are not merely sophisticated cellular pumps that release the inhibitory molecule, GABA. Rather, using electron microscopy and electrophysiological recordings of the properties of the transplanted cells, we have demonstrated that the cells actually integrate into the neural circuitry of the host. And most importantly, the cells survive for a long time, at least six months, which in the mouse, is equivalent to about 20 years in humans. This is very encouraging as we are interested in a long-term approach to treatment.
Our ongoing studies are directed at bringing the technology to the clinic. To this end, we have initiated studies in which we are transplanting human embryonic stem cells modified to take on the properties of the GABAergic inhibitory nerve cells. The techniques for isolating and modifying the cells were developed, in part, by our colleagues at the UCSF Stem Cell program. Our colleagues provided the cells to us and we transplanted them into immunocompromised mice (so that the human cells would not be rejected). Our most exciting findings to date is that these cells, which are the cells that we anticipate will be transplanted in patients, also integrated into the mouse nervous system and effectively reversed the pain condition produced by nerve damage. With continued support of The Facial Pain Research Foundation, our ongoing studies are working to improve the utility of the human cells and to determine the most effective transplantation approaches, including reducing the time that the transplant takes to integrate.