One week after surgery, some of the rats received injections of the HSV vector with GAD, while control rats did not receive the vector. Rats given the transgene vector had significantly lower pain threshold responses to filament touch and heat exposure tests than rats that did not receive the vector.
"We saw a sustained, continuous pain-suppressing effect that began one week after inoculation with the vector and lasted for six weeks," says Marina Mata, M.D., staff neurologist at the VA Ann Arbor Healthcare System, professor of neurology in the U-M Medical School and co-director of the research team. "By seven weeks after inoculation, the pain-blocking effect disappeared, but a second inoculation into the same paw re-established the effect."
In previous research, Mata and Fink have used their HSV vector to deliver other neurotrophic factors and pain-suppressing drugs to spinal ganglion cells. But Fink says the effect of the GAD-expressing vector is substantially greater for neuropathic pain, because it helps correct the reduction of GABA in the spinal cord. He also emphasizes the excellent safety record of the HSV vector, which has produced no side effects or complications in many animal studies.
"I am a clinical neurologist and I see patients with neuropathic pain," Fink says. "These patients suffer tremendously and the treatments available to us now have limited effectiveness. Using our herpes vector to provide targeted gene delivery to the nervous system is a novel approach that shows tremendous promise for the treatment of neuropathic pain."
In future research, the scientists plan to conduct the first phase I safety trial of a related HSV vector in patients with pain caused by terminal cancer, which has spread to bone.