“When we inject our HSV gene carrier under the skin of a laboratory rat, the vector is taken up by sensory nerve terminals in the animal's skin and carried through the axon back to the sensory ganglia cell bodies next to the spinal cord,?says Shuanglin Hao, M.D., Ph.D., a U-M research investigator and first author of the study.
“Since the vector lacks essential viral genes for replication, it remains in the nucleus expressing the GAD enzyme, which triggers nerve terminals in the spinal cord to release GABA,?Fink adds. “As long as the GAD gene remains active, GABA will continue to flood the spinal cord and block the transmission of pain signals to the brain.?/p>
In experiments reported in the Annals of Neurology paper, VA/U-M scientists tied off a nerve root in the sciatic nerve leading to the left hind paw of eight rats in the study. Tying off the nerve root makes the nerve degenerate and release substances that cause pain, according to Fink. A second group of eight rats received sham surgery, with no damage to their sciatic nerve. A third group served as normal controls.
“When we study pain in people, we can ask them if it hurts,?says Fink. “But you can't ask questions of a rat. So we study the animals' behavior to discern whether they are experiencing pain using standard models used to assess pain in rodents.?/p>
One of the effects of neuropathic pain is called allodynia, which means that even ordinary touch feels painful. In both rats and people, scientists measure allodynia by touching the skin with a series of filaments or exposing the skin to small amounts of moderate heat. People with neuropathy perceive the filament's touch or heat as a painful sensation. Rats with neuropathy will lift their paw if the filament or heat produces pain. Rats without neuropathic pain don't even notice. By monitoring whether rats lift their paw, and how long it takes for them to do so, scientists can measure the
Source:University of Michigan