Live GABA neurons kill pain

A major part of the answer to the problem of neuropathic pain, scientists believe, is found in spinal nerve cells that release GABA. If GABA neurons could be kept alive and healthy after peripheral nerve or tissue injury, it’s possible that neuropathic pain could be averted.

Now, University of Texas Medical Branch at Galveston researchers have found a way to, at least partially, accomplish this objective. The key, they determined, is stemming the biochemical assault by reactive oxygen species that are generated in the wake of nerve injury.

“GABA neurons are particularly susceptible to oxidative stress, and we hypothesised that reactive oxygen species contribute to neuropathic sensitisation by promoting the loss of GABA neurons as well as hindering GABA functions,” said UTMB professor Jin Mo Chung, senior author of a paper on the research now online in the journal Pain.

To test this hypothesis – and determine whether GABA neurons could be saved – the researchers conducted a series of experiments in mice that had been surgically altered to simulate the conditions of neuropathic pain. In one key experiment, mice treated with an antioxidant compound for a week after surgery were compared with untreated mice. The antioxidant mice showed less pain-associated behaviour and were found to have far more GABA neurons than the untreated mice.

“So by giving the antioxidant, we lowered the pain behaviour, and when we look at the spinal cords we see the GABA neuron population is almost the same as normal,” Chung said. “That suggested we prevented those neurons from dying, which is a big thing.”

One complication, Chung noted, is a “moderate quantitative mismatch” between the behavioural data and the GABA-neuron counts. While the anti-oxidant mice displayed less pain behaviour, their behavioural improvement wasn’t as substantial as their high number of GABA neurons would suggest. One possibility is that the surviving neurons were somehow impaired, a hypothesis supported by electrophysiological data.

Although no clinical trials are planned in the immediate future, Chung believes anti-oxidants have great potential as a treatment for neuropathic pain. “If this is true and it works in humans, well, any time you can salvage neurons, it’s a good thing,” he said. “Neuropathic pain is very difficult to treat, and I think this is a possibility; a good possibility.”

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