Can a placebo relieve pain in rats?

The logical answer is no, since the placebo effect involves beliefs, expectations, emotions - in a word, the mind. Rats don't have minds.

But rats did indeed respond to a placebo in a University of Florida study, published in the October issue of Pain.

"That was the big finding," said lead researcher John Neubert, a dentist and pain management specialist. "The animals that expected pain relief actually got pain relief when given an inert substance."

Neubert concluded that rats are good stand-ins for humans in research aimed at understanding the mysterious power of placebos.

That conclusion may be a leap, said James D. Herbert, head of the psychology department at Drexel University. Still, he called the study design "very cool and innovative" because the rats had to endure pain to get pleasure.

"Theoretically, that's more like what humans actually face," he said.

The new study, one of the few to look at placebo-induced pain relief in animals, was complex.

Every few days, rats spent 20 minutes in cages through which they could stick their snouts to lick bottles that dispensed sweetened milk. Yum!

The seventh time this happened, the rats stuck their snouts out and, ouch! the holes were hot. Not burning, but hot enough to deter licking.

The eighth time, the holes were not heated. Yum again.

The ninth and tenth times, the holes were again hot. But before facing the nasty portals, the rats received injections of morphine or a placebo, namely saltwater. As expected, rats who got the painkiller licked lustily, while the others often pulled back before lapping the liquid.

For the final session, the hole was hot, and the rats received either the placebo or naloxone - a drug that blocks opioid painkillers such as morphine, as well as natural opioids produced by the brain.

The rats that were switched from morphine to placebo generally kept licking. A few really milked the situation, apparently feeling no pain.

In contrast, licking was lacking among the rats on naloxone and the ones who got saltwater shots throughout the study.

Biologically, how could a placebo work almost as well as morphine? Neubert believes the rats had an expectation of pain relief, which caused their brains to release natural opioids. That's part of the placebo effect in humans.

While Herbert said the theory makes sense, he cautioned against equating human thinking processes, like forming expectations, with conditioning.

"Animals can behave as if they are 'depressed,' " Herbert noted, "but it's not really depression because they don't have the human symbolic system. Animals don't contemplate their own death. Animals don't wonder, 'Does this make me look fat?' "

In any case, Neubert hopes to use rats in placebo-effect studies that would be unethical to do in humans, such as damaging or manipulating brain activity.

"It could pave the way for developing new therapies for chronic pain," he said.

Contact Marie McCullough at 215-854-2720 or mmccullough@phillynews.com.