A class of drugs being developed to stop pain could also obstruct memory formation. The new painkillers aim to block molecules that respond to burning sensations, like those delivered by chili peppers, camphor, and heat from a fire. Those molecules, found on sensory nerve endings, are known as TRPV1 receptors. Blocking those receptors could help with everything from migraines to dental agony.
But TRPV1 blockers could also affect the brain, researchers report in the March 13 Neuron. TRPV1 receptors are also found in the hippocampus, a brain region critical for learning and forming habits.
Researchers led by Julie Kauer at Brown University in Providence, R.I., found that, in rats, manipulating TRPV1 receptors in the hippocampus interferes with the strength of signaling at synapses, the junctions between neurons. When TRPV1 is artificially activated, the signals between neurons weaken, the researchers found. If TRPV1 is blocked, the signals between neurons remain strong. Proper patterns of synapse strengthening and weakening—the process known as synaptic plasticity—are essential for learning and memory.
“It’s kind of a miracle that no one’s found TRPV1 [receptors] in plasticity before,” Kauer says.
The researchers also found that the TRPV1 receptor could be activated by the antiobesity drug rimonabant (sold in Europe as Acomplia).
Rimonabant was developed to block cannabinoid receptors, known to trigger the classic cannabis munchies. Studies have shown that rimonabant reduces weight and also waist circumference, but the U.S. FDA rejected the drug last year because of reports about depression and suicide in some patients.
Kauer wonders whether TRPV1 is responsible for such side effects, although she notes that people would need high doses of the drug to block TRPV1 receptors in the brain.
Raj Padwal of the University of Alberta Hospital in Canada thinks that Kauer’s study won’t do much to sway the FDA. “This study quantifies mechanisms of risk, but not the degree of risk,” says Padwal.
More disconcerting, says Kauer, are painkiller drugs that have been specifically designed to hit TRPV1 receptors. Pain-wise, rodents immune to burning sensations indicate that the drugs are doing their job. But Kauer worries that subtle psychological and cognitive effects might go unnoticed in the rodents.
On the positive side, TRPV1’s dual role opens possible avenues for novel therapies for cognitive disorders such as epilepsy, Kauer says.