Pain receptor in brain may be linked to learning and memory

Scientists have long known that the nervous system receptor known as TRPV1 can affect sensations of pain in the body. Now a group of Brown University scientists has found that these receptors – a darling of drug developers – also may play a role in learning and memory in the brain.

In surprising new research, published in the journal Neuron, Julie Kauer and her team show that activation of TPRV1 receptors can trigger long-term depression, a phenomenon that creates lasting changes in the connections between neurons. These changes in the brain – and the related process of neural reorganization known as long-term potentiation – are believed to be the cellular basis for memory making.

“We’ve known that TRPV1 receptors are in the brain, but this is some of the first evidence of what they actually do there,” Kauer said. “And the functional role we uncovered is unexpected. No one has previously linked these pain receptors to a cellular mechanism underlying memory. So we may have found a whole new player in brain plasticity.”

The study findings have implications for drug development, Kauer said.

The research points out potentially effective new targets for drugs that could prevent memory loss or could possibly treat neural disorders such as epilepsy, Kauer said. The other implication may be cautionary. Drug makers already sell drugs – such as the weight-loss pill rimonabant, which is sold in Europe under the name Acomplia – that can block TRPV1 receptors. Other drugs aimed at reducing pain and inflammation by blocking or activating TRPV1 receptors are in the research pipeline. But drugs that bind to TRPV1 receptors in the central nervous system are likely to influence more than just pain-related functions, Kauer said.

“Our findings suggest the possibility that some of the psychiatric side effects from rimonabant could be due to the blocking of TRPV1 receptors,” she said.

TRPV1, short for transient receptor potential vanilloid subtype, can be found all over the nervous system, including in skin, the spinal cord and the brain. These receptors can sense heat, trigger inflammation and transmit pain. TRPV1 receptors not only respond to heat but also to capsaicin, the compound that creates the spicy kick in chili peppers.

In her study, Kauer, professor of medical science in the Department of Molecular Pharmacology, Physiology and Biotechnology at Brown, treated rat brain tissue from the hippocampus, the brain’s seat of learning and memory, with capsaicin. The team found that this compound activated TRPV1 channels – which alone triggered long-term depression in the brain tissue. Further, rimonabant entirely blocked long-term depression by blocking TRPV1 channels.

The team then tested brain tissue from mice that lacked TRPV1 receptors and found that long-term depression was absent – and that applying capsaicin still couldn’t elicit the changes to the synapses.

Source: Brown University

Related stories:

Researchers discover paradox about general anesthesia: It can increase post-surgical pain
The general anesthesia that puts patients into unconscious sleep so they do not feel surgical pain can increase the discomfort they feel once they wake up, say researchers from Georgetown University Medical Center. They say their findings, the first to scientifically explain what has been anecdotally observed in the clinic, may lead to wider use of the few anesthetics that don't have this side effect, or to the development of new ones.

Study raises caution on new painkillers
A new class of painkillers that block a receptor called TRPV1 may interfere with brain functions such as learning and memory, a new study suggests. The experiments with rat brain found that the TRPV1 receptor regulates a neural mechanism called long-term depression, which is believed to be central to establishing memory pathways in the brain.
Tarantula venom and chili peppers target same pain sensor
Venom from a West Indian tarantula has been shown to cause pain by exciting the same nerve cells in mice that sense high temperatures and the hot, spicy ingredient in chili peppers, UCSF scientists have discovered.
Protein on 'speed' linked to ADHD
A genetic change in the dopamine transporter – one of the brain's dopamine-handling proteins – makes it behave as if amphetamine is present and "run backward," Vanderbilt University Medical Center investigators report this week in The Journal of Neuroscience.
Researchers reveal types of genes necessary for brain development
Researchers from Harvard Medical School and Brandeis University have successfully completed a full-genome RNAi screen in neurons, showing what types of genes are necessary for brain development. Details of the screen and its novel methodology are published July 4th in the open-access journal PLoS Genetics.
Worms do calculus to find meals or avoid unpleasantness
Thanks to salt and hot chili peppers, researchers have found a calculus-computing center that tells a roundworm to go forward toward dinner or turn to broaden the search. It's a computational mechanism, they say, that is similar to what drives hungry college students to a pizza.
Spiritual effects of hallucinogens persist, researchers report
In a follow-up to research showing that psilocybin, a substance contained in "sacred mushrooms," produces substantial spiritual effects, a Johns Hopkins team reports that those beneficial effects appear to last more than a year.
Scientists find how neural activity spurs blood flow in the brain
New research from Harvard University neuroscientists has pinpointed exactly how neural activity boosts blood flow to the brain. The finding has important implications for our understanding of common brain imaging techniques such as fMRI, which uses blood flow in the brain as a proxy for neural activity.

News discussion:

Medicine & Health news