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New Methods For Screening Drugs Could Help Chronic Pain Sufferers - New Understanding How Menthol Affects Ion Channels in Transfer Pain Signals

March 10th 2006

New Methods For Screening Drugs Could Help Chronic Pain Sufferers - New Understanding How Menthol Affects Ion Channels in Transfer Pain Signals

Ardem Patapoutian

New research has found a novel method that could lead to potential advances in pain therapy.  New methodologies could help scientists understand how molecules, like menthol, affect the function of proteins that form ion tunnels found in the cell membrane. These tunnels form a channel that allows specific ions to pass or move across the membrane.   

The Director of the Research, Ardem Patapoutian, said “"Because our ability to sense temperature is closely linked to our ability to sense pain, it is not surprising that the misregulation of temperature-activated ion channels can result in chronic pain syndromes."  Patapoutian is an associate professor at Scripps Research and member of GNF.  He went on to say “In fact, some of these ion channels are considered targets to treat chronic inflammatory and neuropathic pain indications. Understanding how small molecules such as menthol affect the function of these proteins could be crucial in designing future drugs that can either activate or block them."


When the channels are activated, they open allowing an influx of calcium ions into the axon.  Then an electrical signal alerts the neuron, which relays the message to the brain.

Lead author, Michael Bandell, said, "It's a well established method to mutate individual amino acid residues in an ion channel protein and examine the effect that these mutations have on the channel's function. However, the laborious nature of these experiments limits the number of mutant ion channels that can be made and analyzed. Our new high-throughput screening methodology allowed us to analyze 14,000 mutants out of which we isolated five that specifically affected menthol activity. Our experiments yielded significant insights into the functional elements of TRPM8 ion channel protein that would have been difficult to obtain using other mutagenesis methods."  


The scientists utilized this novel mutagenesis and high-throughput screening approach.  The study assayed 14,000 TRPM8 mutants to find mutants that were not enhanced by menthol but were otherwise functioning normally. The scientists' analysis pinpointed a potential interaction site for menthol, as well as a site that translates binding information to ion channel activity.

Since the methodology can be used to screen for activation or inhibition, it could prove to be useful as a general method to analyze the mechanism by which drugs can activate or inhibit ion channels or other receptors.  According to the report appearing in the advanced online version by the journal Nature Neuroscience, the new methodology could be used to identify amino acid residues in certain ion channel proteins and G-protein coupled receptors (proteins involved in stimulus-response pathways) that are involved in the interaction with small molecules that affect their function.


There are an estimated 86 million Americans that suffer from chronic pain.  Many sufferers may obtain either over-the-counter (OTC) remedies or prescription remedies. Others may turn to alterative methods including acupuncture or acupressure. Pain is the number one reason for doctor’s visits according to authors of the book Where it Hurts and Why, Angela Sehgal and Kim Ortloff.

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By Dan Wilson
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Keywords and misspellings:  pane reumatoid rhumatoid rhumatoidal rheumatoidal arthritis arthrites pain

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Copyright 2005 Best Syndication                                            Last Updated Saturday, July 10, 2010 09:50 PM