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Optopharmacology: Use of Light to Treat Pain!
The knowledge of light gated ion channels (the trans-membrane proteins/receptors which function in response to light) in bacterial systems has always fascinated the scientists to control the neural activity of humans (neural function is a result of a number of ion-channels) using light. The first step towards study of response of neural activity to light stimulus in animals was taken in 2003 by Georg Nagel et al. (University of California, San Francisco), through their study on ChR2 i.e Channelrhodopsin-2 (a directly light-gated cation-selective membrane channel) in C. elegans. It was expressed in the muscle cells of the body wall of the worm (an approach called Optogenetics), and it was observed that illumination caused strong contractions of the worm! Similarly, it's expression in mechanosensory neurons of the worm caused a withdrawal movement, naturally evoked by mechanical stimulation. Following video shows an experiment on Optogenetic manipulation of C.elegans behavior (Schultheis et al.,2011):
Similarly, optogenetic experiments were carried out in Drosophila, zebrafish and mice with successful observation of activation/inactivation of neural response upon light stimulus. (One must be clear with the term "Optogenetics" here. It refers to the use of techniques for expression of such genes in the nerve cells that can make them responsive to light". For e.g the expression of ChR2 in the neurons of C.elegans/Drosophilla/Zebrafish/Mice as a part of different experiments is/was an Optogenetic approach). This article is drafted to make you aware about the recent development in Optogenetics approach, which aims at use of "Light" as a drug for pain relief in humans/animals, leading to a new branch of Pharmacology-Optopharmacology!

In a recent Nature Chemical Biology publication of April 2013, Kokel, D. et al. presented his research on the discovery of a new small molecule called optovin that could make the pain sensing neurons responsive to light, without the need of any genetic tools/modification (i.e Optoactivation without optogenetics!). Discovery of Optovin was not a serendipity but a result of an organized research aimed at screening the effect of small molecules on the swimming behavior of Zebrafish. Earlier it was thought that Optovin might have been affecting the visual perception of the zebrafish to mediate the change in swimming behavior, but to the surprise of the research group, it was found that the modus operandi of the molecule is rather through a cation channel TRPA1. The TRP channels are responsible for a variety of sensory perceptions/responses viz vision, taste, temperature and touch. TRPA1, belonging to the family of TRP receptors contributes to illnesses, like neuropathic pain and chronic inflammation, whose control is mediated by optovin (a photochemical as discovered by the group), thus offers a radically new and non-genetic way of controlling the neural activity and thus the pain! Following is an interactive video of David Benett (Kings College London), explaining the role of TRPA1 receptors in Pain Sensation:

What is Optovin?
Optovin is a newly discovered "photochemical", a rhodanine-containing yellow-colored compound with peak absorbance at 415 nm, with no history of discovered biological activity till the research group of Kokel found it's role in the photosensory movements in zebrafish! It's found to be a ligand for TRPA1, but being a photochemical, it's bonding with TRPA1 can be controlled by using light stimuli! As per the reasearch, the photochemical has no adverse affects on the development of the animals (embryonic to adult stages, when tested using upto 10uM conc.). But it has marked affect on the motor neuron excitation in response to "violet" light stimuli.

Suggested Mechanism of Action Of Optovin
The photonic energy of light excites the chemical creating reactive singlet oxygen species, which induces bonding with the TRPA1 receptors (via cysteine residues) through a thioether bonding (-s-O-s-). There was no response to optovin in animals treated with DABCO (1,4-diazabicyclo[2.2.2]octane) a singlet oxygen quencher and those having point mutations leading to lack of cysteine residues at the binding site, confirming the role of singlet oxygen and thioether bonding in Optovin's action.

Scope and Way Ahead:
Optovin emerges as an entirely new class of photochemical, that directly gives access to the activity of TRPA1 receptor(s), the key protein channels responsible for pain sensation/illness/neurological disorders. None of the other photochemicals( like caged glutamate, Azobenzene, DMSO etc) were so safe and effective in-vivo, and that too with profound effects in animal models (all earlier tests were limited to petridish/culture levels). Since the control of TRPA1 through Optovin is by photoactivated thioether bonding, it can easily be reversed by changing the light stimulus. This provides a precise control over the action of optovin and thus TRPA1. The next challenge is to test the ability of optovin's action in other animals (apart from zebrafish and mice). It's activity in gating the transfected human cells has been established already by the group, paving the way for optimizing the chemical characteristics of Optovin, which could make a therapeutic drug for instant light mediated relief from pain!

Let's hope that this research moves forward very fast, and brings the days when we might use a "Torch light" to treat the "Headache"!
Sunil Nagpal
MS(Research) Scholar, IIT Delhi (Alumnus)
Advisor for the Biotech Students portal (
Computational Researcher in BioSciences at a leading MNC

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Optogenetics is involved in tweaking of genes of neurons for making them to become sensitive to light. Technically, Optogenetics technology has been made almost ten years ago from the convergence of optics, genetics, materials science and neuroscience.
Optogenetics has the tendency to allow concise manipulation of brain.Researchers are investigating the factors of optogenetics for treating and comprehending a wide spectrum of brain disorders. These disorders include depression, obsessive-compulsive disorder , Parkinson’s and post-traumatic stress disorder and schizophrenia. Recently, a researcher has confirmed that he had instilled fake memories in optogenetically altered mice which has been applauded by other researchers.

Besides, a physicist holds the view that optogenetics has the ability to alter the way the doctors treat mental disorders. On the contrary, doctors have many contradictions over the use of optogenetics. They say that for treating certain mental disorder , it is of paramount importance to have broader knowledge of neurons overreaction and underactive functions. Thus, researchers have not come up with the gross ideas of treating psychological issues with the help of optogenetics.

Of course researchers are firmed to state that optogenetics has the capability of probing brain in varied ways and symptoms of obsessive-compulsive disorder, depression Parkinson’s, and other diseases are worth citing examples.

Apart from this, it is perceived that if optogenetics has to work over human beings, it would be used by the wealthy people as this kind of treatment may demand more money which may not be affordable by all and sundry. Yes, successful testing of optical neural control therapy on mice by optogenetics pioneer Ed Boyden clearly opines that the things in this technology are going smoothly and adequately.
Oxford optogenetics pioneer claims to have said that optogenetics can be a mean to determine nerve cell groups which cause certain diseases as targets for medicines. Hence, there is dire need of more experiments for altering the functions of neurons.
Sasa Milosevic
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