Optogenetic Stimulation of the Brain to Control Pain

A new study by a University of Texas at Arlington physics team in collaboration with bioengineering and psychology researchers shows for the first time how a small area of the brain can be optically stimulated to control pain.

Samarendra Mohanty, an assistant professor of physics, leads the Biophysics and Physiology Lab in the UT Arlington College of Science. He is co-author on a paper published online Wednesday by the journal PLOS ONE.

Researchers found that by using specific frequency of light to modulate a very small region of the brain called the anterior cingulate cortex, or ACC, they could considerably lessen pain in laboratory mice. Existing electrode based ACC stimulation lacks specificity and leads to activation of both excitatory and inhibitory neurons.

“Our results clearly demonstrate, for the first time, that optogenetic stimulation of inhibitory neurons in ACC leads to decreased neuronal activity and a dramatic reduction of pain behavior,” Mohanty said. “Moreover, we confirmed optical modulation of specific electrophysiological responses from different neuronal units in the thalamus part of the brain, in response to particular types of pain-stimuli.”

The research focused on chemical irritants and mechanical pain, such as that experienced following a pinprick or pinch. Mohanty said the results could lead to increased understanding of pain pathways and strategies for managing chronic pain, which often leads to severe impairment of normal psychological and physical functions.

“While reducing the sensation for chronic pain by optical stimulation, we still want to sense certain types of pain because they tell us to move our hands or legs away from something that is too hot or that might otherwise hurt us if we get too close,” Mohanty said.

This image shows images of the anterior cingulate cortex taken from the study.
GAD1 and GFP positive labeled cells in the anterior cingulate cortex. A: GFP, B: GAD1, C: DAPI, D: GFP+ labeled cells overlaid with GAD1 and DAPI. High magnification image at the anterior cingulate cortex (E: DAPI, F: GAD1, G: GFP, H: co-expression). (I) Number of cells expressing GFP+, GAD1+, or GFP & GAD1 in the ACC. Confocal images of immunostaining of the ACC neurons with GAD1-FITC (J), and YFP-Alexa 555 (K). Scale bar: 50 μm. Image credit: Gu et al./PLOS ONE.

About this pain research

Young-tae Kim, a UT Arlington associate professor of bioengineering and study co-author, said the research could “possibly lead to less invasive methods for treating more severe types of pain without losing important emotional, sensing and behavioral functions.”

Ling Gu, a postdoctoral researcher who worked in the Mohanty lab, is lead author on the PLOS ONE paper, “Pain inhibition by Optogenetic Activation of Specific Anterior Cingulate Cortical Neurons.” Other co-authors are Megan Uhelski, previous UT Arlington doctoral student in psychology, and Sanjay Anand, researchers in bioengineering; Mario Romero-Ortega, an associate professor of bioengineering at UT Dallas; and, Perry Fuchs, UT Arlington professor of psychology.

Recently, Mohanty’s team demonstrated the first near-infrared laser based two-photon optical stimulation of in-depth brain regions.The team now plans to carry out localized non-invasive stimulation of small brain regions such as ACC to better understand and control functioning of brain.

Mohanty’s lab is currently supported by a $384,269 two-year grant from the National Institutes of Health National Institute of Neurological Disorders and Strokes.

Contact: Bridget Lewis – UT Arlington
Source: UT Arlington press release
Image Source: The image is credited to Gu et al./PLOS ONE and is adapted from the research paper
Original Research: Full open access research for “Pain Inhibition by Optogenetic Activation of Specific Anterior Cingulate Cortical Neurons” by Ling Gu, Megan L. Uhelski, Sanjay Anand, Mario Romero-Ortega, Young-tae Kim, Perry N. Fuchs, and Samarendra K. Mohanty in PLOS ONE. Published online February 25 2015 doi:10.1371/journal.pone.0117746

Open Access Neuroscience Abstract

Pain Inhibition by Optogenetic Activation of Specific Anterior Cingulate Cortical Neurons

Cumulative evidence from both humans and animals suggests that the anterior cingulate cortex (ACC) is important for pain-related perception, and thus a likely target for pain relief therapy. However, use of existing electrode based ACC stimulation has not significantly reduced pain, at least in part due to the lack of specificity and likely co-activation of both excitatory and inhibitory neurons. Herein, we report a dramatic reduction of pain behavior in transgenic mice by optogenetic stimulation of the inhibitory neural circuitry of the ACC expressing channelrhodopsin-2. Electrophysiological measurements confirmed that stimulation of ACC inhibitory neurons is associated with decreased neural activity in the ACC. Further, a distinct optogenetic stimulation intensity and frequency-dependent inhibition of spiking activity in the ACC was observed. Moreover, we confirmed specific electrophysiological responses from different neuronal units in the thalamus, in response to particular types of painful stimuli (i,e., formalin injection, pinch), which we found to be modulated by optogenetic control of the ACC inhibitory neurons. These results underscore the inhibition of the ACC as a clinical alternative in inhibiting chronic pain, and leads to a better understanding of the pain processing circuitry of the cingulate cortex.

“Pain Inhibition by Optogenetic Activation of Specific Anterior Cingulate Cortical Neurons” by Ling Gu, Megan L. Uhelski, Sanjay Anand, Mario Romero-Ortega, Young-tae Kim, Perry N. Fuchs, and Samarendra K. Mohanty in PLOS ONE. doi:10.1371/journal.pone.0117746

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