Title : Multi-Characteristic Opsin Gene Delivery for Neuromodulation of Inflammatory and Persistent Pain Sensation in Rodent Model
Pain is an uncomfortable sensation perceived by the nervous system that can have a variety of different causes. Pain can be seen as a complication of disease, emotional states and even as a standalone pathology. The neuroscience of pain is poorly understood. Multiple levels of complex neurological signals are thought to be involved in pain perception and modulation. Treatments for pain symptoms are limited and can be associated with severe, and even potentially deadly, side effects. The Anterior Cingulate Cortex (ACC) within the Corpus Callosum and the Dorsal Root Ganglion (DRG) of the spine are two regions thought to be involved in pain neural pathways and a potential target for neuromodulation. We created a highly sensitive optogenetic actuator Multi-Characteristic Opsin (MCO), which is expressed and targeted to inhibitory (GABAergic) neurons via a Glutamic Acid Decarboxylase promoter. This opsin was delivered to a mouse model through both viral and laser gene delivery methods. With the use of a Bluetooth Stimulator Device, we provided red light stimulation (630 nm) of these inhibitory neurons within the ACC and DRG at multiple stimulation frequencies and intensities. Pain responses and modulation were then investigated via a formalin challenge and sciatic cuff induced neuropathy, which mimicked acute inflammatory and persistent neuropathic models, respectively. We then measured pain responses via standard pain response behaviors such as hind paw lifting and licking. Chronic pain responses were also monitored via preference for cage regions that provided increased light stimulation associated with pain relief. Our results demonstrated that mice that expressed the optogenetic MCO had a significantly decreased pain response in response to both acute and chronic pain assays when subject to red light stimulation. More specifically, most of the decrease of reflexive pain was seen in the delayed, inflammatory phase that occurred around 20 minutes after formalin injection. In the control mice groups that did not express the optogenetic MCO and in the mice that expressed the optogenetic MCO but were not stimulated by red light, there was no significant difference between baseline reflexive pain values. Taken together, the delivery of the optogenetic MCO, coupled with direct red light stimulation of the DRG and ACC neurons, reduced pain sensation in our mice model. Overall, our findings support neuromodulation of GABAergic pathways within the nervous system as potential targets for the reduction of inflammatory and neuropathic pain.
What will audience learn from your presentation?
• The basic neuroscience of pain perception
• the use of formalin for inflammatory pain model in rodents
• How optogenetics can be utilized for neuromodulation
• Other potential targets for neuromodulation that can be investigated with similar methodology include treatment resistant depression, schizophrenia, vibration/touch sensation and many more possibilities.