LASER OPTOGENETIC NEUROMODULATION OF PERIPHERAL NERVE PAIN IN A RODENT MODEL
Arman J Fijany, MD1, Robert Benkowski, MBA1,2, Darryl Narcisse, MD3, Nadeem Al-Adli, BS1 and Samarendra Mohanty, MD4, 1Burnett School of Medicine at Texas Christian University, Fort Worth, TX, 2Designplex Biomedical LLC, Fort Worth, TX, 3Opsin Biotherapeutics, Bedford, TX, 4Nanoscope Technologies, Arlington, TX
Introduction:
Pain management has been a significant target for debate in medicine, economics, and politics for the past few years. Opioid medications are the mainstay of treatment; however, their utilization has severe, potentially life-threatening consequences. There is a need for alternative treatments for patients who present with severe, debilitating pain. Peripheral nerve pain syndromes are poorly understood and often difficult to manage. Here we are investigating the use of optogenetic neuromodulation of cells in the pain pathway with Opsin delivery by functional gold nanorods (fGNR) in hopes of finding an alternative therapy to opioid medications for pain relief. Neuromodulation can potentially ameliorate pain without the severe side effects of contemporary pain therapy.
Methods:
Using a glutamic acid decarboxylase (GAD) promoter, our group delivered our highly sensitive optogenetic modulator Multi-Characteristic Opsin (MCO) to target inhibitory GABAergic Dorsal Root Ganglion (DRG), and spinal neurons in a rodent model. Opsin delivery was accomplished by functional gold nanorods (fGNR) for optogenetic stimulation. Our group has developed an implantable optogenetic pain modulator (OPM) device that can deliver 630 nm red light, which our MCO was specific and sensitive to. We also controlled light delivery – including the frequency and intensity – with a wireless phone application we created. Light intensity was quantified in (uW) within a penetration experiment at three tissue levels (skin, interstitial space, and spinal cord). Gene delivery was confirmed by immunostaining with mCherry. We modeled acute pain using the formalin assay. Each mouse was given a 20-microliter injection of the 1% Formalin solution into their hind paw. Sciatic nerve cuffing and the Von Frey assay were used to model neuropathic pain.
Results:
Gene delivery was confirmed by mCherry staining. Light intensity was confirmed above the threshold at all three levels of delivery. Optogenetic modulation of the spinal cord and associated structures significantly reduced pain responses in the formalin acute pain assay (p < 0.05) and the Von Frey assay (p < 0.05). Within the Von Frey assay, 20 minutes of optogenetic therapy resulted in pain relief that persisted for over 150 minutes.
Conclusion: Our findings show that a minimally invasive sensitization of critical elements in the pain communication and modulation pathway can be used to reduce peripheral nerve pain.
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