Ricardo Vallejo1,2, Ashim Gupta1,2,3, Courtney A Kelley1,2, Alejandro Vallejo1, Jonathan Rink4, Joseph M Williams2, Cynthia L Cass1,2, William J Smith1,5, Ramsin Benyamin1,2,6, David L Cedeño1,2. 1. Millennium Pain Center, Bloomington, IL, USA. 2. Department of Psychology, Illinois Wesleyan University, Bloomington, IL, USA. 3. South Texas Orthopaedic Research Institute, Laredo, TX, USA. 4. Department of Biology, Illinois Wesleyan University, Bloomington, IL, USA. 5. Geisel School of Medicine, Dartmouth College, Hanover, NH, USA. 6. College of Medicine, University of Illinois at Urbana-Champaign, Champaign-Urbana, IL, USA.
Abstract
OBJECTIVE: To investigate the effect of phase polarity and charge balance of spinal cord stimulation (SCS) waveforms on pain behavior and gene expression in a neuropathic pain rodent model. We hypothesized that differing waveforms will result in diverse behavioral and transcriptomics expression due to unique mechanisms of action. MATERIALS AND METHODS: Rats were implanted with a four-contact cylindrical mini-lead and randomly assigned to two control (no-pain and pain model) and five test groups featuring monophasic, as well as charge-unbalanced and charge-balanced biphasic SCS waveforms. Mechanical and cold allodynia were assessed to measure efficacy. The ipsilateral dorsal quadrant of spinal cord adjacent to the lead was harvested post-stimulation and processed to determine gene expression via real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Gene expression, SCS intensity (mA), and behavioral score as percent of baseline (BSPB) were statistically analyzed and used to generate correlograms using R-Studio. Statistical analysis was performed using SPSS22.0, and p < 0.05 was considered significant. RESULTS: As expected, BSPB was significantly lower for the pain model group compared to the no-pain group. BSPB was significantly improved post-stim compared to pre-stim using cathodic, anodic, symmetric biphasic, or asymmetric biphasic 1:2 waveforms; however, BSPB was not restored to Sham levels. RT-PCR analysis showed that eight genes demonstrated a significant difference between the pain model and SCS waveforms and between waveforms. Correlograms reveal a linear correlation between regulation of expression of a given gene in relation to mA, BSPB, or other genes. CONCLUSIONS: Our results exhibit that specific SCS waveforms differentially modulate several key transcriptional pathways that are relevant in chronic pain conditions. These results have significant implications for SCS: whether to move beyond traditional paradigm of neuronal activation to focus also on modulating immune-driven processes.
OBJECTIVE: To investigate the effect of phase polarity and charge balance of spinal cord stimulation (SCS) waveforms on pain behavior and gene expression in a neuropathic pain rodent model. We hypothesized that differing waveforms will result in diverse behavioral and transcriptomics expression due to unique mechanisms of action. MATERIALS AND METHODS: Rats were implanted with a four-contact cylindrical mini-lead and randomly assigned to two control (no-pain and pain model) and five test groups featuring monophasic, as well as charge-unbalanced and charge-balanced biphasic SCS waveforms. Mechanical and cold allodynia were assessed to measure efficacy. The ipsilateral dorsal quadrant of spinal cord adjacent to the lead was harvested post-stimulation and processed to determine gene expression via real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Gene expression, SCS intensity (mA), and behavioral score as percent of baseline (BSPB) were statistically analyzed and used to generate correlograms using R-Studio. Statistical analysis was performed using SPSS22.0, and p < 0.05 was considered significant. RESULTS: As expected, BSPB was significantly lower for the pain model group compared to the no-pain group. BSPB was significantly improved post-stim compared to pre-stim using cathodic, anodic, symmetric biphasic, or asymmetric biphasic 1:2 waveforms; however, BSPB was not restored to Sham levels. RT-PCR analysis showed that eight genes demonstrated a significant difference between the pain model and SCS waveforms and between waveforms. Correlograms reveal a linear correlation between regulation of expression of a given gene in relation to mA, BSPB, or other genes. CONCLUSIONS: Our results exhibit that specific SCS waveforms differentially modulate several key transcriptional pathways that are relevant in chronic pain conditions. These results have significant implications for SCS: whether to move beyond traditional paradigm of neuronal activation to focus also on modulating immune-driven processes.
Authors: Ricardo Vallejo; David C Platt; Jonathan A Rink; Marjorie A Jones; Courtney A Kelley; Ashim Gupta; Cynthia L Cass; Kirk Eichenberg; Alejandro Vallejo; William J Smith; Ramsin Benyamin; David L Cedeño Journal: Brain Sci Date: 2019-10-31
Authors: Benjamin J Main; Josiah A Valk; Nicola Maffulli; Hugo C Rodriguez; Manu Gupta; Ian W Stone; Saadiq F El-Amin; Ashim Gupta Journal: J Orthop Surg Res Date: 2020-11-11 Impact factor: 2.359
Authors: Ashim Gupta; Nicola Maffulli; Hugo C Rodriguez; Cassidy E Lee; Howard J Levy; Saadiq F El-Amin Journal: J Orthop Surg Res Date: 2021-02-18 Impact factor: 2.359
Authors: Ashim Gupta; Nicola Maffulli; Hugo C Rodriguez; Eric W Carson; Randa A Bascharon; Kristin Delfino; Howard J Levy; Saadiq F El-Amin Journal: J Orthop Surg Res Date: 2021-05-31 Impact factor: 2.359
Authors: Ricardo Vallejo; Courtney A Kelley; Ashim Gupta; William J Smith; Alejandro Vallejo; David L Cedeño Journal: Mol Pain Date: 2020 Jan-Dec Impact factor: 3.395