Diagnostic and prognostic biomarkers of nerve injury and/or pain as well as improved pain therapeutics are needed, both on the battlefield to treat injured Service Members and in the civilian sector. Our previous research indicates that there are several differentially expressed (DE) extracellular vesicle-derived microRNAs (EV-miRNAs) isolated from rat plasma following spinal nerve ligation (SNL). As such, EV-miRNAs hold promise as biomarkers and therapeutic targets. The secretome contains biological mediators, including EVs, which are released into the extracellular space. In this study we focus on evaluating EV-non-coding RNAs (ncRNAs), examine effects of SNL on key protein expression in the prefrontal cortex (PFC), and test the secretome’s analgesic properties. To accomplish these goals, anesthetized male Sprague Dawley rats underwent SNL and nociceptive behavior measurements, plasma collection followed by EV RNA isolation, small RNA sequencing, and analysis. Expression of several key proteins in the PFC was determined by Wes/Jess analysis. The secretome bath was applied directly to the ligated nerve and the paw withdrawal threshold (PWT) was measured. We identified differences in several classes of ncRNAs such as piRNAs, snoRNAs, and snRNAs post-SNL. Levels of phosphorylated forms of P70S6K and ERK1 were increased in the dorsal PFC at 15 days post-SNL. Bath application of the secretome directly to the ligated nerve resulted in recovery of the reduced PWT (increased mechanical sensitivity) that is induced by SNL. Here, we have identified specific EV-ncRNAs that could contribute to the formation of pain. Furthermore, we have evaluated a novel product for analgesic efficacy that could function to exploit the underlying mechanisms that contribute to pain development, thus reducing acute pain. This is key in treating Service Members on the battlefield in order to prevent pain chronification.
| Published in | American Journal of Psychiatry and Neuroscience (Volume 10, Issue 2) |
| DOI | 10.11648/j.ajpn.20221002.12 |
| Page(s) | 63-76 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2022. Published by Science Publishing Group |
Secretome, Nociception, Extracellular Vesicles, Analgesia, Spinal Nerve Ligation, Non-coding RNA
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APA Style
Megan Rose Hershfield, Misty Marie Strain, Roger Chavez, Michaela Rae Priess, Alberto Mares, et al. (2022). Exploring the Secretome’s Biomarker and Analgesic Potential. American Journal of Psychiatry and Neuroscience, 10(2), 63-76. https://doi.org/10.11648/j.ajpn.20221002.12
ACS Style
Megan Rose Hershfield; Misty Marie Strain; Roger Chavez; Michaela Rae Priess; Alberto Mares, et al. Exploring the Secretome’s Biomarker and Analgesic Potential. Am. J. Psychiatry Neurosci. 2022, 10(2), 63-76. doi: 10.11648/j.ajpn.20221002.12
AMA Style
Megan Rose Hershfield, Misty Marie Strain, Roger Chavez, Michaela Rae Priess, Alberto Mares, et al. Exploring the Secretome’s Biomarker and Analgesic Potential. Am J Psychiatry Neurosci. 2022;10(2):63-76. doi: 10.11648/j.ajpn.20221002.12
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Download@article{10.11648/j.ajpn.20221002.12,
author = {Megan Rose Hershfield and Misty Marie Strain and Roger Chavez and Michaela Rae Priess and Alberto Mares and Aarti Gautam and George Dimitrov and Ruoting Yang and Alex Valdez Trevino and Col Kenney Wells and Col Thomas Stark and Rasha Hammamieh and John Leo Clifford and Natasha Marie Sosanya},
title = {Exploring the Secretome’s Biomarker and Analgesic Potential},
journal = {American Journal of Psychiatry and Neuroscience},
volume = {10},
number = {2},
pages = {63-76},
doi = {10.11648/j.ajpn.20221002.12},
url = {https://doi.org/10.11648/j.ajpn.20221002.12},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajpn.20221002.12},
abstract = {Diagnostic and prognostic biomarkers of nerve injury and/or pain as well as improved pain therapeutics are needed, both on the battlefield to treat injured Service Members and in the civilian sector. Our previous research indicates that there are several differentially expressed (DE) extracellular vesicle-derived microRNAs (EV-miRNAs) isolated from rat plasma following spinal nerve ligation (SNL). As such, EV-miRNAs hold promise as biomarkers and therapeutic targets. The secretome contains biological mediators, including EVs, which are released into the extracellular space. In this study we focus on evaluating EV-non-coding RNAs (ncRNAs), examine effects of SNL on key protein expression in the prefrontal cortex (PFC), and test the secretome’s analgesic properties. To accomplish these goals, anesthetized male Sprague Dawley rats underwent SNL and nociceptive behavior measurements, plasma collection followed by EV RNA isolation, small RNA sequencing, and analysis. Expression of several key proteins in the PFC was determined by Wes/Jess analysis. The secretome bath was applied directly to the ligated nerve and the paw withdrawal threshold (PWT) was measured. We identified differences in several classes of ncRNAs such as piRNAs, snoRNAs, and snRNAs post-SNL. Levels of phosphorylated forms of P70S6K and ERK1 were increased in the dorsal PFC at 15 days post-SNL. Bath application of the secretome directly to the ligated nerve resulted in recovery of the reduced PWT (increased mechanical sensitivity) that is induced by SNL. Here, we have identified specific EV-ncRNAs that could contribute to the formation of pain. Furthermore, we have evaluated a novel product for analgesic efficacy that could function to exploit the underlying mechanisms that contribute to pain development, thus reducing acute pain. This is key in treating Service Members on the battlefield in order to prevent pain chronification.},
year = {2022}
}
TY - JOUR T1 - Exploring the Secretome’s Biomarker and Analgesic Potential AU - Megan Rose Hershfield AU - Misty Marie Strain AU - Roger Chavez AU - Michaela Rae Priess AU - Alberto Mares AU - Aarti Gautam AU - George Dimitrov AU - Ruoting Yang AU - Alex Valdez Trevino AU - Col Kenney Wells AU - Col Thomas Stark AU - Rasha Hammamieh AU - John Leo Clifford AU - Natasha Marie Sosanya Y1 - 2022/05/10 PY - 2022 N1 - https://doi.org/10.11648/j.ajpn.20221002.12 DO - 10.11648/j.ajpn.20221002.12 T2 - American Journal of Psychiatry and Neuroscience JF - American Journal of Psychiatry and Neuroscience JO - American Journal of Psychiatry and Neuroscience SP - 63 EP - 76 PB - Science Publishing Group SN - 2330-426X UR - https://doi.org/10.11648/j.ajpn.20221002.12 AB - Diagnostic and prognostic biomarkers of nerve injury and/or pain as well as improved pain therapeutics are needed, both on the battlefield to treat injured Service Members and in the civilian sector. Our previous research indicates that there are several differentially expressed (DE) extracellular vesicle-derived microRNAs (EV-miRNAs) isolated from rat plasma following spinal nerve ligation (SNL). As such, EV-miRNAs hold promise as biomarkers and therapeutic targets. The secretome contains biological mediators, including EVs, which are released into the extracellular space. In this study we focus on evaluating EV-non-coding RNAs (ncRNAs), examine effects of SNL on key protein expression in the prefrontal cortex (PFC), and test the secretome’s analgesic properties. To accomplish these goals, anesthetized male Sprague Dawley rats underwent SNL and nociceptive behavior measurements, plasma collection followed by EV RNA isolation, small RNA sequencing, and analysis. Expression of several key proteins in the PFC was determined by Wes/Jess analysis. The secretome bath was applied directly to the ligated nerve and the paw withdrawal threshold (PWT) was measured. We identified differences in several classes of ncRNAs such as piRNAs, snoRNAs, and snRNAs post-SNL. Levels of phosphorylated forms of P70S6K and ERK1 were increased in the dorsal PFC at 15 days post-SNL. Bath application of the secretome directly to the ligated nerve resulted in recovery of the reduced PWT (increased mechanical sensitivity) that is induced by SNL. Here, we have identified specific EV-ncRNAs that could contribute to the formation of pain. Furthermore, we have evaluated a novel product for analgesic efficacy that could function to exploit the underlying mechanisms that contribute to pain development, thus reducing acute pain. This is key in treating Service Members on the battlefield in order to prevent pain chronification. VL - 10 IS - 2 ER -
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