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Autophagy: An Emerging Target for Developing Effective Analgesics

[Image: see text] Inadequate treatment of acute and chronic pain causes depression, anxiety, sleep disturbances, and increased mortality. Abuse and overdose of opioids and the side effects associated with chronic use of NSAID illustrate the need for development of safer and effective pain medication...

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Autores principales: Manivasakam, Palaniyandi, Ravi, Atchayaa, Ramesh, Janani, Bhuvarahamurthy, Divyarathna, Kasirajan, Kalaiyarasi, Vijayapoopathi, Singaravel, Venugopal, Bhuvarahamurthy, Fliri, Anton Franz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018516/
https://www.ncbi.nlm.nih.gov/pubmed/36936313
http://dx.doi.org/10.1021/acsomega.2c06949
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author Manivasakam, Palaniyandi
Ravi, Atchayaa
Ramesh, Janani
Bhuvarahamurthy, Divyarathna
Kasirajan, Kalaiyarasi
Vijayapoopathi, Singaravel
Venugopal, Bhuvarahamurthy
Fliri, Anton Franz
author_facet Manivasakam, Palaniyandi
Ravi, Atchayaa
Ramesh, Janani
Bhuvarahamurthy, Divyarathna
Kasirajan, Kalaiyarasi
Vijayapoopathi, Singaravel
Venugopal, Bhuvarahamurthy
Fliri, Anton Franz
author_sort Manivasakam, Palaniyandi
collection PubMed
description [Image: see text] Inadequate treatment of acute and chronic pain causes depression, anxiety, sleep disturbances, and increased mortality. Abuse and overdose of opioids and the side effects associated with chronic use of NSAID illustrate the need for development of safer and effective pain medication. Working toward this end, an in silico tool based on an emergent intelligence analytical platform that examines interactions between protein networks was used to identify molecular mechanisms involved in regulating the body’s response to painful stimuli and drug treatments. Examining interactions between protein networks associated with the expression of over 20 different pain types suggests that the regulation of autophagy plays a central role in modulation of pain symptoms (see Materials and Methods). Using the topology of this regulatory scheme as an in silico screening tool, we identified that combinations of functions targeted by cannabidiol, myo-inositol, and fish oils with varying ratios of eicosapentaenoic and docosahexaenoic acids are projected to produce superior analgesia. For validating this prediction, we administered combinations of cannabidiol, myo-inositol, and fish oils to rats that received formalin injections in hind paws, prior to substance administration, and showed that analgesic effects produced by these combinations were comparable or superior to known NSAID analgesics, which suggests that these combinations have potential in treatment of pain.
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spelling pubmed-100185162023-03-17 Autophagy: An Emerging Target for Developing Effective Analgesics Manivasakam, Palaniyandi Ravi, Atchayaa Ramesh, Janani Bhuvarahamurthy, Divyarathna Kasirajan, Kalaiyarasi Vijayapoopathi, Singaravel Venugopal, Bhuvarahamurthy Fliri, Anton Franz ACS Omega [Image: see text] Inadequate treatment of acute and chronic pain causes depression, anxiety, sleep disturbances, and increased mortality. Abuse and overdose of opioids and the side effects associated with chronic use of NSAID illustrate the need for development of safer and effective pain medication. Working toward this end, an in silico tool based on an emergent intelligence analytical platform that examines interactions between protein networks was used to identify molecular mechanisms involved in regulating the body’s response to painful stimuli and drug treatments. Examining interactions between protein networks associated with the expression of over 20 different pain types suggests that the regulation of autophagy plays a central role in modulation of pain symptoms (see Materials and Methods). Using the topology of this regulatory scheme as an in silico screening tool, we identified that combinations of functions targeted by cannabidiol, myo-inositol, and fish oils with varying ratios of eicosapentaenoic and docosahexaenoic acids are projected to produce superior analgesia. For validating this prediction, we administered combinations of cannabidiol, myo-inositol, and fish oils to rats that received formalin injections in hind paws, prior to substance administration, and showed that analgesic effects produced by these combinations were comparable or superior to known NSAID analgesics, which suggests that these combinations have potential in treatment of pain. American Chemical Society 2023-03-03 /pmc/articles/PMC10018516/ /pubmed/36936313 http://dx.doi.org/10.1021/acsomega.2c06949 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Manivasakam, Palaniyandi
Ravi, Atchayaa
Ramesh, Janani
Bhuvarahamurthy, Divyarathna
Kasirajan, Kalaiyarasi
Vijayapoopathi, Singaravel
Venugopal, Bhuvarahamurthy
Fliri, Anton Franz
Autophagy: An Emerging Target for Developing Effective Analgesics
title Autophagy: An Emerging Target for Developing Effective Analgesics
title_full Autophagy: An Emerging Target for Developing Effective Analgesics
title_fullStr Autophagy: An Emerging Target for Developing Effective Analgesics
title_full_unstemmed Autophagy: An Emerging Target for Developing Effective Analgesics
title_short Autophagy: An Emerging Target for Developing Effective Analgesics
title_sort autophagy: an emerging target for developing effective analgesics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018516/
https://www.ncbi.nlm.nih.gov/pubmed/36936313
http://dx.doi.org/10.1021/acsomega.2c06949
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