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Intracranial Pharmacotherapy and Pain Assays in Rodents
Published on: April 9, 2019
Autophagy: An Emerging Target for Developing Effective Analgesics
Palaniyandi Manivasakam1, Atchayaa Ravi2, Janani Ramesh2,3
1SystaMedic, Inc., Groton, Connecticut 06355, United States.
Abstract:
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.
Insights
New research identifies cannabidiol, myo-inositol, and fish oils as potential pain relievers. These compounds show promise for safer, effective analgesia, offering an alternative to traditional pain medications.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Inadequate pain management leads to significant health issues, including depression, anxiety, and mortality.
- Opioid abuse and NSAID side effects highlight the urgent need for safer pain therapeutics.
- Understanding pain's molecular mechanisms is crucial for developing novel treatments.
Purpose of the Study:
- To identify molecular targets for improved pain management using an in silico approach.
- To investigate the role of autophagy in pain modulation.
- To discover novel analgesic combinations with improved safety profiles.
Main Methods:
- Utilized an in silico emergent intelligence platform to analyze protein network interactions.
- Examined protein networks associated with over 20 pain types to identify regulatory mechanisms.
- Screened potential therapeutic compounds, including cannabidiol, myo-inositol, and fish oils, for analgesic properties.
Main Results:
- Autophagy regulation was identified as a key factor in pain symptom modulation.
- In silico analysis predicted superior analgesia from combinations of cannabidiol, myo-inositol, and fish oils (EPA/DHA).
- In vivo studies in rats demonstrated that these combinations produced analgesia comparable or superior to NSAIDs.
Conclusions:
- Cannabidiol, myo-inositol, and fish oils represent a promising combination for pain management.
- This novel combination offers a potentially safer and more effective alternative to existing analgesics.
- Further research is warranted to explore the clinical application of these findings in pain treatment.
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