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Intracranial Pharmacotherapy and Pain Assays in Rodents
Published on: April 9, 2019
Novel molecular targets in pain control
1AstraZeneca Research & Development Montreal, Canada. andy.dray@astrazeneca.com
Purpose Of Review:
The complexity of pain processing in clinical pain conditions and in animal models has revealed many time-related changes and an abundance of molecular drug targets. There continues to be insecurity, however, about new target validation in clinical pain and thus most analgesia development is of high risk for evolving new pain therapies. The present review highlights a number of molecular targets being pursued for pain control.
Recent Findings:
Many pain targets are critically dependent on the pain model/lesion type. Neural and glial plasticity, ranging from changes in molecular expression and receptor phosphorylation to profound morphological reorganization, has been described under these conditions. Pain modulation has been shown to involve all major families of regulatory proteins such as the G-protein coupled receptors, ion channels, regulatory enzymes, neurotrophins, and kinases, offering an abundance of targets and therapeutic opportunities for symptomatic pain relief.
Summary:
Many molecular targets have been highlighted with some being the focus of current analgesia research. Some of these (e.g. vanilloid receptor 1, cannabinoid receptor 1, sodium channel NaV 1.8) have been evaluated in animal studies and in preliminary clinical studies, but others are highly novel and riskier analgesia pain targets (e.g. metabotropic glutamate receptors, sensory neurone specific receptors, kinase inhibitors).
Insights
Developing new pain therapies involves identifying molecular targets. This review highlights numerous targets for pain control, including established and novel options, to address the high risks in analgesia development.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Pain processing is complex, with numerous molecular targets identified in clinical and animal studies.
- High risk and uncertainty surround new target validation for developing novel pain therapies.
- Existing analgesia development faces challenges in translating research into effective treatments.
Purpose of the Study:
- To review molecular targets currently being investigated for pain control.
- To highlight the abundance of therapeutic opportunities for symptomatic pain relief.
- To discuss the varying levels of risk associated with different molecular targets.
Main Methods:
- Literature review of current research on molecular targets for pain management.
- Analysis of identified targets based on pain models and lesion types.
- Categorization of targets based on their novelty and stage of clinical evaluation.
Main Results:
- Neural and glial plasticity significantly impact pain modulation, involving diverse molecular mechanisms.
- Major regulatory protein families (GPCRs, ion channels, kinases) offer numerous targets for pain relief.
- Targets range from well-studied (e.g., TRPV1, CNR1, NaV 1.8) to novel and higher-risk options (e.g., mGluRs, KIs).
Conclusions:
- Numerous molecular targets show promise for pain management.
- Established targets have undergone preliminary clinical evaluation, while novel targets represent higher-risk research avenues.
- Continued research into diverse molecular targets is crucial for advancing pain therapy development.
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