Ex Vivo Nerve Cell Identification via Electrical Stimulation
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Solution Overview
Problem
Current pain management therapies are inadequate for chronic neuropathic pain, with many patients not responding to existing medications due to serious side effects and varying responses based on gender or genetic factors, and there is a need for tailored therapeutic agents to address diverse pain pathologies.
Innovation Solution
A method for identifying and distinguishing Aδ-type and C-type nerve cells in ex vivo cell cultures using electrical stimulation with bipolar square waves at specific voltages and frequencies, allowing for the selective activation and modulation of these cells by drug candidates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If broad-spectrum pain medications are used to treat diverse pain pathologies, then a larger patient population may be reached, but serious side effects and addiction risk increase
Solution Approach 1:
The patent segments pain medications by their specific action on different nerve fiber types (Aδ-fibers vs C-fibers). Instead of using broad-spectrum medications that affect multiple fiber types and cause side effects, the invention enables selection of medications tailored to the specific fiber type involved in the patient's pain condition, thereby reducing unnecessary side effects while maintaining effectiveness across diverse pain pathologies.
Solution Approach 2:
The patent applies local quality by matching medications to specific local characteristics of pain pathways (fiber type specificity). By identifying which specific nerve fiber type (Aδ or C) is mediating the pain, clinicians can select medications with targeted action on that fiber type, providing localized therapeutic precision that reduces systemic side effects while maintaining broad applicability across different pain conditions.
2Reliability
If current medications are used for chronic neuropathic pain, then some pain relief may be obtained, but many patients do not respond due to individual variability
Solution Approach 1:
The patent changes the parameter of medication selection from empirical trial-and-error to physiology-based prediction. By using the ex vivo nerve preparation assay to determine a patient's response pattern to test medications, the system predicts which medication will be effective before clinical administration, thereby increasing reliability and reducing response variability associated with individual differences in gender or genetics.
3Measurement precision
If ex vivo nerve preparations are used to test drug selectivity, then specific action on human pain pathways can be identified, but the complexity of the testing system increases
Solution Approach 1:
The patent uses an intermediary ex vivo nerve preparation system that bridges the gap between simple in vitro assays and complex in vivo testing. This intermediary system provides high measurement precision for drug selectivity while avoiding the full complexity of in vivo testing, as the isolated nerve preparations can be tested in a controlled laboratory setting with reduced ethical and technical constraints.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables the development of customized pain treatments by identifying the specific action of drug candidates on human pain pathways, improving pain relief and reducing side effects by matching therapeutic agents with the appropriate nerve cell types.
Implementation Method 1
pulsing the nerve cells with an electrical train of bipolar square waves at two different voltages and two different frequencies
Implementation Method 2
loading the nerve cells with a calcium, sodium, or voltage-sensitive indicator or expressing a genetically encoded calcium, sodium, or voltage-sensitive indicator, detecting activation of the nerve cell by measuring the changes in the signal intensity of the indicator
Data Source
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AI summary
The present invention provides methods of identifying and distinguishing different types of nerve cells in ex vivo cell culture, the method comprising the steps of: a) culturing somato-sensory nerve cells ex vivo, b) loading the nerve cells with a calcium, sodium, or voltage-sensitive indicator or expressing a genetically encoded calcium, sodium, or voltage-sensitive indicator, c) pulsing the nerve cells with an electrical train of bipolar square waves at two different voltages and two different frequencies; wherein the first voltage is 10 V/cm or less (low voltage) and the second voltage is between 12 and 20 V/cm (high voltage); and wherein the first frequency is 5 Hz or less (low frequency) and the second frequency is between 15 and 20 Hz (high frequency), and d) detecting activation of the nerve cell by measuring the changes in the signal intensity of the indicator, wherein low voltage and low frequency activation indicates a first type of cell and activation detected only at high voltage indicates a second type of cell.