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Mechanical Conflict-Avoidance Assay to Measure Pain Behavior in Mice
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Behavioral Battery for Testing Candidate Analgesics in Mice. I. Validation with Positive and Negative Controls.

C M Diester1, E J Santos1, M J Moerke1

  • 1Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.

The Journal of Pharmacology and Experimental Therapeutics
|February 24, 2021
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Summary

This study validates a mouse model for assessing potential pain relief drugs. It uses a combination of pain-stimulated and pain-independent behaviors to accurately identify analgesic effects and avoid false positives.

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Area of Science:

  • Pharmacology and Toxicology
  • Neuroscience and Behavioral Science
  • Pain Research and Management

Background:

  • Preclinical pain research models are crucial for identifying effective analgesics.
  • Existing models can produce false-positive results, complicating the identification of true analgesics.
  • A validated behavioral assay is needed to differentiate analgesic effects from general drug effects.

Purpose of the Study:

  • To evaluate a novel behavioral assay in mice for preclinical assessment of candidate analgesics.
  • To distinguish true analgesic effects from non-specific drug actions using a battery of behaviors.
  • To validate the assay's utility with known analgesics and non-analgesic drugs.

Main Methods:

  • Utilized intraperitoneal injection of dilute lactic acid (IP acid) to induce visceral pain in mice.
  • Measured six behavioral endpoints: pain-stimulated (stretching, facial grimace) and pain-depressed (rearing, nesting) behaviors, plus pain-independent locomotion and nesting.
  • Compared the effects of ketoprofen and oxycodone (positive controls) against diazepam and amphetamine (negative controls) on these behaviors.

Main Results:

  • Ketoprofen demonstrated a clear analgesic profile, alleviating pain behaviors without affecting independent behaviors.
  • Oxycodone showed analgesic effects but required higher doses that impacted some pain-independent behaviors.
  • Negative controls (diazepam, amphetamine) failed to selectively block pain behaviors without altering independent behaviors, confirming their non-analgesic nature in this model.

Conclusions:

  • The validated behavioral assay effectively distinguishes analgesic properties from general motor effects in preclinical drug evaluation.
  • This comprehensive approach using pain-stimulated, pain-depressed, and pain-independent behaviors enhances the reliability of candidate analgesic screening.
  • The study provides a robust framework for improving the preclinical assessment of novel analgesics and reducing the risk of false-positive findings.