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C57BL/6 substrain differences in formalin-induced pain-like behavioral responses.
Esad Ulker1, Martial Caillaud1, Trusha Patel1
1Department of Pharmacology and Toxicology and Translational Research Initiative for Pain and Neuropathy, Virginia Commonwealth University, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
Behavioural Brain Research
|May 20, 2020
Summary
Genetic differences in mouse substrains impact pain sensitivity. C57BL/6 N mice exhibit heightened responses to inflammatory pain compared to C57BL/6 J mice, offering insights for preclinical pain research.
Area of Science:
- Neuroscience
- Genetics
- Pain Research
Background:
- Pain sensitivity and drug responses exhibit significant heritability across species.
- Individual differences in nociception necessitate genetic studies using inbred mouse models.
- Closely related C57BL/6 substrains offer potential for gene mapping in pain research.
Purpose of the Study:
- To investigate behavioral differences between C57BL/6 J and C57BL/6 N mouse substrains in a formalin-induced inflammatory pain model.
- To assess pain-related phenotypes including reflexive responses, nesting, wheel running, sucrose preference, and anxiety-like behavior.
- To evaluate substrain differences at acute (1-h) and persistent (24-h) time points post-formalin injection.
Main Methods:
- Utilized the formalin test, a standard model for tonic inflammatory pain.
- Administered a comprehensive battery of behavioral tests to assess pain phenotypes.
- Compared C57BL/6 J and C57BL/6 N substrains across multiple pain-related measures.
- Analyzed behavioral outcomes at 1-hour and 24-hour intervals post-treatment.
Main Results:
- No significant differences in reflexive thermal or mechanical responses were observed between substrains at 1-hour.
- C57BL/6 N mice displayed increased sensitivity to spontaneous pain-like behaviors.
- Persistent mechanical hypersensitivity was observed in C57BL/6 N mice at 24-hours.
- No sex differences were detected in any of the measured outcome variables.
Conclusions:
- C57BL/6 N substrain exhibits heightened sensitivity and persistent hypersensitivity in an inflammatory pain model compared to C57BL/6 J.
- The formalin test combined with a broad behavioral assessment provides a robust paradigm for genetic studies of pain.
- These findings highlight substrain-specific differences crucial for selecting appropriate mouse models in preclinical pain research.

