Spared nerve injury decreases motivation in long-access homecage-based operant tasks in mice

Author:

Norris Makenzie R.12345ORCID,Becker Léa J.1234ORCID,Bilbily John12346,Chang Yu-Hsuan12345,Borges Gustavo1234,Dunn Samantha S.12345,Madasu Manish K.1234ORCID,Vazquez Chayla R.12345ORCID,Cariello Solana A.1234ORCID,Al-Hasani Ream12345ORCID,Creed Meaghan C.12345ORCID,McCall Jordan G.12345ORCID

Affiliation:

1. Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, United States

2. Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, MO, United States

3. Center for Clinical Pharmacology, St. Louis College of Pharmacy and Washington University School of Medicine, St. Louis, MO, United States

4. Washington University Pain Center, Washington University in St. Louis, St. Louis, MO, United States

5. Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United States

6. Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States

Abstract

Abstract Neuropathic pain causes both sensory and emotional maladaptation. Preclinical animal studies of neuropathic pain-induced negative affect could result in novel insights into the mechanisms of chronic pain. Modeling pain–induced negative affect, however, is variable across research groups and conditions. The same injury may or may not produce robust negative affective behavioral responses across different species, strains, and laboratories. Here, we sought to identify negative affective consequences of the spared nerve injury model on C57BL/6J male and female mice. We found no significant effect of spared nerve injury across a variety of approach-avoidance conflict, hedonic choice, and coping strategy assays. We hypothesized these inconsistencies may stem in part from the short test duration of these assays. To test this hypothesis, we used the homecage-based Feeding Experimentation Device version 3 to conduct 12-hour, overnight progressive ratio testing to determine whether mice with chronic spared nerve injury had decreased motivation to earn palatable food rewards. Our data demonstrate that despite equivalent task learning, spared nerve injury mice are less motivated to work for a sugar pellet than sham controls. Furthermore, when we normalized behavioral responses across all the behavioral assays we tested, we found that a combined normalized behavioral score is predictive of injury state and significantly correlates with mechanical thresholds. Together, these results suggest that homecage-based operant behaviors provide a useful platform for modeling nerve injury-induced negative affect and that valuable pain-related information can arise from agglomerative data analyses across behavioral assays—even when individual inferential statistics do not demonstrate significant mean differences.

Funder

National Institute of Neurological Disorders and Stroke

National Institute on Drug Abuse

Hetlzer Foundation

Rita Allen Foundation

Open Philanthropy Project

McDonnell Center for Cellular and Molecular Neurobiology, Washington University in St. Louis

Department of Anesthesiology and Pain Medicine, University of Washington

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Anesthesiology and Pain Medicine,Neurology (clinical),Neurology

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