Neuropathic Pain, Depressive-like Behaviors and Myeloid Cell Polarization in LysM-eGFP Mice of Both Sexes Following a Moderate Unilateral Cervical SCI
DOI:10.34945/F5GC7C
DATASET CITATION
Richards J. H., Freeman D. D., Detloff M. R. (2024) Neuropathic Pain, Depressive-like Behaviors and Myeloid Cell Polarization in LysM-eGFP Mice of Both Sexes Following a Moderate Unilateral Cervical SCI. Open Data Commons for Spinal Cord Injury. ODC-SCI:940 http://doi.org/10.34945/F5GC7C
ABSTRACT
STUDY PURPOSE: Neuropathic pain is a multifaceted, chronically debilitating condition that has sensory descriminative, affective and cognitive components. Following spinal cord injury (SCI), approximately 60% of individuals are diagnosed with neuropathic pain and comorbid mood disorders, while only ~21% of the general population will experience a mood disorder in their lifetime. These experiments aim to characterize development of pain- and mood-related behaviors and correlate them with the innate immune response post-SCI. While humanizing the rodent is impossible, the results from this study inform clinical literature to closely examine sex-differences reported in humans to better understand the underlying shared etiologies of pain and depressive-like behaviors following CNS trauma. We hypothesize that nociceptive and depressive-like dysregulation occurs after SCI and is associated with aberrant macrophage infiltration in segmental pain centers.
DATA COLLECTED: We completed moderate (40kDyn, 2sec dwell time) unilateral C5 spinal cord contusion on male and female LysM-eGFP reporter mice (age >6weeks) to visualize infiltrating macrophages. von Frey, Hargreaves, open-field and sucrose preference tests were conducted weekly, while the forced swim test and the mechanical conflict avoidance paradigm were only conducted at the terminal timepoint. At 6-weeks post-SCI, mice exhibit nociceptive and depressive-like dysfunction compared to naïve and sham groups. There were no differences between sexes, indicating that sex is not a contributing factor driving nociceptive or depressive-like behaviors after SCI. Group averages based on experimental group revealed that SCI caused persistent mechanical allodynia and thermal hyperalgesia with indications of both learned-helplessness and anhedonia at the terminal timepoint of the experiment. SCI mice displayed increased myeloid cell presence (infiltrating macrophages: LysM+/CD68+, resident macrophages: LysM-/CD68+, microglia: IBA1+) in the lesion epicenter, ipsilateral C7-8 dorsal horn and C7-8 DRGs as evidenced by eGFP, CD68, and Iba1 immunostaining when compared to naïve and sham mice. This was further confirmed by SCI-induced alterations in the expression of genes indicative of myeloid cell activation states and their associated secretome in the dorsal horn and DRGs.
CONCLUSIONS: Utilizing hierarchical cluster analysis, we classified mice based on endpoint nociceptive and depressive-like behavior scores. Approximately 59.3% of SCI mice clustered based on increased paw withdrawal threshold to mechanical stimuli and immobility time in the forced swim test. In conclusion, moderate unilateral cervical SCI caused the development of pain-related and depressive-like behaviors in a subset of mice and these behavioral changes are consistent with immune system activation in the segmental pain pathway.
KEYWORDS
Spinal Cord Injury; Macrophage; Neuroinflammation; Pain; Depression
PROVENANCE / ORIGINATING PUBLICATIONS
RELEVANT LINKS
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DATASET INFO
Contact: Detloff Megan (mrd64@drexel.edu)
Lab: Detloff Lab-Drexel University College of Medicine
ODC-SCI Accession:940
Records in Dataset: 136
Fields per Record: 150
Last updated: 2024-03-14
Date published: 2024-03-14
Downloads: 15
Files: 2
LICENSE
Creative Commons Attribution License (CC-BY 4.0)
FUNDING AND ACKNOWLEDGEMENTS
NIH National Institute for Neurological Disorders and Stroke R01 NS097880 (MRD)
CONTRIBUTORS
- Richards, Jonathan H.
- Drexel University
- Freeman, Daniel D.
- Drexel University
- Detloff, Megan R.
- Drexel University
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