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Intraganglionic CCL2 induced neuropathic pain and depression after unilateral cervical spinal cord contusion in adult male and female LysM-eGFP mice
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Intraganglionic CCL2 induced neuropathic pain and depression after unilateral cervical spinal cord contusion in adult male and female LysM-eGFP mice

Jonathan Richards, Grace Giddings and Megan Detloff
2026
url
https://doi.org/10.34945/f5t603View
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Abstract

CCL2 Depression dorsal root ganglia macrophage Pain
STUDY PURPOSE: Neuropathic pain and depression co-occur in more than half of individuals following spinal cord injury (SCI), yet the sensory and emotional dimensions of pain remain difficult to treat. The dorsal root ganglia (DRG) represent the first relay in the pain pathway and exhibit immune infiltration and altered inflammatory signaling after SCI. Our prior work demonstrated that reducing monocyte derived macrophage infiltration worsens pain outcomes and that pain-like and depressive-like behaviors correlate with reduced anti-inflammatory markers in the DRG, suggesting a failed endogenous immunomodulatory response. Because CCL2 is a monocyte chemoattractant transiently expressed after SCI and has been linked to macrophage recruitment and polarization, this study tested whether augmenting DRG macrophage recruitment via bolus intraganglionic CCL2 delivery would reduce pain-related sensory and emotional dysfunction after cervical SCI. DATA COLLECTED: Adult male and female LysM-eGFP mice received a unilateral moderate C5 contusive SCI or sham laminectomy followed by ipsilateral intraganglionic injection of recombinant mouse CCL2 or vehicle (0.1M PBS) into the C7-8 DRG. Uninjured mice served as naïve controls. Behavioral data included weekly assessments of mechanical sensitivity (von Frey), thermal sensitivity (Hargreaves), locomotor activity and anxiety-like behavior (open field), anhedonia (sucrose preference), and endpoint assessments of operant pain avoidance (mechanical conflict avoidance paradigm), and learned helplessness and coping behavior (forced swim test). Mice were sacrificed for histological analysis at 6 weeks post-SCI. Lesion size and tissue sparing were quantified using Nissl-myelin staining and stereological analysis. Immune outcomes included quantification of macrophage infiltration in injected DRGs using LysM and CD68 labeling to distinguish infiltrating monocyte-derived macrophages from resident populations, as well as assessment of macrophage and microglial activation in spinal cord regions caudal to injury using CD68 and Iba1 immunoreactivity. DATA USAGE NOTES:

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