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Assessing the Effect of Macrophage Derived Small Extracellular Vesicles on Pain Behavior, Inflammation, and Nociceptive Afferent Sprouting after C5 Unilateral Contusion in Female Sprague Dawley Rats
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Assessing the Effect of Macrophage Derived Small Extracellular Vesicles on Pain Behavior, Inflammation, and Nociceptive Afferent Sprouting after C5 Unilateral Contusion in Female Sprague Dawley Rats

Jason Wheeler, Xuan Luo, Corinne Marble, Yuzhen Tian, Seena Ajit and Megan Detloff
2025
url
https://doi.org/10.34945/f53p4xView
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Abstract

dorsal root ganglia nociceptor small extracellular vesicles Plasticity
STUDY PURPOSE: Neuropathic pain is a maladaptive pain condition that occurs following spinal cord injury (SCI), etiologically attributed in part to dysregulated communication between pain processing neurons along the sensory neuroaxis and populations of macrophages and microglia. Recent work highlighted the analgesic potential of small extracellular vesicles (sEVs) derived from lipopolysaccharide (LPS)-stimulated macrophages in preclinical models of inflammatory pain. However, whether sEVs could produce similar effects in models of neuropathic pain remains unexplored. This study investigates whether these sEVs are therapeutically viable in treatment of SCI-induced neuropathic pain, as well as the biological mechanisms by which this analgesia is produced. DATA COLLECTED: Adult (age > 6 weeks, weight >225 g), female Sprague Dawley rats received a C5 unilateral contusion SCI. Two weeks post-injury, SCI rats received an intrathecal injection of either saline vehicle or 10µg of sEVs isolated from untreated (sEV-) or LPS-stimulated (sEV+) RAW264.7 macrophages in 0.1M PBS. von Frey, Hargreaves, and the mechanical conflict avoidance paradigm were performed at 12-, 18-, 26-, and or 35-days post injury to observe how pain behaviors of SCI rats evolved over time in response to SCI and sEV+, sEV-, or saline treatment. Rats were euthanized and perfused at either 18- or 40-days post SCI for immunohistochemistry experiments that examined the plasticity of nociceptive primary afferent distribution and macrophage/microglial presence in the ipsilesional superficial dorsal horn at C7-C8, as well as macrophage number in the ipsilesional C7 dorsal root ganglia (DRG) after intrathecal sEV injection. DATA USAGE NOTES:

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