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Nerve Growth Factor Upregulates IL‐4 And IL‐10 in an Animal Model of Persistent Low Back Pain
Author(s) -
Rigo Lima Carla,
Li Peng,
Martins Daniel,
Little Joshua,
Reed William
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02963
Subject(s) - nerve growth factor , medicine , proinflammatory cytokine , cytokine , saline , isoflurane , anesthesia , inflammation , endocrinology , receptor
Low back pain (LBP) is considered the global leading cause of years lived with disability affecting more than half a billion people. Despite the large direct and indirect impact of LBP on society, the underlying neurobiological mechanisms behind LBP are still poorly understood. Nerve Growth Factor (NGF) has been proposed to contribute to the pathophysiology of persistent pain through several pathways, including the indirect regulation of inflammatory cytokines. We hypothesize that the administration of NGF will increase pro‐ and decrease anti‐inflammatory cytokine levels in an animal model of persistent LBP. Purpose To investigate the pro‐ and anti‐inflammatory cytokine changes induced by nerve growth factor (NGF) intramuscular injections into the lumbar paraspinal muscles in a pre‐clinical model of persistent LBP. Methods Sprague Dawley rats (n=12; 180‐238g; 7 Males, 5 Females) were unilaterally injected with either NGF (50μl; 0.8 μM) or phosphate buffer saline ‐ PBS (50μl; control) on days 0 and 5 in the left multifidus muscle under isoflurane anesthesia (1‐2%/2L O 2 ). On day 12, animals (n=6/group) were anesthetized and blood collected by cardiac puncture. After coagulation (30 min), blood samples were centrifuged at 3000 rpm for 10 min, blood serum collected and frozen at −80°C until cytokine assays were performed. V‐PLEX Proinflammatory Panel 2 Rat Kit (Meso Scale Discovery®) multiplex analysis was conducted to characterize the concentration of cytokines (IFN‐γ, IL‐10, IL‐13, IL‐4, IL‐5, KC/GRO, TNFα, IL‐1β, and IL‐6) in the collected blood. Wilcoxon Rank Sum test was used to assess the differences in cytokine concentration between the NGF and PBS groups. Only values above the minimum test sensitivity for each cytokine were considered for the statistical analysis. Results IL‐4 and IL‐10 concentration levels were statistically significantly higher in NGF‐injected animals when compared to the control group (p=0.0305; Table 1). No other significant differences between groups were found (p > 0.05; Table 1). Conclusion Our preliminary findings suggest an upregulation of anti‐inflammatory cytokines identified at later stages of persistent LBP as an effect of NGF intramuscular injections. Future studies should consider investigating the early effects of NGF on cytokine regulation in persistent models of LBP to better understand the neurobiology underlying this condition.