Premium
Identification of Plasma Biomarkers Involved in Regulation of Inflammatory Pain
Author(s) -
Merritt Christina,
Stutz Sonja,
Covarrubias Obdulia,
Pazdrak Konrad,
Cisneros Irma,
Bossmann Stephan,
Motamedi Massoud,
Cunningham Kathryn
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.s1.03070
Subject(s) - medicine , inflammation , saline , nociception , carrageenan , cytokine , matrix metalloproteinase , anesthesia , pharmacology , receptor
Physicians are challenged in treating pain patients due to the lack of quantifiable, objective methods of measuring pain in the clinic; pain sensation is multifaceted and subjective to each individual. There is a critical need for point‐of‐care quantification of accessible biomarkers to provide objective analyses beyond the subjective pain scales currently employed in clinical care settings. In the present experiment, we employed an animal model to test the hypothesis that blood‐born regulators of the inflammatory response directly associate with an objective behavioral response to inflammatory pain. Upon induction of localized paw inflammation, we measured various cytokines and matrix metalloproteinases ( MMPs ) that are known to participate in the inflammatory response and investigated their relationship to the behavioral response across a 24‐hour period. Methods MaleSprague‐Dawley rats (n=6/group) outfitted with indwelling jugular catheters were injected with 0.1 ml of saline or 0.1 ml of the pro‐inflammatory compound λ‐carrageenan (1%) into the left hindpaw. Quantification of carrageenan‐evoked paw inflammation (paw thickness) and locomotor activity, as well as collection of blood (500 µl) for later biochemical analyses occurred 24 hrs prior to intraplantar injection (baseline) and at four timepoints post‐injection (1‐24 hrs). Plasma was aliquoted from each sample for detection of cytokines (BioPlex Rat Cytokine Panel) and MMPs. Results Intraplantar injection with 1% λ‐carrageenan induced a significant increase in paw thickness across 24 hrs, with peak inflammation observed at 8 hrs ( p <0.05 vs saline). Pearson's correlation analyses revealed that locomotor activity counts negatively correlated with paw inflammation at 8 hrs (r 2 =0.5645, p <0.05), demonstrating impaired locomotion at the peak of paw inflammation. Expression of the chemokines C‐X‐C motif chemokine ligand 1 ( Gro KC ) (r 2 =0.7061, p <0.05) and monocyte chemoattractant protein‐1 ( MCP‐1 ) (r 2 =0.5050, p <0.05) positively correlated with paw inflammation and negatively correlated with locomotor activity at 8 hrs (Gro KC, r 2 =0.6386, p <0.05; MCP‐1, r 2 =0.4150, p <0.05). The ratio of MMP9 to MMP2 activity negatively correlated with paw inflammation (r 2 =0.4759, p <0.05) at 8 hrs. No relationship between MMP9/MMP2 activity and locomotor activity was observed this timepoint. Interestingly, a mixed model ANOVA of the time course of MMP9/MMP2 activity revealed a significant increase at 1 hr ( p <0.05 vs saline). Conclusions We postulate that the chemokines Gro KC and MCP‐1 as well as the ratio of MMP9 to MMP2 activity may serve as predictive biomarkers for the timecourse of inflammation‐associated behavioral deficits. These data define opportunities for the future development of a point‐of‐care device to objectively quantify biomarkers for inflammatory pain states.