Thymulin treatment attenuates inflammatory pain by modulating spinal cellular and molecular signaling pathways.

Abstract

Thymulin is a peptide hormone which is mainly produced by thymic epithelial cells and it has immune-modulatory and anti-inflammatory effects. In this study, we investigated the effects of different doses and various timings of thymulin intraperitoneal administration on spinal microglial activity and intracellular pathways in an inflammatory rat model of Complete Freund's adjuvant (CFA). Thymulin treatment was implemented following CFA-induced inflammation for 21 days. After conducting behavioral tests (edema and hyperalgesia), the cellular and molecular aspects were examined to detect the thymulin effect on inflammatory factors and microglial activity. We demonstrated that thymulin treatment notably reduced thermal hyperalgesia and paw edema induced by CFA. Furthermore, molecular investigations showed that thymulin reduced CFA-induced activation of microglia cells, phosphorylation of p38 MAPK and the production of spinal pro-inflammatory cytokines (TNF-α, IL-6) during the study. Our results suggest that thymulin treatment attenuates CFA-induced inflammation. This effect may be mediated by inhibition of spinal microglia and production of central inflammatory mediators which seems to be associated with the ability of thymulin to reduce p38 MAPK phosphorylation. These data provide evidence of the anti-hyperalgesic effect of thymulin on inflammatory pain and characterize some of the underlying spinal mechanisms.

• Authors: Behzad Nasseri, Jalal Zaringhalam, Samira Daniali, Homa Manaheji, Zahra Abbasnejad, Vida Nazemian
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 70 Pg. 225-234 (May 2019) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 30851702 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Freund's Adjuvant
• Thymic Factor, Circulating
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Disease Models, Animal
• Freund's Adjuvant (immunology)
• Humans
• Inflammation (drug therapy)
• Injections, Intraperitoneal
• Interleukin-6 (metabolism)
• Male
• Microglia (drug effects, physiology)
• Pain (drug therapy)
• Rats
• Rats, Wistar
• Signal Transduction (drug effects)
• Spinal Cord (pathology)
• Thymic Factor, Circulating (therapeutic use)
• Tumor Necrosis Factor-alpha (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)