200 Section - Resolution Phases of Pain and Inflammation

Objectives : To explore the latest published research in resolution phase of pain and inflammation.

Design: We reviewed published data in PubMed, NIH, Google Scholar, within the last 10 years.

Results:
Resolution starts with inflammation. Mediators synthesized from omega-3 polyunsaturated fatty acids of inflammation or resolution called Specialized Pro-resolving Mediators (SPMs) include: Resolvins, Protectins, Maresins, Cysteinyl-SPMs, n-3 Docosapentaenoic acid (DPA)-derived SPMs, and Lipoxins. SPMs act via G protein receptors, expressed by immune and glial cells, and neurons.

Neutrophils release Leukotriene B4. There is switch in PMN-Lipo-Oxygenase pathway expression, from LTs to lipoxins and resolvins.  PMNs initiate phenotypic changes via gene expression regulation.   PGE2/PGD2 stimulate processing of 15-LO mRNA in leukocytes producing Lipoxin. Arachidonic Acid is converted to Lipoxins (LXs), with dual anti-inflammatory/pro-resolving actions.

Early inhibition of COX-2 by NSAIDs is beneficial but “resolution-toxic”.   COX-2 inhibition decreases macrophage phagocytosis of apoptotic PMNs, reduce PGs expression.

Nuclear factor kappa B (NF-κB) has essential role in resolution. Subunits of NF-κB; p50/cRel, p65/cRel, or p50/p50 seem to be involved in transcription of genes of recovery.

Conclusion: Resolution is typically defined as a tightly regulated process that restores tissue homeostasis and prevents the development of chronic disease.

Studies on inflammatory resolution have advanced our understanding of leucocyte trafficking, efferocytosis and pro-inflammatory leucocyte clearance as well as immune-suppressive eicosanoids, specialized immune-regulatory cells and cytokine catabolism. These pathways converge on the termination of acute inflammatory responses.

Development of pro-resolution-based remedies to treat inflammation, is essential in exploring new areas of pharmacology known as “resolution pharmacology”.