Comparative effects of the ω3 polyunsaturated fatty acid derivatives resolvins E1 and D1 and protectin DX in models of inflammation and pain

Abstract

Flávia CS Fonseca,1 Ricardo M Orlando,2 Regina MM Turchetti-Maia,1 Janetti Nogueira de Francischi1 1Department of Pharmacology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 2Department of Chemistry, Exact Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Purpose: Specialized pro-resolving lipid mediators (SPMs), also known as lipoxins, resolvins (Rvs), protectins and maresins, have been implicated in the resolution of the inflammatory process. However, a systematic comparison of their activity in the relief of inflammation and pain models is still lacking.Materials and methods: The effects of Rvs E1 and D1 and protectin DX (PDX) were assessed in rat paws inflamed by the standard proinflammatory stimulus carrageenan or by histamine, 5-hydroxytryptamine, substance P or prostaglandin E2. The experimental outcomes were the mechanical nociceptive threshold and increase in paw volume as a measure of pain and edema formation, respectively. The analgesic and anti-inflammatory activities of the indicated SPMs were also compared with nonsteroidal (indomethacin and celecoxib) and steroidal (dexamethasone) anti-inflammatory drugs.Results: Only RvE1 and RvD1 presented analgesic and anti-inflammatory activities in the carrageenan model, and RvE1 was twice as potent as RvD1. Both substances tended to be better analgesics than anti-inflammatory agents, with a modeling profile similar to steroidal anti-inflammatory drugs. However, proinflammatory effects (edema formation) were also detected when the mediators histamine, 5-hydroxytryptamine or substance P replaced carrageenan as the proinflammatory stimuli. The analgesic and anti-inflammatory effects of resolvins were specifically prevented by an antagonist of the leukotriene B4 receptor 1 (BLT1).Conclusion: Rvs, as analgesic agents, may be better therapeutic agents than nonsteroidal anti-inflammatory drugs, the current choice in the relief of pain of an inflammatory origin. However, the possibility of developing adverse effects cannot be overlooked. Keywords: specialized pro-resolving lipid mediators, edema, nociception, analgesics, anti-inflammatory drug