More than 100 million Europeans are affected by arthritis and other rheumatic diseases that cause stiffness, inflammation and swelling in the joints. Notably, pain is one of the most bothersome symptoms reported by this group of people. Pain not only impairs the ability to function and reduces the quality of life, but also forms the basis for an increasing economical burden. According to the European Pain Network, chronic and recurrent pain accounts for nearly 500 million lost working days and a €34 billion hole in the economy every year across Europe. Acute local inflammation is self-limiting and resolves through an active termination program. Lipoxins and resolvins represent novel classes of lipid mediators that function as “braking signals” in inflammation. My recent work has shown that while systemic injection of lipoxins reduces both pain and edema, spinal delivery reduces inflammatory hyperalgesia without altering the peripheral inflammatory state. The lipoxin receptor, ALXR, was found expressed on spinal astrocytes, indicating that not only neurons, but also spinal non-neuronal cells participate in the regulation of pain signaling. The aim with the proposed studies is to 1) expand this work to examine if lipoxin A4 has anti-hyperalgesic effect in models of chronic inflammatory pain using experimental models of arthritis, 2) to include a second representative of anti-inflammatory lipid mediators, resolvins E1, and 3) to explore the hypothesis that pain may be sustained due to an impaired generation of counter-regulatory mediators. In addition, possible molecular mechanism by which lipoxins control astrocyte activation will be explored in astrocyte cultures. These studies promise to provide insights into novel mechanisms of regulation of spinal sensitization and inflammatory pain, shed light onto the role of non-neuronal cells in spinal nociceptive processing and point to novel drug targets for chronic inflammatory pain.
Field of science
- /natural sciences/biological sciences/biochemistry/biomolecules/lipids
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