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The cross-talk between opioid and TLR4 receptor signaling systems
Hrdličková, Daniela ; Drastichová, Zdeňka (advisor) ; Březina, Jiří (referee)
Opioids are commonly used in clinical practice to treat acute and chronic pain. They stereoselectively bind to opioid receptors and trigger a signal cascade through inhibitory Gi/o- proteins, resulting in analgetic effects. However, their use can lead to various adverse effects, such as the development of addiction, analgetic tolerance, allodynia, hyperalgesia, constipation, and peripheral immunosuppression. Recent studies have found that opioids also bind non- stereoselectively to Toll-like receptor which belongs to innate immune system receptors recognizing lipopolysacharide. Findings suggest that some of these adverse effects may be a result of this interaction. It induces the expression of proinflammatory mediators in the central nervous system, but under certain conditions, it may also suppress inflammation. Communication between these different receptor systems occurs at multiple levels. Understanding these mechanisms could greatly benefit the development of new therapeutic approaches in opioid analgetic treatment, aiming to minimize their adverse effects, it could also lead to the therapeutic use of the antiinflammatory potential of opioids. Keywords: Opioids, Toll-like receptor 4, cellular signaling, inflammation, lipopolysaccharide, cytokine
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