British journal of pharmacology
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The perioperative period is characterized by profound changes in the body's homoeostatic processes. This review seeks to address whether epigenetic mechanisms may influence an individual's reaction to surgery and anaesthesia. Evidence from animal and human studies suggests that epigenetic mechanisms can explain many facets of susceptibility to acute and chronic pain, making them potential therapeutic targets. ⋯ Even though no direct investigations have been carried out, the potential influence of epigenetics on the inflammatory response that follows surgery seems a promising area for research. There is a considerable body of evidence that supports the involvement of epigenetics in the complex process of wound healing. Epigenetics is an important emerging research topic in perioperative medicine, with a huge potential to positively influence patient outcome.
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Recent advances in the understanding of gene regulation have shown there to be much more regulation of the genome than first thought, through epigenetic mechanisms. These epigenetic mechanisms are systems that have evolved to either switch off gene activity altogether, or fine-tune any existing genetic activation. Such systems are present in all genes and include chromatin modifications and remodelling, DNA methylation (such as CpG island methylation rates) and histone covalent modifications (e.g. acetylation, methylation), RNA interference by short interfering RNAs (siRNAs) and long non-coding RNAs (ncRNAs). ⋯ Newer classes of drugs regulate epigenetic mechanisms to counteract disease states in humans. The reports in this issue describe some advances in epigenetic understanding that relate to human disease, and our ability to control these mechanisms by pharmacological means. Increasingly the importance of epigenetics is being uncovered - it is pharmacology that will have to keep pace.
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Store-operated calcium (SOC) channels are thought to play a critical role in immune responses, inflammatory diseases and chronic pain. The aim of this study was to explore the potential role and mechanisms of SOC channels in collagen-induced arthritis (CIA). ⋯ This study provides the first evidence that inhibition of SOC entry prevents and relieves rheumatoid arthritis (RA) and arthritic pain. These effects are probably mediated by a reduction in cytokine levels in the periphery and activation of ERK and CaMKIIα in the spinal cord. These results suggest that SOC channels are potential drug targets for the treatment of RA.
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The locus coeruleus (LC) is the principal nucleus containing the noradrenergic neurons and is a major endogenous source of pain modulation in the brain. Glial cell line-derived neurotrophic factor (GDNF), a well-established neurotrophic factor for noradrenergic neurons, is a major pain modulator in the spinal cord and primary sensory neurons. However, it is unknown whether GDNF is involved in pain modulation in the LC. ⋯ GDNF injection into the LC exerts prolonged analgesic effects on neuropathic pain in rats by enhancing descending noradrenergic inhibition.
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A long-term imbalance between pro- and anti-inflammatory mediators leads to airway remodelling, which is strongly correlated to most of the symptoms, severity and progression of chronic lung inflammation. The Angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis of the renin-angiotensin system is associated with attenuation of acute and chronic inflammatory processes. In this study, we investigated the effects of Ang-(1-7) treatment in a model of chronic allergic lung inflammation. ⋯ Ang-(1-7) exerted beneficial attenuation of three major features of chronic asthma: lung inflammation, airway remodelling and hyperresponsiveness. Our results support an important protective role of Ang-(1-7) in lung inflammation.