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4-Hydroxynonenal, anendogenous aldehyde,causes pain andneurogenicinflammation throughactivation of theirritant receptorTRPA1 Marcello TrevisaniJan SiemensSerena Materazzi2007 год

4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1
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Аннотация: TRPA1 is an excitatory ion channel expressed by a subpopulation of primary afferent somatosensory neurons that contain substance P and calcitonin gene-related peptide. Environmental irritants such as mustard oil, allicin, and acrolein activate TRPA1, causing acute pain, neuropeptide release, and neurogenic inflammation. Genetic studies indicate that TRPA1 is also activated downstream of one or more proalgesic agents that stimulate phospholipase C signaling pathways, thereby implicating this channel in peripheral mechanisms controlling pain hypersensitivity. However, it is not known whether tissue injury also produces endogenous proalgesic factors that activate TRPA1 directly to augment inflammatory pain. Here, we report that recombinant or native TRPA1 channels are activated by 4-hydroxy-2-nonenal (HNE), an endogenous alpha,beta-unsaturated aldehyde that is produced when reactive oxygen species peroxidate membrane phospholipids in response to tissue injury, inflammation, and oxidative stress. HNE provokes release of substance P and calcitonin gene-related peptide from central (spinal cord) and peripheral (esophagus) nerve endings, resulting in neurogenic plasma protein extravasation in peripheral tissues. Moreover, injection of HNE into the rodent hind paw elicits pain-related behaviors that are inhibited by TRPA1 antagonists and absent in animals lacking functional TRPA1 channels. These findings demonstrate that HNE activates TRPA1 on nociceptive neurons to promote acute pain, neuropeptide release, and neurogenic inflammation. Our results also provide a mechanism-based rationale for developing novel analgesic or anti-inflammatory agents that target HNE production or TRPA1 activation.
Год издания: 2007
Авторы: Marcello Trevisani, Jan Siemens, Serena Materazzi, Diana M. Bautista, Romina Nassini, Barbara Campi, Noritaka Imamachi, Eunice Andrè, Riccardo Patacchini, Graeme S. Cottrell, Raffaele Gatti, Allan I. Basbaum, Nigel W. Bunnett, David Julius, Pierangelo Geppetti
Издательство: National Academy of Sciences
Источник: Proceedings of the National Academy of Sciences
Ключевые слова: Ion Channels and Receptors, Pain Mechanisms and Treatments, Neurobiology and Insect Physiology Research
Другие ссылки: Proceedings of the National Academy of Sciences (HTML)
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Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
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