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Our results showed the following. First, a brief pretreatment with a low dose of TNF\u03b1 (1.44 nM, 9 min) enhanced the sensitivity of transient receptor potential vanilloid type 1 (TRPV1) receptors in these neurons in two distinct phases: the inward current evoked by capsaicin was amplified (\u0394 = 247%) immediately following the TNF\u03b1 pretreatment, which gradually declined toward control and then increased again reaching another peak (\u0394 = 384%) after 60\u201390 min. Second, the immediate phase of this potentiating effect of TNF\u03b1 was completely abolished by a pretreatment with a selective cyclooxygenase-2 (COX-2) inhibitor, NS-398, whereas the delayed potentiation was only partially attenuated. Third, in sharp contrast, TNF\u03b1 did not generate any potentiating effect on the responses to non-TRPV1 chemical activators of these neurons. Fourth, the selectivity of the TNF\u03b1 action on TRPV1 was further illustrated by the responses to acid (pH 6.0); TNF\u03b1 did not affect the rapid transient current mediated by acid-sensing ion channels but significantly augmented the slow sustained current mediated by TRPV1 in the same neurons. Fifth, in anesthetized rats, a similar pattern of acute sensitizing effects of TNF\u03b1 on pulmonary C-fiber afferents and the involvement of COX-2 were also clearly shown. In conclusion, a brief pretreatment with TNF\u03b1 induced both immediate and delayed potentiating effects on the TRPV1 sensitivity in pulmonary sensory neurons, and the production of COX-2 arachidonic acid metabolites plays a major role in the immediate sensitizing effect of TNF\u03b1.<\/jats:p>","DOI":"10.1152\/ajplung.00235.2016","type":"journal-article","created":{"date-parts":[[2017,5,19]],"date-time":"2017-05-19T00:25:19Z","timestamp":1495153519000},"page":"L293-L304","source":"Crossref","is-referenced-by-count":22,"title":["Immediate and delayed potentiating effects of tumor necrosis factor-\u03b1 on TRPV1 sensitivity of rat vagal pulmonary sensory neurons"],"prefix":"10.1152","volume":"313","author":[{"given":"Chun-Chun","family":"Hsu","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky;"},{"name":"School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, 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