Acute potentiating effects of tumor necrosis factor-α (TNFα) on the responses of rat vagal pulmonary sensory neurons to capsaicin challenge

TNFα is a proinflammatory cytokine, and plays an important role in the pathogenesis of allergic asthma. A recent study in our lab has demonstrated that a prolonged (24–48 h) treatment with TNFα increased the Ca2+ influx evoked by TRPV1 activators in vagal pulmonary sensory neurons (Am J Physiol 299: 483–492, 2010). The present study was carried out to test the acute effect of transient TNFα treatment on the TRPV1 sensitivity in isolated rat pulmonary sensory neurons. Our results showed: 1) A brief treatment with a low concentration of TNFα (1.44 nM; 9 min) induced a biphasic TRPV1 hypersensitivity in these neurons: the inward current evoked by capsaicin (average concentration 100 nM; 3 s) was enhanced both immediately following the TNFα treatment (Δ=280%), and after a long delay (peak at ~90 min; Δ=382%). 2) The immediate phase of the potentiating effect of TNFα was almost completely abolished by pretreatment with a COX-2 inhibitor, NS-398 (10 μM; 10 min), whereas the delayed phase was only partially attenuated. 3) In contrast, the same TNFα treatment did not generate any potentiating effect on the response to ATP (0.3 – 1.0 μM) challenge in these neurons. In summary, a brief treatment with TNFα induced both immediate and delayed potentiating effects on the TRPV1 sensitivity in isolated pulmonary sensory neurons, and a production of COX-2 arachidonic acid metabolites is probably involved in the immediate sensitizing effect of TNFα. (Supported in part by NIH grant HL96914 & NSC98-2917-I038-101 fellowship from ROC)