Nociceptors, or pain-sensitive receptors, are unique among sensory receptors in that their sensitivity is increased by noxious stimulation. This process, called sensitization or hyperalgesia, is mediated by a variety of proinflammatory factors, including bradykinin, ATP and NGF, which cause sensitization to noxious heat stimuli by enhancing the membrane current carried by the heat-and capsaicingated ion channel, TRPV1. Several different mechanisms for sensitization of TRPV1 have been proposed. Here we show that NGF, acting on the TrkA receptor, activates a signalling pathway in which PI3 kinase plays a crucial early role, with Src kinase as the downstream element which binds to and phosphorylates TRPV1. Phosphorylation of TRPV1 at a single tyrosine residue, Y200, followed by insertion of TRPV1 channels into the surface membrane, explains most of the rapid sensitizing actions of NGF.

Our study documents that smoking is a major risk factor for mortality in China. Continued strengthening of national programs and initiatives for smoking prevention and cessation is needed to reduce smoking-related deaths in China.

Objective To examine factors related to blood pressure (BP) responses to dietary sodium and potassium interventions. Methods We conducted a dietary feeding study that included a 7-day low-salt intervention (51.3 mmol/day), a 7-day high-salt intervention (307.8 mmol/day), and a 7-day high-salt plus potassium supplementation (60 mmol/day) intervention among 1,906 study participants in rural China. BP was measured 9 times during the 3-day baseline observation and during the last 3 days of each intervention phase using a random-zero sphygmomanometer. Results BP responses to low-sodium intervention were significantly greater in women compared to men: –8.1 (95% confidence interval (−8.6 to −7.6) versus −7.0 (−7.5 to −6.6) mmHg for systolic and −4.5 (−4.9 to −4.1) versus −3.4 (−3.8 to −3.0) mmHg for diastolic. Likewise, BP responses to high-sodium interventions were significantly greater in women compared to men: 6.4 (5.9 to 6.8) versus 5.2 (4.8 to 5.7) mmHg for systolic and 3.1 (2.7 to 3.5) versus 1.7 (1.4 to 2.1) mmHg for diastolic (all p<0.001). In addition, systolic BP responses to the sodium interventions increased with age and both systolic and diastolic BP responses to the sodium interventions increased with baseline BP levels. BP responses to potassium supplementation also increased with baseline BP levels. Conclusions These results suggest that female gender, older age, and hypertension increase sensitivity to dietary sodium intervention. Furthermore, low dietary sodium intake may be more effective in reducing BP among these subgroups.

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