4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.

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

Distinct stages of radio frequency emission at the onset of pedestal collapse in KSTAR H-mode plasmas

Using a high-speed and broadband radio frequency (RF) (0.1-1 GHz) spectrum analyzer developed on the KSTAR tokamak, it is found that several distinct stages of RF emission appear at the pedestal collapse in high confinement discharges. Comparison with 2D electron cyclotron emission (ECE) images has revealed that each stage is related to the instantaneous condition at the outboard mid-plane edge. First, high-harmonic ion cyclotron emissions (ICE) are intensified with the appearance of a non-modal filamentary perturbation in the edge within several tens of microseconds before the collapse. Then, the RF emission becomes broad toward high-frequency range (<500 MHz) at the burst onset of the non-modal filament. During the pedestal collapse initiated by the filament burst, rapid chirping (1-3 mu s) appear with additional filament bursts. The strong correlation between the RF spectra and the perturbation structure provides important clues on the stability of edge-localized modes and on the ion dynamics in the plasma boundary