Cutaneous inflammation regulates THIK1 expression in small C-like nociceptor dorsal root ganglion neurons.

Tandem pore-domain Halothane Inhibited K+ channel (THIK1) is a two-pore-domain potassium channel (K2P) present in dorsal root ganglia (DRG). We previously demonstrated that THIK1 mRNA levels in the DRG dropped ipsilaterally 1day after CFA-induced cutaneous inflammation (CFA1). In this study we aimed to identify the currently unknown DRG subpopulations expressing THIK1, and to investigate the relationship between the channel and both inflammatory and spontaneous pain in normal rats. Using a combination of immunohistochemistry, western blotting and behavioural tests, we found that all small neurons and large groups of medium and large DRG neurons express THIK1. Myelinated and unmyelinated fibers, nerve endings in the skin and lamina I and II of the spinal cord also express the channel. THIK1 staining co-localizes with IB4-binding and trkA suggesting that the channel is expressed by nociceptors. At CFA1, both cytoplasmic and edge (membrane-associated) THIK1 staining were significantly reduced only in small neurons ipsilaterally compared to normal. At 4days after inflammation (CFA4), edge THIK1 staining levels in small neurons decreased bilaterally compared to normal. Medium and large size DRG neurons showed no change in THIK1 expression either at CFA1 or CFA4. Ipsilateral (but not contralateral) mean %intensities of THIK1 in small neurons at CFA1 correlated strongly negatively with spontaneous foot lifting (SFL) duration (a marker of spontaneous pain). Thus, nociceptors express THIK1 that can be regulated by cutaneous inflammation. Finally, in vivo siRNA knockdown of THIK1 resulted in longer SFL duration than siRNA scramble-treated rats. Taken together our evidence suggests a potential involvement for THIK1 in pain processing following inflammation.

A fatal case following exposure to zinc chloride and hexachloroethane from a smoke bomb in a fire simulation at a school.

INTRODUCTION: The common mixture for smoke bombs contains zinc oxide and a chlorine donor, which allows for the formation of fine particles of zinc chloride. We report a fatal case of exposure to a smoke bomb used for a fire training exercise at a school. CASE REPORT: A 21-year-old student inhaled zinc oxide/hexachloroethane from a smoke bomb during a fire simulation at a school. Fever and tachypnea began six hours after exposure. Radiological evaluation showed a mixed interstitial-alveolar bilateral infiltrates. Despite supportive care, the patient died of multi-organ failure nine days after inhalation. DISCUSSION: ZnCl inhalation is characterized by a lag period between exposure and evidence of respiratory toxicity, ranging from ten to 32 days, depending on the inhaled dose of ZnCl. Subjects inhaling even a small amount of aerosols from a smoke bomb should be carefully managed in a hospital setting where their respiratory function can be closely monitored. CONCLUSION: This case highlights the risk of serious injury and even death from smoke bombs containing zinc chloride aerosol in schools and suggests that these smoke bombs should not be used for fire simulation or activities where human exposure is suspected, particularly in schools.