Tumor necrosis factor enhances the capsaicin sensitivity of rat sensory neurons

The capacity of the proinflammatory cytokines, tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta), to modulate the sensitivity of isolated sensory neurons grown in culture to the excitatory chemical agent capsaicin was examined. Alterations in capsaicin sensitivity were assessed by quantifying the number of neurons labeled with cobalt after exposure to capsaicin and by recording the whole-cell response from a single neuron to the focal application of capsaicin. A 24 hr pretreatment of the neuronal cultures with TNF alpha (10 or 50 ng/ml), but not IL-1 beta (10 or 50 ng/ml), produced a concentration-dependent increase in the number of cobalt-labeled neurons after exposure to 100 nM capsaicin. The peak increase in the number of labeled neurons was attained after a 4 hr treatment with 10 ng/ml TNF alpha. Similarly, pretreatment with TNF alpha (10 ng/ml for 4, 12, and 24 hr) produced a greater than twofold increase in the average peak amplitude of the inward current evoked by 100 nM capsaicin. Both the TNF alpha-induced increase in labeling and current amplitude were blocked by treating the neuronal cultures with indomethacin before the addition of TNF alpha. Enhancement of the capsaicin-evoked current also was blocked by the specific cyclo-oxygenase-2 inhibitor SC-236. These results indicate that TNF alpha can enhance the sensitivity of sensory neurons to the excitation produced by capsaicin and that this enhancement likely is mediated by the neuronal production of prostaglandins. Isolated sensory neurons grown in culture may prove to be a useful model system in which to explore how prolonged exposure to mediators associated with chronic inflammation alter the regulatory pathways that modulate the excitability of the nervous system

Severe methemoglobinemia secondary to isobutyl nitrite toxicity: the case of the ‘Gold Rush’

Isobutyl nitrite is one of the popular recreational drugs with high abuse potential that is known to cause methemoglobinemia. While inhaling this recreational drug, often referred to as a 'popper', is the typical route of administration, oral ingestion can produce a more rapid and fulminant course of methemoglobinemia. We present the case of a 69-year-old male that presented to our emergency department in extreme, life-threatening methemoglobinemia due to the ingestion of isobutyl nitrite that he obtained from an adult novelty store. The patient had a methemoglobin level above our lab cut-off of 28% and was subsequently treated with two doses of intravenous methylene blue. His hospital course was unremarkable, and he was discharged on Day 2. Methemoglobinemia is a medical emergency that requires a high index of clinical suspicion, prompt recognition, and rapid treatment