Multiple types of sensory neurons respond to irritating volatile organic compounds (VOCs): Calcium fluorimetry of trigeminal ganglion neurons

Abstract

Many volatile organic compounds (VOCs) are significant environmental irritants that stimulate somatosensory nerve endings to produce pain and irritation. We measured intracellular calcium in cultured trigeminal ganglion neurons to characterize the cellular mechanisms and chemical structural determinants underlying sensitivity to VOCs. Trigeminal neurons responded to homologous series of alcohols (C4–C7) as well as saturated and unsaturated aldehydes in a concentration dependent manner. Ranked in terms of threshold to recruit neurons by compounds of the same carbon chain length, enaldehyde<aldehyde<alcohol. Unlike aldehydes and alcohols that displayed ascending concentration curves, recruitment of neurons by enaldehydes (C4–C7) appeared to saturate, consistent with a mechanism that is restricted in its neural distribution. Using pentanol, pentanal and pentenal as model compounds, we found that many but not all cool/cold-sensitive and capsaicin-sensitive neurons responded with increases in intracellular calcium. These VOCs also stimulated other neurons that were insensitive to cooling and capsaicin. Because not all cooling- and all capsaicin-sensitive neurons responded to the model VOCs, it is highly unlikely that known nociceptive ion channels such as TRPV1 or TRPA1 mediate sensitivity to these compounds. For pentanol, pentanal and pentenal, induced calcium influx was dependent on the presence of extracellular calcium. Responses of all neurons to pentanal and pentenal were also dependent upon extracellular sodium. Responses to pentanol were variably dependent on sodium. The distribution of sensitivity suggests that VOC irritation may be mediated by an as yet unidentified mechanism(s) that is/are distributed across different modalities of neurons.