Journal of neuro-oncology
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Journal of neuro-oncology · Aug 2008
Cytosine arabinoside affects the heat and capsaicin receptor TRPV1 localisation and sensitivity in human sensory neurons.
Cytosine arabinoside (Ara C) is a useful chemotherapy agent, used for treating acute myeloid leukaemia, although it may be associated with side effects including painful neuropathy. It is also used for in vitro neuronal studies to limit the proliferation of non-neuronal cells and thereby select nondividing neuronal cells. We studied the effects of Ara C on human dorsal root ganglion (DRG) neurons, especially the expression and sensitivity of the ion channel TRPV1, which responds to noxious heat and capsaicin and is a key mediator of neuropathic pain. ⋯ It is postulated that Ara C treatment blocked insertion of TRPV1 in the cell membrane, resulting in accumulation of the receptors in the cytoplasm, loss of capsaicin sensitivity, and membrane-bound immunostaining, which was restored with a rebound on withdrawal of Ara C. The observed pattern of loss of capsaicin sensitivity, followed by hypersensitivity and recovery, appears to reflect some of the features observed in chemotherapy-induced neuropathy, and may provide a model for developing new treatments and prophylaxis.