The present study links the chloride channels CLCN3 and CLCN5 with the excitatory role of S1P on sensory neurons and for the first time positions CLCN5 channel, which has been well studied in Dent’s disease, an inherited renal disorder characterized by hyperphosphaturia, proteinuria, hypercalciuria and the development of kidney stones, which is often associated with mutations in the CLCN5 gene (Gunther et al., 2003), in the field of nociception and the pain pathway. Here, CLCN3 is linked to nephrolithiasis.