Chronic pain has serious implications on the quality of life of those suffering. Intracellular Ca2+ signaling is an important mechanism underlying the sensing ability of peripheral neurons that mediate pain responses (nociceptors). For instance, Ca2+ release from intracellular stores underlies the excitation of nociceptors by inflammatory mediators (1). An important mechanism for the maintenance of cellular Ca2+ homeostasis is the Ca2+-release activated Ca2+ channel (CRAC). Functional presence of CRAC in peripheral sensory neurons has been reported recently; moreover, a CRAC inhibitor was shown to display analgesic activity (2). However the mechanistic understanding of the role and function of CRAC in sensory nerves is still lacking. Using dorsal root ganglion (DRG) neurons in culture and calcium imaging, we investigated store operated Ca2+ entry (SOCE) in rat DRG neurons and satellite glia cells (SGC). Two CRAC blockers, YM-58483 (3 µM) and Synta-66 (0.5 µM) inhibited SOCE induced by Ca2+ add-back paradigm in DRG neurons by 85.1±7.5% (for control n=40, 6 experiments; for YM-58483 n=44, 7 experiments) and by 55.1±7.8% (for control n=42, 3 experiments; for Synta-66 n=54, 6 experiments) respectively. Interestingly, Synta-66 was less efficacious in TRPV1-positive neurons (identified by response to 1 µM capsaicin) in comparison with TRPV1-negative neurons. Both blockers produced almost complete inhibition of SOCE in SGC. Surprisingly, both YM-58483 and Synta-66 strongly potentiated capsaicin responses in DRG neurons, thus YM-58483 (3 µM) enhanced normalized fluorescence response to capsaicin (F/F0) by 1.63±0.25 (n=26; 5 experiments) while Synta-66 (3 µM) enhanced the response by 1.97±0.14 fold (n=97; 28 experiments). Neither YM-58483 nor Synta-66 on their own produced Ca2+ response in DRG neurons. These findings establish a pharmacological profile of SOCE in sensory neurons and suggest a possible link between SOCE and TRPV1 channels.