Journal
JOURNAL OF NEUROSCIENCE
Volume 23, Issue 14, Pages 6058-6062Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.23-14-06058.2003
Keywords
pain; thermal hyperalgesia; capsaicin receptor; P2Y receptor; ATP; UTP
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The capsaicin receptor transient receptor potential V1 (TRPV1; also known as vanilloid receptor 1) is a sensory neuron-specific ion channel that serves as a polymodal detector of pain-producing chemical and physical stimuli. It has been reported that extracellular ATP potentiates the TRPV1 currents evoked by capsaicin or protons and reduces the temperature threshold for its activation through metabotropic P2Y receptors in a PKC-dependent pathway, suggesting that TRPV1 activation could trigger the sensation of pain at normal body temperature in the presence of ATP. Here, we show that ATP-induced thermal hyperalgesia was abolished in mice lacking TRPV1, suggesting the functional interaction between ATP and TRPV1 at a behavioral level. However, thermal hyperalgesia was preserved in P2Y(1) receptor-deficient mice. Patch-clamp analyses using mouse dorsal root ganglion neurons indicated the involvement of P2Y(2) rather than P2Y(1) receptors. Coexpression of TRPV1 mRNA with P2Y(2) mRNA, but not P2Y(1) mRNA, was determined in the rat lumbar DRG using in situ hybridization histochemistry. These data indicate the importance of metabotropic P2Y(2) receptors in nociception through TRPV1.
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