Distinct ATP receptors on pain-sensing and stretch-sensing neurons

The initial pain from tissue damage may result from the release of cytoplasmic components that act upon nociceptors, the sensors for pain. ATP was proposed to fill this role1,2 because it elicits pain when applied intradermally3 and may be the active compound in cytoplasmic fractions that cause pain4. Moreover, ATP opens ligand-gated ion channels (P2X receptors) in sensory neurons5,6,7 and only sensory neurons express messenger RNA for the P2X3 receptor8,9. To test whether ATP contributes to nociception, we developed a tissue culture system that allows comparison of nociceptive (tooth-pulp afferent) and non-nociceptive (muscle-stretch receptor) rat sensory neurons. Low concentrations of ATP evoked action potentials and large inward currents in both types of neuron. Nociceptors had currents that were similar to those of heterologously expressed channels containing P2X3 subunits, and had P2X3 immunoreactivity in their sensory endings and cell bodies. Stretch receptors had currents that differed from those of P2X3 channels, and had no P2X3 immunoreactivity. These results support the theory that P2X3 receptors mediate a form of nociception, but also suggest non-nociceptive roles for ATP in sensory neurons.

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