DISTINCT ATP RECEPTORS ON PAIN-SENSING AND STRETCH-SENSING NEURONS

The initial pain from tissue damage may result from the release of cyt oplasmic components that act upon nociceptors, the sensors for pain. A TP was proposed to fill this role(1,2) because it elicits pain when ap plied intradermally(3) and may be the active compound in cytoplasmic f ractions that cause pain(4). Moreover, ATP opens ligand-gated ion chan nels (P2X receptors) in sensory neurons(5,6,7) and only sensory neuron s express messenger RNA for the P2X3 receptor(8,9). To test whether AT P contributes to nociception, we developed a tissue culture system tha t allows comparison of nociceptive (tooth-pulp afferent) and non-nocic eptive (muscle-stretch receptor) rat sensory neurons. Low concentratio ns of ATP evoked action potentials and large inward currents in both t ypes of neuron. Nociceptors had currents that were similar to those of heterologously expressed channels containing P2X3 subunits, and had P 2X3 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 P 2X3 receptors mediate a form of nociception, but also suggest non-noci ceptive roles for ATP in sensory neurons.