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

Nature. 1997 May 29;387(6632):505-8. doi: 10.1038/387505a0.


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 role because it elicits pain when applied intradermally and may be the active compound in cytoplasmic fractions that cause pain. Moreover, ATP opens ligand-gated ion channels (P2X receptors) in sensory neurons and only sensory neurons express messenger RNA for the P2X3 receptor. 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials
  • Adenosine Triphosphate / metabolism*
  • Animals
  • Carbocyanines
  • Cell Line
  • Culture Techniques
  • Dental Pulp / innervation
  • Fluorescent Dyes
  • Humans
  • Male
  • Mechanoreceptors / metabolism*
  • Membrane Potentials
  • Muscles / innervation
  • Neurons / metabolism*
  • Neurons, Afferent / metabolism
  • Nociceptors / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2 / metabolism*
  • Receptors, Purinergic P2X3
  • Recombinant Proteins / metabolism


  • Carbocyanines
  • Fluorescent Dyes
  • P2RX3 protein, human
  • P2rx3 protein, rat
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X3
  • Recombinant Proteins
  • 3,3'-dioctadecylindocarbocyanine
  • Adenosine Triphosphate