P2 nucleotide receptors in peripheral nerve trunk

There is considerable interest in the possibility that ATP may function as a peripheral pain mediator. Most of the studies underlying this idea are electrophysiological recordings from sensory cell bodies, as nociceptive axons with diameters of 1 to 3 μm are not accessible by intracellular electrophysiological methods. However, the most important region for conduction of nociceptive information is thin axons in the peripheral nerve trunk. These nociceptive axons are in close contact with ensheathing Schwann cells, which also cannot easily be studied in situ by conventional recording techniques. In this review, we describe new methods that have been used to study the effects of ATP on unmyelinated axons and Schwann cells in intact peripheral nerve preparations. Threshold tracking of compound C fibre potentials and confocal calcium imaging revealed that extracellular ATP has rapid excitatory effects on both axons and Schwann cells in peripheral nerve trunk. Thereby, at least four different ionotropic and metabotropic P2 receptors were separated by pharmacological profiles. These receptors (P2X2/3 on unmyelinated axons; P2Y1, P2Y2, and P2X7 on Schwann cells) would allow for rapid interactions between axons and Schwann cells. It is suggested that purinergic signalling in peripheral nerve trunk contributes not only to pain transduction but might be involved in mechanosensitivity, inflammation, proliferation, and demyelination. Drug Dev. Res. 52:83–88, 2001.