Compression of a peripheral nerve trunk can result in painful sensations. Receptors for ATP (P2X) and adenosine (A2) enhance the axonal excitability of peripheral sensory nerve fibers. It is possible, therefore, that release of ATP due to compression of nerve fibers may activate nociceptive afferents. In the present study, we have used real time measurements of ATP-induced bioluminescence together with electrophysiological recordings of compound action potentials to follow changes in the extracellular ATP concentration of isolated rat spinal roots exposed to mechanical stimuli. Nerve compression for about 8 s resulted in an immediate release of ATP into the extracellular space and in a decrease in the amplitude of compound action potentials. On average, a rise of [ATP] to 60 nM was observed when nerve compression blocked 50% of the myelinated axons. After the compression, the extracellular concentration of ATP returned to the resting level within a few minutes. The importance of ecto-nucleotidases for the recovery period was determined by exposure of isolated spinal roots to high concentrations of ATP and by use of inhibitors of ecto-nucleotidases. It was observed that spinal roots have a high capacity for ATP hydrolysis which is only partially blocked by bg-methylene ATP and ARL 67156. In conclusion, the data indicate that the increase in extracellular ATP and adenosine produced by nerve compression may activate receptors on axons of nociceptive afferent neurons. (SFB 391/A1)