Adenosine triphosphate (ATP) is present in all cells of the body and is assumed to be the key signal for pain because it is released by all kinds of tissue trauma. The cytosol of muscle cells contains ATP at a high concentration (7.6 mM) that can elicit muscle pain following muscle damage or during strong exercise. Studies in anaesthetised rats showed that ATP at a concentration of 7.6 mM excited approx. 60% of the group VI muscle afferents innervating the gastrocnemius-soleus (GS) muscle. ATP-sensitive receptive endings were found among presumably nociceptive and non-nociceptive neurones. In contrast to group IV afferents, group Ia afferents (primary muscle spindle endings) did not react to ATP. 37 % of dorsal root ganglion cells that had been retrogradely labelled with Fast Blue injected into the GS muscle expressed ATP-sensitive P2X3 purinoreceptors. P2X3 receptors were found predominantly in small somata. The frequent expression of the receptor in small somata fits well with the strong excitatory action of ATP on receptive endings with unmyelinated muscle afferents. The responsiveness of group IV afferents to ATP was not altered by an experimental chronic myositis. In myositis animals, group IV units were sensitised to mechanical stimuli but not to ATP.

The data show that ATP not only plays a role in skeletal muscle metabolism, but also may mediate dysaesthesias by exciting non-nociceptive, and muscle pain by stimulating nociceptive, group IV endings.