Recent electrophysiological, behavioral, and biochemical studies revealed that
ATP plays a role in facilitating spinal
pain transmission via ionotropic P2X
nucleotide receptors, although the involvement of metabotropic P2Y
nucleotide receptors remains unclear. In the present study, we examined the effects of i.t. administration of P2Y receptor agonists
UTP,
UDP, and related compounds on nociception in normal rats and
tactile allodynia in a
neuropathic pain model. In the paw pressure test using normal rats, i.t. administration of
UTP (30 and 100 nmol/rat) and
UDP (30 and 100 nmol/rat), but not
UMP (100 nmol/rat) or
uridine (100 nmol/rat), significantly elevated the mechanical nociceptive thresholds, whereas
ATP (30 and 100 nmol/rat) and
alpha,beta-methylene-ATP (10 and 30 nmol/rat) lowered them. Similarly, in the tail-flick test,
UTP (10, 30, and 100 nmol/rat) and
UDP (100 nmol/rat) significantly prolonged the thermal nociceptive latency. In the von Frey filament test on normal rats,
UTP (100 nmol/rat) and
UDP (100 nmol/rat) produced no
allodynia to the tactile stimulus, whereas
ATP (100 nmol/rat) induced a significant and long-lasting
tactile allodynia. In the
neuropathic pain model, in which the sciatic nerves of rats were partially ligated,
UTP (30 and 100 nmol/rat) and
UDP (30 and 100 nmol/rat) produced significant antiallodynic effects. Furthermore,
UTP (100 nmol/rat) and
UDP (100 nmol/rat) caused no motor deficit in the inclined plane test. Taken together, these results suggest that the activation of
UTP-sensitive P2Y(2) and/or P2Y(4) receptors and the
UDP-sensitive
P2Y(6) receptor, in contrast to P2X receptors, produces inhibitory effects on spinal
pain transmission.