Recent evidence suggest that ATP plays a role as an endogenous pain mediator generating and/or modulating pain signaling from the periphery to the spinal cord. In this study we evaluated the effects of intraperitoneal administration of P2 receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), evaluating pain related behaviours and monitoring the expression of Fos, a marker of activated neurons, in an experimental mouse model of neuropathic pain (sciatic nerve tying). The PPADS administration decreased both tactile allodynia and thermal hyperalgesia in a time and dose dependent manner. The dose of 25 mg/kg PPADS completely reversed nociceptive hypersensitivity. Moreover, non-noxious stimulation induced an increase of Fos positive neurons in the spinal cord of animals with tying of sciatic nerve. PPADS administration partially reversed this increase. These results suggest that PPADS reduces neuronal activation at spinal cord level and that P2 receptors are involved in the retrograde signalling progress exciting sensory spinal neurons.