Subcutaneous injection of formalin produces a biphasic profile of pain response: a transient early phase followed by a tonic late phase. A number of studies have indicated that the development of the late phase of formalin pain is dependent upon prolonged changes in central neural function produced by neural activity that is generated during the early phase (i.e. central sensitization). In support of this, the present demonstrates that stimulation- or morphine-produced analgesia derived from the periaqueductal grey (PAG) during the early phase prevents the development of the phase. These results suggest that descending mechanisms of pain inhibition, as reflected by PAG stimulation- and morphine-produced analgesia, can prevent the development of central neural plasticity following injury.