Evidence is presented which suggests that central neural changes occur during the brief early phase after subcutaneous formalin injection that are essential for the expression of pain during the long-lasting (tonic) later phase. First, tonic pain responses to subcutaneous formalin injections are abolished only if the injected hindpaw is locally anesthetized at the time of injection as well as the time of testing (30–60 min later). Second, tonic formalin pain is substantially reduced by brief spinal anesthesia given 5 min before, but not 5 min after the formalin injection.