Acrolein signaling is important during the spinal cord injury, whether it is involved in somatic and emotional pain is not clear.Hydralazine is a potent antihypertensive drug and can scavenge acrolein efficiently.We hypothesized that hydralazine decrease the spinal level acrolein and render analgesic effects with some side effects.The subcutaneous injection of formalin into the left hindpaw induced significant somatic and emotional pain evaluated by the biphasic spontaneous flinch/licking of the injected hindpaw and interphase ultrasonic vocalizations (USVs) during the 1 h window after formalin injection, respectively.The spinal acrolein level significantly increased and the neurons were activated at 2h after formalin challenging.Intraperitoneal(i.p.) injection of hydralazine (at 0.1, 1 or 10 mg/kg bodyweight)at lh before formalin challenging dose-dependently attenuate the formalin induced pain responses with the analgesic ED50 ranging from 0.4 to 1 mg/kg body weight.Furthermore,the neuronal activation and elevated acrolein expression were dose-dependently inhibited.The side effects of i.p.hydralazine on locomotion, anxiety and motor coordination at 1 h after hydralazine administration were evaluated with open field (OF), elevated plus maze (EPM)and rotarod test, respectively, however, with negative findings.The main side effects of hydralazine were the insignificant decrease of the blood pressure and significant increase of the heart rates at high dose (10 mg/kg).Based on the above findings, hydralazine may find its new application of analgesia at a safe dose window (around 1 mg/kg) without causing severe side effects.Our present study suggested that hydralazine may scavenge the formalin induced acrolein increase and the downstream neuronal activation, these events finally lead to the analgesic effect of hydralazine.Hydralazine may serve as a therapeutic option for pain control besides its antihypertensive effect.