Acute postoperative pain can cause detrimental effects on multiple organ systems. To treat pain effectively, a thorough knowledge of the anatomy and physiology of pain and its transmission is necessary. Painful stimuli, like that produced by a surgical incision, can lead to a hyperexcitable state in the spinal cord. This hyperexcitable state can exacerbate postoperative pain. Once the hyperexcitable state has been established, a larger dose of analgesic drug is needed than if hyperexcitability had been prevented. When an analgesic is administered before the bombardment of painful stimuli that occurs with surgical incision, postoperative pain can be greatly diminished. Epidural, intravenous, and intramuscular opioids have been shown to reduce the severity of postoperative pain to a greater extent when administered before surgical stimuli rather than following it.