The intrathecal administration of opioids has emerged as a popular and effective form of postoperative pain control. Intrathecal opioids are able to provide long-lasting analgesia after a single injection. They work by binding to the μ opioid receptors, which are located in the substantia gelatinosa of the dorsal horn of the spinal cord. These receptors are concentration dependent and are typically not activated by systemic doses of opioids. Unlike intrathecal local anesthetics, intrathecal opioids provide analgesia without disrupting sensory, motor, or sympathetic functions.

Because of its hydrophilic properties and potent receptor affinity, preservative-free morphine (i.e., Duramorph or Astramorph) is the ideal opioid for intrathecal use. The onset of analgesic effects is directly proportional to the lipid solubility of the opioid. Preservative-free morphine (along with hydromorphone and meperidine) has a relatively low lipid solubility and its onset of action is delayed for typically 20 to 40 minutes after administration. The hydrophilic nature of the opioid also determines its duration of action. Preservative-free morphine is very hydrophilic and poorly lipid soluble, which extends its duration of analgesic effect up to 12 to 24 hours. Because of its poor lipid solubility, intrathecal morphine remains in the cerebrospinal fluid (CSF) for a prolonged period of time. It is circulated through cerebral spinal bulk flow and eventually rises rostrally to supraspinal levels. Intrathecal morphine, therefore, has bimodal analgesic effects. The first peak is soon after administration and is due to spinal opiate receptor binding. The second peak occurs 12 to 24 hours later and is due to supraspinal binding as the drug is circulated.