Spinal opioid bioavailability in postoperative pain

Pain Pract. 2014 Apr;14(4):350-64. doi: 10.1111/papr.12099. Epub 2013 Jul 8.


Opioids have been used for spinal analgesia for more than a century, and their injection epidurally and intrathecally has a key role in the control of postoperative pain. Since the discovery of the endogenous opioid system, 3 decades ago, their use has become more generalized in obstetric analgesia, the management of chronic pain, and acute postoperative pain. To use opioids effectively for this type of analgesia, it is important to understand the pharmacokinetics and clinical pharmacology of these drugs, specifically those that produce analgesia by an intrinsic spinal mechanism. Evidence from animal and human experiments indicates that hydrophilic opioids (such as hydromorphone and morphine) bind more strongly to specific receptors within the dorsal horn of the spinal cord than lipophilic opioids (such as alfentanil, fentanyl, and sufentanil). This can be understood by considering the spinal cord selectivity and bioavailability of these opioids. This difference is attributable to differences in the pharmacokinetic and pharmacodynamic properties of the 2 groups. It is more difficult for lipophilic opioids to reach and remain at sufficiently high concentrations at the site of action due to their sequestration in epidural fat and rapid plasma clearance from both epidural and intrathecal spaces, resulting in analgesia with a limited spread and duration, as well as the appearance of early supraspinal side effects. In contrast, morphine has very different properties, including greater spinal bioavailability and therefore administered neuraxially, it is suitable choice for the treatment of acute postoperative pain. However, when using morphine, a greater incidence of adverse effects can be expected, and it requires careful patient selection.

Keywords: epidural analgesia; intrathecal analgesia; neuraxial opioid analgesia; opioid receptors; postoperative pain.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / pharmacokinetics*
  • Analgesics, Opioid / therapeutic use*
  • Animals
  • Biological Availability
  • Humans
  • Injections, Spinal / methods*
  • Pain, Postoperative / drug therapy*


  • Analgesics, Opioid