Opioids were first introduced into the central neuraxis in 1979. Since that time, epidurally and intrathecally administered opioids have been used for both acute and chronic pain control and are commonly administered in combination with other neuraxial adjuvant compounds, such as local anesthetics and α₂-adrenoreceptor agonists. The clinical benefits of epidural and intrathecal opioids include excellent analgesia in the absence of motor, sensory, and autonomic blockade. Downstream benefits then occur, which include earlier ambulation and improved pulmonary function.

The sites of action are the opioid receptors found mainly within layers 4 and 5 of the substantia gelatinosa in the dorsolateral horn of the spinal cord. When activated, these receptors inhibit the release of excitatory nociceptive neurotransmitters within the spinal cord. In addition to producing direct spinal effects, neuraxially administered opioids may also activate cerebral opioid receptors when cephalad spread of the drug occurs via cerebrospinal fluid (CSF). Systemic effects may also be seen because some drug is absorbed into the vasculature.

The lipid solubility of each opioid, determined by the octanol/water partition coefficient, is the most critical pharmacokinetic property to consider when administering opioid doses near the neuraxis. Molecular weight, dose, and volume of injectate may also play a role in dural transfer (Table 212-1).

Hydrophilic opioids (those with low octanol/water partition coefficients, e.g. morphine) have a high degree of solubility within the CSF, permitting significant cephalad spread. Therefore, thoracic analgesia may be accomplished when either epidural or intrathecal doses are administered at the lumbar level. The epidural or intrathecal dose of morphine is significantly less than that required to achieve an equianalgesic effect through intravenous administration.

Hydrophilic opioids, used epidurally (Table 212-2), have a slow onset and prolonged duration of action. An initial epidural bolus dose is required, which may be followed by a continuous infusion through an epidural catheter. Because of their slow onset of action, hydrophilic opioids are less suitable for patient-controlled epidural analgesia than are lipophilic opioids. When hydrophilic opioids are used intrathecally, onset of action is more rapid and very low doses are required, resulting in less systemic toxicity. Effective analgesia may be provided for up to 24 h. This method is less expensive because no catheter is used.