Principles of drug delivery
Many studies have demonstrated the efficacy of opioids, such as morphine, in the management
of pain. Pain-relieving drugs can be delivered via several routes of administration, including:

• Systemic delivery - typically given first line
• Intraspinal (epidural and intrathecal) delivery - given when patients experience intolerable side effects on systemic drugs

Barriers to the site of action
One challenge with delivery of pain-relieving drugs is that these drugs are water-soluble.
A collection of anatomical structures exist that slow or prevent water-soluble molecules from entering the brain and nervous system. This natural barrier is called the blood-brain barrier. Systemically delivered pain relieving drugs must cross the blood-brain barrier to reach the site
of action (e.g. morphine must reach the opioid receptors in the dorsal horn). However, because
of their water solubility, these systemically circulating molecules cannot easily pass through the blood-brain barrier. As a result, larger doses of the pain-relieving drugs may be required for efficacy.

Intraspinal pain-relieving drugs (e.g. epidural and Intrathecal morphine) are delivered directly
to the site of pain transmission (thereby bypassing the blood-brain barrier). However, while both epidural and Intrathecal routes transport drugs via CSF circulation, epidurally administered pain-relieving drugs must first cross the dura (the protective outer layer of the spinal cord) before entering the CSF. Therefore, when the epidural route of delivery is used, more time and higher doses are required for the pain-relieving drugs to reach their appropriate receptors in the dorsal horn compared with delivery.

Dosing issues
Dosing issues are of special concern in the systemic delivery of pain-relieving drugs as a result
of the adverse effects associated with these compounds. For example, large doses of systemic opioids may be required to treat severe pain. The larger the dose requirement, the more adverse effects a patient is likely to experience. Therefore, a reduction in pain may be achieved at the cost
of such adverse effects as a reduction in a patient's alertness and mobility, nausea, vomiting, constipation, dizziness and dysphoria.

Due to the substantially lower dose required, intraspinal delivery may offer effective pain relief
with fewer potential adverse effects for patients with chronic intractable pain who are experiencing inadequate pain relief or intolerable side effects on high-dose systemic pain-relieving drugs.
In many cases, the Intrathecal pain-relieving drug dose may be reduced to 1/300th of the oral morphine dose.

. Must cross the dura before reaching the site of action

. Substantially higher dosage required than intraspinal delivery

. Higher dosage required than intrathecal, but lower dosage than systemic delivery

. Lower dosage required
(1/10th epidural, 1/300th oral)

Catheter
The catheter is a small soft tube. The catheter passer is used to help put the catheter in.
One end of the catheter is connected to the pump and the other is placed into the area
surrounding the spinal cord (intrathecal space).

- less sedation and constipation than systemic drugs. [7]
- lower doses than those required with oral and intravenous methods e.g. the equivalent of 1/300th   of an oral dosage of morphine can often provide effective pain relief. [8]

• Patients who are required to change from oral to intrathecal drug administration experience an improvement in long-term pain relief.

Intrathecal drug delivery in CRPS

• In a randomized, double-blind study [9], bolus intrathecal injections of baclofen and continuous intrathecal baclofen were given to 7 women with CRPS type I and II:
  - 86% of patients receiving bolus intrathecal baclofen achieved complete or partial
     resolution of dystonia of the hands.
  - 50% of patients receiving continuous baclofen regained normal hand function, and 33%   also regained their ability of walk.
• In a prospective study in 15 patients with chronic intractable pain who received intraspinal morphine [10], 11 patients experienced 'good to excellent' pain relief, and 6 patients were able to return to work.