INTRATHECAL DRUG DELIVERY IN CHRONIC PAIN

Medtronic Pain Therapies comprise two medical technologies – neurostimulation and intrathecal drug delivery (IDD) – which are indicated to reduce and control, chronic, intractable pain.
Studies have proven that both therapies provide effective pain relief and significant improvements in quality of life for people suffering from severe, chronic pain conditions. In addition, both therapies are reversible and are preceded by screening tests which help predict the patients most likely to benefit from treatment.
Both therapies act on specific structures of the nervous system to reduce and control pain. However, the mechanism of action and type of pain most responsive to each therapy differ. Neurostimulation is most effective for neuropathic pain, whereas IDD is most effective for nociceptive pain. IDD can also be used in cases where the neurostimulation screening trial has been unsuccessful.

 

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 Pain-relieving drugs can be delivered orally, rectally, transdermally or given as an injection (intravenous, subcutaneous, intramuscular). These forms are called systemic delivery because the pain relieving drug circulates throughout the patient’s entire body . Pain-relieving drugs can also be delivered intraspinally. Intraspinal delivery can be given in one of two ways; into the epidural space or into the intrathecal space. Pain-relieving drugs delivered epidurally also circulate systemically. By contrast, pain-relieving drugs delivered intrathecally circulate only in the cerebropsinal fluid (CSF). Intraspinal pain-relieving drugs can be an effective option for patients who experience inadequate pain control or intolerable adverse effects with oral or systemic drugs. Challenges of delivery of pain-relieving drugs Several challenges accompany delivery of pain-relieving drugs, including: ● Barriers to the site of action ● Dosing issues ● Potential adverse events 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.

Figure 1 : The implanted intrathecal drug delivery system

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 IDD 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.

Potential adverse effects of morphine
Regardless of the route of delivery, pain-relieving drugs can cause adverse effects. However, most adverse effects can be effectively managed by reducing the amount of drug circulating systemically in the patient’s body.
As IDD requires a lower dose of pain-relieving drugs than systemic drug delivery, IDD can minimize many of the potential adverse effects of pain relieving drugs or decrease their severity.

Intrathecal drug delivery systems
Intrathecal drug delivery (IDD) delivers small doses of pain-relieving drugs, such as morphine, via a pump (SynchroMed II/SynchroMed EL/Isomed) that is placed surgically under the skin, directly into the CSF. This route of administration offers the potential for more potent analgesia with fewer side effects than systemic routes of administration. Studies have shown that patients treated with intrathecal pain-relieving drugs did not experience
many of the undesirable side effects observed with oral/parenteral narcotics. This is due to the fact that intrathecal drug infusion is directed to the spinal cord (the site of action), meaning that smaller doses are required
than with oral or intravenous methods.
Intrathecal drug delivery system components
An IDD system consists of two basic components that are placed in the body during a surgical procedure:
● Pump
● Catheter

 

Figure 2: The SynchroMed EL Intrathecal drug delivery system	Figure 3: The SynchroMed II Intrathecal drug delivery system

Pump
The pump is a round metal device that stores and automatically releases prescribed amounts of pain medication through the catheter directly into the intrathecal space. The exact dosage, rate and timing prescribed are entered in the pump using a programmer, an external computer-like device that controls the pump’s memory. As the pump has a constant flow rate, the daily dosage has to be calculated before the pump is filled with medication. Information about the prescription is stored in the pump’s memory.
The pump holds a finite amount of medication, which means it needs to be refilled periodically. This is performed by inserting a needle through the skin into the pump’s reservoir. Refill intervals are typically every 1–3 months, although this may vary depending on individual prescriptions.
Medtronic also have a constant rate pump called Isomed which is mainly used for chemotherapy.

Figure 4: The Isomed intrathecal drug delivery system	Figure 5: The fully functioning intrathecal drug delivery system

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).

Functioning intrathecal drug delivery system
The functioning IDD system sends small, programmed amounts of pain-relieving drugs from the pump, through the catheter directly into the CSF in the intrathecal space, where there is a high concentration of receptors.