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Table 4: Dose Ranges and Strength of Evidence for Agents by Diagnosis

Drug Morphine

Typical Dose Strength of Evidence by Diagnosis Range

1–20 mg/day Strong evidence for cancer pain Moderate evidence for non-malignant pain

Hydromorphone 0.5–10 mg/day Same as morphine Fentanyl

0.02–0.3 mg/day Same as morphine Midazolam Baclofen Bupivacaine

Ziconotide Clonidine

0.2–6 mg/day Weak evidence for chronic back pain Anecdotal evidence for neuropathic pain

0.05–0.8 mg/day Strong evidence for spasticity-related pain Moderate evidence for neuropathic pain Weak evidence for central pain

4–30 mg/day Strong evidence for cancer pain Moderate evidence for non-malignant pain

5–19 μg/day Moderate evidence for neuropathic pain

0.03–1 mg/day Moderate evidence for neuropathic pain Weak evidence for back pain Weak evidence for central pain

Dexmedetomidine Not approved Animal model evidence for for human use neuropathic pain


Not approved Animal model evidence for for human use neuropathic pain

is antagonized by direct peripheral vasoconstriction. If a patient is receiving long-term therapy with clonidine, abrupt cessation can result in rebound hypertension.

An alpha-2 agonist with higher receptor affinity than clonidine is dexmedetomidine. An early study evaluating the effects of intrathecal dexmedetomidine on self-mutilation (autotomy), a behavior that may indicate the presence of neuropathic pain, demonstrated that rats injected with dexmedetomidine after unilateral sciatic nerve section autotomized significantly less than those receiving saline or morphine.72 However, dexmedetomidine was unsuccessful in preventing autotomy when injected prophylactically. In another trial studying the effects of intrathecal dexmedetomidine in rats following spinal nerve ligation, dexmedetomidine dose-dependently decreased spontaneous locomotor activity, a behavior believed to signify allodynia.73

In humans,

intrathecal dexmedetomidine has not been studied for chronic pain, but a double-blind study performed in 60 patients undergoing transurethral resection of the prostate found that the addition of either intrathecal dexmedetomidine or clonidine to bupivacaine shortened the onset of sensory and motor blockade, prolonged the duration of the block, and preserved hemodynamic stability.74

Tizanidine is another alpha-2 receptor agonist that has shown positive results in animal models of neuropathic pain. Kawamata et al.75 compared the effects of intrathecal tizanidine and clonidine in rats following sciatic nerve ligation. Dose-dependent reversal of thermal and mechanical hyperalgesia was observed for both drugs, with the highest dosages (5 µg tizanidine and 3 µg clonidine) producing statistically significant effects. Compared with clonidine, tizanidine was associated with a faster onset of action and fewer adverse effects. Tizanidine can occasionally cause liver damage.76

Its intrathecal administration has not

been studied in humans. Table 4 summarizes dose ranges and strength of evidence for agents by diagnosis.

160 Steroids

Corticosteroids have profound and complex anti-inflammatory properties. They inhibit the release of an array of pro-inflammatory mediators (prostaglandins, leukotrienes, cytokines, tissue necrosis factor alpha, and others) from multiple types of leukocytes.77,78

Once used routinely for the

treatment of back pain and lumbar radiculopathy, intrathecal injection of steroids fell from favor in the mid-1980s following its implication in the development of adhesive arachnoiditis.79,80

Although the preservative

polyethylene glycol was blamed in several studies, the intrathecal administration of steroids was nevertheless largely abandoned in favor of the epidural route.81

alternative treatment for refractory post-herpetic neuralgia (PHN).

PHN is a painful neuropathic condition that can occur in up to 10 % of patients following an acute outbreak of herpes zoster. After initial exposure, the varicella zoster virus may lay dormant in the dorsal root ganglia and become activated months to years later.82

The incidence of

noted an almost eight-fold increase in the prevalence of PHN when comparing 24–35-year-olds with those over 75 years of age. Several preventive therapies have shown promise when instituted during the acute zoster outbreak, including antiviral medications,84,85 antidepressants,86

PHN in the population increases with age and is associated with decreased immune function. A 1995 population-based study by Donahue et al.83

tricyclic and zoster vaccine.87 If preventive measures are not

instituted or fail, the treatment of PHN can be challenging; it has been estimated that roughly 2 % of patients with PHN will have ongoing pain five years following their initial outbreak.88

In those in whom conventional

therapies, such as membrane stabilizers, antidepressants, opioids, and topical analgesics, fail, intrathecal steroids can be considered.

Kikuchi and colleagues89 performed a prospective randomized trial

comparing intrathecal with epidural methylprednisolone in 25 patients with chronic PHN pain. Patients were treated four times at one-week intervals and were followed for 24 weeks after treatment. Global pain relief was superior at all data points in the intrathecal group, with 12 of 13 patients reporting good to excellent analgesia throughout the study compared with only two of 12 patients in the epidural group. Of the biochemical markers analyzed, the only statistically significant difference was decreased levels of interleukin-8 in the intrathecal group one week post-treatment and at 24 weeks.

In a prospective, randomized, placebo-controlled study by Kotani et al.,90 277 subjects with PHN of over one year’s duration received intrathecal methylprednisolone plus lidocaine, lidocaine alone, or no intervention. Similar to the Kikuchi study, injections were performed weekly for four weeks. Compared with the lidocaine only and non-intervention groups, those patients treated with methylprednisolone plus lidocaine exhibited significant improvement: 82 of 89 patients receiving intrathecal steroids reported their pain relief as good or excellent at two-year follow-up, compared with only nine of 181 patients in the other two groups.

In order to determine the relative effectiveness of intrathecal midazolam and steroids, Dureja et al. performed a 12-week double-blind study comparing a single injection of midazolam, methylprednisolone, or the combination in 150 patients with PHN. Although all groups significantly improved, the combination group obtained significantly better and

US NEUROLOGY However, intrathecal steroid injections remain an

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