This page contains a Flash digital edition of a book.
Pain


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


Tizanidine


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


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100  |  Page 101  |  Page 102  |  Page 103  |  Page 104  |  Page 105  |  Page 106  |  Page 107  |  Page 108