Kalso et al.14[I] provide some help here. They reviewed 15 randomized placebo controlled trials. Four looked at intravenous opioid testing and included 120 patients, the other 11 compared oral opioids with placebo in 1025 patients. The opioids tested were described as World Health Organization (WHO) step 3 analgesics, including fentanyl, hydromorphone, methadone, morphine, oxy-codone, and oxymorphone and a wide variety of nociceptive and neuropathic pain disorders were treated.
Trials lasted between four days and eight weeks and mean daily opioid doses varied between 30 and 120 mg of morphine, 20-45 mg of oxycodone, and 15 mg of methadone. The maximum daily dose reached in some patients was morphine 300 mg, oxycodone 120 mg, and methadone 80 mg. Trial designs were generally of good quality; however, functional and quality of life outcomes were frequently not evaluated.
The mean reduction in pain intensity with opioids was approximately 30 percent for both nociceptive and neuropathic pain. Five of the studies that assessed function reported no change in a range of measures with one17[II] reporting significant improvement in pain-related disability and two18[II], 19[II] reporting disability scores lower during treatment with oxycodone over placebo.
In summary, the review by Kalso et al.14 suggests that short-term, moderate-dose opioid therapy can produce a modest reduction in both nociceptive and neuropathic pain and may reduce pain-related disability.
Eisenberg et al.15 specifically addressed the efficacy of opioids in neuropathic pain in a systematic review and meta-analysis of RCTs.15[II] These reviewers analyzed 22 articles with neuropathic pain as an inclusion criteria using opioid agonists (partial agonists and agonist-antagonists being excluded) via the oral, rectal, transdermal, intravenous, intramuscular, or subcutaneous routes. Trials were classified as either short term (less than 24 hours; n = 14) or intermediate term (8-56 days; n = 8) with regards to the duration of opioid therapy. In the short-term group, morphine, fentanyl, alfentanil, pethi-dine (meperidine), or codeine were used and most trials were placebo controlled. The short-term studies provided equivocal evidence of opioid efficacy and no conclusions could be made.
In the intermediate group, morphine, oxycodone, methadone, and levorphanol were included; placebo was used in seven of the eight trials. Doses ranged from morphine 20-300 mg per day, oxycodone 20-120 mg per day, methadone 10-80 mg per day, and levorphanol with mean doses of 2.7-8.9 mg per day. The mean pain intensity was reduced by 14/100 VAS points (95 percent CI -18 to -10) in opioid-treated patients; however, the authors had difficulties commenting on functional or quality of life outcomes because the wide range of measures used prevented comparison.
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