October 2003

Dear Readers: Here's the Article for this Month:

Name of article:

Oral opioid therapy for chronic peripheral and central neuropathic pain

Author(s):
Rowbotham MC, Twilling L, Davies PS, Reisner L, Taylor K, Mohr D
N Engl J Med 2003; 348 (13): 1223-32

Foley KM
Opioids and chronic neuropathic pain. Editorial
N Engl J Med 2003; 348 (13): 1279-81

Abstract: 

Although opioid analgesics are frequently used in treating patients with chronic neuropathic pain, only few controlled trials have been performed to evaluate their efficacy, tolerability and dose titration in this clinical setting.

The Authors carried out a double-blind, dose-response study to evaluate the efficacy of low doses of levorphanol with respect to high doses in reducing the severity of treatment-refractory neuropathic pain in patients with either central pain (pain after stroke or focal brain lesion, spinal cord injury, multiple sclerosis) or a peripheral neuropathic pain syndrome (postherpetic neuralgia, peripheral neuropathy or focal peripheral-nerve injury). Levorphanol is a potent mu-opioid agonist which interacts also with K and delta receptors and has a six-to-eight hour duration of analgesic action.

Eighty-one patients were randomly assigned to receive either low-strength (0.15 mg) (38 patients) or high-strength (0.75 mg) (43 patients) levorphanol capsules for 8 weeks (titration and treatment periods) then the doses were tapered over a period of one to 4 weeks. Intake was titrated by the patient to a maximum of 21 capsules/day (7 cps t.i.d. = 3.15 mg or 15.75 mg/day).

The intensity of pain of the previous 24 hours was assessed daily by means of visual analogue scale (0-100 mm). The degree of pain-relief was scored by a verbal scale (0-5). Other assessment tools included the Profile of Mood States, the Multidimensional Pain Inventory, the Symbol-Digit Modalities Test, the Opiate-Agonist Effects Scale and Opiate Withdrawal Scale.

Blood levorphanol levels were evaluated at week 8.

The intensity of pain was significantly reduced in the high-strength group (36%) with respect to the low-strength group (21%)(p=0.02). The patients who received the high dose and completed the trial had pain reduction as great as 48% and 66% of them reported moderate or better pain relief.

Patients in the high-strength group took fewer capsules each day (11.9 +/-5.5 vs 18.3 +/-4.3 p<0.001) corresponding to a mean levorphanol dose of 8.9 mg/day vs. 2.7 mg/day.

Regarding the other outcome measures in both study groups, there were significant improvements in interference in functioning, sleep and affective distress.

By the last seven days of the tapering period, the intensity of pain returned to 96% of the basal levels.

No serious levorphanol-related adverse events occurred.

Why I chose this article.

The treatment of chronic neuropathic pain by means of opioid analgesics is still controversial and discouraged. The results of this study can be added to what is found in literature and indicate how opioids, at high dosages, are efficient in reducing the intensity of neuropathic pain. However, the long-term efficacy and tolerability of different available opioids as well as the efficacy of opioid switching and opioid rotation needs to be investigated further.

Regards,

Carla Ripamonti, MD
Member of the Board of Directors, IAHPC