Potential utility of the peripheral analgesic properties of morphine in stomatitis-related pain: a pilot study.
To determine the potential clinical utility of peripheral opioid action using a clinical model of cancer treatment-induced inflammation and pain that allowed for topical application of morphine in the damaged tissue (oral mucosa). This pilot study followed a two blocks design. Ten patients with painful oral mucositis were enrolled in the first block (dose-response relationship finding) and randomized in two groups to receive oral rinses with 15 ml of either 1 per thousand or 2 per thousand morphine solution. Twenty-two patients were enrolled into the second block (efficacy and safety determination). Additionally, serum concentrations of morphine were measured in five representative patients. In the first block (n=10) a dose-response relationship for topical morphine was found. Rinses with 2 per thousand -morphine solution showed better pain relief (median 80%, range 70-80%) than those with 1 per thousand (median 60%, range 55-70%; P=0.0238). Therefore, subsequent patients enrolled for the second block (n=22) received oral rinses with 2 per thousand -morphine solution. In these patients the time to good (>or=50%) or to complete (100%) pain relief was 28 (+/-12)min after the first mouthwash, and the duration of relief was on average 216 (+/-25)min. Twenty patients (90%) received the successive mouthwashes every 3 h and 10% of them every 2 h. The duration of severe pain at the moment of swallowing was 5.17 (+/-1.47) days. Only six patients needed supplementary analgesia, and the time elapsed before the first supplemental analgesic was 1.18 (+/-0.8) days. The duration of severe functional impairment was 1.52 (+/-1.31) days, thus allowing us to feed the patient by mouth with liquid-food supplementation. During our experiment no systemically active detectable concentrations of morphine were found (GC-MS analysis). The most important side effect attributable to morphine mouthwashes was burning/itching sensation (very mild to mild intensity). Patients with painful chemoradiotherapy-induced stomatitis could be alleviated using topical morphine mouthwashes.
D000284:Administration, Oral; D000287:Administration, Topical; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009407:Nerve Block; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D010147:Pain Measurement; D010865:Pilot Projects; D012996:Solutions; D013280:Stomatitis / Q000150:complications*; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D012996:Solutions; D009020:Morphine