Potential utility of the peripheral analgesic properties of morphine in stomatitis-related pain: a pilot study

Abstract

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.

Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients

“…A case series reported that the topical administration of a 0.08 % morphine gel provided pain relief in six cases of either cutaneous or oral mucosal pain [51]. Two studies, including a RCT, examined the use of a 2 % morphine mouth rinse for the management of pain due to OM in patients receiving chemoradiation for H&N cancer [21,22]. In the RCT, morphine mouth rinse was compared to a "magic mouthwash" containing lidocaine, diphenhydramine, and magnesium aluminum hydroxide.…”

Systematic review of basic oral care for the management of oral mucositis in cancer patients

“…Only three studies were identified that systematically evaluated these mouthwashes, two of which studied prevention [4,20] and one of which studied treatment of OM [8]. Levels of evidence were IV, III, and IV, respectively, and the results were conflicting.…”

Pain syndromes in the setting of haematopoietic stem cell transplantation for haematological malignancies

“…5,22 To control the nociceptive pain component of oral pain associated with mucositis, the potential utility of local topical application of opioids, such as a mouthwash containing 2% morphine, has been proposed. 63 However, the mainstay of analgesic therapy for oral pain associated with OM is the parenteral administration of opioids. For this purpose, tramadol is useful in the control of mild to moderate pain.…”