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Abstract: The discovery of peripheral opioid receptors has become the scientific basis for topical use of opioids in malignant and nonmalignant ulcers and oropharyngeal mucositis. This systematic review aimed to assess the quality of published literature and to examine whether topical opioids are effective in controlling pain in palliative care settings. After a systematic literature review, 19 studies (six randomized controlled trials [RCTs] and 13 case reports) met the inclusion criteria for the review. Eighteen studies favored topical opioids in pain relief, as evidenced by reductions in post-treatment pain scores, but time to onset and duration of analgesia varied widely. Because of the heterogeneity of the studies, meta-analysis was not possible. Despite clear clinical benefits described in small RCTs, there is a deficiency of higher-quality evidence on the role of topical opioids, and more robust primary studies are required to inform practice recommendations. N-of-1 trials should be encouraged for specific clinical circumstances. [Copyright &y& Elsevier]

Abstract: Breakthrough pain is a common and distinct component of cancer pain that is usually managed with normal release opioids (also known as rescue medication) either before or soon after its onset. A prospective survey of hospice inpatients with breakthrough pain was undertaken to characterize their pain and then compare the time to onset of pain relief of their rescue medication. Patients presented with, on average, 1.7 different types of breakthrough pains (range, 1–4). The average number of breakthrough pains was four per day (range, 1–8), and the average duration of breakthrough pain was 35minutes (range, 15–60); most occurred suddenly and unpredictably. Patients used morphine, oxycodone, hydromorphone, methadone, or oral transmucosal fentanyl citrate as rescue medication and the average time to meaningful pain relief following their administration was 31minutes (range, 5–75). No difference was found between morphine, oxycodone, and hydromorphone. Methadone appeared to work faster than morphine (P <0.01) but no faster than oxycodone or hydromorphone, whereas oral transmucosal fentanyl citrate worked faster than morphine, oxycodone, hydromorphone, and methadone (P <0.001). [Copyright &y& Elsevier]

The analgesic effects of morphine applied topically to painful ulcers was assessed in a randomized, double-blind, placebo-controlled, crossover pilot study of five patients with painful sacral sores. Patients were treated for two days with either 10 mg morphine sulfate or placebo (water for injection) applied topically to the ulcer. After a two-day wash-out period, patients were crossed over for a further two days of the alternative treatment. Patients were asked to rate analgesia using a visual analogue scale (VAS) and to document any local or systemic adverse effects. All patients reported lower VAS scores with morphine compared to placebo and no local or systemic adverse events attributable to morphine were noted by either patients or nursing staff. This pilot study suggests that morphine applied topically is an effective method of producing local analgesia, well tolerated by patients, and not associated with systemic adverse effects. [Copyright &y& Elsevier]

Abstract: Context: With many medications available for the management of breakthrough cancer pain (BTCP), physicians may require additional guidance in selecting an appropriate medication to suit an individual patient's needs. Objectives: To identify all the evidence and assess the relative clinical value of currently approved BTCP medications. Methods: Following a systematic literature search (2007–2010), the results of 10 randomized controlled trials investigating the effects of BTCP medications (intranasal fentanyl spray [INFS], fentanyl pectin nasal spray, fentanyl sublingual tablets, fentanyl buccal soluble film, fentanyl buccal tablets, oral transmucosal fentanyl citrate, and morphine sulfate immediate release) were synthesized using a network meta-analysis. The main outcome was pain intensity difference (PID) relative to placebo up to 60 minutes after the intake of medication. Results: INFS, fentanyl pectin nasal spray, fentanyl buccal tablet, and oral transmucosal fentanyl citrate showed greater PIDs relative to placebo than other BTCP medications 15 minutes after intake. All other medications showed greater PIDs relative to placebo at 30 minutes, except morphine sulfate immediate release, which did not show efficacy over placebo until 45 minutes. Only INFS produced clinically meaningful pain relief (absolute PID ≥2) at 15 minutes. Conclusion: From current evidence, although all BTCP medications provided pain relief within the time frames assessed, transmucosal fentanyl medications achieved a greater level of pain relief in a shorter time frame than placebo or oral morphine. [Copyright &y& Elsevier]

Context The successful management of breakthrough pain depends on a combination of adequate assessment, appropriate (individualized) treatment, and adequate re-assessment. Currently, there is no fully validated clinical assessment tool for breakthrough pain in cancer patients. Objectives The aim of this project was to develop and validate a breakthrough pain assessment tool (the BAT) for use in the clinical setting. Methods The content of the BAT was determined by reviewing the medical literature, conducting a Delphi process with experts in breakthrough pain and/or pain assessment and conducting semi-structured interviews with cancer patients with breakthrough pain. The tool was then subjected to a series of standard psychometric tests to assess its factor structure, validity (i.e., content validity, construct validity), reliability (i.e., internal consistency, test-retest reliability), and responsiveness to change. Results The BAT comprised two pages with 14 questions. Factor analysis confirmed the presence of two underlying factors. Psychometric testing confirmed that the tool is valid, reliable, and responsive to change. Conclusion This study provides initial evidence for the validity and reliability of the breakthrough pain assessment tool which may be used to facilitate the management of patients with breakthrough cancer pain in the clinical setting. [ABSTRACT FROM AUTHOR]

Abstract: Context: Breakthrough pain is common in patients with cancer and is a significant cause of morbidity in this group of patients. Objectives: The aim of this study was to characterize breakthrough pain in a diverse population of cancer patients. Methods: The study involved 1000 cancer patients from 13 European countries. Patients were screened for breakthrough pain using a recommended diagnostic algorithm and then questioned about the characteristics and management of their pain. Results: Of the 1000 patients, 44% reported incident pain, 41.5% spontaneous pain, and 14.5% a combination. The median number of episodes was three a day. The median time to peak intensity was 10 minutes, with the median for patients with incident pain being five minutes (P < 0.001). The median duration of untreated episodes was 60 minutes, with the median for patients with incident pain being 45 minutes (P = 0.001). Eight hundred six patients stated that pain stopped them doing something, 66 that it sometimes stopped them doing something, and only 107 that it did not interfere with their activities. Patients with incident pain reported more interference with walking ability and normal work, whereas patients with spontaneous pain reported more interference with mood and sleep. As well, 65.5% of patients could identify an intervention that improved their pain (29.5%, pharmacological; 23%, nonpharmacological; 12%, combination). Regarding medications, 980 patients were receiving an opioid to treat their pain, although only 191 patients were receiving a transmucosal fentanyl product licensed for the treatment of breakthrough pain. Conclusion: Breakthrough cancer pain is an extremely heterogeneous condition. [Copyright &y& Elsevier]

A number of studies have reported the analgesic effect of morphine when applied topically to painful skin ulcers. It has been suggested that morphine may exert a local action, as opioid receptors have been demonstrated on peripheral nerve terminals. In this study, we investigated the bioavailability of topically applied morphine to cutaneous ulcers. Six hospice inpatients with skin ulcers were given morphine sulfate 10 mg in Intrasite gel topically and morphine sulfate 10 mg subcutaneously over 4 hours, at least 48 hours apart, in randomized order. Morphine, morphine-6-glucuronide (M6G), and morphine-3-glucuronide (M3G) were determined in plasma using a specific HPLC method. In five patients morphine and its metabolites were undetectable when applied topically. In one patient (with the largest ulcer), morphine and M6G were detected. The calculated morphine and M6G bioavailability in this patient were 20% and 21%, respectively. M3G was also detected but was below the lower limit of quantitation. When applied topically to ulcers, morphine was not absorbed in the majority of patients, suggesting any analgesic effect would be mediated locally rather than systemically. However, in ulcers with a large surface area, systemic absorption may occur. [Copyright &y& Elsevier]

The analgesic effects of morphine applied topically to painful ulcers was assessed in a randomized, double-blind, placebo-controlled, crossover pilot study of five patients with painful sacral sores. Patients were treated for two days with either 10 mg morphine sulfate or placebo (water for injection) applied topically to the ulcer. After a two-day wash-out period, patients were crossed over for a further two days of the alternative treatment. Patients were asked to rate analgesia using a visual analogue scale (VAS) and to document any local or systemic adverse effects. All patients reported lower VAS scores with morphine compared to placebo and no local or systemic adverse events attributable to morphine were noted by either patients or nursing staff. This pilot study suggests that morphine applied topically is an effective method of producing local analgesia, well tolerated by patients, and not associated with systemic adverse effects. [ABSTRACT FROM AUTHOR]