Pain
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Comparative Study Clinical Trial
Clinical analgesic equivalence for morphine and hydromorphone with prolonged PCA.
A morphine to hydromorphone equivalence ratio of 7:1 has become the accepted standard, but evidence supporting it comes from single dose studies performed before the advent of patient controlled analgesia (PCA). We compared morphine and hydromorphone use with PCA in bone marrow transplantation patients who required opioids for the control of severe oral mucositis over several days or weeks. An exploratory analysis of clinical records from 102 patients (981 patient days) who used PCA opioids for varying periods of up to 50 days suggested a morphine to hydromorphone use ratio of 3:1. ⋯ Thirty-six patients who used morphine and 21 who used hydromorphone contributed data on pain, satisfaction with pain control, and drug consumption. We observed an average morphine/hydromorphone ratio of 3:1. This differs markedly from historical single dose studies used in published dose equivalency recommendations implying that other equivalency ratios in clinical use may be inappropriate.
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N-Methyl-D-aspartate (NMDA) receptor antagonists have been shown to block the development of antinociceptive tolerance to morphine. Assessment of the effects of NMDA antagonists on development of antinociceptive tolerance to selective opioid mu (mu) and delta (delta) agonists, however, has not been reported. In these experiments, selective mu and delta receptor agonists, and morphine, were repeatedly administered to mice either supraspinally (i.c.v.) or systemically (s.c.), alone or after pretreatment with systemic NMDA antagonists. ⋯ Further, MK801 pretreatment also did not affect the development of tolerance to the antinociception resulting from a cold-water swim-stress episode, previously shown to be a delta-opioid mediated effect. These data lead to the suggestion that the mechanisms of tolerance to receptor selective mu and delta opioids may be regulated differently from those associated with morphine. Additionally, these findings emphasize that conclusions reached with studies employing morphine cannot always be extended to 'opiates' in general.
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Plasma and cerebrospinal fluid (CSF) steady-state concentrations (Css) of morphine (M) and the main metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), were determined by high performance liquid chromatography (HPLC) in 21 cancer patients treated with chronic subcutaneous morphine infusion. There was a moderate, but statistically significant correlation between the daily dose of morphine and the concentrations of morphine, M3G and M6G in CSF. A poorer correlation to concentrations were seen in plasma. ⋯ Plasma and CSF concentrations of M3G and CSF concentrations of M6G correlated with administered morphine dose. There was an accumulation of both morphine glucuronides in patients with elevated serum creatinine. Measurements of morphine, M3G and M6G in CSF did not show any overt relationship to analgesia or side effects.
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Clinical Trial
Sequential daily relations of sleep, pain intensity, and attention to pain among women with fibromyalgia.
Fifty women with fibromyalgia syndrome (FS) recorded their sleep quality, pain intensity, and attention to pain for 30 days, using palm-top computers programmed as electronic interviewers. They described their previous night's sleep quality within one-half hour of awakening each day, and at randomly selected times in the morning, afternoon, and evening rated their present pain in 14 regions and attention to pain during the last 30 min. We analyzed the 30-day aggregates cross-sectionally at the across-persons level and the pooled data set of 1500 person-days at the within-persons level after adjusting for between-persons variation and autocorrelation. ⋯ A night of poorer sleep was followed by a significantly more painful day, and a more painful day was followed by a night of poorer sleep. Pain attention and sleep were unrelated at the across-persons level of analysis. But there was a significant bi-directional within-person association between pain attention and sleep quality that was not explained by changes in pain intensity.
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This study, addressing etiologic and pathogenic aspects of fibromyalgia (FM), aimed at examining whether sensory abnormalities in FM patients are generalized or confined to areas with spontaneous pain. Ten female FM patients and 10 healthy, age-matched females participated. The patients were asked to rate the intensity of ongoing pain using a visual analogue scale (VAS) at the site of maximal pain, the homologous contralateral site and two homologous sites with no or minimal pain. ⋯ These findings could be explained in terms of sensitization of primary afferent pathways or as a dysfunction of endogenous systems modulating afferent activity. However, the generalized increase in sensitivity found in FM patients was unrelated to spontaneous pain and thus most likely due to a central nervous system (CNS) dysfunction. The additional hyperphenomena related to spontaneous pain are probably dependent on disinhibition/facilitation of nociceptive afferent input from normal (or ischemic) muscles.