Pain
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Comparative Study Clinical Trial
Secondary hyperalgesia to mechanical but not heat stimuli following a capsaicin injection in hairy skin.
A psychophysical investigation was carried out to examine whether heat hyperalgesia exists within the secondary mechanical hyperalgesia zone surrounding a capsaicin injection site on hairy skin. A non-contact laser stimulator was used to deliver temperature controlled stimuli to sites within and outside the zone of mechanical hyperalgesia. Heat testing was carried out before and after the intradermal injection of 50 micrograms of capsaicin into the volar forearm. ⋯ Thus, there was no evidence for heat hyperalgesia within the zone of secondary hyperalgesia to punctate mechanical stimuli. Though the areas of punctate and stroking hyperalgesia were correlated, no correlation existed between the magnitude of capsaicin evoked pain and the areas mechanical hyperalgesia to punctuate and stroking stimuli or the area of flare. This suggests that independent mechanisms may mediate evoked pain, central sensitization that leads to mechanical hyperalgesia, and axon reflexive flare.
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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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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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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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Rats developed tactile allodynia within days of the onset of diabetes and which persisted for up to 8 weeks. Allodynia was prevented by insulin therapy that maintained normoglycemia while established allodynia was reversed by insulin therapy and normoglycemia of days but not hours duration. Tactile allodynia persisted in diabetic rats that received enough insulin to maintain normal body and foot weights but remained hyperglycemic, whereas this therapy was sufficient to correct other nerve disorders in diabetic rats, including deficits of sensory and motor nerve conduction velocity, nerve blood flow and hyperalgesia during the formalin test. ⋯ Systemic lidocaine treatment alleviated tactile allodynia in nerve injured control rats and both sham-operated and nerve injured diabetic rats. The streptozotocin-diabetic rat develops tactile allodynia that appears to be related to prolonged periods of insulin deficiency or hyperglycemia and which is amenable to treatment with lidocaine. The model may be of use in investigating the efficacy of other potential therapeutic agents for treating painful diabetic neuropathy.