Pain
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The discovery that the endogenous morphine-like peptides named enkephalins are inactivated by two metallopeptidases, neutral endopeptidase and aminopeptidase N, which can be blocked by dual inhibitors, represents a promising way to develop 'physiological' analgesics devoid of the side effects of morphine. A new series of dual aminophosphinic inhibitors of the two enkephalin-catabolizing enzymes has been recently designed. In this study, one of these inhibitors, RB3007, was tested in various assays commonly used to select analgesics (mouse hot-plate test, rat tail-flick test, writhing and formalin tests in mice, and paw pressure test in rats), and the extracellular levels of the endogenous enkephalins in the ventrolateral periaqueductal grey have been measured by microdialysis after systemic administration of RB3007. ⋯ This increase parallels the antinociceptive responses observed. In addition, strong facilitatory effects of subanalgesic doses of the CCK(2) receptor antagonist, PD-134,308 or the synthetic opioid agonist, methadone on RB3007-induced antinociceptive responses were observed. These findings may constitute promising data for future development of a new class of analgesics that could be of major interest in a number of severe and persistent pain syndromes.
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Cyclooxygenase-2 (COX-2) activity in the spinal cord plays a key role in sensitization to sensory stimuli during acute inflammation. In contrast, intrathecal administration of COX-2 specific inhibitors has minimal analgesic effects in an incisional model of postoperative pain. We investigated the role of COX isoforms in this model by examining the expression of COX-1 and the effect of intrathecal COX inhibitors. ⋯ Ketorolac and SC-560 dose-dependently increased withdrawal threshold in this model, but NS-398 had no effect. These results suggest that COX-1 plays an important role in spinal cord pain processing and sensitization after surgery. Increased COX-1 activity could precede the up-regulation of COX-1 protein, and spinally administered specific COX-1 inhibitors may be useful to treat postoperative pain.
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Randomized Controlled Trial Comparative Study Clinical Trial
Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain--results of a randomized double-blinded, placebo-controlled trial.
Phantom limb pain (PLP) associated neuroplastic changes are partly mediated by excitatory amino acids at NMDA receptor sites. This study was undertaken to deduce if NMDA-receptor antagonists may be effective in patients with chronic PLP. Therefore a four week double-blinded, randomized placebo-controlled trial was performed to evaluate the efficacy of 30 mg memantine/day, an orally administrable NMDA receptor antagonist. ⋯ The total number of slight adverse events were comparable in both groups, but the overall number of severe events was higher in the memantine group (P<0.05). This trial failed to demonstrate a significant clinical benefit of the NMDA-receptor antagonist memantine in chronic PLP. The administration of a higher dosage is probably not tolerable.
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Comparative Study
Risk factors for non-specific low back pain in schoolchildren and their parents: a population based study.
A survey of adolescent schoolchildren and their parents through a self-administered questionnaire was conducted to determine the prevalence of low back pain (LBP) in schoolchildren and their parents and to assess its association with exposure to known and presumed risk factors. A previously validated, self-administered questionnaire was used for collecting information on back pain history, anthropometric measures, physical and sports activity, academic problems, hours of leisure sitting, smoking, and alcohol intake. Schoolchildren between the ages of 13 and 15 in schools of the island of Mallorca and their parents (n=16,394) took part in the study. ⋯ There is a strong association between pain in bed or upon rising in both adolescents and adults. Scoliosis, but not LBP, appears to be related to heredity. Further longitudinal studies are necessary to establish risk factors that are predictive for LBP in adolescents.
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Comparative Study
A longitudinal study of the prevalence and characteristics of pain in the first 5 years following spinal cord injury.
A longitudinal cohort study of 100 people with traumatic spinal cord injury (SCI) was performed to determine the prevalence and severity of different types of pain (musculoskeletal, visceral, neuropathic at-level, neuropathic below-level) at 5 years following SCI. Prospective data on the characteristics of pain up to 6 months following injury had been collected previously and allowed comparisons between the presence of pain at different time points. In addition, we sought to determine the relationship between the presence of pain and physical factors related to the injury such as level of lesion, completeness and clinical SCI syndrome. ⋯ Chronic visceral pain occurs in a small percentage of patients and does not correlate with the presence of visceral pain early following injury. Those with neuropathic pain early following their injury are likely to continue to experience ongoing pain and the pain is likely to be severe. In contrast, chronic musculoskeletal pain is more common but less likely to be severe and cannot be predicted by the presence of pain in the first 6 months following injury.