PubMed · 3638158
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L Hanvey, S Post. 1986. Changing patterns in maternity care.. https://pubmed.ncbi.nlm.nih.gov/3638158/
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As the genomic revolution continues to evolve, there is an increasing demand for efficient and reliable tools for functional characterization of individual gene products. Antisense oligonucleotide-mediated knockdown has been used successfully as a functional genomics tool in animal models of pain and analgesia yet skepticism regarding the validity and utility of antisense technology remains. Contributing to this uncertainty are the lack of systematic studies exploring antisense oligonucleotide use in vivo and the many technical and methodological challenges intrinsic to the method. This article reviews the contributions of antisense oligonucleotide-based studies to the field of pain and analgesia and the general principles of antisense technology. A special emphasis is placed on technical issues surrounding the successful application of antisense oligonucleotides in vivo, including sequence selection, antisense oligonucleotide chemistry, DNA controls, route of administration, uptake, dose-dependence, time-course and adequate evaluation of knockdown.
OBJECTIVE: To determine the efficacy of etoricoxib in the treatment of primary dysmenorrhea. METHODS: Seventy-three women were randomly assigned to receive single oral doses of etoricoxib 120 mg, placebo, or naproxen sodium 550 mg at the onset of moderate to severe pain associated with menses. During 3 consecutive menstrual cycles in this double-blind, 3-period, crossover study, pain intensity and pain relief were assessed over the 24-hour period following dosing, and global ratings of therapy were made at 8 and 24 h after dosing. Tolerability was assessed by spontaneous reports of adverse experiences. RESULTS: Etoricoxib 120 mg provided analgesic efficacy superior to placebo for the primary endpoint, total pain relief over 8 h (TOPAR8, p<0.001), and for all secondary endpoints (p<0.050). The analgesic effect of etoricoxib 120 mg over the first 8 h was similar to that of naproxen sodium 550 mg. All treatments were well tolerated. CONCLUSIONS: Etoricoxib 120 mg provided rapid and sustained analgesia that was superior to placebo and similar to that of naproxen sodium 550 mg.
In humans, kappa agonist-antagonist opioids such as nalbuphine have been proposed to produce both analgesia and anti-analgesia by acting at distinct receptors. The anti-analgesia appears to be greater in men, which may contribute to the greater nalbuphine analgesia observed in women. Kappa agonist-antagonists are also known to produce sexually dimorphic antinociception in nonhuman species but are generally more potent in males; anti-analgesia has not been reported in animals. The aim of the present study was to determine if nalbuphine anti-analgesia can be detected in the rat. Since nalbuphine anti-analgesia is more sensitive to naloxone antagonism than its analgesic effect, low doses of naloxone were combined with nalbuphine. Using the Randall-Selitto paw-withdrawal test, nalbuphine (0.5-10 mg/kg) induced dose-dependent antinociception in the rat. The antinociceptive effect of nalbuphine (0.5 or 1 mg/kg) was not enhanced by lower doses of naloxone but was antagonized by higher doses. These data do not support the hypothesis that the naloxone-sensitive anti-analgesic effect of nalbuphine observed in humans is present in the rat and could explain, at least in part, the opposite direction of the sex differences for kappa agonist-antagonist opioid analgesia observed in these two species.