Pharmacology
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One of the most treatable causes of lower back pain and associated sciatica is lumbar disc herniation (LDH), which is characterized by rupture of the hard outer wall (annulus fibrosis) in a lumbar intervertebral disc. In the current study, we aimed to: (1) develop and characterize a rat model of sciatica induced by LDH, while introducing a novel method of epidural catheterization; (2) use this model to evaluate the effect of osthole on pain due to LDH, and (3) gain insight into the mechanisms through which osthole affects sciatica induced by LDH. The results indicate that our newly developed rat model maintained mechanical allodynia for 28 days without reduction. ⋯ Finally, a molecular modeling simulation showed that osthole has unique binding capabilities to both NOS and COX-2. As the model-induced mechanical hyperalgesia response was consistent, and the position of the catheter tip and the extension/spreading of the drug in the epidural space were reliable, this study developed an improved model to study remedies for sciatic pain. Moreover, our studies demonstrate that osthole may be a feasible treatment for the reduction of pain due to hyperalgesia.
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Anesthesia, a state of profound central nervous system suppression, involves a sequence of events that is still not well understood. In the present study, we examined the action of propofol (a sedative-hypnotic drug commonly used as anesthetic) on thalamocortical functional connectivity in rats by using functional connectivity magnetic resonance imaging (fcMRI) with a 3.0-tesla MR scanner. Intraperitoneal injections of propofol (80 or 160 mg/kg) were administered to Sprague-Dawley rats. ⋯ These observations indicate that thalamocortical connectivity may play an important role in propofol anesthesia. We also observed that regionally specific long-range correlations of spontaneous low-frequency physiological fluctuations in BOLD signals may be present across somatosensory networks of the brain in the absence of external stimulation. However, our experiment suggests that fcMRI can be used to investigate brain networks that exhibit correlated fluctuations.
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We investigated whether capsaicin induces itching in skin with existing inflammation. We induced skin inflammation by intradermal injection of complete Freund's adjuvant (CFA) in the neck of mice. Four days later, we injected capsaicin in the same area and counted the number of scratching bouts for 30 min. ⋯ In animals injected with capsaicin into the hind paws, licking behavior was significantly inhibited via a μ-receptor-dependent mechanism. Our results show that TRPV1 activation, which normally induces pain, evokes an itch-related response in the presence of inflammation. This model may be interesting for future studies to explore the mechanism of a painful stimuli-induced itch observed under pathological conditions.
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Randomized Controlled Trial
Co-administration of ondansetron decreases the analgesic efficacy of tramadol in humans.
Tramadol, a central analgesic acting on serotonin neurotransmission, is often co-used with ondansetron, a 5-HT(3) antagonist, for the management of postoperative pain to decrease nausea and vomiting. The aim of the study is to test the hypothesis that this drug combination raises tramadol requirement by patient-controlled analgesia (PCA). ⋯ Tramadol consumption (mg × kg(-1) × h(-1)) was higher in the ondansetron group at the 2-hour time point compared to the control group (0.24 ± 0.1 vs. 0.17 ± 0.16; p = 0.01). Our study suggests that ondansetron acutely reduces the analgesic efficacy of tramadol.
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In most cancer patients, pain is successfully treated with pharmacological measures using opioid analgesics for moderate to severe pain (strong opioids) alone or in combination with adjuvant analgesics (coanalgesics). Opioids for mild to moderate pain (weak opioids) are usually recommended in the treatment of cancer pain of mild to moderate intensity. ⋯ All these drugs are metabolized through CYP2D6, an important enzyme for approximately 25% of all drugs administered in clinical practice. The aim of this review is to summarize data on the impact of CYP2D6 polymorphism on pharmacokinetics, pharmacodynamics and adverse effects of weak opioids.