Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dextromethorphan is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist known to inhibit wind-up and NMDA-mediated nociceptive responses of dorsal horn neurons. Experimental and clinical studies indicate that NMDA-receptor antagonists may potentiate the effect of analgesics such as morphine, local anesthetics and NSAIDs. Results from previous clinical studies of dextromethorphan in postoperative pain are conflicting, possibly related to administration of insufficient doses of the drug. Fifty patients scheduled for non-malignant elective abdominal hysterectomy in general anesthesia were randomized to receive oral dextromethorphan 150 mg, or placebo 1 h before surgery. The patients received patient-controlled analgesia with morphine for 24 h postoperatively as the only analgesic. Patient-controlled analgesia (PCA) morphine consumption was reduced with 30% from 0-4 h after operation in patients receiving dextromethorphan compared with placebo (P=0.02); no differences were observed from 5-24 h postoperatively. There were no significant differences between groups for visual analogue scale scores at rest, during cough, or during mobilization, pressure pain detection thresholds, von Frey hair pain detection thresholds, or peak flow. At 24 h after operation, hyperalgesia to von Frey hair stimulation proximal to the surgical wound was easily detected in 23 of 25 patients receiving dextromethorphan, and in 22 of 25 patients receiving placebo, with no significant difference between groups. Pooled data from both groups showed a weak but significant correlation between the extent of hyperalgesia at 24 h after operation, and total 24 h postoperative PCA morphine consumption (Rs=0.28, P=0.05). Three months postoperatively, hyperalgesia was still detectable in 18 of 22 examined patients in the dextromethorphan group, and in 16 of 23 patients in the placebo group, without statistical differences between groups. There were no significant differences in side-effects (nausea, vomiting, sedation). In conclusion, oral dextromethorphan 150 mg reduced PCA morphine consumption immediately (0-4 h) after hysterectomy, without prolonged effects on pain or wound hyperalgesia. A positive correlation between the magnitude of wound hyperalgesia at 24 h after operation, and total 24 h postoperative PCA morphine consumption was demonstrated.
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PMID:Effect of preoperative oral dextromethorphan on immediate and late postoperative pain and hyperalgesia after total abdominal hysterectomy. 1077 56

This placebo-controlled, double-blind crossover study assessed whether exclusive activation of peripheral opioid receptors results in significant pain reduction. To achieve opioid activity restricted to the periphery, we used a short-term (2 h) low dose infusion of morphine-6-beta-glucuronide (M6G) because M6G does not pass the blood-brain barrier during this time in amounts sufficient to induce CNS effects. The lack of central opioid effects of M6G was confirmed by a lack of change of the pupil size and absence of other opioid-related CNS effects. As a positive control, morphine was infused at a dosage that definitely produced CNS effects. This was evident by a rapid decrease of the pupil size and by other typical opioid-related side effects including nausea, vomiting, itchiness, hiccup and sedation. Three different pain models were employed to evaluate the analgesic effects: (i) cutaneous inflammatory hyperalgesia induced by briefly freezing a small skin area to -30 degrees C ('freeze lesion'); (ii) muscle hyperalgesia induced by a series of concentric and eccentric muscle contractions (DOMS model; delayed onset of muscle soreness); and (iii) pain induced by electrical current (5 Hz sinus stimuli of 0-10 mA). M6G significantly reduced cutaneous hyperalgesia in the 'freeze lesion' model as assessed with von Frey hairs. It also reduced muscle hyperalgesia in the DOMS model. Electrical pain, however, was not affected by M6G. Morphine was significantly more active in the 'freeze lesion' and DOMS model, and also significantly increased the electrical pain threshold and tolerance. Subcutaneous tissue concentrations of M6G and morphine as assessed with microdialysis were about half those of the respective plasma concentrations. The results of the study indicate that M6G has antihyperalgesic effects in inflammatory pain through activation of peripheral opioid receptors. Since this occurs at concentrations that do not cause central opioid effects, M6G might be useful as a peripheral opioid analgesic.
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PMID:Peripheral opioid analgesia in experimental human pain models. 1269 49

We have previously shown that nitric oxide (NO) and cyclic guanosine monophosphate (GMP) may cause headache and migraine. However, not all findings in previous studies can be explained by an activation of the NO-cGMP pathway. Calcitonin gene-related peptide (CGRP) causes headache and migraine in migraine patients, but CGRP receptor activation causes an increase in cyclic adenosine monophosphate (cAMP). In order to investigate the role of cAMP in vascular headache pathogenesis, we studied the effect of cilostazol, an inhibitor of cAMP degradation, in our human experimental headache model. Twelve healthy volunteers were included in a double-blind, randomized, crossover study. Placebo or cilostazol (200 mg p.o.) was administered on two separate study days. Headache was scored on a verbal rating scale (0-10) and mechanical pain thresholds were measured with von Frey hairs. The median peak headache score 0-16 h postdose was 0 (range 0-2) after placebo and 3.5 (range 0-7) after cilostazol (P = 0.003). The median headache curve peaked at 6-9 h postdose. The headaches induced were usually bilateral and pulsating. Nausea occurred in two volunteers, photo- and phonophobia were not seen. Two volunteers had a headache that fulfilled International Headache Society criteria for migraine without aura after cilostazol. No change in mechanical pain thresholds in the forehead was seen (P = 0.25). The headache after cilostazol was equal to or more severe than headache induced by glyceryl trinitrate in previous experiments. The present study thus indicates that increased levels of cAMP may play a role in headache and migraine pathogenesis.
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PMID:The headache-inducing effect of cilostazol in human volunteers. 1705 37

The dried fruits of Forsythia viridissima have been prescribed to relive fever, pain, vomiting, and nausea in traditional medicine. Oxaliplatin (LOHP) is used to treat advanced colorectal cancer; however, it frequently induces peripheral neuropathies. This study was done to evaluate the neuroprotective effects of an aqueous extract of Forsythia viridissima fruits (EFVF) and its major constituents. Chemical constituents from EFVF were characterized and quantified with the UHPLC-diode array detector method, and three major constituents were identified as arctiin, matairesinol, and arctigenin. The in vitro cytotoxicity was measured by the Ez-cytox viability assay, and the in vivo neuroprotection activity was evaluated by a von Frey test in two rodent animal models that were administered LOHP. EFVF significantly alleviated the LOHP-induced mechanical hypersensitivity in the induction model. EFVF also prevented the induction of mechanical hyperalgesia by LOHP in the pre- and co-treatment of LOHP and EFVF. Consistently, EFVF exerted protective effects against LOHP-induced neurotoxicity as well as inhibited neurite outgrowths in PC12 and dorsal root ganglion cells. Among the major components of EFVF, arctigenin and matairesinol exerted protective effects against LOHP-induced neurotoxicity. Therefore, EFVF may be useful for relieving or preventing LOHP-induced peripheral neuropathy in cancer patients undergoing chemotherapy with LOHP.
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PMID:Neuroprotective Effects of an Aqueous Extract of Forsythia viridissima and Its Major Constituents on Oxaliplatin-Induced Peripheral Neuropathy. 3093 31

Chronic pain affects approximately one-third of the population worldwide. The primary goal of animal research is to understand the neural mechanisms underlying pain so better treatments can be developed. Despite an enormous investment in time and money, almost no novel treatments for pain have been developed. There are many factors that contribute to this lack of translation in drug development. The mismatch between the goals of drug development in animals (inhibition of pain-evoked responses) and treatment in humans (restoration of function) is a major problem. To solve this problem, a number of pain-depressed behavioral tests have been developed to assess changes in normal behavior in laboratory animals. The use of home cage wheel running as a pain assessment tool is especially useful in that it is easy to use, provides an objective measurement of the magnitude and duration of pain, and is a clinically relevant method to screen novel drugs. Pain depresses activity in humans and animals, and effective analgesic treatments restore activity. Unlike traditional pain-evoked tests (e.g., hot plate, tail flick, von Frey test), restoration of home cage wheel running evaluates treatments for both antinociceptive efficacy and the absence of disruptive side effects (e.g., sedation, paralysis, nausea). This article reviews the literature using wheel running to assess pain and makes the case for home cage wheel running as an effective and clinically relevant method to screen novel analgesics for therapeutic potential.
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PMID:'Reinventing the wheel' to advance the development of pain therapeutics. 3307 36