Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two new long-acting hydrazone derivatives of 14-hydroxydihydromorphinones have been synthesized, oxymorphazone and naltrexazone. Both derivatives show high affinity for opiate binding sites in vitro, similar to naloxazone, the hydrazone analogue of naloxone. Sodium and manganese shifts imply that naltrexazone, like naloxazone, is a pure antagonist. By contrast, oxymorphazone inhibition of receptor binding is dramatically reduced by sodium and potentiated by manganese, suggesting it is an agonist. When given in vivo, all agents produce a significant inhibition of receptor binding for over 24 h despite extensive washing of the brain homogenates. Oxymorphone, naltrexone, and naloxone are without effect. Twenty-four hours after in vivo administration of oxymorphazone, 82% of mice are still analgetic compared to only 17% of oxymorphone-treated mice (p less than 0.005). Twenty-four hours after naltexazone or naloxazone treatment all mice were protected from morphine analgesia (12 mg/kg; p less than 0.005), while naltrexone- and naloxone-treated animals did not differ significantly from saline-treated controls.
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PMID:Long-acting opiate agonists and antagonists: 14-hydroxydihydromorphinone hydrazones. 615 40

The possibility that divalent cations may antagonize opiate peptide analgesia and stress-induced analgesia was examined. Intracerebroventricular injection of low doses of Ca2+, Mn2+ and Mg2+ antagonized beta-endorphin and methionine-enkephalin analgesia. Ba2+ and Cd2+ were without effect. The ionophore, A23187, significantly antagonized beta-endorphin analgesia and the effect was increased when a low dose of Ca2+ was injected at the same time as the ionophore. Ethylene glycol tetraacetic acid (but not ethylenediamine tetraacetic acid) significantly potentiated endorphin analgesia. Stress-induced analgesia, as determined by increased tail-flick latencies following intraperitoneal injection of acetic acid, was effectively antagonized by naloxone, Ca2+ and Mn2+. The frequency of writhing following acetic acid injection was increased by both naloxone and divalent metal ions, again suggesting antagonism of endogenous opiates. These results confirm previous findings indicating that divalent metal ions (and especially Ca2+) may be involved in the actions of opiates.
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PMID:Modification of endorphin/enkephalin analgesia and stress-induced analgesia by divalent cations, a cation chelator and an ionophore. 682 Nov 93

Acupuncture analgesia is an important issue in veterinary medicine. This study was designed to elucidate central modulation effects in response to electroacupuncture (EA) at different acupoints. Manganese-enhanced functional magnetic resonance imaging was performed in Sprague-Dawley rats after sham acupuncture, sham EA, or true EA at somatic acupoints. The acupoints were divided into 3 groups: group 1, analgesic acupoints commonly used for pain relief, such as Hegu (LI 4); group 2, nonanalgesic acupoints rarely used for analgesic effect such as Neiguan (PC 6); and group 3, acupoints occasionally used for analgesia, such as Zusanli (ST 36). Image acquisition was performed on a 1.5-T superconductive clinical scanner with a circular polarized extremity coil. The results showed that there was no neural activation caused by EA at a true acupoint with shallow needling and no electric current (sham acupuncture). When EA at a true acupoint was applied with true needling but no electric current (sham EA), there was only a slight increase in brain activity at the hypothalamus; when EA was applied at a true acupoint with true needling and an electric current (true EA), the primary response at the hypothalamus was enhanced. Also, there was a tendency for the early activation of pain-modulation areas to be prominent after EA at analgesic acupoints as compared with nonanalgesic acupoints. In conclusion, understanding the linkage between peripheral acupoint stimulation and central neural pathways provides not only an evidence-based approach for veterinary acupuncture but also a useful guide for clinical applications of acupuncture.
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PMID:Different central manifestations in response to electroacupuncture at analgesic and nonanalgesic acupoints in rats: a manganese-enhanced functional magnetic resonance imaging study. 1276 Apr 73

The behavioral effects of manganese chloride at 20 and 40 mg/kg, subcutaneously (sc), were examined in 1-mo-old broiler chickens using the open-field (5 min) and tonic immobility tests. In a separate experiment, chickens were subjected to a pharmacological challenge with the anesthetic combination of xylazine-ketamine following manganese chloride pretreatment at 50 mg/kg, sc. Manganese at 40 mg/kg significantly decreased jumping attempts of the chickens in the open-field test 30 min after the injection when compared with the control (saline) group. Both manganese treatments significantly increased the tonic immobility response of the chickens in a dose-dependent manner in comparison with the control group. Pretreatment with manganese chloride (50 mg/kg, sc) significantly increased the duration of sleep, decreased the latency to onset of analgesia, and increased the duration of analgesia in chickens treated with the anesthetic xylazine-ketamine mixture when compared with the saline control group. The respiratory rate of all anesthetized chickens significantly decreased from respective preanesthetic (time 0) values during the 60-min observation period after injection of the anesthetic. However, 60 min after the anesthetic injection, the respiratory rate of the manganese-treated group was significantly lower than that of the control group. The data suggest a depressant action of acute manganese chloride treatment in chickens.
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PMID:Behavioral effects of acute manganese chloride administration in chickens. 1684 62

Molecular and cellular imaging of neuropathic pain, utilizing the myriad of receptors and inflammatory mediators involved in nociceptive activity, is a promising approach toward objectively identifying peripheral pain generators. Neuropathic conditions arise from injured and inflamed nerves, which have been shown to elaborate several molecular and cellular elements that give rise to the neuropathic phenotype and can be exploited for imaging purposes. As such, in vivo approaches to image neuropathic pain mechanisms include imaging voltage-gated sodium channels with radiolabeled saxitoxin, calcium signaling with manganese-enhanced magnetic resonance imaging, and inflammatory changes and nerve metabolism with (18)F-fluorodeoxyglucose. Imaging approaches exploiting other mediators of nociceptive activity, such as substance P (neurokinin-1) receptor, sigma-1 receptor, and macrophages, have shown promising early advances in animal models. By combining the sensitivity and specificity of molecular imaging with the high anatomical, spatial and contrast resolution afforded by computed tomography and MRI, radiologists can potentially identify sites of nerve injury or neuroinflammation that are implicated as peripheral pain drivers with greater accuracy and confidence. In addition to guiding therapy, these approaches will aid in new drug designs for analgesia and more individualized treatment options.
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PMID:Neuropathic pain mechanisms and imaging. 2576 34