Dopaminergic transmission in the hypothalamic arcuate nucleus to produce acupuncture analgesia in correlation with the pituitary gland

Acupuncture analgesia (AA) caused by low frequency stimulation of the acupuncture point (AP) was abolished by hypophysectomy and adrenalectomy. Termination of the AA producing pathway from the AP to the pituitary gland was in the medial hypothalamic arcuate nucleus (M-HARN). The origin of the descending pain inhibitory system associated with AA was in the posterior HARN (P-HARN). AA in the hypophysectomized rats, and enhanced neuronal activity in the P-HARN that were abolished during acupuncture stimulation, were both restored by intraperitoneal microinjection of 0.5 mg/kg morphine or 0.1 micrograms beta-endorphin into the P-HARN during acupuncture stimulation. Of the analgesia produced by dopamine or beta-endorphin injected into the P-HARN, that caused by beta-endorphin disappeared after denervation of the M-HARN. The P-HARN neurons that responded to acupuncture stimulation also responded to iontophoretic dopamine, but not to iontophoretic morphine nor ultramicroinjected beta-endorphin. The transmission between the M-HARN and P-HARN may be dopaminergic, and beta-endorphin might presynaptically modulate this transmission. Reduction of sodium ions may have been the reason for abolition of AA after adrenalectomy.     

芬太尼／哌替啶致Oddi括约肌痉挛的探讨

２００例择期胆囊切除＋术中胆道造影患者分二组；芬太尼１７ｕｇ／ｋｇ静注（Ｆ组，ｎ＝１００）、哌替啶１ｍｇ／ｋｇ静注。评价两种麻醉性镇痛药致Ｏｄｄｉ括约肌痉挛的发生率，结果：８例病人造影剂不能通过Ｏｄｄｉ括约肌、十二指肠不显影，胆总管下端显示“鸟嘴样”或“假结石”影像，后者３例病人胆总管探查阴性，静注纳络酮０．４ｍｇ后，全部病例造影剂顺利进入十二指肠。结论：硬膜外麻醉辅用小剂量芬太尼／哌替啶时Ｏｄｄ     

白细胞介素—2新的功能位点及其中枢镇痛作用

白细胞介素－２（ＩＬ－２）不仅是重要的免疫调节因子，而且还具有重要的中枢调节作用。本实验以钾离子透入引起大鼠甩尾反应为指标，发现侧脑室注射ＩＬ—２能显著提高动物痛阈，并能被纳洛酮所阻断，表示ＩＬ－２的中枢镇痛作用可能与阿片受体有关。利用基因定位突变技术获得的无免疫活性ＩＬ－２实查体仍具有中枢镇痛作用，表明ＩＬ—２分子上发挥镇痛和免疫调节作用的功能位点是相互独立的。纳洛酮能够阻断ＩＬ—２的中枢镇痛作用，而不能影响ＩＬ—２增殖ＣＴＬＬ－２细胞的作用，提示ＩＬ－２发挥镇痛和免疫调节作用可能通过不同的受体途径。ＩＬ－２分子中第４５位Ｔｙｒ残基突变为Ｖａｌ后，虽仍保留了免疫活性，但丧失了镇痛功能，表示４５位Ｔｙｒ残基是ＩＬ—２发挥中枢镇痛功能的关键残基之一。我们推测ＩＬ—２的镇痛功能位点可能在ＩＬ—２分子中第４５位Ｔｙｒ残基附近区域。     

Neuroendocrine and clinical effects of transdermal 17β-estradiol in postmenopausal women

The neuroendocrine and clinical effects of transdermal 17β-estradiol (rated at 50 μg/day; TTS 50) were studied in 40 postmenopausal women; ten additional postmenopausal women did not receive any drugs. The changes in LH and rectal temperature induced by the infusion of the opioid antagonist naloxone (10 mg i.v. bolus plus 10 mg/h for 4 h) were used to evaluate the central activity of endogenous opioid peptides. TTS 50 increased opioid activity, as evidenced by the restoration of the LH response (P < 0.01) and the enhancement of the hypothermic effect (P < 0.05) of naloxone. A greater reduction in hot flushes was observed in TTS 50-treated subjects than in untreated women, with the maximal effect of TTS 50 achieved after 3 months of therapy. TTS 50 did not modify the concentrations of circulating lipids, glucose or liver enzymes but reduced the biochemical parameters indicative of bone reabsorption. Bone density of the distal radius significantly increased during TTS 50 (P < 0.02), reaching its maximum value after 6 months of therapy. Thereafter bone density declined, but more slowly than in untreated women.

Our data suggest that TTS 50 has marked neuroendocrine effects, that it diminishes the incidence of hot flushes and reduces bone demineralization. By contrast, it has a very little, if any, metabolic impact on the liver or on glucose and lipid metabolism.     

金尔伦治疗急性颅脑损伤的剂量效应研究

目的探讨金尔伦(盐酸纳洛酮)在治疗大鼠液压脑损伤后神经功能恢复和病理损害程度的剂量效应.方法将104只SD大鼠随机分为4组,伤后早期分别腹腔注射0.03 mg/Kg(小剂量组)、0.3 mg/Kg(中剂量组)、3 mg/Kg(大剂量组)金尔伦和等量生理盐水(对照组),连续7 d.结果中、大剂量组动物伤后脑神经功能恢复、脑水肿减轻程度及光、电镜检查显著优于对照组及小剂量组.结论伤后早期使用中剂量和大剂量金尔伦(盐酸纳洛酮)对大鼠液压颅脑损伤有明显的治疗效果.     

Spinal cholinergic and monoamine receptors mediate the antinociceptive effect of morphine microinjected in the periaqueductal gray on the rat tail, but not the feet

The antinociceptive effects of morphine (5 μg) microinjected into the ventrolateral periaqueductal gray were determined using both the tail flick and the foot withdrawal responses to noxious radiant heating in lightly anesthetized rats. Intrathecal injection of appropriate antagonists was used to determine whether the antinociceptive effects of morphine were mediated byα₂-noradrenergic, serotonergic, opioid, or cholinergic muscarinic receptors. The increase in the foot withdrawal response latency produced by microinjection of morphine in the ventrolateral periaqueductal gray was reversed by intrathecal injection of the cholinergic muscarinic receptor antagonist atropine, but was not affected by the a2-adrenoceptor antagonist yohimbine, the serotonergic receptor antagonist methysergide, or the opioid receptor antagonist naloxone. In contrast, the increase in the tail flick response latency produced by morphine was reduced by either yohimbine, methysergide or atropine. These results indicate that microinjection of morphine in the ventrolateral periaqueductal gray inhibits nociceptive responses to noxious heating of the tail by activating descending neuronal systems that are different from those that inhibit the nociceptive responses to noxious heating of the feet. More specifically, serotonergic, muscarinic cholinergic andα₂-noradrenergic receptors appear to mediate the antinociception produced by morphine using the tail flick test. In contrast, muscarinic cholinergic, but not monoamine receptors appear to mediate the antinociceptive effects of morphine using the foot withdrawal response.     

Cardiovascular effects of Leu-enkephalin in the nucleus tractus solitarius of the rat

Microinjections of Leu-enkephalin into the dorsal vagal complex induced hypotension and bradycardia. Both naloxone, given at a dose conferring selectivity for μ receptors, and the S antagonist ICI 154,129 prevented the cardiovascular effects of Leu-enkephalin. Naloxone was also found to decrease the gain of the baroreflex. These results suggest that Leu-enkephalin is involved in cardiovascular regulation through activation of δ-, and possibly μ-, opioid receptors in the dorsal vagal complex.     

Opiate induced feeding is not dependent on the hippocampus

It has been shown that spreading depression of the hippocampus can elicit feeding, and that several opioid peptides elicit spreading depression when injected into the hippocampus. To determine whether such depression is the primary mechanism by which opiates induce feeding, we tested the feeding effects of naloxone, an opiate antagonist, and butorphanol tartrate, a kappa-sigma agonist, on feeding in rats with and without hippocampal lesions. Naloxone tended to reduce intake approximately equally in the two groups. Similarly, the doses of butorphanol that increased intake in sham rats were equally effective in lesioned rats. It was concluded that the hippocampus is not the major structure mediating opiate-induced feeding.     

LHRH messenger RNA in neurons in the intact and castrate male rat forebrain,studied by in situ hybridization

Summary The slow potential change (spc) accompanying spreading depression (SD) was studied in rats and in a seizure-sensitive strain of Mongolian gerbil under three different experimental paradigms, each involving the use of naloxone. Gerbils undergoing electroconvulsive shock treatment displayed SD during the post-ictal phase, which was blocked by the intraperitoneal (i.p.) administration of naloxone (20–50 mg kg^-1). Topical application of naloxone to the exposed cortex of the anaesthetized gerbil and rat blocked the spc of SD evoked by KCl. Microiontophoretic ejection of naloxone during extracellular recordings reversed cell refractoriness following the spc, demonstrated by the observation of a maintained sensitivity to iontophoretic pulses of glutamate. The results suggest a possible involvement of naloxone-sensitive processes in the mechanism responsible for cortical SD.