Role of spinal NMDA receptors, protein kinase C and nitric oxide synthase in the hyperalgesia induced by magnesium deficiency in rats.

1. Magnesium (Mg)-deficient rats develop a mechanical hyperalgesia which is reversed by a N-Methyl-D-Aspartate (NMDA) receptor antagonist. Given that functioning of this receptor-channel is modulated by Mg, we wondered whether facilitated activation of NMDA receptors in Mg deficiency state may in turn trigger a cascade of specific intracellular events present in persistent pain. Hence, we tested several antagonists of NMDA and non-NMDA receptors as well as compounds interfering with the functioning of intracellular second messengers for effects on hyperalgesia in Mg-deficient rats. 2. Hyperalgesic Mg-deficient rats were administered intrathecally (10 microl) or intraperitoneally with different antagonists. After drug injection, pain sensitivity was evaluated by assessing the vocalization threshold in response to a mechanical stimulus (paw pressure test) over 2 h. 3. Intrathecal administration of MgSO4 (1.6, 3.2, 4.8, 6.6 micromol) as well as NMDA receptor antagonists such as MK-801 (0.6, 6.0, 60 nmol), AP-5 (10.2, 40.6, 162.3 nmol) and DCKA (0.97, 9.7, 97 nmol) dose-dependently reversed the hyperalgesia. Chelerythrine chloride, a protein kinase C (PKC) inhibitor (1, 10.4, 104.2 nmol) and 7-NI, a specific nitric oxide (NO) synthase inhibitor (37.5, 75, 150 micromol x kg(-1), i.p.) induced an anti-hyperalgesic effect in a dose-dependent manner. SR-140333 (0.15, 1.5, 15 nmol) and SR-48968 (0.17, 1.7, 17 nmol), antagonists of neurokinin receptors, produced a significant, but moderate, increase in vocalization threshold. 4. These results demonstrate that Mg-deficiency induces a sensitization of nociceptive pathways in the spinal cord which involves NMDA and non-NMDA receptors. Furthermore, the data is consistent with an active role of PKC, NO and, to a lesser extent substance P in the intracellular mechanisms leading to hyperalgesia.

Magnesium and MK-801 have a similar effect in two experimental models of neuropathic pain.

Considering that magnesium and non-competitive NMDA receptor antagonists inhibit the opening of the channel linked to the NMDA receptor, we assessed their effects on mechanical hyperalgesia in two animal models of neuropathic pain (rats with a sciatic nerve ligature and diabetic rats). Our data show that magnesium reverses the hyperalgesia, as does MK-801. These results suggest that magnesium could be an alternative for the treatment of neuropathic pain in patients.

[The exencephaly-anencephaly sequence. Ultrasound diagnosis in early pregnancy]. / Die Exenzephalie-Anenzephalie-Sequenz. Ultraschalldiagnostik in der Frühschwangerschaft.

AIM: In animal studies exencephaly is well described as a precursor of anencephaly. We have evidence that also in the human fetus the transition from exencephaly to anencephaly is possible. METHOD: We diagnosed either exencephaly or anencephaly by high-frequency vaginal ultrasound in 14 human fetuses at gestational ages varying between 9 + 4 and 22 + 3 weeks. RESULTS: In the first trimester exencephaly was the predominant finding, while in the second trimester the classic appearance of anencephaly was seen more often. In one fetus with exencephaly diagnosed at a gestational age of 12 + 2 weeks, where the parents decided not to intervene, the transition to anencephaly was documented by serial ultrasound examinations. CONCLUSIONS: Our findings support an exencephaly-anencephaly sequence also in humans. The cephalic changes resulting in the classic anencephalic appearance are of importance for the first trimester diagnosis with high resolution vaginal probe ultrasound.

Pulsatile administration of gonadotrophin releasing hormone as a diagnostic tool to distinguish hypothalamic from pituitary hypogonadism following neurosurgery.

Nine patients suffering from severe amenorrhoea following neurosurgical or radiotherapy for pituitary tumour or craniopharyngeoma were treated with pulsatile gonadotrophin releasing hormone (GnRH) administration. Seven patients did exhibit ovulatory cycles when GnRH was administered i.v. at a dose of 20 micrograms/pulse, but not at lower doses or when GnRH was administered s.c. Pulsatile GnRH administration may be used to assess the functional integrity of pituitary gonadotrophs and to distinguish pituitary from hypothalamic site of lesion resulting in hypogonadotrophic hypogonadism. It may also be used successfully for treatment of infertility in such patients.

The extravascular channel system in the rostral pituitary of Mugil cephalus (Teleostei) as revealed by use of horseradish peroxidase.

The interlobular spaces, separating the neuro- and the adenohypophysis can be visualized in the pituitary of the Grey Mullet by using the horseradish peroxidase technique. On the one hand, these spaces communicate with the pericapillary spaces. On the other, they are linked with the pericellular spaces in the adenohypophysis and the periaxonal spaces in the neurohypophysis, thus providing a pathway for the exchange of metabolites and hormones between blood system, epithelial cells and the terminal region of the neurosecretory axons. The interlobular spaces branch off between the tips of the corticotrop cells and form a network adjacent to the adeno- and neurohypophyseal interface. It is possible that branches of this network penetrate into the interior of the corticotrops. The probable role of the network is to permit close contact between neurosecretory hormones and the corticotrops and also to enable the corticotrop hormone to reach the capillaries.