Neurochemical studies on the mesolimbic circuitry of antinociception

Previous studies using the technique of microinjection into brain nuclei indicated that the periaqueductal gray (PAG), nucleus accumbens, habenula and amygdala play an essential role in pain modulation and that these nuclei possibly act through a ‘mesolimbic neural loop‘ to exert an analgesic effect, in which Met-enkephalin (MEK) and β-endorphin (β-EP) have been implicated as the two major opioid peptides involved in antinociception. In the present study performed in rabbits, intracranial microinjection was supplemented with push-pull perfusion and radioimmunoassay to determine whether the release of enkephalins (ENK) and β-EP was increased in these nuclei when the putative neural circuit was activated by morphine administered into one of the nuclei. The results showed: (1) microinjection of morphine into the PAG increased the release of ENK and β-EP in the N. accumbens, and vice versa; (2) microinjection of morphine into the N. accumbens increased the release of ENK and β-EP in the amygdala, and vice versa; (3) morphine microinjected into the PAG caused an increase in the release of ENK and β-EP in the amygdala and vice versa, although the release of ENK in PAG was statistically not significant. These results indicate that PAG, N. accumbens and amygdala are connected in a network served by a positive feedback circuitry.     

Infantile spasms. A retrospective study of 105 cases.

This paper is a summary of our observations on 105 cases of infantile spasms. The age of onset was around six months after birth, but the patients came for treatment mainly about one year after onset. Fever of unknown cause, asphyxia, birth injury, infection of the central nervous system, tuberous sclerosis, phenylketonuria and recent immunization etc. were complained. Clinically, it is characterized by head nodding, mental retardation, myoclonic jerks and various neurologic deficits. EEG findings showed classical or modified arrythmia or other epileptiform patterns. About one third of 22 cases examined had abnormal brain stem auditory evoked potentials. Among 42 patients who underwent CT scanning before ACTH treatment, 18 were normal and 7 abnormal; during ACTH treatment 3 normal and 4 abnormal; after completion of treatment, 4 normal and 6 abnormal, suggesting no further atrophy of the brain. Examination of trace elements of the hair by particle-induced X-ray emission (PIXE) method in 23 patients revealed a significant difference in lead, calcium and zinc contents between patients and 101 controls, but no statistical difference in iron and copper contents between the two groups. Sodium valproate, prednisone and ACTH appear to be effective in the treatment of infantile spasms. Eight patients fully recovered, and they can go to school without difficulty. Many patients derived various degrees of improvement to the satisfaction of their parents. Two patients were still amented and often attacked by myoclonus. The effects, side effects of these drugs, and the possible pathogenesis were discussed.

     

Early uptake of 99mTc-C2A in the acute phase of myocardial infarction as a prognostic indicator for follow-up cardiac dysfunction

OBJECTIVE: The C2A domain of Synaptotagmin I is a molecular probe for the specific imaging of cell death. Here we test the hypothesis that the uptake of 99mTc-C2A in the acute phase of an infarction is associated with cardiac dysfunction in follow-ups. METHODS: The left coronary artery was occluded in Sprague-Dawley rats for 0, 10, 20, and 30 min. 99mTc-C2A was injected intravenously at 2 h of reperfusion. Anterior planar images were acquired with one million counts on a gamma camera 3 h after injection. 99mTc-C2A uptake was calculated as the total counts in the left ventricle region minus blood pool signal. The in-vivo signal detected was correlated with wall motion score index at 1 and 3 weeks follow-ups measured by echocardiography. RESULTS: 99mTc-C2A uptake was higher with increased ischemic time (2244+/-852, 4054+/-1223, and 6178+/-1451 for 10, 20, and 30 min ischemia, analysis of variance P<0.001). A significant correlation was found between 99mTc-C2A uptake and wall motion score index at 1 week (R=0.800, P=0.0006) and 3 weeks (R=0.810, P=0.0008). CONCLUSION: In this ischemia/reperfusion model, 99mTc-C2A uptake in the acute phase was associated with functional abnormality at 1 and 3 weeks. This demonstrates the potential diagnostic and prognostic value of 99mTc-C2A as a novel imaging agent.     

Histamine and tryptase modulate asthmatic airway smooth muscle GM-CSF and RANTES release.

Degranulating mast cells are increased in the airway smooth muscle (ASM) of asthmatics, where they may influence ASM function. The aim of the present study was to determine whether histamine and tryptase modulate ASM cell granulocyte-macrophage colony-stimulating factor (GM-CSF) and RANTES (regulated on activation, normal T-cell expressed and secreted) release and also to examine which receptors are involved in this release. Confluent, quiescent ASM cells from asthmatic and nonasthmatic donors were treated with histamine (1 microM-100 microM) with and without histamine receptor antagonist pre-treatment, or the protease-activated receptor (PAR)-2 agonists tryptase (0.5-5 nM) and SLIGKV (100 and 400 microM). The cells were then stimulated with interleukin (IL)-1beta and/or tumour necrosis factor (TNF)-alpha (10 ng.mL(-1)) or left unstimulated for 24 h. Release of GM-CSF and RANTES was determined by ELISA and prostaglandin (PG)E(2) measured by enzyme immunoassay. Neither histamine nor tryptase induced ASM GM-CSF or RANTES secretion. However, histamine increased IL-1beta-induced GM-CSF release and markedly reduced TNF-alpha-induced RANTES release by both asthmatic and nonasthmatic cells to a similar extent, but did not modulate PGE(2) release. All changes involved activation of the histamine H1 receptor as they were partially or fully blocked by chlorpheniramine, but not ranitidine. Tryptase, via its proteolytic activity, also potentiated GM-CSF, but not RANTES, release from asthmatic and nonasthmatic ASM cells induced by both cytokines. PAR-2 involvement in the tryptase potentiation was unlikely because SLIGKV had no effect. In conclusion, mast cells, through histamine and tryptase, may locally modulate airway smooth muscle-induced inflammation in asthma.