Quantitative measurement of changes in calcium channel activity in vivo utilizing dynamic manganese-enhanced MRI (dMEMRI).

The ability of manganese ions (Mn(2+)) to enter cells through calcium ion (Ca(2+)) channels has been used for depolarization dependent brain functional imaging with manganese-enhanced MRI (MEMRI). The purpose of this study was to quantify changes to Mn(2+) uptake in rat brain using a dynamic manganese-enhanced MRI (dMEMRI) scanning protocol with the Patlak and Logan graphical analysis methods. The graphical analysis was based on a three-compartment model describing the tissue and plasma concentration of Mn. Mn(2+) uptake was characterized by the total distribution volume of manganese (Mn) inside tissue (V(T)) and the unidirectional influx constant of Mn(2+) from plasma to tissue (K(i)). The measurements were performed on the anterior (APit) and posterior (PPit) parts of the pituitary gland, a region with an incomplete blood brain barrier. Modulation of Ca(2+) channel activity was performed by administration of the stimulant glutamate and the inhibitor verapamil. It was found that the APit and PPit showed different Mn(2+) uptake characteristics. While the influx of Mn(2+) into the PPit was reversible, Mn(2+) was found to be irreversibly trapped in the APit during the course of the experiment. In the PPit, an increase of Mn(2+) uptake led to an increase in V(T) (from 2.8±0.3 ml/cm(3) to 4.6±1.2 ml/cm(3)) while a decrease of Mn(2+) uptake corresponded to a decrease in V(T) (from 2.8±0.3 ml/cm(3) to 1.4±0.3 ml/cm(3)). In the APit, an increase of Mn(2+) uptake led to an increase in K(i) (from 0.034±0.009 min(-1) to 0.049±0.012 min(-1)) while a decrease of Mn(2+) uptake corresponded to a decrease in K(i) (from 0.034±0.009 min(-1) to 0.019±0.003 min(-1)). This work demonstrates that graphical analysis applied to dMEMRI data can quantitatively measure changes to Mn(2+) uptake following modulation of neural activity.

Assessment of mechanical and thermal thresholds of human C nociceptors during increases in skin sympathetic nerve activity.

OBJECTIVES: The objective of the present study is to investigate the relationship between C-fiber nociceptor sensitivity and skin sympathetic nerve activity during mental arithmetic. METHODS: Single afferent C-fibers were identified simultaneously with spontaneous postganglionic sympathetic discharges and recorded from the peroneal nerve using microneurography in 23 normal subjects. Mechanical and heat thresholds were measured by 'marking' the nociceptor with suprathreshold stimuli, causing increased latency after a subsequent threshold stimulus at rest and during mental arithmetic. Skin sympathetic nerve activity was estimated by counting the number of bursts per minute. RESULTS: Thirty-two single C-fibers were identified. Eleven had polymodal receptors (mechanical and heat sensitive), eight were only sensitive to mechanical stimuli, two were only sensitive to heat stimuli, and 11 were insensitive to both. C-fibers were selected when the ratio of skin sympathetic nerve activity during mental arithmetic to that at rest was over 1.00. In 19 selected mechanical sensitive units, average mechanical threshold was 4.86 at rest and 4.84 during mental arithmetic. In 6 selected heat sensitive units, average heat threshold was 45.0 degrees C at rest and 43.4 degrees C during mental arithmetic. However, differences were not statistically significant. CONCLUSIONS: Physiological sympathetic stimulation did not affect afferent C-fiber nociceptor sensitivity to mechanical and heat stimuli in healthy subjects.