Theta-frequency phase-locking of single anterior cingulate cortex neurons and synchronization with the medial thalamus are modulated by visceral noxious stimulation in rats.

The rodent anterior cingulate cortex (ACC) is critical for visceral pain and pain-related aversive response in chronic visceral hypersensitive (VH) state. Long-term potentiation (LTP), induced by theta burst stimulation (TBS) in the medial thalamus (MT)-ACC pathway, is blocked in VH rats. However, the neuronal intrinsic firing characteristics and the MT-ACC connectivity have not been investigated in visceral pain. Using repetitive distension of the colon and rectum (rCRD) as a sensitization paradigm, we have identified that the spontaneous firing rates of ACC neurons and the CRD-stimulated neuronal firings were increased after repetitive visceral noxious stimulation. This correlates with increases in visceral pain responses (visceromotor responses, VMRs). Two multichannel arrays of electrodes were implanted in the MT and ACC. Recordings were performed in free-moving rats before and after repeated CRD treatment. Power spectral density analysis showed that the local field potential (LFP) recorded in the ACC displayed increases in theta band power (4-10 Hz) that were modulated by rCRD. Neural spike activity in the ACC becomes synchronized with ongoing theta oscillations of LFP. Furthermore, cross correlation analysis showed augmented synchronization of thalamo-ACC theta band LFPs, which was consistent with an increase of neuronal communication between the two regions. In conclusion, these results reveal theta oscillations and theta-frequency phase-locking as prominent features of neural activity in the ACC and a candidate neural mechanism underlying acute visceral pain.

Hypodense eosinophil number relates to clinical severity, airway hyperresponsiveness and response to inhaled corticosteroids in asthmatic subjects.

The phenotypically distinct low-density eosinophil, with its greater inflammatory potential, is increased in asthma. However, the role of hypodense eosinophils in the development of asthma is still unclear. We conducted a double-blind, placebo-controlled study to examine the effect of inhaled corticosteroids on the number of hypodense eosinophils in 27 asthmatic subjects and its relationship with clinical severity. The density profile of eosinophils in the peripheral blood was determined using Percoll density gradient fractionation. Eosinophils recovered from asthmatics were mainly in the lower density fractions (< 1.095 g.ml-1) (63 +/- 3%; n = 27), significantly different from those of normal subjects (27 +/- 2%; n = 7). The proportion of hypodense eosinophils was inversely related to the provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) value (r = -0.75). Patients with mild asthma had a lower percentage of hypodense eosinophils (45 +/- 4%; n = 14) than those with moderate asthma (67 +/- 3%; n = 13). Inhalation of budesonide (800 micrograms.day-1) (n = 15) for 4 weeks, but not placebo, significantly improved the PC20 values by 0.97 doubling dose, forced expiratory volume in one second (FEV1) % predicted by 17%, and peak expiratory flow rate (PEFR) by 15%, and decreased PEFR diurnal variability by 5.4%. The percentage of hypodense eosinophils was significantly decreased from 68 +/- 4 to 47 +/- 4% in the budesonide group (n = 15), but not in the placebo group (n = 12) (63 +/- 4 to 65 +/- 4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between increased hypodense eosinophils in the peripheral blood and bronchial hyperresponsiveness in patients with bronchial asthma.

Eosinophils are the most prominent inflammatory cells involved in the development of bronchial hyperresponsiveness in bronchial asthma. There is evidence that eosinophils in the peripheral blood are a heterogeneous cell population. The heterogeneity of eosinophils in the peripheral blood from 16 patients with mild to moderate bronchial asthma and seven normal subjects was studied using Percoll density fractionation. Eosinophils recovered from patients with bronchial asthma were mainly in the lower density fractions (< 1.095 g/mL), whereas eosinophils from normal subjects were in the higher density fractions (> 1.095 g/mL). The total cell count and the proportion of hypodense eosinophils were highly correlated with the provoking concentration (PC20) of methacholine, which caused a 20% decrease in FEV1 but not in the baseline spirometry. Disease severity, determined on the grounds of clinical history and the peak expiratory flow rate as well as its variability, showed that patients with moderate bronchial asthma had a higher count of hypodense eosinophils than those with mild bronchial asthma. This study shows that eosinophils from asthmatics, when compared with those from control subjects, are heterogeneous and predominantly hypodense cells. Changes in the repartition of the eosinophil subpopulations may be of critical importance in determining the magnitude of the inflammatory response of the airways in bronchial asthma.