Assessment of rectal afferent neuronal function and brain activity in patients with constipation and rectal hyposensitivity.

BACKGROUND: Blunted rectal sensation (rectal hyposensitivity: RH) is present in almost one-quarter of patients with chronic constipation. The mechanisms of its development are not fully understood, but in a proportion, afferent dysfunction is likely. To determine if, in patients with RH, alteration of rectal sensory pathways exists, rectal evoked potentials (EPs) and inverse modeling of cortical dipoles were examined. METHODS: Rectal EPs (64 channels) were recorded in 13 patients with constipation and RH (elevated thresholds to balloon distension) and 11 healthy controls, in response to electrical stimulation of the rectum at 10 cm from the anal verge using a bipolar stimulating electrode. Stimuli were delivered at pain threshold. Evoked potential peak latencies and amplitudes were analyzed, and inverse modeling was performed on traces obtained to determine the location of cortical generators. KEY RESULTS: Pain threshold was higher in patients than controls [median 59 (range 23-80) mA vs 24 (10-55) mA; P = 0.007]. Median latency to the first negative peak was 142 (±24) ms in subjects compared with 116 (±15) ms in controls (P = 0.004). There was no difference in topographic analysis of EPs or location of cortical activity demonstrated by inverse modeling between groups. CONCLUSIONS & INFERENCES: This study is the first showing objective evidence of alteration in the rectal afferent pathway of individuals with RH and constipation. Prolonged latencies suggest a primary defect in sensory neuronal function, while cerebral processing of visceral sensory information appears normal.

Randomised clinical trial: pregabalin attenuates the development of acid-induced oesophageal hypersensitivity in healthy volunteers - a placebo-controlled study.

BACKGROUND: Acid infusion in humans induces primary and secondary oesophageal hypersensitivity. The effects of pregabalin, a centrally-acting modulator of voltage-sensitive calcium channels, on development of acid-induced oesophageal hypersensitivity remain unknown. AIM: To study the effects of pregabalin on development of secondary oesophageal hypersensitivity in healthy humans. METHODS: Placebo-controlled, double-blind, randomised, cross-over study of 15 healthy volunteers (six women, age 21-56 years). After oesophageal manometry, baseline pain thresholds (PTs) to proximal oesophageal electrical stimulation were determined using bipolar ring electrodes. A 30-min infusion of HCl was performed in the distal oesophagus followed by PT measurements at 30 and 90 min. This protocol was repeated after administration of pregabalin (dosing schedule: 75 mg twice daily for 3 days then 150 mg twice daily for 1 day and then 150 mg on the morning of study) or placebo. RESULTS: T0 PTs were similar in patients after receiving placebo or pregabalin [mean (s.d.) 32.9 mA (20.5) vs. 34.1 (15.7), P = 0.42]. Pregabalin reduced development of acid-induced hypersensitivity in the proximal oesophagus at 30 min [mean change in PT (C.I.) placebo -6.2 mA (-11.3 to +1.3) vs. pregabalin +0.20 mA (-2.7 to +3.3)] and 90 min [placebo -3.7 mA (-10.0 to +2.0) vs. pregabalin +0.7 mA (-4.7 to 7.3)] overall P = 0.001. Pregabalin reduced median visual analogue scale score for acid-induced pain (1/10 vs. placebo 3/10, P = 0.027). CONCLUSIONS: Pregabalin attenuates development of secondary hypersensitivity in the proximal oesophagus after distal oesophageal acidification; it may thus have a role in treatment of patients with proven oesophageal pain hypersensitivity.

Modification of standard CMOS technology for cell-based biosensors.

We present an electrode based on complementary metal oxide semiconductor (CMOS) technology that can be made fully biocompatible and chemically inert using a simple, low-cost and non-specialised process. Since these devices are based on ubiquitous CMOS technology, the integrated circuits can be readily developed to include appropriate amplifiers, filters and wireless subsystems, thus reducing the complexity and cost of external systems. The unprocessed CMOS aluminium electrodes are modified using anodisation and plating techniques which do not require intricate and expensive semiconductor processing equipment and can be performed on the bench-top as a clean-room environment is not required. The resulting transducers are able to detect both the fast electrical activity of neurons and the slow changes in impedance of growing and dividing cells. By using standard semiconductor fabrication techniques and well-established technologies, the approach can form the basis of cell-based biosensors and transducers for high throughput drug discovery assays, neuroprosthetics and as a basic research tool in biosciences. The technology is equally applicable to other biosensors that require noble metal or nanoporous microelectrodes.

Relationship between attitudinal hostility and P300 latencies.

1. The purpose of the present study was to determine whether components of the P300 were related to aggression in a normal population. 2. Event-related potentials were recorded from midline sites during a standard pure tone auditory oddball task. 3. Findings indicated significantly prolonged P300 latencies to target stimuli in subjects with higher total aggression and attitudinal hostility scores on the BDHI. 4. The relationship between P300 latency and aggression extends findings in specifically aggressive populations. P300 amplitudes may only be reduced in samples displaying violent or assaultive behaviour.