Functional heterogeneity of calretinin-expressing neurons in the mouse superficial dorsal horn: implications for spinal pain processing.

KEY POINTS: The superficial spinal dorsal horn contains a heterogeneous population of neurons that process sensory inputs. Information on the properties of excitatory interneurons in this region is limited. As calretinin is a protein thought to be restricted to an excitatory population in this region, the aim of this study was to characterize calretinin-expressing neurons. Most calretinin cells (85%) exhibited large A-type potassium currents and delayed firing action potential discharge, and received strong excitatory synaptic input, whereas the remainder exhibited hyperpolarization-activated cation currents and low threshold T-type calcium currents, and tonic- or initial bursting firing patterns, and received weak excitatory synaptic input. These respective features are consistent with properties of excitatory and inhibitory interneuron populations in this region of the spinal cord. Our findings have resolved a previously unidentified population of inhibitory interneurons. Furthermore, the contrasting excitability patterns of excitatory and inhibitory calretinin-expressing neurons suggest that they play distinct roles in spinal sensory processing circuits. ABSTRACT: Neurons in the superficial dorsal horn (SDH) of the spinal cord play an important role in nociceptive, thermal, itch and light touch sensations. Excitatory interneurons comprise ∼65% of all SDH neurons but surprisingly few studies have investigated their role in spinal sensory processing. Here we use a transgenic mouse to study putative excitatory SDH neurons that express the calcium binding protein calretinin (CR). Our immunocytochemical, morphological and electrophysiological analysis identified two distinct populations of CR-expressing neurons, which we termed 'Typical' and 'Atypical'. Typical CR-expressing neurons comprised ∼85% of the population and exhibited characteristic excitatory interneuron properties including delayed firing discharge, large rapid A-type potassium currents, and central, radial or vertical cell morphologies. Atypical neurons exhibited properties consistent with inhibitory interneurons, including tonic firing or initial bursting discharge, Ih currents, and islet cell morphology. Although both Typical and Atypical CR-expressing neurons responded to noxious peripheral stimulation, the excitatory drive onto Typical CR-expressing neurons was much stronger. Furthermore, Atypical CR-expressing cells comprise at least two functionally distinct subpopulations based on their responsiveness to noxious peripheral stimulation and neurochemical profile. Together our data suggest CR expression is not restricted to excitatory neurons in the SDH. Under normal conditions, the contribution of 'Typical' excitatory CR-expressing neurons to overall SDH excitability may be limited by the presence of A-type potassium currents, which limit the effectiveness of their strong excitatory input. Their contribution may, however, be increased in pathological situations where A-type potassium currents are decreased. By contrast, 'Atypical' inhibitory neurons with their excitable phenotype but weak excitatory input may be more easily recruited during increased peripheral stimulation.

Use of dual-energy x-ray absorptiometry (DXA) scans in HIV-infected patients.

Multiple studies have demonstrated increased rates of osteopenia and osteoporosis in HIV-infected patients but there have been no published studies on current screening practices. We conducted a retrospective chart review of 2924 patients attending an urban HIV clinic. Thirty patients (1%) had dual-energy x-ray absorptiometry (DXA) scans. Patients undergoing DXA scans were more likely to be older, women, and have nondetectable HIV viral load and CD4 count ≥200. The most frequently cited indications for screening were perimenopausal or postmenopausal status and HIV infection. Of the patients screened, 96% had osteopenia or osteoporosis with a median T-score of -1.9 and a median of 3.8 osteoporosis risk factors in addition to HIV.  Of the 20 practitioners in the clinic, only 7 had patients with screening DXA scans. DXA scans are underutilized in the HIV population given the high rate of osteopenia and osteoporosis detected in this study.

Development of an accurate portable recording peak-flow meter for the diagnosis of asthma.

This article describes the systematic design of an electronic recording peak expiratory flow (PEF) meter to provide accurate data for the diagnosis of occupational asthma. Traditional diagnosis of asthma relies on accurate data of PEF tests performed by the patients in their own homes and places of work. Unfortunately there are high error rates in data produced and recorded by the patient, most of these are transcription errors and some patients falsify their records. The PEF measurement itself is not effort independent, the data produced depending on the way in which the patient performs the test. Patients are taught how to perform the test giving maximal effort to the expiration being measured. If the measurement is performed incorrectly then errors will occur. Accurate data can be produced if an electronically recording PEF instrument is developed, thus freeing the patient from the task of recording the test data. It should also be capable of determining whether the PEF measurement has been correctly performed. A requirement specification for a recording PEF meter was produced. A commercially available electronic PEF meter was modified to provide the functions required for accurate serial recording of the measurements produced by the patients. This is now being used in three hospitals in the West Midlands for investigations into the diagnosis of occupational asthma. In investigating current methods of measuring PEF and other pulmonary quantities a greater understanding was obtained of the limitations of current methods of measurement, and quantities being measured.(ABSTRACT TRUNCATED AT 250 WORDS)

The accuracy of portable peak flow meters.

BACKGROUND: The variability of peak expiratory flow (PEF) is now commonly used in the diagnosis and management of asthma. It is essential for PEF meters to have a linear response in order to obtain an unbiased measurement of PEF variability. As the accuracy and linearity of portable PEF meters have not been rigorously tested in recent years this aspect of their performance has been investigated. METHODS: The response of several portable PEF meters was tested with absolute standards of flow generated by a computer driven, servo controlled pump and their response was compared with that of a pneumotachograph. RESULTS: For each device tested the readings were highly repeatable to within the limits of accuracy with which the pointer position can be assessed by eye. The between instrument variation in reading for six identical devices expressed as a 95% confidence limit was, on average across the range of flows, +/- 8.5 l/min for the Mini-Wright, +/- 7.9 l/min for the Vitalograph, and +/- 6.4 l/min for the Ferraris. PEF meters based on the Wright meter all had similar error profiles with overreading of up to 80 l/min in the mid flow range from 300 to 500 l/min. This overreading was greatest for the Mini-Wright and Ferraris devices, and less so for the original Wright and Vitalograph meters. A Micro-Medical Turbine meter was accurate up to 400 l/min and then began to underread by up to 60 l/min at 720 l/min. For the low range devices the Vitalograph device was accurate to within 10 l/min up to 200 l/min, with the Mini-Wright overreading by up to 30 l/min above 150 l/min. CONCLUSION: Although the Mini-Wright, Ferraris, and Vitalograph meters gave remarkably repeatable results their error profiles for the full range meters will lead to important errors in recording PEF variability. This may lead to incorrect diagnosis and bias in implementing strategies of asthma treatment based on PEF measurement.