Inhibitory mechanisms are essential in suppressing the development of allodynia and hyperalgesia in the normal animal and there is evidence that loss of inhibition can lead to the development of neuropathic pain. We used Fos expression to map the distribution of tonically inhibited cells in the healthy rat lumbar spinal cord. In a control group, Fos-like immunoreactive (Fos-LI) cells were rare, averaging 7.5+/-2.2 cells (mean+/-SEM; N=13 sections) per 20 microm thick section of dorsal horn. This rose to 103+/-11 (mean+/-SEM; N=20) in picrotoxin-treated rats and to 88+/-11 (mean+/-SEM; N=18) in strychnine-treated rats. These changes were significant (ANOVA; P<0.001). There were marked regional variations in the distribution of Fos-LI cells between picrotoxin- and strychnine-treated animals. Picrotoxin induced a significant increase in the number of Fos-LI cells throughout the dorsal horn (lamina I-VI) while strychnine significantly elevated Fos-like immunoreactivity only in deep laminae (III-VI). For both picrotoxin and strychnine, the increase in Fos-like immunoreactivity peaked in lamina V (at 3579+/-319 and 3649+/-375% of control, respectively; mean+/-SEM) but for picrotoxin an additional peak was observed in the outer part of lamina II (1959+/-196%). Intrathecal administration of both GABAA and glycine receptor antagonists has been shown elsewhere to induce tactile allodynia. The present data suggest that this allodynia could arise due to blockade of tonic GABAA and glycine-receptor mediated inhibition in the deep dorsal horn. GABAA antagonists also induce hypersensitivity to noxious inputs. The blockade of tonic inhibition in the superficial dorsal horn shown here may underlie this hyperalgesia.

Purpose of review More than 230 million people have tested positive for severe acute respiratory syndrome-coronavirus-2 infection globally by September 2021. The infection affects primarily the function of the respiratory system, where ∼20% of infected individuals develop coronavirus-19 disease (COVID-19) pneumonia. This review provides an update on the pathophysiology of the COVID-19 acute lung injury. Recent findings In patients with COVID-19 pneumonia admitted to the intensive care unit, the PaO 2 /FiO 2 ratio is typically <26.7 kPa (200 mmHg), whereas lung volume appears relatively unchanged. This hypoxaemia is likely determined by a heterogeneous mismatch of pulmonary ventilation and perfusion, mainly associated with immunothrombosis, endothelialitis and neovascularisation. During the disease, lung weight, elastance and dead space can increase, affecting respiratory drive, effort and dyspnoea. In some severe cases, COVID-19 pneumonia may lead to irreversible pulmonary fibrosis. Summary This review summarises the fundamental pathophysiological features of COVID-19 in the context of the respiratory system. It provides an overview of the key clinical manifestations of COVID-19 pneumonia, including gas exchange impairment, altered pulmonary mechanics and implications of abnormal chemical and mechanical stimuli. It also critically discusses the clinical implications for mechanical ventilation therapy.

Arterial oxygen partial pressure can increase during inspiration and decrease during expiration in the presence of a variable shunt fraction, such as with cyclical atelectasis, but it is generally presumed to remain constant within a respiratory cycle in the healthy lung. We measured arterial oxygen partial pressure continuously with a fast intra-vascular sensor in the carotid artery of anaesthetized, mechanically ventilated pigs, without lung injury. Here we demonstrate that arterial oxygen partial pressure shows respiratory oscillations in the uninjured pig lung, in the absence of cyclical atelectasis (as determined with dynamic computed tomography), with oscillation amplitudes that exceeded 50 mmHg, depending on the conditions of mechanical ventilation. These arterial oxygen partial pressure respiratory oscillations can be modelled from a single alveolar compartment and a constant oxygen uptake, without the requirement for an increased shunt fraction during expiration. Our results are likely to contribute to the interpretation of arterial oxygen respiratory oscillations observed during mechanical ventilation in the acute respiratory distress syndrome.

Background: Real-time bedside information on regional ventilation and perfusion during mechanical ventilation (MV) may help to elucidate the physiological and pathophysiological effects of MV settings in healthy and injured lungs. We aimed to study the effects of positive end-expiratory pressure (PEEP) and tidal volume (V T ) on the distributions of regional ventilation and perfusion by electrical impedance tomography (EIT) in healthy and injured lungs. Methods: One-hit acute lung injury model was established in 6 piglets by repeated lung lavages (injured group). Four ventilated piglets served as the control group. A randomized sequence of any possible combination of three V T (7, 10, and 15 ml/kg) and four levels of PEEP (5, 8, 10, and 12 cmH 2 O) was performed in all animals. Ventilation and perfusion distributions were computed by EIT within three regionsof-interest (ROIs): nondependent, middle, dependent. A mixed design with one between-subjects factor (group: intervention or control), and two within-subjects factors (PEEP and V T ) was used, with a three-way mixed analysis of variance (ANOVA). Results: Two-way interactions between PEEP and group, and V T and group, were observed for the dependent ROI (p = 0.035 and 0.012, respectively), indicating that the increase in the dependent ROI ventilation was greater at higher PEEP and V T in the injured group than in the control group. A two-way interaction between PEEP and V T was observed for perfusion distribution in each ROI: nondependent (p = 0.030), middle (p = 0.006), and dependent (p = 0.001); no interaction was observed between injured and control groups. Conclusions: Large PEEP and V T levels were associated with greater pulmonary ventilation of the dependent lung region in experimental lung injury, whereas they affected pulmonary perfusion of all lung regions both in the control and in the experimental lung injury groups.