Pyocyanin has recently emerged as an important virulence factor produced by Pseudomonas aeruginosa. The redox-active tricyclic zwitterion has been shown to have a number of potential effects on various organ systems in vitro, including the respiratory, cardiovascular, urological, and central nervous systems. It has been shown that a large number of the effects to these systems are via the formation of reactive oxygen species. The limitations of studies are, to date, focused on the localized effect of the release of pyocyanin (PCN). It has been postulated that, given its chemical properties, PCN is able to readily cross biological membranes, however studies have yet to be undertaken to evaluate this effect. This review highlights the possible manifestations of PCN exposure; however, most studies to date are in vitro. Further high quality in vivo studies are needed to fully assess the physiological manifestations of PCN exposure on the various body systems.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly referred to as statins, are widely used in the treatment of dyslipidaemia, in addition to providing primary and secondary prevention against cardiovascular disease and stroke. Statins’ effects on the central nervous system (CNS), particularly on cognition and neurological disorders such as stroke and multiple sclerosis, have received increasing attention in recent years, both within the scientific community and in the media. Current understanding of statins’ effects is limited by a lack of mechanism-based studies, as well as the assumption that all statins have the same pharmacological effect in the central nervous system. This review aims to provide an updated discussion on the molecular mechanisms contributing to statins’ possible effects on cognitive function, neurodegenerative disease, and various neurological disorders such as stroke, epilepsy, depression and CNS cancers. Additionally, the pharmacokinetic differences between statins and how these may result in statin-specific neurological effects are also discussed.

SARS-CoV-2 is a novel coronavirus that infects cells through the angiotensin-converting enzyme 2 receptor, aided by proteases that prime the spike protein of the virus to enhance cellular entry. Neuropilin 1 and 2 (NRP1 and NRP2) act as additional viral entry factors. SARS-CoV-2 infection causes COVID-19 disease. There is now strong evidence for neurological impacts of COVID-19, with pain as an important symptom, both in the acute phase of the disease and at later stages that are colloquially referred to as "long COVID." In this narrative review, we discuss how COVID-19 may interact with the peripheral nervous system to cause pain in the early and late stages of the disease. We begin with a review of the state of the science on how viruses cause pain through direct and indirect interactions with nociceptors. We then cover what we currently know about how the unique cytokine profiles of moderate and severe COVID-19 may drive plasticity in nociceptors to promote pain and worsen existing pain states. Finally, we review evidence for direct infection of nociceptors by SARS-CoV-2 and the implications of this potential neurotropism. The state of the science points to multiple potential mechanisms through which COVID-19 could induce changes in nociceptor excitability that would be expected to promote pain, induce neuropathies, and worsen existing pain states.

Key points Animal preparations have revealed that moderate synaptic release of serotonin (5‐HT) onto motoneurones enhances motor activity via activation of 5‐HT2 receptors, whereas intense release of 5‐HT causes spillover of 5‐HT to extrasynaptic 5‐HT1A receptors on the axon initial segment to reduce motoneurone activity. We explored if increasing extracellular concentrations of endogenously released 5‐HT (via the selective serotonin reuptake inhibitor paroxetine) influences the ability to perform unfatigued and fatigued maximal voluntary contractions in humans. Following the ingestion of paroxetine, voluntary muscle activation and torque generation increased during brief unfatigued maximal contractions. In contrast, the ability to generate maximal torque with increased 5‐HT availability was compromised under fatigued conditions, which was consistent with paroxetine‐induced reductions in motoneurone excitability and voluntary muscle activation. This is the first in vivo human study to provide evidence that 5‐HT released onto the motoneurones could play a role in central fatigue. Abstract Brief stimulation of the raphe–spinal pathway in the turtle spinal cord releases serotonin (5‐HT) onto motoneurones to enhance excitability. However, intense release of 5‐HT via prolonged stimulation results in 5‐HT spillover to the motoneurone axon initial segment to activate inhibitory 5‐HT1A receptors, thus providing a potential spinal mechanism for exercise‐induced central fatigue. We examined how increased extracellular concentrations of 5‐HT affect the ability to perform brief, as well as sustained, maximal voluntary contractions (MVCs) in humans. Paroxetine was used to enhance 5‐HT concentrations by reuptake inhibition, and three studies were performed. Study 1 (n = 14) revealed that 5‐HT reuptake inhibition caused an ∼4% increase in elbow flexion MVC. However, when maximal contractions were sustained, time‐to‐task failure was reduced and self‐perceived fatigue was higher with enhanced availability of 5‐HT. Study 2 (n = 11) used twitch interpolation to reveal that 5‐HT‐based changes in motor performance had a neural basis. Enhanced 5‐HT availability increased voluntary activation for the unfatigued biceps brachii and decreased voluntary activation of the biceps brachii by 2–5% following repeated maximal elbow flexions. The final study (n = 8) investigated whether altered motoneurone excitability may contribute to 5‐HT changes in voluntary activation. F‐waves of the abductor digiti minimi (ADM) were unaffected by paroxetine for unfatigued muscle and marginally affected following a brief 2‐s MVC. However, F‐wave area and persistence were significantly decreased following a prolonged 60‐s MVC of the ADM. Overall, high serotonergic drive provides a spinal mechanism by which higher concentrations of 5‐HT may contribute to central fatigue.